bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure legend from Circulating Tumor DNA Analysis Detects FGFR2 Amplification and Concurrent Genomic Alterations Associated with FGFR Inhibitor Efficacy in Advanced Gastric Cancer
Authors: Jogo Tomoko , Nakamura Yoshiaki , Shitara Kohei , Bando Hideaki , Yasui Hisateru , Esaki Taito , Terazawa Tetsuji , Satoh Taroh , Shinozaki Eiji , Nishina Tomohiro , Sunakawa Yu , Komatsu Yoshito , Hara Hiroki , Oki Eiji , Matsuhashi Nobuhisa , Ohta Takashi , Kato Takeshi , Ohtsubo Koushiro , Kawakami Takeshi , Okano Naohiro , Yamamoto Yoshiyuki , Yamada Takanobu , Tsuji Akihito , Odegaard Justin I. , Taniguchi Hiroya , Doi Toshihiko , Fujii Satoshi , Yoshino Takayuki
Published: November 2024

Supplementary Figure legend
Supplementary Table S2 from Phase I Study of 2- or 3-Week Dosing of Telisotuzumab Vedotin, an Antibody–Drug Conjugate Targeting c-Met, Monotherapy in Patients with Advanced Non–Small Cell Lung Carcinoma
Authors: Camidge D. Ross , Morgensztern Daniel , Heist Rebecca S. , Barve Minal , Vokes Everett , Goldman Jonathan W. , Hong David S. , Bauer Todd M. , Strickler John H. , Angevin Eric , Motwani Monica , Parikh Apurvasena , Sun Zhaowen , Bach Bruce Allen , Wu Jun , Komarnitsky Philip B. , Kelly Karen
Published: November 2024

Supplementary Table S2 shows time course of peripheral neuropathy development during treatment with Teliso-V monotherapy Q2W and Q3W cohorts and peripheral neuropathy events leading to Teliso-V dose interruption/reduction
Data from GEN-1 in Combination with Neoadjuvant Chemotherapy for Patients with Advanced Epithelial Ovarian Cancer: A Phase I Dose-escalation Study
Authors: Thaker Premal H. , Bradley William H. , Leath Charles A. , Gunderson Jackson Camille , Borys Nicholas , Anwer Khursheed , Musso Lauren , Matsuzaki Junko , Bshara Wiam , Odunsi Kunle , Alvarez Ronald D.
Published: November 2024

AbstractPurpose:
GEN-1 (phIL-12-005/PPC), an IL12 plasmid formulated with polyethyleneglycol-polyethyleneimine cholesterol lipopolymer, has preclinical activity when combined with platinum-taxane intravenous chemotherapy and administered intraperitoneally in epithelial ovarian cancer (EOC) models. OVATION I was a multicenter, nonrandomized, open-label phase IB trial to evaluate the safety, preliminary antitumor activity, and immunologic response to GEN-1 in combination with neoadjuvant chemotherapy (NACT) carboplatin-paclitaxel in patients with advanced EOC.
Patients and Methods:
A total of 18 patients with newly diagnosed stage IIIC and IV EOC were enrolled. A standard 3+3 dose-escalation design tested four GEN-1 doses (36, 47, 61, 79 mg/m2) to determine the maximum tolerated dose and dose-limiting toxicities (DLTs). GEN-1 was administered in eight weekly intraperitoneal infusions starting at cycle 1 week 2 in combination with three 21-day cycles of NACT carboplatin AUC 6 and weekly paclitaxel 80 mg/m2.
Results:
The most common treatment-emergent adverse events at least possibly related were nausea, fatigue, abdominal pain/cramping, anorexia, diarrhea, and vomiting. Eight patients experience grade 4 neutropenia attributed to NACT. No DLTs occurred. A total of 14 patients were evaluable for response and 12 (85.7%) had radiological response (two complete response and 10 partial response) prior to debulking; nine were R0 at debulking and one patient had complete pathologic response. IL12 and its downstream cytokine, IFNγ, increased in peritoneal washings but not as much in blood. Increased levels of myeloid dendritic cells and T-effector memory cells in peritoneal fluid, plus elevated CD8+ T cells and reduced immunosuppression within the tumor microenvironment were found. A median time to treatment failure of 18.4 months (95% confidence interval, 9.2–24.5) was observed in the intention-to-treat population.
Conclusions:
Adding GEN-1 to standard NACT is safe, appears active, and has an impact on the tumor microenvironment.
Data from Circulating Tumor DNA Analysis Detects FGFR2 Amplification and Concurrent Genomic Alterations Associated with FGFR Inhibitor Efficacy in Advanced Gastric Cancer
Authors: Jogo Tomoko , Nakamura Yoshiaki , Shitara Kohei , Bando Hideaki , Yasui Hisateru , Esaki Taito , Terazawa Tetsuji , Satoh Taroh , Shinozaki Eiji , Nishina Tomohiro , Sunakawa Yu , Komatsu Yoshito , Hara Hiroki , Oki Eiji , Matsuhashi Nobuhisa , Ohta Takashi , Kato Takeshi , Ohtsubo Koushiro , Kawakami Takeshi , Okano Naohiro , Yamamoto Yoshiyuki , Yamada Takanobu , Tsuji Akihito , Odegaard Justin I. , Taniguchi Hiroya , Doi Toshihiko , Fujii Satoshi , Yoshino Takayuki
Published: November 2024

AbstractPurpose:
FGFR2 amplification is associated with poor prognosis in advanced gastric cancer and its subclonal heterogeneity has been revealed. Here, we examined whether circulating tumor DNA (ctDNA) was useful for detecting FGFR2 amplification and co-occurring resistance mechanisms in advanced gastric cancer.
Experimental Design:
We assessed genomic characteristics of FGFR2-amplified advanced gastric cancer in a nationwide ctDNA screening study. We also analyzed FGFR2 amplification status in paired tissue and plasma samples with advanced gastric cancer. In addition, we examined patients with FGFR2-amplified advanced gastric cancer identified by ctDNA sequencing who received FGFR inhibitors.
Results:
FGFR2 amplification was more frequently detected by ctDNA sequencing in 28 (7.7%) of 365 patients with advanced gastric cancer than by tissue analysis alone (2.6%–4.4%). FGFR2 amplification profiling of paired tissue and plasma revealed that FGFR2 amplification was detectable only by ctDNA sequencing in 6 of 44 patients, which was associated with a worse prognosis. Two patients in whom FGFR2 amplification was detected by ctDNA sequencing after tumor progression following previous standard chemotherapies but not by pretreatment tissue analysis had tumor responses to FGFR inhibitors. A third patient with FGFR2 and MET co-amplification in ctDNA showed a limitation of benefit from FGFR inhibition, accompanied by a marked increase in the MET copy number.
Conclusions:
ctDNA sequencing identifies FGFR2 amplification missed by tissue testing in patients with advanced gastric cancer, and these patients may respond to FGFR inhibition. The utility of ctDNA sequencing warrants further evaluation to develop effective therapeutic strategies for patients with FGFR2-amplified advanced gastric cancer.
Data from Phase I Study of 2- or 3-Week Dosing of Telisotuzumab Vedotin, an Antibody–Drug Conjugate Targeting c-Met, Monotherapy in Patients with Advanced Non–Small Cell Lung Carcinoma
Authors: Camidge D. Ross , Morgensztern Daniel , Heist Rebecca S. , Barve Minal , Vokes Everett , Goldman Jonathan W. , Hong David S. , Bauer Todd M. , Strickler John H. , Angevin Eric , Motwani Monica , Parikh Apurvasena , Sun Zhaowen , Bach Bruce Allen , Wu Jun , Komarnitsky Philip B. , Kelly Karen
Published: November 2024

AbstractPurpose:
Telisotuzumab vedotin (Teliso-V) is an anti–c-Met–directed antibody–drug conjugate. Here, we present safety and efficacy data from a phase I/Ib study of Teliso-V monotherapy evaluated in once every 2 weeks/once every 3 weeks schedules in patients with non–small cell lung cancer (NSCLC).
Patients and Methods:
During dose escalation, patients received Teliso-V monotherapy intravenously once every 3 weeks (0.15–3.3 mg/kg) or once every 2 weeks (1.6–2.2 mg/kg). The dose-expansion phase enrolled patients with NSCLC and c-Met H-score ≥150 (c-Met+) or MET amplification/exon 14 skipping mutations. Safety, pharmacokinetics, and efficacy were assessed. Herein, the analysis of patients receiving ≥1.6 mg/kg once every 2 weeks or ≥2.4 mg/kg once every 3 weeks Teliso-V is reported.
Results:
Fifty-two patients with NSCLC were enrolled and received ≥1.6 mg/kg Teliso-V once every 2 weeks (n = 28) or ≥2.4 mg/kg Teliso-V once every 3 weeks (n = 24). The most common adverse events were fatigue (54%), peripheral neuropathy (42%), and nausea (38%). No dose-limiting toxicities were observed for Teliso-V once every 2 weeks and once every 3 weeks up to 2.2 and 2.7 mg/kg, respectively. The recommended phase II dose was established at 1.9 mg/kg once every 2 weeks and 2.7 mg/kg once every 3 weeks on the basis of overall safety and pharmacokinetics. Forty of 52 patients were c-Met+ (33 nonsquamous, 6 squamous, 1 mixed histology) and were included in the efficacy-evaluable population. Of those, 9 (23%) had objective responses with median duration of response of 8.7 months; median progression-free survival was 5.2 months.
Conclusions:
Teliso-V monotherapy was tolerated and showed antitumor activity in c-Met+ NSCLC. On the basis of overall safety, pharmacokinetics, and efficacy outcomes, 1.9 mg/kg Teliso-V once every 2 weeks and 2.7 mg/kg once every 3 weeks schedules were selected for further clinical development.
Fig. S1 from Inhibition of SUMOylation Induces Adaptive Antitumor Immunity against Pancreatic Cancer through Multiple Effects on the Tumor Microenvironment
Authors: Erdem Suna , Lee Hyojae James , Shankara Narayanan Jayanth Surya Narayanan , Tharuka Mohottige Don Neranjan , De la Torre Jorge , Ren Tianchen , Kuang Yixuan , Abeywardana Tharindumala , Li Kevin , Berger Allison J. , Lowy Andrew M. , White Rebekah R. , Chen Yuan
Published: November 2024

Fig. S1
Figure S9 from Engineered CAR-NK Cells with Tolerance to H2O2 and Hypoxia Can Suppress Postoperative Relapse of Triple-Negative Breast Cancers
Authors: Liu Yan , Chen Jiahui , Tian Jia , Hao Yu , Ma Xinxing , Zhou Yehui , Feng Liangzhu
Published: November 2024

Figure S9. Flow cytometric analysis of the impact of CAT and/or hydrogel on the phenotype of related CAR-NK cells labeled with anti-CD3-PE-Cy7 or anti-CD56-PE.
Figure S13 from Engineered CAR-NK Cells with Tolerance to H2O2 and Hypoxia Can Suppress Postoperative Relapse of Triple-Negative Breast Cancers
Authors: Liu Yan , Chen Jiahui , Tian Jia , Hao Yu , Ma Xinxing , Zhou Yehui , Feng Liangzhu
Published: November 2024

Figure S13. Individual tumor growth curves of brain metastatic MDA-MB-231 tumor-bearing mice subjected to different treatments (related to Figure 5F).
Endoscopic Resection for Colorectal Tumors
Authors: Hirai Yuichiro , Toyoshima Naoya , Saito Yutaka
Published: November 2024

Background: Endoscopic resection techniques for colorectal tumors are constantly evolving with improvements. Summary: Over the past decade, there has been a paradigm shift toward cold polypectomy for the removal of small lesions (<10 mm), known as the “cold revolution”. In recent years, underwater endoscopic mucosal resection (EMR) has emerged as an alternative to conventional EMR and has been gaining popularity for resection of intermediate and large-sized lesions (≥10 mm). Although colorectal endoscopic submucosal dissection (ESD) requires a high level of advanced skills, improvements in dissection techniques and devices have facilitated the procedure. In Japan, the safety and efficacy of ESD for resecting large lesions (≥20 mm) have been demonstrated in a large-scale, multicenter, prospective cohort study (CREATE-J). ESD is also being increasingly adopted in Western countries. As endoscopic resection continues to advance and include large and more complex defects, a variety of closure techniques and new devices are being developed. Meanwhile, the number of endoscopic resections for T1-colorectal cancer (T1-CRC), including those intended for total excisional biopsy, has been increasing owing to the aging population and improvements in endoscopic technique. Key Messages: This review provides a broad summary of endoscopic resection for colorectal tumors including advancements in closure techniques and devices for mucosal defects, as well as the potential role of endoscopic resection for patients with T1-CRC.
Poor Correlation between Diaphragm Ultrasound and Invasive Gold Standard Technique Derived Respiratory Muscle Strength Assessment in Patients after Hospitalisation for COVID-19
Authors: Friedrich Janina , Regmi Binaya , Jörn Benedikt , Senol Mehdi , Giannoni Alberto , Boentert Matthias , Kahles Florian , Daher Ayham , Dreher Michael , Spiesshoefer Jens
Published: November 2024

Introduction: Individuals who survive acute coronavirus disease 2019 (COVID-19) might experience diaphragm muscle weakness. Diaphragm ultrasound may be an easy-to-obtain bedside tool for determining diaphragm function. However, twitch transdiaphragmatic pressure (twPdi) following magnetic stimulation (MS) of the phrenic nerves is the gold standard for non-volitional assessment of diaphragm strength. This study investigated whether diaphragm thickening ratio (DTR) measured on diaphragm ultrasound reflects diaphragm strength as measured by twPdi following MS of the phrenic nerves or other (volitional) invasively obtained pressure values and could therefore be used to accurately diagnose diaphragm weakness. Methods: One year after discharge, 50 individuals (14 female, age 58 ± 12 years) who had been hospitalised and treated for moderate-severe COVID-19 underwent standard spirometry and diaphragm ultrasound. TwPdi following cervical MS of the phrenic nerve and volitional inspiratory manoeuvres (Sniff and Mueller manoeuvre) were measured using oesophageal and gastric balloon catheters after transnasal placement. Results: At follow-up, no clinically meaningful restrictive lung function impairment was evident on spirometry. On diaphragm ultrasound, diaphragm dysfunction, i.e., an impaired DTR was detected in 24% (12/50) of participants. An objective diagnosis of diaphragm dysfunction, defined as twPdi <16 cm H2O, was made in 60% (30/50) of participants. The measurement results of the two methods did not agree, given that there were many false-negative but also false-positive results, so diaphragm ultrasound diagnosed in parts other patients with diaphragm dysfunction than twPdi. Diaphragm ultrasound had a sensitivity of 26.67% and a specificity of 80.0% in the detection of diaphragm dysfunction (positive predictive value 66.67%, negative predictive value 42.10%). Conclusion: Diagnosis of diaphragm weakness in individuals who have recovered from COVID-19 cannot be made accurately on diaphragm ultrasound (via DTR) but requires twPdi as the gold standard for assessment of diaphragm strength.
The Power of a Good Word: Enhancing the Efficacy of Analgesics in Clinical Settings
Authors: Treister Roi , Cohen Vered , Issa Limor , Beiruti Wiegler Karine , Izakson Alexander , Agostinho Mariana
Published: November 2024

Introduction: Communication between medical staff and patients about treatment efficacy elicits expectations of benefit and improves treatment outcomes. While demonstrated in multiple studies via different research methodologies, uniform communication protocols have not been adopted in clinical practice. Here, we summarize the results of two sister studies aimed at bridging this gap. Methods: Women undergoing C-section (study 1, randomized controlled trial) and patients undergoing general or otolaryngologic surgeries (study 2, control group design) were recruited and assigned to the “regular communication” (RC) or “enhanced communication” (EC) arms. The EC arm received positive information about treatment, while the RC arm received no such information. In both studies, the primary outcome was change in pain intensity; in study 2, an additional outcome was morphine consumption. Results: Eighty women successfully completed study 1, and 102 patients successfully completed study 2. In both studies, significant time*group interactions were observed (p < 0.001). The analgesic effect was virtually twice as large in the EC arm compared to the RC arm. In study 2, in the last two timepoints of assessment, participants in the EC arm also consumed fewer doses of opioids than participants in the RC arm (p < 0.001). No significant differences were found in vital signs. Conclusions: We provide ecological evidence that positive information about treatment significantly decreases pain and opioid consumption during routine clinical care. This study and others could encourage healthcare providers to harness the powerful effects of patients’ expectations of benefit to improve analgesics outcomes and, potentially, the outcomes of other symptoms.
Incidence of Adult Primary Immunoglobulin A Nephropathy among a Racially/Ethnically Diverse Population in the United States
Authors: Sim John J. , Chen Qiaoling , Cannizzaro Nancy , Bhandari Simran K. , Fernandes Ancilla W. , Chang John , Pinto Cibele , Schachter Asher D. , Mathur Mohit
Published: November 2024

Introduction: IgA nephropathy (IgAN), a leading cause of kidney failure worldwide, is one of the most common forms of primary glomerulonephropathy with variability by race and ethnicity. Using a diverse cohort within a large integrated health system in the United States (US), we identified and characterized patients with biopsy-proven IgAN and report annual incidence rates across racial/ethnic groups and standardized to the US nationally. Methods: A cross-sectional study between January 1, 2010, and December 31, 2021 within Kaiser Permanente Southern California was performed. Patients (age >/=18 years) who underwent a native kidney biopsy and identified as having primary IgAN comprised the study population. Laboratory, demographic, and comorbidity information were obtained from the electronic health records. Annual incidence rates were calculated for biopsy-proven IgAN (per 100,000 person-years) and standardized to 2020 US Census. Results: Of 9,392 individuals who underwent kidney biopsy, 606 adult patients were identified with primary IgAN. Crude annual IgAN incidence rates ranged from 1.3 to 2.2 (per 100,000 person-years). US census standardized incidence rate (CI) of IgAN was 1.4 (0.8, 2.0) per 100,000 person-years in the 12-year period. Incidence rate (per 100,000 person-years) was highest among Asian/Pacific Islander (4.5) and Hispanic (1.7) patients and lowest among White (1.2) and Black (0.6) patients. Median estimated glomerular filtration rate (eGFR) was 51 mL/min with median urine protein creatinine ratio (uPCR) 1.8 g/g. Conclusion: Among a large diverse US population within Southern California, we observed an IgAN incidence rate of 1.7 which estimated to a standardized US incidence of 1.4 (per 100,000 person-years) within a 12-year period. Patients appear to be diagnosed at more advanced disease given kidney function and proteinuria at biopsy.
Ultrasonographic Evaluation of Systemic Venous Congestion in Maintenance Hemodialysis Patients during Fluid Removal
Authors: Gudiño-Bravo Pedro , Posada-Martinez Edith L. , Cano-Nieto Mariana M. , Ibarra-Marquez Nikein D. , Leal-Escobar Gabriela , Madero Magdalena , Rodriguez-Iturbe Bernardo , Ivey-Miranda Juan B. , Lopez-Gil Salvador
Published: November 2024

Introduction: Fluid overload is a frequent and serious complication in hemodialysis patients. The combination of multiple point-of-care ultrasound (POCUS) measurements can identify significant venous congestion, but its usefulness to determine ultrafiltration (UF) requirements and dry weight is unknown. Therefore, we evaluated prospectively patients in maintenance hemodialysis to establish the correlations between changes in venous congestion parameters and fluid removal. Methods: This was a prospective, single-center, observational study. POCUS venous congestion measurements were performed in 22 patients during 32 online post-dilutional hemodiafiltration sessions, and findings were correlated with UF volume, central venous pressure, and body water composition determined by multifrequency bioelectric impedance analysis (BIA). Results: The pre-dialysis weight was on average 1.9 kg above the BIA estimated dry weight, the average initial inferior vena cava (IVC) diameter was <2 cm. An initial abnormal hepatic vein (HV) waveform was present in 26% (8) of the measurements. The average UF volume was 2,084 ± 655 mL and correlated with changes in IVC diameter (R = 0.34, 95% CI: [0.18, 0.56], p < 0.05) but not with any other POCUS venous congestion parameters. Normalization of the IVC diameter and HV waveform was observed during the first UF hour in all initially altered measurements. Diameter reduction in the IVC correlated with total body water volume reduction estimated with BIA when measured immediately after fluid removal (R = 0.34, 95% CI: [0.08, 0.56], p < 0.05). Conclusion: Reduction in IVC diameter had a modest but significant correlation with UF volume in our patients on maintenance hemodiafiltration. POCUS may be used to monitor patients during UF.
Comparing Two Peanut Desensitization Protocols in Preschool Children: A Real-World Clinical Practice
Authors: Al Ali Adnan , Sigman Karen , Khalaf Roy , Sillcox Carly , Kaouache Mohammed , Shand Greg , Saker Sarife , McCusker Christine , Ben-Shoshan Moshe
Published: November 2024

Introduction: Peanut allergy is the main food allergy in childhood and poses significant health concerns. This study aimed to critically evaluate the effectiveness and safety of oral immune therapy (OIT) using crushed peanuts versus peanut puffs. Methods: Children with an allergist diagnosed peanut allergy based on a history of an IgE-mediated reaction and a positive skin prick test for peanuts were recruited at the Montreal Children’s Hospital and the Children’s Clinic located in Montreal. Based on age and personal preference, initial doses of peanut were given in either puff (Bamba) or crushed peanut form. Patients continued the same dose for 2–5 weeks at home, filled out a symptom diary, and returned to the clinic for up-dosing until maintenance was reached (2 teaspoons of peanut butter). A continuation ratio regression model was used to evaluate the effect of the allergen type on the severity of anaphylactic and allergic reactions (ARs) during OIT while adjusting for potential confounders. Results: Between October 2020 and June 2023, 191 children (59.6% male; median age 1.95 years) were recruited. Most patients (75.1%) had eczema, and 12.7% had asthma. Oral desensitization was performed using one of two strategies according to the allergist: crushed peanut (n = 60 [31.4%]) and peanut puff (n = 131 [68.6%]). Of the participants, the consumption of puff lowered reaction severity by a factor of 3.94 (95% CI, 1.6–9.6), in comparison to crushed peanuts. Older age markedly elevates the adjusted odds of reacting to a particular severity level as compared to a lower level by 1.20 (95% CI, 1–1.4). Conclusion: Modified peanut desensitization using peanut puffs has shown potential in reducing the severity of ARs in younger children. Older children may experience a higher risk of severe reactions, indicating the need for age-specific approaches to desensitization protocols.
C4b-Binding Protein and Factor H Attenuate NLRP3 Inflammasome-Mediated Signalling Response during Group A Streptococci Infection in Human Cells
Authors: Bettoni Serena , Dziedzic Mateusz , Bierschenk Damien , Chrobak Maja , Magda Michal , Laabei Maisem , King Ben C. , Riesbeck Kristian , Blom Anna M.
Published: November 2024

Introduction: Streptococcus pyogenes (group A streptococcus; GAS) is a pathogen causing over half a million deaths annually worldwide. Human immune cells respond to GAS infection by activating the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines that control infection. We investigated the role of C4b-binding protein (C4BP) and factor H (FH) in the inflammasome response to GAS, as they are recruited by GAS to prevent complement deposition and limit phagocytosis. Methods: The inflammasome response was investigated using primary human cells and the strain GAS-AP1. Cytokine responses were evaluated by ELISA. C4BP internalisation was investigated using confocal microscopy. Activation of the NLRP3 inflammasome components was assessed by Western blotting. Results: Interleukin-1β (IL-1β) release, induced by GAS-AP1, was inhibited by FH which interferes with priming of human cells. In contrast, C4BP restricted the IL-1β response without affecting cell priming. C4BP was engulfed by cells together with bacteria and excluded from low-pH vesicles but localised within the cytosol and near the ASC speck inflammasome complex. C4BP did not inhibit either the inflammasome complex assembly or caspase-1 activation. However, C4BP limited the cleavage of gasdermin D N-terminal fragments by interfering with caspase-1 enzymatic activity. Conclusion: Given that the amount of IL-1β modulates the severity of GAS infection, our results provide new insights into the effect of FH and internalised C4BP to control GAS sensing by inflammasomes.
Ciudadanías empáticas en la escuela
Authors: Valderrama Losada Diana Marcela , Santacoloma Alvarán Juliana
Published: November 2024

El presente artículo reflexiona sobre las posibilidades que ofrece la empatía como capacidad política en el debate sobre las ciudadanías, particularmente, sobre los modos en los que se pueden configurar prácticas pedagógicas en el marco de la consolidación de ciudadanías empáticas en la escuela. A partir de la revisión teórica en relación con las categorías de ciudadanía, empatía y desarrollo humano, y de una reflexión en clave de triangulación crítica, se considera que la emergencia de nuevos paradigmas imaginativos en la concepción de ciudadanía en la escuela posibilita que la empatía potencie ciudadanías participativas por medio de prácticas pedagógicas innovadoras. La empatía como imaginación narrativa posibilita y fortalece el desarrollo de potenciales afectivos, ético-morales, la transformación de conflictos y el potencial comunicativo para promover el diálogo intersubjetivo y el consenso. Asimismo, la educación es la clave para la formación ciudadana empática.
Dinámicas Familiares y Prevención del Consumo Experimental de Sustancias Psicoactivas en Jóvenes.
Authors: Calvo Tafur Verónica Yadith , Hinestroza Rodríguez Susy Yarley
Published: November 2024

En la actualidad, las acciones hacia la prevención del uso experimental de sustancias psicoactivas entre jóvenes, suscita el interés en diversos grupos e instituciones, centrado en diferentes disciplinas. Este interés plantea preguntas alrededor de entornos como la escuela o la familia, para indagar por su responsabilidad frente a este problema. Así, aparece la familia con sus diversas relaciones que pueden resultar contraproducentes afectando el bienestar físico, psicológico, emocional y social de esta población. Por ello, este artículo de revisión da cuenta de algunas investigaciones que abordan las dinámicas familiares como un componente esencial para el desarrollo y la incidencia en las decisiones que toman los jóvenes frente al consumo experimental de SPA. Del mismo modo, este artículo tributa al proyecto BPIN 2020000100461, en relación a las contribuciones, sobre la prevención del consumo de SPA en jóvenes, a partir de analizar las destrezas desarrolladas en las familias abordadas en esta investigación.
Venha a nós o reino do amanhã: uma análise da ideia de salvação e dos elementos religiosos presentes na graphic novel de Mark Waid e Alex Ross
Authors: Rodrigues Iuri Biagioni , Reblin Iuri Andréas
Published: November 2024

It aims to analyze the religiosity and the idea of salvation present in Kingdom Come by Mark Waid (writer) and Alex Ross (artist). For this purpose, the cartographic-critical method developed by researcher Iuri Andreás Reblin will be employed. It analyzes the cited story based on other articles on the subject, especially those focusing on the relationship between the comic book with the biblical text of the Apocalypse of John, and based on relevant theological concepts such as salvation and redemption to identify how they are present in the graphic novel.
Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol–Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis
Authors: Bhatia Harpreet S. , Wandel Simon , Willeit Peter , Lesogor Anastasia , Bailey Keith , Ridker Paul M. , Nestel Paul , Simes John , Tonkin Andrew , Schwartz Gregory G. , Colhoun Helen , Wanner Christoph , Tsimikas Sotirios
Published: November 2024

BACKGROUND:

Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) levels are independently associated with atherosclerotic cardiovascular disease (ASCVD). However, the relationship between Lp(a) level, LDL-C level, and ASCVD risk at different thresholds is not well defined.

METHODS:

A participant-level meta-analysis of 27 658 participants enrolled in 6 placebo-controlled statin trials was performed to assess the association of LDL-C and Lp(a) levels with risk of fatal or nonfatal coronary heart disease events, stroke, or any coronary or carotid revascularization (ASCVD). The multivariable-adjusted association between baseline Lp(a) level and ASCVD risk was modeled continuously using generalized additive models, and the association between baseline LDL-C level and ASCVD risk by baseline Lp(a) level by Cox proportional hazards models with random effects. The joint association between Lp(a) level and statin-achieved LDL-C level with ASCVD risk was evaluated using Cox proportional hazards models.

RESULTS:

Compared with an Lp(a) level of 5 mg/dL, increasing levels of Lp(a) were log-linearly associated with ASCVD risk in statin- and placebo-treated patients. Among statin-treated individuals, those with Lp(a) level >50 mg/dL (≈125 nmol/L) had increased risk across all quartiles of achieved LDL-C level and absolute change in LDL-C level. Even among those with the lowest quartile of achieved LDL-C level (3.1–77.0 mg/dL), those with Lp(a) level >50 mg/dL had greater ASCVD risk (hazard ratio, 1.38 [95% CI, 1.06–1.79]) than those with Lp(a) level ≤50 mg/dL. The greatest risk was observed with both Lp(a) level >50 mg/dL and LDL-C level in the fourth quartile (hazard ratio, 1.90 [95% CI, 1.46–2.48]).

CONCLUSIONS:

These findings demonstrate the independent and additive nature of Lp(a) and LDL-C levels for ASCVD risk, and that LDL-C lowering does not fully offset Lp(a)-mediated risk.
Sestrin2 Attenuates Myocardial Endoplasmic Reticulum Stress and Cardiac Dysfunction During Ischemia/Reperfusion Injury
Authors: Li Xuan , Wang Zhen , Mouton Alan J. , Omoto Ana C. M. , da Silva Alexandre A. , do Carmo Jussara M. , Li Ji , Hall John E.
Published: November 2024

Background

Sesn2 (Sestrin2) is a stress‐induced protein that provides protective effects during myocardial ischemia and reperfusion (I/R) injury, while endoplasmic reticulum (ER) stress may be a pivotal mediator of I/R injury. The goal of this study was to determine whether Sesn2‐mTOR (mammalian target of rapamycin) signaling regulates ER stress during myocardial I/R.

Methods and Results

In vivo cardiac I/R was induced by ligation and subsequent release of the left anterior descending coronary artery in wild‐type (WT) and cardiac‐specific Sesn2 knockout (Sesn2

cKO

) mice. At 6 hours and 24 hours after reperfusion, cardiac function was evaluated, and heart samples were collected for analysis. I/R induced cardiac ER stress and upregulated Sesn2 mRNA and protein levels. Inhibiting ER stress with 4‐phenylbutyric acid reduced infarct size by 37.5%, improved cardiac systolic function, and mitigated myocardial cell apoptosis post‐I/R. Hearts from Sesn2

cKO

mice displayed increased susceptibility to ER stress during I/R compared with WT. Notably, cardiac mTOR signaling was further increased in Sesn2

cKO

hearts compared with WT hearts during I/R. In mice with cardiac Sesn2 deficiency, compared with WT, ER lumen was significantly expanded after tunicamycin‐induced ER stress, as assessed by transmission electron microscopy. Additionally, pharmacological inhibition of mTOR signaling with rapamycin improved cardiac function after tunicamycin treatment and significantly attenuated the unfolded protein response and apoptosis in WT and Sesn2

cKO

mice.

Conclusions

Sesn2 attenuates cardiac ER stress post‐I/R injury via regulation of mTOR signaling. Thus, modulation of the mTOR pathway by Sesn2 could be a critical factor for maintaining cardiac ER homeostasis control during myocardial I/R injury.
Lipoprotein (a) Testing in Patients With Atherosclerotic Cardiovascular Disease in 5 Large US Health Systems
Authors: Shah Nishant P. , Mulder Hillary , Lydon Elizabeth , Chiswell Karen , Hu Xingdi , Lampron Zachary , Cohen Lauren , Patel Manesh R. , Taubes Susan , Song Wenliang , Mulukutla Suresh R. , Saeed Anum , Morin Daniel P. , Bradley Steven M. , Hernandez Adrian F. , Pagidipati Neha J.
Published: November 2024

Background

Lipoprotein (a) is an independent risk factor for atherosclerotic cardiovascular disease. However, lipoprotein (a) testing remains variable and it is unclear what factors influence testing and if testing changes clinical management.

Methods and Results

A retrospective study using electronic medical record data from 5 health systems identified an atherosclerotic cardiovascular disease cohort divided into those with and without a lipoprotein (a) test between 2019 and 2021. Baseline characteristics and lipid‐lowering therapy patterns were assessed. Multivariable regression modeling was used to determine factors associated with lipoprotein (a) testing. Among 595 684 patients with atherosclerotic cardiovascular disease, only 2587 (0.4%) were tested for lipoprotein (a). Those who were older or Black individuals were less likely to have lipoprotein (a) testing, while those with familial hypercholesterolemia, ischemic stroke/transient ischemic attack, peripheral artery disease, prior lipid‐lowering therapy, or low‐density lipoprotein cholesterol ≥130 mg/dL were more likely to be tested. Those with a lipoprotein (a) test, regardless of the lipoprotein (a) value, were more frequently initiated on any statin therapy (30.3% versus 10.6%,
P
 < 0.001), ezetimibe (7.65% versus 0.8%,
P
 < 0.001), or proprotein convertase substilisin/kexin type 9 inhibitor (6.7% versus 0.3%,
P
 < 0.001) compared with those without a test. Those with an elevated lipoprotein (a) level more frequently initiated ezetimibe (11.5% versus 5.9%,
P
 < 0.001) or proprotein convertase substilisin/kexin type 9 inhibitor (10.9% versus 4.8%,
P
 < 0.001).

Conclusions

Lipoprotein (a) testing in patients with atherosclerotic cardiovascular disease is infrequent, with evidence of disparities among older or Black individuals. Testing for lipoprotein (a), regardless of level, is associated with greater initiation of any lipid‐lowering therapy, while elevated lipoprotein (a) is associated with greater initiation of nonstatin lipid‐lowering therapy. There is a critical need for multidisciplinary and inclusive approaches to raise awareness for lipoprotein (a) testing, and its implications on management.
Determination of Genotype and Phenotypes in Pediatric Patients With Biventricular Noncompaction
Authors: Hirono Keiichi , Hata Yukiko , Imamura Teruhiko , Tsuboi Kaori , Takarada Shinya , Okabe Mako , Nakaoka Hideyuki , Ibuki Keijiro , Ozawa Sayaka , Ichimata Shojiro , Nishida Naoki , Iwasaki Hidenori , Urata Susumu , Okada Seigo , Hiratsuji Tomoya , Sakaguchi Heima , Takigiku Kiyohiro , Nakazawa Makoto , Nishihara Eiki , Harada Masako , Matsuo Osamu , Yasuda Kenji , Yoshida Yoko , Namiki Hidemasa , Yasuda Kazushi , Ifuku Toshinobu , Urayama Kotaro , Oka Hideharu , Ogino Kayo , Kato Akio , Kan Nobuhiko , Seki Shunji , Seki Mitsuru , Odanaka Yutaka , Iwashima Satoru , Yoshida Shuichiro , Miyata Toyohisa , Miyamoto Tomoyuki , Watanabe Ken , Kuwabara Naoki , Inuzuka Ryo , Takahashi Yoshihiro , Sakazaki Hisanori , Muneuchi Jun , Kogaki Shigetoyo , Numano Fujito , Kido Sachiko , Nii Masaki , Hoshino Shinsuke , Ishida Hidekazu , Maeda Jun , Hayabuchi Yasunobu , Otsubo Yoshikazu , Ikeda Kazuyuki , Tsukano Shinya , Watanabe Makoto , Momoi Nobuo , Fujii Takanari , Fujioka Tao , Fujino Mitsuhiro , Uchiyama Hiroki , Baba Shigehito , Horigome Hitoshi , Honda Takashi , Suzuki Kazutaka , Ichida Fukiko
Published: November 2024

Background

Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent trabeculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC.

Methods and Results

We recruited children with left ventricular noncompaction from Japanese multi‐institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated cardiomyopathy, or normal function. In these patients, cardiomyopathy‐associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0–6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate (
P
=0.0009).

Conclusions

Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease‐causing genes and phenotype may help identify specific patients with left ventricular noncompaction and mortality‐related cardiac phenotypes.
Intraosseous and Intravenous Epinephrine Administration Routes in Out‐of‐Hospital Cardiac Arrest: Survival and Neurologic Outcomes
Authors: Yang Cheng‐Han , Ng Chip‐Jin , Huang Hsiu‐Ling , Chien Liang‐Tien , Wang Ming‐Fang , Chen Chen‐Bin , Tsai Li‐Heng , Huang Chien‐Hsiung , Tseng Hsiao‐Jung , Chien Cheng‐Yu
Published: November 2024

Background

The rate of survival after out‐of‐hospital cardiac arrest varies depending on the timeliness and effectiveness of prehospital interventions. This study was conducted to compare out‐of‐hospital cardiac arrest outcomes between intravenous and intraosseous routes and between upper and lower extremity routes for drug administration.

Methods and Results

We retrospectively analyzed data (collected using the Utstein template) from 1220 patients who had experienced out‐of‐hospital cardiac arrest in Taiwan's Taoyuan City between January 2021 and August 2023. The patients were stratified into intravenous and intraosseous groups by treatment approach and upper and lower extremity access groups by access site. The study outcomes were survival to discharge, favorable neurologic outcomes (Cerebral Performance Category score 1 or 2), and survival for >2 hours. The study groups were statistically compared before and after propensity score matching. Significant pre–propensity score matching differences were observed between intravenous and intraosseous groups, and the aforementioned study outcomes were better in the intravenous group than in the intraosseous group. However, the between‐group differences became nonsignificant after propensity score matching. Furthermore, lower extremity access and delayed epinephrine administration were associated with worse outcomes. Survival rates fell below 12.6% when time to treatment exceeded 15 minutes, particularly in the cases of intraosseous access and lower extremity access.

Conclusions

This study highlights the benefits of early intervention and upper extremity access for drug administration in patients with out‐of‐hospital cardiac arrest. Intraosseous access may serve as a viable alternative to intravenous access. Timely administration of essential drugs during resuscitation can improve clinical outcomes and thus has implications for emergency medical service training.
First Record of the Genus Arpactophilus Smith, 1863 (Hymenoptera: Crabronidae: Pemphredoninae) outside Australasia with the Description of a New Species from Northeastern India
Authors: AMAL S. , KUMAR P. GIRISH , RAMESHKUMAR A.
Published: November 2024

The aphid wasp genus Arpactophilus Smith, 1863 is reported from India, for the first time outside Australasia. A new species Arpactophilus pulawskii Amal & Girish Kumar sp. nov. is described and illustrated.
Pararhigognostis—a new genus for Plutella stichocentra Meyrick, 1932 (Lepidoptera, Plutellidae), with a redescription of its male and female genitalia
Authors: BARANIAK EDWARD , AGASSIZ DAVID
Published: November 2024

Pararhigognostis Baraniak & Agassiz, gen. nov., is described and illustrated for the enigmatic Plutella stichocentra Meyrick, 1932. The morphology of male and female genitalia is described for the first time, and they serve to distinguish the new genus from all other genera of the family Plutellidae. The new genus is defined by the structure of the valva, long saccus, and shape of socii in the male genitalia, as well as by the shape of antrum and long, very thin apophyses posteriores in the female genitalia. The type species of Pararhigognostis, P. stichocentra, is redescribed. Line drawings of the male and female genitalia of the species are provided.
Comprehensive description of new and known stages of Americabaetis titthion Lugo-Ortiz & McCafferty (Ephemeroptera: Baetidae)
Authors: AMARAL IGOR FERREIRA , SALLES FREDERICO FALCÃO
Published: November 2024

The male imago of Americabaetis titthion is described for the first time. It can be distinguished from other male imagos of the genus by the following combination of characteristics: turbinate portion of the eyes with upper surface ellipsoidal and separated by approximately the width of a lateral ocellus; costal area of fore wings tinged with reddish-brown; presence of pairs of soft, setose protuberances on the meso- and metasternum; subgenital plate slightly concave; forceps with segment I/II slightly tapering medioapically. Supplementary descriptions for the nymph and female imago are provided, as well as the first description of the eggs of a species of the genus.
The Struggle You Can’t See
Authors: Lierman Ash
Published: November 2024

This book offers a comprehensive review of current research on the higher education experiences of neurodivergent undergraduate students and those with invisible disabilities. Grounded in principles of social justice and equity, this work draws from design thinking, the neurodiversity model, and Universal Design for Learning, to explore the context of higher education in relation to neurodivergent and disabled students.

The author discusses findings from literature on the experiences of students with ADHD, dyslexia, autism, psychiatric disabilities, traumatic brain injuries, and disabling chronic physical illnesses. The inclusion of students with chronic illnesses is particularly timely, given the rising prevalence of long COVID symptoms and other lasting health impacts among university-aged individuals. Moreover Ash Lierman, who has extensive experience of serving students marginalized students, gives voice to this community, thus providing both a synthesis of existing research, and highlighting the needs and challenges of the students themselves.

The Struggle You Can’t See serves as a valuable resource for researchers and practitioners seeking to understand and support this underserved population, offering insights for transformational change in higher education.
5. Co-Curricular Campus Life
Authors: Lierman Ash
Published: November 2024

This chapter describes the needs, challenges, and supports that students experience in aspects of campus life outside of instructional settings. These include social life and peer relationships, mental health challenges and needs, the physical environments of campus, and aspects of daily living in on-campus residences.
Development of a rapid method for the simultaneous determination of aminophylline, doxofylline, bromhexine, and ambroxol by HPLC
Authors: Meng Xia , Feng Yunxia , Chen Fuchao , Shi Ming , Fang Baoxia
Published: November 2024

Introduction: Antitussive and expectorant drugs such as aminophylline (APL), doxofylline (DXL), bromhexine hydrochloride (BXH), and ambroxol hydrochloride (AXH), either individually or in combination, are widely used in the prevention and treatment of respiratory diseases. The study aimed to establish a high-performance liquid chromatography (HPLC) method for the simultaneous determination of these four drugs and to investigate their stability in 0.9% sodium chloride injection or 5% glucose injection over 48 hours. Methods: An InertSustain C18 column (150 mm × 4.6 mm, 5 μm) was used. The mobile phase consisted of acetonitrile and 50 mmol·L−1 potassium dihydrogen phosphate solution (pH 4.0) with gradient elution. The flow rate was 0.8 mL·min−1, and the column temperature was maintained at 30°C. The stability of APL, DXL, BXH, and AXH in 0.9% sodium chloride and 5% glucose injections over 48 h was determined using HPLC. Results: APL, DXL, BXH, and AXH showed good linearity within the ranges of 0.01 to 0.20, 0.003–0.06, 0.015–0.30, and 0.016–0.16 mg·mL−1, respectively (r > 0.999). The intraday and interday relative standard deviations were <2%, with recovery rates between 98.4% and 102.2%. The four drugs remained colorless and clear in infusion mixtures. The pH value fluctuated within ±0.3 over 48 hours, and the relative percentage content of the drugs ranged from 95.0% to 105.0%. Conclusion: The established HPLC method is simple, reliable, and stable, allowing for the simultaneous determination of the four antitussive and expectorant drugs. APL, DXL, BXH, and AXH were stable within 48 hours when mixed with 0.9% sodium chloride and 5% glucose injections.
Examining Finnish teachers’ professional agency in the professional community in curriculum reform / Análisis de la agencia profesional de los docentes finlandeses en la comunidad profesional en la reforma curricular
Authors: Laivuori Martti , Toom Auli , Tikkanen Lotta , Pyhältö Kirsi
Published: November 2024

Reforming curriculum is potentially a powerful tool for school development. Harnessing this potential calls for teacher engagement with colleagues for active professional learning, i.e., teachers’ professional agency. However, promoting teachers’ ownership and active involvement in curriculum-making provides a challenge for all levels of policy interpretation. Furthermore, variation in how teachers perceive a curriculum reform, its impact in schools and their agency within the reform are likely to occur. Yet, we still know little about this variation. We address this gap identified in prior literature by examining the individual variation and relationships within and between teachers’ sense of professional agency, perceptions of the large-scale curriculum reform impact and perceptions of overall success of the reform on a national level in the Finnish context. Teachers ( N = 1,531) from 74 schools in Finland participated in the study. Relationships between variables were examined using t-tests and ANOVAs, and latent profile analysis was used to identify professional agency profiles. The results showed that perceptions of reform impact, reform overall success and professional agency varied partly according to gender, school size, school type and teaching experience. Four profiles were identified: High sense of professional agency, Reduced collective efficacy, Active help seekers and Commitment to mutual agreement. High perceived school impact and overall reform success were linked to strong professional agency. The findings imply that development work in the context of curriculum reform can be facilitated by agentic learning in the professional community.