bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: González-Muñoz Teresa , Di Giannatale Angela , García-Silva Susana , Santos Vanesa , Sánchez-Redondo Sara , Savini Claudia , Graña-Castro Osvaldo , Blanco-Aparicio Carmen , Fischer Suzanne , De Wever Olivier , Creus-Bachiller Edgar , Ortega-Bertran Sara , Pisapia David J. , Rodríguez-Peralto Jose L. , Fernández-Rodríguez Juana , Pérez-Portabella Cleofé Romagosa , Alaggio Rita , Benassi Maria Serena , Pazzaglia Laura , Scotlandi Katia , Ratner Nancy , Yohay Kaleb , Theuer Charles P. , Peinado Héctor
Published: September 2023

AbstractPurpose:
Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGFβ coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs.
Experimental Design:
ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell–specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis, were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models.
Results:
ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma-circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis.
Conclusions:
Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease.
Data from A Novel HOXA10-Associated 5 Gene-Based Prognostic Signature for Stratification of Short-Term Survivors of Pancreatic Ductal Adenocarcinoma
Authors: Kisling Sophia G. , Atri Pranita , Shah Ashu , Cox Jesse L. , Sharma Sunandini , Smith Lynette M. , Ghersi Dario , Batra Surinder K.
Published: September 2023

Abstract
Purpose: Despite the significant association of molecular subtypes with poor prognosis in pancreatic ductal adenocarcinoma (PDAC) patients, little effort has been made to identify the underlying pathway(s) responsible for this prognosis. Identifying a clinically relevant prognosis-based gene signature may be the key to improving patient outcomes. Experimental Design: We analyzed the transcriptomic profiles of treatment-naïve surgically resected short- and long-term survivor tumors (GSE62452) for expression and survival, followed by validation in several datasets. These results were corroborated by immunohistochemical analysis of PDAC-resected short- and long-term survivor tumors. The mechanism of this differential survival was investigated using CIBERSORT and pathway analyses. Results: We identified a short-surviving prognostic subtype of PDAC with a high degree of significance (p=0.018). One hundred thirty genes in this novel subtype were found to be regulated by a master regulator, HOXA10, and a five-gene signature derived from these genes, including BANF1, EIF4G1, MRPS10, PDIA4, and TYMS, exhibited differential expression in short-term survivors (STS) and a strong association with poor survival. This signature was further associated with the proportion of T-cells and macrophages found in STS and long-term survivors (LTS), demonstrating a potential role in PDAC immunosuppression. Pathway analyses corroborated these findings, revealing that this HOXA10-driven signature is associated with immune suppression and enhanced tumorigenesis. Conclusions: Overall, these findings reveal the presence of a HOXA10-associated prognostic subtype that can be used to differentiate between STS and LTS patients of PDAC and inform on the molecular interactions that play a role in this poor prognosis.
Abstract IA09: Characterization of hypoxic tumor microenvironment in HPV-negative HNSCC
Authors: Chung Christine H.
Published: September 2023

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) which are often associated with heavy tobacco use has one of the most hypoxic tumor microenvironments (TME) among solid tumors. A hypoxic TME is known to be immunosuppressive due to inhibition of T-cell proliferation and effector cytokine production, unfavorable metabolic competition, upregulation of coinhibitory receptors in T-cells, and recruitment of immunosuppressive cells such as myeloid-derived suppressor cells. However, there is no proven therapeutic strategy to remodel the TME to be less hypoxic and proinflammatory. We determined hypoxic HNSCC based on a Hypoxia-Immune gene expression signature, characterized the immune cells in the TME using multiple immunohistochemical staining, and analyzed the signaling pathways to identify potential therapeutic targets. We found that the hypoxic HNSCC had significantly higher numbers of immunosuppressive cells, and patients with hypoxic HNSCC had worse outcomes after treatment with anti-Programmed Cell Death-1 (PD-1) inhibitors such as pembrolizumab and nivolumab. The gene expression analysis showed hypoxic HNSCC predominantly increased the expression of the epidermal growth factor receptor (EGFR) and transforming growth factor-β (TGF-β) pathway genes. Inhibition of EGFR pathway using cetuximab decreased the expression of hypoxia signature genes, suggesting that it may alleviate the effects of hypoxia and remodel the TME to become more proinflammatory. In addition, recent clinical trials evaluating combination of cetuximab and nivolumab as well as combination of BCA101 (an EGFR and TGF-β dual inhibitor) and pembrolizumab showed a significant response in HPV-negative HNSCC. Our study provides a rationale for treatment strategies combining EGFR- and TGF-β-targeted agents and immunotherapy in the management of HPV-negative, hypoxic HNSCC.

Citation Format: Christine H. Chung. Characterization of hypoxic tumor microenvironment in HPV-negative HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr IA09.
Abstract PO-027: Clinical and genetic associations of biological sex and survival in head and neck squamous cell carcinoma
Authors: Yao Alexandria , Petti Andrew , Mezghani Nadia , Momen-Heravi Fatemeh , Taylor Alison M.
Published: September 2023

Approximately half of all head and neck squamous cell carcinoma (HNSCC) patients die within the five years of diagnosis despite treatment. Some studies have found that women with HNSCC have worse overall prognosis. To investigate the characteristics of HNSCC stratified by biological sex, we analyzed HNSCC samples within the Cancer Genome Atlas dataset from 382 male and 141 female patients. Here, tumors from female patients were more likely to be HPV negative and located in the oral cavity, along with a higher diagnosis age for this patient population. In the tumors of female patients, we also observed increased expression of genes belonged to immune pathways and higher overall immune infiltrate. Although immune infiltrate influences patient prognosis, it did not explain the biological sex disparity in our multivariable Cox proportional hazard model. Instead, across HNSCC, we found that survival differences attributed to biological sex were largely due to differences in diagnosis age and HPV status. However, this was not the case when solely looking at patients with HNSCC in the larynx. In laryngeal HNSCC, women have significantly worse outcome that cannot be attributed to HPV status or other clinical features. Of note, the association of biological sex with outcome in laryngeal HNSCC is also observed in other datasets. The molecular underpinnings of this disparity have not yet been identified, but preliminary analyses suggest different patterns of genomic alterations correlating with biological sex. Our study provides insight into factors that contribute to worse prognosis for females with HNSCC, particularly of the larynx.

Citation Format: Alexandria Yao, Andrew Petti, Nadia Mezghani, Fatemeh Momen-Heravi, Alison M. Taylor. Clinical and genetic associations of biological sex and survival in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-027.
Abstract PO-087: Single-cell transcriptome analysis reveals functional changes in tumor-infiltrating macrophages after nutraceutical momordicine-I treatment in head & neck cancer
Authors: Sur Subhayan , Steele Robert , Ray Ratna B.
Published: September 2023

Head & neck cancer is the sixth most prevalent cancer in the world, and oral cancer is the most common subtype with limited effective treatment options. Therefore, there is a critical need to understand the pathogenesis and therapeutic modalities for successful management of head & neck cancer. Momordicine-I (M-I), an active component of bitter melon extract, displayed anti-tumor activity. However, M-I mediated immune modulation of head & neck tumor microenvironment (TME) remains unknown. To improve the efficacy of therapy, it is important to understand the heterogeneity of head & neck cancer in TME and its modulation following treatment at molecular level. In this study, we showed that M-I inhibits head & neck tumor growth in an immunocompetent mouse model. To understand the in-depth changes in immune system, we analyzed the transcriptome profiles of vehicle treated and M-I-treated tumors using single-cell RNA-sequencing. M-I treatment modulates several molecules in monocyte/macrophage clusters in CD45+ populations. Tumor-associated macrophages (TAMs) are crucial barriers to their antitumor effects. We observed that the expression of Sfln4, a myeloid cell differentiation factor, and Cxcl3, a neutrophil chemoattractant, in the monocyte/macrophage populations was significantly reduced following M-I treatment. We further showed that macrophages need to be in close contact with tumor cells to reduce Sfln4 or Cxcl3 expression, suggesting that TAMs are modulated by M-I treatment. Co-culture of macrophages and tumor cells enhances Nos2 expression following M-I treatment, implicating an alteration of the M2 to M1 phenotype of macrophages. In fact, differential expression of macrophage populations from M-I treated tumors showed downregulation of several M2 macrophage marker genes, and their further validations for functional consequence are underway. Together, our results highlight a potential mechanism of immune modulation by M-I, which may help in the development of a combination therapy for head & neck cancer.

Citation Format: Subhayan Sur, Robert Steele, Ratna B. Ray. Single-cell transcriptome analysis reveals functional changes in tumor-infiltrating macrophages after nutraceutical momordicine-I treatment in head & neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-087.
Supplementary Table S8 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

Median survival time of PC patients treated with gemcitabine and nab-paclitaxel (GnP) and modified FOLFIRINOX (oxaliplatin, irinotecan, and 5-fluorouracil, mFFX) after classification into serum EphA2-NF high (≥50 pg / ml) and low (<50 pg / ml) groups.
Supplementary Table S5 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

Serum EphA2-NF in CA19-9-negative patients with different stages.
Supplementary Table S4 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

Serum EphA2-NF and CA19-9 in PC sera from the validation cohort by stage.
Supplementary Table S2 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

Serum EphA2-NF and CA19-9 levels in PC sera from the test cohort by stage. In this analysis, 82 cases of PC with staging information were utilized in addition to 150 healthy donors (HDs). The cutoff value for EphA2-NF was defined at 50.0 pg / ml (mean + 1 SD of HDs). The cutoff value of CA19-9 was set at 37 U / ml.
Supplementary Table S10 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

Statistical analysis of the Allred score ratio (ASR) of IPMN with and without PC. The chi-square test was performed.
Supplementary Table S1 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

Serum EphA2-NF and CA19-9 levels from 150 healthy donors (HDs), and six patients with pancreatic neuroendocrine tumors (PNETs), 46 patients with intraductal papillary mucinous neoplasms (IPMNs), and 97 PC patients in the test cohort. The cutoff value for EphA2-NF was defined at 50.0 pg / ml (mean + 1 SD of HDs). The cutoff value of CA19-9 was set at 37 U / ml.
Supplementary Fig. S2 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

Determination of cutoff value for CA19-9 and EphA2-NF. (A) PC vs HD and (B) PC vs IPMN + HD
FIGURE 6 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

IHC of the EphA2 cleavage state in IPMN with and without pancreatic cancer. A, Representative images of IPMN cells stained for the EphA2 N-terminus. 0, no staining; 1+, weakly positive staining; 2+, moderately positive staining; 3+, strongly positive staining. Scale bar: 100 μm. B, EphA2 N-terminus staining scores in normal (n = 67), IPMN (n = 89), low-grade IPMN (n = 19), high-grade IPMN (n = 70), IPMN with pancreatic cancer (n = 42), IPMN without pancreatic cancer (n = 47), high-grade IPMN without pancreatic cancer (n = 42), and pancreatic cancer (n = 25). ns, no significance; *, P < 0.05; **, P < 0.01; ***, P < 0.001. C, Representative images of IPMN tissues stained for the EphA2 C-terminus. 0, no staining; 1+, weakly positive staining; 2+, moderately positive staining; 3+, strongly positive staining. Scale bar: 100 μm. D, EphA2 C-terminus staining scores in normal (n = 67), IPMN (n = 89), low-grade IPMN (n = 19), high-grade IPMN (n = 70), IPMN with pancreatic cancer (n = 42), IPMN without pancreatic cancer (n = 47), high-grade IPMN without pancreatic cancer (n = 42), and pancreatic cancer (n = 25). E, Representative images of IPMN with or without pancreatic cancer stained for the EphA2 N- or C-terminus. Scale bar: 50 μm. F, Statistical analysis of the ASR of IPMN with and without pancreatic cancer. The χ2 test was performed. n.s., no significance.
FIGURE 2 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

Diagnostic performance of EphA2-NF and CA19-9 for pancreatic cancer in the test cohort. Dot plots of serum EphA2-NF (A) and CA19-9 (B) levels from 150 HDs, and 6 patients with PNETs, 46 patients with IPMNs, and 97 patients with pancreatic cancer in the test cohort. The cut-off value for EphA2-NF was defined at 50.0 pg/mL (mean + 1 SD of HDs). The cut-off value of CA19-9 was set at 37 U/mL. Dot plots of EphA2-NF (C) and CA19-9 (D) levels in pancreatic cancer sera from the test cohort by stage. In this analysis, 82 cases of pancreatic cancer with staging information were utilized. E, Venn diagrams of EphA2-NF and CA19-9 in patient sera with pancreatic cancer (left, stage I/II/III/IV), early-stage pancreatic cancer (center, stage I/II), and late-stage pancreatic cancer (right, stage III/IV). F, ROC curves of serum EphA2-NF and CA19-9 for differentiating between pancreatic cancer and HDs. G, ROC curve of serum EphA2-NF and CA19-9 for differentiating IPMN and HDs.
FIGURE 1 from EphA2 Proteolytic Fragment as a Sensitive Diagnostic Biomarker for Very Early-stage Pancreatic Ductal Carcinoma
Authors: Sato Shinya , Nakagawa Masatoshi , Terashima Takeshi , Morinaga Soichiro , Miyagi Yohei , Yoshida Eisaku , Yoshimura Toru , Seiki Motoharu , Kaneko Shuichi , Ueno Makoto , Yamashita Taro , Koshikawa Naohiko
Published: September 2023

Antigens and antibody epitopes used in the CLIA. A, Schematic of EphA2 molecules. Wild-type EphA2 is an intact form that contains a transmembrane (TM) cytoplasmic domain. EphA2-NF is an N-terminal fragment released by MT1-MMP processing. EphA2-FL (full-length) is an extracellular form without the TM and cytoplasmic domains. Epitopes of the EphA2 antibodies are shown. SP, ligand-binding signal peptide; CR, cysteine-rich. B, Standard curves of EphA2-NF (circles) and EphA2-FL (squares) for the CLIA using mAbs against 76A1 and 62A1. The detection range of EphA2-NF was 10–105 pg/mL, while the detection of EphA2-FL was negligible (squares).
Divulgação científica e crítica de mídia no canal "Nunca vi 1 cientista" no YouTube
Authors: Miranda Amanda Souza , Guilherme Sofia Franco
Published: September 2023

Este artigo pretende discutir novas formas de apresentação de problemas e soluções da ciência em conteúdo audiovisual para um público amplo, analisando como esse conteúdo circula no Youtube, a partir do caso do canal Nunca vi 1 cientista, com 200 mil inscritos. Pretende-se, com isso, compreender como o conteúdo audiovisual de divulgação científica no YouTube difere de outras propostas já consolidadas da mídia tradicional, em uma abordagem de crítica de mídia que projeta a expansão das narrativas da TV para outras linguagens e dispositivos. Para tanto, selecionamos três episódios do canal sobre um mesmo tema e estudamos suas características centrais, como a linguagem e a performance das comunicadoras. Aspectos de sua circulação também foram mapeados a partir dos comentários da audiência. A conclusão é que esses novos produtos rompem com modelos mais formais de comunicação, como os conteúdos jornalísticos, proporcionando autenticidade na linguagem e nas trocas com a audiência, além de oferecerem uma abordagem crítica de forma acessível e dinâmica.
Rosiglitazone-Mediated Activation of PPARγ Restores HO1 Expression in the Human Preeclamptic Placenta
Authors: Grimaldi Brooke , Kohan-Ghadr Hamid-Reza , Halari Chidambra D. , Nandi Pinki , Kingdom John C. , Drewlo Sascha
Published: September 2023

BACKGROUND:

Preeclampsia is a hypertensive disorder of pregnancy characterized by chronic placental ischemia and suppression of proangiogenic proteins, causing oxidative stress, hypertension, and maternal systemic organ damage. The transcription factor, PPARγ (peroxisome proliferator-activated receptor-γ) promotes healthy trophoblast differentiation but is dysregulated in the preeclampsia placenta. Our study identifies the beneficial impact of Rosiglitazone-mediated PPARγ-activation in the stressed preeclampsia placenta.

METHODS:

We used first trimester placentas, preeclamptic and preterm control placentas, and human trophoblast cell lines to study PPARγ activation.

RESULTS:

Induction of PPARγ activates cell growth and antioxidative stress pathways, including the gene, heme oxygenase 1 (
Hmox1
). Protein expression of both PPARγ and HO1 (heme oxygenase 1) are reduced in preeclamptic placentas, but Rosiglitazone restores HO1 signaling in a PPARγ-dependent manner.

CONCLUSIONS:

Restoring disrupted pathways by PPARγ in preeclampsia offers a potential therapeutic pathway to reverse placental damage, extending pregnancy duration, and reduce maternal sequelae. Future research should aim to understand the full scope of impaired PPARγ signaling in the human placenta and focus on compounds for safe use during pregnancy to prevent severe perinatal morbidity and mortality.
Atoms for Socialism: The Birth of a Czechoslovak-Soviet Nuclear Utopia
Authors: Šmidrkalová Michaela
Published: September 2023

This article focuses on the popular image of the nuclear future of Czechoslovakia in the mid-1950s and analyzes the push for a Czechoslovak-Soviet nuclear utopia. The article describes the foreign orientation of Czechoslovakia's nuclear research through 1955 and the first joint nuclear activities between Czechoslovakia and the Soviet Union. The article also shows how Czechoslovak-Soviet friendship was integrated in practice into the image of the peaceful use of nuclear energy, and it analyzes the image of civilian nuclear activities that was presented to Czechs and Slovaks in a campaign of popularization in the mid-1950s. Soviet “nuclear assistance” to Czechoslovakia, announced in January 1955, corresponded with a change in the popular vision of the nuclear age in Czechoslovakia when a remote nuclear future was transformed into a “lived utopia.”
Coping Strategies During the COVID-19 Pandemic and Self-Determination: A Review of Russian Studies
Authors: Kuznetsova E.A. , Moskvicheva N.L. , Zinovyeva E.V. , Kostromina S.N.
Published: September 2023

Background. The COVID-19 pandemic is a multifaceted stressor. Its impact suggests long-term psychological effects. Self-determination promotes flexibility of goals and actions and helps to overcome the difficulties caused by stress. Objective. To analyze coping strategies during the COVID-19 pandemic presented in Russian scientific studies (RQ1), and their relationship with self-determination (RQ2). Design. Relevant studies (2020–2022) were selected from the Russian citation index (RSCI) database. Strict selection criteria were used. Twenty-four articles were selected for the final review. For dynamic analysis, four stages of the pandemic were identified. Results. Prevailing coping strategies have changed over time. At the beginning of the pandemic, respondents used familiar coping mechanisms. Six months later, active coping strategies were more often used, but deprivation and avoidance strategies increased. A year later, there was an increase in denial and avoidance strategies. Using non-constructive coping strategies may indicate that, due to the long course of the pandemic, meeting basic psychological needs became increasingly frustrated, leading to helplessness, alienation, and lack of control. Later dynamics reflect the growth of effective coping strategies and confirm that when basic needs are blocked for a long time, people seek alternative ways to satisfy them. Conclusion. The dynamics of coping strategies during the pandemic reflected their close relationship with basic psychological needs, as described in the theory of self-determination. The results confirmed the importance of self-determination as a dispositional variable in predicting coping mechanisms.
Medically Unexplained Symptoms among Adults from Russia: An Assessment using the Patient Health Questionnaire-15
Authors: Zolotareva Alena A.
Published: September 2023

Background. The Patient Health Questionnaire-15 (PHQ-15) is one of the most frequently used instruments to measure medically unexplained symptoms in the general population as well as in groups of patients with mental and physical health problems. Objective. This study aimed to examine the psychometric properties of the PHQ-15 in assessing a Russian community sample. Design. A total of 1153 Russian adults age 18 or older participated in this cross-sectional study. They completed the Russian versions of the PHQ-15 and Symptom Check List-90-Revised, SCL-90-R (SCL-90-R). Exploratory and confirmatory factor analyses were used to examine the factor structure of the Russian PHQ-15, and multi-group confirmatory factor analyses were used to test measurement invariance across sex and age. Cronbach’s alpha coefficients and Pearson’s correlation coefficients were used to evaluate the internal reliability and convergent validity of the Russian PHQ-15. Results. Exploratory factor analysis revealed a three-factor solution highlighting pain-fatigue, gastrointestinal, and cardiopulmonary symptoms. Confirmatory factor analysis confirmed a bifactor structure for the Russian PHQ-15 merging general and specific somatic symptoms. A multi-group confirmatory factor analysis showed partial invariance across sex and age. The Russian PHQ-15 demonstrated acceptable Cronbach’s alpha coefficients ranging from 0.72 to 0.75 for specific factors and a good Cronbach’s alpha for the total score (α = 0.85), proving the questionnaire’s internal reliability. Finally, positive correlations between the PHQ-15 and SCL-90-R dimensions, and positive intercorrelations between PHQ-15 specific factors, suggested convergent validity. Conclusion. The Russian PHQ-15 is a reliable and valid instrument for assessing medically unexplained symptoms in the general population. This instrument can be used in diagnostic and counseling settings.
Science, Technology, Engineering, and Mathematics (STEM) Engagement From Parent-Child Interaction in Informal Learning Environments
Authors: Sobel David M.
Published: September 2023

Children’s engagement in science, technology, engineering, and mathematics (STEM) is fundamental to developing scientific literacy. Informal learning environments, such as children’s museums, are a robust setting for fostering STEM engagement, particularly through parent-child interaction. Although the role of STEM learning has been frequently documented in informal learning environments, how children are engaged by STEM topics and STEM’s relation to children’s everyday lives has not been equally well studied. In this article, I suggest that there are ways that parent-child interaction during informal learning opportunities can relate to children’s engagement in STEM activities. A fundamental mechanism underlying this relation is how parents support children’s autonomy as they play together. Parent-child interaction relates to children’s STEM engagement not only in situ but also in how they generalize that behavior to their everyday activities, which opens up promising new lines of research.
Development of ultra-low cycle fatigue life prediction model for structural steel considering the effects of surface roughness, loading frequency, and loading amplitude
Authors: Saleem Aleena , Tamura Hiroshi , Katsuchi Hiroshi
Published: September 2023

Abrasive blast cleaning is often done for steel structures before applying various protective coatings, which produces rough surfaces with changes in fatigue properties. This problem has been addressed in the low- and high-cycle fatigue regimes; however, the effect of surface roughness in combination with different loading parameters on the ultra-low cycle fatigue (ULCF) life has not been reported thus far. To this aim, a total of 59 ULCF tests on designed specimens of SM400 steel with five levels of surface roughness were performed under various loading frequencies and displacement amplitudes. The analysis of experimental results indicates a substantial reduction in fatigue life with an increase in the surface roughness and loading amplitude and a decrease in the loading frequency. Additionally, the strength degradation, dissipation energy, and load–displacement curves are discussed in detail. With the use of experimental data, a new life prediction model characterizing the combined effects of surface roughness, loading frequency, and loading amplitude on the ULCF life is proposed. Moreover, the proposed model is validated by predicting the fatigue life under variable and constant loading amplitude patterns. Comparison between experimental and theoretical results shows that the proposed model accurately estimates the ULCF life within an error band of ±15%, with a reasonable selection of model parameters.
What is the ideal endpoint in early-stage immunotherapy neoadjuvant trials in lung cancer?
Authors: Cameron Robert B. , Hines Jacobi B. , Torri Valter , Porcu Luca , Donington Jessica , Bestvina Christine M. , Vokes Everett , Dolezal James M. , Esposito Alessandra , Garassino Marina C.
Published: September 2023

Numerous clinical trials investigating neoadjuvant immune checkpoint inhibitors (ICI) have been performed over the last 5 years. As the number of neoadjuvant trials increases, attention must be paid to identifying informative trial endpoints. Complete pathologic response has been shown to be an appropriate surrogate endpoint for clinical outcomes, such as event-free survival or overall survival, in breast cancer and bladder cancer, but it is less established for non-small-cell lung cancer (NSCLC). The simultaneous advances reported with adjuvant ICI make the optimal strategy for early-stage disease debatable. Considering the long time required to conduct trials, it is important to identify optimal endpoints and discover surrogate endpoints for survival that can help guide ongoing clinical research. Endpoints can be grouped into two categories: medical and surgical. Medical endpoints are measures of survival and drug activity; surgical endpoints describe the feasibility of neoadjuvant approaches at a surgical level as well as perioperative attrition and complications. There are also several exploratory endpoints, including circulating tumor DNA clearance and radiomics. In this review, we outline the advantages and disadvantages of commonly reported endpoints for clinical trials of neoadjuvant regimens in NSCLC.
Toss a Peach and Get Back a Plum: Impact of Customized Services on Firm Performance
Authors: Xu Yuanbin , Wang Yuchen , Lu Fucai , Xiao Quan
Published: September 2023

The digital economy has led to the diversification of user needs and continuous innovation by firms, and firms are increasingly providing customized services to respond to changing user needs and expect to improve their competitiveness and performance. However, there are few in-depth studies on the mechanisms of the impact of customized services on firm performance and the differences among industries. This study attempts to fill this gap by constructing an econometric model and conducting an empirical study. The results of the analysis of data from firms on Taobao show that: customized services provision has a positive effect on firm performance; differences exist in these positive effects, with the effects ranging from high to low in the raw materials, consumer goods, and industrial goods industries; and customer satisfaction plays a mediating role between customized services and firm performance. This study provides insights for firms to modify, improve, and transform their business strategies in the context of the digital economy.
Machine learning and EEG can classify passive viewing of discrete categories of visual stimuli but not the observation of pain
Authors: Mari Tyler , Henderson Jessica , Ali S. Hasan , Hewitt Danielle , Brown Christopher , Stancak Andrej , Fallon Nicholas
Published: September 2023

Previous studies have demonstrated the potential of machine learning (ML) in classifying physical pain from non-pain states using electroencephalographic (EEG) data. However, the application of ML to EEG data to categorise the observation of pain versus non-pain images of human facial expressions or scenes depicting pain being inflicted has not been explored. The present study aimed to address this by training Random Forest (RF) models on cortical event-related potentials (ERPs) recorded while participants passively viewed faces displaying either pain or neutral expressions, as well as action scenes depicting pain or matched non-pain (neutral) scenarios. Ninety-one participants were recruited across three samples, which included a model development group (n = 40) and a cross-subject validation group (n = 51). Additionally, 25 participants from the model development group completed a second experimental session, providing a within-subject temporal validation sample. The analysis of ERPs revealed an enhanced N170 component in response to faces compared to action scenes. Moreover, an increased late positive potential (LPP) was observed during the viewing of pain scenes compared to neutral scenes. Additionally, an enhanced P3 response was found when participants viewed faces displaying pain expressions compared to neutral expressions. Subsequently, three RF models were developed to classify images into faces and scenes, neutral and pain scenes, and neutral and pain expressions. The RF model achieved classification accuracies of 75%, 64%, and 69% for cross-validation, cross-subject, and within-subject classifications, respectively, along with reasonably calibrated predictions for the classification of face versus scene images. However, the RF model was unable to classify pain versus neutral stimuli above chance levels when presented with subsequent tasks involving images from either category. These results expand upon previous findings by externally validating the use of ML in classifying ERPs related to different categories of visual images, namely faces and scenes. The results also indicate the limitations of ML in distinguishing pain and non-pain connotations using ERP responses to the passive viewing of visually similar images.
The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy
Authors: Tsai Tsung-Han , Su Po-Jung , Huang Shih-Yu , Kuo Ming-Chun , Lin Chang-Ting , Wu Chia-Che , Luo Hao-Lun , Chen Chien-Hsu , Chou Chih-Chi , Liu Ting-Ting , Huang Chun-Chieh , Tsai Kai-Lung , Su Yu-Li
Published: September 2023

Background

While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research.

Method

We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data.

Result

A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004).

Conclusion

The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.
Mechanical properties evaluation of metacarpophalangeal joint prosthesis with new titanium-nickel memory alloy: a cadaver study
Authors: Guo Minzheng , Qi Baochuang , Li Jun , Shi Xiangwen , Ni Haonan , Shi Hongxin , Ren Junxiao , Zhou Xizong , Ye Tao , Yao Ling , Xu Yongqing , Zhang Meichao , Li Chuan
Published: September 2023

Objective

Ni-Ti memory alloys are unusual materials for hard-tissue replacement because of their unique superelasticity, good biocompatibility, high strength, low specific gravity, low magnetism, wear resistance, corrosion resistance and fatigue resistance. The current study aims to evaluate its mechanical properties and provide biomechanical basis for the clinical application of the prosthesis.

Methods

Ten adult metacarpophalangeal joint specimens were randomly divided into a prosthesis group (n = 5, underwent metacarpophalangeal joint prosthesis) and a control group (n = 5, underwent sham operation). Firstly, the axial compression strength was tested with BOSE material testing machine to evaluate its biomechanical strength. Secondly, these specimens were tested for strain changes using BOSE material testing machine and GOM non-contact optical strain measurement system to evaluate the stress changes. Thirdly, fatigue test was performed between groups. Lastly, the mechanical wear of the metacarpophalangeal joint prosthesis was tested with ETK5510 material testing machine to study its mechanical properties.

Results

Axial compression stiffness in the prosthesis group was greater than that in the control group in terms of 30 ° and 60 ° flexion positions (P < 0.05). There was no statistically significant difference between two groups with regards to axial compression stiffness and stress change test (P > 0.05). In the fatigue wear test, the mean mass loss in the prosthesis group’s prosthesis was 17.2 mg and 17.619 mm3, respectively. The mean volume wear rate was 0.12%. There was no statistically significant difference in the maximum pull-out force of the metacarpal, phalangeal, and polymer polyethylene pads between the prosthesis group and the control group specimens.

Conclusions

Ni-Ti memory alloy metacarpophalangeal joint prosthesis conforms to the biomechanical characteristics of metacarpophalangeal joints without implants, and the fatigue strength can fully meet the needs of metacarpophalangeal joint activities after joint replacement.
Is there any difference based on sublingual varices frequency between hypertensive patients and healthy persons?
Authors: Ahadian Hakimeh , Akhavankarbassi Mohammad Hasan , Sabaghzadegan Yasaman , Owlia Fatemeh , Daneshmand Amir Sasha
Published: September 2023

Background

Sublingual varices (SV) are benign vascular lesions that have questionable associations with aging, smoking, and hypertension. This study purposed to evaluate whether SV frequency differs between hypertensive patients and healthy persons.

Methods and Material

This cross-sectional study was conducted on 120 dental patients referred to Yazd Oral Medicine Department. At first sublingual surface of the tongue were examined before the routine oral survey, and blood pressure (BP) was measured in a sitting position. SV were classified into Grade 1 (no/mild), Grade 2 (medium to severe), and Grade 3 (multi-focal). Blood pressure was measured in all participants. Participants based on the obtained BP, divided into normal, prehypertension, stage 1, and 2 groups. Frequency of SV was compared in regarding age, gender, and stage of hypertension. All of the analyses were conducted at a p < 0.05 level of significance by the SPSS22 statistical package using chi-square test.

Results

Out of 120 patients, 84 (70%) had SV. The frequency of SV in patients with hypertension (HT) (86.8%) was significantly higher than in others (48.1%); (p < 0.001). Data analysis showed there was a significant difference between the age groups. There was no significant difference based on SV between two genders. There was no significant difference in the frequency of sublingual varices between males and females. Aging could impact the frequency of SV.

Conclusion

This study revealed that patients with hypertension had more SV. A simple valuable method for dental clinicians to be active in preventive health care is evaluating sublingual surface of tongue.
Leveraging electronic medical records for HIV testing, care, and treatment programming in Kenya—the national data warehouse project
Authors: Ndisha Margaret , Hassan Amin S. , Ngari Faith , Munene Evans , Gikura Mary , Kimutai Koske , Muthoka Kennedy , Murie Lisa Amai , Tolentino Herman , Odhiambo Jacob , Mwele Pascal , Odero Lydia , Mbaire Kate , Omoro Gonza , Kimanga Davies O.
Published: September 2023

Background

Aggregate electronic data repositories and population-level cross-sectional surveys play a critical role in HIV programme monitoring and surveillance for data-driven decision-making. However, these data sources have inherent limitations including inability to respond to public health priorities in real-time and to longitudinally follow up clients for ascertainment of long-term outcomes. Electronic medical records (EMRs) have tremendous potential to bridge these gaps when harnessed into a centralised data repository. We describe the evolution of EMRs and the development of a centralised national data warehouse (NDW) repository. Further, we describe the distribution and representativeness of data from the NDW and explore its potential for population-level surveillance of HIV testing, care and treatment in Kenya.

Main body

Health information systems in Kenya have evolved from simple paper records to web-based EMRs with features that support data transmission to the NDW. The NDW design includes four layers: data warehouse application programming interface (DWAPI), central staging, integration service, and data visualization application. The number of health facilities uploading individual-level data to the NDW increased from 666 in 2016 to 1,516 in 2020, covering 41 of 47 counties in Kenya. By the end of 2020, the NDW hosted longitudinal data from 1,928,458 individuals ever started on antiretroviral therapy (ART). In 2020, there were 936,869 individuals who were active on ART in the NDW, compared to 1,219,276 individuals on ART reported in the aggregate-level Kenya Health Information System (KHIS), suggesting 77% coverage. The proportional distribution of individuals on ART by counties in the NDW was consistent with that from KHIS, suggesting representativeness and generalizability at the population level.

Conclusion

The NDW presents opportunities for individual-level HIV programme monitoring and surveillance because of its longitudinal design and its ability to respond to public health priorities in real-time. A comparison with estimates from KHIS demonstrates that the NDW has high coverage and that the data maybe representative and generalizable at the population-level. The NDW is therefore a unique and complementary resource for HIV programme monitoring and surveillance with potential to strengthen timely data driven decision-making towards HIV epidemic control in Kenya.

Database link

(https://dwh.nascop.org/).
Subcutaneous emphysema and pneumomediastinum following orbital blowout pathological fracture in a cat with nasal lymphoma: a case report
Authors: Oh Ye-In , Hong Heejeong , Kim Tae-hee , Kang Kyuyong , Yoon Junghee , Youn Hwa-Young , Seo Kyoung-Won
Published: September 2023

Background

Subcutaneous emphysema and pneumomediastinum are rare complications associated with orbital blowout pathological fracture.

Case presentation

A 7-year old, castrated male Abbysinian cat presented with anorexia, lethargy, nausea, eyelid swelling, nasal discharge, and sneezing. Based on the clinical and diagnostic work-up, the cat was diagnosed with T cell high-grade nasal lymphoma associated with orbital pathological fracture due to the tumour invasion. After chemotherapy, the cat showed massive subcutaneous emphysema from frontal region to abdomen and pneumomediastinum due to orbital blowout pathological fracture. As the nasal mass decreased in volume; the air had moved from the maxillary sinus to the subcutaneous region and the mediastinum through fascial planes in the head and neck region.

Conclusions

This is a first case report of a massive subcutaneous emphysema and pneumomediastinum due to an orbital blowout pathological fracture following chemotherapy in feline nasal lymphoma in veterinary medicine.
Successful management of in-transit cutaneous squamous cell carcinoma with anti-PD-1 immunotherapy
Authors: Furkert Chris , Martin Richard , Sharma Avinash , Rivalland Gareth
Published: September 2023

This report describes the case of a 70-year-old man with metastatic squamous cell carcinoma (SCC) of the right lower leg. Soon after definitive surgical management of the primary and nodal metastases with curative intent, he relapsed, developing aggressive in-transit metastatic disease and recurrent nodal disease. The patient was treated with systemic immunotherapy alone, which not only prompted the progressive nodal metastases to regress, but also resulted in a complete response of the in-transit disease. This situation is previously undescribed in the medical literature.