bluuebunny/crossref_metadata_2025 huggingface dataset:
DeepSec: a deep learning framework for secreted protein discovery in human body fluids
Authors: Shao Dan , Huang Lan , Wang Yan , He Kai , Cui Xueteng , Wang Yao , Ma Qin , Cui Juan
Published: August 2021

Motivation

Human proteins that are secreted into different body fluids from various cells and tissues can be promising disease indicators. Modern proteomics research empowered by both qualitative and quantitative profiling techniques has made great progress in protein discovery in various human fluids. However, due to the large number of proteins and diverse modifications present in the fluids, as well as the existing technical limits of major proteomics platforms (e.g. mass spectrometry), large discrepancies are often generated from different experimental studies. As a result, a comprehensive proteomics landscape across major human fluids are not well determined.

Results

To bridge this gap, we have developed a deep learning framework, named DeepSec, to identify secreted proteins in 12 types of human body fluids. DeepSec adopts an end-to-end sequence-based approach, where a Convolutional Neural Network is built to learn the abstract sequence features followed by a Bidirectional Gated Recurrent Unit with fully connected layer for protein classification. DeepSec has demonstrated promising performances with average area under the ROC curves of 0.85–0.94 on testing datasets in each type of fluids, which outperforms existing state-of-the-art methods available mostly on blood proteins. As an illustration of how to apply DeepSec in biomarker discovery research, we conducted a case study on kidney cancer by using genomics data from the cancer genome atlas and have identified 104 possible marker proteins.

Availability

DeepSec is available at https://bmbl.bmi.osumc.edu/deepsec/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Satb2 Regulates EphA7 to Control Soma Spacing and Self-Avoidance of Cortical Pyramidal Neurons
Authors: He Chun-Hui , Zhang Lei , Song Ning-Ning , Mei Wan-Ying , Chen Jia-Yin , Hu Ling , Zhang Qiong , Wang Yu-Bing , Ding Yu-Qiang
Published: August 2021

Soma spacing and dendritic arborization during brain development are key events for the establishment of proper neural circuitry and function. Transcription factor Satb2 is a molecular node in regulating the development of the cerebral cortex, as shown by the facts that Satb2 is required for the regionalization of retrosplenial cortex, the determination of callosal neuron fate, and the regulation of soma spacing and dendritic self-avoidance of cortical pyramidal neurons. In this study, we explored downstream effectors that mediate the Satb2-implicated soma spacing and dendritic self-avoidance. First, RNA-seq analysis of the cortex revealed differentially expressed genes between control and Satb2 CKO mice. Among them, EphA7 transcription was dramatically increased in layers II/III of Satb2 CKO cortex. Overexpression of EphA7 in the late-born cortical neurons of wild-type mice via in utero electroporation resulted in soma clumping and impaired self-avoidance of affected pyramidal neurons, which resembles the phenotypes caused by knockdown of Satb2 expression. Importantly, the phenotypes by Satb2 knockdown was rescued by reducing EphA7 expression in the cortex. Finally, ChIP and luciferase reporter assays indicated a direct suppression of EphA7 expression by Satb2. These findings provide new insights into the complexity of transcriptional regulation of the morphogenesis of cerebral cortex.
Proposed Linezolid Dosing Strategies to Minimize Adverse Events for Treatment of Extensively Drug-Resistant Tuberculosis
Authors: Imperial Marjorie Z , Nedelman Jerry R , Conradie Francesca , Savic R M
Published: August 2021

Background

We evaluated Nix-TB trial data (NCT02333799, N = 109) to provide dosing recommendations to potentially minimize linezolid toxicity in patients with extensively drug-resistant tuberculosis. .

Methods

A pharmacokinetic model and toxicodynamic models for peripheral neuropathy, hemoglobin, and platelets were developed. Simulations compared safety outcomes for daily linezolid of 1200 and 600 mg, with and without dose adjustments for toxicity. Severe neuropathy was based on symptom scores from the Brief Peripheral Neuropathy Screen. Severe anemia and thrombocytopenia were defined as ≥ grade 3 adverse events according to the NIAID Division of Microbiology and Infectious Disease Adult Toxicity table.

Results

Predicted concentration-time profiles were a major predictor in all toxicodynamic models. Simulations showed higher percentages of patients with severe neuropathy (median, 19%; 90% confidence interval [CI], 17%–22% vs 5%, 4%–7%) and severe anemia (15%, 12%–17% vs 1%, 0%–2%) between 1200 and 600 mg daily linezolid. No differences in severe thrombocytopenia were observed (median, <1% for both daily doses). Generally, neuropathy occurred after 3 to 6 months of treatment and, with protocol-specified management, reversed within 15 months after onset. Simulations indicated that a >10% decrease in hemoglobin level after 4 weeks of treatment would have maximum sensitivity (82%) and specificity (84%) for predicting severe anemia. Reducing the dose from 1200 to 600 mg triggered by this marker may prevent 60% (90% CI, 45%–72%) of severe anemia.

Conclusions

Simple neuropathy symptom and hemoglobin monitoring may guide linezolid dosing to avoid toxicities, but prospective testing is needed to confirm the benefit-to-risk ratio.
Direct Water-Assisted Laser Desorption/Ionization Mass Spectrometry Lipidomic Analysis and Classification of Formalin-Fixed Paraffin-Embedded Sarcoma Tissues without Dewaxing
Authors: Ogrinc Nina , Caux Pierre-Damien , Robin Yves-Marie , Bouchaert Emmanuel , Fatou Benoit , Ziskind Michael , Focsa Cristian , Bertin Delphine , Tierny Dominique , Takats Zoltan , Salzet Michel , Fournier Isabelle
Published: August 2021

Background

Formalin-fixed paraffin-embedded (FFPE) tissue has been the gold standard for routine pathology for general and cancer postoperative diagnostics. Despite robust histopathology, immunohistochemistry, and molecular methods, accurate diagnosis remains difficult for certain cases. Overall, the entire process can be time consuming, labor intensive, and does not reach over 90% diagnostic sensitivity and specificity. There is a growing need in onco-pathology for adjunct novel rapid, accurate, reliable, diagnostically sensitive, and specific methods for high-throughput biomolecular identification. Lipids have long been considered only as building blocks of cell membranes or signaling molecules, but have recently been introduced as central players in cancer. Due to sample processing, which limits their detection, lipid analysis directly from unprocessed FFPE tissues has never been reported.

Methods

We present a proof-of-concept with direct analysis of tissue-lipidomic signatures from FFPE tissues without dewaxing and minimal sample preparation using water-assisted laser desorption ionization mass spectrometry and deep-learning.

Results

On a cohort of difficult canine and human sarcoma cases, classification for canine sarcoma subtyping was possible with 99.1% accuracy using “5-fold” and 98.5% using “leave-one-patient out,” and 91.2% accuracy for human sarcoma using 5-fold and 73.8% using leave-one-patient out. The developed classification model enabled stratification of blind samples in <5 min and showed >95% probability for discriminating 2 human sarcoma blind samples.

Conclusion

It is possible to create a rapid diagnostic platform to screen clinical FFPE tissues with minimal sample preparation for molecular pathology.
The governance of 5G infrastructure: between path dependency and risk-based approaches
Authors: Radu Roxana , Amon Cedric
Published: August 2021

The fifth generation (5G) wireless technology promises a powerful, reliable and fast infrastructure to match artificial intelligence and Internet of Things developments. But its rollout has stirred strong political tensions around the prominent role that Chinese providers might be allowed to play in building the new networks. Between 2018 and 2020, a few countries have banned—partially or totally—the use of networking equipment produced by Huawei and ZTE, while others have mandated technical and security reviews to mitigate the risks associated with Chinese-origin components in the national 5G infrastructure. This article provides a thematic analysis of the security arguments and policy options emerging in the early days of the 5G debates. Based on key high-level statements, parliamentary debates and legislative acts published from mid-2018 to 2020, we examine perceived risks and threats surfacing in the public discourse, as well as the main regulatory directions emerging in seven countries. Our analysis shows policy alignment across multilateral commitments such as the European Union (EU) or the Five Eyes intelligence alliance. While selected EU member states lean towards risk-based governance and adaptive policies, Five Eyes nations opt for pre-emptive bans of 5G Chinese vendors, revealing path-dependent strategies for the sector. We conclude by discussing the policy reversal experienced by the UK in 2020 and the consolidation of new governance approaches for 5G infrastructure.
Ten-year all-cause death after percutaneous or surgical revascularization in diabetic patients with complex coronary artery disease
Authors: Wang Rutao , Serruys Patrick W , Gao Chao , Hara Hironori , Takahashi Kuniaki , Ono Masafumi , Kawashima Hideyuki , O’leary Neil , Holmes David R , Witkowski Adam , Curzen Nick , Burzotta Francesco , James Stefan , van Geuns Robert-Jan , Kappetein Arie Pieter , Morel Marie-angele , Head Stuart J , Thuijs Daniel J F M , Davierwala Piroze M , O’Brien Timothy , Fuster Valentin , Garg Scot , Onuma Yoshinobu
Published: August 2021

Aims

The aim of this article was to compare rates of all-cause death at 10 years following coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in patients with or without diabetes.

Methods and results

The SYNTAXES study evaluated up to 10-year survival of 1800 patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to receive either PCI or CABG in the SYNTAX trial. Ten-year all-cause death according to diabetic status and revascularization strategy was examined. In diabetics (n = 452), the risk of mortality was numerically higher with PCI compared with CABG at 5 years [19.6% vs. 13.3%, hazard ratio (HR): 1.53, 95% confidence interval (CI): 0.96, 2.43, P = 0.075], with the opposite seen between 5 and 10 years (PCI vs. CABG: 20.8% vs. 24.4%, HR: 0.82, 95% CI: 0.52, 1.27, P = 0.366). Irrespective of diabetic status, there was no significant difference in all-cause death at 10 years between patients receiving PCI or CABG, the absolute treatment difference was 1.9% in diabetics (PCI vs. CABG: 36.4% vs. 34.5%, difference: 1.9%, 95% CI: −7.6%, 11.1%, P = 0.551). Among insulin-treated patients (n = 182), all-cause death at 10 years was numerically higher with PCI (47.9% vs. 39.6%, difference: 8.2%, 95% CI: −6.5%, 22.5%, P = 0.227).

Conclusions

The treatment effects of PCI vs. CABG on all-cause death at 10 years in patients with 3VD and/or LMCAD were similar irrespective of the presence of diabetes. There may, however, be a survival benefit with CABG in patients with insulin-treated diabetes. The association between revascularization strategy and very long-term ischaemic and safety outcomes for patients with diabetes needs further investigation in dedicated trials.

Trial registration

SYNTAX: ClinicalTrials.gov reference: NCT00114972 and SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.
Combining Knowledge- and Data-Driven Fuzzy Approach to Evaluate Shelf-Life of Various Seafood Products
Authors: Moosavi-Nasab Marzieh , Khoshnoudi-Nia Sara
Published: August 2021

Due to the complexity of the deterioration process of seafood products, relying on one indicator is not adequate to determine the quality of such products. Usually, shelf-life was estimated based on various indicators complicating the decision-making process. Decision Support Systems are considered as a good solution. The current study aims to establish a simple and novel fuzzy model based on a combination of knowledge- and data-driven approaches to define a fuzzy quality deterioration index (FQDI) in various seafood products (rainbow trout, threadfin bream, and white shrimp samples) during cold storage. Total volatile basic nitrogen (TVB-N) and psychrotrophic microorganisms counts (PMCs) were determined based on traditional methods. The sensory analysis was performed by a data-driven fuzzy approach. Overall, the shelf-life of the rainbow trout fillet was estimated to be 8 days, based on all the freshness parameters. However, the shelf-life of the Japanese threadfin bream fillet was 5–7 days according to the microbial and chemical parameters, respectively. This time for shrimp samples was 6–8 days using sensory score and TVB-N contents. The results of data-driven fuzzy approach showed all of the quality properties were considered as the ‘Important’–‘Very Important’ (defuzzification score >75). The TVB-N and PMCs were the most and weakest freshness quality properties (defuzzified-values: 84.64 and 78.75, respectively). Based on FQDI, the shelf-life of the rainbow trout, Japanese threadfin bream, and shrimp samples were estimated to be 8, 5, and 7 days, respectively. This method was able to successfully provide a comprehensive deterioration index for evaluating the seafood shelf-life. Such a total index can be considered as a comprehensive output (y variable) to predict seafood freshness by rapid and nondestructive method.
Exercise Therapy Is Effective at Improving Short- and Long-Term Mobility, Activities of Daily Living, and Balance in Older Patients Following Hip Fracture: A Systematic Review and Meta-Analysis
Authors: Hulsbæk Signe , Juhl Carsten , Røpke Alice , Bandholm Thomas , Kristensen Morten Tange
Published: August 2021

Background

A systematic review and meta-analysis was performed to evaluate the short- and long-term effects of exercise therapy on physical function, independence, and well-being in older patients following hip fracture and, secondly, whether the effect was modified by trial-level characteristics such as intervention modality, duration, and initiation timepoint.

Method

Medline, CENTRAL, Embase, CINAHL, and PEDro were searched up to November 2020. Eligibility criteria were randomized controlled trials investigating the effect of exercise therapy on physical function, independence, and well-being in older patients following hip fracture, initiated from time of surgery up to 1 year.

Results

Forty-nine studies involving 3 905 participants showed a small-to-moderate effect of exercise therapy at short term (end of intervention) on mobility (standardized mean difference [SMD] 0.49, 95% confidence interval [CI]: 0.22–0.76); activities of daily living (ADL) (SMD 0.31, 95% CI: 0.16–0.46); lower limb muscle strength (SMD 0.36, 95% CI: 0.13–0.60); and balance (SMD 0.34, 95% CI: 0.14–0.54). At long term (closest to 1 year), small-to-moderate effects were found for mobility (SMD 0.74, 95% CI: 0.15–1.34), ADL (SMD 0.42, 95% CI: 0.23–0.61), balance (SMD 0.50, 95% CI: 0.07–0.94), and health-related quality of life (SMD 0.31, 95% CI: 0.03–0.59). Certainty of evidence was evaluated using Grading of Recommendations Assessment, Development and Evaluation ranging from moderate to very low, due to study limitation and inconsistency.

Conclusion

We found low certainty of evidence for a moderate effect of exercise therapy on mobility in older patients following hip fracture at end of treatment and follow-up. Further, low evidence was found for small-to-moderate short-term effect on ADL, lower limb muscle strength and balance.

Clinical Trials Registration Number

CRD42020161131
Presence of birth companion—a deterrent to disrespectful behaviours towards women during delivery: an exploratory mixed-method study in 18 public hospitals of India
Authors: Singh Shalini , Goel Richa , Gogoi Aparajita , Caleb-Varkey Leila , Manoranjini Mercy , Ravi Tina , Rawat Deewanshi
Published: August 2021

Birthing women require support, particularly emotional support, during the process of labour and delivery. Traditionally, across cultures, this support was made available by the continuous presence of a companion during labour, childbirth and the immediate post-partum period. However, this practice is not universal, especially in health facilities in low- and middle-income countries. This cross-sectional study was conducted in 18 tertiary health care facilities of India using a mixed-method approach. The quantitative data were collected to document the number of birthing women, birth companions and healthcare providers in the labour rooms, and the typology of disrespect and abuse (D&A) faced by women. This was followed by in-depth interviews with 55 providers to understand their perspective on the various dimensions of D&A and the challenges they face to provide respectful care. This article explores the status of birth companionship in India and its plausible associations with D&A faced by birthing women in public facilities. Our study reveals that birth companionship is still not a common practice in Indian public hospitals. Birth companions were present during less than half of the observational period, also less than half of the birthing women were accompanied by a birth companion. Lack of hospital policy, space constraints, overcrowding and privacy concerns for other patients were cited as reasons for not allowing birth companions in the labour rooms, whose supportive roles, both for women and providers, were otherwise widely acknowledged during the qualitative interviews. Also, the presence of birth companions was found to be critically negatively associated with occurrences of D&A of birthing women. We contend that owing to the high pressure on the public hospitals in India, birth companions can be a low-cost intervention model for promoting respectful maternity care. However, adequate infrastructure is a critical aspect to be taken care of.
COVID-19 response in South-East Asia: promoting healthcare quality through political engagement
Authors: Rana Bhupendra Kumar
Published: August 2021

Coronavirus disease-2019 (COVID-19), a disease caused by coronavirus severe acute respiratory syndrome coronavirus 2, led to a pandemic that affected every region of the world. The World Health Organization South-East Asia Region (SEARO) is composed of 11 countries: Bangladesh, Bhutan, Democratic People’s Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and Timor-Leste. Each of these countries faced different challenges in tackling COVID-19 depending upon their resources and health system. However, in general it was evidenced that no country was prepared to handle such a pandemic. Two strategies were adopted globally: closing the international borders and restricting movement within countries. These measures were adopted throughout the SEARO.
Early antimicrobial stewardship team intervention on appropriateness of antimicrobial therapy in suspected sepsis: a randomized controlled trial
Authors: Rashidzada Zohal , Cairns Kelly A , Peel Trisha N , Jenney Adam W , Doyle Joseph S , Dooley Michael J , Cheng Allen C
Published: August 2021

Objectives

There has been concern that the imperative to administer rapid antimicrobials in septic patients may result in inappropriate antimicrobial use. We aimed to determine the impact of early antimicrobial stewardship (AMS) team intervention in patients with Medical Emergency Team (MET) calls for suspected sepsis.

Methods

We performed a randomized controlled trial of non-ICU inpatients who had a MET call for suspected sepsis. Patients were randomized to standard care (management of antimicrobial therapy by the treating team) or early targeted intervention (AMS review 48 h post-MET call). The primary outcome was appropriateness of antimicrobial therapy 72 h post-MET call, as determined by a panel of blinded infectious diseases physicians.

Results

In total, 90 patients were enrolled; 45 were randomly allocated to the intervention group, and 45 to the control group. More patients in the AMS intervention group were receiving appropriate antimicrobials 72 h following the MET call (67% versus 44%, P = 0.03). In the intervention group, 27 recommendations were made by the AMS team; 74% of recommendations were accepted, including 30% of cases where antimicrobials were discontinued or de-escalated. There were non-significant differences in total duration of antimicrobial therapy (8.7 versus 10.7 days, P = 0.39), sepsis-related ICU-admission rates (13% versus 18%, P = 0.56) and sepsis-related in-hospital mortality (7% versus 9%, P = 0.71) between intervention and control groups, respectively.

Conclusions

AMS team intervention resulted in significant improvement in appropriateness of antimicrobial therapy following MET calls due to suspected sepsis. Targeted AMS review should be implemented to support early antimicrobial de-escalation and optimization in patients with suspected sepsis.
Peritoneal mesothelioma with invasion of the urinary bladder 20 years post radiation therapy for colon adenocarcinoma
Authors: Ong Mingjing Nicole , Asamu Abdul Samad , Pace Keith , Bugeja Simon
Published: August 2021

We present the case of a 66-year-old male with a history of iatrogenic bladder injury and radiation therapy for colon adenocarcinoma 20 years prior. A computed tomography of the thorax, abdomen and pelvis, reported a presacral mass with invasion to the bladder, ureters and lymph nodes. An initial bladder biopsy was histologically inconclusive. A later biopsy taken during emergency bypass surgery for small bowel obstruction, while the patient was positive for coronavirus disease of 2019, concluded that the mass was a peritoneal mesothelioma of epithelioid origin. The combination management of cytoreductive surgery with intraperitoneal chemotherapy has been a near universal standard of care for epithelioid peritoneal mesothelioma provided that the patient is an appropriate candidate for surgical interventions. To the best of our knowledge, this is the first case report of malignant peritoneal mesothelioma as a second primary carcinoma, many years after exposure to radiation therapy for colon adenocarcinoma.
Red Blood Cell Alloimmunization Rates and Related Factors of Patients with Thalassemia in Shiraz, Iran
Authors: Kasraian Leila , Khodadi Elahe , Talei Abolfazl , Morvarid Mohamad Reza , Haddadi Davood , Foruozandeh Hossein
Published: August 2021

Objective

The development of antibodies against red blood cell (RBC) antigens is one of the most significant adverse effects of chronic blood transfusions. This study aimed to estimate the frequency and causes of RBC immunization in patients with major thalassemia.

Methods

The findings could help determine the limitation of current practices and help future developments in the selection of suitable blood units for the transfusion support of patients with thalassemia.

Results

The alloimmunization rate was detected in 52 of 650 patients with major thalassemia (8%). The most frequent antibodies were against K (50%), D (26%), and E (15.4%). Sex, age, and splenectomy did not have any impact on the immunization rate. Immunization was lower in patients who had received only leuko-reduced blood units.

Conclusion

It is recommended that antibody screening before the first transfusion and extended RBC matching particularly for the most frequent antigens (ABO/Rh/Kell) should be performed for patients with thalassemia.
Secular dynamics of a test particle perturbed by a Miyamoto–Nagai disc
Authors: Liu Tao , Gong Shengxia , Liao Xinhao
Published: August 2021

We study the secular behaviour of a test particle orbiting a dominant central body and perturbed by a Miyamoto–Nagai (MN) disc. We derive a quadrupole-level secular Hamiltonian of this system, which involves a dimensionless parameter η that is used to characterize the flattening of MN disc. (The smaller η, the flatter disc; and η = 0 gives the infinitely thin Kuzmin disc.) We find that, in the quadrupole approximation, the perturbation of the MN disc can give rise to the von Zeipel–Lidov–Kozai (ZLK)-like dynamics and depending on the value of η the dynamics has two different manifestations: (i) when η < 1/3, the test particle’s behaviour is similar to that described in the classical ZLK problem. In particular, as η increases from 0 to 1/3, the critical inclination for the large eccentricity oscillations decreases from $26{_{.}^{\circ}}56$ to 0°, ; (ii) when η > 1/3, the orbital evolution of the test particle and the phase-space morphology are opposite to the classical ZLK case. This leads to a striking result that the test particle cannot remain on a near-coplanar orbit if its eccentricity is sufficiently large. However, as η increases further the ZLK-like dynamics would be gradually suppressed by the spherical term in the Hamiltonian. We also survey the global secular dynamics numerically in which the quadrupole approximation is no longer valid.
Dynamics of binary black holes in low-mass young star clusters
Authors: Rastello Sara , Mapelli Michela , Di Carlo Ugo N , Iorio Giuliano , Ballone Alessandro , Giacobbo Nicola , Santoliquido Filippo , Torniamenti Stefano
Published: August 2021

Young star clusters are dynamically active stellar systems and are a common birthplace for massive stars. Low-mass star clusters (∼300–103 M⊙) are more numerous than massive systems and are characterized by a two-body relaxation time-scale of a few Myr: the most massive stars sink to the cluster core and dynamically interact with each other even before they give birth to compact objects. Here, we explore the properties of black holes (BHs) and binary black holes (BBHs) formed in low-mass young star clusters, by means of a suite of 105 direct N-body simulations with a high original binary fraction (100 per cent for stars with mass >5 M⊙). Most BHs are ejected in the first ∼20 Myr by dynamical interactions. Dynamical exchanges are the main formation channel of BBHs, accounting for ∼40–80 per cent of all the systems. Most BBH mergers in low-mass young star clusters involve primary BHs with mass <40 M⊙ and low-mass ratios are extremely more common than in the field. Comparing our data with those of more massive star clusters (103 − 3 × 104 M⊙), we find a strong dependence of the percentage of exchanged BBHs on the mass of the host star cluster. In contrast, our results show just a mild correlation between the mass of the host star cluster and the efficiency of BBH mergers.
Noisy neighbours: inference biases from overlapping gravitational-wave signals
Authors: Antonelli Andrea , Burke Ollie , Gair Jonathan R
Published: August 2021

Understanding and dealing with inference biases in gravitational-wave (GW) parameter estimation when a plethora of signals are present in the data is one of the key challenges for the analysis of data from future GW detectors. Working within the linear signal approximation, we describe generic metrics to predict inference biases on GW source parameters in the presence of confusion noise from unfitted foregrounds, from overlapping signals that coalesce close in time to one another, and from residuals of other signals that have been incorrectly fitted out. We illustrate the formalism with simplified, yet realistic, scenarios appropriate to third-generation ground-based (Einstein Telescope) and space-based (LISA) detectors, and demonstrate its validity against Monte Carlo simulations. We find it to be a reliable tool to cheaply predict the extent and direction of the biases. Finally, we show how this formalism can be used to correct for biases that arise in the sequential characterization of multiple sources in a single data set, which could be a valuable tool to use within a global-fit analysis pipeline.
Brightest cluster galaxies are statistically special from z = 0.3 to z = 1
Authors: Dalal Roohi , Strauss Michael A , Sunayama Tomomi , Oguri Masamune , Lin Yen-Ting , Huang Song , Park Youngsoo , Takada Masahiro
Published: August 2021

We study brightest cluster galaxies (BCGs) in ∼5000 galaxy clusters from the Hyper Suprime-Cam (HSC) Subaru Strategic Program. The sample is selected over an area of 830 deg2 and is uniformly distributed in redshift over the range of z = 0.3−1.0. The clusters have stellar masses in the range of 1011.8−1012.9M⊙. We compare the stellar mass of the BCGs in each cluster to what we would expect if their masses were drawn from the mass distribution of the other member galaxies of the clusters. The BCGs are found to be ‘special’, in the sense that they are not consistent with being a statistical extreme of the mass distribution of other cluster galaxies. This result is robust over the full range of cluster stellar masses and redshifts in the sample, indicating that BCGs are special up to a redshift of z = 1.0. However, BCGs with a large separation from the centre of the cluster are found to be consistent with being statistical extremes of the cluster member mass distribution. We discuss the implications of these findings for BCG formation scenarios.
Twice exploration of tRNA +1 frameshifting in an elongation cycle of protein synthesis
Authors: Gamper Howard , Mao Yujia , Masuda Isao , McGuigan Henri , Blaha Gregor , Wang Yuhong , Xu Shoujun , Hou Ya-Ming
Published: August 2021

Inducing tRNA +1 frameshifting to read a quadruplet codon has the potential to incorporate a non-natural amino acid into the polypeptide chain. While this strategy is being considered for genome expansion in biotechnology and bioengineering endeavors, a major limitation is a lack of understanding of where the shift occurs in an elongation cycle of protein synthesis. Here, we use the high-efficiency +1-frameshifting SufB2 tRNA, containing an extra nucleotide in the anticodon loop, to address this question. Physical and kinetic measurements of the ribosome reading frame of SufB2 identify twice exploration of +1 frameshifting in one elongation cycle, with the major fraction making the shift during translocation from the aminoacyl-tRNA binding (A) site to the peptidyl-tRNA binding (P) site and the remaining fraction making the shift within the P site upon occupancy of the A site in the +1-frame. We demonstrate that the twice exploration of +1 frameshifting occurs during active protein synthesis and that each exploration is consistent with ribosomal conformational dynamics that permits changes of the reading frame. This work indicates that the ribosome itself is a determinant of changes of the reading frame and reveals a mechanistic parallel of +1 frameshifting with –1 frameshifting.
Le caractère d’ordre public du principe de la libre transmissibilité des actions en droit des sociétés commerciales de l’OHADA
Authors: Tsopbeing Marcel Williams
Published: August 2021

In order to protect various interests and guarantee legal certainty, the OHADA legislator has provided the essential rules for each form or category of company. Thus, the distinction between joint stock companies and public limited companies is based, in particular, on free negotiability and/or the free transferability of shares. To preserve this distinction, the principle of the free transferability of shares is of a public policy nature and therefore justifies a restriction of the contractual freedom of the partners. The latter may in fact have recourse to agreements relating to the transfer of shares (approval clause, preemption clause, inalienability clause) only on condition that this does not entail the abolition of the principle of the free transferability of shares.
Nucleic acid vaccines and CpG oligodeoxynucleotides for allergen immunotherapy
Authors: Jacquet Alain
Published: August 2021

Purpose of review

Molecular forms of allergen-specific immunotherapy (AIT) are continuously emerging to improve the efficacy of the treatment, to shorten the duration of protocols and to prevent any side effects. The present review covers the recent progress in the development of AIT based on nucleic acid encoding allergens or CpG oligodeoxynucleotides (CpG-ODN).

Recent findings

Therapeutic vaccinations with plasmid deoxyribonucleic acid (DNA) encoding major shrimp Met e 1 or insect For t 2 allergen were effective for the treatment of food or insect bite allergy in respective animal models. DNA expressing hypoallergenic shrimp tropomyosin activated Foxp3+ T regulatory (Treg) cells whereas DNA encoding For t 2 down-regulated the expression of pruritus-inducing IL-31. Co-administrations of major cat allergen Fel d 1 with high doses of CpG-ODN reduced Th2 airway inflammation through tolerance induction mediated by GATA3+ Foxp3hi Treg cells as well as early anti-inflammatory TNF/TNFR2 signaling cascade. Non-canonical CpG-ODN derived from Cryptococcus neoformans as well as methylated CpG sites present in the genomic DNA from Bifidobacterium infantis mediated Th1 or Treg cell differentiation respectively.

Recent studies on plasmid DNA encoding allergens evidenced their therapeutic potential for the treatment of food allergy and atopic dermatitis. Unmethylated or methylated CpG-ODNs were shown to activate dose-dependent Treg/Th1 responses. Large clinical trials need to be conducted to confirm these promising preclinical data. Moreover, tremendous success of messenger ribonucleic acid (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 must encourage as well the re-exploration of mRNA vaccine platform for innovative AIT.
Changes in Rates of Hospitalizations due to Cannabis Harms in Ontario, Canada Before the Legalization of Nonmedical Cannabis: Retrospective Population-level Study Between 2003 and 2017
Authors: Zygmunt Austin , Tanuseputro Peter , Brown Catherine , Lima Isac , Rhodes Emily , Myran Daniel
Published: August 2021

Objectives

To assess the burden of hospitalizations due to cannabis harms in Ontario, Canada before Canada’s legalization of nonmedical cannabis.

Methods

We conducted a retrospective population-level study that included all individuals living in Ontario between 2003 and 2017. We described patterns of hospitalizations due to cannabis harms in men and women by demographics, socioeconomic factors, and mental health comorbidities. We calculated annual crude rates of hospitalizations due to cannabis harms and assessed time trends using Poisson regression models.

Results

There were 39,092 hospitalizations due to cannabis harms among 32,811 unique individuals. Annual hospitalizations due to a cannabis harm increased by 176% between 2003 and 2017 (1712 vs 4730), with increases noted for all age groups and sexes. Rates of hospitalizations due to cannabis harms were greater in young adults, low-income individuals, and those with mental health comorbidities. Overall, the rate of hospitalizations due to cannabis harms increased on average by 7.8% per year (95% CI 7.5–8.0). Women aged 15 to 24 experienced the largest average annual increase (12.2% per year, 95% CI 11.5 to 12.8).

Conclusions

There are distinct patterns of hospitalizations due to cannabis harms in different priority populations. Young women aged 15 to 24 are a key demographic that is disproportionately burdened with a rapid increase in hospitalizations due to cannabis harms. Jurisdictions considering new approaches to cannabis control policy and addiction services should consider the rising burden of harms faced by youth and young adults when planning interventions.
Power and Privilege
Authors: Gallups Sarah F. , Ejem Deborah , Rosenzweig Margaret Q.
Published: August 2021

Despite advances in cancer care, inequalities in race, ethnicity, and social class in breast cancer outcomes still exist. Interpersonal communication is a critical piece to addressing health disparities and it is a core component of the oncology patient navigator role. While widely used, the concept of interpersonal communication is vague, understudied, and requires better clarification to promote equity in health communication. The aim of this article is to investigate the concept of interpersonal communication through a critical lens. Findings from this critical analysis identified a gap in the current literature addressing the intersections of race, gender, and social class.
Validation of the AO Spine Sacral Classification System: Reliability Among Surgeons Worldwide
Authors: Schroeder Gregory D. , Karamian Brian A. , Canseco Jose A. , Vialle Luiz R. , Kandziora Frank , Benneker Lorin M. , Rajasekaran Shanmuganathan , Holstein Jörg H. , Schnake Klaus J. , Kurd Mark F. , Dvorak Marcel F. , Vialle Emiliano N. , Joaquim Andrei F. , Kanna Rishi M. , Fehlings Michael , Wilson Jefferson R. , Chapman Jens R. , Krieg James C. , Kleweno Conor P. , Firoozabadi Reza , Öner F. Cumhur , Kepler Christopher K. , Vaccaro Alexander R.
Published: August 2021

Objectives:

To (1) demonstrate that the AO Spine Sacral Classification System can be reliably applied by general orthopaedic surgeons and subspecialists universally around the world and (2) delineate those injury subtypes that are most difficult to classify reliably to refine the classification before evaluating clinical outcomes.

Design:

Agreement study.

Setting:

All-level trauma centers, worldwide.

Participants:

One hundred seventy-two members of the AO Trauma and AO Spine community.

Intervention:

The AO Sacral Classification System was applied by each surgeon to 26 cases in 2 independent assessments performed 3 weeks apart.

Main Outcome Measurements:

Interobserver reliability and intraobserver reproducibility.

Results:

A total of 8097 case assessments were performed. The kappa coefficient for interobserver agreement for all cases was 0.72/0.75 (assessment 1/assessment 2), representing substantial reliability. When comparing classification grading (A/B/C) regardless of subtype, the kappa coefficient was 0.84/0.85, corresponding to excellent reliability. The kappa coefficients for interobserver reliability were 0.95/0.93 for type A fractures, 0.78/0.79 for type B fractures, and 0.80/0.83 for type C fractures. The overall kappa statistic for intraobserver reliability was 0.82 (range 0.18–1.00), representing excellent reproducibility. When only evaluating morphology type (A/B/C), the average kappa value was 0.87 (range 0.18–1.00), representing excellent reproducibility.

Conclusion:

The AO Spine Sacral Classification System is universally reliable among general orthopaedic surgeons and subspecialists worldwide, with substantial interobserver and excellent intraobserver reliability.
Efficacy and Safety of Locally Injected Tranexamic Acid in Hip Fracture Patients: A Retrospective Review
Authors: Witmer Daniel , Solomito Matthew J. , Kumar Mandeep , Shearier Emily , Davis Stephen
Published: August 2021

Objective:

To determine whether locally injected tranexamic acid (TXA) used in the surgical treatment of fragility hip fractures can lower transfusion rates without increasing the risk of complications.

Design:

Retrospective comparative cohort.

Setting:

Tertiary referral orthopaedic specialty hospital, Level I trauma center.

Patients/Participants:

A total of 490 patients (252 patients received TXA) 50 years of age and older who underwent surgery for a low-energy fragility fracture of the proximal femur between March 2018 and February 2020 were included in this study.

Intervention:

Use of locally injected TXA at the time of wound closure.

Main Outcome:

The main outcomes of this study were the number of patients requiring postoperative blood transfusions, incidences of venous thromboembolism, and surgical site infections.

Results:

A statistically significant difference was noted in the frequency of transfusion between patients who received TXA compared with those who did not receive TXA (33% vs. 43%, respectively) (P = 0.034). There were no significant differences in venous thromboembolism incidence (0.4% vs. 0.8% TXA vs. No TXA) (P = 0.526) or infections (0.4% vs. 0.4% TXA vs. No TXA) (P = 0.965). Regression analysis indicated that the use of TXA reduced the need for postoperative blood transfusion by 31% (odds ratio: 0.688, 95% CI: 0.477–0.993, P = 0.045).

Conclusion:

Locally injected TXA significantly reduced the need for postoperative transfusion in the surgical treatment of fragility hip fractures. In addition, there was no increased risk of complications in those receiving TXA versus those who did not. Locally injected TXA seems to be both a safe and effective way to reduce postoperative blood transfusions in patients with fragility hip fractures.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Regulations of expressions of rat/human sulfotransferases by anticancer drug, nolatrexed, and micronutrients
Authors: Maiti Smarajit , MaitiDutta Sangita , Chen Guangping
Published: August 2021

Cancer is related to the cellular proliferative state. Increase in cell-cycle regulatory function augments cellular folate pool. This pathway is therapeutically targeted. A number of drugs influences this metabolism, that is, folic acid, folinic acid, nolatrexed, and methotrexate. Our previous study showed methotrexate influences on rat/human sulfotransferases. Present study explains the effect of nolatrexed (widely used in different cancers) and some micronutrients on the expressions of rat/human sulfotransferases. Female Sprague-Dawley rats were treated with nolatrexed (01–100 mg/kg) and rats of both sexes were treated to folic acid (100, 200, or 400 mg/kg) for 2-weeks and their aryl sulfotransferase-IV (AST-IV; β-napthol sulfation) and sulfotransferase (STa; DHEA sulfation) activities, protein expression (western blot) and mRNA expression (RT-PCR) were tested. In human-cultured hepatocarcinoma (HepG2) cells nolatrexed (1 nM–1.2 mM) or folinic acid (10 nM–10 μM) were applied for 10 days. Folic acid (0–10 μM) was treated to HepG2 cells. PPST (phenol catalyzing), MPST (dopamine and monoamine), DHEAST (dehydroepiandrosterone and DHEA), and EST (estradiol sulfating) protein expressions (western-blot) were tested in HepG2 cells. Present results suggest that nolatrexed significantly increased sulfotransferases expressions in rat (protein, STa, F = 4.87, P < 0.05/mRNA, AST-IV, F = 6.702, P < 0.014; Student’s t test, P < 0.01–0.05) and HepG2 cells. Folic acid increased sulfotransferases activity/protein in gender-dependant manner. Both folic and folinic acid increased several human sulfotransferases isoforms with varied level of significance (least or no increase at highest dose) in HepG2 cells pointing its dose-dependent multiphasic responses. The clinical importance of this study may be furthered in the verification of sulfation metabolism of several exogenous/endogenous molecules, drug–drug interaction and their influences on cancer pathophysiological processes. Further studies are necessary.
Circular RNA circ-CCT3 promotes bortezomib resistance in multiple myeloma via modulating miR-223-3p/BRD4 axis
Authors: Liu Dan , Wang Yaya , Li Haiming , Peng Sida , Tan Huo , Huang Zhenqian
Published: August 2021

Multiple myeloma is a frequent hematologic malignancy. Bortezomib is the first-line drug for multiple myeloma chemotherapy. The present study aimed to investigate the potential role and mechanism of circular RNA chaperonin containing TCP1 subunit 3 (circ-CCT3) in bortezomib resistance of multiple myeloma. The levels of circ-CCT3, microRNA-223-3p (miR-223-3p), and bromodomain-containing 4 (BRD4) were detected by quantitative real-time PCR or western blot. Cell Counting Kit-8 (CCK-8) method was used to measure the half-inhibitory concentration of bortezomib and cell viability. Cell cycle distribution, apoptosis, proliferation and migration were determined by flow cytometry, 5-ethynyl-2′-deoxyuridine, and wound healing assay. The levels of relevant proteins were checked via western blot. The binding association between miR-223-3p and circ-CCT3/BRD4 was validated via a dual-luciferase reporter assay. Circ-CCT3 and BRD4 were upregulated, while miR-223-3p was downregulated in bortezomib-resistant multiple myeloma patients and cells. Silencing of circ-CCT3 enhanced the sensitivity of bortezomib-resistant multiple myeloma cells to bortezomib. Circ-CCT3 knockdown weakened bortezomib resistance via modulating miR-223-3p. Moreover, miR-223-3p increased bortezomib sensitivity by inhibiting BRD4. Downregulation of circ-CCT3 attenuated bortezomib resistance of multiple myeloma via regulating miR-223-3p/BRD4 pathway, which provided a new potential target for multiple myeloma chemoresistance.
A meta-analysis on overall survival and safety outcomes in patients with nonmetastatic castration-resistant prostate cancer treated with novel hormonal agents
Authors: Rizzo Alessandro , Oderda Marco , Mollica Veronica , Merler Sara , Morelli Franco , Fragomeno Benedetta , Taveri Elena , Sorgentoni Giulia , Santoni Matteo , Massari Francesco
Published: August 2021

Several novel androgen receptor (AR)-inhibitors have been introduced for nonmetastatic castration-resistant prostate cancer (nmCRPC) treatment, with the improvement of survival outcomes which need to be balanced against the risk of adverse events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating enzalutamide, apalutamide and darolutamide in nmCRPC patients, to assess overall survival (OS), incidence and risk of adverse drug events, adverse-events-related death and adverse-events-related treatment discontinuation. We selected three RCTs (SPARTAN, PROSPER and ARAMIS). New hormonal agents administration resulted in better OS, despite the increased risk of several any grade and grade 3–4 adverse events. In the decision-making process, careful evaluation of expected adverse events, patients’ comorbidities and maintenance of quality of life are mandatory.
Case report: ado-trastuzumab as second-line treatment in HER2 positive salivary duct carcinoma
Authors: Taha Tarek , Billan Salem
Published: August 2021

The objective of this report is to present the use and efficacy of ado-trastuzumab as an advanced line of therapy in salivary duct carcinoma (SDC) patient. An 84-year-old gentleman diagnosed with metastatic salivary duct tumor harboring overexpressed human epidermal growth factor receptor-2 has gone through resection surgery. The first line of treatment included initial doublet chemotherapy combined with trastuzumab, which was continued later as maintenance. PET-CT follow-up for 4 years has demonstrated no evidence of disease. However, upon recurrence, use of Ado-trastuzumab emtansine was prompted as second-line of treatment. This targeted patient-tailored therapy has accomplished a complete response. The effectiveness of ado-trastuzumab emtansine was notable within a short time period of two treatment cycles leading to full recovery. Specific agents aimed at altered oncogenes should be considered as a potential drug of choice in neoadjuvant HER2 positive SDC.