bluuebunny/crossref_metadata_2025 huggingface dataset:
Non calcium phosphate binders - Is there any evidence of benefit
Authors: Jadav Paresh R. , Husain S. Ali , Mohan Sumit , Crew Russell
Published: March 2022

Purpose of review

Low-level evidence and opinion-based clinical practice guidelines highlight the substantial uncertainty in the practice patterns of hyperphosphatemia management in patients with chronic kidney disease (CKD). This manuscript reviews the evidence for the choice of phosphate binders and its impact on clinical outcomes.

Recent findings

Phosphate binders are among the most common medications prescribed for patients on dialysis. Clinical practice guidelines recommend lowering phosphate levels toward normal range and restricting calcium-based binders in all CKD patients. There is substantial gap in the evidence underlying these recommendations with lack of any placebo-controlled, randomized trials showing survival benefits for any class of phosphate-binders. Despite the lack of evidence for specific phosphate target or if lowering phosphate improves survival, use of phosphate binders has remained central strategy in approach to hyperphosphatemia. Use of binders has added to the cost and contributed significant pill burden. Restriction of calcium-based binders to avoid positive calcium balance and consequent vascular calcification risk has a physiological rationale and weight of observational studies.

There is currently no conclusive evidence that definitively guides the choice of any specific binders for management of hyperphosphatemia in patients with CKD. Use of noncalcium-based binders has a theoretical advantage in restricting total calcium intake to decrease the risk of vascular calcification but no proven benefits for mortality.
Holmium: yttrium-aluminum-garnet laser with Moses: does it make a difference?
Authors: Corsini Christian , de Angelis Mario , Villa Luca , Somani Bhaskar K. , Pietropaolo Amelia , Montorsi Francesco , Goumas Ioannis Kartalas , Traxer Olivier , Salonia Andrea , Ventimiglia Eugenio
Published: March 2022

Purpose of review

Moses effect is an inherent physical principle of Ho:YAG laser functioning. Moses Technology is a pulse modulation modality of Ho:YAG laser, which became commercially available for the treatment of two urological conditions: urinary stones and benign prostatic obstruction. The purpose of this narrative review is to distinguish between Moses effect and Moses Technology, as well as to summarize the latest evidence on Moses Technology and its main application in the urological field.

Recent findings

During laboratory lithotripsy, Moses Technology seems to reduce stone retropulsion and determine higher ablation volume compared with regular lithotripsy. However, this technology presents similar characteristics to long pulse Ho:YAG laser, and several studies showed no significant difference between Moses Technology and standard lasers. When used in prostate enucleation, Moses Technology promises to reduce operating time by increasing the efficiency of prostate resection and improve the hemostasis. Moreover, some studies state that it is possible to reduce the HoLEP morbidity. Despite this, the clinical impact of the time reduction remains uncertain and different studies either present relevant limitations or are burdened by significant bias.

Although Moses effect has been extensively described and characterized, and several studies have been published on the usage of Moses Technology for both laser lithotripsy and laser enucleation of the prostate with Holmium YAG, solid clinical evidence on the real improvement of surgical outcomes is still missing.
Implications of DNA damage repair alterations for the management of prostate cancer
Authors: Lozano Rebeca , Olmos David , Castro Elena
Published: March 2022

Purpose of review

In this review, we summarize the prevalence of alterations in DNA damage repair (DDR) genes in prostate cancer, their clinical significance, the therapeutic strategies developed to take advantage of the impaired tumour ability to repair DNA and the diagnostic approaches available to identify patients likely to benefit from DDR-targeting agents.

Recent findings

DDR alterations are more frequent in metastatic than in localized prostate cancer and some of them associate with aggressive disease whereas the significance of others remain unclear. The most appropriate management approach for DDR-defective prostate cancer patients is unknown. Clinical trials have demonstrated the efficacy of different poly-ADP ribose polymerase inhibitors (PARPi) to treat metastatic castration-resistant prostate cancer patients with BRCA1/2 alterations, although there may be other DDR alterations that sensitize patients to these drugs. Multiple strategies to target DDR defects are being investigated, including PARPi in combination, platinum-based chemotherapy and immunotherapy, both in earlier and late disease stages. Optimization of molecular testing is paramount for the implementation of precision oncology in prostate cancer.

Certain DDR defects present in prostate cancer have prognostic and therapeutic implications whereas the significance of other DDR alterations is yet to be elucidated.
Patient Experience With Vascular Access Management Informs Satisfaction With Overall Hospitalization Experience
Authors: Omkar Prasad Rohini , Chew Timothy , Giri Jayant R. , Hoerauf Klaus
Published: March 2022

Peripheral intravenous catheter (PIVC) insertion is a common invasive procedure performed during hospitalization. The present study reports results from a survey of 543 patients who have had PIVC insertion during their hospital stay in Singapore and the Philippines during the period between November 2018 and February 2019. The survey assessed the importance of 5 domains of patient-centered care on patient satisfaction with their hospitalization experience, including pain management, infection prevention, health care provider competence with vascular access, physical comfort, and effectiveness of communication during vascular access management. Health care provider competence, infection prevention, and pain management ranked as the most important determinants of patient satisfaction. Patients were more likely to lose their trust in health care providers and express anxiety if they experienced multiple needle insertion attempts or PIVC-related complications, whereas patients who were satisfied with their PIVC insertion were more likely to express satisfaction with their overall hospital stay. Improving vascular access management with a focus on enhancing vascular access skills, infection prevention, and pain management may improve patient satisfaction.
The induced membrane technique in animal models: a systematic review
Authors: Sun Hening , Godbout Charles , Hali Kalter , Momic Jovana , Schemitsch Emil H. , Nauth Aaron
Published: March 2022

Objectives:

The induced membrane technique (IMT) is a 2-stage surgical approach that has become increasingly popular to manage bone defects. Preclinical investigations have been conducted to better understand and define several aspects of this technique. This review summarizes the literature regarding the IMT performed in animal models and identifies potential future directions.

Data Sources:

Biosis Citation Index, Ovid Embase, and Ovid MEDLINE databases were searched from inception up to June 23, 2021 for articles related to the IMT.

Study Selection:

Animal studies involving the use of the IMT for segmental defects in long bones were selected. Only full-length original research articles published in English or French were included.

Data Extraction:

Two authors extracted the data from the selected studies and a third author verified the accuracy of the information.

Data Synthesis:

Information concerning the animal model, the surgical procedures, and the outcome measures were recorded for each study and compiled.

Conclusions:

Forty-seven studies were included in this review. Twenty-nine studies (62%) performed both stages of the technique, but only 8 (17%) reported on radiographic union rates explicitly and 5 (11%) included biomechanical testing. A large proportion of the preclinical literature on the IMT has failed to report on radiographic union as an outcome. While studies reporting membrane properties are valuable, they may not provide information that translates into clinical practice or further clinical research if the ultimate outcome of bony healing is not considered. Future animal studies of the IMT should consider this in their study design.
Usefulness of real-time RT-PCR to understand the kinetics of SARS-CoV-2 in blood: a prospective study
Authors: Zurita-Cruz Nelly Daniela , Martín-Ramírez Alexandra , Rodríguez-Serrano Diego Aníbal , González-Álvaro Isidoro , Roy-Vallejo Emilia , De la Cámara Rafael , García-Rodrigo Leticia Fontán , Domingo Laura Cardeñoso
Published: March 2022

Background

SARS-CoV-2 viral load and kinetics assessed in serial blood samples from hospitalised COVID-19 patients by RT-PCR are poorly understood.

Methods

We conducted an observational, prospective case series study in hospitalised COVID-19 patients. Clinical outcome data (Intensive Care Unit admission and mortality) were collected from all patients until discharge. Viremia was determined longitudinally during hospitalisation, in plasma and serum samples using two commercial and standardised RT-PCR techniques approved for use in diagnosis of SARS-CoV-2. Viral load (copies/mL and log10) was determined with quantitative TaqPath™COVID-19 test.

Results

SARS-CoV-2 viremia was studied in 57 hospitalised COVID-19 patients. Persistent viremia (PV) was defined as two or more quantifiable viral loads detected in blood samples (plasma/serum) during hospitalisation. PV was detected in 16 (28%) patients. All of them, except for one who rapidly progressed to death, cleared viremia during hospitalisation. Poor clinical outcome occurred in 62.5% of patients with PV, while none of the negative patients or those with sporadic viremia presented this outcome (p<0.0001). Viral load was significantly higher in patients with PV than in those with Sporadic Viremia (p<0.05). Patients presented PV for a short period of time: median time from admission was 5 days (Range=2-12) and 4.5 days (Range=2-8) for plasma and serum samples, respectively. Similar results were obtained with all RT-PCR assays for both types of samples.

Conclusions

Detection of persistent SARS-CoV-2 viremia, by real time RT-PCR, expressed as viral load over time, could allow identifying hospitalised COVID-19 patients at risk of poor clinical outcome.

Highlights

Commercial RT-PCR techniques could be used to monitor SARS-CoV-2 viremia kinetics.

SARS-CoV-2 persistent viremia is related with poor outcome in COVID-19 patient.

SARS-Cov-2 viremia kinetics could be used as a biomarker of poor prognosis.

Plasma samples are the best choice for analysis of SARS-CoV-2 viremia kinetics.
Reconstructing subdistrict-level population denominators in Yemen after six years of armed conflict and forced displacement
Authors: Checchi Francesco , Koum Besson Emilie Sabine
Published: March 2022

Introduction

Yemen has experienced widespread insecurity since 2014, resulting in large-scale internal displacement. In the absence of reliable vital events registration, we tried to reconstruct the evolution of Yemen’s population between June 2014 and September 2021, at subdistrict (administrative level 3) resolution, while accounting for growth and internal migration.

Methods

We reconstructed subdistrict-month populations starting from June 2014 WorldPop gridded estimates, as a function of assumed birth and death rates, estimated changes in population density, net internal displacement to and from the subdistrict and assumed overlap between internal displacement and WorldPop trends. Available displacement data from the Displacement Tracking Matrix (DTM) project were subjected to extensive cleaning and imputation to resolve missingness, including through machine learning models informed by predictors such as insecurity. We also modelled the evolution of displaced groups before and after assessment points. To represent parameter uncertainty, we complemented the main analysis with sensitivity scenarios.

Results

We estimated that Yemen’s population rose from about 26.3M to 31.1M during the seven-year analysis period, with considerable pattern differences at sub-national level. We found that some 10 to 14M Yemenis may have been internally displaced during 2015-2016, about five times United Nations estimates. By contrast, we estimated that the internally displaced population had declined to 1-2M by September 2021.

Conclusions

This analysis illustrates approaches to analysing the dynamics of displacement, and the application of different models and data streams to supplement incomplete ground observations. Our findings are subject to limitations related to data quality, model inaccuracy and omission of migration outside Yemen. We recommend adaptations to the DTM project to enable more robust estimation.
VinDr-Mammo: A large-scale benchmark dataset for computer-aided diagnosis in full-field digital mammography
Authors: Nguyen Hieu T. , Nguyen Ha Q. , Pham Hieu H. , Lam Khanh , Le Linh T. , Dao Minh , Vu Van
Published: March 2022

Mammography, or breast X-ray, is the most widely used imaging modality to detect cancer and other breast diseases. Recent studies have shown that deep learning-based computer-assisted detection and diagnosis (CADe/x) tools have been developed to support physicians and improve the accuracy of interpreting mammography. However, most published datasets of mammography are either limited on sample size or digitalized from screen-film mammography (SFM), hindering the development of CADe/x tools which are developed based on full-field digital mammography (FFDM). To overcome this challenge, we introduce VinDr-Mammo – a new benchmark dataset of FFDM for detecting and diagnosing breast cancer and other diseases in mammography. The dataset consists of 5,000 mammography exams, each of which has four standard views and is double read with disagreement (if any) being resolved by arbitration. It is created for the assessment of Breast Imaging Reporting and Data System (BI-RADS) and density at the breast level. In addition, the dataset also provides the category, location, and BI-RADS assessment of non-benign findings. We make VinDr-Mammo publicly available on https://physionet.org/ as a new imaging resource to promote advances in developing CADe/x tools for breast cancer screening.
Short-term drop in antibody titer after the third dose of SARS-CoV-2 BNT162b2 vaccine in adults
Authors: Herzberg Jonas , Fischer Bastian , Becher Heiko , Becker Ann-Kristin , Honarpisheh Human , Guraya Salman Yousuf , Strate Tim , Knabbe Cornelius
Published: March 2022

Little is known about the longevity of antibodies after a third dose of BNT162b2 (BioNTech/Pfizer). Therefore, the serum antibody levels were evaluated after the third dose of BNT162b2 which dropped significantly within 11 weeks from 4155.59 ± 2373.65 BAU/ml to 2389.10 ± 1433.90 BAU/ml, p-value <0.001 but remained higher than after the second dose.

These data underline the positive effect of third dose of BNT162b2 but shows a rapid and significant drop of antibodies within a short span of time.

Trial Registration

This trial was prospectively registered in the German Clinical Trial Register (DRKS00021270).
Evaluation of the Causal Relationship Between Smoking and Schizophrenia in Asia
Authors: Su Mei-Hsin , Lai Rou-Yi , Lin Yen-Feng , Chen Chia-Yen , Feng Yen-Chen A. , Hsiao Po-Chang , Wang Shi-Heng
Published: March 2022

Cigarette smoking has been suggested to be associated with the risk of schizophrenia (SCZ) in observational studies. A significant causal effect of smoking on SCZ has been reported in the European population using the Mendelian randomization (MR) approach; however, no evidence of causality was found in participants from East Asia (EAS). Using the Taiwan Biobank (TWBB, sample size up to 79,989), we conducted genome-wide association studies (GWAS) to identify susceptibility loci for smoking behavior, which included the initiation of smoking and the onset age. To maximize the power of genetic discovery in the EAS population, we meta-analyzed GWAS from the TWBB and Biobank Japan (BBJ, sample size up to 165,436) for smoking traits. The GWAS for SCZ was taken from the Asia Psychiatric Genomics Consortium, which included 22,778 cases and 35,362 controls. We performed a two-sample MR to estimate the causality of smoking behavior on SCZ in the EAS population. In TWBB, we identified one novel locus that met genome-wide significance for onset age. In a meta-analysis of TWBB and BBJ, we identified two novel loci for smoking initiation. In MR, a marginal significance was found for the causality of smoking initiation on SCZ (odds ratio (OR) = 4.00, 95% confidence interval (CI) = 0.89–18.01,P= 0.071). Later onset age for smoking was causally associated with a lower risk of SCZ (OR for a per-year increase in onset = 0.96, 95% CI = 0.91–1.01) with a marginal significance (P= 0.098).
Intra-membrane client recognition potentiates the chaperone functions of Calnexin
Authors: Bloemeke Nicolas , Meighen-Berger Kevin , Hitzenberger Manuel , Bach Nina C. , Parr Marina , Coelho Joao P.L. , Frishman Dmitrij , Zacharias Martin , Sieber Stephan A. , Feige Matthias J.
Published: March 2022

One third of the human proteome are membrane proteins. They are particularly vulnerable to misfolding, often requiring assistance by molecular chaperones. Calnexin (CNX), one of the most abundant ER chaperones, plays an important role in membrane protein biogenesis and engages clients via its sugar-binding lectin domain.

Using mass spectrometric analyses, we show that Calnexin (CNX) interacts with a large number of non-glycosylated membrane proteins, suggesting additional binding modes. We find that misfolded membrane proteins are preferentially bound by CNX and that CNX uses its single transmembrane domain (TMD) for client recognition. Combining experimental and computational approaches, we systematically dissect signatures for intramembrane client recognition by CNX and identify sequence motifs within the CNX TMD region that mediate client binding. Building on this, we show that intramembrane client binding potentiates the chaperone functions of CNX.

Together, this study reveals a widespread role of CNX client recognition in the lipid bilayer, which synergizes with its established lectin-based substrate binding. Molecular chaperones thus can combine different interaction modes to support the biogenesis of the diverse eukaryotic membrane proteome.
Template-based assembly of proteomic short reads forde novoantibody sequencing and repertoire profiling
Authors: Schulte Douwe , Peng Weiwei , Snijder Joost
Published: March 2022

Antibodies can target a vast molecular diversity of antigens. This is achieved by generating a complementary diversity of antibody sequences though somatic recombination and hypermutation. A full understanding of the antibody repertoire in health and disease therefore requires dedicatedde novosequencing methods. Next generation cDNA sequencing methods have laid the foundation of our current understanding of the antibody repertoire, but these methods share one major limitation in that they target the antibody-producing B-cells, rather than the functional secreted product in bodily fluids. Mass spectrometry-based methods offer an opportunity to bridge this gap between antibody repertoire profiling and bulk serological assays, as they can access antibody sequence information straight from the secreted polypeptide products. In a step to meeting the challenge of MS-based antibody sequencing, we present a fast and simple software tool (Stitch) to map proteomic short reads to user-defined templates with dedicated features for both monoclonal antibody sequencing and profiling of polyclonal antibody repertoires. We demonstrate the use of Stitch by fully reconstructing 2 monoclonal antibody sequences with >98% accuracy (including I/L assignment); sequencing a Fab from patient serum isolated by reversed-phase LC fractionation against a high background of homologous antibody sequences; sequencing antibody light chains from urine of multiple-myeloma patients; and profiling the IgG repertoire in sera from patients hospitalized with COVID-19. We demonstrate that Stitch assembles a comprehensive overview of the antibody sequences that are represented in the dataset and provides an important first step towards analyzing polyclonal antibodies and repertoire profiling.
Erbb4 deletion from fast-spiking interneurons causes psychosis-relevant neuroimaging phenotypes
Authors: Kiemes A. , Serrano Navacerrada M. E. , Kim E. , Randall K. , Simmons C. , Rojo Gonzalez L. , Petrinovic M.M. , Lythgoe D.J. , Rotaru D. , Di Censo D. , Hirshler L. , Barbier E. L. , Vernon A. C. , Stone J. M. , Davies C. , Cash D. , Modinos G.
Published: March 2022

Converging lines of evidence suggest that dysfunction of cortical parvalbumin-expressing (PV+) GABAergic interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and levels of glutamatergic metabolites, and decreases in binding of GABAA α5 receptors and the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between PV+ interneuron dysfunction and these neuroimaging readouts have yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal PV+ interneurons leads to several synaptic, behavioral and cognitive phenotypes relevant to psychosis in mice. Here, we investigated how this PV+ interneuron disruption affects the hippocampal in vivo neuroimaging readouts in the Erbb4 model. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n=12) and their wild-type littermates (Erbb4F/F, n=12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Erbb4 mutant mice showed significantly elevated CBF and glutamine levels, as well as decreased SV2A density compared to wild-type littermates. No significant GABAA receptor density differences were identified. These findings demonstrate that specific disruption of cortical PV+ interneurons in mice recapitulate some of the key neuroimaging findings in psychosis patients, and link PV+ interneuron deficits to non-invasive, translational measures of brain function and neurochemistry that can be used across species.
Algae community structure and relation to environmental factors in the Hulanhe Wetland, Northeast China
Authors: Hui Hongkuan , Wang Min , Li Yunlong , Liu Yubin
Published: March 2022

The distribution characteristic of algae community was evaluated in eight sampling sites based on a monthly survey during May to October 2020 and 2021 in the Hulanhe Wetland, Northeast China. Algae and water environmental factors including water temperature (T), pH, Conductivity (Cond.), biochemical oxygen demand (BOD), chemical oxygen demand (COD), total organic carbons (TOC), total phosphorus (TP) and nitrogen (TN) were investigated, and a total of 216 taxa were identified by microscope. The algae community was dominated by Bacillariophyta, Chlorophyta and Euglenophyta. Species such asMelosira granulate, Cyclotella meneghiniana, Navicula cryptocephalaandPandorina morumwere the most common species. Significant difference of the algae composition and abundance were found in the different sampling sites. Species composition in H8 were different variously with other sites, provide a good chance for us to study the tolerance of the species, compared with other sites, several pollution indicator species were observed. According to canonical correspondence analysis (CCA), TN and TP were the main environmental factors affecting the distribution of algae. Furthermore, temperature and dissolved oxygen were also important to the algae community. It is suggested that the relationship between algae community and environmental factors can point to new directions in future studies on the water quality and habitat conditions in a wetland.
The origin, epidemiology and phylodynamics of HIV-1 CRF47_BF
Authors: Hill Gracelyn , Pérez-Losada Marcos , Delgado Elena , Benito Sonia , Montero Vanessa , Gil Horacio , Sánchez Mónica , Cañada-García Javier , García-Bodas Elena , Crandall Keith A. , Thomson Michael M ,   The Spanish Group for the Study of New HIV Diagnoses
Published: March 2022

CRF47_BF is a circulating recombinant form (CRF) of the human immunodeficiency virus type 1 (HIV-1), the etiological agent of AIDS. CRF47_BF represents one of 19 CRFx_BFs and has a geographic focus in Spain, where it was first identified in 2010. Since its discovery, CRF47_BF has expanded considerably in Spain, predominantly through heterosexual contact (∼56% of the infections). Little is known, however, about the origin and diversity of this CRF or its epidemiological correlates, as very few samples have been available so far. This study conducts a phylogenetic analysis with representatives of all CRFx_BF sequence types along with HIV-1 M Group subtypes to place the CRF47_BF sequences in a definitive phylogenetic context. The CRFx_BF sequences cluster into a single, not well supported, clade that includes their dominant parent subtypes (subtype B and subtype F). This clade also includes subtype D and excludes subsubtype F2. The CRF47_BF sequences all share a most recent common ancestor. Further analysis of this clade couples CRF47_BF protease-reverse transcriptase sequences and epidemiological data from an additional 87 samples collected throughout Spain, coupled with additional CRF47_BF database sequences from Brazil and Spain to investigate the origin and phylodynamics of CRF47_BF. The Spanish region with the highest proportion of CRF47_BF samples in the data set was the Basque Country (43.7%) with Navarre next highest at 19.5%. We include in our analysis epidemiological data on host sex, mode of transmission, time of collection, and geographic region. The phylodynamic analysis indicates that CRF47_BF originated in Brazil around 1993-1994 and spread to Spain from Brazil in approximately 1999-2000. The virus spread rapidly throughout Spain with increasing population sizes prior to 2010 and again between 2010 and 2017 with population declines to 2019 and a steady state through 2020. Three strongly supported clusters associated with Spanish regions (Basque Country, Navarre, and Aragon), together comprising 60.8% of the Spanish samples, were identified, one of which was also associated with transmission among men who have sex with men. The expansion in Spain of CRF47_BF, together with that of other CRFs and subtype variants of South American origin, previously reported, reflects the increasing relationship between the South American and European HIV-1 epidemics.
A non-coding single nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation
Authors: Yanchus Connor , Drucker Kristen L. , Kollmeyer Thomas M. , Tsai Ricky , Liang Minggao , Jiang Lingyan , Pawling Judy , Ali Asma , Decker Paul , Kosel Matt , Panda Arijit , Malik Ahmad , Al-Zahrani Khalid N. , Hernandez J. Javier , Ahmed Musaddeque , Loganathan Sampath Kumar , Trcka Daniel , Michaelraj Antony , Fortin Jerome , Mazrooei Parisa , Zhou Lily , Elia Andrew , Lupien Mathieu , He Housheng Hansen , Wang Liguo , Abyzov Alexej , Dennis James W. , Wilson Michael D. , Wrana Jeffrey , Lachance Daniel , Wrensch Margaret , Wiencke John , Pennacchio Len A. , Dickel Diane E. , Visel Axel , Taylor Michael , Zadeh Gelareh , Dirks Peter , Eckel-Passow Jeanette E. , Mak Tak , Kvon Evgeny , Jenkins Robert B. , Schramek Daniel
Published: March 2022

Establishing causal links between inherited polymorphisms and cancer risk is challenging. Here, we focus on the single nucleotide polymorphism rs55705857 (A>G), which confers a 6-fold increased risk of IDH-mutant low-grade glioma (LGG) and is amongst the highest genetic associations with cancer. By fine-mapping the locus, we reveal that rs55705857 itself is the causal variant and is associated with molecular pathways that drive LGG. Mechanistically, we show that rs55705857 resides within a brain-specific enhancer, where the risk allele disrupts OCT2/4 binding, allowing increased interaction with the Myc promoter and increased Myc expression. To functionally test rs55705857, we generated an IDH1R132H-driven LGG mouse model and show that mutating the highly conserved, orthologous mouse rs55705857 locus dramatically accelerated tumor development from 463 to 172 days and increased penetrance from 30% to 75%. Overall, our work generates new LGG models and reveals mechanisms of the heritable predisposition to lethal glioma in ∼40% of LGG-patients.
Non-literal language processing is jointly supported by the language and Theory of Mind networks: Evidence from a novel meta-analytic fMRI approach
Authors: Hauptman Miriam , Blank Idan , Fedorenko Evelina
Published: March 2022

Going beyond the literal meaning of utterances is key to communicative success. However, the mechanisms that support non-literal inferences remain debated. Using a novel meta-analytic approach, we evaluate the contribution of linguistic, social-cognitive, and executive mechanisms to non-literal interpretation. We identified 74 fMRI experiments (n=1,430 participants) from 2001-2021 that contrasted non-literal language comprehension with a literal control condition, spanning ten phenomena (e.g., metaphor, irony, indirect speech). Applying the activation likelihood estimation approach to the 825 activation peaks yielded six left-lateralized clusters. We then evaluated the locations of both the individual-study peaks and the clusters against probabilistic functional atlases (cf. macroanatomy, as is typically done) for three candidate brain networks—the language-selective network (Fedorenko et al., 2011), which supports language processing, the Theory of Mind (ToM) network (Saxe & Kanwisher, 2003), which supports social inferences, and the domain-general Multiple-Demand (MD) network (Duncan, 2010), which supports executive control. These atlases were created by overlaying individual activation maps of participants who performed robust and extensively validated ‘localizer’ tasks that target each network in question (n=806 for language; n=198 for ToM; n=691 for MD). We found that both the individual-study peaks and the ALE clusters fell primarily within the language network and the ToM network. These results suggest that non-literal processing is supported by both i) mechanisms that process literal linguistic meaning, and ii) mechanisms that support general social inference. They thus undermine a strong divide between literal and non-literal aspects of language and challenge the claim that non-literal processing requires additional executive resources.
A versatile pattern-forming cortical circuit based on Rho, F-actin, Ect2, and RGA-3/4
Authors: Michaud Ani , Leda Marcin , Swider Zachary T. , Kim Songeun , He Jiaye , Landino Jennifer , Valley Jenna R. , Huisken Jan , Goryachev Andrew B. , von Dassow George , Bement William
Published: March 2022

Many cells can generate complementary traveling waves of actin filaments (F-actin) and cytoskeletal regulators. This phenomenon, termed cortical excitability, results from coupled positive and negative feedback loops of cytoskeletal regulators. The nature of these feedback loops, however, remains poorly understood. We assessed the role of the Rho GAP RGA-3/4 in the cortical excitability that accompanies cytokinesis in both frog and starfish. RGA-3/4 localizes to the cytokinetic apparatus, “chases” Rho waves in an F-actin-dependent manner and, when co-expressed with the Rho GEF Ect2, is sufficient to convert the normally quiescent, immature Xenopus oocyte cortex into a dramatically excited state. Experiments and modeling show that changing the ratio of RGA-3/4 to Ect2 produces a range of cortical behaviors from pulses to complex waves of Rho activity. We conclude that RGA-3/4, Ect2, Rho and F-actin form the core of a circuit that drives a diverse range of cortical behaviors, and demonstrate that the immature oocyte is a powerful model for characterizing these dynamics.

Michaud et al. identify Ect2 and RGA-3/4 as core components of the cortical excitability circuit associated with cytokinesis. Additionally, they demonstrate that the immature Xenopus oocyte is a powerful model for characterizing excitable dynamics.
Neuroendocrinology of the lung revealed by single cell RNA sequencing
Authors: Kuo Christin S. , Darmanis Spyros , Diaz de Arce Alex , Liu Yin , Almanzar Nicole , Wu Timothy T.H. , Quake Stephen R. , Krasnow Mark A.
Published: March 2022

Pulmonary neuroendocrine cells (PNECs) are sensory epithelial cells that transmit airway status to the brain via sensory neurons and locally via CGRP and GABA. Several other neuropeptides and neurotransmitters have been detected in various species, but the number, targets, functions, and conservation of PNEC signals are largely unknown. We used scRNAseq to profile hundreds of the rare mouse and human PNECs. This revealed >40 PNEC neuropeptide and peptide hormone genes, most cells expressing unique combinations of 5-18 genes. Peptides are packaged in separate vesicles, release presumably regulated by the distinct, multimodal combinations of sensors expressed by each PNEC. Expression of cognate receptors predicts an array of local targets, and we show the new PNEC signal angiotensin directly activates innervating sensory neurons. Many signals lack lung targets so may have endocrine activity like those of PNEC- derived carcinoid tumors. PNECs are an extraordinarily rich and diverse signaling hub rivaling the enteroendocrine system.
Ultrastructural characterisation of young and aged dental enamel by atomic force microscopy
Authors: Leiva-Sabadini Camila , Schuh Christina MAP , Barrera Nelson P , Aguayo Sebastian
Published: March 2022

Recent advances in atomic force microscopy (AFM) have allowed the characterisation of dental-associated biomaterials and biological surfaces with high-resolution and minimal sample preparation. In this context, the topography of dental enamel – the hardest mineralised tissue in the body – has been explored with AFM-based approaches at the micro-scale. With age, teeth are known to suffer changes that can impact their structural stability and function; however, changes in enamel structure because of ageing have not yet been explored with nanoscale resolution. Therefore, the aim of this exploratory work was to optimise an approach to characterise the ultrastructure of dental enamel and determine potential differences in topography, hydroxyapatite (HA) crystal size, and surface roughness at the nanoscale associated to ageing. For this, a total of six teeth were collected from human donors from which enamel specimens were prepared. By employing AC mode imaging, HA crystals were characterised in both transversal and longitudinal orientation with high-resolution in environmental conditions. Sound superficial enamel displayed the presence of a pellicle-like coating on its surface, that was not observable on cleaned specimens. Acidetching exposed crystals that were imaged and morphologically characterised in highresolution at the nanoscale in both the external and internal regions of enamel in older and younger specimens. Our results demonstrated important individual variations in HA crystal width and roughness parameters across the analysed specimens; however, an increase in surface roughness and decrease in HA width was observed for the pooled older external enamel group compared to younger specimens. Overall, high-resolution AFM was an effective approach for the qualitative and quantitative characterisation of human dental enamel ultrastructure at the nanometre range. Future work should focus on exploring the ageing of dental enamel with increased sample sizes to compensate for individual differences as well as other potential confounding factors such as behavioural habits and mechanical forces.
Automated detection of axonal damage along white matter tracts in acute severe traumatic brain injury
Authors: Maffei Chiara , Gilmore Natalie , Snider Samuel B. , Foulkes Andrea S. , Bodien Yelena G. , Yendiki Anastasia , Edlow Brian L.
Published: March 2022

New techniques for individualized assessment of white matter integrity are needed to detect traumatic axonal injury (TAI) and predict outcomes in critically ill patients with acute severe traumatic brain injury (TBI). Diffusion MRI tractography has the potential to quantify white matter microstructure in vivo and has been used to characterize tract-specific changes following TBI. However, tractography is not routinely used in the clinical setting to assess the extent of TAI, in part because focal lesions reduce the robustness of automated methods. Here, we propose a pipeline that combines automated tractography reconstructions of 40 white matter tracts with multivariate analysis of along-tract diffusion metrics to assess the presence of TAI in individual patients with acute severe TBI. We used the Mahalanobis distance to identify abnormal white matter tracts in each of 18 patients with acute severe TBI as compared to 33 healthy subjects. In all patients for which a FreeSurfer anatomical segmentation could be obtained (17 of 18 patients), including 13 with focal lesions, the automated pipeline successfully reconstructed a mean of 37.5 +/- 2.1 white matter tracts without the need for manual intervention. A mean of 2.5 +/- 2.1 tracts resulted in partial or failed reconstructions and needed to be reinitialized upon visual inspection. The pipeline detected at least one abnormal tract in all patients (mean: 9.07 +/- 7.91) and could accurately discriminate between patients and controls (AUC: 0.91). The individual patients’ profiles showed the number and neuroanatomic location of abnormal tracts varied across patients and levels of consciousness. The premotor, temporal, and parietal sections of the corpus callosum were the most commonly damaged tracts (in 10, 9, and 8 patients respectively), consistent with histological studies of TAI. TAI measures were not associated with concurrent behavioral measures of consciousness. In summary, we provide proof-of-principle evidence that an automated tractography pipeline has translational potential to detect and quantify TAI in individual patients with acute severe traumatic brain injury.
Accelerating Minimap2 for accurate long read alignment on GPUs
Authors: Sadasivan Harisankar , Maric Milos , Dawson Eric , Iyer Vishanth , Israeli Johnny , Narayanasamy Satish
Published: March 2022

Long read sequencing technology is becoming increasingly popular for Precision Medicine applications like Whole Genome Sequencing (WGS) and microbial abundance estimation. Minimap2 is the state-of-the-art aligner and mapper used by the leading long read sequencing technologies, today. However, Minimap2 on CPUs is very slow for long noisy reads. ∼60-70% of the run-time on a CPU comes from the highly sequential chaining step in Minimap2. On the other hand, most Point-of-Care computational workflows in long read sequencing use Graphics Processing Units (GPUs). We present minimap2-accelerated (mm2-ax), a heterogeneous design for sequence mapping and alignment where minimap2’s compute intensive chaining step is sped up on the GPU and demonstrate its time and cost benefits.

We extract better intra-read parallelism from chaining without loosing mapping accuracy by forward transforming Minimap2’s chaining algorithm. Moreover, we better utilize the high memory available on modern cloud instances apart from better workload balancing, data locality and minimal branch divergence on the GPU. We show mm2-ax on an NVIDIA A100 GPU improves the chaining step with 5.41 - 2.57X speedup and 4.07 - 1.93X speedup : costup over the fastest version of Minimap2, mm2-fast, benchmarked on a Google Cloud Platform instance of 30 SIMD cores.
NDF is a transcription factor that stimulates elongation by RNA polymerase II
Authors: Fei Jia , Xu Jun , Li Ziwei , Xu Kevin , Wang Dong , Kassavetis George A. , Kadonaga James T.
Published: March 2022

RNA polymerase II (Pol II) elongation is a critical step in gene expression. Here we found that NDF, which was identified as a bilaterian nucleosome-destabilizing factor, is also a Pol II transcription factor that stimulates elongation with plain DNA templates in the absence of nucleosomes. NDF binds directly to Pol II and enhances elongation by a different mechanism than that used by transcription factor TFIIS. Moreover, yeast Pdp3, which is related to NDF, binds to Pol II and stimulates elongation. Thus, NDF is a Pol II binding transcription elongation factor that is localized over gene bodies and is conserved from yeast to humans.
Tetra-μ-acetato-κ8
O:O′-bis[(3-chloropyridine-κN)ruthenium(II,III)](Ru—Ru) hexafluoridophosphate 1,2-dichloroethane monosolvate
Authors: Aquino Anthony J. , Gerrior Daniel , Cameron T. Stanley , Robertson Katherine N. , Aquino Manuel A.S.
Published: March 2022

The title compound, [Ru2(μ-O2CCH3)4(C5H4ClN)2]PF6·C2H4Cl2, was obtained via a rapid substitution reaction of 3-chloropyridine for water in [Ru2(μ-O2CCH3)4(H2O)2]PF6 in 2-propanol and subsequent crystallization from a dichloroethane solution. The cationic diruthenium(II,III) tetraacetate core lies on a crystallographic inversion center with Ru—Ru and Ru—N bond lengths of 2.2738 (3) and 2.2920 (17) Å, respectively. The Ru—Ru—N bond angle is close to linear at 176.48 (4)°, and a significant π-stacking interaction of 3.5649 (16) Å is seen between overlapping pyridine rings of adjacent cations.
Millennials' online perceptions: the role of cultural characteristics in creating e-loyalty
Authors: Li Jie , Ul Haq Junaid , Hussain Sajjad
Published: March 2022

Purpose

Millennials, a cohort of young consumers, are the primary group of shoppers via e-commerce. This study aims to identify Chinese individual cultural values in millennials and examine the role of perceived shopping (hedonic and utilitarian) values in creating e-loyalty.

Design/methodology/approach

Data were collected from 296 Chinese millennials who use online shopping websites and apps. Confirmatory factor analysis was used to examine the validity and reliability of the methodology. Structural equation modeling was employed to test the proposed hypotheses.

Findings

All hypotheses were supported except one: the respondents rejected the impact of the face value on utilitarianism. The findings confirmed that Chinese individual cultural characteristics (face and Yuan) impact perceived shopping values (hedonic and utilitarian). Furthermore, these shopping values significantly influence e-loyalty.

Research limitations/implications

The study's findings suggest some implications that academicians and market practitioners should consider. Additional implications for business managers focus on cultural characteristics, strong local teams, market-based approaches and long-term strategies.

Originality/value

The present work highlights the online shopping behavior of Chinese millennials by exploring e-loyalty, considering its two dimensions.
Effects of replacement of fat and NaCl by hydrolyzed collagen and mix of herbs on quality properties of chicken hamburger
Authors: Santana Neto Deocleciano Cassiano de , de Lima Flávio Bruno Soares , Freire Luís Flávio da Silva , Santos Vanessa da Costa , Rodrigues David Santos , Ferreira Valquiria Cardoso da Silva , Grisi Cristiani Viegas Brandão , Silva Fábio Anderson Pereira da
Published: March 2022

Purpose

This study aims to assess the influence of partial and simultaneous substitution of fat and sodium by hydrolyzed collagen and mix of herbs (MH) in chicken hamburgers, on the physical properties and proximal composition.

Design/methodology/approach

Five formulations were developed: (1) HCON–without adding collagen and MH; (2) C25M25–adding 25% of collagen and 25% of MH; (3) C25M50–adding 25% of collagen and 50% of MH; (4) C50M25–adding 50% of collagen and 25% of MH and (5) C50M50–adding 50% of collagen and 50% of MH. Chicken hamburgers were analyzed by proximal composition, sodium content, collagen and color analysis. The influence of treatments on texture profile, cooking performance and lipid oxidation of chicken hamburger was also investigated.

Findings

There was reduction in lipid and sodium for modified formulations compared with the HCON. There was great influence for some parameters, such as luminosity, cooking performance and texture profile. The formulation C50M50 showed the best cooking performance when compared to the others.

Originality/value

The formulation adding 50% of collagen and 50% of MH showed the highest yield and water retention (WR), with the least reduction in diameter and shrinkage, as well as presenting the best indexes of the texture profile and the lowest oxidation index, being recommended as the best combination of fat and sodium replacement.
Experiencing tensions, regulatory focus and employee creativity: the moderating role of hierarchical level
Authors: Liu Zhiqiang , Ouyang Xi , Pan Xiaoqing
Published: March 2022

Purpose

This study aims to explore how employees respond to tensions in groups and whether experiencing tensions could spur on their creativity (including radical and incremental creativity). Through integrating the literature on tension and regulatory focus theory, this study develops a model depicting the process from experiencing tensions to creativity via regulatory foci. This study further investigates the moderating effect of employees’ hierarchical level on these processes.

Design/methodology/approach

A two-wave survey was conducted with a sample of 375 employees in China. MPLUS was used to examine the moderated mediation model.

Findings

The results show that experiencing tensions can simultaneously activate employees’ prevention focus and promotion focus, both of which in turn influence radical and incremental creativity. Specifically, prevention focus mediates the negative relationship between experiencing tensions and the two aforementioned types of creativity, and promotion focus mediates the positive relationship between experiencing tensions and radical creativity. Employees’ hierarchical level significantly buffers the link between experiencing tensions and prevention focus.

Practical implications

Organizations should optimize their work design to simplify the role demand of employees in the early stages of their careers. Top-tier employees should be encouraged and empowered to think and act with a paradoxical approach, which can drive them to generate more creative outcomes. Besides, when aiming to discover radical ideas, managers should emphatically cultivate employees’ promotion focus.

Originality/value

This study contributes to the literature on tension through revealing and testing the dual paths resulted by employees’ experiencing tensions. It also advances current research by contrasting the effects of experiencing tensions on different types of creativity.