bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARATIVE PROTEIN PROFILE ANALYSIS OF DIFFERENTIALLY EXTRACTED WHOLE CELL BACTERIAL PROTEIN DERIVED FROM SALMONELLA TYPHI AND INVASIVE NON-TYPHOIDAL SALMONELLA
Authors: Abdul Lateef Khan Khairunnisa , Sheik Abdul Kader Zainoodin
Published: June 2023

Typhoid fever is an endemic disease that has been acknowledged as a major global health burden. Typhoid fever is a neglected re-emerging infectious disease that is transmitted through fecal oral route. Nevertheless, non-typhoidal Salmonella outbreak has been increasing globally with large number of cases involving immunocompromised individuals. The clinical diagnosis of typhoid is difficult due to the overlapping symptoms of typhoid fever, non-typhoidal Salmonella, and other associated febrile diseases, which causes to delayed treatment. Herein, this study aims to provide a reproducible, discriminative protein fingerprint of two different Salmonella serovars using a differential extraction procedure comprising of whole cell protein (WCP), cell surface protein (CSP) and surface-depleted whole cell protein (sdWCP) derived from whole cell bacterial protein of Salmonella Typhi (S.Typhi) and Salmonella spp (S.spp). In the present research, we perform comparative analysis to characterize protein profiles of two differentially extracted Salmonella serovars by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and dendrogram analysis. The findings showed that the proteins were reproducible in optimized concentration. Separation of protein into three different extractions revealed discriminative protein profiles with major and micro-heterogenicity. We observed the diverseness of differentially extracted proteins between two strains which provided an effective adjunct that can be used in identification of Salmonella strains. The results achieved when differential extraction procedure was applied, provides a promising, future opportunity for further immunoproteomic classifications.
Ultrasound and pathology findings of adenomyoepithelioma in the breast: a case report
Authors: Zhang Xiaowei , Wu Kangbin , Fu Saiping
Published: June 2023

.
How easy is to perform a tendon SWE examination?
Authors: Solomon Carolina
Published: June 2023

.
Strategic Operations in Baseball: “Maximizing the Window”
Authors: Cialone William , Newland Brianna L.
Published: June 2023

This is a fictional case based on the acquisition and use of talent within Major League Baseball club the New York Mets using “sabermetrics.” The case introduces students to three disparate approaches to acquiring and utilizing talent with the strategic aim to maximize the Mets’ “championship window.” The case primarily uses examples from the Los Angeles Dodgers, the Los Angeles Angels of Anaheim, and the Tampa Bay Rays to compare successful and unsuccessful strategies. With the data and strategies presented, this case presents a scenario for Jalen Burkes, the fictitious assistant to the General Manager for the Mets during the Major League Baseball offseason. This case develops within the theoretical framework of workforce differentiation theory and is suitable for student learning about strategic decision making and human resource management. Specifically, students are challenged to consider whether to keep free agents on the roster based on how talent is acquired and used to put the Mets in the best possible position to compete for a championship in the next season.
A Comparison of Host Responses to Infection with Wild-Type Avian Influenza Viruses in Chickens and Tufted Ducks
Authors: Naguib Mahmoud M. , Eriksson Per , Jax Elinor , Wille Michelle , Lindskog Cecilia , Bröjer Caroline , Krambrich Janina , Waldenström Jonas , Kraus Robert H. S. , Larson Göran , Lundkvist Åke , Olsen Björn , Järhult Josef D. , Ellström Patrik
Published: June 2023

Our current findings highlight important aspects of IAV infection in birds that have implications for our understanding of its zoonotic ecology. In contrast to mallards where the intestinal tract is the main site of IAV replication, chickens and tufted ducks show limited or no signs of intestinal infection suggesting that the fecal-oral transmission route might not apply to all bird IAV host species.
Work-related respiratory health conditions among construction workers: a systematic narrative review
Authors: Boadu Elijah Frimpong , Okeke Sylvester Reuben , Boadi Caleb , Osei Bonsu Emmanuel , Addo Isaac Yeboah
Published: June 2023

Background

Emerging evidence in both developed and developing countries indicate that occupational health hazards and diseases among construction workers constitute a significant public health challenge. While occupational health hazards and conditions in the construction sector are diverse, a burgeoning body of knowledge is emerging about respiratory health hazards and diseases. Yet, there is a notable gap in the existing literature in terms of comprehensive syntheses of the available evidence on this topic. In light of this research gap, this study systematically reviewed the global evidence on occupational health hazards and related respiratory health conditions among construction workers.

Methods

Using meta-aggregation, guided by the Condition (respiratory health conditions), Context (construction industry) and Population (construction workers) (CoCoPop) framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, literature searches were conducted on Scopus, PubMed, Web of Science and Google Scholar for relevant studies on respiratory health conditions affecting construction workers. Four eligibility criteria were used in scrutinising studies for inclusion. The quality of the included studies was assessed based on Joanna Briggs Institute’s Critical Appraisal tool, while the reporting of the results was guided by the Synthesis Without Meta-analysis guidelines.

Results

From an initial pool of 256 studies from the various databases, 25 studies published between 2012 and October 2022 were identified as meeting the inclusion criteria. In all, 16 respiratory health conditions were identified, with cough (ie, dry and with phlegm), dyspnoea/breathlessness and asthma emerging as the top three respiratory conditions among construction workers. The study identified six overarching themes of hazards that are associated with respiratory health conditions among construction workers. These hazards include exposure to dust, respirable crystalline silica, fumes, vapours, asbestos fibres and gases. Smoking and extended period of exposure to the respiratory hazard were found to increase the risk of contracting respiratory diseases.

Conclusions

Our systematic review indicates that construction workers are exposed to hazards and conditions that have adverse effects on their health and well-being. Given the considerable impact that work-related health hazards can have on the health and socioeconomic well-being of construction workers, we suggest that the implementation of a comprehensive occupational health programme is essential. Such a programme would extend beyond the mere provision of personal protective equipment and would incorporate a range of proactive measures aimed at controlling the hazards and mitigating the risk of exposure to the occupational health hazards.
Persistent villous atrophy predicts development of complications and mortality in adult patients with coeliac disease: a multicentre longitudinal cohort study and development of a score to identify high-risk patients
Authors: Schiepatti Annalisa , Maimaris Stiliano , Raju Suneil A , Green Olivia L , Mantica Giulia , Therrien Amelie , Flores-Marin David , Linden Justin , Fernández-Bañares Fernando , Esteve Maria , Leffler Daniel , Biagi Federico , Sanders David S
Published: June 2023

Objective

Persistent villous atrophy (pVA) in coeliac disease (CD) despite a gluten-free diet (GFD) has unclear meaning. We aimed to (i) study the relationship between pVA and long-term outcomes and (ii) develop a score to identify patients at risk of pVA.

Design

This is a multicentre retrospective-prospective study consisting of a study cohort (cohort 1) and an external validation cohort (cohort 2) of patients with biopsy-proven CD diagnosed between 2000 and 2021. Cohort 1 was used to (i) compare long-term outcomes between patients with and without pVA (Marsh ≥3a) at follow-up biopsy and (ii) to develop a score to evaluate the risk of pVA, which was validated in cohort 2.

Results

Of 2211 patients, 694 (31%) underwent follow-up duodenal biopsy and were included in the study cohort (491F, 44±16 years). 157/694 (23%) had pVA. Risk of complications (HR 9.53, 95% CI 4.77 to 19.04, p<0.001) and mortality (HR 2.93, 95% CI 1.43 to 6.02, p<0.01) were increased in patients with pVA. A 5-point score was developed and externally validated (receiver operating characteristic area under the curve 0.78, 95% CI 0.68 to 0.89) to stratify patients by risk of pVA: low (0–1 points, 5% pVA), intermediate (2 points, 16% pVA) and high (3–5 points, 73% pVA). Predictors for pVA used in the score were age at diagnosis ≥45 years (OR 2.01, 95% CI 1.21 to 3.34, p<0.01), classical pattern of CD (OR 2.14, 95% CI 1.28 to 3.58, p<0.01), lack of clinical response to GFD (OR 2.40, 95% CI 1.43 to 4.01, p<0.001) and poor GFD adherence (OR 48.9, 95% CI 26.1 to 91.8, p<0.001).

Conclusions

Risk of complications and mortality were increased in patients with pVA. We developed a score to identify patients at risk of pVA and in need of histological reassessment and closer follow-up.
Incidence of persistent opioid use following traumatic injury
Authors: Mauck Matthew C , Zhao Ying , Goetzinger Amy M , Tungate Andrew S , Spencer Alex B , Lal Asim , Barton Chloe E , Beaudoin Francesca , McLean Samuel A
Published: June 2023

Introduction

Major traumatic injuries are a known risk factor for persistent opioid use, but data describing the relationship between specific traumatic injuries and opioid use is lacking.

Methods

We used insurance claims data from January 1, 2001 to December 31, 2020 to estimate the incidence of new persistent opioid use in three hospitalized trauma populations: individuals hospitalized after burn injury (3809, 1504 of whom required tissue grafting), individuals hospitalized after motor vehicle collision (MVC; 9041), and individuals hospitalized after orthopedic injury (47, 637). New persistent opioid use was defined as receipt of ≥1 opioid prescriptions 90–180 days following injury in an individual with no opioid prescriptions during the year prior to injury.

Results

New persistent opioid use was observed in 12% (267/2305) of individuals hospitalized after burn injury with no grafting, and 12% (176/1504) of burn injury patients requiring tissue grafting. In addition, new persistent opioid use was observed in 16% (1454/9041) of individuals hospitalized after MVC, and 20% (9455/47, 637) of individuals hospitalized after orthopedic trauma. In comparison, rates of persistent opioid use in all trauma cohorts (19%, 11, 352/60, 487) were greater than the rates of persistent opioid use in both non-traumatic major surgery (13%) and non-traumatic minor surgery (9%).

Conclusions

These data demonstrate that new persistent opioid use frequently occurs in these common hospitalized trauma populations. Improved interventions to reduce persistent pain and opioid use in patients hospitalized after these and other traumas are needed.
Paradoxical mid-crustal displacements and stratigraphic continuity: structural evolution of the northeastern Paleoproterozoic Amer belt, Nunavut, Canada
Authors: White Joseph Clancy , Calhoun Lydia , Jefferson Charles W.
Published: June 2023

The structural geology of the northeastern Paleoproterozoic Amer belt, central Nunavut, has been evaluated in light of new field mapping combined with legacy data and independently acquired subsurface geophysics data. Proterozoic sequences Ps1–Ps4 of the Amer supergroup unconformably overlie Archean basement. Of these sequences, Ps1–Ps3 have been intensely deformed (D1) in association with the Snowbird Orogeny (2.05–1.865 Ga). Ps4 was deposited unconformably on the first three sequences and exhibits none of the D1 effects. Deformation within Ps4 is slight compared to the underlying sequences and is restricted to D2 folding that occurred in the 1.84–1.81 Ga Hudsonian Orogeny. Deformation of sequences Ps1–Ps3 forms the core of this study. D1 comprises imbricate thrusting, intersequence detachment, and three generations of isoclinal folding and transposition. The stratigraphic order is maintained in many areas by decoupling of sequence packages along incompetent units so as not to “mix” lithologies; there is a fundamental mechanical stratigraphy. Within sequences, transposition can be otherwise intense. The resultant architecture is a shallowly southwest-dipping sequence of tectonically rotated and transposed layering (primary and tectonic) similar in many ways in orientation regardless of whether preserved with original bedding features or completely transposed. D1 folding is characterized by recumbent folds, noncylindrical folds that are sometimes rooted in detachments, verging to the northeast. D2 folding is controlled by the pre-existing large-scale D1 fabric, resulting in the overturned synforms that parallel the belt. Post-D2 fault modification of northern side of the belt along northwest-trending faults is interpreted to relate to extension and exhumation.
Polymerase chain reaction-based typing methods and protein profiling analysis of Acinetobacter baumannii isolated from environmental and clinical sources from South India
Authors: Nayak Srajana , Aanice D’Almeida , Andria Dsouza , Pai Archana , Maiti Biswajit
Published: June 2023

Acinetobacter baumannii is an opportunistic pathogen known for causing hospital-acquired infections. The natural habitat includes soil, water, sewage, and drains, but it is also detected in infected individuals’ blood, pus, and respiratory pathways. Due to its resilient nature, it is known to be a causative agent for outbreaks. Therefore, it is crucial to understand the genetic similarity between clinical and environmental isolates. The study aimed to find the genetic relationships between clinical and environmental isolates using PCR-based typing methods such as enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR), random amplified polymorphic DNA (RAPD), and repetitive extragenic palindromic sequence-based PCR (Rep-PCR). Additionally, outer membrane protein (OMP) and whole cell protein (WCP) profiles were also used. The PCR-based methods, ERIC-PCR and Rep-PCR, showed decreased genetic similarity between clinical and environmental isolates (66% and 58%, respectively). However, RAPD showed relatively higher genetic similarity (91%). The OMP and WCP profiles showed varied banding patterns between the clinical and environmental isolates in the 29–43 kDa region. The PCR-based methods proved to be a reliable and reproducible technique. The OMP and WCP profiles, though not as discriminatory as the molecular typing methods, could help identify the most and least commonly occurring protein bands and thus help in typing clinical and environmental A. baumannii isolates.
Comparison of behavioural and transcriptional responses to a heat stressor between freshly collected and an inbred strain of Lymnaea
Authors: Rivi Veronica , Batabyal Anuradha , Benatti Cristina , Tascedda Fabio , Blom Joan M. C. , Lukowiak Ken
Published: June 2023

Different populations of organisms occurring across varying thermal regimes show diversity in responses to heat stress. We use a “common garden experimental” approach designed to deal with phenotypic plasticity to study in Lymnaea stagnalis (Linnaeus, 1758) the behavioural and molecular responses to a heat shock in laboratory-inbred snails (W-strain) and freshly collected snails (Stony strain) from ponds. In the W-strain, which has been reared under standardized temperatures for generations, the exposure to 30 °C for 1 h (heat shock, HS) when experienced after a novel “taste” results in a taste-specific aversion known as the “Garcia effect”. This learned avoidance requires the upregulation of heat shock proteins (HSPs). In contrast, freshly collected Stony strain, which experiences temperature fluctuations regularly, does not exhibit a Garcia effect. Here, we found that (1) Stony-strain snails have higher basal mRNA levels of HSPs than W-strain ones; (2) in the W-strain, the training procedure to cause the Garcia effect upregulates the mRNA levels of HSPs and key neuroplasticity-related genes such as CREB1 and GRIN1; (3) in Stony-strain snails, the same training procedure fails to alter the mRNA levels of those targets. These data suggest that Stony-strain snails do not perceive the HS as a stressor because of the higher HSP basal mRNA levels, which may confer a higher thermal tolerance.
The Casimir interaction in a nonlocal electrolyte slab
Authors: Moradian A. , Seyedzahed A.
Published: June 2023

In this paper, the Casimir force per unit area across a nonlocal slab of an electrolyte between two semispaces of ordinary materials has been studied through the scattering approach. Because of the insufficiency of Maxwell’s boundary conditions, additional boundary conditions are used as well. The numerical calculations show that for polystyrene semispaces at small separations, ascending the concentration causes intensifying the Casimir pressure. However, it is illustrated that in the case of silver substrates the Casimir pressure has the same amount for two electrolyte concentrations and this intensification does not occur by increasing the concentration. At small separations for polystyrene semispaces, the Hamaker coefficient has two different magnitudes corresponding to 90 and 0.9[Formula: see text]mM concentrations, but for silver substrates the Hamaker coefficient starts from the same value for both concentrations.
Risks to the Public
Authors: Neumann Peter G.
Published: June 2023

ChatBots and Generative AI more generally have really opened up a deluge of RISKS items in the past few months, along with an increased awareness of risks relating to arti - cial intelligence. This issue includes just the tip of the iceberg with one-liners on that subject, where it is almost impossible to summarize all the risks. PGN
Know Thy Ransomware Response: A Detailed Framework for Devising Effective Ransomware Response Strategies
Authors: Bajpai Pranshu , Enbody Richard
Published: June 2023

Ransomware has evolved into one of the most severe cyberthreats against private and public sectors alike. Organizations are inundated with a barrage of intrusion attempts that ultimately morph into full-scale ransomware attacks. Efforts to combat these threats tend to primarily focus on detection and prevention, and while thwarting an attack is always the best approach, we must additionally improve our response and recovery efforts with a post-breach mindset. Assume that the defenses have failed and the risk has materialized. Are we then prepared to best salvage the situation with efficient, ransomware-specific incident response procedures? In this work, we present a ransomware response framework that can be leveraged to create highly effective ransomware response strategies. We provide a level of detail in this framework that balances adaptability versus actionability that both technical and executive stakeholders will find of use.
Prevalence of Depression and Its Associated Factors among Prisoners in North Wollo Zone, Northeastern Ethiopia: A Cross-Sectional Study
Authors: Tegegne Kindie Mekuria , Demeke Solomon Moges , Lemma Mekonnin Tesfa , Kassie Ayelign Mengesha
Published: June 2023

Background. Depression is a psychiatric disorder that is characterized by persistent sadness and a lack of interest or pleasure in previously rewarding and enjoyable activities. It is one of the leading mental disorders among prisoners worldwide. However, little attention is given to this condition, especially in developing countries. Hence, this study was aimed at assessing the prevalence of depression and its associated factors among prisoners in North Wollo Zone Correctional Institutions, Ethiopia. Methods. A cross-sectional study was carried out among 407 prisoners from November 20 to December 20, 2020. A simple random sampling technique was employed to select the study participants, and the Patient Health Questionnaire-9 (PHQ-9) was utilized to measure the prevalence of depression among prisoners. Data analyses were done using SPSS version 20 software program. Descriptive and inferential statistics including bivariate and multivariable regression analyses were run to assess the association between depression and the independent variables, and a

p

value of less than 0.05 was taken to declare statistically significant values. Results. A total of 407 prisoners participated in the study, making the response rate 96.9%. The mean age of the participants was

31.7
±
12.83

. Forty-one percent of them were between the ages of 18 and 27 years. In this study, the prevalence of depression was 55.5%. Age 38-47 (

AOR
=
4.29

;

95
%
CI
=
1.51

, 12.20), having children (

AOR
=
2.75

;

95
%
CI
=
1.40

, 5.42), sentences for 5-10 years and over 10 years (

AOR
=
6.26

;

95
%
CI
=
3.19

, 12.30 and

AOR
=
7.71

;

95
%
CI
=
3.47

, 17.17, respectively), having a history of mental illness (

AOR
=
5.22

;

95
%
CI
=
2.39

, 11.36), having two or more stressful life events (

AOR
=
6.61

;

95
%
CI
=
2.73

, 15.96), and poor social support (

AOR
=
8.13

;

95
%
CI
=
3.43

, 19.27) were significantly associated with depression. Conclusions. In this study, more than half of the study participants were found having depression which is relatively higher compared with other previous studies across the globe. Moreover, different variables including the inmate’s age of 38-47 years, having children, a sentence of 5-10 and over 10 years, history of mental illness, having two or more stressful life events, and poor social support were factors significantly associated with depression. Thus, awareness creation for police officers and prison managers about depression screening in prison and treatment programs including psychological counseling and cognitive behavioral therapy for prisoners are recommended.
Design and Fabrication of a High Performance Microfluidic Chip for Blood Plasma Separation: Modelling and Prediction of System Behaviour via CFD Method
Authors: Amini Hossein , Sokhansanj Amin , Akrami Mohammad , Haririan Ismaeil
Published: June 2023

This paper presents a single-step microfluidic system designed for passive separation of human fresh blood plasma using direct capillary forces. Our microfluidic system is composed of a cylindrical well between upper and lower channel pairs produced by soft photolithography. The microchip was fabricated based on hydrophobicity differences upon suitable cylindrical surfaces using gravitational and capillary forces and lateral migration of plasma and red blood cells. The plasma radiation was applied to attach the polymeric segment (polydimethylsiloxane (PDMS)) to the glass. Meanwhile, Tween 80 was used as a surfactant to increase the hydrophobicity of the lateral channel surfaces. This led to the higher movement of whole blood, including plasma. Fick’s law of diffusion was validated for this diffusion transfer, the Navier–Stokes equation was used for the momentum balance, and the Laplace equation was utilized for the dynamics of the mesh. A model with high accuracy using the COMSOL Multiphysics software was created to predict the capillary forces and chip model validation. RBCs (red blood cells) were measured by the H3 cell counter instrument, by which 99% plasma purity was achieved. Practically, 58.3% of the plasma was separated from the blood within 12 min. Correlation between plasma separation results obtained from software and experimental data showed a coefficient of determination equal to 0.9732. This simple, rapid, stable, and reliable microchip can be considered as a promising candidate for providing plasma in point-of-care diagnostics.
False-Positive Phencyclidine (PCP) Result on 11-Panel Urine Drug Screen (UDS) in a 17-Year-Old Adolescent with Long-Term Venlafaxine Use
Authors: Kim Hyun Sue , Jain Aakash , Kablinger Anita S.
Published: June 2023

Venlafaxine is an antidepressant belonging to the class of serotonin–norepinephrine reuptake inhibitors that are US Food and Drug Administration-approved to treat and manage symptoms of depression, anxiety, and other mood disorders in adults. We describe an adolescent patient who likely had a false-positive phencyclidine result detected with an 11-panel urine drug screen in an outpatient setting of long-term use of therapeutic venlafaxine extended release for the treatment of recurrent major depressive disorder and generalized anxiety disorder. We believe that this may be the first published case report to characterize this phenomenon in a young patient in the absence of an acute overdose.
Supplementary Table S6 from Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis
Authors: Goldman Omer , Adler Lital N. , Hajaj Emma , Croese Tommaso , Darzi Naama , Galai Sivan , Tishler Hila , Ariav Yarden , Lavie Dor , Fellus-Alyagor Liat , Oren Roni , Kuznetsov Yuri , David Eyal , Jaschek Rami , Stossel Chani , Singer Oded , Malitsky Sergey , Barak Renana , Seger Rony , Erez Neta , Amit Ido , Tanay Amos , Saada Ann , Golan Talia , Rubinek Tamar , Sang Lee Joo , Ben-Shachar Shay , Wolf Ido , Erez Ayelet
Published: June 2023

Supplementary Table S6 lists the genes regulated by HNF4a
Supplementary Table S7 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: June 2023

Table S7: Transcriptomics analysis of shCEBPA#2 versus shCTL
Supplementary Table S5 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: June 2023

Table S5: GSEA results in FLT3-ITD PDX AML cells in vivo-treated with GILT or Veh.
Supplementary Table S2 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: June 2023

Table S2: EnrichR analysis of FLT3 gene signatures
Supplementary Extended Data 1 from Early Infiltration of Innate Immune Cells to the Liver Depletes HNF4α and Promotes Extrahepatic Carcinogenesis
Authors: Goldman Omer , Adler Lital N. , Hajaj Emma , Croese Tommaso , Darzi Naama , Galai Sivan , Tishler Hila , Ariav Yarden , Lavie Dor , Fellus-Alyagor Liat , Oren Roni , Kuznetsov Yuri , David Eyal , Jaschek Rami , Stossel Chani , Singer Oded , Malitsky Sergey , Barak Renana , Seger Rony , Erez Neta , Amit Ido , Tanay Amos , Saada Ann , Golan Talia , Rubinek Tamar , Sang Lee Joo , Ben-Shachar Shay , Wolf Ido , Erez Ayelet
Published: June 2023

Supplementary Extended Data 1 describes the FACS gating startegy
Supplementary Table S14 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: June 2023

Table S14: PUFA/MUFA ratios in phospholipids
Supplementary Table S12 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: June 2023

Table S12: gene signatures used to analyze RNA-seq data from patients with AML before/after GILT
Supplementary Table S2 from Mitochondrial-Encoded Complex I Impairment Induces a Targetable Dependency on Aerobic Fermentation in Hürthle Cell Carcinoma of the Thyroid
Authors: Frank Anderson R. , Li Vicky , Shelton Spencer D. , Kim Jiwoong , Stott Gordon M. , Neckers Leonard M. , Xie Yang , Williams Noelle S. , Mishra Prashant , McFadden David G.
Published: June 2023

Supplementary Table S2 shows nuclear genome variants identified in NCI-237-R PDX through whole-exome sequencing.
Supplementary Table S10 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: June 2023

Table S10: EnrichR analysis of CEBPA_UP signature
Supplementary Table S1 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: June 2023

Table S1: Transcriptome analysis of FLT3-ITD cell lines after FLT3 inhbition
Supplementary Information v.2 from C/EBPα Confers Dependence to Fatty Acid Anabolic Pathways and Vulnerability to Lipid Oxidative Stress–Induced Ferroptosis in FLT3-Mutant Leukemia
Authors: Sabatier Marie , Birsen Rudy , Lauture Laura , Mouche Sarah , Angelino Paolo , Dehairs Jonas , Goupille Léa , Boussaid Ismael , Heiblig Maël , Boet Emeline , Sahal Ambrine , Saland Estelle , Santos Juliana C. , Armengol Marc , Fernández-Serrano Miranda , Farge Thomas , Cognet Guillaume , Simonetta Federico , Pignon Corentin , Graffeuil Antoine , Mazzotti Céline , Avet-Loiseau Hervé , Delos Océane , Bertrand-Michel Justine , Chedru Amélie , Dembitz Vilma , Gallipoli Paolo , Anstee Natasha S. , Loo Sun , Wei Andrew H. , Carroll Martin , Goubard Armelle , Castellano Rémy , Collette Yves , Vergez François , Mansat-De Mas Véronique , Bertoli Sarah , Tavitian Suzanne , Picard Muriel , Récher Christian , Bourges-Abella Nathalie , Granat Fanny , Kosmider Olivier , Sujobert Pierre , Colsch Benoit , Joffre Carine , Stuani Lucille , Swinnen Johannes V. , Guillou Hervé , Roué Gael , Hakim Nawad , Dejean Anne S. , Tsantoulis Petros , Larrue Clément , Bouscary Didier , Tamburini Jerome , Sarry Jean-Emmanuel
Published: June 2023

Supplementary materials and methods
Data from Mitochondrial-Encoded Complex I Impairment Induces a Targetable Dependency on Aerobic Fermentation in Hürthle Cell Carcinoma of the Thyroid
Authors: Frank Anderson R. , Li Vicky , Shelton Spencer D. , Kim Jiwoong , Stott Gordon M. , Neckers Leonard M. , Xie Yang , Williams Noelle S. , Mishra Prashant , McFadden David G.
Published: June 2023

Abstract
A metabolic hallmark of cancer identified by Warburg is the increased consumption of glucose and secretion of lactate, even in the presence of oxygen. Although many tumors exhibit increased glycolytic activity, most forms of cancer rely on mitochondrial respiration for tumor growth. We report here that Hürthle cell carcinoma of the thyroid (HTC) models harboring mitochondrial DNA-encoded defects in complex I of the mitochondrial electron transport chain exhibit impaired respiration and alterations in glucose metabolism. CRISPR–Cas9 pooled screening identified glycolytic enzymes as selectively essential in complex I–mutant HTC cells. We demonstrate in cultured cells and a patient-derived xenograft model that small-molecule inhibitors of lactate dehydrogenase selectively induce an ATP crisis and cell death in HTC. This work demonstrates that complex I loss exposes fermentation as a therapeutic target in HTC and has implications for other tumors bearing mutations that irreversibly damage mitochondrial respiration.
Significance:
HTC is enriched in somatic mtDNA mutations predicted to affect complex I of the electron transport chain (ETC). We demonstrate that these mutations impair respiration and induce a therapeutically tractable reliance on aerobic fermentation for cell survival. This work provides a rationale for targeting fermentation in cancers harboring irreversible genetically encoded ETC defects.
Data from A Compendium of Syngeneic, Transplantable Pediatric High-Grade Glioma Models Reveals Subtype-Specific Therapeutic Vulnerabilities
Authors: McNicholas Michael , De Cola Antonella , Bashardanesh Zahedeh , Foss Amelia , Lloyd Cameron B. , Hebert Steven , Faury Damien , Andrade Augusto Faria. , Jabado Nada , Kleinman Claudia L. , Pathania Manav
Published: June 2023

Abstract
Pediatric high-grade gliomas (pHGGs) are lethal, incurable brain tumors frequently driven by clonal mutations in histone genes. They often harbor a range of additional genetic alterations that correlate with different ages, anatomical locations, and tumor subtypes. We developed models representing 16 pHGG subtypes driven by different combinations of alterations targeted to specific brain regions. Tumors developed with varying latencies and cell lines derived from these models engrafted in syngeneic, immunocompetent mice with high penetrance. Targeted drug screening revealed unexpected selective vulnerabilities— H3.3G34R/PDGFRAC235Y to FGFR inhibition, H3.3K27M/PDGFRAWT to PDGFRA inhibition, and H3.3K27M/PDGFRAWT and H3.3K27M/PPM1DC/PIK3CAE545K to combined inhibition of MEK and PIK3CA. Moreover, H3.3K27M tumors with PIK3CA, NF1 and FGFR1 mutations were more invasive and harbored distinct additional phenotypes, such as exophytic spread, cranial nerve invasion and spinal dissemination. Collectively, these models reveal that different partner alterations produce distinct effects on pHGG cellular composition, latency, invasiveness, and treatment sensitivity.
TABLE 1 from NCI 7977: A Phase I Dose-Escalation Study of Intermittent Oral ABT-888 (Veliparib) plus Intravenous Irinotecan Administered in Patients with Advanced Solid Tumors
Authors: Cecchini Michael , Walther Zenta , Wei Wei , Hafez Navid , Pilat Mary Jo , Boerner Scott A. , Durecki Diane E. , Eder Joseph P. , Schalper Kurt A. , Chen Alice P. , LoRusso Patricia
Published: June 2023

Baseline characteristics
Table S2 from Immunological characterization and T-cell receptor repertoires of expanded tumor-infiltrating lymphocytes in renal cell carcinoma patients
Authors: Lee Moon Hee , Theodoropoulos Jason , Huuhtanen Jani , Bhattacharya Dipabarna , Järvinen Petrus , Tornberg Sara , Nísen Harry , Mirtti Tuomas , Uski Ilona , Kumari Anita , Peltonen Karita , Draghi Arianna , Donia Marco , Kreutzman Anna , Mustjoki Satu
Published: June 2023

Supplementary Table S2 shows the list of all markers, antibodies and their catalog numbers used for multi-parameter flow cytometry immunophenotyping, co-culture and T-cell activation assays.
Figure S9 from Immunological characterization and T-cell receptor repertoires of expanded tumor-infiltrating lymphocytes in renal cell carcinoma patients
Authors: Lee Moon Hee , Theodoropoulos Jason , Huuhtanen Jani , Bhattacharya Dipabarna , Järvinen Petrus , Tornberg Sara , Nísen Harry , Mirtti Tuomas , Uski Ilona , Kumari Anita , Peltonen Karita , Draghi Arianna , Donia Marco , Kreutzman Anna , Mustjoki Satu
Published: June 2023

Figure S9 shows the correlation of overlapping clonotypes between the REP TILs and pre-REP TILs.
Figure S15 from Immunological characterization and T-cell receptor repertoires of expanded tumor-infiltrating lymphocytes in renal cell carcinoma patients
Authors: Lee Moon Hee , Theodoropoulos Jason , Huuhtanen Jani , Bhattacharya Dipabarna , Järvinen Petrus , Tornberg Sara , Nísen Harry , Mirtti Tuomas , Uski Ilona , Kumari Anita , Peltonen Karita , Draghi Arianna , Donia Marco , Kreutzman Anna , Mustjoki Satu
Published: June 2023

Figure S15 shows pathway enrichment analyses for the pre-REP TILs and REP TILs, as well as the abundance of the RCC-associated motifs found in the UMAP T-cell clusters for each tumor sample.
Figure S11 from Immunological characterization and T-cell receptor repertoires of expanded tumor-infiltrating lymphocytes in renal cell carcinoma patients
Authors: Lee Moon Hee , Theodoropoulos Jason , Huuhtanen Jani , Bhattacharya Dipabarna , Järvinen Petrus , Tornberg Sara , Nísen Harry , Mirtti Tuomas , Uski Ilona , Kumari Anita , Peltonen Karita , Draghi Arianna , Donia Marco , Kreutzman Anna , Mustjoki Satu
Published: June 2023

Figure S11 shows treemaps of various clonotypes found in the patient samples and the matches to viral-specific TCRs.
Data from Immunologic Characterization and T cell Receptor Repertoires of Expanded Tumor-infiltrating Lymphocytes in Patients with Renal Cell Carcinoma
Authors: Lee Moon Hee , Theodoropoulos Jason , Huuhtanen Jani , Bhattacharya Dipabarna , Järvinen Petrus , Tornberg Sara , Nísen Harry , Mirtti Tuomas , Uski Ilona , Kumari Anita , Peltonen Karita , Draghi Arianna , Donia Marco , Kreutzman Anna , Mustjoki Satu
Published: June 2023

The successful use of expanded tumor-infiltrating lymphocytes (TIL) in adoptive TIL therapies has been reported, but the effects of the TIL expansion, immunophenotype, function, and T cell receptor (TCR) repertoire of the infused products relative to the tumor microenvironment (TME) are not well understood. In this study, we analyzed the tumor samples (n = 58) from treatment-naïve patients with renal cell carcinoma (RCC), “pre-rapidly expanded” TILs (pre-REP TIL, n = 15) and “rapidly expanded” TILs (REP TIL, n = 25) according to a clinical-grade TIL production protocol, with single-cell RNA (scRNA)+TCRαβ-seq (TCRαβ sequencing), TCRβ-sequencing (TCRβ-seq), and flow cytometry. REP TILs encompassed a greater abundance of CD4+ than CD8+ T cells, with increased LAG-3 and low PD-1 expressions in both CD4+ and CD8+ T cell compartments compared with the pre-REP TIL and tumor T cells. The REP protocol preferentially expanded small clones of the CD4+ phenotype (CD4, IL7R, KLRB1) in the TME, indicating that the largest exhausted T cell clones in the tumor do not expand during the expansion protocol. In addition, by generating a catalog of RCC-associated TCR motifs from >1,000 scRNA+TCRαβ-seq and TCRβ-seq RCC, healthy and other cancer sample cohorts, we quantified the RCC-associated TCRs from the expansion protocol. Unlike the low-remaining amount of anti-viral TCRs throughout the expansion, the quantity of the RCC-associated TCRs was high in the tumors and pre-REP TILs but decreased in the REP TILs. Our results provide an in-depth understanding of the origin, phenotype, and TCR specificity of RCC TIL products, paving the way for a more rationalized production of TILs.
Significance:
TILs are a heterogenous group of immune cells that recognize and attack the tumor, thus are utilized in various clinical trials. In our study, we explored the TILs in patients with kidney cancer by expanding the TILs using a clinical-grade protocol, as well as observed their characteristics and ability to recognize the tumor using in-depth experimental and computational tools.
Efficacy of Co-Medications in Patients with Alcoholic Liver Disease
Authors: Itzel Timo , Falconer Thomas , Roig Ana , Daza Jimmy , Park Jimyung , Cheong Jae Youn , Park Rae Woong , Wiest Isabella , Ebert Matthias P , Hripcsak George , Teufel Andreas
Published: June 2023

Background: Alcoholic liver disease (ALD) is still increasing and leads to acute liver injury but also liver cirrhosis and subsequent complications such as liver failure or hepatocellular carcinoma (HCC). As most patients fail to achieve alcohol abstinence, it is essential to identify alternative treatment options in order to improve the outcome of ALD patients. Methods: Evaluating two large cohorts of patients with ALD from the USA and Korea with a total of 12,006 patients, we investigated the effect on survival of aspirin, metformin, metoprolol, dopamine, and dobutamine drugs in patients with ALD between 2000 and 2020. Patient data were obtained through the “The Observational Health Data Sciences and Informatics consortium,” an open-source, multi-stakeholder, and interdisciplinary collaborative effort. Results: The use of aspirin (p = 0.000, p = 0.000), metoprolol (p = 0.002, p = 0.000), and metformin (p = 0.000, p = 0.000) confers a survival benefit for both AUSOM- and NY-treated cohorts. Need of catecholamines dobutamine (p = 0.000, p = 0.000) and dopamine (p = 0.000, p = 0.000) was strongly indicative of poor survival. β-Blocker treatment with metoprolol (p = 0.128, p = 0.196) or carvedilol (p = 0.520, p = 0.679) was not shown to be protective in any of the female subgroups. Conclusion: Overall, our data fill a large gap in long-term, real-world data on patients with ALD, confirming an impact of metformin, acetylsalicylic acid, and β-blockers on ALD patient’s survival. However, gender and ethnic background lead to diverse efficacy in those patients.
Recent Advancements in Ependymoma: Challenges and Therapeutic Opportunities
Authors: Bertrand Kelsey C , Klimo Paul
Published: June 2023

Background: Ependymoma is one of the most common malignant pediatric brain tumors and can be difficult to treat. Over the last decade, much progress has been made in the understanding of the underlying molecular drivers within this group of tumors, but clinical outcomes remain unchanged. Summary: Here, we review the most recent molecular advances in pediatric ependymoma, evaluate results of recent clinical trials and discuss the ongoing challenges in the field and questions that remain. Key Messages: The field of ependymoma has vastly changed over the last several decades with ten distinct molecular subgroups now described, but much progress needs to be made in developing new therapeutic strategies and targets.