bluuebunny/crossref_metadata_2025 huggingface dataset:
LMPred: predicting antimicrobial peptides using pre-trained language models and deep learning
Authors: Dee William
Published: March 2022

Motivation

Antimicrobial peptides (AMPs) are increasingly being used in the development of new therapeutic drugs in areas such as cancer therapy and hypertension. Additionally, they are seen as an alternative to antibiotics due to the increasing occurrence of bacterial resistance. Wet-laboratory experimental identification, however, is both time-consuming and costly, so in silico models are now commonly used in order to screen new AMP candidates.

Results

This paper proposes a novel approach for creating model inputs; using pre-trained language models to produce contextualized embeddings, representing the amino acids within each peptide sequence, before a convolutional neural network is trained as the classifier. The results were validated on two datasets—one previously used in AMP prediction research, and a larger independent dataset created by this paper. Predictive accuracies of 93.33% and 88.26% were achieved, respectively, outperforming previous state-of-the-art classification models.

Availability and implementation

All codes are available and can be accessed here: https://github.com/williamdee1/LMPred_AMP_Prediction.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
InParanoid-DIAMOND: faster orthology analysis with the InParanoid algorithm
Authors: Persson Emma , Sonnhammer Erik L L
Published: March 2022

Predicting orthologs, genes in different species having shared ancestry, is an important task in bioinformatics. Orthology prediction tools are required to make accurate and fast predictions, in order to analyze large amounts of data within a feasible time frame. InParanoid is a well-known algorithm for orthology analysis, shown to perform well in benchmarks, but having the major limitation of long runtimes on large datasets. Here, we present an update to the InParanoid algorithm that can use the faster tool DIAMOND instead of BLAST for the homolog search step. We show that it reduces the runtime by 94%, while still obtaining similar performance in the Quest for Orthologs benchmark.

Availability and implementation

The source code is available at (https://bitbucket.org/sonnhammergroup/inparanoid).

Supplementary information

Supplementary data are available at Bioinformatics online.
Fixation and preservation contribute to distortion in vertebrate museum specimens: a 10-year study with the lizardAnolis sagrei
Authors: Maayan Inbar , Reynolds R Graham , Goodman Rachel M , Hime Paul M , Bickel Ryan , Luck E Allen , Losos Jonathan B
Published: March 2022

Preservation of museum specimens depends on chemical fixation and preservation, processes that might distort the original material. Relatively few studies have examined the effects of preservation in potentially susceptible soft-bodied taxa, such as herpetofauna, and those that have rarely extend over more than a few months. We collected six common morphological measurements from the same set of radiographed specimens of the Neotropical lizard Anolis sagrei over nearly 10 years to investigate whether morphometric changes result from fixation in formalin and/or subsequent long-term preservation in ethanol. Snout–vent length declined by 3.5% on average over 10 years, starting almost immediately with fixation and continuing to decline during fluid preservation, eventually levelling off at 40 weeks and beyond. The mostly ossified component of snout–vent length, spine length, declined by 2% on average, but the decline did not begin until fluid preservation commenced and continued throughout the duration of the study. Other characters showed significant decline over the course of the study. Our findings suggest caution when combining fresh and preserved specimens or specimens of different preservation ages, because a decline in snout–vent length but not in other allometrically proportional characters will introduce error when correcting characters for body size in preserved animals.
An Update on Laboratory-Based Diagnostic Biomarkers for Multiple Sclerosis and Beyond
Authors: Saadeh Ruba S , Ramos Paola A , Algeciras-Schimnich Alicia , Flanagan Eoin P , Pittock Sean J , Willrich Maria Alice
Published: March 2022

Background

Multiple sclerosis (MS) is an immune-mediated central nervous system (CNS) inflammatory demyelinating disease in which analysis of clinical presentation, imaging studies, and laboratory tests aid in diagnosis.

Content

This review discusses laboratory tests ordered to rule out and rule in MS, such as the traditional measurement of cerebrospinal fluid (CSF) IgG index and oligoclonal bands. Biomarkers discovered in the past 2 decades, such as aquaporin-4 (AQP4) antibodies and myelin oligodendrocyte glycoprotein (MOG) antibodies, have been incorporated into clinical practice in the diagnosis of disorders referred to as MS mimics. The importance of test selection, assay methodology, optimal sample for testing, and diagnostic utility of these biomarkers is reviewed. Other laboratory testing that can aid in the differentiation between MS and these biomarker-defined CNS demyelinating diseases is described. There is a focus on emerging biomarkers such as the use of kappa immunoglobulin free light chain concentration in CSF and kappa CSF index measurement as an alternative to oligoclonal bands which has a potential for an improvement in laboratory workflows. Finally, the role of biomarkers of disease activity and prognosis are discussed, including neurofilament light chain, glial fibrillary acidic protein, and myelin basic protein. Future perspectives with improved laboratory testing tools and discovery of additional biomarkers are provided.

Laboratory testing for demyelinating disorders using CSF and serum are routine practices that can benefit from an update, as novel biomarker-defined entities have reduced the potential for MS misdiagnosis, and CSF/serum biomarkers reinstated in the diagnostic criteria of MS.
Sublethal pesticide exposure influences behaviour, but not condition in a widespread Australian lizard
Authors: Contador-Kelsall Isabella , Maute Kimberly , Story Paul , Hose Grant C , French Kristine
Published: March 2022

Assessment of non-target impacts of pesticides used widely in agriculture and pest management rarely considers reptiles. Despite their integral role in all ecosystems, particularly arid ecosystems, reptiles are not included in risk assessments. Two pesticides used in agricultural pest management are fipronil and fenitrothion. Here, we used a field-based BACI design experiment in semi-arid Australia to investigate the impact of these pesticides on basic physiological and behavioural parameters of a common arid-zone lizard species, Pogona vitticeps. Fipronil and fenitrothion were applied at ecologically relevant doses via oral gavage. Before and after dosing, blood, physical activity and body condition parameters were assessed. We found that temperature significantly influenced lizard activity in the morning period of movement; however, fipronil-treated individuals moved at least 49% less than fenitrothion-treated and control lizards from 7 days after dosing through to the end of the experiment. Physiological measures did not change significantly before or after exposure to both pesticides; however, other indicators showed evidence of exposure, which remained for the entirety of our monitoring period. On average, cholinesterase inhibition was still >30% compared with control lizards at the end of 4 weeks, and fipronil sulfone blood residues remained at 0.219 μg/ml. Our study provides novel insights into the impacts that common pesticides have on widespread lizard species. We show that an ecologically relevant low dose of fipronil alters the behaviour of P. vitticeps, which has the potential to impact longer-term survivability. Persistence of both pesticides in the blood of all treatment lizards throughout the experiment indicates they are unable to clear these toxins within a month of being exposed. This may be significant for compounding exposure and latent toxicity. These findings highlight the susceptibility that reptiles have to a selection of common pesticides and the inherent need for higher prominence in wildlife ecotoxicological research.
High-circulating gut microbiota-dependent metabolite trimethylamine N-oxide is associated with poor prognosis in pulmonary arterial hypertension
Authors: Yang Yicheng , Zeng Qixian , Gao Jianing , Yang Beilan , Zhou Jingjing , Li Ke , Li Li , Wang Anxin , Li Xin , Liu Zhihong , Luo Qin , Zhao Zhihui , Liu Bingyang , Xue Jing , Jiang Xue , Konerman Matthew C , Zheng Lemin , Xiong Changming
Published: March 2022

Aims

We aimed to examine the hypothesis that circulating trimethylamine-N-oxide (TMAO) levels serve as a biomarker in pulmonary arterial hypertension (PAH), and to determine whether 3,3-dimethyl-1-butanol (DMB), a TMAO inhibitor, exerted a protective effect in monocrotaline (MCT)-induced PAH rats.

Methods and results

In-patients with PAH were prospectively recruited from the Fuwai Hospital. Fasting blood samples were obtained to assess the TMAO levels and other laboratory values during the initial and second hospitalization. In a MCT-induced PAH rat, a normal diet and water supplemented with or without 1% DMB were administered for 4 weeks. The TMAO levels, haemodynamic examinations, changes in organ-tissue, and molecular levels were evaluated. In total, 124 patients with PAH were enrolled in this study. High TMAO levels were correlated with increased disease severity and poor prognosis even after adjusting for confounders. The TMAO levels in the rats decreased in the MCT + DMB group, accompanied by improved haemodynamic parameters, decreased right ventricular hypertrophy, and amelioration of pulmonary vascular remodelling. The decrease in abnormal apoptosis, excessive cell proliferation, transforming growth factor-β expression, and restoration of endothelial nitric oxide synthase after DMB treatment further explained the amelioration of PAH.

Conclusion

Increased TMAO levels were associated with poor prognosis in patients with PAH, and DMB played a protective effect in MCT-induced PAH rat.
Layer-specific Nos3 expression and genotypic distribution in bicuspid aortic valve aortopathy
Authors: Hill Jennifer C , Billaud Marie , Richards Tara D , Kotlarczyk Mary P , Shiva Sruti , Phillippi Julie A , Gleason Thomas G
Published: March 2022

OBJECTIVES

We hypothesized that expression and activity of nitric oxide synthase-3 enzyme (Nos3) in bicuspid aortic valve (BAV) aortopathy are related to tissue layer and Nos3 genotype.

METHODS

Gene expression of Nos3 and platelet and endothelial cell adhesion molecule-1 (Pecam1) and NOS activity were measured in intima-containing media and adventitial specimens of ascending aortic tissue. The presence of 2 Nos3 single-nucleotide polymorphisms (SNPs; −786T/C and 894G/T) was determined for non-aneurysmal (NA) and aneurysmal patients with BAV (n = 40, 89, respectively); patients with tricuspid aortic valve (TAV) and aneurysm (n = 151); and NA patients with TAV (n = 100).

RESULTS

Elevated Nos3 relative to Pecam1 and reduced Pecam1 relative to a housekeeping gene were observed within intima-containing aortic specimens from BAV patients when compared with TAV patients. Lower Nos3 in the adventitia of aneurysmal specimens was noted when compared with specimens of NA aorta, independent of valve morphology. NOS activity was similar among cohorts in media/intima and decreased in the diseased adventitia, relative to control patients. Aneurysmal BAV patients exhibited an under-representation of the wild-type genotype for −786 SNP. No differences in genotype distribution were noted for 894 SNP. Primary intimal endothelial cells from patients with at least 1 C allele at −786 SNP exhibited lower Nos3 when compared with wild-type cells.

CONCLUSIONS

These findings of differential Nos3 in media/intima versus adventitia depending on valve morphology or aneurysm reveal new information regarding aneurysmal pathophysiology and support our ongoing assertion that there are distinct mechanisms giving rise to ascending aortopathy in BAV and TAV patients.
The genome sequence of the lesser marbled fritillary, Brenthis ino, and evidence for a segregating neo-Z chromosome
Authors: Mackintosh Alexander , Laetsch Dominik R , Baril Tobias , Foster Robert G , Dincă Vlad , Vila Roger , Hayward Alexander , Lohse Konrad
Published: March 2022

The lesser marbled fritillary, Brenthis ino (Rottemburg, 1775), is a species of Palearctic butterfly. Male Brenthis ino individuals have been reported to have between 12 and 14 pairs of chromosomes, a much-reduced chromosome number than is typical in butterflies. Here, we present a chromosome-level genome assembly for Brenthis ino, as well as gene and transposable element annotations. The assembly is 411.8 Mb in length with a contig N50 of 9.6 Mb and a scaffold N50 of 29.5 Mb. We also show evidence that the male individual from which we generated HiC data was heterozygous for a neo-Z chromosome, consistent with inheriting 14 chromosomes from one parent and 13 from the other. This genome assembly will be a valuable resource for studying chromosome evolution in Lepidoptera, as well as for comparative and population genomics more generally.
Engineering efficient termination of bacteriophage T7 RNA polymerase transcription
Authors: Calvopina-Chavez Diana G , Gardner Mikaela A , Griffitts Joel S
Published: March 2022

The bacteriophage T7 expression system is one of the most prominent transcription systems used in biotechnology and molecular-level research. However, T7 RNA polymerase is prone to read-through transcription due to its high processivity. As a consequence, enforcing efficient transcriptional termination is difficult. The termination hairpin found natively in the T7 genome is adapted to be inefficient, exhibiting 62% termination efficiency in vivo and even lower efficiency in vitro. In this study, we engineered a series of sequences that outperform the efficiency of the native terminator hairpin. By embedding a previously discovered 8-nucleotide T7 polymerase pause sequence within a synthetic hairpin sequence, we observed in vivo termination efficiency of 91%; by joining 2 short sequences into a tandem 2-hairpin structure, termination efficiency was increased to 98% in vivo and 91% in vitro. This study also tests the ability of these engineered sequences to terminate transcription of the Escherichia coli RNA polymerase. Two out of 3 of the most successful T7 polymerase terminators also facilitated termination of the bacterial polymerase with around 99% efficiency.
Contemporary outcomes of cardiac surgery patients supported by the intra-aortic balloon pump
Authors: Lorusso Roberto , Heuts Samuel , Jiritano Federica , Scrofani Roberto , Antona Carlo , Actis Dato Guglielmo , Centofanti Paolo , Ferrarese Sandro , Matteucci Matteo , Miceli Antonio , Glauber Mattia , Vizzardi Enrico , Sponga Sandro , Vendramin Igor , Garatti Andrea , de Vincentis Carlo , De Bonis Michele , Ajello Silvia , Troise Giovanni , Dalla Tomba Margherita , Serraino Filiberto
Published: March 2022

OBJECTIVES

Although the intra-aortic balloon pump (IABP) has been the most widely adopted temporary mechanical support device in cardiac surgical patients, its use has declined. The current study aimed to evaluate the occurrence and predictors of early mortality and complication rates in contemporary cardiac surgery patients supported by an IABP.

METHODS

A multicentre, retrospective analysis was performed of all consecutive cardiac surgical patients receiving perioperative balloon pump support in 8 centres between January 2010 to December 2019. The primary outcome was early mortality, and secondary outcomes were balloon-associated complications. A multivariable binary logistic regression model was applied to evaluate predictors of the primary outcome.

RESULTS

The study cohort consisted of 2615 consecutive patients. The median age was 68 years [25th percentile 61, 75th percentile 75 years], with the majority being male (76.9%), and a mean calculated 30-day mortality risk of 10.0%. Early mortality was 12.7% (n = 333), due to cardiac causes (n = 266), neurological causes (=22), balloon-related causes (n = 5) and other causes (n = 40). A composite end point of all vascular complications occurred in 7.2% of patients, and leg ischaemia was observed in 1.3% of patients. The most important predictors of early mortality were peripheral vascular disease [odds ratio (OR) 1.63], postoperative dialysis requirement (OR 10.40) and vascular complications (OR 2.57).

CONCLUSIONS

The use of the perioperative IABP proved to be safe and demonstrated relatively low complication rates, particularly for leg ischaemia. As such, we believe that specialists should not be held back to use this widely available treatment in high-risk cardiac surgical patients when indicated.
Inverse Mean Curvature Flow With Singularities
Authors: Choi Beomjun , Hung Pei-Ken
Published: March 2022

This paper concerns the inverse mean curvature flow (IMCF) running from the boundary of a convex body that has no regularity assumption. We study the evolution of singularities by looking at the blow-up tangent cone around each singular point. We prove that the cone also evolves by the IMCF and that each singularity is removed when the evolving cone becomes flat. As a result, we derive the exact waiting time for a weak solution to become a smooth solution. In particular, necessary and sufficient condition for the existence of a smooth classical solution is given.
Determination of Oxaliplatin and Curcumin in Combination via Micellar HPLC and Its Method Validation
Authors: Tiwari Ankita , Bose Devasish , Mishra Pooja , Jain Ankit , Jain Sanjay K
Published: March 2022

Background

A micellar-HPLC method was developed for the determination of oxaliplatin (OHP) and curcumin (CUR) employing a C18 column [4.6 × 250 mm, particle size (dp)  = 5 µm] and diode array detector.

Objective

A rapid, cost-effective, environmentally friendly, time-efficient, easy-to-handle, and safe method was developed.

Methods

The conditions were optimized for the estimation of OHP and CUR: 0.15 M sodium dodecyl sulfate (SDS) in 6% (v/v) pentanol buffered to pH 5.0 with a flow rate of 1.0 mL/min, injection volume of 20 µL, and detection at 325 nm. Different analytical parameters, including linearity, accuracy, precision, robustness, specificity, LOD, and LOQ, were determined in compliance with the International Council on Harmonisation (ICH) guidelines.

Results

The LOD (S/N = 3) of OHP was 0.004 µg/mL and for CUR it was 0.005 µg/mL. The calibration curves for OHP and CUR were linear over the range 0.015–10 µg/mL (determination coefficient r2 = 0.9999) and 0.015–10 µg/mL (r2 = 0.9994), respectively.

Conclusion

The drugs were eluted in <12 min and the developed method was applicable for analyzing multiple samples per day. Moreover, it was determined to be robust and was used to quantify OHP and CUR in mice serum/blood. The method could pave the way for quantitative analysis of these drugs during the development of a pharmaceutical preparation for the treatment of colorectal cancer.

Highlights

A simple, cost-effective, eco-friendly HPLC method was developed to simultaneously estimate oxaliplatin and curcumin. The developed method was validated as per the ICH guidelines.
Sleep Quality Among Burn Survivors and the Importance of Intervention: A Systematic Review and Meta-Analysis
Authors: Hutchinson Kelly Ann , Karmali Sarah Amirali , Abi-Jaoude Joanne , Edwards Thomas , Homsy Christopher
Published: March 2022

Burn survivors undergo a plethora of physiologic disturbances that can greatly affect the quality of life (QOL) and healing processes. This review aimed to systematically examine sleep quality among individuals with burns and to explore the effectiveness of interventions using a meta-analytic approach. A systematic review of the literature was conducted by searching for articles using various databases. Titles and abstracts were screened and full texts of retained articles were assessed based on eligibility criteria. Methodological quality was ascertained in all articles using various scales. Overall, 5323 articles were screened according to titles and abstracts and 25 articles were retained following full-text screening. Of the 25 articles, 17 were assessed qualitatively, while 8 were included in the meta-analysis. Based on the qualitative analysis, sleep was found to be negatively affected in patients with burn injuries. The subsample of eight articles included in the meta-analysis showed an overall weighted mean effect size (Hedges’s g) of 1.04 (SE = 0.4, 95% CI, z = 3.0; P < 0.01), indicating a large, positive effect of the intervention on sleep quality for patients with burn injuries. This review was able to demonstrate the detrimental effects of burn injury on sleep quality. Several interventions have been examined throughout the literature and have shown to be beneficial for sleep quality. However, there is great heterogeneity between existing interventions. The results from this review suggest that further research is needed before recommendations can be made as to which intervention is most effective at improving sleep in patients suffering from burn injuries.
Does Information About AI Regulation Change Manager Evaluation of Ethical Concerns and Intent to Adopt AI?
Authors: Cuéllar Mariano-Florentino , Larsen Benjamin , Lee Yong Suk , Webb Michael
Published: March 2022

We examine the impacts of potential artificial intelligence (AI) regulations on managers’ perceptions on ethical issues related to AI and their intentions to adopt AI technologies. We conduct a randomized online survey experiment on more than a thousand managers in the United States. We randomly present managers with different proposed AI regulations, and ask about ethical issues related to AI and their intentions related to AI adoption. We find that information about AI regulation increases manager perception of the importance of safety, privacy, bias/discrimination, and transparency issues related to AI. However, there is a tradeoff; regulation information reduces manager intent to adopt AI technologies. Moreover, information about regulation increases manager intent to spend on developing AI strategy including ethical issues at the cost of investing in AI adoption, such as providing AI training to current employees or purchasing AI software packages. (JEL: K24, L21, L51, O33, O38)
Pulmonary vein thrombosis following a right upper lobectomy preceding acute arterial occlusion: a case report
Authors: Ohashi Takuya , Kawago Mitsumasa , Hirai Yoshimitsu , Kiyoi Megumi , Miyasaka Miwako , Yata Yumi , Kawaji Mari , Fusamoto Aya , Iguchi Hideto , Nakanishi Hitomi , Nishimura Yoshiharu
Published: March 2022

Our medical team observed a right upper lobe nodule in a 78-year-old man who was treated with warfarin for chronic atrial fibrillation. The nodule was diagnosed as adenocarcinoma via intraoperative frozen sectioning. We performed video-assisted right upper lobectomy and mediastinal lymph node dissection. Warfarin was discontinued in the perioperative period. However, unfractionated heparin was administered. Nonetheless, the patient developed acute arterial occlusion of the lower extremities on post-operative day 7. Contrast-enhanced computed tomography showed thrombosis in the right upper lobe pulmonary vein stump, which was considered to be the cause of the acute arterial occlusion. The patient underwent emergency thrombectomy following which his symptoms immediately improved. Herein, we report a rare case of pulmonary vein thrombosis occurring after a right upper lobectomy. Our findings may facilitate effective clinical decision-making.
Differentially Private Synthesis and Sharing of Network Data Via Bayesian Exponential Random Graph Models
Authors: Liu Fang , Eugenio Evercita C , Jin Ick Hoon , Bowen Claire Mckay
Published: March 2022

Network data often contain sensitive relational information. One approach to protecting sensitive information while offering flexibility for network analysis is to share synthesized networks based on the information in originally observed networks. We employ differential privacy (DP) and exponential random graph models (ERGMs) and propose the DP-ERGM method to synthesize network data. We apply DP-ERGM to two real-world networks. We then compare the utility of synthesized networks generated by DP-ERGM, the DyadWise Randomized Response (DWRR) approach, and the Synthesis through Conditional distribution of Edge given nodal Attribute (SCEA) approach. In general, the results suggest that DP-ERGM preserves the original information significantly better than two other approaches in network structural statistics and inference for ERGMs and latent space models. Furthermore, DP-ERGM satisfies node DP through modeling the global network structure with ERGM, a stronger notion of privacy than the edge DP under which DWRR and SCEA operate.
A Review of GnRH Antagonists as Treatment for Abnormal Uterine Bleeding-Leiomyoma (AUB-L) and Their Influence on the Readiness of Service Members
Authors: Wright Danielle , Kim Ji Won , Lindsay Halle , Catherino William H
Published: March 2022

Introduction

Not too long ago, Lupron Depot® (leuprolide acetate), an injectable gonadotropin-releasing hormone (GnRH) agonist, was the only Food and Drug Administration (FDA) approved GnRH analog used to clinically treat abnormal uterine bleeding associated with uterine leiomyoma (AUB-L) when second-line medical management was warranted; however, the FDA has now approved elagolix and relugolix, GnRH antagonists, to be treatment options as well. This is a review of GnRH antagonists for the management of uterine fibroids reviewing their treatment efficacy, side effect profile, and current use in military medicine.

Methods

This is a review of studies from multiple electronic databases (Pubmed, ACOG, FDA, U.S. Military Guidelines) published between 1990 and 2021. Keywords used for the search include GnRH antagonist, elagolix, relugolix, uterine leiomyoma, and abnormal uterine bleeding. Our inclusion criteria for articles reviewed were: systematic reviews with the listed keywords, multicenter randomized trials, and meta-analyses. The DODI on Medical Standards for Medical Service, Air Force Aerospace Medicine Waiver Guide, Navy Guidance Aeromedical Reference and Waiver Guide, and the Army Regulation 40-501 Standards of Medical Fitness were used to review the military standards and current restrictions placed on service members.

Results

Thirty-three articles were reviewed and summarized.

Conclusion

Uterine leiomyoma can impact service members’ eligibility and fitness for duty. The oral administration of elagolix and relugolix adds convenience to this drug class through its oral administration while lengthening the duration of treatment up to 24 months. All military medical facilities should advocate for the well-being of their service members by stocking all options available. Health care providers should collaborate with patients in making the best therapy choice that is suited for their lifestyle and military occupation.
En Route Critical Care Evacuations From Rarely Utilized Partner Medical Treatment Facilities: A Case Series With Lessons Learned
Authors: Davis William T , Cheney Mark , Trueblood Wesley , Runyon Shane , Cruz Inez , Clemons Melissa , Strilka Richard
Published: March 2022

Retaining lessons learned from Critical Care Air Transport (CCAT) missions is essential given the recent decrease in operational currency among CCAT personnel. The objective of this case series was to identify and analyze logistical lessons learned from recent critical care transports involving foreign medical treatment facilities with sufficient detail for the CCAT community to incorporate these lessons into future readiness and sustainment training. The provider from each mission submitted a mission narrative with lessons learned. A qualitative analysis of lessons learned described themes from the lessons, as well as similarities and differences from included missions. Three missions were reviewed and four distinct mission stages were identified: (1) pre-mission, (2) at U.S. aircraft, (3) away from U.S. aircraft, and (4) post-mission. Pre-mission lessons learned included the need for professional civilian attire for deployed CCAT teams and the limited availability of pre-mission clinical information. Lessons learned at the aircraft included the following: the need for flexible mission timelines, coordinate and pre-plan transitions with foreign medical teams when possible, and plan for difficult environmental conditions if flight line transfer is required. Lessons learned away from the aircraft included communication challenges between CCAT and the aircraft, contingency planning for narcotic transports, and equipment interoperability issues. Post-mission lessons learned included the need for written communication to disseminate information to the CCAT community. This case series described logistical challenges that present during transport missions involving foreign hospitals. This published series will enable dissemination to the en route care community for possible incorporation into future training.
Outcome of rituximab treatment in Japanese patients with ANCA-associated vasculitis in daily clinical practice: A two-centre study in Fukushima, Japan
Authors: Yashiro-Furuya Makiko , Sato Shuzo , Akanuma Momo , Sato Kairi , Suzuki Eiji , Kanno Takashi , Matsumoto Haruki , Temmoku Jumpei , Fujita Yuya , Matsuoka Naoki , Asano Tomoyuki , Kobayashi Hiroko , Watanabe Hiroshi , Migita Kiyoshi
Published: March 2022

Objectives

Rituximab (RTX) efficacy for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has been reported in large randomized studies; however, the efficacy of RTX in Japanese AAV patients, especially the elderly, is not well known. We aimed to determine the clinical efficacy of RTX in Japanese AAV patients including elderly patients.

Methods

This study included 78 AAV patients newly diagnosed with AAV and treated in Fukushima Medical University Hospital or Ohta-Nishinouchi Hospital from April 2004 to September 2019. Clinical records were retrospectively reviewed, and clinical efficacy and outcome (1-year survival) between the RTX treatment group (23 cases) and the conventional therapy group (immunosuppressive therapy other than RTX, 55 cases) were compared. We also analysed the clinical efficacy and outcome in elderly-onset (>75 years) AAV patients.

Results

The RTX group showed similar efficacy and 1-year survival compared to the conventional therapy group. Conversely, after 6 months of treatment, prednisolone doses significantly decreased in the RTX group compared to the conventional therapy group (p < 0.01). In the elderly-onset AAV patients, clinical efficacy and outcome were not significantly different.

Conclusions

RTX was effective in Japanese AAV patients and may be useful for prompt tapering of prednisolone doses, even in elderly-onset AAV patients.
Management review of scleroderma renal crisis: An update with practical pointers
Authors: Foocharoen Chingching , Tonsawan Pantipa , Pongkulkiat Patnarin , Anutrakulchai Sirirat , Mahakkanukrauh Ajanee , Suwannaroj Siraphop
Published: March 2022

Scleroderma renal crisis (SRC) represents severe, fatal internal organ involvement brought on by systemic sclerosis. A high rate of renal replacement therapy and mortality persists despite various treatments. Depending on the stage of SRC, a vasodilator called angiotensin-converting enzyme inhibitor is the treatment of choice. The efficacy of various other vasodilators (i.e. endothelin-1 receptor antagonist) and complement cascade blocker for SRC have been investigated; however, no randomized control trial has been conducted. A new approach has been proposed for the management of SRC, categorized by specific clinical features of narrowly defined SRC and systemic sclerosis-thrombotic microangiopathy. SRC prophylaxis using angiotensin-converting enzyme inhibitor might be harmful, leading to a poor renal outcome, so the pathogenesis of SRC needs to be clarified in order to identify other possible preventions or therapies.
Arthritis remission with partial cartilage restoration in a 9-year-old female with hip chondrolysis following treatment with adalimumab
Authors: Fotis Lampros , Kanellopoulos Anastasios , Papakonstantinou Olympia
Published: March 2022

Hip chondrolysis is observed primarily or secondary to other diseases and is a rare but yet debilitating disease, characterised by loss of cartilage of the femoral epiphysis and significant restriction of motion. We present the case of a 9-year-old female diagnosed with hip chondrolysis associated with probable juvenile psoriatic arthritis. Avoidance of weight-bearing activities and treatment with corticosteroids, methotrexate, and adalimumab followed by aquatic therapy resulted in clinical and radiographic improvement as well as partial cartilage regeneration.
Difficulties of diagnosing idiopathic hypertrophic pachymeningitis in children: Case report and literature review
Authors: Nicho Naoki , Nozawa Tomo , Murase Ayako , Hayashibe Ren , Tanoshima Reo , Okubo Risa , Hattori Seira , Nishimura Kenichi , Ohya Takashi , Ito Shuichi
Published: March 2022

Hypertrophic pachymeningitis (HP) is a rare inflammatory disorder characterised by local or diffuse thickening of the cranial and spinal dura mater. HP occurs owing to idiopathic or secondary causes, including autoimmune disease, infection, and trauma. HP has mainly been reported in adults, with few reported cases in children. We encountered an 11-year-old boy with idiopathic HP who presented with chronic inflammation and daily occipital headache. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) helped us to diagnose him with HP. He was successfully treated with corticosteroids and azathioprine with no recurrence. We also conducted a literature review of childhood-onset HP and found only 16 cases, including our patient. Seven patients had idiopathic HP, and the remaining nine had secondary HP, including two with rheumatic disease. The most common clinical symptoms were headache (68.8%) and cranial nerve-related symptoms (68.8%). Inflammatory laboratory markers were elevated in 60% of patients with available data. Fifteen cases were diagnosed using Gd-enhanced MRI. The main initial treatment was steroids and/or immunosuppressants, to which 87.5% of patients responded. However, two patients with HP associated with trauma and neuroblastoma (12.5%) died, and seven patients (43.8%) had left cranial nerve-related sequelae. As the prognosis for childhood HP is poor, early diagnosis and treatment are essential. Children with headache, cranial nerve symptoms, and elevated inflammatory marker levels should be suspected of having HP and Gd-enhanced MRI should be considered.
Down-regulated Th17 cells in a patient with familial Mediterranean fever associated with amyloid A amyloidosis in the treatment of canakinumab
Authors: Goto Takeshi , Miyazaki Yusuke , Nakayamada Shingo , Shiraishi Naoki , Yoshinaga Takeshi , Tanaka Yoshiya , Nakamura Tadashi
Published: March 2022

Autoinflammatory diseases are innate immune-mediated inflammatory disorders, unlike autoimmune diseases, which are characterised by abnormalities in adoptive immunity, although autoimmune and autoinflammatory diseases have certain similar clinical features. Familial Mediterranean fever (FMF), the most common monogenic autoinflammatory disease, is associated with mutations in the MEFV gene that encodes pyrin, which results in inflammasome activation and uncontrolled production of interleukin (IL)-1β. Regular use of colchicine, the primary drug for FMF treatment, prevents febrile attacks and reduces the long-term risk of subsequent complications of amyloid A (AA) amyloidosis. However, a minority of FMF patients develop colchicine resistance, and anti-IL-1β treatment with canakinumab, which is a genetically modified human IgG subclass type 1 (IgG1) monoclonal antibody specific for human IL-1β, was beneficial in inhibiting inflammation in such patients. Here, we present a patient with FMF associated with AA amyloidosis, who was treated with canakinumab and demonstrated down-regulated Th17 cells and activated Th17 cells (from 21.4% to 12.8%, and from 1.45% to 0.83%, respectively) in peripheral blood, as shown by immunophenotyping via multicolour flow cytometry and by disease activity and improved laboratory inflammatory surrogate markers—C-reactive protein (CRP) and serum AA protein (SAA). CRP had values within normal limits, but SAA did not (Spearman’s rank correlation coefficient; ρ = 0.133). We report that SAA and IL-1β may differentiate Th17 cells from CD4+-naïve T cells, and we discuss interactions between autoinflammation and autoimmunity as a model based on this case, through modes of action with IL-1β and SAA. This report is the first demonstrating that an IL-1β antagonist may reduce Th17 cells in FMF as a therapeutic option.
Identification of potential modifier genes in Chinese patients with Wilson disease
Authors: Zhou Donghu , Jia Siyu , Yi Liping , Wu Zhen , Song Yi , Zhang Bei , Li Yanmeng , Yang Xiaoxi , Xu Anjian , Li Xiaojin , Zhang Wei , Duan Weijia , Li Zhenkun , Qi Saiping , Chen Zhibin , Ouyang Qin , Jia Jidong , Huang Jian , Ou Xiaojuan , You Hong
Published: March 2022

The mutations in modifier genes may contribute to some inherited diseases including Wilson disease (WD). This study was designed to identify potential modifier genes that contribute to WD. A total of 10 WD patients with single or no heterozygous ATP7B mutations were recruited for whole-exome sequencing (WES). Five hundred and thirteen candidate genes, of which the genetic variants present in at least two patients, were identified. In order to clarify which proteins might be involved in copper transfer or metabolism processes, the isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify the differentially expressed proteins between normal and CuSO4-treated cell lines. Thirteen genes/proteins were identified by both WES and iTRAQ, indicating that disease-causing variants of these genes may actually contribute to the aberrant copper ion accumulation. Additionally, the c.86C > T (p.S29L) mutation in the SLC31A2 gene (coding CTR2) has a relative higher frequency in our cohort of WD patients (6/191) than reported (0.0024 in gnomAD database) in our healthy donors (0/109), and CTR2S29L leads to increased intracellular Cu concentration and Cu-induced apoptosis in cultured cell lines. In conclusion, the WES and iTRAQ approaches successfully identified several disease-causing variants in potential modifier genes that may be involved in the WD phenotype.
Functions of consciousness: conceptual clarification
Authors: Niikawa Takuya , Miyahara Katsunori , Hamada Hiro Taiyo , Nishida Satoshi
Published: March 2022

There are many theories of the functions of consciousness. How these theories relate to each other, how we should assess them, and whether any integration of them is possible are all issues that remain unclear. To contribute to a solution, this paper offers a conceptual framework to clarify the theories of the functions of consciousness. This framework consists of three dimensions: (i) target, (ii) explanatory order, and (iii) necessity/sufficiency. The first dimension, target, clarifies each theory in terms of the kind of consciousness it targets. The second dimension, explanatory order, clarifies each theory in terms of how it conceives of the explanatory relation between consciousness and function. The third dimension, necessity/sufficiency, clarifies each theory in terms of the necessity/sufficiency relation posited between consciousness and function. We demonstrate the usefulness of this framework by applying it to some existing scientific and philosophical theories of the functions of consciousness.
Response: Collective Moral Agents and Their Collective-Level Virtues
Authors: MacKay Kathryn
Published: March 2022

In this short piece, I attempt to respond to some of the challenges raised by Jessica Nihlén Fahlquist and Karen Meagher in their commentaries on my paper, ‘Public Health Virtue Ethics’. While these authors have made many insightful and challenging remarks, I mostly focus on two questions here: first, about the nature of collectives as moral agents, in response to Nihlén Fahlquist, and second, about the concept of a collective-level virtue, in response to Meagher.
How Do Inheritances Shape Wealth Inequality? Theory and Evidence from Sweden
Authors: Nekoei Arash , Seim David
Published: March 2022

This article aims to measure and understand the role of inheritances in shaping wealth inequality. We use a quasi-experimental design and Swedish administrative data to document that the average heir depletes her inheritance within a decade while the inheritances of wealthy heirs remain intact. These different depletion rates are not due to different consumption or labour supply responses but due to different rates of return on inherited wealth. Upon their receipt, inheritances reduce relative measures of wealth inequality, such as top shares or percentile ratios. Theoretically, this reduction in inequality could be due to either a compressed inheritance distribution or similar chances of having wealthy parents (high intergenerational mobility). Empirically, the first force is more significant in Sweden. Within a decade, however, the effect is reversed: inheritances increase wealth inequality since the different depletion rates widen the inequality in inherited wealth over time. This implies that inheritance taxation can reduce long run wealth inequality only through the taxation of wealthy heirs.
URANIUM AND 210PO RADIONUCLIDES IN DRINKING WATER IN SOUTHERN BULGARIA AND EXPECTED RADIATION DOSES
Authors: Slavchev Bozhidar , Tonev Dimitar , Dobrev Lyuben , Geleva Elena , Veleva Blagorodka , Protohristov Hristo , Goutev Nikolay , Demerdjiev Anguel , Dimitrova Desislava
Published: March 2022

The activity concentrations of the naturally occurring radionuclides 238U, 234U and 210Po have been determined for the first time in drinking water from certain sources in Southern Bulgaria using nuclear and radiochemical methods. The results obtained for the water samples vary in the intervals 0.6–678 mBq l−1 for 238U, 1.4–1484 mBq l−1 for 234U, <0.3–13.6 mBq l−1 for 210Po and 1.04–10.6 for the 234U/238U ratio. The annual effective dose from 238U, 234U and 210Po ranges from 1.09 to 44.1 μSv y−1, 0.78 to 46.8 μSv y−1 and 0.77 to 62.8 μSv y−1 for infants, children and adults, respectively. The annual effective dose due to consumption of drinking water is below the individual dose criterion of 100 μSv y−1 recommended by the World Health Organization. The natural radioactivity of the water sources investigated is below the national and international limits.
A Step Towards Validation of High-Throughput Sequencing for the Identification of Plant Pathogenic Oomycetes
Authors: Espindola Andres S. , Cardwell Kitty , Martin Frank N. , Hoyt Peter R. , Marek Stephen M. , Schneider William , Garzon Carla D.
Published: March 2022

The advancement in high-throughput sequencing (HTS) technology allows the detection of pathogens without the need for isolation or template amplification. Plant regulatory agencies worldwide are adopting HTS as a prescreening tool for plant pathogens in imported plant germplasm. The technique is a multipronged process and, often, the bioinformatic analysis complicates detection. Previously, we developed E-probe diagnostic nucleic acid analysis (EDNA), a bioinformatic tool that detects pathogens in HTS data. EDNA uses custom databases of signature nucleic acid sequences (e-probes) to reduce computational effort and subjectivity when determining pathogen presence in a sample. E-probes of Pythium ultimum and Phytophthora ramorum were previously validated only using simulated HTS data. However, HTS samples generated from infected hosts or pure culture may vary in pathogen concentration, sequencing bias, and data quality, suggesting that each pathosystem requires further validation. Here, we used metagenomic and genomic HTS data generated from infected hosts and pure culture, respectively, to further validate and curate e-probes of Pythium ultimum and Phytophthora ramorum. E-probe length was found to be a determinant of diagnostic sensitivity and specificity; 80-nucleotide e-probes increased the diagnostic specificity to 100%. Curating e-probes to increase specificity affected diagnostic sensitivity only for 80-nucleotide Pythium ultimum e-probes. Comparing e-probes with alternative databases and bioinformatic tools in their speed and ability to find Pythium ultimum and Phytophthora ramorum demonstrated that, although pathogen sequence reads were detected by other methods, they were less specific and slower when compared with e-probes.
Improving Accuracy in Documenting Cardiopulmonary Arrest Events
Authors: Joseph Bridgid , Sulmonte Kimberlyann , DeSanto-Madeya Susan , Koeniger-Donohue Rebecca , Cocchi Michael
Published: March 2022

Purpose:

Traditional paper documentation of cardiopulmonary arrest (CPA) events is often inaccurate and incomplete. Electronic documentation supports appropriate process improvements and optimal patient care and contributes to greater accuracy in national databases from which national benchmarks are derived. The aim of this quality improvement initiative was to compare the timeliness and accuracy of paper-based versus electronic documentation of live CPA events.

Methods:

Nurses on four medical–surgical pilot units received training on the use of a handheld electronic device with a documentation app (Full Code Pro) to document live CPA events. The data were downloaded into an Excel file and compared for completeness and accuracy with the data downloaded from the LIFEPAK 15 defibrillator using CODE-STAT 10.0 software. Electronic documentation and traditional paper documentation of events from units where the intervention wasn't implemented (control units) were also compared with the CODE-STAT data.

Results:

There were 26 CPA events: six on the pilot units were documented using the electronic app, 12 on the pilot units were documented using the paper-based method (the latter were excluded from analysis), and eight on the control units were documented using the existing paper forms. Data accuracy was significantly greater in the electronic group compared with the paper-based group for recorded rhythm (100% versus 13%, P = 0.01) and end-tidal carbon dioxide (67% versus 0%, P = 0.02). The electronic method significantly outperformed the paper-based method in legibility (100% versus 13%, P < 0.01). Staff reported increased satisfaction with the electronic documentation method.

Conclusion:

Using electronic handheld devices to document live resuscitation events demonstrated the inaccuracies of paper-based documentation, supporting the findings of previous studies. Electronic documentation was superior to paper in overall documentation quality and allowed providers to identify and quickly document the initial rhythm of the event. A larger study using electronic documentation to capture more ventricular fibrillation and ventricular tachycardia arrests would show a greater accuracy of timing, which would have large positive effects on overall resuscitation quality.
Autism Spectrum Disorder
Authors: Volkert Delene , Ortelli Tracy A.
Published: March 2022

Resources to help promote patients' and families' well-being.
Incidence of Postoperative Delirium Is Similar with Regional and General Anesthesia
Authors: Rosenberg Karen
Published: March 2022

According to this study:

In older adults undergoing hip fracture surgery, regional anesthesia without sedation didn't significantly reduce the incidence of postoperative delirium compared with general anesthesia.
Bisphosphonates Likely Beneficial for Most Older Women with Osteoporosis
Authors: Rosenberg Karen
Published: March 2022

According to this study:

A meta-analysis suggests that the short-term benefits of bisphosphonate therapy likely outweigh the short-term harms for most older postmenopausal women who have osteoporosis.