bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Fig. 2 from MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell–intrinsic Amplification of Type I IFN Signaling
Authors: Ghukasyan Razmik , Liang Keke , Chau Kevin , Li Luyi , Chan Charlotte , Abt Evan R. , Le Thuc , Park Joon Y. , Wu Nanping , Premji Alykhan , Damoiseaux Robert , Luu Tony , Labora Amanda , Rashid Khalid , Link Jason M. , Radu Caius G. , Donahue Timothy R.
Published: June 2023

Supplementary Fig. 2 Tumor growth is inhibited by STING agonism and MEK inhibition in vivo.
Supplementary Figure S3 from A Bifunctional PARP-HDAC Inhibitor with Activity in Ewing Sarcoma
Authors: Ramos Louise , Truong Sarah , Zhai Beibei , Joshi Jay , Ghaidi Fariba , Lizardo Michael M. , Shyp Taras , Kung Sonia H.Y. , Rezakhanlou Alireza M. , Oo Htoo Zarni , Adomat Hans , Le Bihan Stephane , Collins Colin , Bacha Jeffrey , Brown Dennis , Langlands John , Shen Wang , Lallous Nada , Sorensen Poul H. , Daugaard Mads
Published: June 2023

Replicates of cell cycle assays and statistics
Figure S7 from BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non–Small Cell Lung Cancer
Authors: Lim Sun Min , Fujino Toshio , Kim Chulwon , Lee Gwanghee , Lee Yong-Hee , Kim Dong-Wan , Ahn Jin Seok , Mitsudomi Tetsuya , Jin Taiguang , Lee Sang-Yoon
Published: June 2023

Supplementary Figure 7. Duration of treatment and tumor response in all patients in QD dosing cohorts by dose level.
Supplementary Figure S2 from A Bifunctional PARP-HDAC Inhibitor with Activity in Ewing Sarcoma
Authors: Ramos Louise , Truong Sarah , Zhai Beibei , Joshi Jay , Ghaidi Fariba , Lizardo Michael M. , Shyp Taras , Kung Sonia H.Y. , Rezakhanlou Alireza M. , Oo Htoo Zarni , Adomat Hans , Le Bihan Stephane , Collins Colin , Bacha Jeffrey , Brown Dennis , Langlands John , Shen Wang , Lallous Nada , Sorensen Poul H. , Daugaard Mads
Published: June 2023

Replicate graphs of cell viability assays and comparison of cell viability assay methods
Figure S6 from BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non–Small Cell Lung Cancer
Authors: Lim Sun Min , Fujino Toshio , Kim Chulwon , Lee Gwanghee , Lee Yong-Hee , Kim Dong-Wan , Ahn Jin Seok , Mitsudomi Tetsuya , Jin Taiguang , Lee Sang-Yoon
Published: June 2023

Supplementary Figure 6. Analysis of BBT-176 using in vivo models. A, Body weight changes in Ba/F3 EGFR 19Del/C797S, EGFR 19Del/T790M/C797S and patient-derived xenograft models. The patient-derived xenograft was derived from a patient with poorly-differentiated adenocarcinoma harboring an EGFR 19Del/T790M/C797S mutation. B, BBT-176 activity in a LU1235 EGFR 19Del patient-derived xenograft model. Abbreviations: PDX, patient-derived xenograft; PO, orally; QD, once daily.
Figure S4 from BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non–Small Cell Lung Cancer
Authors: Lim Sun Min , Fujino Toshio , Kim Chulwon , Lee Gwanghee , Lee Yong-Hee , Kim Dong-Wan , Ahn Jin Seok , Mitsudomi Tetsuya , Jin Taiguang , Lee Sang-Yoon
Published: June 2023

Supplementary Figure 4. Western blot of Ba/F3 cells with the EGFR 19Del/T790M/C797S mutation after BBT-176 treatment, alone and combined with cetuximab.
Supplementary Table S3 from Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non–Small Cell Lung Cancer: The Piedmont Study
Authors: Eisner Joel R. , Mayhew Gregory M. , Davison James M. , Beebe Kirk D. , Shibata Yoichiro , Guo Yuelong , Farhangfar Carol , Farhangfar Farhang , Uronis Joshua M. , Conroy Jeffrey M. , Milburn Michael V. , Hayes David Neil , Mileham Kathryn F.
Published: June 2023

Relationship of the expression of individual genes (ATIC, GART, DHFR, MTHFD1L or TYMS) with survival.
Supplemental Figure 2 from Genetic Alterations Detected by Circulating Tumor DNA in HER2-Low Metastatic Breast Cancer
Authors: Hensing Whitney L. , Gerratana Lorenzo , Clifton Katherine , Medford Arielle J. , Velimirovic Marko , Shah Ami N. , D'Amico Paolo , Reduzzi Carolina , Zhang Qiang , Dai Charles S. , Denault Elyssa N. , Bagegni Nusayba A. , Opyrchal Mateusz , Ademuyiwa Foluso O. , Bose Ron , Behdad Amir , Ma Cynthia X. , Bardia Aditya , Cristofanilli Massimo , Davis Andrew A.
Published: June 2023

Supplemental Figure 2. Interaction between HER2-low status and oncogenic pathways on overall survival.
Supplementary Methods S1 from Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non–Small Cell Lung Cancer: The Piedmont Study
Authors: Eisner Joel R. , Mayhew Gregory M. , Davison James M. , Beebe Kirk D. , Shibata Yoichiro , Guo Yuelong , Farhangfar Carol , Farhangfar Farhang , Uronis Joshua M. , Conroy Jeffrey M. , Milburn Michael V. , Hayes David Neil , Mileham Kathryn F.
Published: June 2023

Development of the 48-gene LUAD nearest centroid classifier
Supplemental Figure 1 from Genetic Alterations Detected by Circulating Tumor DNA in HER2-Low Metastatic Breast Cancer
Authors: Hensing Whitney L. , Gerratana Lorenzo , Clifton Katherine , Medford Arielle J. , Velimirovic Marko , Shah Ami N. , D'Amico Paolo , Reduzzi Carolina , Zhang Qiang , Dai Charles S. , Denault Elyssa N. , Bagegni Nusayba A. , Opyrchal Mateusz , Ademuyiwa Foluso O. , Bose Ron , Behdad Amir , Ma Cynthia X. , Bardia Aditya , Cristofanilli Massimo , Davis Andrew A.
Published: June 2023

Supplemental Figure 1. Mutation distribution for the PIK3CA gene in the overall study population divided by HER2-status.
Supplementary Figure S2 from Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non–Small Cell Lung Cancer: The Piedmont Study
Authors: Eisner Joel R. , Mayhew Gregory M. , Davison James M. , Beebe Kirk D. , Shibata Yoichiro , Guo Yuelong , Farhangfar Carol , Farhangfar Farhang , Uronis Joshua M. , Conroy Jeffrey M. , Milburn Michael V. , Hayes David Neil , Mileham Kathryn F.
Published: June 2023

Expression of Genes Associated with Antifolate (Pemetrexed) Activity by LUAD Subtype.
Figure S5 from BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non–Small Cell Lung Cancer
Authors: Lim Sun Min , Fujino Toshio , Kim Chulwon , Lee Gwanghee , Lee Yong-Hee , Kim Dong-Wan , Ahn Jin Seok , Mitsudomi Tetsuya , Jin Taiguang , Lee Sang-Yoon
Published: June 2023

Supplementary Figure 5. Growth inhibition by BBT-176 with and without cetuximab in BBT-176-resistant clones. IC50 values were measured 3 days later and cell growth was plotted relative to untreated control cells (mean ± SD). Abbreviation: BR(1/2), BBT-176-resistant (clone 1/2).
Figure S3 from BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non–Small Cell Lung Cancer
Authors: Lim Sun Min , Fujino Toshio , Kim Chulwon , Lee Gwanghee , Lee Yong-Hee , Kim Dong-Wan , Ahn Jin Seok , Mitsudomi Tetsuya , Jin Taiguang , Lee Sang-Yoon
Published: June 2023

Supplementary Figure 3. Activity of osimertinib in EGFR 19Del-derived BBT-176-resistant clones. Abbreviation: BR(1/2), BBT-176-resistant (clone 1/2).
Figure S1 from BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non–Small Cell Lung Cancer
Authors: Lim Sun Min , Fujino Toshio , Kim Chulwon , Lee Gwanghee , Lee Yong-Hee , Kim Dong-Wan , Ahn Jin Seok , Mitsudomi Tetsuya , Jin Taiguang , Lee Sang-Yoon
Published: June 2023

Supplementary Figure 1. Growth inhibition by BBT-176 with and without cetuximab in EGFR 19Del and EGFR L858R-derived mutants. Abbreviation: N/E, not evaluable.
Data from A Multiparameter Molecular Classifier to Predict Response to Neoadjuvant Lapatinib plus Trastuzumab without Chemotherapy in HER2+ Breast Cancer
Authors: Veeraraghavan Jamunarani , Gutierrez Carolina , De Angelis Carmine , Davis Robert , Wang Tao , Pascual Tomas , Selenica Pier , Sanchez Katherine , Nitta Hiroaki , Kapadia Monesh , Pavlick Anne C. , Galvan Patricia , Rexer Brent , Forero-Torres Andres , Nanda Rita , Storniolo Anna M. , Krop Ian E. , Goetz Matthew P. , Nangia Julie R. , Wolff Antonio C. , Weigelt Britta , Reis-Filho Jorge S. , Hilsenbeck Susan G. , Prat Aleix , Osborne C. Kent , Schiff Rachel , Rimawi Mothaffar F.
Published: June 2023

AbstractBackground:
Clinical trials reported 25% to 30% pathologic complete response (pCR) rates in HER2+ patients with breast cancer treated with anti-HER2 therapies without chemotherapy. We hypothesize that a multiparameter classifier can identify patients with HER2-“addicted” tumors who may benefit from a chemotherapy-sparing strategy.
Patients and Methods:
Baseline HER2+ breast cancer specimens from the TBCRC023 and PAMELA trials, which included neoadjuvant treatment with lapatinib and trastuzumab, were used. In the case of estrogen receptor–positive (ER+) tumors, endocrine therapy was also administered. HER2 protein and gene amplification (ratio), HER2-enriched (HER2-E), and PIK3CA mutation status were assessed by dual gene protein assay (GPA), research-based PAM50, and targeted DNA-sequencing. GPA cutoffs and classifier of response were constructed in TBCRC023 using a decision tree algorithm, then validated in PAMELA.
Results:
In TBCRC023, 72 breast cancer specimens had GPA, PAM50, and sequencing data, of which 15 had pCR. Recursive partitioning identified cutoffs of HER2 ratio ≥ 4.6 and %3+ IHC staining ≥ 97.5%. With PAM50 and sequencing data, the model added HER2-E and PIK3CA wild-type (WT). For clinical implementation, the classifier was locked as HER2 ratio ≥ 4.5, %3+ IHC staining ≥ 90%, and PIK3CA-WT and HER2-E, yielding 55% and 94% positive (PPV) and negative (NPV) predictive values, respectively. Independent validation using 44 PAMELA cases with all three biomarkers yielded 47% PPV and 82% NPV. Importantly, our classifier's high NPV signifies its strength in accurately identifying patients who may not be good candidates for treatment deescalation.
Conclusions:
Our multiparameter classifier differentially identifies patients who may benefit from HER2-targeted therapy alone from those who need chemotherapy and predicts pCR to anti-HER2 therapy alone comparable with chemotherapy plus dual anti-HER2 therapy in unselected patients.
Data from Genetic Alterations Detected by Circulating Tumor DNA in HER2-Low Metastatic Breast Cancer
Authors: Hensing Whitney L. , Gerratana Lorenzo , Clifton Katherine , Medford Arielle J. , Velimirovic Marko , Shah Ami N. , D'Amico Paolo , Reduzzi Carolina , Zhang Qiang , Dai Charles S. , Denault Elyssa N. , Bagegni Nusayba A. , Opyrchal Mateusz , Ademuyiwa Foluso O. , Bose Ron , Behdad Amir , Ma Cynthia X. , Bardia Aditya , Cristofanilli Massimo , Davis Andrew A.
Published: June 2023

AbstractIntroduction:
About 50% of breast cancers are defined as HER2-low and may benefit from HER2-directed antibody–drug conjugates. While tissue sequencing has evaluated potential differences in genomic profiles for patients with HER2-low breast cancer, genetic alterations in circulating tumor DNA (ctDNA) have not been well described.
Materials and Methods:
We retrospectively analyzed 749 patients with metastatic breast cancer (MBC) and ctDNA evaluation by Guardant360 from three academic medical centers. Tumors were classified as HER2-low, HER2-0 (IHC 0) or HER2-positive. Single-nucleotide variants, copy-number variants, and oncogenic pathways were compared across the spectrum of HER2 expression. Overall survival (OS) was evaluated by HER2 status and according to oncogenic pathways.
Results:
Patients with HER2-low had higher rates of PIK3CA mutations [relative risk ratio (RRR), 1.57; P = 0.024] compared with HER2-0 MBC. There were no differences in ERBB2 alterations or oncogenic pathways between HER2-low and HER2-0 MBC. Patients with HER2-positive MBC had more ERBB2 alterations (RRR, 12.43; P = 0.002 for amplification; RRR, 3.22; P = 0.047 for mutations, in the hormone receptor–positive cohort), fewer ERS1 mutations (RRR, 0.458; P = 0.029), and fewer ER pathway alterations (RRR, 0.321; P < 0.001). There was no difference in OS for HER2-low and HER2-0 MBC [HR, 1.01; 95% confidence interval (CI), 0.79–1.29], while OS was improved in HER2-positive MBC (HR, 0.32; 95% CI, 0.21–0.49; P < 0.001).
Conclusions:
We observed a higher rate of PIK3CA mutations, but no significant difference in ERBB2 alterations, oncogenic pathways, or prognosis, between patients with HER2-low and HER2-0 MBC. If validated, our findings support the conclusion that HER2-low MBC does not represent a unique biological subtype.
PD-1 Monotherapy Reigns Supreme in Adjuvant Melanoma…But for How Long?
Authors: Augustin Ryan C. , Luke Jason J.
Published: June 2023

The results of CheckMate-238 led to the original FDA approval of anti–PD-1 therapy in high-risk, resectable melanoma. In this CCR Translations, we discuss the 5-year update of this pivotal trial and contextualize its results in the face of limited survival data, neoadjuvant therapy, next-generation biomarkers, and novel immunotherapy combinations.

See related article by Larkin et al., p. 3352
Supplementary Table S6 from Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function
Authors: Renauer Paul , Park Jonathan J. , Bai Meizhu , Acosta Arianny , Lee Won-Ho , Lin Guang Han , Zhang Yueqi , Dai Xiaoyun , Wang Guangchuan , Errami Youssef , Wu Terence , Clark Paul , Ye Lupeng , Yang Quanjun , Chen Sidi
Published: June 2023

Supplementary Table S6
Supplementary Table S1 from Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function
Authors: Renauer Paul , Park Jonathan J. , Bai Meizhu , Acosta Arianny , Lee Won-Ho , Lin Guang Han , Zhang Yueqi , Dai Xiaoyun , Wang Guangchuan , Errami Youssef , Wu Terence , Clark Paul , Ye Lupeng , Yang Quanjun , Chen Sidi
Published: June 2023

Supplementary Table S1
Supplementary Video 1 from Metronomic administration of topotecan alone and in combination with docetaxel inhibits epithelial-mesenchymal transition in aggressive variant prostate cancers
Authors: MITRA GHOSH TARASWI , Mazumder Suman , Davis Joshua , YADAV JYOTI , AKINPELU AYUBA , ALNAIM AHMED , KUMAR HARISH , WALIAGHA RAZAN , Church Bird Allison E , Rais-Bahrami Soroush , Bird R. Curtis , Mistriotis Panagiotis , MISHRA AMARJIT , Yates Clayton C. , MITRA AMIT K , Arnold Robert D
Published: June 2023

Supplementary Video 1
Supplementary Methods from Metronomic administration of topotecan alone and in combination with docetaxel inhibits epithelial-mesenchymal transition in aggressive variant prostate cancers
Authors: MITRA GHOSH TARASWI , Mazumder Suman , Davis Joshua , YADAV JYOTI , AKINPELU AYUBA , ALNAIM AHMED , KUMAR HARISH , WALIAGHA RAZAN , Church Bird Allison E , Rais-Bahrami Soroush , Bird R. Curtis , Mistriotis Panagiotis , MISHRA AMARJIT , Yates Clayton C. , MITRA AMIT K , Arnold Robert D
Published: June 2023

Supplementary Methods
TABLE 1 from Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Authors: Cecchini Michael , Zhang Janie Y. , Wei Wei , Sklar Jeffrey , Lacy Jill , Zhong Minghao , Kong Yong , Zhao Hongyu , DiPalermo Jassim , Devine Lesley , Stein Stacey M. , Kortmansky Jeremy , Johung Kimberly L. , Bindra Ranjit S. , LoRusso Patricia , Schalper Kurt A.
Published: June 2023

Baseline characteristics
Supplementary Table 1 from Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Authors: Cecchini Michael , Zhang Janie Y. , Wei Wei , Sklar Jeffrey , Lacy Jill , Zhong Minghao , Kong Yong , Zhao Hongyu , DiPalermo Jassim , Devine Lesley , Stein Stacey M. , Kortmansky Jeremy , Johung Kimberly L. , Bindra Ranjit S. , LoRusso Patricia , Schalper Kurt A.
Published: June 2023

Supplementary Table 1: Study representativeness table.
Supplementary Figure 4 from Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Authors: Cecchini Michael , Zhang Janie Y. , Wei Wei , Sklar Jeffrey , Lacy Jill , Zhong Minghao , Kong Yong , Zhao Hongyu , DiPalermo Jassim , Devine Lesley , Stein Stacey M. , Kortmansky Jeremy , Johung Kimberly L. , Bindra Ranjit S. , LoRusso Patricia , Schalper Kurt A.
Published: June 2023

Supplementary Figure 4: The change in PBMCs for patients with clinical benefit (blue) and no benefit (red).
Supplementary Figure 1 from Quantitative DNA Repair Biomarkers and Immune Profiling for Temozolomide and Olaparib in Metastatic Colorectal Cancer
Authors: Cecchini Michael , Zhang Janie Y. , Wei Wei , Sklar Jeffrey , Lacy Jill , Zhong Minghao , Kong Yong , Zhao Hongyu , DiPalermo Jassim , Devine Lesley , Stein Stacey M. , Kortmansky Jeremy , Johung Kimberly L. , Bindra Ranjit S. , LoRusso Patricia , Schalper Kurt A.
Published: June 2023

Supplementary Figure 1: Survival Analysis.
Endovascular Transcatheter Aortic Valve Replacement Outcomes in Hypertrophic Cardiomyopathy: Insights from the National Inpatient Sample (2014–2018)
Authors: Vyas Rohit , Nazir Salik , Ahuja Keerat Rai , Minhas Abdul Mannan Khan , Elzanaty Ahmed , Mir Tanveer , Sheikh Mujeeb
Published: June 2023

Background: Outcomes of patients with hypertrophic cardiomyopathy (HCM) following transcatheter aortic valve replacement (TAVR) remain largely unknown. Objectives: This study sought to assess the clinical characteristics and outcomes of HCM patients following TAVR. Methods: We queried the National Inpatient Sample from 2014 to 2018 for TAVR hospitalizations with and without HCM, creating a propensity-matched cohort to compare outcomes. Results: 207,880 patients that underwent TAVR during the study period, 810 (0.38%) had coexisting HCM. In the unmatched population, TAVR patients with HCM compared to those without HCM, were more likely to be female, had a higher prevalence of heart failure, obesity, cancer, and history of pacemaker/implantable cardioverter defibrillation, and were more likely to have nonelective and weekend admissions (p for all <0.05). TAVR patients without HCM had higher prevalence of coronary artery disease, prior percutaneous coronary intervention, prior coronary artery bypass grafting, and peripheral arterial disease compared to their counterparts (p for all <0.05). In the propensity-matched cohort, TAVR patients with HCM had significantly higher incidence of in-hospital mortality, acute kidney injury/hemodialysis, bleeding complications, vascular complications, permanent pacemaker requirement, aortic dissection, cardiogenic shock, and mechanical ventilation requirement. Conclusion: Endovascular TAVR in HCM patients is associated with an increased incidence of in-hospital mortality and procedural complications.
Recent Advances in Systemic Therapy for Advanced Intrahepatic Cholangiocarcinoma
Authors: Yoo Changhoon , Hyung Jaewon , Chan Stephen L.
Published: June 2023

Background: The incidence of intrahepatic cholangiocarcinoma (IHCCA) is rising around the world. The disease is becoming a major global health issue. Conventionally, most patients with cholangiocarcinoma present with advanced disease and systemic therapy is the mainstay of treatment. This review discusses recent advances in systemic treatments for patients with IHCCA. Summary: The addition of durvalumab to a gemcitabine plus cisplatin regimen has significantly improved overall survival in the phase 3 TOPAZ-1 trial and is currently recommended as a standard first-line treatment. The phase 3 ABC-06 and phase 2b NIFTY trials have shown the benefit of second-line fluoropyrimidine plus oxaliplatin, and fluoropyrimidine plus nanoliposomal irinotecan, respectively. They have provided a treatment option for patients without actionable alterations who progressed to first-line therapy. For patients with actionable genomic alterations, including FGFR2 rearrangement, IDH1 mutation, BRAF mutation, and ERBB2 amplification, targeted agents have shown encouraging efficacy in several phase 2–3 trials, and are recommended as subsequent treatments. Immune checkpoint inhibitors are being investigated for the treatment of previously treated patients, although only a small proportion of patients showed durable responses. Key Messages: Recent advances in systemic treatments have improved clinical outcomes in patients with advanced IHCCA. However, most patients eventually show resistance to the treatment, and tumor progression occurs within a year. Indeed, there should be further efforts to improve the outcomes of patients with advanced IHCCA.
BAG3 Overexpression Attenuates Ischemic Stroke Injury by Activating Autophagy and Inhibiting Apoptosis
Authors: Liu Xia , Ye Qinlian , Huang Zhengzheng , Li Xiuping , Zhang Liping , Liu Xuan , Wu Yun-Cheng , Brockmeier Ulf , Hermann Dirk M. , Wang Ya-Chao , Ren Lijie
Published: June 2023

BACKGROUND:

The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to autophagy with changes in BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia in mice. BAG3 is an antiapoptotic-cochaperone that is directly involved in cellular protein quality control as a mediator for selective macroautophagy. Here, we aimed to investigate the role of BAG3 in ischemic stroke.

METHODS:

Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation were used to mimic cerebral ischemia in vivo and in vitro. The UPS inhibitor MG132 and autophagy inhibitor 3-MA (3-methyladenine) were administered to mice to identify how BAG3 was involved after MCAO/R. Adeno-associated virus and lentiviral vector were used to regulate BAG3 expression in vivo and in vitro, respectively. Behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, and Hematoxylin & Eosin staining were performed to evaluate cerebral injury following MCAO/R, and a Cell Counting kit-8 assay was conducted to assess oxygen-glucose deprivation/reoxygenation–induced injury in cells. Brain tissues and cell lysates were collected and analyzed for UPS activation, autophagy, and apoptosis.

RESULTS:

The UPS inhibitor alleviated MCAO injury in mice and increased autophagy and BAG3 expression, whereas the autophagy inhibitor exacerbated MCAO/R-induced injury. In addition, BAG3 overexpression significantly improved neurological outcomes, reduced infarct volume in vivo, and enhanced cell survival by activating autophagy and suppressing apoptosis in vitro.

CONCLUSIONS:

Our findings indicate that BAG3 overexpression activates autophagy and inhibits apoptosis to prevent cerebral ischemia/reperfusion and hypoxia/reoxygenation injury, suggesting a potential therapeutic benefit of BAG3 expression in cerebral ischemia.
Transcranial Direct Current Stimulation Reverses Stroke-Induced Network Alterations in Mice
Authors: Blaschke Stefan J. , Vlachakis Susan , Pallast Niklas , Walter Helene L. , Volz Lukas J. , Wiedermann Dirk , Fink Gereon R. , Hoehn Mathias , Aswendt Markus , Schroeter Michael , Rueger Maria A.
Published: June 2023

BACKGROUND:

Beyond focal effects, stroke lesions impact the function of distributed networks. We here investigated (1) whether transcranial direct current stimulation (tDCS) alters the network changes induced by cerebral ischemia and (2) whether functional network parameters predict the therapeutic efficacy of tDCS in a mouse model of focal photothrombotic stroke.

METHODS:

Starting 3 days after stroke, cathodal tDCS (charge density=39.6 kC/m²) was applied over 10 days in male C57Bl/6J mice under light anesthesia over the lesioned sensory-motor cortex. Functional connectivity (resting-state functional magnetic resonance imaging) was evaluated for up to 28-day poststroke, with global graph parameters of network integration computed.

RESULTS:

Ischemia induced a subacute increase in connectivity accompanied by a significant reduction in characteristic path length, reversed by 10 days of tDCS. Early measures of functional network alterations and the network configuration at prestroke baseline predicted spontaneous and tDCS-augmented motor recovery.

DISCUSSION:

Stroke induces characteristic network changes throughout the brain that can be detected by resting-state functional magnetic resonance imaging. These network changes were, at least in part, reversed by tDCS. Moreover, early markers of a network impairment and the network configuration before the insult improve the prediction of motor recovery.
Efficacy of Angioscopy for the Detection of Mobile Carotid Artery Lesions
Authors: Fukutome Kenji , Aketa Shuta , Mitsui Takaaki , Shiraishi Yuki , Hayami Hiromichi , Murakami Yasutaka , Matsuoka Ryuta , Shiba Mikio , Tei Rinsei , Shin Yasushi , Motoyama Yasushi
Published: June 2023

Case presentation

A 78‐year‐old man with a mobile lesion was diagnosed with thrombus using carotid ultrasonography, but the lesion was not completely resolved with dual antiplatelet and anticoagulation therapy. Direct visualization by angioscopy showed a white mobile plaque. The carotid artery was stented with a double‐layered stent, as the plaque persisted despite continuing the medical treatment and was linked to an increased risk of cerebral embolism. The plaque was attached to the arterial wall, and it subsequently disappeared. The patient recovered well and no further emboli were observed.

Conclusions

Angioscopy is effective for identifying lesions under direct vision. The characteristics and dynamics of plaques may be viewed via angioscopy, which aids in making treatment‐related decisions, particularly in the case of carotid artery plaques.
Maupertuis and the Reshaping of Natural History in Eighteenth-Century France
Authors: Storni Marco
Published: June 2023

In this paper, I analyze a momentous change in eighteenth century French life sciences. Whereas in the first half of the century the conception of natural history as the systematic collection of facts had been most successful, at mid-century a new approach emerged. This approach was characterized by an accent on general philosophical themes rather than on observation and experiment. I study the grounds and features of this historical shift through the work of Maupertuis, who published papers in institutional (or Baconian) natural history in his early years, but then adopted a more speculative approach to the life sciences.
Richard Lavenham’s Tractatus terminorum naturalium
Authors: Hanke Miroslav
Published: June 2023

The late fourteenth-century English Carmelite Richard Lavenham was a prolific author of Latin and vernacular treatises on logic, physics, philosophy, and theology. Among other works pertaining to natural philosophy, he authored the short Tractatus terminorum naturalium, preserved in three complete or almost complete late fourteenth- or early fifteenth-century copies, with the opening passage preserved in three other manuscripts. The text is fundamentally a redaction of the Heytesburian Termini naturales, a brief glossary of technical vocabulary of the natural philosophy and physics of the Oxford Calculators, supplemented by additional textual and pictorial material. As such, Lavenham’s treatise is a specific branch of an influential tradition of school texts that took the form of elementary treatises, additional glosses, quaestio-commentaries, and excerpts.
Local Communities and Archaeological Sites in Tunisia: A Case Study at Dougga (Ancient Thugga) about Cultural Memory and Cultural Markers in the Longue Durée
Authors: Whitehouse John , Harize Sami
Published: June 2023

The experience and legends of local communities in Tunisia who lived within archaeological sites and shared long-standing connections with those sites has been poorly recognised and documented. The extent to which elements of the cultural memory of local communities refer back to the pre-Islamic period has often been hinted at, but rarely explored in detail. The aim of this paper is to examine the relationship between local communities and archaeological sites in Tunisia, and the extent to which modern cultural memory in a community embeds elements or cultural markers from the Roman, Punic and Numidian past. This case study examines the cult of Oum Khoula at the site of Dougga (ancient Thugga). The marabout of Oum Khoula is in the cisterns of Aïn El-Hammam, at the end of the major Roman aqueduct to Dougga. Oum Khoula is remembered by local inhabitants as associated with a range of legends stretching back to the Roman and pre-Roman past. The cult has continued to be revered to the modern day. Whether the cultural memory illustrated by the cult of Oum Khoula at Dougga represents continuity with the past cannot be proved or disproved and is ultimately not the important issue. The cult of Oum Khoula at Dougga represents an example of the persistence of references from Numidian, Punic and Roman periods in the Maghreb. That cultural memory is a function of the community’s sense of place and significant references to that place derive from the archaeological remains and its associated oral traditions and symbols found at Dougga. The question of how modern archaeologists respond to and interpret this cultural memory is discussed.
The Dangers of Desire: Medieval Franciscans as Book Owners
Authors: Welch Anna
Published: June 2023

The Order of the Friars Minor faced a dilemma from the outset: their Rule of life, written by their founder St Francis of Assisi, included a strict adherence to the ideal of absolute poverty (that is, living without property, even property held in common), and yet it was impossible to fulfil their pastoral activities in the community without at least one type of property – liturgical books. In both the earlier (1209/10–1221) and later (1223) Rules, St Francis discussed the ownership of books, but not their production. Surviving manuscripts and archival records alert us to the fact that friars did produce their own liturgical books and act as the scribes and illuminators of books made for others. As both producers and owners of illuminated manuscripts, the friars engaged in a careful navigation of the relationship between beauty (permissible as an expression of invisible divine beauty, as defined by Hugh of St Victor) and luxury. It was all too easy (as the Franciscan Durand of Champagne bemoaned) for friars to desire ‘beautiful … and … curiously illuminated [books, rather] than true and well corrected ones’. This essay explores the ways in which friars negotiated the issues of poverty, beauty and luxury, and how they expressed and satisfied their desire for books, drawing on examples from the library of the Sacro Convento in Assisi.
When Churches Discovered the Digital Divide: Overcoming Technological Inaccessibility, Hesitancy & Digital Reluctance During the covid-19 Pandemic
Authors: Campbell Heidi A
Published: June 2023

During the pandemic, many church leaders had to learn to manage a digital divide present within their congregations, which they were not aware of. This article explores the nature and traits of the digital divide many American churches encountered during this pandemic, based on a study of focus groups involving 478 church leaders from Indiana. This study identifies four specific challenges they faced in adopting digital media and adapting their services to the online environment, revealed by this digital divide. Specifically, this article explores the lack of internet accessibility digital literacy, generational gaps in digital knowledge, and dealing with in and dividuals who were resistant to change digital media, who could be described as exhibiting technological hesitancy or digital reluctance. These challenges are looked at through the lens of digital justice and argue the digital divide realized within churches during the Covid-19 pandemic has theological implications.
Tiberian Dagesh Lene
Authors: Howard Jonathan
Published: June 2023

In the previous installment of Textus, Yehonatan Wormser acutely argued that the so-called dagesh lene in the standard Tiberian tradition was pronounced as a geminate consonant, effectively neutralising the distinction between lene and forte. This he did by invoking the “principle of economy” and comparing the dagesh to the shewa, as well as by drawing evidence from Karaite transcriptions and non-standard Tiberian manuscripts. I argue that his claim is not supported by his evidence: the transcriptions and non-standard manuscripts do not reflect the mainstream Tiberian tradition, but rather a late development; and the principle of economy does not apply in the cases of complementary distribution. Wormser’s analogy between dagesh and shewa is also addressed.
Sex-association experiments reveal the true identity of Physetopoda lampedusia (Invrea, 1957) (Hymenoptera, Mutillidae, Smicromyrmini)
Authors: MATIAS RAFAEL
Published: June 2023

Arthropod biodiversity is still insufficiently known in large areas of Europe, such as the Iberian Peninsula, regarding several insect groups. Mutillid wasps (Mutillidae), markedly sexually dimorphic ectoparasitic species, are poorly known Hymenoptera, with a number of species awaiting formal description and others known only from one sex. Sexual associations have been historically difficult to establish for most mutillid wasp species; in an European context, the species in tribe Smicromyrmini, particularly in the genera Smicromyrme Thomson, 1870 and Physetopoda Schuster, 1949, have presented the biggest challenges. In this paper, the hitherto unknown male of Physetopoda lampedusia (Invrea, 1957) is recognized as Ephutomma montarcense ((Mercet MS.) Giner Marí, 1944), with the former name falling into synonymy. A total of 63 females identified as P. lampedusia and 35 males identified as E. montarcense were collected in Portugal from 1999–2022. The correct sex association was confirmed through pairing experiments in captivity and is supported by circumstantial field observations in situ. Redescriptions of both male and female, as well as behavioural notes, are presented. Ephutomma montarcense is new for Portugal and its distribution is thus extended to Lampedusa Island (Italy) and Morocco, where it had been recorded as P. lampedusia, with Ephutomma representing a new genus for these three countries. The reliability of the method used, as well as the generic position and authorship of the species are briefly discussed.
On the Fijian endemic Nesobasis brachycerca Tillyard, 1924 (Odonata: Coenagrionidae) with first description of the female and updated description of the male
Authors: RASHNI BINDIYA , DONNELLY THOMAS , SAKITI-WAQA HILDA , OSBORNE-NAIKATINI TAMARA , RAITUVA JONE , MAIWAQA MANOA , MAIWAQA PENAIA VALEVESI , MARINOV MILEN
Published: June 2023

Nesobasis brachycerca Tillyard, 1924 specimens have been sampled during the course of an ongoing PhD study investigating the utility of Odonata individuals for assessing the conservation importance of the Fijian freshwater resources. Material was analysed and compared to all published records on this taxon. We here provide the first morphological description (by supposition) of the female of N. brachycerca, update the morphological characteristics of the male and present some habitat specifications measured in the field.
4. Can Palestinians Regain the Initiative for Ending the Occupation?
Authors: Hawwash Kamel
Published: June 2023

In this chapter I describe the work of the Palestine Strategy Study Group (PSSG). I received an invitation to a workshop joining a group of Palestinians from the West Bank and the Diaspora at the Dead Sea, Jordan. The approach came from an International Peace and Security think-tank, the Oxford Research Group (ORG), based in London. The approach seemed interesting because the proposal was to get together a group of Palestinian politicians, academics, businessmen and activists from different political backgrounds and from different regions of the world. Prior to this most initiatives were about ‘dialogue’ between Palestinians and Israelis and have singularly failed to produce a positive outcome. The title of the project was ‘Regaining the Initiative: Exploring Palestinian Strategic Options’.
7. Dismantling the Image of the Palestinian Homosexual: Exploring the Role of Alqaws
Authors: AlQaisiya Wala , Hilal Ghaith , Maikey Haneen
Published: June 2023

The Zionist colonization of Palestine holds at its premise racial, sexual, and gendered discourses through which colonial power is exercised. It is through the production and creation of certain types of knowledge and specific domains of truth that the colonial regime perpetuates and reinforces its mechanisms and modes of governments on the colonizers, making them internalize a certain conduct. This paper seeks to understand the means through which the Zionist colonial regime influences the production of specific objects of knowledge: sexuality and the image of the homosexual in Palestine. It wants to pinpoint the ways through which its power hinges on the bodies and desires of the colonized and, specifically, how the image of homosexuals came to be perceived and understood in determined ways within the Palestinian context and throughout its recent history.
11. The Oslo Accords and Palestine’s Political Economy in the Shadow of Regional Turmoil
Authors: Hanieh Adam
Published: June 2023

Given the preponderant weight of the question of Palestine to Middle East politics, it is striking how little substantive discussion there has been around issues of its political economy. In stark contrast to other parts of the region—where sharp analyses of capitalist development and the strategies adopted by states and ruling elites are regularly dissected and debated—Palestine remains largely viewed as a ‘humanitarian issue.’ Much solidarity work (both in the Arab world and further afield) typically emphasizes the violation of Palestinian rights and the enormous suffering this entails, rather than Palestine’s connection to the wider region and its articulation with forms of imperialist power. Placed in a category of its own, Palestine has become an exception that somehow defies the analytical tools used to unpack and comprehend neighboring states. In this chapter I aim to present a counter-narrative to this exceptionalism by examining some aspects of the political economy of Palestine, particularly through the period that has followed the 1993 Oslo Accords. Officially known as the Declaration of Principles on Interim Self-Government Arrangements, the Oslo Accords were signed between the Palestine Liberation Organization (PLO) and the Israeli government on 13 September 1993.
Track and catenary reconstruction from aerial images for the realistic analysis of rail electrification systems
Authors: Rebelo JM , Antunes P , Ambrósio J , Pombo J
Published: June 2023

Currently, the modelling of the railway catenaries for straight tracks is well understood and demonstrated via an accepted number of applications and an international benchmark. However, in the presence of a general track geometry, including curved tracks, challenges still remain. The fundamental difficulty is how to address the catenary layout in the presence of curves for a long railway track in which a large number of catenary sections are defined. To support the catenary design, e.g. in new electrification projects, it is fundamental to identify the track geometry, which is not always accessible to the overhead line engineers. This work purposes a novel approach for track geometry reconstruction using aerial views. The reconstruction methodology is based on the general geometry rules for track design. The track geometry obtained is then used as the reference to define the layout of the catenary. The Network Rail Series 1 overhead equipment is used here and the 3D finite element model of the catenary is built on the curved track geometry. The results of this work demonstrate, not only the advances proposed to study more realistically the pantograph-catenary interaction, but also the need to consider general curved tracks in acceptance and interoperability studies.
Readmission and associated clinical factors among individuals admitted with bipolar affective disorder at a psychiatry facility in Uganda
Authors: Abaatyo Joan , Kaggwa Mark Mohan , Favina Alain , Olagunju Andrew T.
Published: June 2023

Background

Bipolar affective disorder (BAD) is a common severe mental health condition with a relapsing course that may include periods of hospital re-admissions. With recurrent relapses and admissions, the course, prognosis, and patient’s overall quality of life can be affected negatively. This study aims to explore the rates and clinical factors associated with re-admission among individuals with BAD.

Method

This study used data from a retrospective chart review of all records of patients with BAD admitted in 2018 and followed up their hospital records for four years till 2021 at a large psychiatric unit in Uganda. Cox regression analysis was used to determine the clinical characteristics associated with readmission among patients diagnosed with BAD.

Results

A total of 206 patients living with BAD were admitted in 2018 and followed up for four years. The average number of months to readmission was 9.4 (standard deviation = 8.6). The incidence of readmission was 23.8% (n = 49/206). Of those readmitted during the study period, 46.9% (n = 23/49) and 28.6% (n = 14/49) individuals were readmitted twice and three times or more, respectively. The readmission rate in the first 12 months following discharge was 69.4% (n = 34/49) at first readmission, 78.3% (n = 18/23) at second readmission, and 87.5% (n = 12/14) at third or more times. For the next 12 months, the readmission rate was 22.5% (n = 11/49) for the first, 21.7% (n = 5/23) for the second, and 7.1% (n = 1/14) for more than two readmissions. Between 25 and 36 months, the readmission rate was 4.1% (n = 2/49) for the first readmission and 7.1% (n = 1/14) for the third or more times. Between 37 and 48 months, the readmission rate was 4.1% (n = 2/49) for those readmitted the first time. Patients who presented with poor appetite and undressed in public before admission were at increased risk of being readmitted with time. However, the following symptoms/clinical presentations, were protective against having a readmission with time, increased number of days with symptoms before admission, mood lability, and high energy levels.

Conclusion

The incidence of readmission among individuals living with BAD is high, and readmission was associated with patients’ symptoms presentation on previous admission. Future studies looking at BAD using a prospective design, standardized scales, and robust explanatory model are warranted to understand causal factors for hospital re-admission and inform management strategies.
Knowledge and attitudes of Chinese medical postgraduates toward research ethics and research ethics committees: a cross-sectional study
Authors: Liu Xing , Wang Xianxiong , Wu Ying , Yu Haitao , Yang Min , Khoshnood Kaveh , Luo Esther , Wang Xiaomin
Published: June 2023

Background

Research ethics provides the ethical standards for conducting sound and safe research. The field of medical research in China is rapidly growing and facing various ethical challenges. However, in China, little empirical research has been conducted on the knowledge and attitudes of medical postgraduates toward research ethics and RECs. It is critical for medical postgraduates to develop a proper knowledge of research ethics at the beginning of their careers. The purpose of this study was to assess the knowledge and attitudes of medical postgraduates toward research ethics and RECs.

Methods

This cross-sectional study was conducted from May to July 2021 at a medical school and two affiliated hospitals in south-central China. The instrument of the study was an online survey that was distributed via WeChat.

Results

We found that only 46.7% were familiar with the ethical guidelines for research with human subjects. In addition, 63.2% of participants were familiar with the RECs that reviewed their research, and 90.7% perceived RECs as helpful. However, only 36.8% were fully aware of the functions of RECs. In the meantime, 30.7% believed that review by an REC would delay research and make it more difficult for researchers. Furthermore, most participants (94.9%) believed that a course on research ethics should be mandatory for medical postgraduates. Finally, 27.4% of the respondents considered the fabrication of some data or results to be acceptable.

Conclusion

This paper serves to suggest that research ethics education should be prioritized in medical ethics curriculum, and course syllabi or teaching methods should be revised to provide medical postgraduates with a deeper understanding of the principles, regulations, and specifics of research ethics. We also recommend that RECs provide diverse approaches in their review procedure to facilitate the understanding of medical postgraduates of the functions and processes of RECs and to enhance their awareness of research integrity.
Evaluation of a multiphasic parasite clearance profile after treatment of experimental human infection with the investigational anti-malarial M5717 using segmented mixed effect models
Authors: Yin Xiaoyan , Li Ying , Bagchus Wilhelmina , Yalkinoglu Özkan , Bezuidenhout Deon , Tappert Aliona , McCarthy James , Marquart Louise , Oeuvray Claude
Published: June 2023

Background

Evaluation of parasite clearance patterns in experimental human infection trials helps increase understanding of drug action. In a previously reported phase Ib trial of a new investigational anti-malarial drug M5717, parasite clearance showed a biphasic linear pattern: slow removal phase with a near flat clearance rate followed by a fast clearance phase with a steep slope. In this study three statistical approaches were implemented and compared to estimate the parasite clearance rate for each phase and the time point corresponding to the change of clearance rates (changepoint between the two phases).

Methods

Data using three M5717 doses 150 mg (n = 6), 400 mg (n = 8), 800 mg (n = 8) were used to estimate biphasic clearance rates. Three models were investigated: firstly, segmented mixed models with estimated changepoint—models with/without random effects in various parameters were compared. Secondly, a segmented mixed model using grid search—this method is similar to the first except that changepoints were not estimated, instead they were selected based on model fit from given candidate values. Thirdly, a two-stage approach whereby a segmented regression model fit to each participant followed by a meta-analysis method. Hourly rate of parasite clearance (HRPC) interpreted as the percentage of parasites removed each hour was calculated.

Results

The three models generated similar results. Using segmented mixed models, the estimated changepoints after treatment in hours (95% CI) were: 150 mg: 33.9 (28.7, 39.1); 400 mg: 57.4 (52.5, 62.4); and 800 mg: 52.8 (47.4, 58.1). For all three treatment groups, there was nearly no clearance before the changepoints, but rapid clearance in the second phase (HRPC [95% CI]): 150 mg: 16.8% (14.3, 19.1%); 400 mg: 18.6% (16.0, 21.1%); and 800 mg: 11.7% (9.3, 14.1%).

Conclusions

All three statistical approaches are effective tools to characterize the bi-phasic clearance of M5717 in the phase 1b experimental Plasmodium falciparum malaria human infection study. The statistical approaches produced similar results to estimate the two-phase clearance rates and the changepoint for each treatment dose of M5717. However, the segmented mixed model with random changepoints has several advantages: it is computationally efficient, provides precision for changepoint estimates and is robust concerning outlying datapoints or individuals.