bluuebunny/crossref_metadata_2025 huggingface dataset:
PMSG in ewes: A Practical and Efficient Step for Superovulation
Authors: Somanjaya R , Fuah A M , Rahayu S , Setiadi MA , Abdullah L
Published: December 2021

Ewes have a prolific nature, but in reality, the average number of lambs (litter size) is still around 120%. The application of the PMSG (Pregnant Mare Serum Gonadotrophyn) hormone aims as a superovulation agent for obtaining twins in one birth. PMSG is a non-pituitary gonadotrophyn hormone that has the same function as FSH ((Follicle Stimulating Hormone) and LH (Luteinizing Hormone) which stimulates follicular and ovulation growth. Various methods of applying the PMSG hormone to the ewes were quite diverse and produced different responses. Which method is considered the most practical and efficient is the main topic in this paper. Details of the discussion in this paper include the nature and biochemical characteristics of PMSG, the performance of PMSG as a superovulation agent, the comparison of PMSG with other reproductive hormones to the superovulation response in ruminants, and the impact of PMSG on superovulation in ewes.
Investigation of the effect of cutting parameters on the milling process of cryogenically treated aluminum alloy with cryogenically treated and untreated inserts, using the Taguchi and Gray Relational Analysis methods
Authors: Samtaş Gürcan , Bektaş Berat Serhat
Published: December 2021

The aluminum 6061 alloy is commonly employed in the automotive industry in the manufacture of rims, panels and even the chasses of vehicles and has excellent machinability. In this study, the surface of the cryogenically processed aluminum 6061-T651 alloy was milled using both untreated and cryogenically treated TiN-TiCN-Al2O3-coated cutting inserts. The Taguchi L18 orthogonal array was chosen as the experimental design. As the cutting parameters in the experiments, two different cutting inserts (untreated and cryogenically treated, TiN-TiCN-Al2O3-coated), three different cutting speeds (250, 350 and 450 m min−1) and three different feed rates (0.15, 0.30 and 0.45 mm/rev) were used. After each experiment, the surface roughness and wear values of the cutting inserts were measured, the latter after repeating the experiment five times. Wear and roughness values were optimized using the Taguchi method. Additionally, Gray Relational Analysis (GRA) was used for the combined optimization of wear and roughness values. The optimized findings determined using Taguchi optimization for minimum surface roughness were the cryogenically treated cutting insert, 250 m min−1cutting speed and 0.45 mm/rev feed rate. The optimized findings for wear were the cryogenically treated cutting insert, 350 m min−1cutting speed and 0.30 mm/rev feed rate. In the optimization with GRA, the common optimum parameters for surface roughness and wear were the cryogenically treated cutting insert, 250 m min−1cutting speed and 0.15 mm/rev feed rate. According to the Taguchi and GRA results, the cryogenically treated cutting inserts performed the best in terms of minimum wear and surface roughness. The Gray-based Taguchi methodology proposed in this study was found to be effective in solving the decision-making problem in multi-specific results as wear and surface roughness.
Improving the bending resistance of double-layer printed flexible OLEDs with PEDOT: PSS-PEO composite HIL films
Authors: Wang Yan , Zhang DongYu , Gao Qiang
Published: December 2021

Flexible organic light-emitting diodes (OLEDs) are expected to have excellent device performance and mechanical robustness in many areas, such as wearable electronics and display devices. For the traditional materials of OLED anode, indium tin oxide (ITO) is undoubtedly the most mature transparent conductive electrode available. However, the brittle and rigid nature of ITO severely limit the development of flexible OLED (FOLED). In this work, a solution blending film consisting of poly (3,4 ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT: PSS) and poly (ethylene oxide) (PEO) was used as a hybrid hole injection layer, where PEO polymer in the composite films can greatly improve the bending resistance of device. The printed FOLEDs doped with PEO exhibit impressive mechanical durability, maintaining 80.4% of its maximum external quantum efficiency after 1000 bends at a radius of curvature of 10 mm, compared to 46.3% for the counterpart without PEO doping.
Nanocrystals of metal halide perovskites and their analogues as scintillators for x-ray detection
Authors: Chen Huiwen , Li Yunlong , Zhao Bo , Ming Jun , Xue Dongfeng
Published: December 2021

Scintillators are widely used for x-ray detection in various fields, such as medical diagnostics, industrial inspection and homeland security. Nanocrystals (NCs) of metal halide perovskites (MHPs) and their analogues showed great advantages as x-ray scintillators due to their cheap manufacturing, fast decay time, and room temperature scintillation from quantum confinement effect. However, there are still many challenges unsolved for further industrialization. Herein, it is necessary to summarize the progress of scintillators based on NCs of MHPs and their analogues. In the first section, the scintillation mechanism and key parameters are outlined. Then, various NCs of MHPs and their analogues used as scintillators are reviewed. Finally, the challenges and outlook are discussed. It is believed that NCs of MHPs and their analogues are favorable for large-area and flexible x-ray detectors.
Conditions for electronic hybridization between transition-metal dichalcogenide monolayers and physisorbed carbon-conjugated molecules
Authors: Krumland Jannis , Cocchi Caterina
Published: December 2021

Hybridization effects play a crucial role in determining the electronic properties of hybrid inorganic/organic interfaces. To gain insight into these important interactions, we perform a first-principles study based on hybrid density-functional theory including spin–orbit coupling, focusing on eight representative systems formed by two carbon-conjugated molecules—pyrene and perylene—physisorbed on the transition-metal dichalcogenide monolayers (TMDCs) MoS2, MoSe2, WS2, and WSe2. By means of band unfolding techniques, we analyze the band structures of the considered materials, identifying the contributions of the individual constituents as well as the signatures of their hybridization. Based on symmetry and energetic arguments, we derive general conditions for electronic hybridization between conjugated molecules and underlying TMDCs even when the former do not lie planar on the latter, thus providing the key to predict how their mutual arrangement affect their electronic interactions.
Heterologous expression of a polyketide synthase ACRTS2 in Aspergillus oryzae produces host-selective ACR toxins: coproduction of minor metabolites
Authors: Kotani Akari , Ozaki Taro , Takino Junya , Mochizuki Susumu , Akimitsu Kazuya , Minami Atsushi , Oikawa Hideaki
Published: December 2021

Previously, we succeeded to produce the core structure of the host-selective ACR toxin (1) on brown leaf spot on rough lemon when the polyketide synthase ACRTS2 gene was heterologously expressed in Aspergillus oryzae (AO). To confirm the production of 1 in AO, the detection limit and suppressing decarboxylation were improved, and these efforts led us to conclude the direct production of 1 instead of its decarboxylation product. During this examination, minor ACR-toxin-related metabolites were found. Their structure determination enabled us to propose a decarboxylation mechanism and a novel branching route forming byproducts from the coupling of the dihydropyrone moiety of 1 with the acetaldehyde and kojic acid abundant in AO. The involvement of putative cyclase ACRTS3 in the chain release of linear polyketide was excluded by the coexpression analysis of ACRTS2 and ACRTS3. Taken together, we concluded that the production of 1 in AO is solely responsible for ACRTS2.
Left circumflex artery injury following surgical mitral valve replacement: a case report
Authors: Gaba Prakriti , Kaneko Tsuyoshi , Kochar Ajar , Sung Jonathan , O’Gara Patrick T , Bhatt Deepak L
Published: December 2021

Background

Mitral valve (MV) repair or replacement surgery is indicated for a variety of conditions. Although uncommon, damage to the left circumflex (LCx) coronary artery, which courses in close proximity to the MV annulus, is a devastating complication.

Case summary

This report describes the case of a 63-year-old woman following re-operative MV replacement. Shortly after being transferred to the surgical intensive care unit after MV replacement, her EKG was notable for persistent inferolateral ST-segment elevations and reciprocal ST-segment depressions. Emergency transthoracic echocardiogram revealed a reduced left ventricular ejection fraction of 35–40% and mid to distal lateral wall motion hypokinesis. She was emergently taken to the cardiac catheterization laboratory where coronary angiography demonstrated complete occlusion of her mid LCx artery. She underwent urgent percutaneous coronary intervention of the lesion and was started on dual antiplatelet treatment, anticoagulation for comorbid atrial fibrillation, as well as guideline directed medical therapy with improvement in her EKG changes and cardiac function.

Conclusion

Prompt diagnosis and recognition of LCx injury is crucial. Management involves immediate percutaneous recanalization or surgical coronary bypass grafting.
Recurrent ST-elevation myocardial infarction: a case report of a rare complication of caseous mitral annular calcification
Authors: Singh Nikhil , Shah Atman P , Torregrossa Gianluca , Blair John E
Published: December 2021

Background

Caseous mitral annular calcification (MAC) is an under-diagnosed division of calcific mitral valve disease that has recently been reported to have increased propensity for embolic disease. Early recognition of this entity as a cause of embolic disease can lead to prevention of occlusive vascular disease and long-standing complications.

Case summary

We present the case of a patient with end-stage renal disease who presented for evaluation of chest pain and was found to have ST-segment myocardial infarction. Despite thrombectomy and stenting, he had multiple recurrent events, and imaging evaluation demonstrated caseous MAC with mobile components. He was taken for surgical replacement of the mitral valve, with pathology confirming diagnosis.

Discussion

Caseous MAC may represent an increased risk of embolic disease. Better understanding of this pathology and it’s propensity for embolic disease will be important to best determine treatment plans and timing of operative intervention.
Predilection or Prediction? Country Selection for the President's Daily Intelligence Brief, 1961–1977
Authors: Lebovic James H
Published: December 2021

A study of the daily briefings of US presidents by the intelligence community offers a useful test of whether governments can surmount intragovernmental influences in the acquisition and processing of information. A finding that the briefs somehow anticipate events would suggest that governments—their leaders and organizations—rise above political incentives and institutional practices to approach the rationality that realist and liberal scholars attribute to states. This study, thus, examines which countries appear in (the now declassified) daily intelligence briefs of the 1961–(January)1977 period, covering the Kennedy, Johnson, Nixon, and Ford years. It not only finds evidence that the selection of countries for the briefs favors countries referenced in prior briefs (per the foreign-policy literature) but also finds significant evidence that the appearance of countries, in the briefs, anticipates their increased activity in the period to follow (per a rational model).
Selection for seed size has uneven effects on specialized metabolite abundance in oat (Avena sativaL.)
Authors: Brzozowski Lauren J , Hu Haixiao , Campbell Malachy T , Broeckling Corey D , Caffe Melanie , Gutiérrez Lucía , Smith Kevin P , Sorrells Mark E , Gore Michael A , Jannink Jean-Luc
Published: December 2021

Plant breeding strategies to optimize metabolite profiles are necessary to develop health-promoting food crops. In oats (Avena sativa L.), seed metabolites are of interest for their antioxidant properties, yet have not been a direct target of selection in breeding. In a diverse oat germplasm panel spanning a century of breeding, we investigated the degree of variation of these specialized metabolites and how it has been molded by selection for other traits, like yield components. We also ask if these patterns of variation persist in modern breeding pools. Integrating genomic, transcriptomic, metabolomic, and phenotypic analyses for three types of seed specialized metabolites—avenanthramides, avenacins, and avenacosides—we found reduced heritable genetic variation in modern germplasm compared with diverse germplasm, in part due to increased seed size associated with more intensive breeding. Specifically, we found that abundance of avenanthramides increases with seed size, but additional variation is attributable to expression of biosynthetic enzymes. In contrast, avenacoside abundance decreases with seed size and plant breeding intensity. In addition, these different specialized metabolites do not share large-effect loci. Overall, we show that increased seed size associated with intensive plant breeding has uneven effects on the oat seed metabolome, but variation also exists independently of seed size to use in plant breeding. This work broadly contributes to our understanding of how plant breeding has influenced plant traits and tradeoffs between traits (like growth and defense) and the genetic bases of these shifts.
Combining genetic resources and elite material populations to improve the accuracy of genomic prediction in apple
Authors: Cazenave Xabi , Petit Bernard , Lateur Marc , Nybom Hilde , Sedlak Jiri , Tartarini Stefano , Laurens François , Durel Charles-Eric , Muranty Hélène
Published: December 2021

Genomic selection is an attractive strategy for apple breeding that could reduce the length of breeding cycles. A possible limitation to the practical implementation of this approach lies in the creation of a training set large and diverse enough to ensure accurate predictions. In this study, we investigated the potential of combining two available populations, i.e., genetic resources and elite material, in order to obtain a large training set with a high genetic diversity. We compared the predictive ability of genomic predictions within-population, across-population or when combining both populations, and tested a model accounting for population-specific marker effects in this last case. The obtained predictive abilities were moderate to high according to the studied trait and small increases in predictive ability could be obtained for some traits when the two populations were combined into a unique training set. We also investigated the potential of such a training set to predict hybrids resulting from crosses between the two populations, with a focus on the method to design the training set and the best proportion of each population to optimize predictions. The measured predictive abilities were very similar for all the proportions, except for the extreme cases where only one of the two populations was used in the training set, in which case predictive abilities could be lower than when using both populations. Using an optimization algorithm to choose the genotypes in the training set also led to higher predictive abilities than when the genotypes were chosen at random. Our results provide guidelines to initiate breeding programs that use genomic selection when the implementation of the training set is a limitation.
Fusion transcripts and their genomic breakpoints in polyadenylated and ribosomal RNA–minus RNA sequencing data
Authors: Hoogstrate Youri , Komor Malgorzata A , Böttcher René , van Riet Job , van de Werken Harmen J G , van Lieshout Stef , Hoffmann Ralf , van den Broek Evert , Bolijn Anne S , Dits Natasja , Sie Daoud , van der Meer David , Pepers Floor , Bangma Chris H , van Leenders Geert J L H , Smid Marcel , French Pim J , Martens John W M , van Workum Wilbert , van der Spek Peter J , Janssen Bart , Caldenhoven Eric , Rausch Christian , de Jong Mark , Stubbs Andrew P , Meijer Gerrit A , Fijneman Remond J A , Jenster Guido W
Published: December 2021

Background

Fusion genes are typically identified by RNA sequencing (RNA-seq) without elucidating the causal genomic breakpoints. However, non–poly(A)-enriched RNA-seq contains large proportions of intronic reads that also span genomic breakpoints.

Results

We have developed an algorithm, Dr. Disco, that searches for fusion transcripts by taking an entire reference genome into account as search space. This includes exons but also introns, intergenic regions, and sequences that do not meet splice junction motifs. Using 1,275 RNA-seq samples, we investigated to what extent genomic breakpoints can be extracted from RNA-seq data and their implications regarding poly(A)-enriched and ribosomal RNA–minus RNA-seq data. Comparison with whole-genome sequencing data revealed that most genomic breakpoints are not, or minimally, transcribed while, in contrast, the genomic breakpoints of all 32 TMPRSS2-ERG–positive tumours were present at RNA level. We also revealed tumours in which the ERG breakpoint was located before ERG, which co-existed with additional deletions and messenger RNA that incorporated intergenic cryptic exons. In breast cancer we identified rearrangement hot spots near CCND1 and in glioma near CDK4 and MDM2 and could directly associate this with increased expression. Furthermore, in all datasets we find fusions to intergenic regions, often spanning multiple cryptic exons that potentially encode neo-antigens. Thus, fusion transcripts other than classical gene-to-gene fusions are prominently present and can be identified using RNA-seq.

Conclusion

By using the full potential of non–poly(A)-enriched RNA-seq data, sophisticated analysis can reliably identify expressed genomic breakpoints and their transcriptional effects.
The Effects of Political Incivility on Political Trust and Political Participation: A Meta-Analysis of Experimental Research
Authors: Van’t Riet Jonathan , Van Stekelenburg Aart
Published: December 2021

A great deal of experimental research has focused on how political incivility affects ordinary citizens. A common finding is that incivility reduces political trust. Effects on political participation have also been investigated, but seem less consistent across studies. The results of a systematic review and meta-analysis, including a total of 24 manuscripts containing 35 studies, revealed that the estimated effect of political incivility on political trust was significant, Hedges’ g = −0.19 [95% CI: −0.30, −0.09]. The effect was small, however, and some indication of publication bias was found. The effect was stronger when the incivility was communicated through video versus other media, and for studies conducted in the United States versus Europe. The estimated effect of political incivility on political participation was almost non-existent, g = −0.02 [−0.11, 0.08], although it was significantly stronger (more negative) for studies conducted in Europe rather than in the United States.
Cold War Psychiatry, Extremism, and Expertise: The “Special Committee on the Political Abuse of Psychiatry”
Authors: Heath-Kelly Charlotte
Published: December 2021

Throughout the history of psychiatric ethical professionalization, the question of the “extremist” contextualizes and frames the limits of medical practice. Using archival research at the Royal College of Psychiatrists, the article explores how professional committees debated medical ethics after evidence of psychiatric participation in national security measures against dissidents. British, American, and global professional associations organized a prominent struggle against Soviet membership of the World Psychiatric Association in the 1970s and 1980s—reconstituting the field of professional expertise through Cold War geopolitics. The Special Committee on the Political Abuse of Psychiatry was formed in 1978 at the British Royal College of Psychiatry to publicize the medical detention of dissidents in the USSR and to pursue the expulsion of the USSR delegation from global professional fora. In doing so, it constituted an identity for Global Mental Health (vis-à-vis Soviet abusive practice) as impartial, objective, and uncompromised. However, this article explores the many ambiguities that complicate the performative constitution of Western psychiatry as good, and Soviet psychiatry as bad—reflecting on the political dynamics, and philosophy of science, which underwrote the struggle for global expertise.
Factors associated with bovine respiratory disease case fatality in feedlot cattle
Authors: Blakebrough-Hall Claudia , Hick Paul , Mahony T J , González Luciano A
Published: December 2021

Bovine respiratory disease (BRD) is the primary cause of morbidity and mortality in cattle feedlots. There is a need to understand what animal health and production factors are associated with increased mortality risk due to BRD. The aim of the present study was to explore factors associated with BRD case fatality in feedlot cattle. Four pens totaling 898 steers were monitored daily for visual signs of BRD such as difficult breathing and coughing, and animals exhibiting signs of BRD were taken to the hospital shed for further examination and clinical measures. Blood samples were obtained at feedlot entry and at time of first BRD pull from animals diagnosed with BRD (n = 121) and those that died due to BRD confirmed by postmortem examination (n = 16; 13.2% case fatality rate). Mixed-effects linear regression models were used to estimate differences in animal health and production factors and the relative concentrations of 34 identified blood metabolites between animals that survived versus those that died. Generalized linear mixed-effects models were used to obtain the odds of being seronegative (at both feedlot entry and first BRD pull) to 5 BRD viruses and having a positive nasal swab result at the time of first pull in died and survived animals. Animals that died from BRD had lower average daily gain (ADG), reduced weight at first BRD pull, higher visual BRD scores and received more treatments for BRD compared with animals that survived BRD (P < 0.05). The odds of being seronegative for bovine viral diarrhea virus 1 (BVDV-1) were 5.66 times higher for animals that died compared with those that survived (P = 0.013). The odds of having a positive bovine coronavirus nasal swab result were 13.73 times higher in animals that died versus those that survived (P = 0.007). Animals that died from BRD had higher blood concentrations of α glucose chain, β-hydroxybutyrate, leucine, phenylalanine, and pyruvate compared with those that survived (P < 0.05). Animals that died from BRD had lower concentrations of acetate, citrate, and glycine compared with animals that survived (P < 0.05). The results of the current study suggest that ADG to first BRD pull, weight at first BRD pull, visual BRD score, the number of BRD treatments, seronegativity to BVDV-1, virus positive to BCoV nasal swab, and that certain blood metabolites are associated with BRD case fatality risk. The ability of these measures to predict the risk of death due to BRD needs further research.
Application of seismic multiattribute machine learning to determine coal strata thickness
Authors: Wu Yanhui , Wang Wei , Zhu Guowei , Wang Peng
Published: December 2021

The coal mining industry is developing automated and intelligent coal mining processes. Accurate determination of the geological conditions of working faces is an important prerequisite for automated mining. The use of machine learning to extract comprehensive attributes from seismic data and the application of that data to determine the coal strata thickness has become an important area of research in recent years. Conventional coal strata thickness interpretation methods do not meet the application requirements of mines. Determining the coal strata thickness with machine learning solves this problem to a large extent, especially for issues of exploration accuracy. In this study, we use seismic exploration data from the Xingdong coal mine, with the 1225 working face as the research object, and we apply seismic multiattribute machine learning to determine the coal strata thickness. First, through optimal selection, we perform seismic multiattribute extraction and optimal multiparameter selection by selecting the seismic attributes with good responses to the coal strata thickness and extracting training samples. Second, we optimise the model through a trial-and-error method and use machine learning for training. Finally, we illustrate the advantages of this method using actual data. We compare the results of the proposed model with results based on a single attribute, The results show that application of seismic multiattribute machine learning to determine coal strata thickness meets the requirements of geological inspection and has a good application performance and practical significance in complex areas.
Biot's equations-based reservoir parameter inversion using deep neural networks
Authors: Xiong Fansheng , Yong Heng , Chen Hua , Wang Han , Shen Weidong
Published: December 2021

Reservoir parameter inversion from seismic data is an important issue in rock physics. The traditional optimisation-based inversion method requires high computational expense, and the process exhibits subjectivity due to the nonuniqueness of generated solutions. This study proposes a deep neural network (DNN)-based approach as a new means to analyse the sensitivity of seismic attributes to basic rock-physics parameters and then realise fast parameter inversion. First, synthetic data of inputs (reservoir properties) and outputs (seismic attributes) are generated using Biot's equations. Then, a forward DNN model is trained to carry out a sensitivity analysis. One can in turn investigate the influence of each rock-physics parameter on the seismic attributes calculated by Biot's equations, and the method can also be used to estimate and evaluate the accuracy of parameter inversion. Finally, DNNs are applied to parameter inversion. Different scenarios are designed to study the inversion accuracy of porosity, bulk and shear moduli of a rock matrix considering that the input quantities are different. It is found that the inversion of porosity is relatively easy and accurate, while more information is needed to make the inversion more accurate for bulk and shear moduli. From the presented results, the new approach makes it possible to realise accurate and pointwise inverse modelling with high efficiency for actual data interpretation and analysis.
Fracture characteristics of basic roof and mechanism of strata behavior in a pillarless working face
Authors: Guo Shuai , Tai Yang , Wang Zi-Wei , Shi Bo-Wen , Yang Kun
Published: December 2021

As a research hotspot, pillarless coal mining technology has a high resource recovery rate and low roadway surrounding rock stress. To grasp the three-dimensional fracture characteristics of the basic roof is the basic to reveal the strata behavior mechanism in the pillarless working face. Thus, aiming at pillarless coal mining, the analytical solution of three-dimensional fracture mechanics models of a basic roof was analyzed by elastic thin plate theory; the principal stress distribution of a basic roof being cut by continuous artificial fractures and discontinuous artificial fractures was analyzed; the fracture characteristics of the basic roof was revealed and the strata behavior mechanism was obtained. The following conclusions can be drawn: (i) an ‘O + X’ fracture occurred in the basic roof of a traditional working face, while an opposite-trapezoid-shaped or ≡-shaped fracture was generated in the pillarless working face. (ii) When the basic roof broke, the trapezoidal or rectangular hinged plate traversed the entire pillarless working face, causing the end supports to be pressured, while the trapezoidal hinged plate did not traverse the entire traditional working face and the end supports were not pressured. (iii) The break of a basic roof induced by artificial fractures in pillarless mining reduced or even eliminated the triangular hinged plate area along the goaf edges, making a roadway in the stress relief zone. (iv) Compared with the fractures in traditional roadways and in a discontinuous roof-cutting roadway, continuous fractures could minimize surrounding rock stress and make it easy to maintain a roof-cutting roadway.
Evaluating the Efficacy of a Screening Protocol for Severe Acute Respiratory Syndrome Coronavirus 2 Virus in Asymptomatic Preoperative/Preprocedural Patients at a Military Hospital
Authors: Barber Cooper , Syski Andrew , Leaird Jennifer , Call R Christopher , Williams Ann , Learn Peter
Published: December 2021

Introduction

Facing the COVID-19 pandemic, many hospitals implemented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening protocols before aerosol-generating procedures (AGPs) in an effort to protect patients and health care workers. Given the limited prior evidence on the effectiveness of such protocols, we report the process improvement experience at a military treatment facility.

Materials and Methods

We evaluated the outcomes of patients undergoing AGPs from March to September 2020, divided into three cohorts: a preprotocol (PP) cohort who did not receive screening, an early testing (ET) cohort representing the early months of the screening protocol, and a late testing (LT) cohort managed under adaptive modifications to the screening protocol. We recorded identifiable post-procedure COVID-19 diagnoses. The study was approved as a process improvement protocol and was determined not to meet criteria for human subject research through an institutional approval process.

Results

Across the three cohorts, 4520 procedures were performed: 422 PP, 1297 ET, and 2801 LT. Among 4098 procedures in the ET and LT cohorts, 12 asymptomatic patients tested positive for SARS-CoV-2 (0.29% positivity rate). One left the health system before completing the procedure and another proceeded urgently under COVID precautions, while 10 were rescheduled and completed at a later date; 7 were cleared using a test-based strategy, while 3 were cleared using a time-based strategy. Of 445 patients who had SARS-CoV-2 tests performed within 30 days following their procedures, three patients with negative preoperative tests had a positive test within 30 days, all in the LT cohort but had evidence of acquiring the infection after the procedure or had a false-positive test.

Conclusions

Our strategy of preprocedural SARS-CoV-2 testing successfully identified asymptomatic infected patients before surgery. Care was delayed for most of these patients without apparent detriment. Adaptation to a time-based strategy for clearance might reduce such delays, but other considerations may still influence how soon procedures should be completed after a positive test.
Interluekin-6 inhibitors for the treatment of adult-onset Still’s disease
Authors: Kaneko Yuko
Published: December 2021

Adult-onset Still’s disease is a systemic inflammatory disease characterized by high spiking fever, arthritis, evanescent skin rash, leukocytosis, and hyperferritinemia. The pathogenesis of adult-onset Still’s disease has not been fully understood yet; however, multiple proinflammatory cytokines, such as IL-1β and IL-6, play important roles in the development of adult-onset Still’s disease. IL-6 is a multifunctional cytokine that accelerates the differentiation of macrophages and cytotoxic T-cells and chemotaxis of neutrophils and macrophages. Serum concentrations of IL-6 well correlate with disease activity of adult-onset Still’s disease, and blockade of IL-6 has been proven to be effective in active adult-onset Still’s disease. This review will focus on the recent understanding of the role of proinflammatory cytokines of adult-onset Still’s disease and the efficacy of IL-6 inhibitors for the treatment of adult-onset Still’s disease.
Phenotypic landscape of systemic lupus erythematosus: An analysis of the Kyoto Lupus Cohort
Authors: Iwasaki Takeshi , Doi Hiroshi , Tsuji Hideaki , Tabuchi Yuya , Hashimoto Motomu , Kitagori Koji , Akizuki Shuji , Murakami Kosaku , Nakashima Ran , Yoshifuji Hajime , Yamamoto Wataru , Tanaka Masao , Ohmura Koichiro , Morinobu Akio
Published: December 2021

Objectives

The present study aimed to clarify comprehensive relationships among the clinical variables of systemic lupus erythematosus (SLE).

Methods

We retrospectively surveyed 32 clinical variables in 581 patients and conducted comprehensive association studies among SLE clinical phenotypes. A univariate analysis of all possible combinations was performed, and the results of phenotypic correlations were reduced into two dimensions. We also created a regression formula using L1 regularisation (LASSO) to calculate the probability of exhibiting each phenotype.

Results

The univariate analysis identified 26 correlations, including multiple phenotypes with low complement. Some unpredicted correlations were identified, including fever and the anti-Sm antibody (odds ratio; OR = 2.3, p = 1.6 × 10–5) or thrombocytopenia and psychosis (OR = 3.7, p = 3.2 × 10–5). The multivariate analysis accurately estimated the probability of exhibiting each phenotype (area under the curve > 0.7) in 10 out of 20 phenotypes.

Conclusions

The present results show the phenotypic architecture of SLE and represent a model for estimating the probability of exhibiting each phenotype. They also offer insights into the pathology of SLE and estimating the probability of the onset of new phenotypes in clinical practice.
The dominant TP53 hotspot mutation in
IDH
-mutant astrocytoma, R273C, has distinctive pathologic features and sex-specific prognostic implications
Authors: Marker Daniel F , Agnihotri Sameer , Amankulor Nduka , Murdoch Geoffrey H , Pearce Thomas M
Published: December 2021

Background

Infiltrative astrocytic tumors with and without isocitrate dehydrogenase (IDH) mutation frequently contain mutations in the TP53 tumor suppressor gene. Disruption of normal p53 protein activity confers neoplastic cells with a number of oncogenic properties and is a common feature of aggressive malignancies. However, the high prevalence of TP53 mutation and its pathogenic role in IDH-mutant (IDHmut) astrocytoma is not well understood.

Methods

We performed a retrospective analysis of molecular and clinical data from patients with IDHmut astrocytoma at the University of Pittsburgh Medical Center between 2015 and 2019 as our initial cohort. We validated and expanded our findings using molecular and clinical data from The Cancer Genome Atlas.

Results

We show that the TP53 mutational spectrum in IDHmut astrocytomas is dominated by a single hotspot mutation that codes for the R273C amino acid change. This mutation is not enriched in IDH-wildtype astrocytomas. The high prevalence of TP53R273C mutation is not readily explained by known mutagenic mechanisms, and TP53R273C mutant tumors have lower transcriptional levels of proliferation-related genes compared to IDHmut astrocytomas harboring other forms of mutant p53. Despite lower proliferation, TP53R273C mutant tumors tend to progress more quickly and have a shorter overall survival than those with other TP53 mutations, particularly in male patients.

Conclusions

Our findings suggest that compared to other TP53 mutations, IDHmut astrocytomas may select for TP53R273C mutations during tumorigenesis. The genotype, sex, and mutation-specific findings are clinically relevant and should prompt further investigation of TP53R273C.
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Monoclonal Antibody MHAA4549A in Patients With Acute Uncomplicated Influenza A Infection
Authors: Lim Jeremy J , Dar Sadia , Venter Dirk , Horcajada Juan P , Kulkarni Priya , Nguyen Allen , McBride Jacqueline M , Deng Rong , Galanter Joshua , Chu Tom , Newton Elizabeth M , Tavel Jorge A , Peck Melicent C
Published: December 2021

Background

MHAA4549A, a human monoclonal antibody targeting the influenza A hemagglutinin stalk, neutralizes influenza A virus in animal and human volunteer challenge studies. We investigated the safety and tolerability, efficacy, and pharmacokinetics of MHAA4549A in outpatients with acute, uncomplicated influenza A infection.

Methods

This was a phase 2, randomized, double-blind, placebo-controlled trial of single intravenous (IV) doses of 3600 mg or 8400 mg of MHAA4549A or IV placebo in adult outpatients testing positive for influenza A. Patients were enrolled across 35 sites in 6 countries. Randomization and dosing occurred within ≤72 hours of symptom onset; the study duration was 14 weeks. The primary end point was the nature and frequency of adverse events (AEs). Secondary end points included median time to alleviation of all influenza symptoms, effects on nasopharyngeal viral load and duration of viral shedding, and MHAA4549A serum pharmacokinetics.

Results

Of 125 randomized patients, 124 received study treatment, with 99 confirmed positive for influenza A by central testing. The frequency of AEs between the MHAA4549A and placebo groups was similar; nausea was most common (8 patients; 6.5%). MHAA4549A serum exposure was confirmed in all MHAA4549A-treated patients and was dose-proportional. No hospitalizations or deaths occurred. Between the MHAA4549A and placebo groups, no statistically significant differences occurred in the median time to alleviation of all symptoms, nasopharyngeal viral load, or duration of viral shedding.

Conclusions

While MHAA4549A was safe and well tolerated with confirmed exposure, the antibody did not improve clinical outcomes in patients with acute uncomplicated influenza A infection.
How Teaching in Underserved Schools Affects Beliefs about Education Inequality and Reform
Authors: Conn Katharine M , Lovison Virginia S , Mo Cecilia Hyunjung
Published: December 2021

What effect does experience as a teacher—the street-level bureaucrat of the education system—have on one’s education policy opinions and beliefs? We consider the case of Teach For America (TFA), a prominent alternative teacher preparation provider with an admissions process that generates quasi-random variation in applicants’ likelihood of being a teacher. We leverage this variation using a regression discontinuity design and collect outcome data by surveying TFA applicants regarding education inequality and reform. We find that teaching in underserved schools leads individuals to favor more structural as opposed to individualistic explanations for poor student outcomes. When asked to evaluate education reform strategies to address education inequality, we find that these teachers are more likely to support policy prescriptions that improve both student outcomes and teachers’ working conditions, namely investments that expand access to school-based services (e.g., meals, counselors) for low-income children. Similarly, teaching experience causes no change in support, and in some cases, less support for policy levers that do not unambiguously improve student outcomes or teachers’ working conditions, such as market-based school reforms. Moreover, experience in the classroom cultivates greater optimism in the potential of educators and schools.
Combined intermittent and sustained hypoxia is a novel and deleterious cardio-metabolic phenotype
Authors: Zhen Xin , Moya Esteban A , Gautane Mary , Zhao Huayi , Lawrence Elijah S , Gu Wanjun , Barnes Laura A , Yuan Jason X-J , Jain Pritesh P , Xiong Mingmei , Catalan Serra Pablo , Pham Luu V , Malhotra Atul , Simonson Tatum S , Mesarwi Omar A
Published: December 2021

Study Objectives

Chronic obstructive pulmonary disease and obstructive sleep apnea overlap syndrome is associated with excess mortality, and outcomes are related to the degree of hypoxemia. People at high altitudes are susceptible to periodic breathing, and hypoxia at altitude is associated with cardio-metabolic dysfunction. Hypoxemia in these scenarios may be described as superimposed sustained hypoxia (SH) plus intermittent hypoxia (IH), or overlap hypoxia (OH), the effects of which have not been investigated. We aimed to characterize the cardio-metabolic consequences of OH in mice.

Methods

C57BL/6J mice were subjected to either SH (FiO2 = 0.10), IH (FiO2 = 0.21 for 12 h, and FiO2 oscillating between 0.21 and 0.06, 60 times/hour, for 12 h), OH (FiO2 = 0.13 for 12 h, and FiO2 oscillating between 0.13 and 0.06, 60 times/hour, for 12 h), or room air (RA), n = 8/group. Blood pressure and intraperitoneal glucose tolerance test were measured serially, and right ventricular systolic pressure (RVSP) was assessed.

Results

Systolic blood pressure transiently increased in IH and OH relative to SH and RA. RVSP did not increase in IH, but increased in SH and OH by 52% (p < .001) and 20% (p = .001). Glucose disposal worsened in IH and improved in SH, with no change in OH. Serum low- and very-low-density lipoproteins increased in OH and SH, but not in IH. Hepatic oxidative stress increased in all hypoxic groups, with the highest increase in OH.

Conclusions

OH may represent a unique and deleterious cardio-metabolic stimulus, causing systemic and pulmonary hypertension, and without protective metabolic effects characteristic of SH.
Equity: now assisting volunteers? A case comment on Khan v Mahmood [2021] EWHC 597 (Ch)
Authors: Freeman Matthew , Pullar Zachariah
Published: December 2021

The decision in Khan v Mahmood is a further example in recent years of the High Court grappling with the issue of when a gift, imperfect at law, might yet be complete in equity. The case is notable for how it treated (or omitted to treat) key authorities on imperfect gifts; its approach to, and analysis of the Pennington v Waine ‘unconscionability’ test; and the broader implications of the direction of travel established by Pennington for equity’s conventional stance that it ‘will not assist a volunteer’.
New insights into colorectal cancer liver metastasis carcinogenesis and its effect with moxibustion
Authors: Song Ya-Fang , Pei Li-Xia , Guo Jing , Zhuang Yi , Wang Yu-Hang , Zhao Ting-Ting , Chen Lu , Zhou Jin-Yong , Sun Jian-Hua
Published: December 2021

Background

Chemotherapeutic drugs creates severe adverse reactions for colorectal cancer. Moxibustion confers clinical benefits for postoperative patients undergoing chemotherapy, it will fill the blank period of western medicine treatment and provide useful help for tumor patients to prevent recurrence and metastasis, but the physiological mechanisms behind the antitumor effects are unclear. This study was aimed to determine the effect and characterize the differential cytokines and gene expression profiles in intrasplenic transplanted GFP-HCT-116 cells-induced tumors model by Pre-Mox, Post-Mox and Pre-Post-Mox intervention.

Methods

Human CRC cells with GFP fluorescence were implanted via intrasplenic injection into Balb/c nude mice spleens. Moxibustion stimulation was applied to the BL18 and ST36 acupoints. The model control (MC) group were given no treatment. Pre-Mox mice were received moxibustion for 2 weeks before HCT-116 cell injection. Post-Mox mice received moxibustion for 3 weeks after CRC cell injection. Pre-Post-Mox mice received moxibustion for 5 weeks (2 weeks before and 3 weeks after CRC cell injection). Peripheral bloods were collected, pooled and assayed using a RayBio® mouse inflammation antibody array. Multi-Analyte Suspension Array was opted for verification. RNA isolated from liver paracancerous tissues from the control group and the experimental groups was subjected to RNA-seq, and then screened out significant differences for in-depth verification.

RESULTS

The results showed that moxibustion stimulation increased the survival rate and decreased CRC liver metastasis. With the help of Multi-Analyte Suspension Array and RNA-seq, we screened significant differential expression of cytokines and RNA, then further verified them. The metastasis rate decreased significantly from 100% (10/10, MC group) to 50% (6/12, Pre-Mox group), to 46% (6/13, Post-Mox group), and further to 25% (3/12, Pre-Post-Mox group). Cytokine chips were used significant differences were found in MIP-3α, MDC, IL-6, and IL-1a. Transcriptomic analysis suggested that the low-dose combination of Pre-Mox and Post-Mox modulated larger gene sets than the single treatment. We identified a small subset of genes, like APOA4, IGFBP5, IGFBP6, TIMP1, and MGP, as potential molecular targets involved in the preventive action of the combination of Pre-Mox and Post-Mox.

Conclusions

Taken together, the current results provide the first evidence in support of the chemopreventive effect of a combination of Pre-Mox and Post-Mox in CRC. Moreover, the cytokines and transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from colonic cancer to liver metastasis as well as the cancer inhibitory effects and potential molecular targets of Pre-Post-Mox.
Understanding barriers to consumers to stop washing raw poultry through in-depth interviews
Authors: Gilman Abigail , Henley Shauna C. , Quinlan Jennifer
Published: December 2021

Purpose

Foodborne illness from poultry may be associated with improper handling that results in cross contamination. Washing of raw poultry is one practice that can lead to cross contamination. Some consumers continue to wash raw poultry after learning that not washing raw poultry is the safe behavior. There is a need to better understand why some consumers continue this practice and identify barriers to them adopting the correct behavior.

Design/methodology/approach

This research utilized qualitative, in-depth interviews to understand some consumer's barriers to adopting the behavior of not washing raw poultry. The interview questioning route was iteratively developed and designed to allow both structure and flexibility. Questions were anchored in the Transtheoretical Model of Behavior Change. Interviews (N = 23) were conducted over Zoom. Thematic analysis identified themes around consumers' resistance to adopting the correct behavior for handling raw poultry.

Findings

Results from the thematic analysis indicate that chicken preparation methods were primarily influenced by family. A desire to control the process of preparing food, lack of trust in chicken processing, and the habitual nature of the behavior all contributed to the continuation of washing raw poultry. Over half of the participants (61%) expressed interest in changing behaviors in the future. Needing supporting scientific evidence, and an alternative behavior to replace washing were two key factors to support the development of future public health messaging.

Originality/value

This study investigates the barriers to safe raw poultry handling utilizing in-depth interviews and contributes to the development of more effective public health messaging.