bluuebunny/crossref_metadata_2025 huggingface dataset:
Rickettsia
disrupts and reduces endothelial tight junction protein zonula occludens-1 in association with inflammasome activation
Authors: Velatooru Loka Reddy , Arroyave Esteban , Rippee-Brooks Meagan D. , Burch Megan , Yang Ethan , Zhu Bing , Walker David H. , Zhang Yang , Fang Rong
Published: December 2024

Rickettsia
spp. cause life-threatening diseases in humans. The fundamental pathophysiological changes in fatal rickettsial diseases are disrupted endothelial barrier and increased microvascular permeability. However, it remains largely unclear how rickettsiae induce microvascular endothelial injury. In the present study, we demonstrated that
Rickettsia conorii
infection disrupts the continuous immunofluorescence expression of the interendothelial tight junction protein, zonula occludens-1 (ZO-1), in infected monolayers of microvascular endothelial cells (MVECs), accompanied by significantly diminished total expression levels of ZO-1. Interestingly,
R. conorii
activated inflammasome in MVECs, as evidenced by cleaved caspase-1 and IL-1β in the cell lysates in association with significantly elevated expression levels of nucleotide binding and oligomerization domain, leucine-rich repeat, and pyrin containing protein 3 (NLRP3). Furthermore, selective inhibition of NLRP3 by MCC950 significantly suppressed the activation and cleavage of caspase-1 induced by
R. conorii
in endothelial cells, which further prevented the disruption of interendothelial junctions and reduction of ZO-1 expression. Of note, pharmaceutical inhibition of NLRP3 mitigated the disrupted endothelial integrity caused by
R. conorii
, measured by fluorescein isothiocyanate-dextran passage in a Transwell assay, independent of bacterial growth and cellular cytotoxicity. Taken together, our results suggest that
R. conorii
affected microvascular endothelial junction integrity likely via diminishing and interrupting the junctional protein ZO-1 in association with activating NLRP3 inflammasome. These data not only highlight the potential of ZO-1 as a biomarker for
Rickettsia
-induced microvascular injury but also provide insight into targeting NLRP3 inflammasome/ZO-1 signaling as a potentially adjunctive therapeutic approach for severe rickettsioses.
Excellent capability for molecular detection of
Aedes
-borne dengue, Zika, and chikungunya viruses but with a need for increased capacity for yellow fever and Japanese encephalitis viruses: an external quality assessment in 36 European laboratories
Authors: Presser Lance D. , Baronti Cécile , Moegling Ramona , Pezzi Laura , Lustig Yaniv , Gossner Céline M. , Reusken Chantal B. E. M. , Charrel Rémi N. ,   on behalf of EVD-LabNet
Published: December 2024

Mosquito-borne viruses represent a large global health burden. With geographic expansion of competent vectors for chikungunya virus (CHIKV), dengue virus (DENV), and Zika virus (ZIKV) in Europe, it is anticipated that the number of autochthonous cases of these tropical viruses in Europe will increase. Therefore, regular assessment of diagnostic capabilities in Europe is important. Our aim was to evaluate the mosquito-borne virus molecular detection capability of expert European laboratories by conducting an external quality assessment in October 2023. Molecular panels included 12 plasma samples: one alphavirus (CHIKV), four orthoflaviviruses (ZIKV, yellow fever virus [YFV], DENV, and Japanese encephalitis virus [JEV]), and two negative control samples. Mosquito-borne virus detection was assessed among 36 laboratories in 24 European countries. Adequate capabilities were lacking for YFV and JEV. Many laboratories relied on a mix of laboratory-developed tests (some of which were pan-orthoflavivirus or pan-alphavirus in combination with sequencing) and commercial assays. 47.2% of laboratories characterized all external quality assessment (EQA) samples correctly. Correct result rates were 100% for CHIKV and ZIKV and >99% for DENV, but laboratories lacked capacity, specificity, and sensitivity for JEV and YFV. Three of the viruses in this panel emerged and transiently circulated in Europe: CHIKV, ZIKV, and DENV. Molecular detection was excellent for those viruses, but <50% is accurate for the remainder of the panel. With the possibility or continuation of imported cases and a growing global concern about climate change and vector expansion, progress toward rapid, accurate mosquito-borne virus diagnostics in Europe is recommended, as well as regular EQAs to monitor it.

IMPORTANCE

The external quality assessment (EQA) focused on
Aedes
-borne viruses: chikungunya virus (CHIKV), dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV). Japanese encephalitis virus, an orthoflavivirus that is spread by mosquito species belonging to the genus
Culex
, was included in the quality assessment as well. CHIKV, DENV, and ZIKV have proven potential for transient and limited circulation in Europe upon introduction of viremic travelers returning to
Aedes albopictus
-endemic regions. Results of this EQA were excellent for those viruses, but <50% is accurate for the remainder of the panel (YFV and Japanese encephalitis virus). Considering imported cases and the threat of climate change and competent vector expansion, progress toward rapid, accurate mosquito-borne virus diagnostics in Europe is recommended.
Inhibition and evasion of neutrophil microbicidal responses by
Legionella longbeachae
Authors: Hanford Hannah E. , Price Christopher T. D. , Uriarte Silvia , Abu Kwaik Yousef
Published: December 2024

Legionella
species evade degradation and proliferate within alveolar macrophages as an essential step for the manifestation of disease. However, most intracellular bacterial pathogens are restricted in neutrophils, which are the first line of innate immune defense against invading pathogens. Bacterial degradation within neutrophils is mediated by the fusion of microbicidal granules to pathogen-containing phagosomes and the generation of reactive oxygen species (ROS) by the phagocyte NADPH oxidase complex. Here, we show that human neutrophils fail to trigger microbicidal processes and, consequently, fail to restrict
L. longbeachae
. In addition, neutrophils infected with
L. longbeachae
fail to undergo a robust pro-inflammatory response, such as degranulation and IL-8 production. Here, we identify three strategies employed by
L. longbeachae
for evading restriction by neutrophils and inhibiting the neutrophil microbicidal response to other bacteria co-inhabiting in the same cell. First,
L. longbeachae
excludes the cytosolic and membrane-bound subunits of the phagocyte NADPH oxidase complex from its phagosomal membrane independent of the type 4 secretion system (T4SS). Consequently, infected neutrophils fail to generate robust ROS in response to
L. longbeachae
. Second,
L. longbeachae
impedes the fusion of azurophilic granules to its phagosome and the phagosomes of bacteria co-inhabiting the same cell through T4SS-independent mechanisms. Third,
L. longbeachae
protects phagosomes of co-inhabiting bacteria from degradation by ROS through a
trans
-acting T4SS-dependent mechanism. Collectively, we conclude that
L. longbeachae
evades restriction by human neutrophils
via
T4SS-independent mechanisms and utilizes
trans
-acting T4SS-dependent mechanisms for inhibition of neutrophil ROS generation throughout the cell cytosol.

IMPORTANCE

Legionella longbeachae
is commonly found in soil environments where it interacts with a wide variety of protist hosts and microbial competitors. Upon transmission to humans
, L. longbeachae
invades and replicates within alveolar macrophages, leading to the manifestation of pneumonia. In addition to alveolar macrophages, neutrophils are abundant immune cells acting as the first line of defense against invading pathogens. While most intracellular bacterial species are killed and degraded by neutrophils, we show that
L. longbeachae
evades degradation. The pathogen impairs the major neutrophils’ microbicidal processes, including the fusion of microbicidal granules to the pathogen-containing vacuole. By inhibiting of assembly of the phagocyte NADPH oxidase complex, the pathogen blocks neutrophils from generating microbicide reactive oxygen species. Overall,
L. longbeachae
employs unique virulence strategies to evade the major microbicidal processes of neutrophils.
Draft genome sequences of three xerophilic
Aspergillus
section
Restricti
species isolated from house dust in Japan
Authors: Hagiuda Ryo , Hirose Dai
Published: December 2024

We present the nuclear and complete mitochondrial genome sequences of
Aspergillus clavatophorus
NBRC 116038,
Aspergillus magnivesiculatus
NBRC 116037, and
Aspergillus verrucosus
NBRC 115547
T
, all isolated from house dust in Japan. These sequence data are crucial for elucidating the evolutionary characteristics of section
Restricti
, a unique taxon comprising exclusively xerophilic species.
Clade-specific long-read sequencing increases the accuracy and specificity of the
gyrB
phylogenetic marker gene
Authors: Nichols Robert G. , Davenport Emily R.
Published: December 2024

Phylogenetic marker gene sequencing is often used as a quick and cost-effective way of evaluating microbial composition within a community. While 16S rRNA gene sequencing (16S) is commonly used for bacteria and archaea, other marker genes are preferable in certain situations, such as when 16S sequences cannot distinguish between taxa within a group. Another situation is when researchers want to study cospeciation of host taxa that diverged much more recently than the slowly evolving 16S rRNA gene. For example, the bacterial gyrase subunit B (
gyrB
) gene has been used to investigate cospeciation between the microbiome and various hominid species. However, to date, only primers that generate short-read Illumina MiSeq-length amplicons exist to investigate
gyrB
of the Bacteroidaceae, Bifidobacteriaceae, and Lachnospiraceae families. Here, we update this methodology by creating
gyrB
primers for the Bacteroidaceae, Bifidobacteriaceae, and Lachnospiraceae families for long-read PacBio sequencing and characterize them against established short-read
gyrB
primer sets. We demonstrate both bioinformatically and analytically that these longer amplicons offer more sequence space for greater taxonomic resolution, lower off-target amplification rates, and lower error rates with PacBio CCS sequencing versus established short-read sequencing. The availability of these long-read
gyrB
primers will prove to be integral to the continued analysis of cospeciation between bacterial members of the gut microbiome and recently diverging host species.

IMPORTANCE

Previous studies have shown that the marker gene gyrase subunit B (
gyrB
) can be used to study codiversification between the gut microbiome and hominids. However, only primers for short-read sequencing have been developed which have limited resolution for subspecies assignment. In the present study, we create new
gyrB
primer sets for long-read sequencing approaches and compare them to the existing short-read
gyrB
primers. We show that using longer reads leads to better taxonomic resolution, lower off-target amplification, and lower error rates, which are vital for accurate estimates of codiversification.
Impact of rapid antibiotic susceptibility testing for Gram-negative bacteremia varies by pathogen type and resistance: a secondary analysis of the RAPIDS GN trial
Authors: Banerjee Ritu , Giri Abhigya , Komarow Lauren , Souli Maria , Doernberg Sarah B. , Patel Robin ,   on behalf of the Antibacterial Resistance Leadership Group
Published: December 2024

In this secondary analysis of 386 subjects with Gram-negative bacteremia enrolled in the RAPIDS GN trial, rapid antibiotic susceptibility testing had a greater benefit on the management of bacteremia caused by antibiotic-resistant compared to antibiotic-susceptible isolates, especially for
Escherichia coli, Klebsiella
species
,
and
Proteus
species.

IMPORTANCE

Rapid blood culture diagnostics are costly, and their use has not demonstrated clear clinical benefit for patients with Gram-negative sepsis, possibly because prior trials did not enroll sufficient numbers of patients with antibiotic-resistant infections. This analysis of patients with sepsis previously enrolled in a randomized controlled clinical trial demonstrates that rapid susceptibility testing of bacteria from blood cultures had the greatest impact for patients with antibiotic-resistant infections. Specifically, after rapid testing results were reported, patients infected with resistant bacteria received appropriate antibiotic therapy more quickly than patients with susceptible bacteria. These findings highlight the need to evaluate blood culture diagnostics in areas with high antibiotic resistance where these diagnostics are likely to have the greatest impact.
Soft Mode Behavior in Transition Metal Doped SrTiO3 Thin Films on MgO Substrates
Authors: Melentev A. V. , Zhukova E. S. , Nekrasov B. M. , Stolyarov V. S. , Frolov A. S. , Savinov M. , Bush A. A. , Kozlov V. I. , Gorshunov B. P. , Talanov M. V.
Published: December 2024

The ferroelectric soft mode in polycrystalline pristine SrTiO3 and weakly doped SrTiO3:M (M = 2 at % Fe, Ni, Mn, Co) thin films on (001) MgO substrates has been studied using time-domain terahertz spectroscopy. Spectra of real and imaginary parts of film permittivity were determined in the frequency range of 5–100 cm–1 at temperatures between 5 and 300 K. Central frequency and dielectric contribution of the ferroelectric soft mode show Barrett-like temperature dependencies similar to crystalline SrTiO3. Large negative values of Curie temperature and enhanced positive values of Barrett quantum temperatures are discovered indicating that doped SrTiO3 thin films are farther from ferroelectric phase transition than SrTiO3 crystals.
Males have higher psychological readiness to return to sports than females after anterior cruciate ligament reconstruction: a systematic review and meta-analysis
Authors: Obradovic Anja , Manojlovic Marko , Rajcic Aleksandra , Jankovic Stefan , Andric Nikola , Ralic Vuk , Zlicic Tamara , Aleksic Branko , Ninkovic Srdjan , Veraksa Aleksander , Drid Patrik
Published: December 2024

Objectives

To examine sex differences in psychological readiness to return to sport following anterior cruciate ligament (ACL) reconstruction as well as to determine whether males and females separately fulfilled cut-off values (≥65) of psychological readiness necessary to return to sport.

Information sources

Web of Science, Scopus and PubMed were comprehensively searched from inception to January 2024 to identify relevant studies.

Eligibility criteria

Observational investigations that compared males and females with a history of ACL reconstruction concerning psychological readiness to return to sport.

Risk of bias

Studies were rated using the Methodological Index for Non-Randomised Studies.

Included studies

Only 11 reports fulfilled the eligibility criteria and were included in the quantitative analysis. A total of 2618 participants were subjected to the primary ACL reconstruction, out of 1631 males and 987 females. Psychological readiness to return to sport was evaluated approximately 9±2.9 months following surgery.

Synthesis of results

The main findings demonstrated that males had slightly higher psychological readiness to return to the sport than females (standardised mean difference 0.33; 95% CI 0.14 to 0.52; p=0.0007; I2=77%) after ACL surgery. In addition, the mean psychological readiness to return to the sport of males was 70.1±8.8 points and of females 65.1±8.8 points, indicating that both sexes exceeded recommendations necessary to return to sport.

Conclusion

Males had slightly higher psychological readiness to return to sport than females approximately 9±2.9 months after ACL reconstruction and both sexes exceeded the highlighted recommendations necessary to return to sport.

PROSPERO registration number

CRD42024497769: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024497769.
Association between NT-proBNP levels and risk of atrial fibrillation: a systematic review and meta-analysis of cohort studies
Authors: Wang Wanyue , Zhou Tao , Li Jinyue , Yuan Chenxi , Li Chenyang , Chen Shufeng , Shen Chong , Gu Dongfeng , Lu Xiangfeng , Liu Fangchao
Published: December 2024

Background and aims

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established biomarker in clinical practice, particularly for heart failure, but its role in predicting atrial fibrillation (AF) risk is not fully understood. This meta-analysis aimed to evaluate the association between NT-proBNP levels and AF incidence, and to explore the potential of NT-proBNP in enhancing AF risk prediction models.

Methods

We systematically searched databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) up to August 2024 for prospective studies that reported associations between baseline NT-proBNP levels and incident AF. HRs or relative risks (RRs) with 95% CIs were pooled using random-effects models.

Results

This analysis included 136 089 participants from 16 cohorts, with 8017 incident AF cases. Elevated NT-proBNP levels were associated with a higher risk of developing AF (top vs bottom quartile, RR=3.84, 95% CI 3.03 to 4.87; per SD increment, RR=1.70, 95% CI 1.54 to 1.88). A significant non-linear dose-response relationship was observed (P
non-linearity
<0.05), and stronger associations were noted in older populations and when serum samples were used. Adding NT-proBNP to traditional AF risk models improved predictive accuracy, suggesting its value in AF risk stratification.

Conclusions

NT-proBNP levels are strongly associated with an increased risk of AF, particularly in older adults. Incorporating NT-proBNP into risk prediction models may enhance early identification of individuals at risk of AF, with potential implications for population-based screening.

PROSPERO registration number

CRD42024538714.
Rationale and design of the randomised, controlled Percutaneous coronary intervention using Assisted Robotic TechnologY (PARTY) trial
Authors: Leung James , Xu James , French John K , Kachwalla Hashim , Kaddapu Krishna , Badie Tamer , Mussap Christian , Rajaratnam Rohan , Leung Dominic Y , Lo Sidney T , Juergens Craig
Published: December 2024

Introduction

Percutaneous coronary intervention (PCI) is performed by interventional cardiologists who, over their career, are exposed to substantial X-ray radiation and also face potential musculoskeletal injuries from the prolonged wearing of heavy protective equipment. Patients are also at risk from radiation exposure. Robotic-assisted PCI (R-PCI) allows millimetre control of the coronary guide-catheter, guidewires and intracoronary devices via three joysticks and touchscreens located within in a shielded ‘cockpit’, away from radiation. Initial studies have demonstrated efficacy and safety of R-PCI with significant radiation reductions. However, these studies are non-randomised, registry based or observational data with short clinical follow-up. We aim to perform the first randomised controlled trial investigating R-PCI compared with manual PCI (M-PCI) with longer clinical follow-up.

Methods and analysis

The Percutaneous coronary intervention using Assisted Robotic TechnologY (PARTY) trial is a single-centre, prospective, randomised, open-label clinical trial comparing R-PCI to M-PCI. Eligible patients between 18 and 85 years undergoing coronary angiography, and are subsequently deemed to require PCI, will be screened. A key exclusion criterion is if the operator determines that the participant or coronary anatomy is unsuitable for R-PCI. Patients will be randomised to R-PCI or M-PCI in a 1:1 fashion. The primary outcome is radiation exposure to the patient, as measured by personal radiation dosimeters. Other procedural, safety and efficacy outcomes will be compared. Patients will be followed up until hospital discharge (or 72 hours, whichever occurs first), and then by telephone at 30 and 365 days.

Trial registration number

ACTRN12623000480684.
Effect of displaced abomasum on milk production, reproductive performance, and culling of Holstein dairy cattle in Iran
Authors: Asgari Zeinab , Sadeghi-Sefidmazgi Ali , Pakdel Abbas , Shahinfar Saleh
Published: December 2024

Displaced abomasum (DA) is an important digestive condition that adversely affects the economic performance and the productive lifespan of a dairy cow. Due to increasing DA incidence in recent years, the present research was performed to estimate the potential effects of DA on the performance of Iranian Holstein. Production data were analyzed using a linear mixed model. Cox proportional hazard regression was used to assess the associations of DA occurrence with the time from calving to first service, pregnancy (in 120 and 220 DIM, respectively) and culling. The least-square means showed that DA was significantly ( P < 0.0001) associated with reduced milk, fat, and protein yields, especially during peak milk production. Results of survival analyzes showed that DA could be associated with reduced probability pregnancy in the first service at 120 DIM (hazard ratio = 0.57; 95% CI = 0.51–0.64), and at 220 DIM (hazard ratio = 0.81; 95% CI = 0.76–0.86) and with an increased hazard of culling in the same lactation (hazard ratio = 3.85; 95% CI = 3.13–4.74). Considering negative effects of DA in dairy cows, it can be concluded, quantitative knowledge of the consequences of DA may convince dairy farmers to apply preventive strategies to reduce the incidence of DA in the herd.
Solitary wave solutions, bifurcation theory, and sensitivity analysis in the modified unstable nonlinear Schrödinger equation
Authors: Shakeel Muhammad , Liu Xinge
Published: December 2024

This study examines the modified unstable nonlinear Schrödinger model, a fundamental nonlinear physical model vital for depicting optical solitary wave solutions and their evolution in dynamic fiber optics. The propagation of waves in nonlinear dispersive media is of great significance, presenting new opportunities for data processing in communication systems and generating ultrafast light pulses. Applying a wave transformation reduces the nonlinear Schrödinger equation to an ordinary differential equation, and an extended direct algebraic method is used to derive various soliton solutions. The novelty lies in using this method to uncover various soliton forms, which are then explored through graphical representations in 2D, 3D, and contour plots. The phase portraits and bifurcation theory also qualitatively assess the undisturbed planar system. Sensitivity analysis under different initial conditions indicates how the soliton solutions adapt to changes in system parameters. The outcomes confirm that the presented approach effectively evaluates soliton solutions across diverse nonlinear models, contributing to the understanding of wave propagation in slightly stable and unstable media.
MRI‐Based Morphometric Comparison of Lower Leg Muscles and Tendons in Individuals With Medial Tibial Stress Syndrome
Authors: de Oliveira Lucas Nogueira , Durigan João Luiz Quagliotti , Sanchez Caroline Ribeiro , Mansur Henrique , Rosa Andressa Beatriz Beltrão , Marquetti Rita de Cássia
Published: December 2024

Runners frequently suffer from medial tibial stress syndrome (MTSS), often linked to excessive eccentric muscle contractions causing periosteal traction by the muscles in the deep posterior compartment. However, the effects of MTSS on these muscles and tendons remain underexplored. This study is aimed at investigating changes in muscle and tendon volumes in this compartment, as well as cross‐sectional area measurements, using magnetic resonance imaging. Thirty individuals were divided into two groups: MTSS (n = 18; mean age 30.3 ± 12.4) and control (n = 12; age 35.2 ± 9.2). The anterior, deep posterior, superficial posterior, and lateral compartment muscles, along with their respective tendons, were compared between groups, and possible sex differences were also evaluated. The deep posterior compartment showed a significant volume difference of 0.41 cm3/kg3/4 in the MTSS group (p = 0.034), primarily due to the flexor hallucis longus (FHL), which had a 0.55 cm3/kg3/4 greater normalized volume (17.12% greater mean muscle volume) compared to controls (p = 0.023; Cohen d = 0.895). No association between sex and MTSS was found (p = 0.752). In conclusion, the FHL muscle exhibited increased normalized volume in the MTSS group compared to controls, with no sex‐related differences in MTSS. Clinicians should consider the assessment of FHL muscle volume in routine evaluations of patients presenting with symptoms suggestive of MTSS.
Cytokine Release Syndrome After CAR T‐Cell Therapy in a 35‐Year‐Old Patient With Pneumocystis jiroveci Pneumonia and Cytomegalovirus Viremia
Authors: Helms Kristina A.
Published: December 2024

Background: The risk of cytokine release syndrome (CRS) in patients with infections prior to chimeric antigen receptor T‐cell (CAR T‐cell) therapy represents an important and underreported event. Patients with active infections needing prompt CAR T‐cell therapy to treat aggressive hematologic malignancies remain a clinical challenge.

Case Report: This case describes the clinical course of a 35‐year‐old male patient with relapsed/refractory T‐cell/histiocyte‐rich large B‐cell lymphoma who received axicabtagene ciloleucel. The patient developed ASTCT Grade II CRS on day +5, necessitating hospital admission and intravenous antibiotics, dexamethasone and tocilizumab. The patient was found to have a Pneumocystis jirovecii pneumonia (PJP) infection 3 days prior to CAR T‐cell infusion and cytomegalovirus (CMV) viremia 3 days after CAR T‐cell infusion. He received TMP‐SMX for 21 days to treat PJP and valganciclovir to treat CMV viremia. PET/CT on day +26 demonstrated near resolution of pulmonary nodules and significant partial response of disease according to Deauville criteria.

Conclusion: This case highlights the risk of CRS in immunocompromised patients with infections, and presents a unique case of CRS associated with PJP and CMV infections. Although the patient’s clinical course was fraught with complications, he achieved a significant partial response to CAR T‐cell therapy with the help of a multidisciplinary medical team.
Supplementary Source Data2 from Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Preleukemic Cells
Authors: Liu Xiaoyu , Liu Yu , Rao Qing , Mei Yihan , Xing Haiyan , Gu Runxia , Mou Junli , Chen Manling , Ding Fan , Xie Wanqing , Tang Kejing , Tian Zheng , Wang Min , Qiu Shaowei , Wang Jianxiang
Published: December 2024

all metabolite intensities(patients)
Supplementary Data from Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Preleukemic Cells
Authors: Liu Xiaoyu , Liu Yu , Rao Qing , Mei Yihan , Xing Haiyan , Gu Runxia , Mou Junli , Chen Manling , Ding Fan , Xie Wanqing , Tang Kejing , Tian Zheng , Wang Min , Qiu Shaowei , Wang Jianxiang
Published: December 2024

Supplementary methods, tables,figures and figure legends
Table S7 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Gene lists and sources for each DC-associated gene set used in the scRNA-seq analysis of CD45+ immune cells from the KPC1 shNC/shATG7 syngeneic PDAC tumors
Table S5 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Relationship Between Cancer Cell-LC3 Expression and Clinicopathologic Factors
Figure S6 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Inhibiting autophagy in cancer cells increases the accumulation of intracellular antigens
Supplementary Data from CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression
Authors: Rong Zeyin , Xu Jin , Yang Jianhui , Wang Wei , Tang Rong , Zhang Zifeng , Tan Zhen , Meng Qingcai , Hua Jie , Liu Jiang , Zhang Bo , Liang Chen , Yu Xianjun , Shi Si
Published: December 2024

Supplementary Materials and methods Supplementary Figures S1 to S17 Supplementary Tables S1 to S7
Figure S1 from Combined Autophagy Inhibition and Dendritic Cell Recruitment Induces Antitumor Immunity and Enhances Immune Checkpoint Blockade Sensitivity in Pancreatic Cancer
Authors: Oyama Koki , Nakata Kohei , Tsutsumi Chikanori , Hayashi Masataka , Zhang Bo , Mochida Yuki , Shinkawa Tomohiko , Hirotaka Kento , Zhong Pingshan , Date Satomi , Luo Haizhen , Kubo Akihiro , Higashijima Nobuhiro , Yamada Yutaka , Abe Toshiya , Ideno Noboru , Koikawa Kazuhiro , Iwamoto Chika , Ikenaga Naoki , Ohuchida Kenoki , Onishi Hideya , Morisaki Takashi , Kuba Keiji , Oda Yoshinao , Nakamura Masafumi
Published: December 2024

Analysis of human PDAC tumors reveals a negative correlation between autophagy in cancer cells and DC activation
Supplementary Table 4 from Induction of the TEAD Coactivator VGLL1 by Estrogen Receptor–Targeted Therapy Drives Resistance in Breast Cancer
Authors: Gemma Carolina , Lai Chun-Fui , Singh Anup K. , Belfiore Antonino , Portman Neil , Milioli Heloisa Z. , Periyasamy Manikandan , Raafat Sara , Nicholls Alyssa J. , Davies Claire M. , Patel Naina R. , Simmons Georgia M. , Fan Hailing , Nguyen Van T.M. , Magnani Luca , Rakha Emad , Martin Lesley-Ann , Lim Elgene , Coombes R. Charles , Pruneri Giancarlo , Buluwela Laki , Ali Simak
Published: December 2024

Supplementary Table 4
Supplementary Data from Targeting SHCBP1 Inhibits Tumor Progression by Restoring Ciliogenesis in Ductal Carcinoma
Authors: Shi Wengui , Li Lianshun , Zhao Huiming , Li Zhengyang , Ma Zhijian , Gu Qianlin , Ye Huili , Jiang Xiangyan , Dong Yuman , Qin Long , Zhou Huinian , Yu Zeyuan , Jiao Zuoyi
Published: December 2024

Supplementary Figures and Tables
Supplementary Tables 1-2 from Inhibition of JNK Signaling Overcomes Cancer-Associated Fibroblast-Mediated Immunosuppression and Enhances the Efficacy of Immunotherapy in Bladder Cancer
Authors: Cui Chengying , Zhang Haojie , Yang Congcong , Yin Mingwei , Teng Xinkun , Yang Miaomiao , Kong Dejie , Zhang Jinzhi , Peng Weidong , Chu Zhimin , Wang Jingjing , Sun Yating , Kang Liping , Lyu Bin , Gao Qian , Wu Mingqing , Wang Yongqiang , Li Yang
Published: December 2024

Supplementary Tables 1-2
Supplementary Table S7 from Large-Scale Comparative Analysis of Canine and Human Osteosarcomas Uncovers Conserved Clinically Relevant Tumor Microenvironment Subtypes
Authors: Patkar Sushant , Mannheimer Joshua , Harmon Stephanie A. , Ramirez Christina J. , Mazcko Christina N. , Choyke Peter L. , Brown Gregory Thomas , Turkbey Baris , LeBlanc Amy K. , Beck Jessica A.
Published: December 2024

Gene set enrichment analysis results of cancer Hallmark pathways enriched in the IE (Immune Enriched) TME subtype
Supplementary Table S3 from Large-Scale Comparative Analysis of Canine and Human Osteosarcomas Uncovers Conserved Clinically Relevant Tumor Microenvironment Subtypes
Authors: Patkar Sushant , Mannheimer Joshua , Harmon Stephanie A. , Ramirez Christina J. , Mazcko Christina N. , Choyke Peter L. , Brown Gregory Thomas , Turkbey Baris , LeBlanc Amy K. , Beck Jessica A.
Published: December 2024

QuPath (v0.5.0) Macrophage density (number of CD204 positive cells per mm2) outputs for each case that passed quality review.
Supplementary Table S10 from Large-Scale Comparative Analysis of Canine and Human Osteosarcomas Uncovers Conserved Clinically Relevant Tumor Microenvironment Subtypes
Authors: Patkar Sushant , Mannheimer Joshua , Harmon Stephanie A. , Ramirez Christina J. , Mazcko Christina N. , Choyke Peter L. , Brown Gregory Thomas , Turkbey Baris , LeBlanc Amy K. , Beck Jessica A.
Published: December 2024

Demographics and clinical outcome data of all canines from the DOG2 cohort that had bulk tumor transcriptomic profiles.
Supplementary Table S4 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Table S4. Clinicopathological findings in cases treated with Atezo+Bev therapy
Supplementary Figure S2 from Spatial Dynamics of T- and B-Cell Responses Predicts Clinical Outcome of Resectable and Unresectable Hepatocellular Carcinoma
Authors: Kurebayashi Yutaka , Sugimoto Katsutoshi , Tsujikawa Hanako , Matsuda Kosuke , Nomura Rui , Ueno Akihisa , Masugi Yohei , Yamazaki Ken , Effendi Kathryn , Takeuchi Hirohito , Itoi Takao , Hasegawa Yasushi , Abe Yuta , Kitago Minoru , Ojima Hidenori , Sakamoto Michiie
Published: December 2024

Figure S2. Example of histocytometric analysis
Supplementary Table 1 from Reverse Selection Designs for Accommodating Multiple Control Arms
Authors: Samorodnitsky Sarah , Othus Megan , LeBlanc Michael , Wu Michael C.
Published: December 2024

Supplementary Table 1. Comparing the reverse selection design (RSD) to a three-arm and a two-arm dealer’s choice design with a slow event rate.
Table S3 from Anlotinib plus TQB2450, a PD-L1 Antibody, in Patients with Advanced Alveolar Soft Part Sarcoma: A Single-Arm, Phase II Trial
Authors: Tan Zhichao , Wu Yan , Fan Zhengfu , Gao Tian , Guo Wei , Bai Chujie , Xue Ruifeng , Li Shu , Zhang Lu , Wang Xinyu , Jia Ling , Liu Jiayong
Published: December 2024

Immune cell percentage
Supplementary clean1 from Trastuzumab Deruxtecan with Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study
Authors: Hamilton Erika , Galsky Matthew D. , Ochsenreither Sebastian , Del Conte Gianluca , Martín Miguel , De Miguel Maria José , Yu Evan Y. , Williams Anja , Gion Maria , Tan Antoinette R. , Agrawal Laila , Rutten Annemie , Machiels Jean-Pascal , Cresta Sara , Debruyne Philip R. , Hennequin Audrey , Moreno Victor , Minchom Anna , Valdes-Albini Frances , Petrylak Daniel , Li Li , Tsuchihashi Zenta , Suto Fumitaka , Cheng Fu-Chih , Kandil Maha , Barrios Daniel , Hurvitz Sara
Published: December 2024

Supplementary tracked
Figure S1 from Anlotinib plus TQB2450, a PD-L1 Antibody, in Patients with Advanced Alveolar Soft Part Sarcoma: A Single-Arm, Phase II Trial
Authors: Tan Zhichao , Wu Yan , Fan Zhengfu , Gao Tian , Guo Wei , Bai Chujie , Xue Ruifeng , Li Shu , Zhang Lu , Wang Xinyu , Jia Ling , Liu Jiayong
Published: December 2024

Spider plot of responses
Supplementary Table S1 from Phase Ib Study of the Immunocytokine Simlukafusp Alfa (FAP-IL2v) in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Hansen Aaron R. , Gomez-Roca Carlos A. , Robbrecht Debbie G. J. , Verlingue Loic , Italiano Antoine , Bauman Julie E. , Steeghs Neeltje , Prenen Hans , Fayette Jérôme , Spicer James , Niu Jiaxin , Habigt Christin , Schneider Meike , Evers Stefan , Sleiman Nassim , Dejardin David , Ardeshir Caroline , Schmid Daniela , Boetsch Christophe , Charo Jehad , Kraxner Anton , Teichgräber Volker , Keshelava Nino , Bonomi Marcelo R.
Published: December 2024

Supplementary Table S1. Representativeness of study participants.
Supplementary Methods S1 from Phase Ib Study of the Immunocytokine Simlukafusp Alfa (FAP-IL2v) in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Hansen Aaron R. , Gomez-Roca Carlos A. , Robbrecht Debbie G. J. , Verlingue Loic , Italiano Antoine , Bauman Julie E. , Steeghs Neeltje , Prenen Hans , Fayette Jérôme , Spicer James , Niu Jiaxin , Habigt Christin , Schneider Meike , Evers Stefan , Sleiman Nassim , Dejardin David , Ardeshir Caroline , Schmid Daniela , Boetsch Christophe , Charo Jehad , Kraxner Anton , Teichgräber Volker , Keshelava Nino , Bonomi Marcelo R.
Published: December 2024

Supplementary Methods. Includes Eligibility criteria for the clinical study, Study Treatment, DLT Criteria, Tumor Response Assessment, and Pharmacodynamic Methods.
Supplementary Figure S3 from Phase Ib Study of the Immunocytokine Simlukafusp Alfa (FAP-IL2v) in Combination with Cetuximab in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Hansen Aaron R. , Gomez-Roca Carlos A. , Robbrecht Debbie G. J. , Verlingue Loic , Italiano Antoine , Bauman Julie E. , Steeghs Neeltje , Prenen Hans , Fayette Jérôme , Spicer James , Niu Jiaxin , Habigt Christin , Schneider Meike , Evers Stefan , Sleiman Nassim , Dejardin David , Ardeshir Caroline , Schmid Daniela , Boetsch Christophe , Charo Jehad , Kraxner Anton , Teichgräber Volker , Keshelava Nino , Bonomi Marcelo R.
Published: December 2024

Supplementary Figure S3. Pharmacodynamic changes and associated clinical outcomes.
Table 2 from First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies
Authors: Lakhani Nehal J. , Papadopoulos Kyriakos P. , Johnson Melissa Lynne , Park Haeseong , Wang Ding , Yap Timothy A. , Dowlati Afshin , Maki Robert G. , Ulahannan Susanna , Lynce Filipa , Kelly Karen , Williamson Stephen , Malhotra Jyoti , Chen Shuquan , Gonzalez Ortiz Ana , Jankovic Vladimir , Paccaly Anne , Masinde Sheila , Mani Jayakumar , Lowy Israel , Gullo Giuseppe , Sims Tasha , Kroog Glenn
Published: December 2024

Summary of TEAE regardless of attribution.
Supplementary Material 1 from First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies
Authors: Lakhani Nehal J. , Papadopoulos Kyriakos P. , Johnson Melissa Lynne , Park Haeseong , Wang Ding , Yap Timothy A. , Dowlati Afshin , Maki Robert G. , Ulahannan Susanna , Lynce Filipa , Kelly Karen , Williamson Stephen , Malhotra Jyoti , Chen Shuquan , Gonzalez Ortiz Ana , Jankovic Vladimir , Paccaly Anne , Masinde Sheila , Mani Jayakumar , Lowy Israel , Gullo Giuseppe , Sims Tasha , Kroog Glenn
Published: December 2024

Supplementary Material
Figure 2 from First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies
Authors: Lakhani Nehal J. , Papadopoulos Kyriakos P. , Johnson Melissa Lynne , Park Haeseong , Wang Ding , Yap Timothy A. , Dowlati Afshin , Maki Robert G. , Ulahannan Susanna , Lynce Filipa , Kelly Karen , Williamson Stephen , Malhotra Jyoti , Chen Shuquan , Gonzalez Ortiz Ana , Jankovic Vladimir , Paccaly Anne , Masinde Sheila , Mani Jayakumar , Lowy Israel , Gullo Giuseppe , Sims Tasha , Kroog Glenn
Published: December 2024

A, Clinical activitya and (B) changes to target lesion over time in patients treated with monotherapy to combination therapy. aBest overall response is calculated on the basis of tumor change from the start of combination treatment. bTumor response for this patient was calculated as the best change in tumor size from the start of combination therapy. Triangles denote the last tumor assessment on fianlimab monotherapy. Figure only includes patients who had both baseline and postbaseline target lesion assessments; not all patients had these assessments—therefore some patients may not be shown in this figure. Three patients (3/16, 18.8%) were not evaluated in this treatment group. DL, dose level; IV, intravenous; Q3W, every 3 weeks; SOD, sum of diameters.
Figure 1 from First-in-Human Dose-Escalation Study of Fianlimab, an Antilymphocyte Activation Gene-3 Antibody, with Cemiplimab in Patients with Advanced Malignancies
Authors: Lakhani Nehal J. , Papadopoulos Kyriakos P. , Johnson Melissa Lynne , Park Haeseong , Wang Ding , Yap Timothy A. , Dowlati Afshin , Maki Robert G. , Ulahannan Susanna , Lynce Filipa , Kelly Karen , Williamson Stephen , Malhotra Jyoti , Chen Shuquan , Gonzalez Ortiz Ana , Jankovic Vladimir , Paccaly Anne , Masinde Sheila , Mani Jayakumar , Lowy Israel , Gullo Giuseppe , Sims Tasha , Kroog Glenn
Published: December 2024

A, Clinical activity and (B) changes to target lesion over time in patients treated with fianlimab plus cemiplimab. Figure only includes patients who had both baseline and postbaseline target lesion assessments; not all patients had these assessments–therefore some patients may not be shown in this figure. Seven patients (7/47, 14.9%) were not evaluated in this treatment group. DL, dose level; IV, intravenous; Q3W, every 3 weeks; SOD, sum of diameters.
Supplementary Data 1 from Circulating Chromogranin A as a Surveillance Biomarker in Patients with Carcinoids—The CASPAR Study
Authors: Meng Qing H. , Halfdanarson Thorvardur R. , Bornhorst Joshua A. , Jann Henning , Shaheen Shagufta , Shi Run Zhang , Schwabe Andrej , Stade Katrin , Halperin Daniel M.
Published: December 2024

Supplementary data for CASPAR pilot study, tables and figures
Figure 3 from Circulating Chromogranin A as a Surveillance Biomarker in Patients with Carcinoids—The CASPAR Study
Authors: Meng Qing H. , Halfdanarson Thorvardur R. , Bornhorst Joshua A. , Jann Henning , Shaheen Shagufta , Shi Run Zhang , Schwabe Andrej , Stade Katrin , Halperin Daniel M.
Published: December 2024

Kaplan–Meier plots with proportion of progression-free patients with GEP-NET (%) during 24 months of follow-up in the intention-to-diagnose population, with stratification by primary tumor site (A; largest subgroups—pancreas and small intestine), presence of autonomous hormone secretion syndrome (B), tumor grade (C), treatment type (D), binary CgA at baseline (E), and binary ΔCgA at the first follow-up visit (F). The gray part in F indicates the period when 75% of the first follow-up visits after baseline occurred in the test-positive group (2–7 months, comparable time window in the test-negative group). Below each panel, the numbers of patients at risk are indicated for each timepoint and stratum. HR for comparison of the second (red) vs. the first stratum (blue), with 95% CI in brackets; P values are obtained from log-rank tests. D, HR for comparison with stratum “no agent and no procedure:” “only SSA” 0.66 (P = 0.37), “other agents or combinations” 1.19 (P = 0.70), and “procedure with or without SSA” 1.03 (P = 0.96). SSA, somatostatin analogues.
Supplementary Table S5 from Efficacy, Safety, and Influence on the Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1–Positive NSCLC: A Phase II Trial (EAST ENERGY)
Authors: Aokage Keiju , Koyama Shohei , Kumagai Shogo , Nomura Kotaro , Shimada Yoshihisa , Yoh Kiyotaka , Wakabayashi Masashi , Fukutani Miki , Furuya Hideki , Miyoshi Tomohiro , Tane Kenta , Samejima Joji , Taki Tetsuro , Hayashi Takuo , Matsubayashi Jun , Ishii Genichiro , Nishikawa Hiroyoshi , Ikeda Norihiko , Tsuboi Masahiro
Published: December 2024

Supplementary Table S5: Surgical methods and approaches in patients who underwent surgery.
Supplementary Table S2 from Efficacy, Safety, and Influence on the Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1–Positive NSCLC: A Phase II Trial (EAST ENERGY)
Authors: Aokage Keiju , Koyama Shohei , Kumagai Shogo , Nomura Kotaro , Shimada Yoshihisa , Yoh Kiyotaka , Wakabayashi Masashi , Fukutani Miki , Furuya Hideki , Miyoshi Tomohiro , Tane Kenta , Samejima Joji , Taki Tetsuro , Hayashi Takuo , Matsubayashi Jun , Ishii Genichiro , Nishikawa Hiroyoshi , Ikeda Norihiko , Tsuboi Masahiro
Published: December 2024

Supplementary Table S2: Representativeness of Study Participants.
Data from Large-Scale Comparative Analysis of Canine and Human Osteosarcomas Uncovers Conserved Clinically Relevant Tumor Microenvironment Subtypes
Authors: Patkar Sushant , Mannheimer Joshua , Harmon Stephanie A. , Ramirez Christina J. , Mazcko Christina N. , Choyke Peter L. , Brown Gregory Thomas , Turkbey Baris , LeBlanc Amy K. , Beck Jessica A.
Published: December 2024

AbstractPurpose:
Osteosarcoma is an aggressive bone cancer lacking robust biomarkers for personalized treatment. Despite its scarcity in humans, it is relatively common in adult pet dogs. This study aimed to analyze clinically annotated bulk tumor transcriptomic datasets of canine and patients with human osteosarcoma to identify potentially conserved patterns of disease progression.
Experimental Design:
Bulk transcriptomic data from 245 pet dogs with treatment-naïve appendicular osteosarcoma were analyzed using deconvolution to characterize the tumor microenvironment (TME). The TME of both primary and metastatic tumors derived from the same dog was compared, and its impact on canine survival was assessed. A machine learning model was developed to classify the TME based on its inferred composition using canine tumor data. This model was applied to eight independent human osteosarcoma datasets to assess its generalizability and prognostic value.
Results:
This study found three distinct TME subtypes of canine osteosarcoma based on cell type composition of bulk tumor samples: immune enriched, immune enriched dense extracellular matrix-like, and immune desert. These three TME-based subtypes of canine osteosarcomas were conserved in humans and could predict progression-free survival outcomes of human patients, independent of conventional prognostic factors such as percent tumor necrosis post standard of care chemotherapy treatment and disease stage at diagnosis.
Conclusions:
These findings demonstrate the potential of leveraging data from naturally occurring cancers in canines to model the complexity of the human osteosarcoma TME, offering a promising avenue for the discovery of novel biomarkers and developing more effective precision oncology treatments.