bluuebunny/crossref_metadata_2025 huggingface dataset:
Automatic Assessment of Rail Squat Defects by Sensor Fusion
Authors: Scalera Antonio , Carotti Luca , Antuofermo Pasquale , Pace Pietro , Calegari Alan
Published: June 2024

Railway infrastructure is the backbone of global transportation systems, necessitating constant attention to safety and reliability. Recent years have witnessed an increasing focus on monitoring rail defects, particularly surface defects known as squats. Traditionally squats are identified through labor-intensive visual inspection, ultrasonic inspection, and eddy currents; the need for more efficient and accurate detection methods has led to Axle Box Acceleration (ABA) use and the development of new methods based on machine vision systems. However, today still challenges persist in terms of quantity of defects generated and consequent severity level assignment. This paper introduces a novel approach to automatically assess rail squat defects through the fusion of machine vision data with vertical acceleration measurements from a train’s axle box.

Our methodology involves data collection from both the machine vision and the ABA systems during regular operations. The integration of these data sources aims to correlate visual anomalies with the wheel dynamic behavior, focusing on squat defect location and severity. This integration aims to identify squats in their very early stage with a rate close to 100% and to automatically classify their severity level.
A Thy-1–negative immunofibroblast population emerges as a key determinant of fibrotic outcomes to biomaterials
Authors: Abebayehu Daniel , Pfaff Blaise N. , Bingham Grace C. , Miller Andrew E. , Kibet Mathew , Ghatti Surabhi , Griffin Donald R. , Barker Thomas H.
Published: June 2024

Fibrosis-associated fibroblasts have been identified across various fibrotic disorders, but not in the context of biomaterials, fibrotic encapsulation, and the foreign body response. In other fibrotic disorders, a fibroblast subpopulation defined by Thy-1 loss is strongly correlated with fibrosis yet we do not know what promotes Thy-1 loss. We have previously shown that Thy-1 is an integrin regulator enabling normal fibroblast mechanosensing, and here, leveraging nonfibrotic microporous annealed particle (MAP) hydrogels versus classical fibrotic bulk hydrogels, we demonstrate that
Thy1
−/−
mice mount a fibrotic response to MAP gels that includes inflammatory signaling. We found that a distinct and cryptic α–smooth muscle actin–positive Thy-1
−
fibroblast population emerges in response to interleuklin-1β (IL-1β) and tumor necrosis factor–α (TNFα). Furthermore, IL-1β/TNFα-induced Thy-1
−
fibroblasts consist of two distinct subpopulations that are strongly proinflammatory. These findings illustrate the emergence of a unique proinflammatory, profibrotic fibroblast subpopulation that is central to fibrotic encapsulation of biomaterials.
Programmable nonreciprocal Poynting effect enabled by lattice metamaterials
Authors: Dong Le , Zhou Kun , Wang Dong
Published: June 2024

Shear nonreciprocity, implying unequal shear forces in opposite shear directions, can be achieved by arranging structures asymmetrically. However, the nonreciprocal Poynting effect, i.e., unequal normal stresses induced by the same shear displacements to the left and right, has not been fully explored. We discover the nonreciprocal Poynting effect using a generalized directional truss model. Inspired by this discovery, the cylindrical lattice metamaterials constructed from antisymmetric curled microstructures are used as a case study to generate the nonreciprocal Poynting effect. We develop a design framework that integrates digital generation, finite deformation theory, finite element modeling, and three-dimensional printing to program the nonreciprocal Poynting effect. Applications such as bionic Poynting effect matching, wave energy converter, and unidirectional motion limitation are demonstrated. This framework allows the one-to-one mapping between the torque and normal forces, paving the way for designing soft devices with precise force transmission capabilities.
Sensory evidence for complex communication and advanced sociality in early ants
Authors: Taniguchi Ryo , Grimaldi David A. , Watanabe Hidehiro , Iba Yasuhiro
Published: June 2024

Advanced social behavior, or eusociality, has been evolutionarily profound, allowing colonies of ants, termites, social wasps, and bees to dominate competitively over solitary species throughout the Cenozoic. Advanced sociality requires not just nestmate cooperation and specialization but refined coordination and communication. Here, we provide independent evidence that 100-million-year-old Cretaceous ants in amber were social, based on chemosensory adaptations. Previous studies inferred fossil ant sociality from individual ants preserved adjacent to others. We analyzed several fossil ants for their antennal sensilla, using original rotation imaging of amber microinclusions, and found an array of antennal sensilla, specifically for alarm pheromone detection and nestmate recognition, sharing distinctive features with extant ants. Although Cretaceous ants were stem groups, the fossilized sensilla confirm hypotheses of their complex sociality.
Targeting T cell plasticity in kidney and gut inflammation by pooled single-cell CRISPR screening
Authors: Enk Leon U. B. , Hellmig Malte , Riecken Kristoffer , Kilian Christoph , Datlinger Paul , Jauch-Speer Saskia L. , Neben Tobias , Sultana Zeba , Sivayoganathan Varshi , Borchers Alina , Paust Hans-Joachim , Zhao Yu , Asada Nariaki , Liu Shuya , Agalioti Theodora , Pelczar Penelope , Wiech Thorsten , Bock Christoph , Huber Tobias B. , Huber Samuel , Bonn Stefan , Gagliani Nicola , Fehse Boris , Panzer Ulf , Krebs Christian F.
Published: June 2024

Pro-inflammatory CD4
+
T cells are major drivers of autoimmune diseases, yet therapies modulating T cell phenotypes to promote an anti-inflammatory state are lacking. Here, we identify T helper 17 (T
H
17) cell plasticity in the kidneys of patients with antineutrophil cytoplasmic antibody–associated glomerulonephritis on the basis of single-cell (sc) T cell receptor analysis and scRNA velocity. To uncover molecules driving T cell polarization and plasticity, we established an in vivo pooled scCRISPR droplet sequencing (iCROP-seq) screen and applied it to mouse models of glomerulonephritis and colitis. CRISPR-based gene targeting in T
H
17 cells could be ranked according to the resulting transcriptional perturbations, and polarization biases into T helper 1 (T
H
1) and regulatory T cells could be quantified. Furthermore, we show that iCROP-seq can facilitate the identification of therapeutic targets by efficient functional stratification of genes and pathways in a disease- and tissue-specific manner. These findings uncover T
H
17 to T
H
1 cell plasticity in the human kidney in the context of renal autoimmunity.
Overexpression of
Malat1
drives metastasis through inflammatory reprogramming of the tumor microenvironment
Authors: Martinez-Terroba Elena , Plasek-Hegde Leah M. , Chiotakakos Ioannis , Li Vincent , de Miguel Fernando J. , Robles-Oteiza Camila , Tyagi Antariksh , Politi Katerina , Zamudio Jesse R. , Dimitrova Nadya
Published: June 2024

Expression of the long noncoding RNA (lncRNA) metastasis–associated lung adenocarcinoma transcript 1 (
MALAT1
) correlates with tumor progression and metastasis in many tumor types. However, the impact and mechanism of action by which
MALAT1
promotes metastatic disease remain elusive. Here, we used CRISPR activation (CRISPRa) to overexpress
MALAT1/Malat1
in patient-derived lung adenocarcinoma (LUAD) cell lines and in the autochthonous K-ras/p53 LUAD mouse model.
Malat1
overexpression was sufficient to promote the progression of LUAD to metastatic disease in mice. Overexpression of
MALAT1/Malat1
enhanced cell mobility and promoted the recruitment of protumorigenic macrophages to the tumor microenvironment through paracrine secretion of CCL2/Ccl2.
Ccl2
up-regulation was the result of increased global chromatin accessibility upon
Malat1
overexpression. Macrophage depletion and Ccl2 blockade counteracted the effects of
Malat1
overexpression. These data demonstrate that a single lncRNA can drive LUAD metastasis through reprogramming of the tumor microenvironment.
Supplemental Material: Multistage melt/fluid modification of lithospheric mantle beneath the circum-cratonic orogenic belt: Evidence from the Tuoyun peridotite xenoliths
Authors: Bian Xiao , Su Yuping , al. et
Published: June 2024

Table S1: Major-element concentrations of olivines from Tuoyun peridotite xenoliths. Table S2: Major-element concentrations of orthopyroxenes from Tuoyun peridotite xenoliths. Table S3: Major-element concentrations of clinopyroxenes from Tuoyun peridotite xenoliths. Table S4: Major-element concentrations of spinels from Tuoyun peridotite xenoliths. Table S5: Major-element concentrations of secondary mineral and glass from Tuoyun peridotite xenoliths. Table S6: Trace-element concentrations of clinopyroxenes from Tuoyun peridotite xenoliths. Table S7: Trace-element concentrations of orthopyroxenes from Tuoyun peridotite xenoliths.
Complicated retroperitoneal diverticulitis presenting with abscess and acute limb ischemia
Authors: Gunasingha Rathnayaka Mudiyanselage Kalpanee D , Seoudi Hani , Mirza Sohail , Endicott Kendal
Published: June 2024

This case highlights a rare presentation of diverticulitis of the sigmoid colon with perforation into the retroperitoneum complicated by abscess, vertebral osteomyelitis and acute lower extremity ischemia. A late 40-year-old man presented to an emergency department with acute ischemia of his left lower extremity. He was tachycardic with a leucocytosis, an unremarkable abdominal exam and a pulseless, insensate and paralysed left lower extremity. Imaging revealed sigmoid thickening, an abscess adjacent to iliac vasculature and occlusion of the left popliteal artery. The abscess came in contact with prior spine anterior lumbar interbody fusion (ALIF) hardware at L5–S1 vertebrae. The patient was taken urgently to the operating room for embolectomy, thrombectomy and fasciotomy. He was started on antibiotics and later underwent operative drainage with debridement for osteomyelitis. Non-operative management of the complicated diverticulitis failed, necessitating open sigmoidectomy with colostomy. 1 year later, he was symptom-free and the colostomy was reversed.
Accidental calcium, magnesium, potassium and sodium oxybates (Xywave) overdose: mistiming of a single night’s narcolepsy medication leading to respiratory failure requiring mechanical ventilation
Authors: McIntosh Braden W , Mayeux Charles
Published: June 2024

While typically thought of as an illicit substance, oxybate salts or gamma-hydroxybutyrate (GHB) has more recently been prescribed to treat narcolepsy by enhancing night-time sleep resulting in decreased daytime drowsiness. This case involves a college-aged female with prescribed GHB for narcolepsy who took her second nightly dose too early. This resulted in mental depression, respiratory failure, intubation and mechanical ventilation. The patient was successfully extubated in the intensive care unit several hours later with no residual morbidity. We were unable to identify any prior reports of mixed-salt oxybate toxicity following mistimed drug administration. This case should serve as a warning to emergency physicians to be on the lookout for GHB as part of the differential diagnosis for patients with narcolepsy presenting with altered mental status. It should also serve as a warning to patients and prescribers that this medication can have outcomes that require immediate medical intervention.
Granulomatous amoebic encephalitis due toAcanthamoebaspp complicating multidrug-resistant tuberculous meningitis in an immunocompetent individual
Authors: Mondal Debasis , Bhunia Prantick Kumar , Bhattacharya Dipamoy , Sarkar Ashim
Published: June 2024

Granulomatous amoebic encephalitis due toAcanthamoebaspp is a rare, near-fatal central nervous system infection. It is often seen in immunocompromised individuals. Here we describe a survivor of this infection who was co-infected with multidrug-resistant tuberculosis. He presented to us with features of meningitis and a history of chronic cough. The chest X-ray was classical for pulmonary tuberculosis. Neuroimaging was suggestive of encephalitis; herpes simplex virus PCR was negative. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis. Wet mounts revealed trophozoites ofAcanthamoeba. Currently, he is being treated with oral bedaquiline, levofloxacin, linezolid, clofazimine, cycloserine and pyridoxine for tuberculosis. He received intravenous amikacin and oral cotrimoxazole and fluconazole forAcanthamoebainfection for 1 month. The resolution was confirmed by repeating the CSF wet mount, culture and neuroimaging. He was then discharged with oral rifampicin, cotrimoxazole and fluconazole. He is currently under our close follow-up.
Mentalising imagery therapy for family dementia caregivers: protocol for a scoping review
Authors: Jiang Xue , Jiang Hu
Published: June 2024

Introduction

Dementia is a growing public health concern, and providing long-term care for individuals affected by this condition is challenging for their family caregivers. While researchers have explored various intervention options to provide psychological support for dementia caregivers, mentalising imagery therapy (MIT) has gained significant recognition as an effective programme. Despite its significance and effectiveness, there is a lack of comprehensive scoping reviews of MIT in dementia caregiving. Thus, conducting such a review can provide valuable insights into the status and outcomes of MIT, identify gaps in existing research and provide recommendations for a more effective clinical practice.

Methods and analysis

This study proposes a scoping review conducted according to the Joanna Briggs Institute, Arksey and O’Malley’s methodological framework, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension. PubMed, Web of Science, Embase, Scopus, CINAHL and PsycINFO databases will be searched while grey literature will be retrieved via Google Scholar. Covidence will be used to manage the literature selection process and remove duplicate publications. Two researchers will independently screen the literature according to the inclusion criteria, with any discrepancies resolved through discussions with a third researcher. Data will be presented in a structured tabular format, with a narrative synthesis providing an overview of the findings on the identified research gaps and the effectiveness of MIT in the field of dementia caregiving.

Ethics and dissemination

In a scoping review, no ethical approval is necessary. The results will be published in a peer-reviewed journal.

Trial registration number

The scoping review protocol has been registered with Open Science Framework (https://doi.org/10.17605/OSF.IO/FHRG8).
Decision aids for female BRCA mutation carriers: a scoping review
Authors: McGarrigle Sarah A , Prizeman Geraldine , Spillane Carol , Byrne Niamh , Drury Amanda , Polus Manria , Mockler David , Connolly Elizabeth M , Brady Anne-Marie , Hanhauser Yvonne P
Published: June 2024

Objectives

Women who inherit a pathogenicBRCA1orBRCA2mutation are at substantially higher risk of developing breast and ovarian cancer than average. Several cancer risk management strategies exist to address this increased risk. Decisions about which strategies to choose are complex, personal and multifactorial for these women. Decision aids (DAs) are tools that assist patients in making health-related decisions. The aim of this scoping review was to map evidence relating to the development and testing of patient DAs for cancer unaffectedBRCAmutation carriers.

Design

Scoping review conducted according to the Joanna Briggs Institute’s (JBI’s) scoping review methodological framework.

Data sources

MEDLINE, EMBASE, CINAHL, Web of Science. No restrictions applied for language or publication date. A manual search was also performed.

Eligibility criteria for selecting studies

Studies on DAs for cancer risk management designed for or applicable to women with a pathogenicBRCA1orBRCA2mutation who are unaffected by breast or ovarian cancer.

Data extraction and synthesis

Data were extracted using a form based on the JBI instrument for extracting details of studies’ characteristics and results. Data extraction was performed independently by two reviewers. Extracted data were tabulated.

Results

32 evidence sources relating to development or testing of 21 DAs were included. Four DAs were developed exclusively for cancer unaffected BRCA mutation carriers. Of these, two covered all guideline recommended risk management strategies for this population though only one of these was readily available publicly in its full version. All studies investigating DA effectiveness reported a positive effect of the DA under investigation on at least one of the outcomes evaluated, however only six DAs were tested in randomised controlled trials.

Conclusion

This scoping review has mapped the landscape of the literature relating to developing and testing, DAs applicable to cancer unaffectedBRCAmutation carriers.
Low-dose naltrexone for post-COVID fatigue syndrome: a study protocol for a double-blind, randomised trial in British Columbia
Authors: Naik Hiten , Cooke Erin , Boulter Travis , Dyer Roger , Bone Jeffrey N , Tsai Melody , Cristobal Jaymie , McKay R Jane , Song Xiaowei , Nacul Luis
Published: June 2024

Introduction

A significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-viral fatigue syndromes. There remains no clear pharmacological therapy for patients with this subtype of PCC, which can be referred to as post-COVID fatigue syndrome (PCFS). A low dose of the opioid antagonist naltrexone (ie, low-dose naltrexone (LDN)) has emerged as an off-label treatment for treating fatigue and other symptoms in PCC. However, only small, non-controlled studies have assessed LDN in PCC, so randomised trials are urgently required.

Methods and analysis

A prospective, randomised, double-blind, parallel arm, placebo-controlled phase II trial will be performed to assess the efficacy of LDN for improving fatigue in PCFS. The trial will be decentralised and open to eligible individuals throughout the Canadian province of British Columbia (BC). Participants will be recruited through the province-wide Post-COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN) and research volunteer platform (REACH BC). Eligible participants will be 19–69 years old, have had a confirmed or physician-suspected SARS-CoV-2 infection at least 3 months prior and meet clinical criteria for PCFS adapted from the Institute of Medicine ME/CFS criteria. Individuals who are taking opioid medications, have a history of ME/CFS prior to COVID-19 or history of significant liver disease will be excluded. Participants will be randomised to an LDN intervention arm (n=80) or placebo arm (n=80). Participants in each arm will be prescribed identical capsules starting at 1 mg daily and follow a prespecified schedule for up-titration to 4.5 mg daily or the maximum tolerated dose. The trial will be conducted over 16 weeks, with assessments at baseline, 6, 12 and 16 weeks. The primary outcome will be fatigue severity at 16 weeks evaluated by the Fatigue Severity Scale. Secondary outcomes will include pain Visual Analogue Scale score, overall symptom severity as measured by the Patient Phenotyping Questionnaire Short Form, 7-day step count and health-related quality of life measured by the EuroQol 5-Dimension questionnaire.

Ethics and dissemination

The trial has been authorised by Health Canada and approved by The University of British Columbia/Children’s and Women’s Health Centre of British Columbia Research Ethics Board. On completion, findings will be disseminated to patients, caregivers and clinicians through engagement activities within existing PCC and ME/CFS networks. Results will be published in academic journals and presented at conferences.

Trial registration number

NCT05430152.
Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial
Authors: D'Aragon Frederick , Selzner Markus , Breau Ruth , Masse Marie-Hélène , Lamontagne Francois , Masse Mélanie , Chassé Michael , Carrier François-Martin , Cardinal Héloïse , Chaudhury Prosanto , Weiss Matthew , Lauzier Francois , Turgeon Alexis F , Frenette Anne-Julie , Bolduc Brigitte , Ducharme Anique , Lamarche Caroline , Couture Etienne , Holdsworth Sandra , Bertholz Liz , Talbot Heather , Slessarev Marat , Luke Patrick , Boyd John Gordon , Shamseddin M Khaled , Burns Karen E A , Zaltzman Jeffrey , English Shane , Knoll Greg , Dhanani Sonny , Healey Andrew , Hanna Steven , Rochwerg Bram , Oczkowski Simon J W , Treleaven Darin , Meade Maureen
Published: June 2024

Introduction

Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk.

Methods and analysis

We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation.

Ethics and dissemination

We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309).

Trial registration number

NCT05148715.
Real-world clinical effectiveness of ustekinumab in the treatment of Crohn’s disease in the East Midlands UK
Authors: White Jonathan Richard , Ahmad Saqib , Ashraf Fahad , Foley Stephen , Din Said , Das Ronit Kumar , Charles Nina Mary , Pinheiro João , Palejwala Altaf , Wright Pamela , Andiappan Manoharan , Alexander Myriam , Uddin Burhan , Hoshen Deloar , Elphick David , Qamar Tufail , Rezwan Nivin , Hamza Mohammad Viquaruddin , Glover John , Robinson Richard , Gopakumar Veena , Sajjad Aamir , Shahzad Muhammad , Moran Gordon
Published: June 2024

Objectives

To evaluate the effectiveness of ustekinumab in treating Crohn’s disease (CD) in a UK real-world setting.

Design

This was a multicentre, retrospective observational study of patients (aged ≥18 years) with CD or inflammatory bowel disease of unclassified type (IBDU) starting ustekinumab between 11 November 2016 and 1 August 2020 across eight English hospitals. The primary objective was to determine the proportion of patients achieving corticosteroid-free remission at week 52 for patients with CD/IBDU following initiation with ustekinumab. Corticosteroid-free remission was defined as achieving a clinical Harvey-Bradshaw Index (HBI) score of ≤4 and corticosteroid-free status.

Results

The analysis included 422 patients with CD/IBDU. Corticosteroid-free remission was 41% (68/166) at week 16, 41% (47/115) at week 30 and 48% (38/80) at week 52. Clinical remission was 51% (85/166) at week 16 and 50% (40/80) at week 52. Clinical response was 34% (43/125) at week 16 and 32% (17/53) at week 52. Objective remission was 40% (4/10) at week 16 and 70% (7/10) at week 52. Corticosteroid-free remission at week 52 was achieved in patients with previous exposure to 1–2 biologics and/or small oral molecules (56%; 35/63), those without surgical history (64%; 16/25), and those without penetrating disease (54%; 29/54). Patients who achieved clinical remission at week 16 were more likely to achieve corticosteroid-free remission at week 52 (70%; 14/20) versus those who did not (20%; 4/20). In total, 37 adverse events occurred in 21 patients.

Conclusion

This multicentre study provides real-world experience of ustekinumab in patients with CD/IBDU in England.
Endovascular management of saccular aneurysms of the proximal A1 segment: technical particularities and long term outcomes
Authors: Liao Liang , Muszynski Patricio , Zhu François , Harsan Oana , Lopes De Medeiros Luana , Bracard Serge , Anxionnat René
Published: June 2024

Background

Saccular aneurysms of the proximal A1 segment (SAPA1) are rare, but their treatment is challenging and scarcely described in the literature. We report the immediate and long term outcomes of their endovascular management.

Methods

We retrospectively analyzed all consecutive SAPA1cases treated endovascularly at our center between 2003 and 2023. Per procedural complications and radioclinical outcomes were prospectively recorded.

Results

Among 2468 patients followed up for aneurysms, 12 (0.49%) had an SAPA1(average age 53.8±9.6 years, 9 women). The SAPA1averaged 3.3 mm, all posteriorly oriented. Ten were ruptured (83.3%). Initial treatments included conventional coiling or balloon assisted coiling (CC/BAC) for nine aneurysms, and proximal A1 segment focal occlusion (PA1FO) for three. Initial occlusion was deemed satisfactory in all instances: total occlusion in eight cases (67%) and subtotal occlusion in four cases (33%). Four aneurysmal perforations occurred (33%), all during CC/BAC on ruptured aneurysms. Over a 10.2 year average follow-up, six recanalizations (50%) were noted, all after initial CC/BAC: three were early (≤14 days), with one causing fatal rebleeding. No recanalizations after PA1FO was observed (five in total, two as a complement after CC/BAC). Favorable clinical outcomes (modified Rankin Scale score of 0–2) were seen in 91% of cases (11/12) at the last follow-up.

Conclusions

Selective coiling of the aneurysmal sac is technically difficult due to their small size and the complex microcatheterization pathway. This method presents a significant risk of aneurysmal perforation, especially in ruptured cases, and a high rate of recanalization. PA1FO, when collateralization permits, appears to be a reliable therapeutic alternative offering favorable long term outcomes.
Selective cooling and squeezing in a lossy optomechanical closed loop embodying an exceptional surface
Authors: Sütlüoğlu Ege Beyza , Bulutay Ceyhun
Published: June 2024

A closed-loop, lossy optomechanical system consisting of one optical and two degenerate mechanical resonators is computationally investigated. This system constitutes an elementary synthetic plaquette derived from the loop phase of the intercoupling coefficients. In examining a specific quantum attribute, we delve into the control of quadrature variances within the resonator selected through the plaquette phase. An amplitude modulation is additionally applied to the cavity-pumping laser to incorporate mechanical squeezing. Our numerical analysis relies on the integration-free computation of steady-state covariances for cooling and the Floquet technique for squeezing. We provide physical insights into how non-Hermiticity plays a crucial role in enhancing cooling and squeezing in proximity to exceptional points. This enhancement is associated with the behavior of complex eigenvalue loci as a function of the intermechanical coupling rate. Additionally, we demonstrate that the parameter space embodies an exceptional surface, ensuring the robustness of exceptional point singularities under experimental parameter variations. However, the pump laser detuning breaks away from the exceptional surface unless it resides on the red-sideband by an amount sufficiently close to the mechanical resonance frequency. Finally, we show that this disparate parametric character entitles frequency-dependent cooling and squeezing, which is of technological importance.
Navigating the Cyborg Classroom: Telepresence Robots, Accessibility Challenges, and Inclusivity in the Classroom
Authors: Elmimouni Houda , Šabanović Selma , Rode Jennifer A.
Published: June 2024

Telepresence robots, designed to bridge physical distances, have unique capabilities and inherent limitations when deployed in classroom environments. This study examines these aspects, focusing on how telepresence robots facilitate or hinder classroom accessibility and inclusivity. Based on field study results from participatory observations, surveys and interviews with 22 participants, we present and catalogue the operational capabilities of telepresence robots, such as mobility and interaction potential, alongside their limitations in areas like sensory perception and social presence. Our findings reveal a nuanced landscape where telepresence robots act as both enablers and barriers in the classroom. This duality raises the question of whether these robots can be considered “disabled” in certain contexts and how this perceived disability impacts remote students’ inclusion in classroom dynamics. Finally, we present use recommendations to improve classroom experience and telepresence design.
Circulating Lineage 3 Recombination with NADC30‐Like and NADC34‐Like Betaarterivirus suid 2 in Taiwan
Authors: Lee Chi-Fen , Chang Yen-Chen , Chang Hui-Wen
Published: June 2024

Porcine respiratory and reproductive syndrome (PRRS) caused by Betaarterivirus suid leads to severe economic losses. The emergence of highly pathogenic Betaarterivirus suid 2 (PRRSV‐II), such as NADC30 and NADC34, has been reported in the USA and several Asian countries. NADC30‐like PRRSV‐II was first reported in 2018 in Taiwan. To investigate the PRRSV variants currently circulating in Taiwan, sequences covering ORF2‐5 of Taiwan PRRSV isolates collected between 2020 and 2023 were analyzed. Phylogenetic analysis of the ORF5 nucleotide sequence indicated that most of the Taiwan isolates were clustered in lineage 3 and three isolates were grouped in lineage 1 and were closely related to the NADC34 strain. Interestingly, these three NADC34‐like Taiwan PRRSV isolates carried amino acid deletions similar to NADC30 and were more closely related to NADC30 strains than the NADC34 strains in the Nsp2 gene. Next‐generation sequencing and recombination detection program showed potential recombination of lineage 3 with NADC30‐ and NADC34‐like PRRSV‐II. Our results suggest the presence of circulating mosaic recombinants and lineage 3 PRRSV‐II in Taiwan during 2020 and 2023.
Supplementary Table S4 from m6A Modification Promotes EMT and Metastasis of Castration-Resistant Prostate Cancer by Upregulating NFIB
Authors: Shu Feng , Liu Hao , Chen Xiaohui , Liu Ye , Zhou Jiangli , Tang Lei , Cao Wanwei , Yang Shanshan , Long Yili , Li Rongna , Wang Hao , Wang Hongsheng , Jiang Guanmin
Published: June 2024

Proteins that bind with NFIB rather than IgG, in both NFIB_1 and NFIB_2 samples.
Supplementary Table S1-2 from m6A Modification Promotes EMT and Metastasis of Castration-Resistant Prostate Cancer by Upregulating NFIB
Authors: Shu Feng , Liu Hao , Chen Xiaohui , Liu Ye , Zhou Jiangli , Tang Lei , Cao Wanwei , Yang Shanshan , Long Yili , Li Rongna , Wang Hao , Wang Hongsheng , Jiang Guanmin
Published: June 2024

The sequences of the siRNAs are listed in Supplementary Table S1. And the sequences of the primers, ChIP primers and MeRIP primers used are listed in Supplementary Table S2.
Figure 3 from Deuterium Metabolic Imaging Differentiates Glioblastoma Metabolic Subtypes and Detects Early Response to Chemoradiotherapy
Authors: Low Jacob C.M. , Cao Jianbo , Hesse Friederike , Wright Alan J. , Tsyben Anastasia , Alshamleh Islam , Mair Richard , Brindle Kevin M.
Published: June 2024

3D 2H CSI of [6,6-2H2]glucose metabolism in A11 and S2 tumors, in normal-appearing brain tissue, and in brain tissue in tumor-free mice. A-C, Representative spectrum from a voxel within the brain of a tumor-free mouse (A), and representative spectra from voxels within the tumor and normal-appearing brain of A11 (B) and S2 (C) tumor–bearing animals injected with 2 g/kg [6,6-2H2]glucose. Fits to the spectra are shown in color: red, water; green, glucose; blue, Glx; and purple, lactate. The tumor is outlined in yellow on the T2-weighted 1H image. The locations of the CSI voxels are indicated by the boxes. The spectra are the sum of six 10-minute spectra acquired from 3 × 3 × 9 mm voxels. D-F, Comparison of 2H-labeled glucose (D), Glx (E), and lactate (F) concentrations in the brains of tumor-free mice and the normal-appearing brain of mice bearing A11 and S2 tumors. G-I, Comparison of 2H-labeled glucose (G), Glx (H), and lactate (I) concentrations in A11 tumors and adjacent normal-appearing brain tissue. J-L, Comparison of 2H-labeled glucose (J), Glx (K), and lactate (L) concentrations in S2 tumors and adjacent normal-appearing brain tissue. ns, not significant; *, P < 0.05; ***, P < 0.001.
Figure 2 from Deuterium Metabolic Imaging Differentiates Glioblastoma Metabolic Subtypes and Detects Early Response to Chemoradiotherapy
Authors: Low Jacob C.M. , Cao Jianbo , Hesse Friederike , Wright Alan J. , Tsyben Anastasia , Alshamleh Islam , Mair Richard , Brindle Kevin M.
Published: June 2024

Coil-localized 2H MRS differentiates metabolic subtypes of GBM in vivo. A-E, Representative summed 5-minute 2H spectra from tumor-free mice (A) and tumor-bearing mice with A11 (B), U87 (C), S2 (D), and AT5 tumors (E) acquired over a period of 60 minutes following an i.v. injection of 2 g/kg [6,6′-2H2]glucose. The summed spectra overlaid with the corresponding peak fits are shown. F-I, Concentrations of HDO (F), glucose (G), Glx (H), and lactate (I) determined from the fitted peaks in individual 5-minute spectra. J-L, The average concentrations of 2H-labeled glucose (J), Glx (K), and lactate (L) measured between 20 and 65 minutes following injection of [6,6′-2H2] glucose in the four tumor models and in tumor-free animals. A one-way ANOVA showed that there were no significant differences in the labeled glucose concentration in the four tumor models and in tumor-free mice, but there were significant differences in the concentrations of labeled lactate and Glx between the glycolytic and mitochondrial subtype tumors and between the concentrations of labeled lactate in the glycolytic subtype tumors and the tumor-free animals. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Figure 1 from Deuterium Metabolic Imaging Differentiates Glioblastoma Metabolic Subtypes and Detects Early Response to Chemoradiotherapy
Authors: Low Jacob C.M. , Cao Jianbo , Hesse Friederike , Wright Alan J. , Tsyben Anastasia , Alshamleh Islam , Mair Richard , Brindle Kevin M.
Published: June 2024

Metabolic characterization of GBM tumor cells in vitro. A, ECAR measurements. There were no significant differences between A11 and U87 cells (P = 0.427) or between S2 and AT5 cells (P = 0.494). B, OCR measurements. There were no significant differences between S2 and AT5 cells (P = 0.920) or between A11 and U87 cells (P = 0.127). C, OCR/ECAR ratio. There were no significant differences between S2 and AT5 cells (P = 0.996) or between A11 and U87 cells (P = 0.378). D,2H MRS measurements of 2H-labeled lactate produced by A11, S2, and AT5 cells incubated for 4 hours in glucose-free neurobasal media and U87 cells incubated in glucose-free DMEM, both supplemented with 10 mmol/L [6,6′-2H2]glucose. E and F, HSQC 1H-13C MRS measurements of 13C-labeled lactate (E) and Glx (F) measured in cell extracts obtained by chloroform–methanol extraction following incubation for 6 hours in glucose-free media supplemented with 10 mmol/L [U-13C]glucose. Proton signal intensities in the spectra are reported relative to the TMSP standard. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
Figure S8 from Fc-Silent Anti-TIGIT Antibodies Potentiate Antitumor Immunity without Depleting Regulatory T Cells
Authors: Piovesan Dana , de Groot Amber E. , Cho Soonweng , Anderson Amy E. , Ray Rebecca D. , Patnaik Amita , Foster Paul G. , Mitchell Casey G. , Lopez Espinoza Alejandra Y. , Zhu Wandi S. , Stagnaro Carlo E. , Singh Hema , Zhao Xiaoning , Seitz Lisa , Walker Nigel P. , Walters Matthew J. , Sivick Kelsey E.
Published: June 2024

Figure S8
Figure S4 from Fc-Silent Anti-TIGIT Antibodies Potentiate Antitumor Immunity without Depleting Regulatory T Cells
Authors: Piovesan Dana , de Groot Amber E. , Cho Soonweng , Anderson Amy E. , Ray Rebecca D. , Patnaik Amita , Foster Paul G. , Mitchell Casey G. , Lopez Espinoza Alejandra Y. , Zhu Wandi S. , Stagnaro Carlo E. , Singh Hema , Zhao Xiaoning , Seitz Lisa , Walker Nigel P. , Walters Matthew J. , Sivick Kelsey E.
Published: June 2024

Figure S4
Supplementary figures from Oncogenic KRAS Induces Arginine Auxotrophy and Confers a Therapeutic Vulnerability to SLC7A1 Inhibition in Non–Small Cell Lung Cancer
Authors: Gai Xiameng , Liu Yingluo , Lan Xiaojing , Chen Luoyi , Yuan Tao , Xu Jun , Li Yize , Zheng Ying , Yan Yiyang , Yang Liya , Fu Yixian , Tang Shuai , Cao Siyuwei , Dai Xiaoyang , Zhu Hong , Geng Meiyu , Ding Jian , Pu Congying , Huang Min
Published: June 2024

Supplementary figure S1-5
Supplementary Figure S7 from Integration of Pan-Cancer Cell Line and Single-Cell Transcriptomic Profiles Enables Inference of Therapeutic Vulnerabilities in Heterogeneous Tumors
Authors: Zhang Weijie , Maeser Danielle , Lee Adam , Huang Yingbo , Gruener Robert F. , Abdelbar Israa G. , Jena Sampreeti , Patel Anand G. , Huang R. Stephanie
Published: June 2024

Supplementary Figure S7
Supplementary Figures from Oncogene-Driven Non–Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations
Authors: Huang Chen-Yang , Jiang Nanhai , Shen Meixin , Lai Gillianne G. , Tan Aaron C. , Jain Amit , Saw Stephanie P. , Ang Mei Kim , Ng Quan Sing , Lim Darren W. , Kanesvaran Ravindran , Tan Eng Huat , Tan Wan Ling , Ong Boon-Hean , Chua Kevin L. , Anantham Devanand , Takano Angela M. , Lim Kiat Hon , Tam Wai Leong , Sim Ngak Leng , Skanderup Anders J. , Tan Daniel S. , Rozen Steven G.
Published: June 2024

Supplementary Figures
Supplementary Figure S4 from Integration of Pan-Cancer Cell Line and Single-Cell Transcriptomic Profiles Enables Inference of Therapeutic Vulnerabilities in Heterogeneous Tumors
Authors: Zhang Weijie , Maeser Danielle , Lee Adam , Huang Yingbo , Gruener Robert F. , Abdelbar Israa G. , Jena Sampreeti , Patel Anand G. , Huang R. Stephanie
Published: June 2024

Supplementary Figure S4
Supplementary Figure S3 from Integration of Pan-Cancer Cell Line and Single-Cell Transcriptomic Profiles Enables Inference of Therapeutic Vulnerabilities in Heterogeneous Tumors
Authors: Zhang Weijie , Maeser Danielle , Lee Adam , Huang Yingbo , Gruener Robert F. , Abdelbar Israa G. , Jena Sampreeti , Patel Anand G. , Huang R. Stephanie
Published: June 2024

Supplementary Figure S3
Supplementary Figure S1 from Integration of Pan-Cancer Cell Line and Single-Cell Transcriptomic Profiles Enables Inference of Therapeutic Vulnerabilities in Heterogeneous Tumors
Authors: Zhang Weijie , Maeser Danielle , Lee Adam , Huang Yingbo , Gruener Robert F. , Abdelbar Israa G. , Jena Sampreeti , Patel Anand G. , Huang R. Stephanie
Published: June 2024

Supplementary Figure S1
Data from Oncogenic KRAS Induces Arginine Auxotrophy and Confers a Therapeutic Vulnerability to SLC7A1 Inhibition in Non–Small Cell Lung Cancer
Authors: Gai Xiameng , Liu Yingluo , Lan Xiaojing , Chen Luoyi , Yuan Tao , Xu Jun , Li Yize , Zheng Ying , Yan Yiyang , Yang Liya , Fu Yixian , Tang Shuai , Cao Siyuwei , Dai Xiaoyang , Zhu Hong , Geng Meiyu , Ding Jian , Pu Congying , Huang Min
Published: June 2024

Abstract
The urea cycle is frequently rewired in cancer cells to meet the metabolic demands of cancer. Elucidation of the underlying mechanism by which oncogenic signaling mediates urea cycle reprogramming could help identify targetable metabolic vulnerabilities. In this study, we discovered that oncogenic activation of KRAS in non–small cell lung cancer (NSCLC) silenced the expression of argininosuccinate synthase 1 (ASS1), a urea cycle enzyme that catalyzes the production of arginine from aspartate and citrulline, and thereby diverted the utilization of aspartate to pyrimidine synthesis to meet the high demand for DNA replication. Specifically, KRAS signaling facilitated a hypoacetylated state in the promoter region of the ASS1 gene in a histone deacetylase 3–dependent manner, which in turn impeded the recruitment of c-MYC for ASS1 transcription. ASS1 suppression in KRAS-mutant NSCLC cells impaired the biosynthesis of arginine and rendered a dependency on the arginine transmembrane transporter SLC7A1 to import extracellular arginine. Depletion of SLC7A1 in both patient-derived organoid and xenograft models inhibited KRAS-driven NSCLC growth. Together, these findings uncover the role of oncogenic KRAS in rewiring urea cycle metabolism and identify SLC7A1-mediated arginine uptake as a therapeutic vulnerability for treating KRAS-mutant NSCLC.
Significance:
ASS1 deficiency is induced by mutant KRAS in NSCLC to facilitate DNA synthesis and creates a dependency on SLC7A1, revealing dietary arginine restriction and SLC7A1 inhibition as potential therapeutic strategies.
Data from Oncogene-Driven Non–Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations
Authors: Huang Chen-Yang , Jiang Nanhai , Shen Meixin , Lai Gillianne G. , Tan Aaron C. , Jain Amit , Saw Stephanie P. , Ang Mei Kim , Ng Quan Sing , Lim Darren W. , Kanesvaran Ravindran , Tan Eng Huat , Tan Wan Ling , Ong Boon-Hean , Chua Kevin L. , Anantham Devanand , Takano Angela M. , Lim Kiat Hon , Tam Wai Leong , Sim Ngak Leng , Skanderup Anders J. , Tan Daniel S. , Rozen Steven G.
Published: June 2024

Abstract
Non–small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these “nonsmoking-related oncogenes” (NSRO) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared with typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and nonsmokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC data sets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to the regulation of the cell cycle. These findings suggest that, whereas the genomic landscape is similar between NSRO-driven NSCLC in smokers and nonsmokers, smoking still affects the tumor phenotype independently of genomic alterations.
Significance:
Non-small cell lung cancers driven by nonsmoking-related oncogenes do not harbor genomic scars caused by smoking regardless of smoking history, indicating that the impact of smoking on these tumors is mainly nongenomic.
Supplementary Table S1 from A Phase I Trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies
Authors: Kalogera Eleftheria , Nevala Wendy K. , Finnes Heidi D. , Suman Vera J. , Schimke Jill M. , Strand Carrie A. , Kottschade Lisa A. , Kudgus Rachel A. , Buhrow Sarah A. , Becher Laura R. , Geng Liyi , Glaser Gretchen E. , Grudem Megan E. , Jatoi Aminah , Klampe Carolyn M. , Kumar Amanika , Langstraat Carrie L. , McWilliams Robert R. , Wahner Hendrickson Andrea E. , Weroha S. John , Yan Yiyi , Reid Joel M. , Markovic Svetomir N. , Block Matthew S.
Published: June 2024

Representativeness of Study Population
Supplementary Figure S2 from A Phase I Trial of Nab-Paclitaxel/Bevacizumab (AB160) Nano-Immunoconjugate Therapy for Gynecologic Malignancies
Authors: Kalogera Eleftheria , Nevala Wendy K. , Finnes Heidi D. , Suman Vera J. , Schimke Jill M. , Strand Carrie A. , Kottschade Lisa A. , Kudgus Rachel A. , Buhrow Sarah A. , Becher Laura R. , Geng Liyi , Glaser Gretchen E. , Grudem Megan E. , Jatoi Aminah , Klampe Carolyn M. , Kumar Amanika , Langstraat Carrie L. , McWilliams Robert R. , Wahner Hendrickson Andrea E. , Weroha S. John , Yan Yiyi , Reid Joel M. , Markovic Svetomir N. , Block Matthew S.
Published: June 2024

Paclitaxel Pharmacokinetics in Cynomolgus Monkeys
Supplementary Figure 1 from Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma
Authors: Öfverholm Ingegerd , Wallander Karin , Haglund Cecilia , Chellappa Venkatesh , Wejde Johan , Gellerbring Anna , Wirta Valtteri , Renevey Annick , Caceres Eva , Tsagkozis Panagiotis , Mayrhofer Markus , Papakonstantinou Andri , Linder-Stragliotto Christina , Bränström Robert , Larsson Olle , Lindberg Johan , Lin Yingbo , Haglund de Flon Felix
Published: June 2024

Figure S1
Supplementary Data 4 from Comprehensive Genomic Profiling Alters Clinical Diagnoses in a Significant Fraction of Tumors Suspicious of Sarcoma
Authors: Öfverholm Ingegerd , Wallander Karin , Haglund Cecilia , Chellappa Venkatesh , Wejde Johan , Gellerbring Anna , Wirta Valtteri , Renevey Annick , Caceres Eva , Tsagkozis Panagiotis , Mayrhofer Markus , Papakonstantinou Andri , Linder-Stragliotto Christina , Bränström Robert , Larsson Olle , Lindberg Johan , Lin Yingbo , Haglund de Flon Felix
Published: June 2024

Table S4
Supplementary Table 3 from Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC
Authors: Pang Lanlan , Huang Yihua , Zhuang Weitao , Zhang Yaxiong , Liao Jun , Hao Yue , Hao Feng , Wang Guoqian , Chen Ze-xin Chase , Zhu Yu , Li Mengzhen , Song Zhengbo , Deng Bo Peng , Li Jing , Zhang Li , Fang Wenfeng
Published: June 2024

Supplementary Table 3. List of genes included in the Mygene Diagnostics NGS panel. (Ion AmpliSeq Colon and Lung Cancer Research Panel v2 and Ion AmpliSeq RNA Fusion gene list)
Supplementary Table 1 from Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC
Authors: Pang Lanlan , Huang Yihua , Zhuang Weitao , Zhang Yaxiong , Liao Jun , Hao Yue , Hao Feng , Wang Guoqian , Chen Ze-xin Chase , Zhu Yu , Li Mengzhen , Song Zhengbo , Deng Bo Peng , Li Jing , Zhang Li , Fang Wenfeng
Published: June 2024

Supplementary Table 1. Representativeness of Study Participants
Supplementary Figure 5 from Co-occurring EGFR p.E709X Mutation Mediates Primary Resistance to the Third-Generation EGFR-TKIs in EGFR p.G719X-Mutant Patients with Advanced NSCLC
Authors: Pang Lanlan , Huang Yihua , Zhuang Weitao , Zhang Yaxiong , Liao Jun , Hao Yue , Hao Feng , Wang Guoqian , Chen Ze-xin Chase , Zhu Yu , Li Mengzhen , Song Zhengbo , Deng Bo Peng , Li Jing , Zhang Li , Fang Wenfeng
Published: June 2024

Supplementary Figure 5. Structural modeling of EGFR p.G719A/E709K in a complex with afatinib.