bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radioiodine Therapy in Pediatric Differentiated Thyroid Cancer
Authors: Kumar Praveen , Damle Nishikant Avinash , Bal Chandrasekhar 
Published: October 2022

Abstract
Thyroid cancer is very rare in children. 131I therapy after thyroidectomy is established in pediatric differentiated thyroid cancer (DTC). Pediatric DTC guideline is silent on the optimum amount of 131I that could be safely and effectively administered to children who are more radiosensitive. Like adult DTC, children are also given 131I therapy empirically based either on age or body weight. Pediatric DTC guideline recommends that patient-specific dosimetry is important in children. Still, due to the low incidence rate and the practical difficulties of dosimetry, it has neither been established nor adopted in routine practice. This review article aims to discuss current approaches of 131I therapy in children and young adult patients with DTC and dosimetric data obtained by several investigators. Efforts are required to simplify dosimetric procedures and precise results, especially in determining lesion size. We prefer 3-dimensional dosimetry over planar dosimetry, where lesion size could be measured accurately. 124I PET/CT-based dosimetry is expected to give accurate dosimetric results. The most challenging aspect is that no randomized controlled trials are available to compare the empiric 131I therapy results versus dosimetry-based treatment outcomes in children and young adults. Suppose dosimetry-based 131I therapy could be shown to have better outcomes, namely, successful ablation rate, better disease-free survival, and lesser treatment-emergent adverse events than empirical 131I treatment. In that case, one can argue in favor of the former. Unfortunately, no convincing study is currently available. Thus, there is a need for a randomized control trial to settle this issue.
Clinical Forecasting usingEx VivoDrug Sensitivity Profiling of Acute Myeloid Leukemia
Authors: Andersen Aram N. , Brodersen Andrea M. , Ayuda-Durán Pilar , Piechaczyk Laure , Tadele Dagim Shiferaw , Baken Lizet , Fredriksen Julia , Stoksflod Mia , Lenartova Andrea , Fløisand Yngvar , Enserink Jorrit M. 
Published: October 2022

AbstractAcute Myeloid Leukemia (AML) is a heterogeneous malignancy involving the clonal expansion of myeloid stem and progenitor cells in the bone marrow and peripheral blood. Most AML patients eligible for potentially curative treatment receive intensive chemotherapy. Risk stratification is used to optimize treatment intensity and transplant strategy, and is mainly based on cytogenetic screening for structural chromosomal alterations and targeted sequencing of a selection of common mutations. However, the forecasting accuracy of treatment response remains modest. Recently,ex vivodrug screening has gained traction for its potential in personalized treatment selection, as well as a tool for identifying and mapping patient groups based on relevant cancer dependencies. We systematically evaluated the use of drug sensitivity profiling for predicting patient survival and clinical response to chemotherapy in a cohort of AML patients. We compared computational methodologies for scoring drug efficacy and characterized tools to counter noise and batch-related confounders pervasive in high-throughput drug testing. We show thatex vivodrug sensitivity profiling is a robust and versatile approach to patient prognostics that comprehensively maps functional signatures of treatment response and disease progression. In conclusion,ex vivodrug profiling can accurately assess risk of individual AML patients and may guide clinical decision-making.
Are female scientists underrepresented in self-correcting science for honest error?
Authors: Ribeiro MD , Mena-Chalco J , Rocha KA , Pedrotti M , Menezes P , Vasconcelos SMR 
Published: October 2022

AbstractRetractions are among the effective measures to strengthen the self-correction of science and the quality of the literature. When it comes to self-retractions for honest errors, exposure of one’s own failures is not a trivial matter for researchers. However, self-correcting data, results and/or conclusions has increasingly been perceived as good research practice, although rewarding such practice challenges traditional models of research assessment. In this context, it is timely to investigate who have self-retracted for honest error in terms of country, field, and gender. We show results on these three factors, focusing on gender, as data is scarce on the representation of female scientists in efforts to set the research record straight. We collected 3,822 retraction records, including research articles, review papers, meta-analyses, letters, and others, from the Retraction Watch Database (2010-2021). We screened the dataset collected for research articles retracted for honest error, excluding retractions by publishers, editors, or third parties, and those mentioning any investigation issues. We then categorized the records according to country, field, and gender, after selecting research articles with a sole corresponding author. Our results show that female scientists account for 25% of self-retractions for honest error, with the highest share for women affiliated with US institutions.
Lysosomal swelling and lysis mediate delivery of C3 toxins to their cytoplasmic targets
Authors: Turner Madison , Plumb Jonathan , Merrill A. Rod , Grinstein Sergio , Westman Johannes 
Published: October 2022

AbstractUnlike other cholera-like toxins that contain separate binding/translocation and catalytic subunits, C3-like mono-ADP-ribosyltransferases consist of a single subunit that serves both functions. The manner whereby C3 toxins reach the host cell cytoplasm is poorly understood and was addressed in this study by monitoring the fate of fluorescently-labelled C3larvinA. Following binding to the macrophage membrane in a discontinuous, punctate pattern, the toxin was internalized, traversing the endocytic pathway to reach lysosomes. Strikingly, the lysosomes of C3larvinA-treated cells underwent massive swelling over the course of 1-4 hrs. Lysosomal swelling preceded the extensive rearrangement of the cellular F-actin caused by ADP-ribosylation of cytosolic Rho-GTPases. This suggested that lysosome swelling might be required for escape of the toxin into the cytoplasm where the GTPases reside. Accordingly, preventing swelling by osmotic manipulation or by arresting macropinocytosis precluded the F-actin rearrangement. Toxin-induced swelling was associated with leakage of sulforhodamine B and dextran from the lysosomes, implying membrane rupture or activation of mechano-sensitive pores, enabling the toxin itself to reach the cytosol. Finally, comparison of the cellular traffic and actin remodelling activities of C3larvinA with that of two related toxins, C3larvintruncand Plx2A, highlighted the importance of the N-terminal α1-helix for lysosomal swelling and successful infection.
Deciphering the non-coding code of pathogenicity and sexual differentiation in the human malaria parasite
Authors: Batugedara Gayani , Lu Xueqing M. , Abel Steven , Chahine Zeinab , Hristov Borislav , Williams Desiree , Hollin Thomas , Wang Tina , Cort Anthony , Lenz Todd , Thompson Trevor , Prudhomme Jacques , Tripathi Abhai K. , Xu Guoyue , Cudini Juliana , Dogga Sunil , Lawniczak Mara , Stafford Noble William , Sinnis Photini , Le Roch Karine G. 
Published: October 2022

AbstractThe complex life cycle ofPlasmodium falciparumrequires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. However, this cascade of transcripts is unlikely to be regulated by the limited number of identified parasite-specific transcription factors. Increasing evidence now suggests a major role for epigenetic mechanisms in gene expression in the parasite. In eukaryotes, many lncRNAs have been identified and shown to be pivotal regulators of genome structure and gene expression. To investigate the regulatory roles of lncRNAs inP. falciparumwe explored the intergenic lncRNA distribution in nuclear and cytoplasmic subcellular locations. Using nascent RNA expression profiles, we identified a total of 1,768 lncRNAs, of which 58% were identified as novel lncRNAs inP. falciparum. The subcellular localization and stage-specific expression of several putative lncRNAs were validated using RNA fluorescence in situ hybridization (RNA-FISH). Additionally, the genome-wide occupancy of several candidate nuclear lncRNAs was explored using Chromatin Isolation by RNA Purification (ChIRP). ChIRP-seq of candidate lncRNAs revealed that lncRNA occupancy sites within the parasite genome are focal and sequence-specific with a particular enrichment for several parasite-specific gene families, including those involved in pathogenesis, erythrocyte remodeling, and regulation of sexual differentiation. We further validated the function of one specific lncRNA (lncRNA-ch14) using the CRISPR-Cas9 genome editing tool. Genomic and phenotypic analysis of the △lncRNA-ch14 line demonstrated the importance of this lncRNA in sexual differentiation and sexual reproduction. Our findings bring a new level of insight into the role of lncRNAs in pathogenicity, gene regulation and sexual differentiation. These findings also open new avenues for targeted approaches towards therapeutic strategies against the deadly malaria parasite.
Mechanical thrombectomy of the anterior circulation ischemic stroke whatever the low-volume operator : comparison to a 90 days follow-up
Authors: Herpe Guillaume , Dumas Victor , Guillevin Rémy 
Published: October 2022

BackgroundTo date, benefit of successful recanalization of acute stroke has been described mainly for high volume operator.PurposeTo evaluate if a successful MT performed by a low-volume operator is a strong predictor of patient’s good clinical outcome.Materials and MethodsA consecutive monocentric observational study from June 1, 2016 to December 31, 2018 at the University Hospital of Poitiers. Patient management included mechanical thrombectomy and eventual IVT. The interventional neuroradiologist on duty classified the recanalization according a standardized mTICI reading grid. ∆mRS was defined as the difference between 90 days and initial mRS. Association were studied using Chi-square test and Pearson’s and Fisher’s correlation with a threshold at 0.05. The main criterion was the reliability between mTICI and ∆mRS.ResultsAmong the 304 MT, 127 patients were finally included. High mTICI score was significantly associated with high ∆mRS (p = 0.04), using the mTICI dichotomization, patients with successful MT had significantly better outcome than patient with lower mTICI whatever the initial mRS (p = 0.008). There was a correlation between age categories greater than or equal to 80 y.o (p=0.03) and high initial NIHSS categories greater than or equal to 18 (p=0.004) with regard to the ∆mRS. No statistical significance were obtained between sexe (p=0.63), diabetes mellitus (p=0.25), VIT (p=0.16) and thrombus’s lateralization (p=0.26) with regard to ∆mRS.ConclusionThis study highlights the place and performances of low-volume operator in the treatment of acute stroke.Summary StatementDespite low-volume operators, a successful mechanical thrombectomy is a strong prognostic factor for good clinical outcome.Key Results- Mechanical thrombectomy performed in a low volume center is a safe therapy and strongly linked to good clinical outcome.- Our low volume-operators centre has reached a high reperfusion rate and a majority of good clinical outcome- This study highlights the place and performances of low-volume operator in the treatment of acute stroke.
Impact of weight-bearing and sex-stratified differences in risk factors of bone loss on bone mineral density in HIV conditions – findings of the Nigeria HIV-BMD study: An observational study
Authors: Ibeneme Sam Chidi , Fortwengel Gerhard , Okoye Ifeoma Joy , Okenwa Wilfred Okwudili , Ezuma Amarachi Destiny , Nwosu Akachukwu Omumuagwula , Ibeneme Georgian Chiaka , Nnamani Amaka , Limaye Dnyanesh , Fneish Firas , Myezwa Hellen , Philip Okere , Iloanusi Nneka , Ajidahun Adedayo Tunde , Ulasi Ifeoma 
Published: October 2022

AbstractBackgroundBiomechanical loading exerts an osteogenic stimulus; thus, bone mineral density(BMD) may vary in weight-bearing and non-weight-bearing bones. Therefore, weight-bearing activities could modulate sex-, HAART- and HIV-related BMD loss.MethodA cross-sectional observational study of 503 people living with HIV (PLWH) selected by convenience sampling at Enugu State University Teaching Hospital, Nigeria, was conducted from September 2015 to September 2016. The BMD of toe or weight-bearing(BMDtoe) and thumb or non-weight-bearing(BMDthumb) bones were measured with Xrite 331C densitometer and compared using independent t-test. Impact of the risk factors (age, weight, body mass index-BMI, duration of HIV, height and types of HAART) of bone loss and their relationships with the BMD were compared across the sexes using multivariate, and univariate regression analyses, at p<0.05,two-tailed.ResultParticipants comprised of females(378/75.1%), males(89/17.7%) and others(36/7.16%) without gender specificity, with mean age=37.2±9.79years, and BMI=25.6±5.06kg/m. HAART-experienced participants’ (352/69.98%) mean HAART-exposure duration was 4.54±3.51years. BMDtoe(−0.16±0.65g/cm3) was higher(p<0.05) than BMDthumb(−0.93±0.44g/cm3), and differed across the BMI classes (p=0.000003;d=0.998), and was accounted for inpost hocanalysis by normal weight versus underweight BMI classes (p=<0.001). BMDtoewas positively correlated with height (r=0.13,r2=0.0169;p<0.05), and males were taller than females(p<0.001). Females accounted for 90%(9/10) cases of osteopenia and 71.43%(5/7) osteoporosis. Males were older(p=0.002) while females had greater BMI (p=0.02), lower median BMDtoe(p=0.005) and BMDthumb(p=0.005).ConclusionHigher BMD in weight-bearing bones, and lower BMDtoein underweight (sub-optimal loading) BMI class suggest a role for osteogenic stimulus and fat metabolism in bone loss. Females being younger/heavier, would have greater loading/osteogenic stimulus reinforced by lesser age-related BMD changes. Males being taller would have greater bone marrow adipose tissue that promote osteogenesis through paracrine mechanisms. Therefore, higher BMD in males should be partly explained by height-related metabolic surrogates and sex-hormonal differences. Greater BMD In females’ weight-bearing bones implies that loading ameliorates physiological tendencies towards lower BMD.
Increased levels of inflammatory molecules in blood of Long COVID patients point to thrombotic endotheliitis
Authors: Turner Simone , Naidoo Caitlin A , Usher Thomas J , Kruger Arneaux , Venter Chantelle , Laubscher Gert Jacobus , Khan M Asad , Kell Douglas B , Pretorius Etheresia 
Published: October 2022

ABSTRACTThe prevailing hypotheses for the persistent symptoms of Long COVID have been narrowed down to immune dysregulation and autoantibodies, widespread organ damage, viral persistence, and fibrinaloid microclots (entrapping numerous inflammatory molecules) together with platelet hyperactivation. Here we demonstrate significantly increased concentrations of Von Willebrand Factor, platelet factor 4,serum amyloid A, α-2antiplasmin E-selectin, and platelet endothelial cell adhesion molecule-1, in the soluble part of the blood. It was noteworthy that the mean level of α-2-antiplasmin exceeded the upper limit of the laboratory reference range in Long COVID patients, and the other 5 were significantly elevated in Long COVID patients as compared to the controls. This is alarming if we take into consideration that a significant amount of the total burden of these inflammatory molecules has previously been shown to be entrapped inside fibrinolysis-resistant microclots (thus decreasing the apparent level of the soluble molecules). We also determined that by individually adding E-selectin and PECAM-1 to healthy blood, these molecules may indeed be involved in protein-protein interactions with plasma proteins (contributing to microclot formation) and platelet hyperactivation. This investigation was performed as a laboratory model investigation and the final exposure concentration of these molecules was chosen to mimic concentrations found in Long COVID. We conclude that presence of microclotting, together with relatively high levels of six inflammatory molecules known to be key drivers of endothelial and clotting pathology, points to thrombotic endotheliitis as a key pathological process in Long COVID. This has implications for the choice of appropriate therapeutic options in Long COVID.SENTENCE SUMMARYThe presence of fibrinaloid microclots and multiple inflammatory molecules in the soluble part of blood points to thrombotic endotheliitis as a key pathological process in Long COVID.
Synergistic Combined-proteomics Guided Mapping strategy identifies mTOR mediated phosphorylation of LARP1 in nutrient responsiveness and dilated cardiomyopathy
Authors: Tan Meng-Kwang Marcus , Sobota Radoslaw M. , Wong Esther SM , Vardy Leah A. , Burke Brian , Stewart Colin L. 
Published: October 2022

AbstractIncreased activity of the mammalian target of rapamycin (mTOR) signalling pathway, a crucial nutrient sensor, exacerbates ageing and ageing-related diseases, including cancer and heart failure. To further elucidate the physiological role of the serine/threonine kinase mTOR, we devised a novel tractable proteomics strategy that combines interaction proteomics, proximity-based proteomics and quantitative phosphoproteomics to identify interactors with and potential substrates of mTOR. We identified 58 candidate mTOR substrates, several of which were further validated. Interestingly, several of these candidate mTOR substrates are involved in various aspects of RNA biology, including regulating stability and processing. We characterized in-depth one of the validated mTOR substrates, LARP1, an RNA binding protein. mTOR-dependent phosphorylation of LARP1 is nutrient-sensitive and controls the RNA-binding ability of LARP1. We show that mTOR activity and LARP1 and LARP1 phosphorylation levels are increased in a congenital mouse model of dilated cardiomyopathy (DCM) caused by a mutation in the Lamin A gene. This implicates LARP1 in the development of DCM.
The translational role of SOS1 in colorectal cancer
Authors: Alem Diego , Yang Xinrui , Beato Francisca , Sarcar Bhaswati , Tassielli Alexandra F. , Dai Ruifan , Hogenson Tara L. , Park Margaret A. , Jiang Kun , Cai Jianfeng , Yuan Yu , Fernandez-Zapico Martin E. , Tan Aik Choon , Fleming Jason B. , Xie Hao 
Published: October 2022

AbstractBackgroundIt has been challenging to develop agents directly targetingKRASdriver mutations in colorectal cancer (CRC). Recent efforts have focused on developing inhibitors targeting SOS1 as an attractive approach forKRAS-mutant cancers. Here, we aimed to study the translational role of SOS1 in CRC using patient-derived organoids (PDOs).MethodIn this study, we used CRC PDOs as preclinical models to evaluate their sensitivity to SOS1 inhibitor BI3406 and its cellular effects. We utilized large CRC datasets including GENIE cohort, TCGA PanCancer Atlas, and CPTAC-2 cohort to study the significance of molecular alterations of SOS1 in CRC. To identify potential predictive markers, we performed immunohistochemistry (IHC) on CRC tissue for SOS1/2 protein expression and RNA sequencing to identify discriminative gene sets for sensitivity to SOS1 inhibition. The findings were validated by DepMap data forSOS1dependency.ResultCRC PDOs instead of cell lines had differential sensitivities to BI3406. There was a significant correlation between SOS1 and SOS2 mRNA expressions (Spearman’s ρ 0.56, p<0.001). SOS1/2 protein expression by IHC were universal with heterogeneous patterns in cancer cells but only minimal to none in surrounding non-malignant cells. SOS1 protein expression was associated with worse overall survival in patients withRAS/RAFmutant CRC (p=0.04). We also found that SOS1/SOS2 protein expression ratio > 1 by IHC (p=0.03) instead ofKRASmutation (p=1) was a better predictive marker to BI3406 sensitivity of CRC PDOs. This was concordant with the significant correlation between SOS1/SOS2 protein expression ratio by mass spectrometry and SOS1 dependency score. RNA-seq and gene set enrichment analysis revealed differentially expressed genes and 7 enriched gene sets involving cholesterol homeostasis, epithelial mesenchymal transition, and TNFα/NFκB signaling in BI3406-resistant CRC PDOs. We further discovered that GTP-bound RAS level underwent rebound at 48 hours upon treatment with BI3406 even in BI3406-sensitive PDOs with no change of KRAS effector genes downstream. Cellular adaptation mechanisms to SOS1 inhibition may involve upregulation of SOS1/2 mRNA and SOS1 protein expressions, which may be overcome by SOS1 knockdown/degradation or synergistic effect of BI3406 with trametinib.ConclusionIn summary, CRC PDOs could serve as better models for translational study of SOS1 in CRC. High SOS1 protein expression was a worse prognostic factor in CRC. High SOS1/SOS2 protein expression ratio predicted sensitivity to SOS1 inhibition and dependency. Our preclinical findings supported further clinical development of SOS1-targeting agents in CRC.
Role of a board of directors and corporate governance in a state-owned enterprise
Authors: Thompson Renée M. , Alleyne Philmore 
Published: October 2022

Purpose
This study aims to investigate measures established to ensure board of directors (BODs) in a state-owned enterprise (SOE) meets the organization for economic cooperation and development (OECD, 2015) guidelines criteria: how they perform their advising and control roles, and interactions within the boardroom using agency theory and OECD guidelines.

Design/methodology/approach
This research adopts a qualitative approach of a board within a SOE in Barbados involving several stages of data collection. A case study approach was used involving interviews of nine board members and seven key management staff, analysis of board minutes and annual reports.

Findings
BODs follow majority of the OECD (2015) guidelines for good governance. The Chairman allowed full discussion and input from BODs. The board members’ diverse qualifications and skills added value to the organization. However, appointments to the board were heavily slanted toward political considerations which at times may have skewed judgments. Boardroom interactions reflected quality contributions from the BODs. Decision-making was lengthy and tedious. Boardroom atmosphere could be territorial.

Research limitations/implications
Political interference remains an issue facing BODs in executing their roles. This study did not observe board meetings but perceived views via the lens of BODs and management.

Originality/value
This paper adds to the existing body of knowledge of SOE board governance based on OECD (2015) guidelines and how the board performs its advising and control roles. Insights are gained on how board processes contribute to boardroom interaction by using agency theory as the theoretical framework.