bluuebunny/crossref_metadata_2025 huggingface dataset:
EXAMINING THE DETERMINANTS OF THE LEVEL OF INFORMALIZATION OF MICRO-ENTERPRISES IN A DEVELOPMENTAL URBAN CONTEXT
Authors: OMOLOBA JOSEPH , ESTAY CHRISTOPHE
Published: March 2023

This study aims to identify the key determinants of the level of informalization of micro-enterprises in Nigeria. We seek to understand the motives of entrepreneurs doing business in different segments of the informal sector and to clarify further the relationship between formal and informal economic activity. To fill the research gap, we developed a theoretical framework that focuses on a decision matrix regarding the level of informality. The quantitative approach involved a sample of 120 entrepreneurs operating in the Nigerian informal economy. Our results show that institutional constraints significantly affect the decision to engage in the informal sector. The institutional constraint is related to ambiguity in tax assessment and business registration policies and procedures, including the mismanagement of those in power. We conclude that the presence of informal firms is not always as harmful as it sometimes is considered to be.
Is intestinal transport dysfunctional in COVID-19-related diarrhea?
Authors: Sandle Geoffrey I. , Herod Morgan R. , Fontana Juan , Lippiat Jonathan D. , Stockley Peter G.
Published: March 2023

Diarrhea, often severe, is a recognized and frequently early symptom during acute COVID-19 infection and may persist or develop for the first time in patients with long-COVID, with socioeconomic consequences. Diarrheal mechanisms in these cases are poorly understood. There is evidence for disruption of intestinal epithelial barrier function and also for changes in the gut microbiome, which is critical for gut immunity and metabolism. Whether the SARS-CoV-2 virus has adverse effects on intestinal transport proteins is unclear. However, the ability of the virus to inhibit expression and activity of an aldosterone-regulated epithelial sodium (Na+) channel (ENaC) present in human distal colon, which is responsible for Na+ and water salvage, points to possible disruption of other intestinal transport proteins during COVID-19 infection. In this Perspective, we develop this idea by highlighting possible intestinal transport protein targets for the SARS-CoV-2 virus and discussing how their interactions might be explored in the laboratory.
PPAR-γ Activation Alleviates Osteoarthritis through Both the Nrf2/NLRP3 and PGC-1α/Δψm Pathways by Inhibiting Pyroptosis
Authors: Feng Zhencheng , Huang Qiuxiang , Zhang Xingliang , Xu Pengfei , Li Siming , Ma Dongli , Meng Qingqi
Published: March 2023

Osteoarthritis (OA) is a common degenerative joint disease with a gradually increasing morbidity in the aging and obese population. Emerging evidence has implicated pyroptosis in the etiology of OA and it may be recognized as a therapeutic target in OA. We have previously reported regarding another disease that peroxisome proliferator-activated receptor gamma (PPAR-γ) activation exerts an anti-inflammatory effect by suppressing the nucleotide-binding and oligomerization domain-like receptor containing protein (NLRP) 3 inflammasome. However, the relationship between PPAR-γ and NLRP3-mediated pyroptosis in OA cartilage and its underlying mechanisms is fully unclear. In this study, we found that the level of NLRP3-mediated pyroptosis in severe lateral femoral condyle cartilage wear in the knee of an OA patient was significantly higher than that in the mild lateral femoral condyle cartilage wear areas. Moreover, in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced primary chondrocytes and knee OA rat models, we demonstrated that activation of PPAR-γ by pioglitazone (Piog) attenuated LPS/ATP-induced chondrocyte pyroptosis and arthritis. These effects were partially counteracted by either blocking the nuclear factor erythroid-2-related factor (Nrf2)/NLRP3 or PGC1-α/Δψm signaling pathway. Simultaneous depression of these two signaling pathways can completely abrogate the protective effects of Piog on OA and chondrocytes. Taken together, Piog protects OA cartilage against pyroptosis-induced damage by simultaneously activating both the Nrf2/NLRP3 and PGC-1α/Δψm pathways, which enhances antioxidative and anti-inflammatory responses as well as mitochondrial biogenesis. Therefore, Piog may be a promising agent for human OA cartilage damage in future clinical treatments.
Small Bowel Obstruction in Postpartum Vaginal Delivery due to Prior Abdominal Adhesions Case Report
Authors: Yang Liubin , Kao Lydia
Published: March 2023

Intestinal obstruction rarely occurs after uncomplicated vaginal deliveries. Here, we present a case of a multiparous woman with a history of prior appendectomy presenting with generalized, nonspecific abdominal pain that was out of proportion to exam findings. Initial abdominal X-ray was nonspecific, and subsequent computed tomography (CT) abdomen showed closed small bowel obstruction requiring surgical repair. We present a case of intestinal obstruction occurring within 24 hours of uncomplicated vaginal delivery with a risk factor of a prior appendectomy surgery and the use of CT abdomen and pelvis to expedite diagnose.
On the Multimodal Resolution of a Search Sequence in Virtual Reality
Authors: Klowait Nils
Published: March 2023

In virtual reality (VR), participants may not always have hands, bodies, eyes, or even voices—using VR helmets and two controllers, participants control an avatar through virtual worlds that do not necessarily obey familiar laws of physics; moreover, the avatar’s bodily characteristics may not neatly match our bodies in the physical world. Despite these limitations and specificities, humans get things done through collaboration and the creative use of the environment. While multiuser interactive VR is attracting greater numbers of participants, there are currently few attempts to analyze the in situ interaction systematically. This paper proposes a video-analytic detail-oriented methodological framework for studying virtual reality interaction. Using multimodal conversation analysis, the paper investigates a nonverbal, embodied, two-person interaction: two players in a survival game strive to gesturally resolve a misunderstanding regarding an in-game mechanic—however, both of their microphones are turned off for the duration of play. The players’ inability to resort to complex language to resolve this issue results in a dense sequence of back-and-forth activity involving gestures, object manipulation, gaze, and body work. Most crucially, timing and modified repetitions of previously produced actions turn out to be the key to overcome both technical and communicative challenges. The paper analyzes these action sequences, demonstrates how they generate intended outcomes, and proposes a vocabulary to speak about these types of interaction more generally. The findings demonstrate the viability of multimodal analysis of VR interaction, shed light on unique challenges of analyzing interaction in virtual reality, and generate broader methodological insights about the study of nonverbal action.
Experimental Study on the Smoke Temperature Decrease near Natural Vents Induced by Air Entrainment in a Tunnel Fire
Authors: Yu Hai , Yang Yunhao , Yin Jiyao , Deng Peng , Sun Yanlong , Zhou Lin , Liu Zhenguo
Published: March 2023

Previous studies have shown that there is a large difference in the temperature of smoke in the upstream and downstream of a vertical shaft, but no quantitative study on the subject has been conducted. In this paper, a model experimental test was conducted to study the effect of a natural vertical shaft on the distribution of smoke temperature in tunnel fires. A laser sheet was used as an assisting tool to show the smoke flow field. A series of tests were conducted with shaft heights varying from 0.2 m to 1.2 m and a heat release rate (HRR) of 9 kW, 17 kW, 29 kW, and 65 kW. The entrainment phenomenon around the vertical shaft was analyzed, and the results showed that the amount of fresh air entrainment is the main reason for the temperature decrease in upstream and downstream smoke temperatures. Based on the experimental results, an empirical model for predicting the amount of fresh air entrainment and a prediction model of the downstream smoke temperature were proposed, and the predicted values are in good agreement with the experimental values.
Supplementary materials and methods and Supplementary figure legends revised from Tumor-Infiltrating B Lymphocyte Profiling Identifies IgG-Biased, Clonally Expanded Prognostic Phenotypes in Triple-Negative Breast Cancer
Authors: Harris Robert J. , Cheung Anthony , Ng Joseph C.F. , Laddach Roman , Chenoweth Alicia M. , Crescioli Silvia , Fittall Matthew , Dominguez-Rodriguez Diana , Roberts James , Levi Dina , Liu Fangfang , Alberts Elena , Quist Jelmar , Santaolalla Aida , Pinder Sarah E. , Gillett Cheryl , Hammar Niklas , Irshad Sheeba , Van Hemelrijck Mieke , Dunn-Walters Deborah K. , Fraternali Franca , Spicer James F. , Lacy Katie E. , Tsoka Sophia , Grigoriadis Anita , Tutt Andrew N.J. , Karagiannis Sophia N.
Published: March 2023

Supplementary materials and methods and Supplementary figure legends revised
Supplementary Table S7 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Table S7: GO analysis of the BioID assay.
Figure S2 from Tumor Mutational Burden as a Predictor of Survival with Durvalumab and/or Tremelimumab Treatment in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Wildsmith Sophie , Li Weimin , Wu Song , Stewart Ross , Morsli Nassim , Raja Rajiv , Zhang Qu , Ye Jiabu , He Philip , Shetty Jagdish , Yovine Alejandro , Holoweckyj Nicholas , Real Katia , Walker Jill , Wrona Magdalena , de los Reyes Melissa , Barker Craig , Whiteley Jessica , Haddad Robert , Licitra Lisa , Ferris Robert , Fayette Jérôme , Zandberg Dan P. , Siu Lillian L. , Mesía Ricard
Published: March 2023

FIG S2. Kaplan-Meier plot of OS in the durvalumab monotherapy, durvalumab plus tremelimumab and SoC treatment arms in the NLR ≤ 7 subgroup (A) and NLR > 7 subgroup (B) in EAGLE.
Supplementary Table S4 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Table S4: Hits from the genome-wide shRNA screen in αEPHA2-Cond cells.
Figure S1 from Tumor Mutational Burden as a Predictor of Survival with Durvalumab and/or Tremelimumab Treatment in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Authors: Wildsmith Sophie , Li Weimin , Wu Song , Stewart Ross , Morsli Nassim , Raja Rajiv , Zhang Qu , Ye Jiabu , He Philip , Shetty Jagdish , Yovine Alejandro , Holoweckyj Nicholas , Real Katia , Walker Jill , Wrona Magdalena , de los Reyes Melissa , Barker Craig , Whiteley Jessica , Haddad Robert , Licitra Lisa , Ferris Robert , Fayette Jérôme , Zandberg Dan P. , Siu Lillian L. , Mesía Ricard
Published: March 2023

FIG S1. TMB distribution in samples from HAWK and CONDOR (A) and EAGLE (B).
Supplementary Table S3 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Table S3: GO analysis of phosphorylated proteins differentially expressed in αEPHA2-Cond and cIgG-Tr cells.
Supplementary Table S3 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

Representativeness of Study Participants
Supplementary Materials and Methods1 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

-Supplementary Materials
Supplementary Table S1 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

All adverse events on trial
Figure S6 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Fig. S6. EPHA2, c-MET and EGFR levels in human tumors.
Supplementary Protocol S1 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

Study protocol
Figure S4 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Fig. S4. A. Heatmap of the shRNA screen hits that are enriched in the top 15 GO processesgenerated using GSEA software. B. Gene Set Enrichment Analysis plots of the top 15 GOprocess for the shRNA screen data produced by GSEA software used to generate the heatmap inA.
Figure S3 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Fig. S3. A. Correlation cluster for both the replicates and different timepoints of the screeningdata. B. Fold-change distribution from the normalized shRNA intensity for the αEPHA2-Condand cIgG-Tr cells at different time points. C. Precision-recall curves after applying BAGELalgorithm to the screening data. F measure provided in the inset represents the harmonic mean ofprecision & recall of the screen.
Supplementary Figure S5 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

Supplementary Figure 5. Comparison of outcomes between patients that were PD-L1 positive vs. negative A) Progression-free survival and B) Overall survival comparison
Figure S1 from A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2–Bispecific Antibody for Combination Cancer Therapy
Authors: El Zawily Amr , Vizeacoumar Frederick S. , Dahiya Renuka , Banerjee Sara L. , Bhanumathy Kalpana K. , Elhasasna Hussain , Hanover Glinton , Sharpe Jessica C. , Sanchez Malkon G. , Greidanus Paul , Stacey R. Greg , Moon Kyung-Mee , Alexandrov Ilya , Himanen Juha P. , Nikolov Dimitar B. , Fonge Humphrey , White Aaron P. , Foster Leonard J. , Wang Bingcheng , Toosi Behzad M. , Bisson Nicolas , Mirzabekov Tajib A. , Vizeacoumar Franco J. , Freywald Andrew
Published: March 2023

Fig. S1. The amino acid sequence of EPHA2 extracellular portion composed of ligand bindingdomain followed by sushi-like domain and two sequential fibronectin-like domains is highlyconserved among mammals.
Supplementary Figure S4 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

Supplementary Figure 4. Comparison of outcomes between patients treated with prior systemic therapies vs. not A) Progression-free survival and B) Overall survival comparison
Supplementary Figure S3 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

Supplementary Figure 3: Comparison of outcomes between patients treated with prior chemotherapy vs. not A) Progression-free survival and B) Overall survival comparison
Supplementary Figure S2 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

Consort diagram of the clinical trial.Abbreviations: OS, overall survival; PFS, progression-free survival
Supplementary Figure S1 from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

Study Schema. This is a single-arm, phase II trial combining durvalumab and cetuximab in patients with recurrent/metastatic HNSCC. Patients received the loading dose of cetuximab followed by the addition of durvalumab with weekly cetuximab doses. CT scans were done every eight weeks. Blood draws for correlatives occurred at screening, after the loading dose of cetuximab, and after the first dose of durvalumab and cetuximab combined.Abbreviations: CT, computed tomography; POD, progression of disease
Data from Durvalumab plus Cetuximab in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: An Open-label, Nonrandomized, Phase II Clinical Trial
Authors: Gulati Shuchi , Crist McKenzie , Riaz Muhammed Kashif , Takiar Vinita , Lehn Maria , Monroe Ilaina , Palackdharry Sarah , Kurtzweil Nicky , Jandarov Roman , Harun Nusrat , Wise-Draper Trisha M.
Published: March 2023

AbstractPurpose:
The efficacy of cetuximab is poor in metastatic head and neck squamous cell carcinoma (HNSCC). Cetuximab initiates natural killer (NK) cell–mediated antibody-dependent cellular cytotoxicity, with resultant recruitment of immune cells and suppression of antitumor immunity. We hypothesized that adding an immune-checkpoint inhibitor (ICI) could overcome this and lead to an enhanced antitumor response.
Patients and Methods:
A phase II study of cetuximab and durvalumab in metastatic HNSCC was conducted. Eligible patients had measurable disease. Patients who had received both cetuximab and an ICI were excluded. The primary endpoint was objective response rate (ORR) by RECIST 1.1 at 6 months.
Results:
As of April 2022, 35 patients enrolled, of whom 33 received at least 1 dose of durvalumab and were included in the response analysis. Eleven patients (33%) had received prior platinum-based chemotherapy, 10 an ICI (30%), and 1 patient (3%) cetuximab. ORR was 39% (13/33) with a median duration of response of 8.6 months [95% confidence interval (CI): 6.5–16.8]. Median progression-free and overall survivals were 5.8 months (95% CI: 3.7–14.1) and 9.6 months (95% CI: 4.8–16.3), respectively. There were 16 grade 3 treatment-related adverse events (TRAE) and one grade 4 TRAE, with no treatment-related deaths. Overall and progression-free survival did not correlate with PD-L1 status. NK cell cytotoxic activity was increased by cetuximab and further increased with the addition of durvalumab in responders.
Conclusions:
The combination of cetuximab and durvalumab demonstrated durable activity with a tolerable safety profile in metastatic HNSCC and warrants further investigation.
Supplementary Table S4 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: March 2023

Supplementary Table S4 shows the genes analyzed for significant differential expression in control vs. LPS and LPS vs. SAHA groups.
Supplementary Table S3 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: March 2023

Supplementary Table S3 shows the distribution of differentially methylated regions (DMRs) in the promoter region in control vs. LPS and LPS vs. SAHA comparisons.
Supplementary Table S2 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: March 2023

Supplementary Table S2 shows the list of metabolites that were examined among control, LPS, and LPS + SAHA groups after 3 and 24 h treatments.
Supplementary Fig. S3 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: March 2023

Supplementary Fig. S3 shows the correlation between RNA-seq gene expression and DNA-seq CpG methylation.
Supplementary Fig. S2 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: March 2023

Supplementary Fig. S2 shows the changes in metabolic profile after suberoylanilide hydroxamic acid (SAHA) treatment for 3 and 24 h.
Supplementary Fig. S1 from Metabolomic, DNA Methylomic, and Transcriptomic Profiling of Suberoylanilide Hydroxamic Acid Effects on LPS-Exposed Lung Epithelial Cells
Authors: Chou Pochung Jordan , Sarwar Md Shahid , Wang Lujing , Wu Renyi , Li Shanyi , Hudlikar Rasika R. , Wang Yujue , Su Xiaoyang , Kong Ah-Ng
Published: March 2023

Supplementary Fig. S1 shows the top metabolites regulated by suberoylanilide hydroxamic acid (SAHA) treatment in lipopolysaccharide (LPS)-treated BEAS-2B cells.
Supplementary Methods SM1 from Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing
Authors: Anaya Jordan , Sidhom John-William , Cummings Craig A. , Baras Alexander S.
Published: March 2023

Additional details on data processing and effects of genetic ancestry.
Table S3 from Systemic LRG1 expression in melanoma is associated with disease progression and recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L. M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C. J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: March 2023

Table S3 shows the patient characteristics PRADO
Supplemental Table ST2. TMB regression metrics for different ancestries. from Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing
Authors: Anaya Jordan , Sidhom John-William , Cummings Craig A. , Baras Alexander S.
Published: March 2023

All metrics are from cross validation with counts of all mutations, hotspots, and nonsynonymous mutations as the input. MAE: mean absolute error. MAE and Spearman rank-order correlation are calculated for samples with panel TMB greater than or equal to 5.
Supplemental Table ST1. Detection rates of somatic, exomic TMB > 10 (t) based on stratification by panel-derived TMB measures. from Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing
Authors: Anaya Jordan , Sidhom John-William , Cummings Craig A. , Baras Alexander S.
Published: March 2023

The detection rate of the observed true somatic, exomic TMB being greater than the threshold (t) of 10 based on the various panel derived measures as designated. The linear model and mixture model values are derived from the data in Figure 1 of the manuscript. ŷ: model prediction
Table S1 from Systemic LRG1 expression in melanoma is associated with disease progression and recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L. M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C. J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: March 2023

Table S1 shows an overview evaluated immuno-oncology markers by Olink proteomic assay
Supplemental Figure S2. Effect of ancestry on germline filtering and model fits. from Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing
Authors: Anaya Jordan , Sidhom John-William , Cummings Craig A. , Baras Alexander S.
Published: March 2023

(A) Numbers of germline variants which passed the different filtering criteria for different ancestries. (B) Model fits for models trained on the different cohorts for stringent tumor-only data. (C) Model fits for models trained on the different cohorts for permissive tumor-only data.
Supplemental Figure S1. Box plots of the data represented in Table 1. from Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing
Authors: Anaya Jordan , Sidhom John-William , Cummings Craig A. , Baras Alexander S.
Published: March 2023

Mean of the deviations represented as a dashed line.
Figure S4 from Systemic LRG1 expression in melanoma is associated with disease progression and recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L. M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C. J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: March 2023

Figure S4 shows the serum analysis using Olink proteomic assay
Data SD1 from Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing
Authors: Anaya Jordan , Sidhom John-William , Cummings Craig A. , Baras Alexander S.
Published: March 2023

The panel inputs in Data S1 contain all variants which fell within the coordinates of the respective panels and coverage WIGs and CDS and divided by the covered panel CDS size in Mb. As a result these counts include synonymous mutations as well as hotspots. Because germline data is potentially sensitive information we anonymized the sample names. Samples which had less than 400 germline counts in the 4 Mb region prior to filtering were excluded from the germline inputs.
Figure S1 from Systemic LRG1 expression in melanoma is associated with disease progression and recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L. M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C. J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: March 2023

Figure S1 shows a flowchart of patients OpACIN-neo study
Data from Systemic LRG1 expression in melanoma is associated with disease progression and recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L. M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C. J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: March 2023

Abstract
The response rates upon neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma are higher as compared to stage IV disease. Given that successful ICB depends on systemic immune response, we hypothesized that systemic immune suppression might be a mechanism responsible for lower response rates in late-stage disease, and also potentially with disease recurrence in early-stage disease. Plasma and serum samples of cohorts of melanoma patients were analyzed for circulating proteins using mass spectrometry proteomic profiling and Olink proteomic assay. A cohort of paired samples of patients with stage III that progressed to stage IV disease (n=64) was used to identify markers associated with higher tumor burden. Baseline patient samples from the OpACIN-neo study (n=83) and PRADO study (n=49; NCT02977052) were used as two independent cohorts to analyze whether the potential identified markers are also associated with disease recurrence after neoadjuvant ICB therapy. When comparing baseline proteins overlapping between patients with progressive disease and patients with recurrent disease, we found leucine-rich alpha-2-glycoprotein 1 (LRG1) to be associated with worse prognosis. Especially non-responder patients to neoadjuvant ICB (OpACIN-neo) with high LRG1 expression had a poor outcome with an estimated 36-month event-free survival of 14% as compared to 83% for non-responders with a low LRG1 expression (P = 0.014). This finding was validated in an independent cohort (P = 0.0021). LRG1 can be used as a biomarker to identify patients with high risk for disease progression and recurrence, and might be a target to be combined with neoadjuvant ICB.
Data from Probabilistic Mixture Models Improve Calibration of Panel-derived Tumor Mutational Burden in the Context of both Tumor-normal and Tumor-only Sequencing
Authors: Anaya Jordan , Sidhom John-William , Cummings Craig A. , Baras Alexander S.
Published: March 2023

Background:
Tumor mutational burden (TMB) has been investigated as a biomarker for immune checkpoint blockade (ICB) therapy. Increasingly, TMB is being estimated with gene panel–based assays (as opposed to full exome sequencing) and different gene panels cover overlapping but distinct genomic coordinates, making comparisons across panels difficult. Previous studies have suggested that standardization and calibration to exome-derived TMB be done for each panel to ensure comparability. With TMB cutoffs being developed from panel-based assays, there is a need to understand how to properly estimate exomic TMB values from different panel-based assays.
Design:
Our approach to calibration of panel-derived TMB to exomic TMB proposes the use of probabilistic mixture models that allow for nonlinear relationships along with heteroscedastic error. We examined various inputs including nonsynonymous, synonymous, and hotspot counts along with genetic ancestry. Using The Cancer Genome Atlas cohort, we generated a tumor-only version of the panel-restricted data by reintroducing private germline variants.
Results:
We were able to model more accurately the distribution of both tumor-normal and tumor-only data using the proposed probabilistic mixture models as compared with linear regression. Applying a model trained on tumor-normal data to tumor-only input results in biased TMB predictions. Including synonymous mutations resulted in better regression metrics across both data types, but ultimately a model able to dynamically weight the various input mutation types exhibited optimal performance. Including genetic ancestry improved model performance only in the context of tumor-only data, wherein private germline variants are observed.
Significance:
A probabilistic mixture model better models the nonlinearity and heteroscedasticity of the data as compared with linear regression. Tumor-only panel data are needed to properly calibrate tumor-only panels to exomic TMB. Leveraging the uncertainty of point estimates from these models better informs cohort stratification in terms of TMB.
The Death of Pyotr Ilyich Tchaikovsky: The Result of Treatment with Arsenic?
Authors: Dijkmans Ben , de Leeuw Peter
Published: March 2023

No abstract applicable.
Reversible Hypothalamic Obesity in a Girl with Suprasellar Tuberculoma
Authors: Rochtus Anne , Lagae Lieven , Jansen Katrien , De Somer Lien , Vermeulen François , de Zegher Francis
Published: March 2023

Introduction: Suprasellar tuberculoma are extremely rare in children and most of those patients present with headache, vomiting, visual disturbances, and hypofunction of the pituitary gland. In this case report, we present a girl with tuberculosis, who developed significant weight gain in combination with pituitary dysfunction, which recovered after antituberculosis treatment. Case Presentation: An 11-year old girl presented with headache, fever and anorexia that progressively evolved into an encephalopathic status with cranial nerves III and VI paresis. Brain MRI showed meningeal contrast capture along cranial nerves II (including optic chiasm), III, V and VI bilaterally and multiple contrast enhancing brain parenchyma lesions. Tuberculin skin test was negative but interferon-gamma release assay was positive. The clinical and radiological working diagnosis was consistent with tuberculous meningoencephalitis. Pulse corticosteroids for 3 days and quadruple antituberculosis therapy were started and the girl demonstrated obvious improvement of her neurological symptoms. However, after a few months of therapy she developed remarkable weight gain (+20 kg in 1 year) and growth arrest. Her hormone profile revealed insulin resistance (homeostasis model assessment-estimated insulin resistance [HOMA-IR] 6.8) despite putative growth hormone deficiency (circulating insulin-like growth factor-I [IGF-I] 104 μg/L [−2.4 SD]). Follow-up brain MRI showed a decrease in basal meningitis, but increased parenchymal lesions in the suprasellar region extending medially into the nucleus lentiformis, with now a voluminous tuberculoma at this site. Antituberculosis treatment was continued for a total of 18 months. The patient improved clinically, she regained her pre-illness Body Mass Index (BMI) SDS and her growth rate increased slightly. On the hormonal side, disappearance of insulin resistance (HOMA-IR 2.5) and an increase in IGF-I (175 μg/L, −1.4 SD) was noted, and her last brain MRI showed a remarkable volume reduction of the suprasellar tuberculoma. Conclusion: Suprasellar tuberculoma can have a very dynamic presentation during the active stage of the disease, which can be reversed by prolonged antituberculosis treatment. Previous studies showed that the tuberculous process can also cause long term and irreversible changes in the hypothalamic-pituitary axis. Prospective studies are however needed in the pediatric population to know the exact incidence and type of pituitary dysfunction.
Notas sobre opilões
Authors: Soares B. M.
Published: March 2023

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Uma nova espécie de tetracha (Col. Cicindelidae)
Authors: Lane Frederico
Published: March 2023

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As Práticas Pedagógicas no Ensino da Língua Alemã: Afetos Positivos
Authors: Campos Vanja Ramos Vieira de , Leite Sérgio Antônio da Silva
Published: March 2023

Este trabalho tem como objetivo analisar as práticas pedagógicas adotadas por  professores de língua alemã, de diversos estados do país, a partir das bases teóricas de Vigotski (2009 [1934]; 2018 [1926])e Wallon (1978 [1942]; 2010 [1941]), correlacionando-as às propostas de interações entre os sujeitos (aluno) e os diversos objetos de conhecimento (áreas e conteúdos escolares), no contexto da globalização. Dessa forma, abordamos a mediação do professor de alemão, levando em conta os elementos capazes de afetar positivamente o aluno e de promover sua aproximação e interesse pela língua alemã ou, ao contrário, o seu afastamento e aversão. A partir da aplicação de questionário elaborado com 11 questões fechadas, estabelecemos inferências a partir da correlação entre os registros e as possibilidades de afetar positivamente os alunos, no sentido de promover um movimento de aproximação dos alunos à língua alemã. Concluímos que o grupo de 85 docentes respondentes desenvolve práticas pedagógicas no ensino de alemão capazes de afetar positivamente seus alunos e, desse modo, alcançar resultados de sucesso. Destaca-se a abordagem de temas socioculturais associados às expectativas de desempenho linguístico e às implicações para a vida social do aluno.
A mente corporificada: como os gestos revelam a fluência conceptual no processo de aprendizagem de alemão como língua estrangeira
Authors: Barbosa Adriana Fernandes
Published: March 2023

Neste artigo, pretendo demonstrar como estruturas cognitivas subjacentes aos verbos (in)separáveis do alemão podem ser reveladas pelos gestos produzidos por uma professora bilíngue alemão/português e duas alunas brasileiros durante uma aula de alemão como língua estrangeira. A aula foi filmada e os gestos foram posteriormente anotados de acordo com o Sistema de Anotação Linguística para Gestos (LASG). A análise multimodal das interações forneceu evidências empíricas do pensamento conceptual corporificado, uma vez que os gestos das participantes retrataram esquemas imagéticos e mapeamentos metafóricos subjacentesaosverbos estudados, indicando que essas estruturas estão cognitivamente ativas para as participantes durante a interação. Além disso, a análise dos gestos ajuda a esclarecer alguns aspectos cognitivos inerentes ao processo de aprendizagem de L2, o que corrobora a inclusão de conceitos como competência metafórica e fluência conceitual nas discussões sobre o ensino e aprendizagem de L2.
Methylation-Based Biological Age and Hypertension Prevalence and Incidence
Authors: Kresovich Jacob K. , Sandler Dale P. , Taylor Jack A.
Published: March 2023

Background:

Hypertension is common in older individuals and is a major risk factor for cardiovascular disease. Blood DNA methylation profiles have been used to derive metrics of biological age that capture age-related physiological change, disease risk, and mortality. The relationships between hypertension and DNA methylation-based biological age metrics have yet to be carefully described.

Methods:

Among 4419 women enrolled in the prospective Sister Study cohort, DNA methylation data generated from whole blood samples collected at baseline were used to calculate 3 biological age metrics (PhenoAgeAccel, GrimAgeAccel, DunedinPACE). Women were classified as hypertensive at baseline if they had high blood pressure (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) or reported current use of antihypertensive medication. New incident cases of hypertension during follow-up were identified via self-report on annual health questionnaires.

Results:

All 3 DNA methylation metrics of biological age were positively associated with prevalent hypertension at baseline (per 1-SD increase; PhenoAgeAccel, adjusted odds ratio, 1.16 [95% CI, 1.05–1.28]; GrimAgeAccel, adjusted odds ratio, 1.28 [95% CI, 1.14–1.45]; DunedinPACE, adjusted odds ratio, 1.16 [95% CI, 1.03–1.30]). Among 2610 women who were normotensive at baseline, women with higher biological age were more likely to be diagnosed with incident hypertension (per 1-SD increase; PhenoAgeAccel, adjusted hazard ratio, 1.09 [95% CI, 0.97–1.23]; GrimAgeAccel, adjusted hazard ratio, 1.16 [95% CI, 0.99–1.36]; DunedinPACE, adjusted hazard ratio, 1.16 [95% CI, 1.01–1.33]).

Conclusions:

Methylation-based biological age metrics increase before a hypertension diagnosis and appear to remain elevated in the years after clinical diagnosis and treatment.
Carotid Artery Stiffness Mechanisms Are Associated With End Organ Damage and All‐Cause Mortality: MESA (Multi‐Ethnic Study of Atherosclerosis)
Authors: Pewowaruk Ryan , Korcarz Claudia , De Boer Ian , Kestenbaum Bryan , Heckbert Susan R. , Tedla Yacob G. , Gepner Adam D.
Published: March 2023

Background

Arterial stiffness can be separated into 2 main mechanisms: (1) load‐dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between stiffness mechanisms and end organ damage is unknown.

Methods and Results

MESA (Multi‐Ethnic Study of Atherosclerosis) participants with carotid ultrasound were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 mm Hg blood pressure with participant‐specific models. Load‐dependent stiffness was the difference of total and structural stiffness. Associations with incident chronic kidney disease (CKD), dementia, and mortality were assessed with adjusted Cox models. During 14.3±4.8 years of follow‐up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (hazard ratio [HR], per 1 m/s, 1.04 [95% CI, 1.01–1.08],
P
=0.02) and dementia (HR, 1.06 [95% CI, 1.01–1.12],
P
=0.03) but not CKD (HR, 1.03 [95% CI, 0.98–1.08],
P
=0.33). Structural cPWV was significantly associated with mortality (HR, 1.04 [95% CI, 1.00–1.08],
P
=0.04) but not CKD (HR, 1.00 [95% CI, 0.94–1.05],
P
=0.86) or dementia (HR, 1.06 [95% CI, 0.99–1.13],
P
=0.06). Load‐dependent cPWV was significantly associated with CKD (HR, 1.38 [95% CI, 1.17–1.63],
P
<0.001) but not mortality (HR, 1.11 [95% CI, 0.99–1.25],
P
=0.07) or dementia (HR, 1.14 [95% CI, 0.94–1.38],
P
=0.19).

Conclusions

The mechanisms of arterial stiffness were associated with all‐cause mortality and CKD. Structural stiffness was associated with all‐cause mortality, and load‐dependent stiffness was associated with CKD. Total stiffness was associated with dementia but load‐dependent and structural stiffness were not.
Stage 1 Hypertension and the 10‐Year and Lifetime Risk of Cardiovascular Disease: A Prospective Real‐World Study
Authors: Peng Xinyi , Jin Cheng , Song Qirui , Wu Shouling , Cai Jun
Published: March 2023

Background

The 10‐year and lifetime cardiovascular disease risk in the population with stage 1 hypertension and the effects of recovery from and progression of stage 1 hypertension remain undetermined.

Methods and Results

This prospective cohort study included 96 268 individuals with blood pressure measurements obtained in 2006 and again in 2010. The 10‐year cardiovascular disease risk was estimated using the multivariable Cox proportional hazards model, and the lifetime risk was calculated using a modified survival analysis that accounted for the competing risk of death. Stage 1 hypertension was detected in 30.83% of the cohort. The 10‐year cardiovascular disease risk was 2.80%, and the lifetime risk was 16.61%. Compared with the normal blood pressure group, the stage 1 hypertension group had a 35% higher 10‐year risk (hazard ratio [HR], 1.35 [95% CI, 1.19–1.52]) and a 36% higher lifetime risk (HR, 1.36 [95% CI, 1.25–1.49]). By 2010, 12.57% of the participants with stage 1 hypertension had progressed to stage 2, with a significant 156% increase in 10‐year risk (HR, 2.56 [95% CI, 2.11–3.11]) and an increased lifetime risk of 129% (HR, 2.29 [95% CI, 1.89–2.77]). There was no appreciable change in risk in those with stage 1 hypertension whose blood pressure returned to the normal‐elevated range.

Conclusions

Stage 1 hypertension was associated with a significant increase in 10‐year and lifetime cardiovascular disease risk. Progression to stage 2 hypertension was associated with a marked increase in lifetime risk. The current guidelines require revision to promote early detection and appropriate management of blood pressure.