bluuebunny/crossref_metadata_2025 huggingface dataset:
Occurrence, Antimicrobial Resistance, and Virulence Profiles of Salmonella Serovars Isolated from Wild Reptiles in South Africa
Authors: Mlangeni Lungile N. , Ramatla Tsepo , Lekota Kgaugelo E. , Price Cormac , Thekisoe Oriel , Weldon Che
Published: January 2024

Reptiles are carriers of an array of microorganisms, including significant zoonotic bacteria of the genus Salmonella, which cause a disease referred to as salmonellosis that affects both animals and humans. This study investigated the occurrence of Salmonella serovars in wild reptiles at Timbavati Private Game Reserve in Limpopo Province, South Africa, and examined their virulence and antimicrobial resistance gene profiles. A total of 19 wild reptiles were sampled, which resulted in 30 presumptive Salmonella isolates. The isolates were identified using polymerase chain reaction (PCR) by amplifying the invA gene and were further confirmed by 16S rRNA gene sequencing. Salmonella serovars were detected in chameleons (36.8%), lizards (31.6%), snakes (15.8%), and tortoises (15.8%). The use of 16S rRNA gene sequencing revealed that Salmonella enterica subsp. enterica serovar Salamae (30%), S. enterica subsp. enterica (16.7%), S. enterica subsp. enterica serovar Typhimurium (13.3%), and S. enterica subsp. enterica serovar Indiana (13.3%) were the four most common subspecies among the investigated 30 isolates. Detected virulence genes included pagN (100%), hilA (96.7%), ssrB (96.7%), prgH (86.7%), and marT (86.7%). The isolates exhibited resistance to nalidixic acid (43.3%) and kanamycin (43.3%), followed by streptomycin (16.7%) and ciprofloxacin (3.3%). Antibiotic‐resistant genes were detected as follows: strA, strB, qnrA, qnrS, parC, aadA, aac(6′)‐Ib, and aac(6′)-Ib-cr at 33.3%, 6.7%, 16.7, 13.3%, 10%, 23.3%, 6.7%, and 10%, respectively. The findings highlight the necessity of educational initiatives aimed at reducing reptile‐related infections. Effective antibiotic treatment appears promising for infection, given the minimal drug resistance observed in reptile Salmonella serovars in the current study.
Impacts of Grazing on the Selected Features of Herbaceous Species and Harvested Dry Matter Yield of Natural Pasture
Authors: Desta Alemu Gashe , Yimenu Shashie Ayele , Teshale Workinesh Tiruneh , Tessema Berhanu Alemu , Tessma Mesganaw Addis
Published: January 2024

This study evaluated how grazing influenced the specific features of herbaceous species (basal cover, species richness, evenness, and diversity) as well as dry matter yield in the northwestern highlands of Ethiopia. For this study, the natural pastures were divided into three strata based on grazing types (grazing exclusion areas, controlled grazing, and continuous grazing). The areas in each grazing type were divided into two randomly selected (100 m × 50 m) sampling blocks. Then, each of the separated areas was divided into five 10 m × 10 m, and in each subdivided plot, (0.5 m × 0.5 m) were placed across the plots. Thus, a total of 30 (0.5 m × 0.5 m) quadrats were used to evaluate the effect of grazing on the basal cover, species richness, diversity, and dry matter yield of the herbaceous pasture layers. As the results showed, there were significant differences in dry matter yield, basal cover, species richness, evenness, and diversity among grazing areas. The dry matter yield, basal cover, species richness, and diversity were significantly (P<0.05) higher in both grazing exclusion and controlled grazing areas than in continuous grazing areas. Therefore, to increase the dry matter yield of natural pasture and to ensure sustainable livestock production, the livestock producers in the study areas should practice either a cut-carry system or a controlled grazing system.
Impact of Tool Eccentricity on Acoustic Logging Response in Horizontal Wells: Insights from Physical Simulation Experiments
Authors: Zhang Yuanjun , Wu Dong , Liao Maojie , Shi Xuewen , Chen Feng , Zhang Chengguang , Cai Ming , Tang Jun
Published: January 2024

Horizontal wells are extensively utilized in the development of unconventional reservoirs. However, the logging responses and formation evaluation in horizontal wells can be impacted by factors like anisotropy and tool eccentricity. To investigate the influence of tool eccentricity on acoustic logging response, physical simulation experiments of array acoustic logging were conducted in a scaled borehole formation model under different tool eccentricity conditions. The experimental data were analyzed, and the findings revealed that when the receiver array is parallel to the borehole axis, the P-wave slowness and S-wave slowness remain unaffected by tool eccentricity. However, the amplitudes of the P-wave and S-wave decrease significantly with increasing tool eccentricity, following an approximate negative exponential pattern. Additionally, when the transmitter is centered and the receiver array intersects the borehole axis at an angle, the wave velocities increase significantly with tool eccentricity, with the P-wave velocity showing a faster increase. Conversely, when the transmitter is eccentric and the receiver array intersects the borehole axis at an angle, the wave velocity decreases notably with tool eccentricity, and the P-wave velocity decreases even faster. These findings contribute to a better understanding of the impact of tool eccentricity on array acoustic logging response in horizontal wells and offer guidance for developing correction schemes to address this effect.
Systemic Tofacitinib Treatment in Pediatric Patients with Resistant Alopecia Areata
Authors: Öksüm Solak Eda , Borlu Murat
Published: January 2024

Alopecia areata (AA) significantly impacts mental health and quality of life in children. While current treatments often offer limited efficacy, noticeable remission occurs in responsive cases. Recent advancements in understanding AA’s pathogenesis have sparked hope for Janus kinase (JAK) inhibitors as potential treatments. However, studies on this promising avenue remain limited. Our retrospective evaluation of pediatric patients treated with systemic tofacitinib for alopecia showed significant improvements, notably at the 12‐month mark, with only one patient experiencing an upper respiratory infection as a side effect. Nevertheless, our study’s retrospective design and small patient cohort highlight limitations. Larger randomized studies are crucial to comprehensively explore the efficacy and potential of JAK inhibitors in pediatric AA treatment.
Usage of the Fuzzy Adomian Decomposition Method for Solving Some Fuzzy Fractional Partial Differential Equations
Authors: Saeed Nagwa A. , Pachpatte Deepak B.
Published: January 2024

In this study, we examine the numerical solutions of nonlinear fuzzy fractional partial differential equations under the Caputo derivative utilizing the technique of fuzzy Adomian decomposition. This technique is used as an alternative method for obtaining approximate fuzzy solutions to various types of fractional differential equations and also investigated some new existence and uniqueness results of fuzzy solutions. Some examples are given to support the effectiveness of the proposed technique. We present the numerical results in graphical form for different values of fractional order and uncertainty γ∈0,1.
A Multicenter, Randomized, Open‐Label Study to Compare the Effects of Gemigliptin Add‐on or Escalation of Metformin Dose on Glycemic Control and Safety in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Treated with Metformin and SGLT‐2 Inhibitors (SO GOOD Study)
Authors: Kim Hae Jin , Noh Jung Hyun , Moon Min Kyong , Choi Sung Hee , Ko Seung-Hyun , Rhee Eun-Jung , Hur Kyu Yeon , Jeong In-Kyung
Published: January 2024

Background. We aimed to compare efficacy and safety between gemigliptin add‐on and escalation of the metformin dose in patients with inadequately controlled type 2 diabetes mellitus (T2DM) despite treatment with metformin and SGLT2 inhibitors. Methods. This study was a multicenter, randomized, open‐label, active‐controlled, parallel‐group comparative study. Patients with T2DM uncontrolled on metformin and SGLT2 inhibitors were randomized to receive gemigliptin 50 mg as an add‐on (GEM group, n = 37) or escalation of the metformin dose (500 mg, MET group, n = 38) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to week 24. Results. At weeks 12 and 24, the reduction in HbA1c levels was significantly greater in the GEM group than in the MET group (GEM vs. MET = −0.64% ± 0.34% vs. −0.36% ± 0.50%, p = 0.009 at week 12; −0.61% ± 0.35% vs. −0.33% ± 0.70%, p = 0.045 at week 24). The proportions of patients who achieved target HbA1c levels of <7.0% at weeks 12 and 24 and <6.5% at week 12 were greater in the GEM group than in the MET group. An index of β‐cell function was also significantly improved in the GEM group. The safety profiles were similar between the two groups. Conclusions. Gemigliptin add‐on therapy may be more effective than metformin dose escalation in patients with T2DM insufficiently controlled using metformin and SGLT2 inhibitors, without safety concerns. This trial is registered with CRIS_number: KCT0003520.
Lung Cancer in Ever- and Never-Smokers: Findings from Multi-Population GWAS Studies
Authors: Li Yafang , Xiao Xiangjun , Li Jianrong , Han Younghun , Cheng Chao , Fernandes Gail F. , Slewitzke Shannon E. , Rosenberg Susan M. , Zhu Meng , Byun Jinyoung , Bossé Yohan , McKay James D. , Albanes Demetrios , Lam Stephen , Tardon Adonina , Chen Chu , Bojesen Stig E. , Landi Maria T. , Johansson Mattias , Risch Angela , Bickeböller Heike , Wichmann H-Erich , Christiani David C. , Rennert Gad , Arnold Susanne M. , Goodman Gary E. , Field John K. , Davies Michael P.A. , Shete Sanjay , Marchand Loïc Le , Liu Geoffrey , Hung Rayjean J. , Andrew Angeline S. , Kiemeney Lambertus A. , Sun Ryan , Zienolddiny Shanbeh , Grankvist Kjell , Johansson Mikael , Caporaso Neil E. , Cox Angela , Hong Yun-Chul , Lazarus Philip , Schabath Matthew B. , Aldrich Melinda C. , Schwartz Ann G. , Gorlov Ivan , Purrington Kristen S. , Yang Ping , Liu Yanhong , Bailey-Wilson Joan E. , Pinney Susan M. , Mandal Diptasri , Willey James C. , Gaba Colette , Brennan Paul , Xia Jun , Shen Hongbing , Amos Christopher I.
Published: January 2024

Background:

Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.

Methods:

We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer.

Results:

Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10−8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior.

Conclusions:

We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies.

Impact:

Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.
Supplementary Figure S1 from Inhibition of PORCN Blocks Wnt Signaling to Attenuate Progression of Oral Carcinogenesis
Authors: Peña-Oyarzún Daniel , Flores Tania , Torres Vicente A. , Quest Andrew F.G. , Lobos-González Lorena , Kretschmar Catalina , Contreras Pamela , Maturana-Ramírez Andrea , Criollo Alfredo , Reyes Montserrat
Published: January 2024

Characterization of the in vitro human oral carcinogenesis model
Supplementary Table S2 from Overall Survival and Exploratory Biomarker Analyses of Abemaciclib plus Trastuzumab with or without Fulvestrant versus Trastuzumab plus Chemotherapy in HR+, HER2+ Metastatic Breast Cancer Patients
Authors: Tolaney Sara M. , Goel Shom , Nadal Jorge , Denys Hannelore , Borrego Manuel R. , Litchfield Lacey M. , Liu Jiangang , Appiah Adams K. , Chen Yanyun , André Fabrice
Published: January 2024

Updated adverse event overview.
Supplementary Figure S3 from Tumor Volume Growth Rates and Doubling Times during Active Surveillance of IDH-mutant Low-Grade Glioma
Authors: Bhatia Ankush , Moreno Raquel , Reiner Anne S. , Nandakumar Subhiksha , Walch Henry S. , Thomas Teena M. , Nicklin Philip J. , Choi Ye , Skakodub Anna , Malani Rachna , Prabhakaran Vivek , Tiwari Pallavi , Diaz Maria , Panageas Katherine S. , Mellinghoff Ingo K. , Bale Tejus A. , Young Robert J.
Published: January 2024

Supplementary Figure S3. Next-Intervention-Free Survival and overall survival.
Supplementary Table S12 from Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma
Authors: Petrylak Daniel P. , Eigl Bernhard J. , George Saby , Heath Elisabeth I. , Hotte Sebastien J. , Chism David D. , Nabell Lisle M. , Picus Joel , Cheng Susanna Y. , Appleman Leonard J. , Sonpavde Guru P. , Morgans Alicia K. , Pourhosseini Pourya , Wu Ruishan , Standley Laura , Croitoru Ruslan , Yu Evan Y.
Published: January 2024

Supplementary Table S12. Statistical Assessment of Dose Proportionality for MMAE, Power Model, PK Analysis Set
Supplementary Table S5 from Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study
Authors: Drew Yvette , Kim Jae-Weon , Penson Richard T. , O'Malley David M. , Parkinson Christine , Roxburgh Patricia , Plummer Ruth , Im Seock-Ah , Imbimbo Martina , Ferguson Michelle , Rosengarten Ora , Steeghs Neeltje , Kim Min Hwan , Gal-Yam Einav , Tsoref Daliah , Kim Jae-Hoon , You Benoit , De Jonge Maja , Lalisang Roy , Gort Eelke , Bastian Sara , Meyer Kassondra , Feeney Laura , Baker Nigel , Ah-See Mei-Lin , Domchek Susan M. , Banerjee Susana
Published: January 2024

Immune-mediated AEs
Supplementary Table S2 from Proteomic Profiling of Advanced Melanoma Patients to Predict Therapeutic Response to Anti-PD-1 Therapy
Authors: Zila Nina , Eichhoff Ossia M. , Steiner Irene , Mohr Thomas , Bileck Andrea , Cheng Phil F. , Leitner Alexander , Gillet Ludovic , Sajic Tatjana , Goetze Sandra , Friedrich Betty , Bortel Patricia , Strobl Johanna , Reitermaier René , Hogan Sabrina A. , Martínez Gómez Julia M. , Staeger Ramon , Tuchmann Felix , Peters Sophie , Stary Georg , Kuttke Mario , Elbe-Bürger Adelheid , Hoeller Christoph , Kunstfeld Rainer , Weninger Wolfgang , Wollscheid Bernd , Dummer Reinhard , French Lars E. , Gerner Christopher , Aebersold Ruedi , Levesque Mitchell P. , Paulitschke Verena
Published: January 2024

Antibodies used for immunofluorescence staining on a melanoma tissue microarray (TMA).
Table S3 from Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy
Authors: Zhang Mingming , Zhou Linghui , Zhao Houli , Zhang Yanlei , Wei Guoqing , Hong Ruimin , Wu Wenjun , Xu Huijun , Wang Linqin , Ni Fang , Cui Jiazhen , Peng Shuixiu , Huang Chih-Hua , Chang Alex H. , Hu Yongxian , Huang He
Published: January 2024

Supplementary table S3 Other Adverse Events Associated with Treatment Occurring in Two or More Patients
Figure S7 from Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy
Authors: Zhang Mingming , Zhou Linghui , Zhao Houli , Zhang Yanlei , Wei Guoqing , Hong Ruimin , Wu Wenjun , Xu Huijun , Wang Linqin , Ni Fang , Cui Jiazhen , Peng Shuixiu , Huang Chih-Hua , Chang Alex H. , Hu Yongxian , Huang He
Published: January 2024

Supplementary figure S7 Progression-free survival (PFS) and cumulate incidence of relapse (CIR) among patients with extramedullary disease (EMD). A: PFS; B: CIR. Extramedullary disease was defined as paraskeletal soft-tissue masses, soft-tissue masses spreading outside the bone marrow (outside BM), or both.
Figure S3 from Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy
Authors: Zhang Mingming , Zhou Linghui , Zhao Houli , Zhang Yanlei , Wei Guoqing , Hong Ruimin , Wu Wenjun , Xu Huijun , Wang Linqin , Ni Fang , Cui Jiazhen , Peng Shuixiu , Huang Chih-Hua , Chang Alex H. , Hu Yongxian , Huang He
Published: January 2024

Supplementary figure S3 Bar graphs of cytokine production in the supernatants of CAR T-cells co-cultured with BCMA+ RPMI8226 cells using untransduced T cells as controls, determined by Luminex Assays (ThermoFisher Scientific).
Data from Analysis of tumor microenvironment changes after neoadjuvant chemotherapy with or without bevacizumab in advanced ovarian cancer (GEICO-89T/MINOVA study).
Authors: Tavira Beatriz , Iscar Teresa , Manso Luis , Santaballa Ana , Gil-Martin Marta , García García Yolanda , Romeo Margarita , Iglesias Maria , de Juan Ferré Ana , Barretina-Ginesta Maria Pilar , Manzano Aránzazu , Gaba Lydia , Rubio María Jesús , de Andrea Carlos E. , González-Martín Antonio
Published: January 2024

Abstract
Purpose: The aim of our study was to elucidate the impact of bevacizumab added to neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment and correlate the changes with the clinical outcome of the patients. Experimental Design: Immunohistochemistry and multiplex immunofluorescence for lymphoid and myeloid lineage markers were performed in matched tumor samples from 23 ovarian cancer patients enrolled in GEICO 1205/NOVA clinical study before NACT and at the time of interval cytoreductive surgery. Results: Our results showed that the addition of bevacizumab to NACT plays a role mainly on lymphoid populations at the stromal compartment, detecting a significant decrease of CD4+ T cells, an increase of CD8+ T cells and an upregulation effector/regulatory cells ratio (CD8+/CD4+FOXP3+). None of the changes observed were detected in the intra-epithelial site in any arm (NACT or NACT-bevacizumab). No differences were found in myeloid lineage (macrophages-like). The percentage of Treg populations and effector/regulatory cell ratio in the stroma were the only two variables significative associated with PFS. Conclusions: The addition of bevacizumab to NACT did not have an impact on PFS in the GEICO 1205 study. However, at cellular level, changes in CD4+, CD8+lymphocyte populations, and CD8+/CD4+FOXP3 ratio have been detected only at the stromal site. Based on our results, we hypothesize about the existence of mechanisms of resistance that could prevent the trafficking of T effector cells into the epithelial component of the tumor as a potential explanation for the lack of efficacy of ICI in the first line of advanced EOC.
Data from Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors
Authors: Hayashi Takahiro , Tateishi Kensuke , Matsuyama Shinichiro , Iwashita Hiromichi , Miyake Yohei , Oshima Akito , Honma Hirokuni , Sasame Jo , Takabayashi Katsuhiro , Sugino Kyoka , Hirata Emi , Udaka Naoko , Matsushita Yuko , Kato Ikuma , Hayashi Hiroaki , Nakamura Taishi , Ikegaya Naoki , Takayama Yutaro , Sonoda Masaki , Oka Chihiro , Sato Mitsuru , Isoda Masataka , Kato Miyui , Uchiyama Kaho , Tanaka Tamon , Muramatsu Toshiki , Miyake Shigeta , Suzuki Ryosuke , Takadera Mutsumi , Tatezuki Junya , Ayabe Junichi , Suenaga Jun , Matsunaga Shigeo , Miyahara Kosuke , Manaka Hiroshi , Murata Hidetoshi , Yokoyama Takaakira , Tanaka Yoshihide , Shuto Takashi , Ichimura Koichi , Kato Shingo , Yamanaka Shoji , Cahill Daniel P. , Fujii Satoshi , Shankar Ganesh M. , Yamamoto Tetsuya
Published: January 2024

AbstractPurpose:
The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay.
Experimental Design:
FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability.
Results:
After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL.
Conclusions:
The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.
Molecular and Pathologic Characterization of YAP1-Expressing Small Cell Lung Cancer Cell Lines Leads to Reclassification as SMARCA4-Deficient Malignancies
Authors: Ng Jin , Cai Ling , Girard Luc , Prall Owen W.J. , Rajan Neeha , Khoo Christine , Batrouney Ahida , Byrne David J. , Boyd Danielle K. , Kersbergen Ariena J. , Christie Michael , Minna John D. , Burr Marian L. , Sutherland Kate D.
Published: January 2024

Purpose:

The classification of small cell lung cancer (SCLC) into distinct molecular subtypes defined by ASCL1, NEUROD1, POU2F3, or YAP1 (SCLC-A, -N, -P, or -Y) expression, paves the way for a personalized treatment approach. However, the existence of a distinct YAP1-expressing SCLC subtype remains controversial.

Experimental Design:

To better understand YAP1-expressing SCLC, the mutational landscape of human SCLC cell lines was interrogated to identify pathogenic alterations unique to SCLC-Y. Xenograft tumors, generated from cell lines representing the four SCLC molecular subtypes, were evaluated by a panel of pathologists who routinely diagnose thoracic malignancies. Diagnoses were complemented by transcriptomic analysis of primary tumors and human cell line datasets. Protein expression profiles were validated in patient tumor tissue.

Results:

Unexpectedly, pathogenic mutations in SMARCA4 were identified in six of eight SCLC-Y cell lines and correlated with reduced SMARCA4 mRNA and protein expression. Pathologist evaluations revealed that SMARCA4-deficient SCLC-Y tumors exhibited features consistent with thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UT). Similarly, the transcriptional profile SMARCA4-mutant SCLC-Y lines more closely resembled primary SMARCA4-UT, or SMARCA4-deficient non–small cell carcinoma, than SCLC. Furthermore, SMARCA4-UT patient samples were associated with a YAP1 transcriptional signature and exhibited strong YAP1 protein expression. Together, we found little evidence to support a diagnosis of SCLC for any of the YAP1-expressing cell lines originally used to define the SCLC-Y subtype.

Conclusions:

SMARCA4-mutant SCLC-Y cell lines exhibit characteristics consistent with SMARCA4-deficient malignancies rather than SCLC. Our findings suggest that, unlike ASCL1, NEUROD1, and POU2F3, YAP1 is not a subtype defining transcription factor in SCLC.

See related commentary by Rekhtman, p. 1708
Table S4 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Table S4: Gene expression differences in epithelial cells, endothelial cells and fibroblasts of BRCA2 mutation carrier compared to non-carrier.
Table S3 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Table S3: Gene expression differences in epithelial cells, endothelial cells and fibroblasts of BRCA1 mutation carrier compared to non-carrier.
Source data file 1 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Contains unprocessed images and raw data used to generate graphs
Figure S2 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Figure S2: Expression differences of select ERα-responsive and hormone sensitive cell marker genes in BRCA1 or BRCA2 mutation carriers compared to non-carriers.
FIGURE 8 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Immortalized breast epithelial cells from BRCA1 or BRCA2 mutation carriers overexpressing PIK3CAH1047R mutant generate tumors in NSG mice. A, Frequency of tumor formation. Number of animals injected and those that developed tumors in each of the experiments are shown. For unknown reasons, tumors in BRCA1+PIK3CAH1047R cells injected animals in the second experimental series were flatter and appeared only after 12 weeks of tumor cell injection but were histologically breast epithelial cell-derived tumors. B, Tumor growth patterns. Although tumor cell implant site contained a nodule till 6 weeks after implant, those measurements were not taken into consideration as such a nodule is likely due to Matrigel and subsequently disappeared in case of non-carrier cells carrying PIK3CAH1047R mutation. Nodules that remained past 6 weeks or appeared subsequently were considered as tumors. C, IHC characterization of tumors. Tumors developed from BRCA1 mutant cells show heterogenous expression patterns of luminal markers ERα and GATA3. Tumors developed from BRCA2 mutation carriers are ERα-negative but expressed variable levels of GATA3.
FIGURE 7 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Immortalized BRCA1- or BRCA2-mutant cells display elevated NFκB activity. A, PIK3CAH1047R distinctly influences differentiation properties of immortalized BRCA1 and BRCA2 mutation carriers. Vector control or PIK3CAH1047R-expressing breast epithelial cell lines from non-carriers (KTB34 and KTB39) and BRCA1 or BRCA2 mutation carriers were stained with indicated antibodies and characterized by flow cytometry (n = 3). Representative data are shown. PIK3CAH1047R robustly increased EpCAM expression and increased differentiated phenotype of BRCA1-mutant cells. CD49f+/EpCAM+ cells increased from 12% to 36% whereas CD49f+/EpCAM− cells decreased from 80% to 34% upon PIK3CAH1047R overexpression. B, BRCA1 mutant cells display elevated phosphorylation of p65, a NFκB subunit, which indirectly suggests activation of NFκB. Expression levels of PIK3CA in cells transduced with PIK3CA-mutant virus are shown. Regular growth media condition had to be used to detect PIK3CA-mutant overexpression because of robust induction of endogenous PIK3CA upon serum starvation. An antibody that preferentially recognizes PIK3CAH1047R mutant was used in the Western blot analysis. The same extract was used to measure pAKT(S473) and AKT to ensure that PIK3CAH1047R is functional in transduced cells. C, Approximately 30% of breast cancers in BRCA1 or BRCA2 mutation carriers carry PIK3CA mutations. Data were generated using cBioportal (54). D, Immortalized BRCA1 or BRCA2 mutant cells but not cells from non-carriers are sensitive to DMAPT. PIK3CAH1047R-overexpressing cells, irrespective of BRCA mutation status, were sensitive to DMAPT (statistical test used—one-way ANOVA). E, Immortalized cell lines from BRCA1 or BRCA2 mutation carriers express higher levels of MIR205HG (statistical test used—unpaired t test). Note that PIK3CAH1047R, which robustly induced differentiation of BRCA1-mutant cells, reduced MIR205HG levels in these cells. P values, *<0.05; **<0.01. Immortalized BRCA1/2-mutant cells express BRCA1 and BRCA2 transcripts at variable levels with BRCA2-mutant cells expressing significantly higher levels of BRCA1 transcripts compared with non-carrier cells (statistical test used—one-way ANOVA).
FIGURE 6 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Breast epithelial cells of BRCA1 and BRCA2 mutation carriers display distinct signaling pathway activation. Signaling pathways active in epithelial cells of BRCA1 (top two) and BRCA2 (bottom 2) compared with epithelial cells of non-carriers are shown.
FIGURE 2 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Overlay of BRCA1 and BRCA2 single-cell map over the single-cell map of breast tissues from non-carriers. A, Overlay of BRCA1 carrier-derived single-cell atlas with that of non–carrier-derived atlas. Non–carrier-derived atlas has been described previously (10). Few minor clusters found in non-carrier atlas show limited overlap with BRCA1 mutation carrier-derived clusters (clusters 18, 20, and 21, oval in the center). All three are epithelial cell clusters. B, Overlay of BRCA2-derived single-cell atlas with non–carrier-derived atlas. Clusters 15 and 20, both epithelial clusters, are underrepresented in BRCA2 carriers. C, Overlay of BRCA1 carrier-derived single-cell atlas with that of BRCA2 carrier-derived single-cell atlas. A minor cluster (cluster 19) is underrepresented in BRCA1 compared with BRCA2 carrier-derived single-cell atlas.
FIGURE 1 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Single-cell atlas of breast tissues of BRCA1 and BRCA2 mutation carriers compared with breast tissues of non-carriers. A, tSNE plots showing single-cell map of the breast tissues from the right and left breast tissues of a 45-year-old BRCA1 mutation carrier. B, tSNE plots showing single-cell map of the breast tissues from 67 years old (left) and 39 years old (right) BRCA2 mutation carriers. C, UMAP showing integrated data from all samples sequenced. D, UMAP of individual sample overlay with cluster numbers.
Orbital Edema Secondary to a Sphenoidal Mass as the Presenting Symptom of High-Risk Precursor B-Cell Acute Lymphoblastic Leukemia
Authors: Lo Cody , Aziz Rem , Denstedt James T. , Feng Zhao X. , Fournier Annick V.
Published: January 2024

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, known to present with ocular manifestations in rare cases. Case Presentation: We describe the case of a 9-year-old previously healthy male who developed a 2-day history of periocular swelling and was found on MRI to have a large sphenoidal mass. Further work up showed involvement of the spinal cord, iliac crests, and kidneys. His initial blood work showed no hematological abnormalities. A bone marrow biopsy taken from the iliac crest demonstrated >90% B lymphoblasts and flow cytometry was positive for CD19. Overall, his investigations were consistent with a diagnosis of precursor B-cell ALL (pre B-ALL). His neuro-ophthalmic exam showed right-sided subtle periocular edema, decreased palpebral fissure height, and proptosis. Posterior exam showed mild nasal elevation of the right optic disc without vessel obscuration and mild tortuosity of the peripheral vessels. He otherwise had no overt signs of afferent or efferent dysfunction despite the proximity of the mass to his optic nerve and globe. Conclusion: This case demonstrates that high-risk pre B-ALL, a childhood cancer not commonly associated with orbital manifestations, can present with orbital edema and normal leukocyte count in an otherwise healthy child.
Pathological Complete Response to Pembrolizumab plus Axitinib Combination following Serious Immune-Related Adverse Events in an Advanced Renal Cell Carcinoma Patient with a History of Rheumatoid Arthritis
Authors: Bergamini Marco , Dalla Volta Alberto , Valcamonico Francesca , Caramella Irene , Buffoni Martina , Munari Enrico , Fisogni Simona , Zanotelli Tiziano , Suardi Nazareno Roberto , Berruti Alfredo
Published: January 2024

Immune checkpoint inhibitors (ICIs)-based combinations have improved survival outcomes of advanced renal cell carcinoma (RCC) patients and are currently recommended as first-line treatment options. Rheumatoid arthritis (RA) is a systemic autoimmune disease (AD) of unknown etiology characterized by a chronic inflammatory process involving joints and extra-articular organs. Patients with AD are usually excluded from large randomized clinical trials investigating immunotherapeutic drugs. Therefore, little is known about clinical outcomes of patients with a history of RA treated with ICIs in real-world practice. In the present study, we report the clinical outcome of an advanced RCC patient with a history of RA treated with pembrolizumab in combination with axitinib. The patient experienced serious immune-related adverse events (irAEs) and achieved pathological complete response following only one ICI administration. Our case report shows that ICI-based combinations can be administered efficaciously in advanced RCC patients with a history of AD. However, a close monitoring of these patients is required, given the risk of irAEs and clinical exacerbations of symptoms associated with the preexisting AD. Moreover, prospective clinical data are needed to assess the hypothesis of a correlation between the onset of irAEs and AD flares and responses and survival outcomes to ICIs.
National Trends in Allergic Rhinitis and Chronic Rhinosinusitis and COVID-19 Pandemic-Related Factors in South Korea, from 1998 to 2021
Authors: Lee Hojae , Park Jaeyu , Lee Myeongcheol , Kim Hyeon Jin , Kim Minji , Kwon Rosie , Lee Seung Won , Koyanagi Ai , Smith Lee , Kim Min Seo , Rhee Sang Youl , Cho Joong Ki , Kim Sunyoung , Rahmati Masoud , Yon Dong Keon
Published: January 2024

Introduction: Existing studies provide insights into the prevalence and environmental factors associated with allergic rhinitis (AR) and chronic rhinosinusitis (CRS) globally. However, limitations still persist in these studies, particularly regarding cohort sizes and the duration of follow-up periods, indicating a need for more comprehensive and long-term research in these fields. Our study aimed to investigate the prevalence, long-term trends, and underlying factors of these conditions in the general population of adult participants (≥19 years) in Korea. Method: We analyzed data from adult participants (≥19 years) from the Korea National Health and Nutrition Examination Survey (KNHANES) study to determine the prevalence of AR and CRS from 1998 to 2021. To analyze prevalence trends before and during the COVID-19 pandemic, we employed a weighted linear regression model and obtained β-coefficients with 95% confidence intervals (CI). Results: Between 1998 and 2021, over a span of 24 years, the comprehensive KNHANES study included 146,264 adult participants (mean age: 47.80 years, standard deviation: 16.49 years; 66,177, 49.3% men). The prevalence of AR and CRS increased from 1998 to 2021, with AR prevalence rising from 5.84% (95% CI, 5.57–6.10) in 1998–2005 to 8.99% (8.09–9.91) in 2021 and CRS from 1.84% (1.70–1.97) in 1998–2005 to 3.70% (3.18–4.23) in 2021. However, the increasing trend has slowed down during the COVID-19 pandemic era. Conclusions: The significance of continuous monitoring and focused interventions for AR and CRS is underscored by this study. The observed deceleration in the rising prevalence of AR and CRS during the pandemic indicates the possibility of beneficial impacts from lifestyle modifications triggered by the pandemic. These findings call for additional research to explore potential protective effects in greater depth.
Management of Sinistral Portal Hypertension after Pancreaticoduodenectomy
Authors: Mansour Nabeel , Sirtl Simon , Angele Martin K. , Wildgruber Moritz
Published: January 2024

Background: Sinistral, or left-sided, portal hypertension (SPH) is a rare cause of upper gastrointestinal (GI) hemorrhage resulting from obstruction of the splenic vein. Venous drainage from the spleen via collaterals can result in venous hemorrhage into both the retroperitoneal and intra-abdominal spaces due to increased venous blood pressure in peripancreatic and gastroduodenal vasculature. SPH can occur secondary to pancreatitis with thrombosis of the splenic vein. Another possible cause is the surgical ligation of the splenic vein as part of pancreaticoduodenectomy (PD). Although splenectomy has been traditionally considered as the treatment of choice to relieve venous hypertension, individual concepts for each patient have to be developed. Considering the venous collateral drainage pathways, a comprehensive approach involving surgical, endoscopic, and interventional radiology interventions may be necessary to address the underlying cause of variceal bleeding. Among these approaches, splenic artery embolization (SAE) has demonstrated efficacy in mitigating the adverse effects associated with elevated venous outflow pressure. Summary: This review summarizes key imaging findings in SPH patients after PD and highlights the potential of minimally invasive embolization for curative treatment of variceal hemorrhage. Key Messages: (i) SPH is a potential consequence after major pancreas surgery. (ii) Collateral flow can lead to life-threatening abdominal bleeding. (iii) Depending on the origin and localization of the bleeding, a dedicated management is required, frequently involving interventional radiology techniques.
Dapagliflozin Does Not Protect against Adriamycin-Induced Kidney Injury in Mice
Authors: Cha Jin Joo , Park Hye-jin , Yoo Ji Ae , Ghee Jungyeon , Cha Dae Ryong , Kang Young Sun
Published: January 2024

Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors target SGLT2 in renal proximal tubules and promote glycosuria in type 2 diabetes mellitus in humans and animal models, resulting in reduced blood glucose levels. Although clinical trials have shown that SGLT2 inhibitors attenuate the progression of chronic kidney disease, there have been concerns regarding SGLT2-induced acute kidney injury. In this study, we investigated the effect of SGLT2 inhibitors on adriamycin-induced kidney injury in mice. Methods: Seven-week-old balb/c mice were injected with adriamycin 11.5 mg/kg via the tail vein. Additionally, dapagliflozin was administered via gavage for 2 weeks. The mice were divided into five groups: vehicle, dapagliflozin 3 mg/kg, adriamycin, adriamycin plus dapagliflozin 1 mg/kg, and adriamycin plus dapagliflozin 3 mg/kg. Results: Adriamycin injection reduced the body weight and food and water intakes. Dapagliflozin also decreased the body weight and food and water intakes. Fasting blood glucose and urine volume were not altered by either adriamycin or dapagliflozin. Once adriamycin-induced kidney injury had developed, there were no differences in systolic blood pressure among the groups. Dapagliflozin did not alleviate proteinuria in adriamycin-induced kidney injury. Adriamycin induced significant glomerular and interstitial injury, but dapagliflozin did not attenuate these changes in renal injury. Interestingly, SGLT2 expressions were different between the cortex and medulla of kidneys by dapagliflozin treatment. Dapagliflozin increased SGLT2 expression in medulla, not in cortex. Conclusion: Dapagliflozin had no effect on proteinuria or inflammatory changes such as glomerular and tubular damages in adriamycin-induced kidney injury. Our study suggests that dapagliflozin does not protect against adriamycin-induced kidney injury. More experimental studies regarding the effects of SGLT2 inhibitors on various kidney diseases are needed to clarify the underlying mechanisms.
Modelos de explicação científica, inferência da melhor explicação e a história da dupla-hélice do DNA
Authors: Sardi Gabriel Chiarotti
Published: January 2024

O presente artigo objetiva realizar um estudo de caso que aplica o modelo de inferência da melhor explicação (inference to the best explanation, IBE) de Peter Lipton ao episódio histórico da construção do modelo de dupla-hélice do DNA, no século XX. Procura avaliar a eficiência de tal modelo quando confrontado com a história da ciência e em que medida é capaz de rivalizar com ou superar outros modelos de explicação já consolidados na literatura de filosofia da ciência, tais como os modelos nomológico-dedutivo e indutivo-estatístico de Carl Hempel, o modelo de relevância estatística de Wesley Salmon, ou, ainda, o modelo pragmático de explicação de Bas van Fraassen. Por fim, a conclusão apresentada é que o modelo de inferência da melhor explicação se mostra mais eficaz para ilustrar esse episódio da história da genética do que as outras propostas filosóficas analisadas.
efectos de las patentes de materiales genéticos en la investigación científica-biológica. Un análi-sis legal y filosófico
Authors: Salvi Nicolás
Published: January 2024

En este trabajo nos proponemos analizar los efectos que tienen en la genética y la microbiología la aplicación de las leyes de propiedad intelectual, en su forma de derechos de patentes. A través del estudio de la historia de estas áreas de la biología, argumentamos porque nos parece errónea, desde el punto de vista jurídico y filosófico, la patentabilidad de los genes y genomas que provienen total o parcialmente de la naturaleza. Demostraremos cómo esta práctica legal acarrea una gran cantidad de valores no-epistémicos y concepciones ético-políticas que afectan de lleno a las investigaciones biológicas que forman parte del negocio biotecnológico y generan un desmesurado choque de cosmovisiones con culturas ajenas al sistema liberal-capitalista.
La funzione anti-dialogica. Condizioni di incongruenza negli scambi di battute della poesia italiana del Novecento
Authors: Martini Giulia
Published: January 2024

A análise das trocas presentes nos livros de poesia italiana do século XX mostrou um recurso horizontal ao expediente do dialogismo em chave disfuncional e pragmaticamente patológica, entre comunicações gagas, interrompidas, conflitantes ou sem sentido; o diálogo, em outras palavras, não se manifesta como uma adesão íntima a uma comunicação consonantal e recíproca, mas se refere ao mau funcionamento da própria comunicação. Do Canti di Castelvecchio  (1903) de Giovanni Pascoli à Composita solvantur  (1994) de Franco Fortini, os episódios líricos que contêm interações verbais parecem originar-se e remeter a uma 'função antidialógica': proliferam as conversas patológicas, as falhas posicionais, as interações conflituosas, as falhas pragmáticas; os falantes tendem a interagir de forma disfuncional e deslógica, abundam mal-entendidos, silêncios e reticências, falta cooperação, como se os atores fossem construídos para não se comunicar. A presente contribuição visa, assim, a enquadrar a função antidialógica que acabamos de esboçar através da comparação entre algumas amostras textuais e os principais módulos de incongruência pragmática, introduzidos primeiro a partir de uma classificação dos atos de fala, depois através do aprofundamento de um poema paradigmático.