bluuebunny/crossref_metadata_2025 huggingface dataset:
From wolves to humans: oral microbiome resistance to transfer across mammalian hosts
Authors: Podar Nicholas A. , Carrell Alyssa A. , Cassidy Kira A. , Klingeman Dawn M. , Yang Zamin , Stahler Erin A. , Smith Douglas W. , Stahler Daniel R. , Podar Mircea
Published: February 2024

The mammalian mouth is colonized by complex microbial communities, adapted to specific niches, and in homeostasis with the host. Individual microbes interact metabolically and rely primarily on nutrients provided by the host, with which they have potentially co-evolved along the mammalian lineages. The oral environment is similar across mammals, but the diversity, specificity, and evolution of community structure in related or interacting mammals are little understood. Here, we compared the oral microbiomes of dogs with those of wild wolves and humans. In dogs, we found an increased microbial diversity relative to wolves, possibly related to the transition to omnivorous nutrition following domestication. This includes a larger diversity of Patescibacteria than previously reported in any other oral microbiota. The oral microbes are most distinct at bacterial species or strain levels, with few if any shared between humans and canids, while the close evolutionary relationship between wolves and dogs is reflected by numerous shared taxa. More taxa are shared at higher taxonomic levels including with humans, supporting their more ancestral common mammalian colonization followed by diversification. Phylogenies of selected oral bacterial lineages do not support stable human-dog microbial transfers but suggest diversification along mammalian lineages (apes and canids). Therefore, despite millennia of cohabitation and close interaction, the host and its native community controls and limits the assimilation of new microbes, even if closely related. Higher resolution metagenomic and microbial physiological studies, covering a larger mammalian diversity, should help understand how oral communities assemble, adapt, and interact with their hosts.

IMPORTANCE

Numerous types of microbes colonize the mouth after birth and play important roles in maintaining oral health. When the microbiota-host homeostasis is perturbed, proliferation of some bacteria leads to diseases such as caries and periodontitis. Unlike the gut microbiome, the diversity of oral microbes across the mammalian evolutionary space is not understood. Our study compared the oral microbiomes of wild wolves, dogs, and apes (humans, chimpanzees, and bonobos), with the aim of identifying if microbes have been potentially exchanged between humans and dogs as a result of domestication and cohabitation. We found little if any evidence for such exchanges. The significance of our research is in finding that the oral microbiota and/or the host limit the acquisition of exogenous microbes, which is important in the context of natural exclusion of potential novel pathogens. We provide a framework for expanded higher-resolution studies across domestic and wild animals to understand resistance/resilience.
Annotated whole-genome sequences of fermentative and spoilage associated Bacilli and proteobacteria autochthonous to commercial cucumber fermentation
Authors: Page Clinton A. , Simpson Sheron , Pérez-Díaz Ilenys M. , Rivers Adam R.
Published: February 2024

We report 36 whole-genome sequences, along with annotations, of fermentative (
n
= 12) and spoilage associated (
n
= 6) lactic acid bacteria,
Lysinibacillus
(
n
= 3),
Streptococcus
(
n
= 1), and Proteobacteria (
n
= 14) isolated from commercial cucumber fermentations. Fifty-three percent of the genome sequence assemblies consist of 1–4 contigs, and the remainder have fewer than 16.
Complete genome sequence of a novel papillomavirus in Siamese fighting fish (
Betta splendens
) from Trinidad and Tobago
Authors: Blake Lemar , Phillips Savage A. Carla , Soto Esteban , Oura Christopher , Brown-Jordan Arianne , Raines Clayton , Buck Christopher B. , Iwanowicz Luke R.
Published: February 2024

Here, we announce the complete genome of a previously undescribed papillomavirus from a betta fish,
Betta splendens
. The genome is 5,671 bp with a GC content of 38.2%. Variants were detected in public databases. This genome is most similar to papillomaviruses that infect sea bass (52.9 % nucleotide identity).
Complete reference genomes of two ceftriaxone-resistant
Neisseria gonorrhoeae
strains identified in routine surveillance in Bangkok, Thailand, using Nanopore Q20+ chemistry, VolTRAX V2b, and Illumina sequencing
Authors: Sangprasert Pongsathorn , Golparian Daniel , Paopang Porntip , Girdthep Natnaree , Lawung Ratana , Gopinath Deyer , Thammawijaya Panithee , Kittiyaowanarn Rossaphorn , Unemo Magnus
Published: February 2024

Ceftriaxone-resistant
Neisseria gonorrhoeae
strains, mostly associated with Asia, threaten gonorrhea treatment. We report the reference genomes of two ceftriaxone-resistant isolates found in routine surveillance in Bangkok, Thailand. The genomes belonged to the more antimicrobial-susceptible genomic lineage B, illustrating that both ceftriaxone-resistant strains and the mosaic
penA
-60.001 ceftriaxone-resistance determinant are spreading.
Resistance, mechanism, and fitness cost of specific bacteriophages for
Pseudomonas aeruginosa
Authors: Feng Luozhu , Chen Huanchang , Qian Changrui , Zhao Yining , Wang Weixiang , Liu Yan , Xu Mengxin , Cao Jianming , Zhou Tieli , Wu Qing
Published: February 2024

The bacteriophage is an effective adjunct to existing antibiotic therapy; however, in the course of bacteriophage therapy, host bacteria will develop resistance to bacteriophages, thus affecting the efficacy. Therefore, it is important to describe how bacteria evade bacteriophage attack and the consequences of the biological changes that accompany the development of bacteriophage resistance before the bacteriophage is applied. The specific bacteriophage vB3530 of
Pseudomonas aeruginosa
(
P. aeruginosa
) has stable biological characteristics, short incubation period, strong
in vitro
cleavage ability, and absence of virulence or resistance genes. Ten bacteriophage-resistant strains (TL3780-R) were induced using the secondary infection approach, and the plaque assay showed that vB3530 was less sensitive to TL3780-R. Identification of bacteriophage adsorption receptors showed that the bacterial surface polysaccharide was probably the adsorption receptor of vB3530. In contrast to the TL3780 parental strain, TL3780-R is characterized by the absence of long lipopolysaccharide chains, which may be caused by base insertion of
wzy
or deletion of
galU
. It is also intriguing to observe that, in comparison to the parent strain, the bacteriophage-resistant strains TL3780-R mostly exhibited a large cost of fitness (growth rate, biofilm formation, motility, and ability to produce enhanced pyocyanin). In addition, TL3780-R9 showed increased susceptibility to aminoglycosides and chlorhexidine, which may be connected to the loss and down-regulation of
mexX
expression. Consequently, these findings fully depicted the resistance mechanism of
P. aeruginosa
to vB3530 and the fitness cost of bacteriophage resistance, laying a foundation for further application of bacteriophage therapy.

IMPORTANCE

The bacteriophage is an effective adjunct to existing antibiotic therapy; However, bacteria also develop defensive mechanisms against bacteriophage attack. Thus, there is an urgent need to deeply understand the resistance mechanism of bacteria to bacteriophages and the fitness cost of bacteriophage resistance so as to lay the foundation for subsequent application of the phage. In this study, a specific bacteriophage vB3530 of
P. aeruginosa
had stable biological characteristics, short incubation period, strong
in vitro
cleavage ability, and absence of virulence or resistance genes. In addition, we found that
P. aeruginosa
may lead to phage resistance due to the deletion of
galU
and the base insertion of
wzy
, involved in the synthesis of lipopolysaccharides. Simultaneously, we showed the association with the biological state of the bacteria after bacteria acquire bacteriophage resistance, which is extremely relevant to guide the future application of therapeutic bacteriophages.
Genomic epidemiology and antifungal-resistant characterization of
Candida auris
, Colombia, 2016–2021
Authors: Misas Elizabeth , Escandón Patricia L. , Gade Lalitha , Caceres Diego H. , Hurst Steve , Le Ngoc , Min Brian , Lyman Meghan , Duarte Carolina , Chow Nancy A.
Published: February 2024

Since 2016, in Colombia, ongoing transmission of
Candida auris
has been reported in multiple cities. Here, we provide an updated description of
C. auris
genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from
C. auris
cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from
C. auris
cases were described in a phylogenetic analysis. All
C. auris
cases were clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogotá, Colombia, which grouped with isolates from Venezuela. The largest cluster (
N
= 166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from César; of these, 85% (
N
= 22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% (
N
= 38) were resistant to amphotericin B. Mutations in the
ERG11
and
TAC1B
genes were identified in fluconazole-resistant isolates. This work describes molecular mechanisms associated with
C. auris
antifungal resistance in Colombia. Overall,
C. auris
cases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades of
C. auris
into Colombia.

IMPORTANCE

Candida auris
is an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission of
C. auris
and provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this provide information about the evolving
C. auris
burden that could help guide public health strategies to control
C. auris
spread.
Cathodic voltage-controlled electrical stimulation and betadine decontaminate nosocomial pathogens from implant surfaces
Authors: Gupta Tripti Thapa , Zumpano Bernadette , Opalinski Jacob , Ritchey Riley , Winter Nathan , Nodzo Scott R. , Canty Mary
Published: February 2024

Periprosthetic joint infection (PJI) after total joint arthroplasty is a major concern requiring multiple surgeries and antibiotic interventions.
Staphylococcus aureus
,
Pseudomonas aeruginosa
, and
Escherichia coli
are the predominant causes of these infections. Due to biofilm formation, antibiotic treatment for patients with PJI can prolong resistance, further complicating the use of current treatments. Previous research has shown that cathodic voltage-controlled electrical stimulation (CVCES) is an effective technique to prevent/treat implant-associated biofilm infections on titanium (Ti) surfaces. This study thus evaluated the efficacy of CVCES via the use of 10% betadine alone and in combination with CVCES to eradicate lab-grown biofilms on cemented and cementless cobalt–chromium (CoCr) and Ti surfaces. CVCES treatment alone for 24 hours demonstrated no detectable CFU for
E. coli
and
P. aeruginosa
biofilms on cementless CoCr implants. In the presence of cement,
E. coli
biofilms had 10
6
CFUs/implant remaining after CVCES treatment alone; however,
P. aeruginosa
biofilms on cemented implants were reduced to below detectable limits. The use of 10% betadine treatment for 3 minutes followed by 24-hour CVCES treatment brought CFU levels to below detectable limits in
E. coli
and
P. aeruginosa
. The same was true for
S. aureus
biofilms on cementless patellofemoral implants as well as femoral and tibial implants. These treatment methods were not sufficient for eradication of
S. aureus
biofilms on cemented implants. These results suggest that CVCES alone and CVCES with 10% betadine are effective approaches to treating biofilms formed by certain bacterial species potentially leading to the treatment of PJI.

IMPORTANCE

Periprosthetic joint infections (PJIs) are problematic due to requiring multiple surgeries and antibiotic therapies that are responsible for increased patient morbidity and healthcare costs. These infections become resistant to antibiotic treatment due to the formation of biofilms on the orthopedic surfaces. Cathodic voltage-controlled electrical stimulation (CVCES) has previously been shown to be an effective technique to prevent and treat biofilm infections on different surfaces. This study shows that CVCES can increase the efficacy of 10% betadine irrigation used in debridement, antibiotics, and implant retention by 99.9% and clear infection to below detection limits. PJI treatments are at times limited, and CVCES could be a promising technology to improve patient outcomes.
Pericardiocentesis versus window formation in malignant pericardial effusion: trends and outcomes
Authors: Lee Jaeoh , Kim Kyu , Gwak Seo-Yeon , Lee Hyun-Jung , Cho Iksung , Hong Geu-Ru , Ha Jong-Won , Shim Chi Young
Published: February 2024

Objectives

Malignant pericardial effusion (MPE) in patients with cancer is associated with poor prognosis. This study aimed to compare clinical outcomes in patients with cancer who underwent pericardiocentesis versus pericardial window formation.

Methods

In the present study, 765 consecutive patients with cancer (mean age 58.4 years, 395 men) who underwent pericardial drainage between 2003 and 2022 were retrospectively analysed. All-cause death and MPE recurrence were compared based on the drainage method (pericardiocentesis vs pericardial window formation) and time period (period 1: 2003–2012; period 2: 2013–2022).

Results

Pericardiocentesis was performed in 639 (83.5%) patients and pericardial window formation in 126 (16.5%). There was no difference in age, sex distribution, proportion of metastatic or relapsed cancer, and chemotherapy status between the pericardiocentesis and pericardial window formation groups. Difference was not found in all-cause death between the two groups (log-rank p=0.226) regardless of the period. The pericardial window formation group was associated with lower MPE recurrence than the pericardiocentesis group (6.3% vs 18.0%, log-rank p=0.001). This advantage of pericardial window formation was more significant in period 2 (18.1%vs1.3%, log-rank p=0.005). In multivariate analysis, pericardial window formation was associated with lower MPE recurrence (HR: 0.31, 95% CI: 0.15 to 0.63, p=0.001); younger age, metastatic or relapsed cancer, and positive malignant cells in pericardial fluid were associated with increased recurrence.

Conclusion

In patients undergoing pericardial drainage for MPE, pericardial window formation showed mortality outcomes comparable with pericardiocentesis and was associated with lower incidence of MPE recurrence.
Improved methods to estimate days and temperature to fifty percent mortality of winter wheat (Triticum aestivum L.) under low-temperature flooding and ice encasement
Authors: Husiny Jaber , Ficht Alexandra , Whiting Rachel , Booker Helen , Hooker David C. , McElroy Michel , Lyons Eric
Published: February 2024

Low-temperature flooding and ice encasement (LTFIE) cause variable survival of winter wheat ( Triticum aestivum L.) in Ontario, which limits the adoption of wheat into crop rotations by growers. The development of novel cultivars capable of withstanding LTFIE is a promising avenue for improvement, but the methods used to assess the survival of winter wheat under LTFIE are restricted. This study developed updated methods to determine the survival of wheat cultivars under LTFIE using controlled environments and, to our knowledge, is the first method since the 1980s to use Canadian eastern soft red winter wheat (CESRW) to conduct cold tolerance studies. Chamber-acclimated plants of AC Carberry (spring wheat control), Branson (CESRW), CM614 (CESRW), and Norstar (hardy Canadian western red winter control) cultivars were used to estimate the days (LD50) and temperature (LT50) to reach 50% mortality under ice and without ice treatments. Norstar had the longest LD50 at 33 days, Branson and CM614 had similar LD50 of 18 and 20 days, and AC Carberry did not reach an LD50 as it died early in both treatments. The LT50 of each cultivar was different; Norstar had the lowest LT50 (−13.6 °C day 0 and −13.2 °C day 7), and AC Carberry had the highest LT50 (−6.6 °C day 0 and −2.7 °C day 7). The detailed methods developed in this study were more reliable compared to older methods based on the more accurate reported LD50 and LT50 of the cultivars, therefore, these methods can be used to screen winter cereals for LTFIE in the future.
Antisymmetric tensor field and Cheshire Cat smile of the local conformal symmetry
Authors: Shapiro Ilya L.
Published: February 2024

The conformal version of the antisymmetric second-order tensor field in four spacetime dimensions does not have gauge invariance extensively discussed in the literature for more than half a century. Our first observation is that, when coupled to fermions, only the conformal version provides renormalizability of the theory at the one-loop level. General considerations are supported by the derivation of one-loop divergences in the fermionic sector, indicating good chances for asymptotic freedom. The arguments concerning one-loop renormalizability remain valid in the presence of self-interactions and the masses for both fermion and antisymmetric tensor fields. In the flat spacetime limit, even regardless the conformal symmetry has gone, there is an expectation to meet renormalizability in all loop orders.
Efficacy of Minimally Invasive Ulnar Superficialis Slip Resection for Unfavourable Results after Trigger Finger Release
Authors: USAMI Satoshi , KAWAHARA Sanshiro , INAMI Kohei , SONOKI Kentaro , TAKEMITSU Masashi
Published: February 2024

Background: This study aimed to evaluate the efficacy of ulnar superficial slip resection (USSR) for improving hand function after unfavourable results after triggering finger release using a minimally invasive approach.

Methods: We evaluated 17 consecutive fingers of 16 patients who complained of unfavourable outcomes after primary trigger finger release. The chief complaints of the two index and 15 middle fingers were proximal interphalangeal (PIP) joint pain during movement, flexion contracture of the PIP joint and snapping at the A2 pulley in eight, seven and two fingers, respectively. The joint arc of the active range of motion and extension loss of the PIP joint, grip strength, visual analogue score (VAS) of PIP joint pain and Quick Disability of the Arm, Shoulder and Hand were evaluated before and after surgery.

Results: Thirteen fingers could release joint contracture and snapping by the USSR procedure. However, four fingers of three patients required total flexor digitorum superficialis resection to resolve the unsatisfactory conditions of the intraoperative decision. The joint arc of active range of motion and extension loss of the PIP joint, grip strength and VAS score significantly improved (mean of 16.1 months follow-up). Finally, 15 patients (88.2%) were satisfied with the symptom relief outcomes.

Conclusions: USSR is an effective and satisfactory procedure for unfavourable conditions after trigger finger release, including PIP joint pain, joint contracture and snapping at the A2 pulley.

Level of Evidence: Level IV (Therapeutic)
Inferring Phylogenetic Networks Using Algebraic Geometry
Authors: Gross Elizabeth , Rhodes John
Published: February 2024

Reconstructing the network of life from molecular data is a complicated task. How can computational algebraic geometry play a role?
Guidelines for the Regularization of Gammas in Batch Normalization for Deep Residual Networks
Authors: Kim Bum Jun , Choi Hyeyeon , Jang Hyeonah , Kim Sang Woo
Published: February 2024

L
2
regularization for weights in neural networks is widely used as a standard training trick. In addition to weights, the use of batch normalization involves an additional trainable parameter γ, which acts as a scaling factor. However,
L
2
regularization for γ remains an undiscussed mystery and is applied in different ways depending on the library and practitioner. In this article, we study whether
L
2
regularization for γ is valid. To explore this issue, we consider two approaches: (1) variance control to make the residual network behave like an identity mapping and (2) stable optimization through the improvement of effective learning rate. Through two analyses, we specify the desirable and undesirable γ to apply
L
2
regularization and propose four guidelines for managing them. In several experiments, we observed that applying
L
2
regularization to applicable γ increased 1% to 4% classification accuracy, whereas applying
L
2
regularization to inapplicable γ decreased 1% to 3% classification accuracy, which is consistent with our four guidelines. Our proposed guidelines were further validated through various tasks and architectures, including variants of residual networks and transformers.
Research on the Aerodynamic Noise Characteristics of Heat Exchanger Tube Bundles Based on a Hybrid URANS‐FWH Method
Authors: Huang Guofeng , Wang Heng , Tian Sheng , Tan Wei
Published: February 2024

This paper examines the aerodynamic noise characteristics of heat exchanger tube bundles, with the objective of exploring the frequency and directional features of noise under nonacoustic resonance conditions, to provide assistance in determining acoustic resonance. To predict the flow‐induced noise of tube bundles, this study employs a hybrid URANS‐FWH method. The transition SST model of URANS is used to accurately simulate the turbulent flow field and obtain precise statistical data on turbulence. The FWH equation is utilized to predict and evaluate the intensity and spectral characteristics of the tube bundle noise. The research findings indicate that the noise generated by the heat exchanger tube bundle is affected by pressure pulsations resulting from vortex motion in the deeper regions of the tube bundles. Notably, within specific frequency ranges, the noise intensity experiences a significant enhancement, potentially triggering complex modes of acoustic resonance. This resonance phenomenon poses safety concerns for equipment and threatens the wellbeing of personnel. Consequently, this study provides a solid theoretical foundation for predicting and controlling noise in heat exchanger tube bundles, offering valuable guidance for practical applications.
Fatal Coronary Artery Anomaly Concealed in Young Athletes with Exertional Syncope
Authors: Ifuku Toshinobu , Nakatani Keigo , Ueno Kentaro , Yamashita Naoto , Imoto Yutaka
Published: February 2024

Background. Syncope is a common symptom in children, many of which are benign and do not require treatment. Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital malformation but can be a risk for serious cardiovascular events, including sudden death as well as cardiogenic syncope. Case Report. We describe the case of a 14‐year‐old boy who suffered an initial syncope and afebrile seizure during a soccer game. A detailed medical history and imaging studies led to the diagnosis of the anomalous aortic origin of the left main coronary artery with an intramural course (AAOLCA‐IM). Conclusion. Symptomatic AAOLCA‐IM has the highest risk of sudden death among AAOCA, and surgical repair may be performed. Onset during exercise or preceding chest symptoms are suspicious signs of cardiogenic syncope and should be considered for cardiovascular imaging evaluation.
Reliability Analysis of Compressive Fatigue Life of Cement Concrete under Temperature Differential Cycling
Authors: Tao Chengyun , Dong Lin , Yu Tianlai , Chen Qian
Published: February 2024

Cement concrete, as an extensively used engineering material, is omnipresent in various infrastructure projects such as bridges and roads. However, these structures often need to operate for extended periods under varying and harsh environmental conditions, facing not only complex vehicular loads but also the effects of temperature differential cycling. Consequently, understanding how temperature differential cycling impacts the compressive fatigue life of cement concrete has become a pivotal research topic. In this study, through a comprehensive experimental design, the fatigue life of cement concrete under typical temperature difference conditions (20–60°C) and different number of temperature differential cycling (60, 120, 180, 240, 300) was tested at three stress levels (0.70, 0.75, 0.85). Statistical analysis was conducted to obtain the Weibull distribution parameters of the compressive fatigue life of cement concrete. The Pf–S–N relationship of concrete considering reliability was analyzed, and a fatigue life prediction model under different reliability probabilities was established. The results show that the fatigue life of concrete subjected to temperature differential cycling follows a two‐parameter Weibull distribution well. From the Pf–N curve, it can be seen that, regardless of the stress level, the calculated fatigue life under the same reliability probability decreases with the increase of temperature differential cycling times. At a 95% reliability probability, the decrease can reach 77.5%–87.5%. Based on the exponential function, a concrete fatigue life prediction model based on different reliability levels was established. Using this model, the S–lgN curve was plotted, and it was found that, regardless of the temperature differential cycling, an increase in reliability probability could lead to a 7.3%–14.4% reduction in logarithmic fatigue life (lgN). Additionally, this study also defined a fatigue life safety factor related to the number of temperature differential cycling and reliability probability, aiming to provide a theoretical basis for the design of cement concrete materials under the coupled environment of temperature differential cycling and fatigue loading.
Supplementary Table S1 from Osimertinib Covalently Binds to CD34 and Eliminates Myeloid Leukemia Stem/Progenitor Cells
Authors: Xia Li , Liu Jie-Yang , Yang Meng-Ying , Zhang Xue-Hong , Jiang Yue , Yin Qian-Qian , Luo Chen-Hui , Liu Hong-Chen , Kang Zhi-Jie , Zhang Cheng-Tao , Gao Bei-Bei , Zhou Ai-Wu , Cai Hai-Yan , Waller Edmund K. , Yan Jin-Song , Lu Ying
Published: February 2024

Comparative analysis of tyrosine-phosphorylated peptides identified in vehicle or osimertinib treated CD34+ cells purified from three AML patients by LC-MS.
Figure S5 from PTEN Lipid Phosphatase Activity Suppresses Melanoma Formation by Opposing an AKT/mTOR/FRA1 Signaling Axis
Authors: Xu Xiaonan , Bok Ilah , Jasani Neel , Wang Kaizhen , Chadourne Manon , Mecozzi Nicol , Deng Ou , Welsh Eric A. , Kinose Fumi , Rix Uwe , Karreth Florian A.
Published: February 2024

Figure S5
Data from RNA Methyltransferase FTSJ3 Regulates the Type I Interferon Pathway to Promote Hepatocellular Carcinoma Immune Evasion
Authors: Zhuang Qiuyu , Dai Zhiguo , Xu Xuechun , Bai Shaoyi , Zhang Yindan , Zheng Youshi , Xing Xiaohua , Hu En , Wang Yingchao , Guo Wuhua , Zhao Bixing , Zeng Yongyi , Liu Xiaolong
Published: February 2024

Abstract
Immunotherapies such as immune checkpoint blockade have achieved remarkable success in treating cancer. Unfortunately, response rates have been limited in multiple cancers including hepatocellular carcinoma (HCC). The critical function of epigenetics in tumor immune evasion and antitumor immunity supports harnessing epigenetic regulators as a potential strategy to enhance the efficacy of immunotherapy. Here, we discovered a tumor-promoting function of FTSJ3, an RNA 2′-O-methyltransferase, in HCC by suppressing antitumor immune responses. FTSJ3 was upregulated in hepatocellular carcinoma, and high FTSJ3 expression correlated with reduced patient survival. Deletion of FTSJ3 blocked HCC growth and induced robust antitumor immune responses. Mechanistically, FTSJ3 suppressed double-stranded RNA (dsRNA)–induced IFNβ signaling in a 2′-O-methyltransferase manner. Deletion of RNA sensors in HCC cells or systemic knockout of type I IFN receptor IFNAR in mice rescued the in vivo tumor growth defect caused by FTSJ3 deficiency, indicating that FTSJ3 deletion suppresses tumor growth by activating the RNA sensor–mediated type I IFN pathway. Furthermore, FTSJ3 deletion significantly enhanced the efficacy of programmed cell death protein 1 (PD-1) immune checkpoint blockade. The combination of FTSJ3 deficiency and anti–PD-1 antibody treatment effectively eradicated tumors and increased the survival time. In conclusion, this study reveals an epigenetic mechanism of tumor immune evasion and, importantly, suggests FTSJ3-targeting therapies as potential approach to overcome immunotherapy resistance in patients with HCC.
Significance:
Hepatocellular carcinoma cells use 2′-O-methylation catalyzed by FTSJ3 for immune evasion by suppressing abnormal dsRNA-mediated type I IFN responses, providing a potential target to activate antitumor immunity and enhance immunotherapy efficacy.
Figure S3 from Clinical and Immunologic Features of Germline Pathogenic Variant–Positive Patients with Melanoma
Authors: Shen Alan , Arbesman Michelle , Lodha Roshan , Rayman Patricia , Bungo Brandon , Ni Ying , Chan Timothy , Gastman Brian , Ko Jennifer , Diaz-Montero C. Marcela , Arbesman Joshua , Funchain Pauline
Published: February 2024

MSS and PMN-MDSC differences by known and putative melanoma variants.
Supplemental Table S5 from Aneuploidy Landscape in Precursors of Ovarian Cancer
Authors: Wang Yeh , Douville Christopher , Chien Yen-Wei , Wang Brant G. , Chen Chi-Long , Pinto Andre , Smith Saron Ann , Drapkin Ronny , Chui M. Herman , Numan Tricia , Vang Russell , Papadopoulos Nickolas , Wang Tian-Li , Shih Ie-Ming
Published: February 2024

Table cluster determining correlation between STIC growth patterns and molecular classifications.
Table S1 from PD-1 Blockade Induces Reactivation of Nonproductive T-Cell Responses Characterized by NF-κB Signaling in Patients with Pancreatic Cancer
Authors: Ali Lestat R. , Lenehan Patrick J. , Cardot-Ruffino Victoire , Dias Costa Andressa , Katz Matthew H.G. , Bauer Todd W. , Nowak Jonathan A. , Wolpin Brian M. , Abrams Thomas A. , Patel Anuj , Clancy Thomas E. , Wang Jiping , Mancias Joseph D. , Reilley Matthew J. , Stucky Chee-Chee H. , Bekaii-Saab Tanios S. , Elias Rawad , Merchant Nipun , Slingluff Craig L. , Rahma Osama E. , Dougan Stephanie K.
Published: February 2024

processed sequencing data
TCR raw data 2 from PD-1 Blockade Induces Reactivation of Nonproductive T-Cell Responses Characterized by NF-κB Signaling in Patients with Pancreatic Cancer
Authors: Ali Lestat R. , Lenehan Patrick J. , Cardot-Ruffino Victoire , Dias Costa Andressa , Katz Matthew H.G. , Bauer Todd W. , Nowak Jonathan A. , Wolpin Brian M. , Abrams Thomas A. , Patel Anuj , Clancy Thomas E. , Wang Jiping , Mancias Joseph D. , Reilley Matthew J. , Stucky Chee-Chee H. , Bekaii-Saab Tanios S. , Elias Rawad , Merchant Nipun , Slingluff Craig L. , Rahma Osama E. , Dougan Stephanie K.
Published: February 2024

TCR contigs
Supplementary Table S7 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Reasons for Treatment Discontinuation by Concomitant Chemotherapy
Supplementary Table S3 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Dose-escalation levels part 1
Supplementary Figure S3 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Plasma Elraglusib Concentrations 3.3 mg/kg Elraglusib plus Doxorubicin Regimen
Supplementary Figure S18 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Cytokine Responses in Patients Treated with Elraglusib Monotherapy
Supplementary Figure S15 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Days on Study by Cancer Histology in Part 1
Supplementary Figure S13 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Median PFS and OS by Combination Treatment Backbone in Part 2
Supplementary Figure S12 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Overall Survival by Elraglusib Dose Level in Part 1
Supplementary Figure S11 from Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies
Authors: Carneiro Benedito A. , Cavalcante Ludimila , Mahalingam Devalingam , Saeed Anwaar , Safran Howard , Ma Wen Wee , Coveler Andrew L. , Powell Steven , Bastos Bruno , Davis Elizabeth , Sahai Vaibhav , Mikrut William , Longstreth James , Smith Sheri , Weisskittel Taylor , Li Hu , Borden Brittany A. , Harvey R. Donald , Sahebjam Solmaz , Cervantes Andrés , Koukol Austin , Mazar Andrew P. , Steeghs Neeltje , Kurzrock Razelle , Giles Francis J. , Munster Pamela
Published: February 2024

Days on Study by Elraglusib Dose Level in Part 1
Supplementary Figure 4 from Neoadjuvant Selicrelumab, an Agonist CD40 Antibody, Induces Changes in the Tumor Microenvironment in Patients with Resectable Pancreatic Cancer
Authors: Byrne Katelyn T. , Betts Courtney B. , Mick Rosemarie , Sivagnanam Shamilene , Bajor David L. , Laheru Daniel A. , Chiorean E. Gabriela , O'Hara Mark H. , Liudahl Shannon M. , Newcomb Craig , Alanio Cécile , Ferreira Ana P. , Park Byung S. , Ohtani Takuya , Huffman Austin P. , Väyrynen Sara A. , Dias Costa Andressa , Kaiser Judith C. , Lacroix Andreanne M. , Redlinger Colleen , Stern Martin , Nowak Jonathan A. , Wherry E. John , Cheever Martin A. , Wolpin Brian M. , Furth Emma E. , Jaffee Elizabeth M. , Coussens Lisa M. , Vonderheide Robert H.
Published: February 2024

Figure S4 shows the raw multiplex serum cytokine analysis data from Figure 4, and the antibody list and the gating strategy for the CyTOF analysis, all performed on the peripheral blood samples.
Data from Clinical and Immunologic Features of Germline Pathogenic Variant–Positive Patients with Melanoma
Authors: Shen Alan , Arbesman Michelle , Lodha Roshan , Rayman Patricia , Bungo Brandon , Ni Ying , Chan Timothy , Gastman Brian , Ko Jennifer , Diaz-Montero C. Marcela , Arbesman Joshua , Funchain Pauline
Published: February 2024

AbstractPurpose:
Malignant melanoma represents the most lethal skin cancer with germline predispositions thought to comprise 10% to 15% of all melanoma cases. No studies to date examine the immunologic features that may differentiate survival differences between germline pathogenic variant (gPV)–positive patients with melanoma from gPV-negative patients with melanoma.
Experimental Design:
Adult patients with melanoma and clinical characteristics suggesting hereditary predisposition to cancer were prospectively recruited to undergo germline testing and flow cytometric analysis of peripheral immune suppressor cells.
Results:
In this cohort, gPV-positive patients (n = 72) had a significantly improved melanoma-specific survival (MSS) compared with gPV-negative patients (n = 411; HRadj, 0.32; 95% CI, 0.13–0.82; P = 0.01). These survival improvements among gPV-positive patients were most apparent among cutaneous melanoma subtypes (HRadj, 0.12; 95% CI, 0.016–0.86; P = 0.03) and numerically improved in later-stage (IIB–IV) patients (HRadj, 0.34; 95% CI, 0.10–1.11; P = 0.06). Further, gPV-positive patients had a significantly lower level of total circulating PMN-MDSC compared with gPV-negative patients (P = 0.01), which was most apparent in those diagnosed with later stages (IIB–IV) of melanoma (P = 0.009). Finally, a significant upregulation of inflammatory transcriptome signatures in later-stage gPV-positive patients (n = 21) was observed in comparison with gPV-negative patients (n = 173) in the cutaneous melanoma cohort (SKCM) of The Cancer Genome Atlas (TCGA).
Conclusions:
gPV-positive patients with melanoma exhibit improved MSS in addition to reduced peripheral PMN-MDSC and an enhanced inflammatory microenvironment.
Supplementary Table S10-1 from Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models
Authors: Friese-Hamim Manja , Ortiz Ruiz Maria J. , Bogatyrova Olga , Keil Marina , Rohdich Felix , Blume Beatrix , Leuthner Birgitta , Czauderna Frank , Hahn Diane , Jabs Julia , Jaehrling Frank , Heinrich Timo , Kellner Roland , Chan Katherine , Tong Amy H.Y. , Wienke Dirk , Moffat Jason , Blaukat Andree , Zenke Frank T.
Published: February 2024

Summary of area under the curve values for in vivo RCC PDX study
Supplementary Figure S6-2 from Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models
Authors: Friese-Hamim Manja , Ortiz Ruiz Maria J. , Bogatyrova Olga , Keil Marina , Rohdich Felix , Blume Beatrix , Leuthner Birgitta , Czauderna Frank , Hahn Diane , Jabs Julia , Jaehrling Frank , Heinrich Timo , Kellner Roland , Chan Katherine , Tong Amy H.Y. , Wienke Dirk , Moffat Jason , Blaukat Andree , Zenke Frank T.
Published: February 2024

EF1a-1 knockdown (96 hours) in A549 or HCT116 cancer cells, which were treated for 24 hours with DMSO or 1E−07 M of M8891 and analyzed for the presence of MetEF1a-1 by Simple Western using the generated rabbit monoclonal antibody MKV-3-165-11.
Supplementary Figure S5-4 from Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models
Authors: Friese-Hamim Manja , Ortiz Ruiz Maria J. , Bogatyrova Olga , Keil Marina , Rohdich Felix , Blume Beatrix , Leuthner Birgitta , Czauderna Frank , Hahn Diane , Jabs Julia , Jaehrling Frank , Heinrich Timo , Kellner Roland , Chan Katherine , Tong Amy H.Y. , Wienke Dirk , Moffat Jason , Blaukat Andree , Zenke Frank T.
Published: February 2024

Immuno-analytical verification of EF1a-1 as MetAP2 substrate: bEND3 cells were treated by DMSO (control) and 1E−07 M TNP-470.
Supplementary Figure S5-2 from Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models
Authors: Friese-Hamim Manja , Ortiz Ruiz Maria J. , Bogatyrova Olga , Keil Marina , Rohdich Felix , Blume Beatrix , Leuthner Birgitta , Czauderna Frank , Hahn Diane , Jabs Julia , Jaehrling Frank , Heinrich Timo , Kellner Roland , Chan Katherine , Tong Amy H.Y. , Wienke Dirk , Moffat Jason , Blaukat Andree , Zenke Frank T.
Published: February 2024

Protein identification: stained bands (upper and lower) were excised, trypsin in-gel digested, and analyzed by peptide mapping using MALDI MS
Supplementary Figure S11-2 from Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models
Authors: Friese-Hamim Manja , Ortiz Ruiz Maria J. , Bogatyrova Olga , Keil Marina , Rohdich Felix , Blume Beatrix , Leuthner Birgitta , Czauderna Frank , Hahn Diane , Jabs Julia , Jaehrling Frank , Heinrich Timo , Kellner Roland , Chan Katherine , Tong Amy H.Y. , Wienke Dirk , Moffat Jason , Blaukat Andree , Zenke Frank T.
Published: February 2024

Body weight curves of RCC PDX model RXF-SMTCA75-bearing mice treated with vehicle, M8891 (100 mg/kg, daily, per os), sunitinib (40 mg/kg, daily, per os), or the combination are shown
Supplementary Figure S1-2 from Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models
Authors: Friese-Hamim Manja , Ortiz Ruiz Maria J. , Bogatyrova Olga , Keil Marina , Rohdich Felix , Blume Beatrix , Leuthner Birgitta , Czauderna Frank , Hahn Diane , Jabs Julia , Jaehrling Frank , Heinrich Timo , Kellner Roland , Chan Katherine , Tong Amy H.Y. , Wienke Dirk , Moffat Jason , Blaukat Andree , Zenke Frank T.
Published: February 2024

Increasing concentrations of M8891 (3E−10M to 1E−05M) were tested in a murine MetAP2 enzyme assay
Figure S2 from CD38 x ICAM-1 Bispecific Antibody Is a Novel Approach for Treating Multiple Myeloma and Lymphoma
Authors: Chen Xiaocheng , Wong Oi Kwan , Reiman Lauren , Sherbenou Daniel W. , Post Leonard
Published: February 2024

Fc-gamma receptor binding
Supplementary Table 3 from An Antibody–Drug Conjugate Directed to Tissue Factor Shows Preclinical Antitumor Activity in Head and Neck Cancer as a Single Agent and in Combination with Chemoradiotherapy
Authors: Bakema Jantine E. , Stigter-van Walsum Marijke , Harris Jeffrey R. , Ganzevles Sonja H. , Muthuswamy Anantharaman , Houtkamp Mischa , Plantinga Theo S. , Bloemena Elisabeth , Brakenhoff Ruud H. , Breij Esther C.W. , van de Ven Rieneke
Published: February 2024

Median survival combined treatment TV and radiotherapy
Supplementary Fig. S5 from Amelioration of Tumor-promoting Microenvironment via Vascular Remodeling and CAF Suppression Using E7130: Biomarker Analysis by Multimodal Imaging Modalities
Authors: Ito Ken , Yamaguchi Masayuki , Semba Taro , Tabata Kimiyo , Tamura Moe , Aoyama Muneo , Abe Takanori , Asano Osamu , Terada Yasuhiko , Funahashi Yasuhiro , Fujii Hirofumi
Published: February 2024

Analysis of vasculature markers in the FaDu xenograft models
Supplementary Figure S3 from An Antibody–Drug Conjugate Directed to Tissue Factor Shows Preclinical Antitumor Activity in Head and Neck Cancer as a Single Agent and in Combination with Chemoradiotherapy
Authors: Bakema Jantine E. , Stigter-van Walsum Marijke , Harris Jeffrey R. , Ganzevles Sonja H. , Muthuswamy Anantharaman , Houtkamp Mischa , Plantinga Theo S. , Bloemena Elisabeth , Brakenhoff Ruud H. , Breij Esther C.W. , van de Ven Rieneke
Published: February 2024

Improved efficacy of chemotherapy when combined with tisotumab vedotin
Supplementary Fig. S2 from Amelioration of Tumor-promoting Microenvironment via Vascular Remodeling and CAF Suppression Using E7130: Biomarker Analysis by Multimodal Imaging Modalities
Authors: Ito Ken , Yamaguchi Masayuki , Semba Taro , Tabata Kimiyo , Tamura Moe , Aoyama Muneo , Abe Takanori , Asano Osamu , Terada Yasuhiko , Funahashi Yasuhiro , Fujii Hirofumi
Published: February 2024

E7130 reduced Tenascin-C (TN-C) expression levels in the FaDu and OSC-19 squamous cell carcinoma of the head and neck xenografted tumors
Supplemental Table S2 from Amelioration of Tumor-promoting Microenvironment via Vascular Remodeling and CAF Suppression Using E7130: Biomarker Analysis by Multimodal Imaging Modalities
Authors: Ito Ken , Yamaguchi Masayuki , Semba Taro , Tabata Kimiyo , Tamura Moe , Aoyama Muneo , Abe Takanori , Asano Osamu , Terada Yasuhiko , Funahashi Yasuhiro , Fujii Hirofumi
Published: February 2024

Panel of antibodies used for the mass cytometry assay
Table S4 from SKP2 Knockout in Rb1/p53–Deficient Mouse Models of Osteosarcoma Induces Immune Infiltration and Drives a Transcriptional Program with a Favorable Prognosis
Authors: Ferrena Alexander , Wang Jichuan , Zhang Ranxin , Karadal-Ferrena Burcu , Al-Hardan Waleed , Singh Swapnil , Borjihan Hasibagan , Schwartz Edward L. , Zhao Hongling , Oktay Maja H. , Yang Rui , Geller David S. , Hoang Bang H. , Zheng Deyou
Published: February 2024

Multivariable model results from four Cox models, where each variable was loaded with Metastasis at diagnosis as a covariable
Figure S1 from SKP2 Knockout in Rb1/p53–Deficient Mouse Models of Osteosarcoma Induces Immune Infiltration and Drives a Transcriptional Program with a Favorable Prognosis
Authors: Ferrena Alexander , Wang Jichuan , Zhang Ranxin , Karadal-Ferrena Burcu , Al-Hardan Waleed , Singh Swapnil , Borjihan Hasibagan , Schwartz Edward L. , Zhao Hongling , Oktay Maja H. , Yang Rui , Geller David S. , Hoang Bang H. , Zheng Deyou
Published: February 2024

Transcription factor and oncogene signature overrepresentation analysis in TKO vs DKO