bluuebunny/crossref_metadata_2025 huggingface dataset:
A Case Study of Furunculosis following an Ayurvedic Oil Massage, Sudation Therapy, and Lessons to Learn
Authors: Kulkarni Satyajit Pandurang , Kulkarni Pallavi Satyajit , Kumar S.
Published: February 2024

India has a long history of using sudation therapy and oil massage as Ayurvedic treatments. However, nothing is known about its side effects, and just two studies have identified side effects as cutaneous adverse drug reactions brought on by Ayurvedic oil massage. We are presenting the example of a 72-year-old adult man who visited our hospital and had his right knee massaged with Nirgudi oil followed by sudation therapy. Erythema, papules, itchiness, and scorching pain were some of his symptoms. However, these sensations only partially abated once we quit sudation therapy. Our investigation demonstrates that a Nirgudi oil massage or sudation causes the skin reaction associated with furunculosis. This case report illustrates the necessity of being aware of Panchakarma-related consequences and suggests that medical practitioners, patients, and product makers take into account the likelihood of such a reaction following Nirgudi oil massage and sudation therapy as a precaution.
First Report of a Novel Goose Adenovirus Outbreak in Lion Head Gooses in China
Authors: Liu Rongchang , Sun Minhua , Lan Qin , Zhang Jiaxue , Liang Qizhang , Fu Guanghua , Liao Ming , Huang Yu
Published: February 2024

In April 2022, a novel Goose adenovirus (GoAdV) isolated from diseased Lion head gooses exhibiting swelling and hemorrhage of liver and kidney, accumulation of fluid in pericardial, in Fujian province of China. The GoAdV was propagated in goose embryo fibroblasts (GEFs), the morphological properties of the virions were studied by electron microscopy, and the full genome sequence was determined and analyzed. The results revealed that the infected cells became round and clustered like grapes, virions accumulated and were arranged in crystal lattice formations in the nucleus of GEFs with a diameter of ∼80 nm. The new isolate (named CH‐FJZZ‐202201) has a viral genome size of 43,480 bp and shared 96.69% sequence identity with GoAdV‐4 (P29), representing the species Goose aviadenovirus A. Phylogenetic analysis showed that CH‐FJZZ‐202201 was in the same genetic evolutionary branch with the viruses of Aviadenovirus and was the closest relative to GoAdV‐4 P29/Hungary. This is the first report of the GoAdV‐4 outside of Hungary, indicating the reemergence of new AdV strains in China.
Efficient Multistage License Plate Detection and Recognition Using YOLOv8 and CNN for Smart Parking Systems
Authors: Safran Mejdl , Alajmi Abdulmalik , Alfarhood Sultan
Published: February 2024

Smart parking systems play a vital role in enhancing the efficiency and sustainability of smart cities. However, most existing systems depend on sensors to monitor the occupancy of parking spaces, which entail high installation and maintenance costs and limited functionality in tracking vehicle movement within the car park. To address these challenges, we propose a multistage learning-based approach that leverages existing surveillance cameras within the car park and a self-collected dataset of Saudi license plates. The approach combines YOLOv5 for license plate detection, YOLOv8 for character detection, and a new convolutional neural network architecture for improved character recognition. We show that our approach outperforms the single-stage approach, achieving an overall accuracy of 96.1% versus 83.9% of the single-stage approach. The approach is also integrated into a web-based dashboard for real-time visualization and statistical analysis of car park occupancy and vehicle movement with an acceptable time efficiency. Our work demonstrates how existing technology can be leveraged to improve the efficiency and sustainability of smart cities.
An Updated Comprehensive Review of Plants and Herbal Compounds with Antiasthmatic Effect
Authors: Rajizadeh Mohammad Amin , Najafipour Hamid , Bejeshk Mohammad Abbas
Published: February 2024

Background. Asthma is a common disease with rising prevalence worldwide, especially in industrialized countries. Current asthma therapy with traditional medicines lacks satisfactory success, hence the patients’ search for alternative and complementary treatments for their diseases. Researchers have conducted many studies on plants with antiallergic and antiasthmatic effects in recent decades. Many of these plants are now used in clinics, and searching for their mechanism of action may result in creating new ideas for producing more effective drugs. Purpose. The goal of this review was to provide a compilation of the findings on plants and their active agents with experimentally confirmed antiasthmatic effects. Study Design and Method. A literature search was conducted from 1986 to November 2023 in Scopus, Springer Link, EMBASE, Science Direct, PubMed, Google Scholar, and Web of Science to identify and report the accumulated knowledge on herbs and their compounds that may be effective in asthma treatment. Results. The results revealed that 58 plants and 32 herbal extracted compounds had antiasthmatic activity. Also, 32 plants were shown to have anti-inflammatory and antioxidative effects or may act as bronchodilators and potentially have antiasthmatic effects, which must be investigated in future studies. Conclusion. The ability of herbal medicine to improve asthma symptoms has been confirmed by clinical and preclinical studies, and such compounds may be used as a source for developing new antiasthmatic drugs. Moreover, this review suggests that many bioactive compounds have therapeutic potential against asthma.
Biogas Production through Anaerobic Codigestion of Distillery Wastewater Sludge and Disposable Spent Yeast
Authors: Duguma Abu , Bekele Tadele , Geda Abera
Published: February 2024

The ongoing industrial transformation in developing countries, including Ethiopia, has resulted in a significant increase in harmful pollutants in the environment. Various industrial activities release toxic wastewater sludge and spent yeast into the surrounding ecosystem, posing risks to public health and the environment. However, these waste materials have the potential for energy extraction and recycling. This study aimed to investigate and harness the biogas potential through anaerobic codigestion of distillery wastewater sludge and waste yeast. The researchers employed a response surface approach utilizing Box–Behnken experimental designs (BBD) to assess the three key experimental parameters influencing biogas yield: pH levels (6, 7, and 8), volume ratio (85, 92, and 99%), and temperature (33, 36.5, and 40°C). Before and after the digestion process, the researchers measured the total solids (TS), biological oxygen demand (BOD5), chemical oxygen demand (COD), and pH of all substrates. Additionally, measurements of temperature, total nitrate, and total phosphate were taken before digestion. The methane yield was modeled using a second‐order polynomial through the BBD method in Design Expert software, with a p value threshold of ≤5%. The results showed that the maximum methane yield of 61.18% was achieved at a pH of 7, a temperature of 36.5°C, and a volume ratio of 92%. Conversely, the lowest methane yield of 40.13% was obtained at a pH of 6, a temperature of 33°C, and a volume ratio of 92%. The linear and quadratic values of the model (A, B, C, A2, B2, and C2) were determined to be significant terms, with p values ≤5%. Overall, the biogas yields obtained from the anaerobic codigestion of distillery wastewater and waste yeast were promising. This process has the potential to effectively remove BOD5, COD, and TS from distillery spent wash and sludge. The findings suggest that anaerobic codigestion could be a viable approach for both energy production and waste management in the setting of distillery waste.
The Interplay of Varicoceles, Sperm Epigenetics, and Male Infertility: A Focused, Contemporary Review
Authors: Sollender Grace E. , Belarmino Andre , Furtado Thiago P. , Osadchiy Vadim , Mills Jesse N. , Pellegrini Matteo , Eleswarapu Sriram V.
Published: February 2024

Despite the wide recognition of varicocele as a contributor to infertility, its exact pathophysiologic mechanism is not fully understood. As the field of male infertility continues to see progress in new diagnostic and therapeutic technologies, we sought to obtain a robust understanding of the interplay of varicoceles, oxidative stress, DNA methylation, and male infertility. We performed a comprehensive review of the contemporary literature in PubMed using search terms and keywords associated with varicoceles, DNA methylation, and male infertility. The most important findings from the literature review were included in this report. Articles were selected based on quality and relevance to the topic. Eight studies were included in this review. These studies discuss DNA methylation and varicocele‐associated male infertility through evaluation of sperm parameters, DNA methylation, DNA fragmentation, and other relevant factors. Our review of the literature on varicocele‐associated sperm DNA methylation indicates that global hypomethylation occurs in association with varicoceles. Some data suggest a dose‐dependent effect of varicocele grade on sperm DNA methylation, with the greatest magnitude changes seen in grades II and III varicoceles. While changes in DNA methylation patterns would be expected following varicocelectomy, such changes were not found to be statistically significant in one study reviewed here. However, current human studies are limited by small sample size and short follow‐up time. Future clinical and preclinical studies with robust sample sizes and hypothesis‐driven investigations are necessary to further understand the relationship between DNA methylation patterns and varicocele‐associated male infertility.
Effectiveness of Calcium Hydroxide and Gingerols Mixture as a Novel Obturation Material for Infected Root in Primary Teeth: A Randomized Clinical Trial
Authors: Qasem Fathi A. , Awad Salwa M. , Elagamy Rizk A.
Published: February 2024

Introduction. The tendency to use dental materials of plant origin is one of the prevailing trends in dentistry to reduce exposure to materials that could have some toxic impact in the long term. Objective. To evaluate the efficacy of calcium hydroxide combined with gingerols (Ginge‐Cal) as a novel obturation material for treating infected primary teeth and decreasing the recurrence of infection. Materials and Methods. The study was conducted on 30 lower primary molars with infected pulp for children aged 4–8 years. The sample was randomly divided into two groups depending on the tested obturation material: Ginge‐Cal group and the Metapex group. The evaluation was done by different parameters clinically and radiographically at various intervals up to 12 months. Results. Based on chi‐squared and McNamara’s test with a 5% significance level, the clinical results indicated that Ginge‐Cal group was more effective than the Metapex group in reducing or eliminating pain (P = 0.467) after 1 week, sensitivity to percussion (P = 0.090) at 3 months of follow‐up, purulent swelling (P = 0.444) at 6 and 9 months of follow‐up, fistula, and tooth mobility. The radiographic results, based on the periapical and furcation area radiolucency at 12 months of follow‐up, favored Ginge‐Cal group over the Metapex group (P = 0.683), (P = 0.456), respectively. There were no statistically significant differences in pathological root resorption and periodontal space. The differences within the Ginge‐Cal group were directly influenced by the time intervals in a statistically significant manner, ranging from (P = 0.004) to (P < 0.001). The success percentage was 87.5% for Ginge‐Cal group and 64.3% for Metapex group. Conclusions. Ginge‐Cal can be considered a promising material for treating the infected root canal when used as an obturation material for the infected root canal. This trial is registered with NCT05181813.
Older Adults’ Experiences of Using Strategies to Maintain and Foster Social Participation: A Systematic Review with Metasynthesis of Qualitative Studies
Authors: Körlof L. , Nyman A. , Isaksson G. , Larsson E.
Published: February 2024

Social participation is positively associated with older adults’ health. Health‐care services, therefore, need to empower older adults to adapt to the social changes that accompany aging. This systematic review, with a metasynthesis of qualitative studies, aimed to describe and develop an understanding of home‐dwelling older adults’ (65 yrs+) experiences of using strategies to maintain and foster their social participation. The main search was performed in March 2022 using the PubMed, CINAHL, PsycINFO, and AMED databases and included peer‐reviewed articles published between 2012 and 2022. A total of 35 full‐text articles from 15 different countries were included and assessed for quality by the assessment tool for qualitative studies provided by the Critical Appraisal Skills Programme (CASP). The metasynthesis resulted in the main theme: strategically creating routines that foster social participation and two main categories: inward‐looking strategies for social participation and outward‐looking strategies for social participation. Each main category contained three subcategories. The findings suggest that for perceiving social participation, it is important for older adults to create routines with patterns of activities and to be able to engage in these activities. The findings further reflect that older adults use earlier experiences of social participation to facilitate the making of routines. This indicates that health‐care interventions supporting older adults’ social participation must be applied early and with a health‐promotive focus. Conclusively, researchers need to develop interventions that support older adults in healthy activity patterns by raising awareness of how to use inward‐looking and outward‐looking strategies to create routines for social participation. The findings further suggest that older adults’ possibilities for social participation could be supported by designing accessible venues that facilitate spontaneous meetings and encourage older adults’ own choices and initiatives for social participation.
Evaluation of Dietary Essential Amino Acid Supplementation on Growth, Digestive Capacity, Antioxidant, and Intestine Health of the Juvenile Redclaw Crayfish, Cherax quadricarinatus
Authors: Jiang Zongzheng , Qian Dunwei , Liang Zhenye , Wu Sen , Han Fenglu , Xu Chang , Chi Meili , Li Erchao
Published: February 2024

The present study was an 8‐week feeding trial investigating the effects of lysine and threonine supplementation in vegetable‐based diets on growth, antioxidative capacity, and gut microbiota of juvenile redclaw crayfish, Cherax quadricarinatus (initial weight 11.52 ± 0.23 g). The lysine and threonine were supplemented to formulate five isonitrogenous (37%) and isolipidic (9%) diets containing 0% (control), 0.2% lysine (L0.2), 0.2% threonine (T0.2), 0.4% lysine (L0.4), and 0.4% threonine (T0.4), respectively. Compared to the control, weight gain rate (WGR) and specific growth rate (SGR) of C. quadricarinatus significantly increased with increasing dietary lysine and threonine supplementation from 0.2% to 0.4% (P < 0.05). Hepatopancreas trypsin activity significantly increased with increasing levels of lysine and threonine in diets (P < 0.05). However, the pepsin, lipase, and amylase activities were not affected by dietary levels of lysine and threonine (P > 0.05). Compared with the control, crayfish in T0.4 and L0.4 showed significantly higher glutathione peroxidase (GPx) activity (P < 0.05), lower alanine aminotransferase (ALT) activity, and lower malondialdehyde (MDA) content (P < 0.05). Supplementation with 0.4% lysine significantly changed the composition of the gut microbiota (P < 0.05), which showed a significantly increased relative abundance of Proteobacteria and decreased Firmicutes, Actinomycetes, and Pontomyces (P < 0.05). The PICRUSt analysis demonstrated that the abundance of the metabolism and cellular processes pathways in the L0.4 group were markedly decreased compared with the control (P < 0.05). Meanwhile, a tighter interaction of the microbiota community in crayfish was observed in the T0.4 experimental group. In conclusion, these results suggested that dietary supplementation with 0.4% threonine could significantly promote growth and improve microbial health in juvenile C. quadricarinatus.
Fibroblasts in the Aged Pancreas Drive Pancreatic Cancer Progression
Authors: Zabransky Daniel J. , Chhabra Yash , Fane Mitchell E. , Kartalia Emma , Leatherman James M. , Hüser Laura , Zimmerman Jacquelyn W. , Delitto Daniel , Han Song , Armstrong Todd D. , Charmsaz Soren , Guinn Samantha , Pramod Sneha , Thompson Elizabeth D. , Hughes Steven J. , O'Connell Jennifer , Egan Josephine M. , Jaffee Elizabeth M. , Weeraratna Ashani T.
Published: February 2024

Pancreatic cancer is more prevalent in older individuals and often carries a poorer prognosis for them. The relationship between the microenvironment and pancreatic cancer is multifactorial, and age-related changes in nonmalignant cells in the tumor microenvironment may play a key role in promoting cancer aggressiveness. Because fibroblasts have profound impacts on pancreatic cancer progression, we investigated whether age-related changes in pancreatic fibroblasts influence cancer growth and metastasis. Proteomics analysis revealed that aged fibroblasts secrete different factors than young fibroblasts, including increased growth/differentiation factor 15 (GDF-15). Treating young mice with GDF-15 enhanced tumor growth, whereas aged GDF-15 knockout mice showed reduced tumor growth. GDF-15 activated AKT, rendering tumors sensitive to AKT inhibition in an aged but not young microenvironment. These data provide evidence for how aging alters pancreatic fibroblasts and promotes tumor progression, providing potential therapeutic targets and avenues for studying pancreatic cancer while accounting for the effects of aging.

Significance:

Aged pancreatic fibroblasts secrete GDF-15 and activate AKT signaling to promote pancreatic cancer growth, highlighting the critical role of aging-mediated changes in the pancreatic cancer microenvironment in driving tumor progression.

See related commentary by Isaacson et al., p. 1185
Supplementary Table 7 from Alveolar Differentiation Drives Resistance to KRAS Inhibition in Lung Adenocarcinoma
Authors: Li Zhuxuan , Zhuang Xueqian , Pan Chun-Hao , Yan Yan , Thummalapalli Rohit , Hallin Jill , Torborg Stefan , Singhal Anupriya , Chang Jason C. , Manchado Eusebio , Dow Lukas E. , Yaeger Rona , Christensen James G. , Lowe Scott W. , Rudin Charles M. , Joost Simon , Tammela Tuomas
Published: February 2024

Supplementary Table 7 shows the date and anatomic site of human patient tissue harvest.
Figure 6 from ESR1 F404 Mutations and Acquired Resistance to Fulvestrant in ESR1-Mutant Breast Cancer
Authors: Kingston Belinda , Pearson Alex , Herrera-Abreu Maria Teresa , Sim Li-Xuan , Cutts Rosalind J. , Shah Heena , Moretti Laura , Kilburn Lucy S. , Johnson Hannah , Macpherson Iain R. , Ring Alistair , Bliss Judith M. , Hou Yingwei , Toy Weiyi , Katzenellenbogen John A. , Chandarlapaty Sarat , Turner Nicholas C.
Published: February 2024

Compound F404 mutations are sensitive to novel SERDs. A–D, Compound mutations of D538G-F404L in MCF7 cells, along with single mutations and wild-type, with sensitivity to elacestrant (A), camizestrant (B), 4OH tamoxifen (C), and giredestrant (D), assessed after 6 days treatment with CellTiter Glo viability assay. n = 4 mean with SD. E, Representative clonongenic assays grown in indicated concentrations of elacestrant, camizestrant, 4OH tamoxifen, and giredestrant for 14 days. F, MCF7 cells were cotransfected with the indicated ESR1 expression constructs ERE-luciferase reporter and control construct. Cells were treated with indicated concentrations of fulvestrant, elacestrant, camizestrant, 4OH tamoxifen, and giredestrant in the presence of 1 nmol/L estradiol for 24 hours, and ERE-luciferase activity was assessed. Two-way repeated-measures ANOVA with Sidak multiple comparisons test, n = 3 mean with SD; *, P < 0.05.
Figure 1 from Combined Immunotherapy Improves Outcome for Replication-Repair-Deficient (RRD) High-Grade Glioma Failing Anti–PD-1 Monotherapy: A Report from the International RRD Consortium
Authors: Das Anirban , Fernandez Nicholas R. , Levine Adrian , Bianchi Vanessa , Stengs Lucie K. , Chung Jiil , Negm Logine , Dimayacyac Jose Rafael , Chang Yuan , Nobre Liana , Ercan Ayse B. , Sanchez-Ramirez Santiago , Sudhaman Sumedha , Edwards Melissa , Larouche Valerie , Samuel David , Van Damme An , Gass David , Ziegler David S. , Bielack Stefan S. , Koschmann Carl , Zelcer Shayna , Yalon-Oren Michal , Campino Gadi Abede , Sarosiek Tomasz , Nichols Kim E. , Loret De Mola Rebecca , Bielamowicz Kevin , Sabel Magnus , Frojd Charlotta A. , Wood Matthew D. , Glover Jason M. , Lee Yi-Yen , Vanan Magimairajan , Adamski Jenny K. , Perreault Sebastien , Chamdine Omar , Hjort Magnus Aasved , Zapotocky Michal , Carceller Fernando , Wright Erin , Fedorakova Ivana , Lossos Alexander , Tanaka Ryuma , Osborn Michael , Blumenthal Deborah T. , Aronson Melyssa , Bartels Ute , Huang Annie , Ramaswamy Vijay , Malkin David , Shlien Adam , Villani Anita , Dirks Peter B. , Pugh Trevor J. , Getz Gad , Maruvka Yosef E. , Tsang Derek S. , Ertl-Wagner Birgit , Hawkins Cynthia , Bouffet Eric , Morgenstern Daniel A. , Tabori Uri
Published: February 2024

Patients with RRD-HGG treated with ICI (n = 75). A, Cohort characteristics. B, Flow of patients with RRD-HGGs treated with ICIs and salvage regimens. MEK-i, MEK inhibitor. C, Progression-free (PFS1) and overall survival (OS1) on anti–PD-1/PDL1 monotherapy. D, Overall survival (OS2) for 55 patients progressing on monotherapy stratified by continued (n = 38) or no ICI (n = 17). PPAP, polymerase proofreading associated polyposis syndrome; CMMRD, constitutional mismatch repair deficiency syndrome.
Supplementary Table 6 from Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression
Authors: Hasselluhn Marie C. , Decker-Farrell Amanda R. , Vlahos Lukas , Thomas Dafydd H. , Curiel-Garcia Alvaro , Maurer H. Carlo , Wasko Urszula N. , Tomassoni Lorenzo , Sastra Stephen A. , Palermo Carmine F. , Dalton Tanner C. , Ma Alice , Li Fangda , Tolosa Ezequiel J. , Hibshoosh Hanina , Fernandez-Zapico Martin E. , Muir Alexander , Califano Andrea , Olive Kenneth P.
Published: February 2024

Epithelial network.

Regulatory network for PDAC-associated epithelial cells, listing the inferred transcriptional targets (Target) for each regulatory protein (Regulator). Association weight (AW) and association mode (AM) are scores to quantify strength/direction of interaction. Sign indicates directionality of the interaction (1 = transactivating, -1 = transrepressing).
Supplementary Table S4 from Receptor-interacting Protein Kinase 2 Is an Immunotherapy Target in Pancreatic Cancer
Authors: Sang Wenhua , Zhou Yiduo , Chen Haiyan , Yu Chengxuan , Dai Lisi , Liu Zhongkun , Chen Lang , Fang Yimin , Ma Panpan , Wu Xiangji , Kong Hao , Liao Wenting , Jiang Hong , Qian Junbin , Wang Da , Liu Yun-Hua
Published: February 2024

Supplementary Table S4. Primers used for qPCR or generating knockout/knockdown constructs.
Supplementary Table 2 from NKG2A Is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple-Negative Breast Cancer
Authors: Taylor Brandie C. , Sun Xiaopeng , Gonzalez-Ericsson Paula I. , Sanchez Violeta , Sanders Melinda E. , Wescott Elizabeth C. , Opalenik Susan R. , Hanna Ann , Chou Shu-Ting , Van Kaer Luc , Gomez Henry , Isaacs Claudine , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Pietenpol Jennifer A. , Balko Justin M.
Published: February 2024

Differentially expressed gene list for single-cell RNA sequencing.
SUPPLEMENTARY DATA FIGURES from Receptor-interacting Protein Kinase 2 Is an Immunotherapy Target in Pancreatic Cancer
Authors: Sang Wenhua , Zhou Yiduo , Chen Haiyan , Yu Chengxuan , Dai Lisi , Liu Zhongkun , Chen Lang , Fang Yimin , Ma Panpan , Wu Xiangji , Kong Hao , Liao Wenting , Jiang Hong , Qian Junbin , Wang Da , Liu Yun-Hua
Published: February 2024

Supplementary Figure S1. In vivo CRISPR screens to identify critical drivers of immune evasion; Supplementary Figure S2. Effects of Ripk2 depletion on tumor growth; Supplementary Figure S3. RIPK2 is overexpressed in human and mouse PDAC tissues; Supplementary Figure S4. Ablation of RIPK2 disrupts the desmoplastic TME; Supplementary Figure S5. RIPK2 modulates the immune profile and impairs anti-tumor T cell response; Supplementary Figure S6. RIPK2 restricts the activation and effector states of CD8+ T cells by impairing antigen presentation; Supplementary Figure S7. RIPK2 promotes MHC-I trafficking to lysosomes via NBR1; Supplementary Figure S8. RIPK2 ubiquitination promotes NBR1-mediated MHC-I degradation; Supplementary Figure S9. RIPK2 ablation potentiates the efficacy of PD-1 blockade; Supplementary Figure S10. Diagram illustrating RIPK2-mediated degradation of MHC I through autophagy–lysosome system.
Supplementary Data Materials Text from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Description of Supplementary Materials and Methods
Supplementary Table 6 from Alveolar Differentiation Drives Resistance to KRAS Inhibition in Lung Adenocarcinoma
Authors: Li Zhuxuan , Zhuang Xueqian , Pan Chun-Hao , Yan Yan , Thummalapalli Rohit , Hallin Jill , Torborg Stefan , Singhal Anupriya , Chang Jason C. , Manchado Eusebio , Dow Lukas E. , Yaeger Rona , Christensen James G. , Lowe Scott W. , Rudin Charles M. , Joost Simon , Tammela Tuomas
Published: February 2024

Supplementary Table 6 shows the TotalSeqB hashtag oligonucleotide-conjugated antibodies.
Supplementary Table 3 from Alveolar Differentiation Drives Resistance to KRAS Inhibition in Lung Adenocarcinoma
Authors: Li Zhuxuan , Zhuang Xueqian , Pan Chun-Hao , Yan Yan , Thummalapalli Rohit , Hallin Jill , Torborg Stefan , Singhal Anupriya , Chang Jason C. , Manchado Eusebio , Dow Lukas E. , Yaeger Rona , Christensen James G. , Lowe Scott W. , Rudin Charles M. , Joost Simon , Tammela Tuomas
Published: February 2024

Supplementary Table 3 shows mouse AT1-like LUAD signature genes.
Supplementary Table 8 from Tumor Explants Elucidate a Cascade of Paracrine SHH, WNT, and VEGF Signals Driving Pancreatic Cancer Angiosuppression
Authors: Hasselluhn Marie C. , Decker-Farrell Amanda R. , Vlahos Lukas , Thomas Dafydd H. , Curiel-Garcia Alvaro , Maurer H. Carlo , Wasko Urszula N. , Tomassoni Lorenzo , Sastra Stephen A. , Palermo Carmine F. , Dalton Tanner C. , Ma Alice , Li Fangda , Tolosa Ezequiel J. , Hibshoosh Hanina , Fernandez-Zapico Martin E. , Muir Alexander , Califano Andrea , Olive Kenneth P.
Published: February 2024

Lymphoid network.

Regulatory network for PDAC-associated lymphoid cells, listing the inferred transcriptional targets (Target) for each regulatory protein (Regulator). Association weight (AW) and association mode (AM) are scores to quantify strength/direction of interaction. Sign indicates directionality of the interaction (1 = transactivating, -1 = transrepressing).
Supplementary Data Figure S3 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Figure S3 showing that removal of mutant TP53 does not impair the ability of diverse human cancer cell lines to adapt to conditions of stress
Supplementary Data Figure S26 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Figure S26 showing that removal of mutant TP53 does not impact in vivo tumor growth upon transplantation of WCB139T human colon cancer derived organoids into NSG mice
Supplementary Data Figure S15 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Figure S15 showing that removal of mutant TP53 does not impair in vivo tumor growth of certain human cancer cell lines
Supplementary Data Figure S14 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Figure S14 showing that CRISPR-HDR mediated conversion of mutant TP53 into wt TP53 causes a growth disadvantage in human cancer cell lines
Supplementary Data Figure S1 from Loss-of-Function but Not Gain-of-Function Properties of Mutant TP53 Are Critical for the Proliferation, Survival, and Metastasis of a Broad Range of Cancer Cells
Authors: Wang Zilu , Burigotto Matteo , Ghetti Sabrina , Vaillant François , Tan Tao , Capaldo Bianca D. , Palmieri Michelle , Hirokawa Yumiko , Tai Lin , Simpson Daniel S. , Chang Catherine , Huang Allan Shuai , Lieschke Elizabeth , Diepstraten Sarah T. , Kaloni Deeksha , Riffkin Chris , Huang David C.S. , Li Wai Suen Connie S.N. , Garnham Alexandra L. , Gibbs Peter , Visvader Jane E. , Sieber Oliver M. , Herold Marco J. , Fava Luca L. , Kelly Gemma L. , Strasser Andreas
Published: February 2024

Supplementary Figure S1 confirming the removal of mutant TP53 in diverse human cancer cell lines
FIGURE 4 from Functional Heterogeneity in MET Pathway Activation in PDX Models of Osimertinib-resistant EGFR-driven Lung Cancer
Authors: Roper Nitin , El Meskini Rajaa , Maity Tapan , Atkinson Devon , Day Amanda , Pate Nathan , Cultraro Constance M. , Pack Svetlana , Zgonc Valerie , Weaver Ohler Zoe , Guha Udayan
Published: February 2024

Heterogeneity in MET polysomy and MET amplification in osimertinib-resistant EGFR-mutant NSCLC. A, Representative phospho-MET IHC (several are reused from Fig. 2D), MET FISH images and MET FISH scoring from PDXs with MET polysomy. B, Representative phospho-MET IHC, MET FISH images and MET FISH scoring from longitudinally collected tumor samples from patient LAT006 at first progression on osimertinib, second progression after osimertinib rechallenge, and upon further progression on chemoimmunotherapy. Scale bars, 50 µm.
Identification and Characterization of a Small Molecule Bcl-2 Functional Converter
Authors: Kopparapu Prasad R. , Pearce Martin C. , Löhr Christiane V. , Duong Cathy , Jang Hyo Sang , Tyavanagimatt Shanthakumar , O'Donnell Edmond F. , Nakshatri Harikrishna , Kolluri Siva K.
Published: February 2024

Cancer cells exploit the expression of anti-apoptotic protein Bcl-2 to evade apoptosis and develop resistance to therapeutics. High levels of Bcl-2 leads to sequestration of pro-apoptotic proteins causing the apoptotic machinery to halt. In this study, we report discovery of a small molecule, BFC1108 (5-chloro-N-(2-ethoxyphenyl)-2-[(4-methoxybenzyol)amino]benzamide), which targets Bcl-2 and converts it into a pro-apoptotic protein. The apoptotic effect of BFC1108 is not inhibited, but rather potentiated, by Bcl-2 overexpression. BFC1108 induces a conformational change in Bcl-2, resulting in the exposure of its BH3 domain both in vitro and in vivo. BFC1108 suppresses the growth of triple-negative breast cancer xenografts with high Bcl-2 expression and inhibits breast cancer lung metastasis. This study demonstrates a novel approach to targeting Bcl-2 using BFC1108, a small molecule Bcl-2 functional converter that effectively induces apoptosis in Bcl-2–expressing cancers.

Significance:

We report the identification of a small molecule that exposes the Bcl-2 killer conformation and induces death in Bcl-2–expressing cancer cells. Selective targeting of Bcl-2 and elimination of cancer cells expressing Bcl-2 opens up new therapeutic avenues.
Gastric Adenocarcinoma with Enteroblastic Differentiation Resected through Endoscopic Submucosal Dissection: A Case Report
Authors: Ishikawa Akira , Nakamura Koki
Published: February 2024

Introduction: Gastric adenocarcinoma with enteroblastic differentiation (GAED) is a rare histological type of gastric adenocarcinoma that occurs in the stomach and is known for its aggressive behavior. GAED is diagnosed histopathologically and is often advanced at the time of diagnosis. Case Presentation: We report the case of a 70-year-old male with a 20-mm superficial depressed lesion on the anterior wall of the antrum. Histological examination of the endoscopic submucosal dissection specimen revealed that the tumor was composed of dilated or slit-like branching tubules; additionally, the tumor cells had clear cytoplasm resembling that of the fetal digestive tract. Immunohistochemically, the tumor cells were positive for Glypican-3 and alpha-fetoprotein. A pathological diagnosis of GAEDs was established. GAED was found in approximately 30% of all the tumor cells and showed lymphatic invasion. The patient has been under recurrence-free follow-up for approximately 1 year after the endoscopic submucosal dissection. Conclusion: In order to detect a large number of cases, immunostaining should be aggressively performed if morphological findings are suspicious for GAED.
Plasma S1P Orchestrates the Reverse Transendothelial Migration of Aortic Intimal Myeloid Cells in Mice
Authors: Polenz Chanele K. , Scipione Corey A. , Hyduk Sharon J. , Althagafi Marwan G. , Ibrahim Hisham M. , Cybulsky Myron I.
Published: February 2024

BACKGROUND:

Myeloid cells (MCs) reside in the aortic intima at regions predisposed to atherosclerosis. Systemic inflammation triggers reverse transendothelial migration (RTM) of intimal MCs into the arterial blood, which orchestrates a protective immune response that clears intracellular pathogens from the arterial intima. Molecular pathways that regulate RTM remain poorly understood. S1P (sphingosine-1-phosphate) is a lipid mediator that regulates immune cell trafficking by signaling via 5 G-protein–coupled receptors (S1PRs [S1P receptors]). We investigated the role of S1P in the RTM of aortic intimal MCs.

METHODS:

Intravenous injection of lipopolysaccharide was used to model a systemic inflammatory stimulus that triggers RTM. CD11c
+
intimal MCs in the lesser curvature of the ascending aortic arch were enumerated by en face confocal microscopy. Local gene expression was evaluated by transcriptomic analysis of microdissected intimal cells.

RESULTS:

In wild-type C57BL/6 mice, lipopolysaccharide induced intimal cell expression of
S1pr1
,
S1pr3
, and
Sphk1
(a kinase responsible for S1P production). Pharmacological modulation of multiple S1PRs blocked lipopolysaccharide-induced RTM and modulation of S1PR1 and S1PR3 reduced RTM in an additive manner. Cre-mediated deletion of
S1pr1
in MCs blocked lipopolysaccharide-induced RTM, confirming a role for myeloid-specific S1PR1 signaling. Global or hematopoietic deficiency of
Sphk1
reduced plasma S1P levels, the abundance of CD11c
+
MCs in the aortic intima, and blunted lipopolysaccharide-induced RTM. In contrast, plasma S1P levels, the abundance of intimal MCs, and lipopolysaccharide-induced RTM were rescued in

Sphk1
−/−

mice transplanted with
Sphk1

+/+

or mixed
Sphk1

+/+

and

Sphk1
−/−

bone marrow. Stimulation with lipopolysaccharide increased endothelial permeability and intimal MC exposure to circulating factors such as S1P.

CONCLUSIONS:

Functional and expression studies support a novel role for S1P signaling in the regulation of lipopolysaccharide-induced RTM and the homeostatic maintenance of aortic intimal MCs. Our data provide insight into how circulating plasma mediators help orchestrate intimal MC dynamics.
Neighborhood Disadvantage and Risk of Heart Failure: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Malla Gargya , Long D. Leann , Cherrington Andrea , Goyal Parag , Guo Boyi , Safford Monika M. , Khodneva Yulia , Cummings Doyle M. , McAlexander Tara P. , DeSilva Shanika , Judd Suzanne E. , Hidalgo Bertha , Levitan Emily B. , Carson April P.
Published: February 2024

BACKGROUND:

Heart failure (HF) affects >6 million US adults, with recent increases in HF hospitalizations. We aimed to investigate the association between neighborhood disadvantage and incident HF events and potential differences by diabetes status.

METHODS:

We included 23 645 participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), a prospective cohort of Black and White adults aged ≥45 years living in the continental United States (baseline 2005–2007). Neighborhood disadvantage was assessed using a
Z
score of 6 census tract variables (2000 US Census) and categorized as quartiles. Incident HF hospitalizations or HF-related deaths through 2017 were adjudicated. Multivariable-adjusted Cox regression was used to examine the association between neighborhood disadvantage and incident HF. Heterogeneity by diabetes was assessed using an interaction term.

RESULTS:

The mean age was 64.4 years, 39.5% were Black adults, 54.9% females, and 18.8% had diabetes. During a median follow-up of 10.7 years, there were 1125 incident HF events with an incidence rate of 3.3 (quartile 1), 4.7 (quartile 2), 5.2 (quartile 3), and 6.0 (quartile 4) per 1000 person-years. Compared to adults living in the most advantaged neighborhoods (quartile 1), those living in neighborhoods in quartiles 2, 3, and 4 (most disadvantaged) had 1.30 (95% CI, 1.06–1.60), 1.36 (95% CI, 1.11–1.66), and 1.45 (95% CI, 1.18–1.79) times greater hazard of incident HF even after accounting for known confounders. This association did not significantly differ by diabetes status (interaction
P
=0.59). For adults with diabetes, the adjusted incident HF hazards comparing those in quartile 4 versus quartile 1 was 1.34 (95% CI, 0.92–1.96), and it was 1.50 (95% CI, 1.16–1.94) for adults without diabetes.

CONCLUSIONS:

In this large contemporaneous prospective cohort, neighborhood disadvantage was associated with an increased risk of incident HF events. This increase in HF risk did not differ by diabetes status. Addressing social, economic, and structural factors at the neighborhood level may impact HF prevention.
Cost of Cardiovascular Disease Event and Cardiovascular Disease Treatment–Related Complication Hospitalizations in the United States
Authors: Tajeu Gabriel S. , Ruiz-Negrón Natalia , Moran Andrew E. , Zhang Zugui , Kolm Paul , Weintraub William S. , Bress Adam P. , Bellows Brandon K.
Published: February 2024

BACKGROUND:

Cardiovascular disease (CVD) is among the costliest conditions in the United States, and cost-effectiveness analyses can be used to assess economic impact and prioritize CVD treatments. We aimed to develop standardized, nationally representative CVD events and selected possible CVD treatment–related complication hospitalization costs for use in cost-effectiveness analyses.

METHODS:

Nationally representative costs were derived using publicly available inpatient hospital discharge data from the 2012-2018 National Inpatient Sample. Events were identified using the principal
International Classification of Diseases
,
Ninth Revision
and
International Classification of Diseases
,
Tenth Revision
codes. Facility charges were converted to costs using charge-to-cost ratios, and total costs were estimated by applying a published professional fee ratio. All costs are reported in 2021 US dollars. Mean costs were estimated for events overall and stratified by age, sex, and survival status at discharge. Annual costs to the US health care system were estimated by multiplying the mean annual number of events by the mean total cost per discharge.

RESULTS:

The annual mean number of hospital discharges among CVD events was the highest for heart failure (1 087 000 per year) and cerebrovascular disease (800 600 per year). The mean cost per hospital discharge was the highest for peripheral vascular disease ($33 700 [95% CI, $33 300–$34 000]) and ventricular tachycardia/ventricular fibrillation ($32 500 [95% CI, $32 100–$32 900]). Hospitalizations contributing the most to annual US health care costs were heart failure ($19 500 [95% CI, $19 300–$19 800] million) and acute myocardial infarction ($18 300, [95% CI, $18 200–$18 500] million). Acute kidney injury was the most frequent possible treatment complication (515 000 per year), and bradycardia had the highest mean hospitalization costs ($17 400 [95% CI, $17 200–$17 500]).

CONCLUSIONS:

The hospitalization cost estimates and statistical code reported in the current study have the potential to increase transparency and comparability of cost-effectiveness analyses for CVD in the United States.
Safety and Effectiveness of the High-Sensitivity Cardiac Troponin HEART Pathway in Patients With Possible Acute Coronary Syndrome
Authors: Mahler Simon A. , Ashburn Nicklaus P. , Paradee Brennan E. , Stopyra Jason P. , O’Neill James C. , Snavely Anna C.
Published: February 2024

BACKGROUND:

The HEART Pathway (History, Electrocardiogram, Age, Risk factors, Troponin) can be used with high-sensitivity cardiac troponin to risk stratify emergency department patients with possible acute coronary syndrome. However, data on whether a high-sensitivity HEART Pathway (hs-HP) are safe and effective is lacking.

METHODS:

An interrupted time series study was conducted at 5 North Carolina sites in 26 126 adult emergency department patients being investigated for possible acute coronary syndrome and without ST-segment–elevation myocardial infarction. Patients were accrued into 16-month preimplementation and postimplementation cohorts with a 6-month wash-in phase. Preimplementation (January 2019 to April 2020), the traditional HEART Pathway was used with 0- and 3-hour contemporary troponin measures (Siemens). In the postimplementation period (November 2020 to February 2022), a modified hs-HP was used with 0- and 2-hour high-sensitivity cardiac troponin (Beckman Coulter) measures. The primary safety and effectiveness outcomes were 30-day all-cause death or myocardial infarction and 30-day hospitalizations. These outcomes and early discharge rate (emergency department discharge without stress testing or coronary angiography) were determined from health records and death index data. Outcomes were compared preimplementation versus postimplementation using χ
2
tests and multivariable logistic regression to adjust for potential confounders.

RESULTS:

Preimplementation and postimplementation cohorts included 12 317 and 13 809 patients, respectively, of them 52.7% (13 767/26 126) were female with a median age of 54 years (interquartile range, 42–66). Rates of 30-day death or MI were 6.8% (945/13 809) postimplementation and 7.7% (948/12 317) preimplementation (adjusted odds ratio, 1.00 [95% CI, 0.90–1.11]). hs-HP implementation was associated with 19.9% (95% CI, 18.7%–21.1%) higher early discharges (post versus pre: 63.6% versus 43.7%; adjusted odds ratio, 2.22 [95% CI, 2.10–2.35]). The hs-HP was also associated with 16.1% (95% CI, 14.9%–17.3%) lower 30-day hospitalizations (postimplementation versus preimplementation, 31.4% versus 47.5%; adjusted odds ratio, 0.51 [95% CI, 0.48–0.54]). Among early discharge patients, death or myocardial infarction occurred in 0.5% (41/8780) postimplementation versus 0.4% (22/5383) preimplementation (
P
=0.61).

CONCLUSIONS:

hs-HP implementation is associated with increased early discharges without increasing adverse events. These findings support the use of a modified hs-HP to improve chest pain care.
Alpha Oscillations and Temporal Binding Windows in Perception—A Critical Review and Best Practice Guidelines
Authors: Schoffelen Jan-Mathijs , Pesci Ugo Giulio , Noppeney Uta
Published: February 2024

An intriguing question in cognitive neuroscience is whether alpha oscillations shape how the brain transforms the continuous sensory inputs into distinct percepts. According to the alpha temporal resolution hypothesis, sensory signals arriving within a single alpha cycle are integrated, whereas those in separate cycles are segregated. Consequently, shorter alpha cycles should be associated with smaller temporal binding windows and higher temporal resolution. However, the evidence supporting this hypothesis is contentious, and the neural mechanisms remain unclear. In this review, we first elucidate the alpha temporal resolution hypothesis and the neural circuitries that generate alpha oscillations. We then critically evaluate study designs, experimental paradigms, psychophysics, and neurophysiological analyses that have been employed to investigate the role of alpha frequency in temporal binding. Through the lens of this methodological framework, we then review evidence from between-subject, within-subject, and causal perturbation studies. Our review highlights the inherent interpretational ambiguities posed by previous study designs and experimental paradigms and the extensive variability in analysis choices across studies. We also suggest best practice recommendations that may help to guide future research. To establish a mechanistic role of alpha frequency in temporal parsing, future research is needed that demonstrates its causal effects on the temporal binding window with consistent, experimenter-independent methods.