bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S4 from Paradoxical Activation of Oncogenic Signaling as a Cancer Treatment Strategy
Authors: Dias Matheus Henrique , Friskes Anoek , Wang Siying , Fernandes Neto Joao M. , van Gemert Frank , Mourragui Soufiane , Papagianni Chrysa , Kuiken Hendrik J. , Mainardi Sara , Alvarez-Villanueva Daniel , Lieftink Cor , Morris Ben , Dekker Anna , van Dijk Emma , Wilms Lieke H.S. , da Silva Marcelo S. , Jansen Robin A. , Mulero-Sánchez Antonio , Malzer Elke , Vidal August , Santos Cristina , Salazar Ramón , Wailemann Rosangela A.M. , Torres Thompson E.P. , De Conti Giulia , Raaijmakers Jonne A. , Snaebjornsson Petur , Yuan Shengxian , Qin Wenxin , Kovach John S. , Armelin Hugo A. , te Riele Hein , van Oudenaarden Alexander , Jin Haojie , Beijersbergen Roderick L. , Villanueva Alberto , Medema Rene H. , Bernards Rene
Published: July 2024

Figure S4: Combined toxicity of LB-100 and Adavosertib in CRC models (A) Dose-response assays show the effect of Adavosertib in 7 CRC models. Cell viability was estimated by resazurin fluorescence after 5 days in the presence of the drug or DMSO control. The normalized values are plotted. (B) Long-term viability assays show 7 CRC models treated with LB-100 or Adavosertib at the indicated concentrations. Treatments were refreshed every 2-3 days, and the cells were grown for 10-14 days before fixing, staining, and imaging. (C) IncuCyte-based proliferation assays from 7 CRC models in the absence or presence of LB-100, Adavosertib, or the combination at the indicated concentrations. (D) Dose-response assays show the toxicity of LB-100 and Adavosertib in BJ and HaCaT cells compared to the average across the 7 CRC cell lines listed in the supplementary table S1. Cell viability was estimated by resazurin fluorescence after 5 days in the presence of the drug or DMSO control. The normalized values are plotted. (E) Synergy matrices and scores for the combination of LB-100 and Adavosertib in BJ and HaCaT cells. Cells were treated with 5 concentrations of LB-100 (1, 2, 3, 4, and 5 µM) or Adavosertib (100, 200, 300, 400, and 500 nM) and all respective permutations for 4 days. The percentage of cell viability for each condition was estimated by resazurin fluorescence and normalized to DMSO controls. Synergyfinder.org web tool was used to calculate the ZIP synergy scores and generate the plots.
Data from CD8-Targeted IL2 Unleashes Tumor-Specific Immunity in Human Cancer Tissue by Reviving the Dysfunctional T-cell Pool
Authors: Kaptein Paulien , Slingerland Nadine , Metoikidou Christina , Prinz Felix , Brokamp Simone , Machuca-Ostos Mercedes , de Roo Guido , Schumacher Ton N.M. , Yeung Yik A. , Moynihan Kelly D. , Djuretic Ivana M. , Thommen Daniela S.
Published: July 2024

Abstract
Tumor-specific CD8+ T cells are key effectors of antitumor immunity but are often rendered dysfunctional in the tumor microenvironment. Immune-checkpoint blockade can restore antitumor T-cell function in some patients; however, most do not respond to this therapy, often despite T-cell infiltration in their tumors. We here explored a CD8-targeted IL2 fusion molecule (CD8–IL2) to selectively reactivate intratumoral CD8+ T cells in patient-derived tumor fragments. Treatment with CD8–IL2 broadly armed intratumoral CD8+ T cells with enhanced effector capacity, thereby specifically enabling reinvigoration of the dysfunctional T-cell pool to elicit potent immune activity. Notably, the revival of dysfunctional T cells to mediate effector activity by CD8–IL2 depended on simultaneous antigen recognition and was quantitatively and qualitatively superior to that achieved by PD-1 blockade. Finally, CD8–IL2 was able to functionally reinvigorate T cells in tumors resistant to anti–PD-1, underscoring its potential as a novel treatment strategy for patients with cancer.

Significance: Reinvigorating T cells is crucial for response to checkpoint blockade therapy. However, emerging evidence suggests that the PD-1/PD-L1 axis is not the sole impediment for activating T cells within tumors. Selectively targeting cytokines toward specific T-cell subsets might overcome these barriers and stimulate T cells within resistant tumors.

See related article by Moynihan et al., p. 1206 (32).
Data from IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity
Authors: Moynihan Kelly D. , Kumar Manu P. , Sultan Hussein , Pappas Danielle C. , Park Terrence , Chin S. Michael , Bessette Paul , Lan Ruth Y. , Nguyen Henry C. , Mathewson Nathan D. , Ni Irene , Chen Wei , Lee Yonghee , Liao-Chan Sindy , Chen Jessie , Schumacher Ton N.M. , Schreiber Robert D. , Yeung Yik A. , Djuretic Ivana M.
Published: July 2024

Abstract
IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively. AB248 recapitulated IL2’s effects on CD8+ T cells in vitro and induced selective expansion of CD8+T cells in primates. In mice, an AB248 surrogate demonstrated superior antitumor activity and enhanced tolerability as compared with an untargeted IL2Rβγ agonist. Efficacy was associated with the expansion and phenotypic enhancement of tumor-infiltrating CD8+ T cells, including the emergence of a “better effector” population. These data support the potential utility of AB248 in clinical settings.

Significance: The full potential of IL2 therapy remains to be unlocked. We demonstrate that toxicity can be decoupled from antitumor activity in preclinical models by limiting IL2 signaling to CD8+ T cells, supporting the development of CD8+ T cell–selective IL2 for the treatment of cancer.

See related article by Kaptein et al. p. 1226.
Supplementary Table S10 from Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC–Alarmin Axis
Authors: Vincelette Nicole D. , Yu Xiaoqing , Kuykendall Andrew T. , Moon Jungwon , Su Siyuan , Cheng Chia-Ho , Sammut Rinzine , Razabdouski Tiffany N. , Nguyen Hai V. , Eksioglu Erika A. , Chan Onyee , Al Ali Najla , Patel Parth C. , Lee Dae H. , Nakanishi Shima , Ferreira Renan B. , Hyjek Elizabeth , Mo Qianxing , Cory Suzanne , Lawrence Harshani R. , Zhang Ling , Murphy Daniel J. , Komrokji Rami S. , Lee Daesung , Kaufmann Scott H. , Cleveland John L. , Yun Seongseok
Published: July 2024

Cell-cell interaction analyses.
Supplementary Table S1-16 from Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC–Alarmin Axis
Authors: Vincelette Nicole D. , Yu Xiaoqing , Kuykendall Andrew T. , Moon Jungwon , Su Siyuan , Cheng Chia-Ho , Sammut Rinzine , Razabdouski Tiffany N. , Nguyen Hai V. , Eksioglu Erika A. , Chan Onyee , Al Ali Najla , Patel Parth C. , Lee Dae H. , Nakanishi Shima , Ferreira Renan B. , Hyjek Elizabeth , Mo Qianxing , Cory Suzanne , Lawrence Harshani R. , Zhang Ling , Murphy Daniel J. , Komrokji Rami S. , Lee Daesung , Kaufmann Scott H. , Cleveland John L. , Yun Seongseok
Published: July 2024

Table S1. Demographics of Moffitt Total Cancer Care MF patients. Table S2. Demographic Profile of trisomy 8+ TN-MF patients and HDs used in scRNA-seq analysis and PDX studies. Table S3. List of genes used for PROGENy analysis of human BM cells. Table S4. Demographics of TN-MF patients. Table S5. Clinical parameters of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC studies. Table S6. Clinical parameters of Scl-CreERT+/-;Rosa26LSL-MYC/LSL-MYC in vivo studies. Table S7. Clinical parameters in competitive transplant studies. Table S8. Comparison of gene expression profiles of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC vs. Mx1-Cre+/-;Rosa26+/+ mouse. Table S9. List of genes used for PROGENy analysis of mouse BM cells. Table S10. Cell-cell interaction analyses. Table S11. Clinical parameters of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC;S100a9-/- studies. Table S12. Clinical parameters of S100a9 transgenic mouse studies. Table S13. Clinical parameters of Tasquinimod efficacy studies in MYC-driven MF. Table S14. Clinical parameters of MYCi975 efficacy studies in MYC-driven MF. Table S15: Key Resources Table. Table S16: Sequence Information.
Supplementary Figures S5-S9 from Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC–Alarmin Axis
Authors: Vincelette Nicole D. , Yu Xiaoqing , Kuykendall Andrew T. , Moon Jungwon , Su Siyuan , Cheng Chia-Ho , Sammut Rinzine , Razabdouski Tiffany N. , Nguyen Hai V. , Eksioglu Erika A. , Chan Onyee , Al Ali Najla , Patel Parth C. , Lee Dae H. , Nakanishi Shima , Ferreira Renan B. , Hyjek Elizabeth , Mo Qianxing , Cory Suzanne , Lawrence Harshani R. , Zhang Ling , Murphy Daniel J. , Komrokji Rami S. , Lee Daesung , Kaufmann Scott H. , Cleveland John L. , Yun Seongseok
Published: July 2024

Figure S5. Changes in signaling in BM of trisomy 8+ TN-MF patient and MYC MF mice. Figure S6. Effects of silencing S100a9 in MYC-driven MF or overexpression of S100a9. Figure S7. Effects of inhibition of S100a9 or MYC in MYC-driven MF. Figure S8. Synthesis and Characterization of Tasquinimod. Figure S9. Synthesis and Characterization of MYCi975.
Supplementary Figures S1-S4 from Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC–Alarmin Axis
Authors: Vincelette Nicole D. , Yu Xiaoqing , Kuykendall Andrew T. , Moon Jungwon , Su Siyuan , Cheng Chia-Ho , Sammut Rinzine , Razabdouski Tiffany N. , Nguyen Hai V. , Eksioglu Erika A. , Chan Onyee , Al Ali Najla , Patel Parth C. , Lee Dae H. , Nakanishi Shima , Ferreira Renan B. , Hyjek Elizabeth , Mo Qianxing , Cory Suzanne , Lawrence Harshani R. , Zhang Ling , Murphy Daniel J. , Komrokji Rami S. , Lee Daesung , Kaufmann Scott H. , Cleveland John L. , Yun Seongseok
Published: July 2024

Figure S1. Landscape of somatic mutations and cytogenetics in Moffitt MF cohort. Figure S2. Effects of enforced MYC expression in HSCs in vivo. Figure S3. MYC-induced changes in hematopoietic sub-populations and colony forming potential. Figure S4. The JAK/STAT, PI3K/AKT, MEK/ERK, and alarmin pathways in MYC-driven MF.
Table S1 from Genotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells
Authors: Rozenbaum Meir , Fluss Reut , Marcu-Malina Victoria , Sarouk Ifat , Meir Amilia , Elitzur Sarah , Zinger Tal , Jacob-Hirsch Jasmine , Saar Efrat G. , Rechavi Gideon , Jacoby Elad
Published: July 2024

Patient characteristics
Figure S1 from Genotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells
Authors: Rozenbaum Meir , Fluss Reut , Marcu-Malina Victoria , Sarouk Ifat , Meir Amilia , Elitzur Sarah , Zinger Tal , Jacob-Hirsch Jasmine , Saar Efrat G. , Rechavi Gideon , Jacoby Elad
Published: July 2024

Viability of CAR-T cells from ATM+/+, ATM+/- and ATM-/- donors at the end of production
Data from Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Authors: Mo George , Lee Sang Y. , Coffey David G. , Voillet Valentin , Kirsch Ilan R. , Gottardo Raphael , Smythe Kimberly S. , Yeung Cecilia C.S. , Greenbaum Adam , Green Damian J. , Maloney David G. , Till Brian G.
Published: July 2024

Abstract
Chimeric antigen receptor (CAR) T-cell therapy produces high response rates in refractory B-cell non–Hodgkin lymphoma, but long-term data are minimal to date. In this study, we present long-term follow-up of a pilot trial testing a CD20-targeting third-generation CAR in patients with relapsed B-cell lymphomas following cyclophosphamide-only lymphodepletion. Two of the three patients in the trial, with mantle cell lymphoma and follicular lymphoma, had remissions lasting more than 7 years, though they ultimately relapsed. The absence of B-cell aplasia in both patients suggested a lack of functional CAR T-cell persistence, leading to the hypothesis that endogenous immune responses were responsible for these long-term remissions. Correlative immunologic analyses supported this hypothesis, with evidence of new humoral and cellular antitumor immune responses proximal to clinical response time points. Collectively, our results suggest that CAR T-cell therapy may facilitate epitope spreading and endogenous immune response formation in lymphomas.

Significance: Two of three patients treated with CD20-targeted CAR T-cell therapy had long-term remissions, with evidence of endogenous antitumor immune response formation. Further investigation is warranted to develop conditions that promote epitope spreading in lymphomas.
Data from Trisomy 8 Defines a Distinct Subtype of Myeloproliferative Neoplasms Driven by the MYC–Alarmin Axis
Authors: Vincelette Nicole D. , Yu Xiaoqing , Kuykendall Andrew T. , Moon Jungwon , Su Siyuan , Cheng Chia-Ho , Sammut Rinzine , Razabdouski Tiffany N. , Nguyen Hai V. , Eksioglu Erika A. , Chan Onyee , Al Ali Najla , Patel Parth C. , Lee Dae H. , Nakanishi Shima , Ferreira Renan B. , Hyjek Elizabeth , Mo Qianxing , Cory Suzanne , Lawrence Harshani R. , Zhang Ling , Murphy Daniel J. , Komrokji Rami S. , Lee Daesung , Kaufmann Scott H. , Cleveland John L. , Yun Seongseok
Published: July 2024

Abstract
Despite advances in understanding the genetic abnormalities in myeloproliferative neoplasms (MPN) and the development of JAK2 inhibitors, there is an urgent need to devise new treatment strategies, particularly for patients with triple-negative (TN) myelofibrosis (MF) who lack mutations in the JAK2 kinase pathway and have very poor clinical outcomes. Here we report that MYC copy number gain and increased MYC expression frequently occur in TN-MF and that MYC-directed activation of S100A9, an alarmin protein that plays pivotal roles in inflammation and innate immunity, is necessary and sufficient to drive development and progression of MF. Notably, the MYC-S100A9 circuit provokes a complex network of inflammatory signaling that involves numerous hematopoietic cell types in the bone marrow microenvironment. Accordingly, genetic ablation of S100A9 or treatment with small molecules targeting the MYC-S100A9 pathway effectively ameliorates MF phenotypes, highlighting the MYC–alarmin axis as a novel therapeutic vulnerability for this subgroup of MPNs.

Significance: This study establishes that MYC expression is increased in TN-MPNs via trisomy 8, that a MYC-S100A9 circuit manifest in these cases is sufficient to provoke myelofibrosis and inflammation in diverse hematopoietic cell types in the BM niche, and that the MYC-S100A9 circuit is targetable in TN-MPNs.
Data from Genotoxicity Associated with Retroviral CAR Transduction of ATM-Deficient T Cells
Authors: Rozenbaum Meir , Fluss Reut , Marcu-Malina Victoria , Sarouk Ifat , Meir Amilia , Elitzur Sarah , Zinger Tal , Jacob-Hirsch Jasmine , Saar Efrat G. , Rechavi Gideon , Jacoby Elad
Published: July 2024

Abstract
Somatic variants in DNA damage response genes such as ATM are widespread in hematologic malignancies. ATM protein is essential for double-strand DNA break repair. Germline ATM deficiencies underlie ataxia–telangiectasia (A–T), a disease manifested by radiosensitivity, immunodeficiency, and predisposition to lymphoid malignancies. Patients with A–T diagnosed with malignancies have poor tolerance to chemotherapy or radiation. In this study, we investigated chimeric antigen receptor (CAR) T cells using primary T cells from patients with A–T (ATM−/−), heterozygote donors (ATM+/−), and healthy donors. ATM−/− T cells proliferate and can be successfully transduced with CARs, though functional impairment of ATM−/− CAR T-cells was observed. Retroviral transduction of the CAR in ATM−/− T cells resulted in high rates of chromosomal lesions at CAR insertion sites, as confirmed by next-generation long-read sequencing. This work suggests that ATM is essential to preserve genome integrity of CAR T-cells during retroviral manufacturing, and its lack poses a risk of chromosomal translocations and potential leukemogenicity.

Significance: CAR T-cells are clinically approved genetically modified cells, but the control of genome integrity remains largely uncharacterized. This study demonstrates that ATM deficiency marginally impairs CAR T-cell function and results in high rates of chromosomal aberrations after retroviral transduction, which may be of concern in patients with DNA repair deficiencies.
Figure 3 from Cancer-Related Fatigue and the Additive Effect of Treatment in the Context of Lymphoma: An Analysis of the Lymphoma Coalition’s 2022 Global Patient Survey
Authors: Kalloger Steve E. , Watson Amanda , Sajkowski Shawn , Warwick Lorna
Published: July 2024

Estimation of the contribution of treatment to CRF, stratified across lymphoma subtypes including CLL. Values are derived from Eq. A in the Methods section.
The Effect Of Public Information Systems On Auditors' Performance In Public Accounting Firms
Authors: Galih Supraja  , Abel Desiyanti Manik
Published: July 2024

The right information system will allow an auditor to obtain it excellence and improve performance. This research aims to test and provide empirical evidence about the influence of public information systems on auditor performance. The sample used in this research consisted of from junior to senior auditors who work at Public Accounting Firms (M. Lian Dalimunthe and Partners). Types of research is comparative causal research. The type of data used is Primary data, with data collected from 30 questionnaires. Deep sample selection method This research uses the Convenience Sampling method, analysis is carried out using using Multivariate analysis. The data analysis model used is simple linear regression analysis, with quality testing The data used is a validity test and a reliability test. The classic assumption test used is the test normality and heteroscedasticity tests. Hypothesis testing used is the t-test and coefficient of determination (R2). Descriptive statistics are also used to help analyze data by describing the data collected. The results of this research using simple linear regression analysis, the results of the research provides empirical evidence that there is a significant influence between public information systems on performance auditors with results below 0.05 (<0.05), namely 0.000 < 0.05, obtained a tcount of 5.590. This partially proving the results of the statistical tests show that the public information system has an effect positive and significant on auditor performance.
The Influence of Financial Distress, Auditor Switching, Profitability, Audit Quality on Audit Delay
Authors: Windy Permatasari  , Cahyati Ari Dewi
Published: July 2024

Audit delay is the period for completing the annual financial report audit, namely from the date the company's books are closed to the date stated in the independent auditor's report. The length of the audit delay affects the value of the audited financial statements. This research aims to find out whether Financial Distress, Auditor Switching, Profitability, and Audit Quality affect Audit Delay. The data used in this research is secondary data in the form of audited financial reports. This research population was obtained using methods from non-cyclical consumer sector companies listed on the IDX during the 2020-2022 period. Based on predetermined criteria, a sample of 129 companies was obtained. The analytical method used is multiple linear regression analysis with the STATA 17 software tool. The research results show that financial distress affects audit delay. Meanwhile, auditor switching, profitability, and audit quality do not affect audit delay.
The Influence of Female Chief Executive Officer and Female Chief Financial Officer on Earnings Management in Manufacturing Companies in The Consumption Goods Industry Sector Registered on the BEI in 2021-2022
Authors: Sakiah Maisaroh  , Nidia Anggreni Das  , Rita Dwi Putri
Published: July 2024

This research aims to analyze the influence of Female CEO and Female CFO on Earning Management. This research was conducted on consumer goods industrial sector companies listed on the IDX in 2021-2022, the sample was selected using a purposive sampling method and the data that passed the selection were 36 companies. The research results show that Female CEO (X1) has no significant effect on Earnings Management (Y). This is proven by using the t-value of 0.287 < t table 1.996 and a significant value of 0.775 > 0.05. Female CFO (X2) has no significant effect on Earnings Management (Y). This was proven using the t-value of |0.284| < ttable 1.996 and a significant value of 0.777 > 0.05. After that, Female CEO (X1) and Female CFO (X2) do not simultaneously influence Earning Management (Y). This result is proven by the F-value of 0.076 < Ftable and a significant value of 0.973 > 0.05
Management of Village Fund Allocation in Realizing Good Governance in Pematang Tujuh Village, Pontianak
Authors: Dini Lestary  , Lilis Suryani
Published: July 2024

This study aims to examine the management of the Village Fund Allocation in Pematang Tujuh Village, Rasau Jaya Subdistrict, Kubu Raya Regency, by implementing the principles of Good Governance. This research uses a case study method with a descriptive qualitative approach, employing data collection techniques such as observation, interviews, and documentation. The study involved three respondents as sources of information. The findings reveal that the planning stage adheres to the Ministry of Home Affairs Regulation No. 113 of 2014, starting with Dusun Meetings and Village Development Planning Meetings (Musrenbangdes), involving the active participation of the Pematang Tujuh Village community. The Village Institution's involvement in the preparation of the Village Medium-Term Development Plan (RPJM Desa) and the Village Government Work Plan (RKP Desa) is discussed in Musrenbangdes meetings, subsequently organized by a special team. The results of these meetings are then displayed on announcement boards and billboards. In the implementation stage, the management of the Village Fund Allocation is carried out by a management team responsible for the Accountability Report (SPJ), involving the Pematang Tujuh Village community in the execution of activities. All activities related to budget implementation are announced on the website and notice boards.
Factors Affecting the Growth of SME Sales in the Tourism Sector of Tanjungpinang City
Authors: Muhammad Fachri Riauan  , Hendy Satria  , Andres Putranta Sitepu  , Aulia Dewi Gizta  , Sri Kurnia
Published: July 2024

The aim of research is to determine the influence of e-payment, makloon, and sales promotion on sales growth of SMEs in the tourism sector in Tanjungpinang. The research involved a sample of 91 respondents using the slovin technique. The method used in this research is a quantitative method. The research object consists of small and medium enterprises (SMEs) operating in the tourism sector in Tanjungpinang City. Data collection wa carried out through respondents filling out questionnaires. The research results indicate that partially, e-payment has a significant impact on sales growth, makloon (outsourcing) influences but not significantly on sales growth, and sales promotion significantly influences sales growth. Simultaneously, it is shown that e-payment, makloon, and sales promotion collectively have a simultaneous impact on sales growth.
The Influence of Gross Regional Domestic Product, Number of Population, and Number of Nusantara Tourists on Regional Original Income
Authors: Haiqal Imansyah  , Bambang Sambodo  , Alamsyahbana Muhammad Isa , Rezario Febrianta Chandra  , Masyitah As Sahara
Published: July 2024

The aim of this research is to find out whether the original income of districts/cities in Aceh Province is influenced by GRDP, population and number of domestic tourists. The total sample is 23 regencies/cities in Aceh Province. Quantitative methods are used as research methods, with the data used being secondary data obtained through publications and the official website of the Indonesian Central Statistics Agency, the Directorate General of Financial Balance (DJPK), and the Information and Documentation Management Officer (PPID). The research results partially prove that regional original income is not influenced by GRDP, population and number of domestic tourists. This was proven in the partial test, the significance value resulting from all independent variables was less than 0.05. However, regional original income is jointly (simultaneously) influenced by GRDP, population and number of domestic tourists, as can be seen in the simultaneous test with an f-count value of 13.91490 which is greater than the f-table of 2.745915. Based on the research results, the conclusion that can be drawn is that local revenue in the District/City of Aceh Province is not partially influenced by GRDP, population and number of domestic tourists. But simultaneously PAD can be influenced by GRDP, population and number of domestic tourists. So that districts/cities in Aceh Province are considered to be less able to utilize regional resources that can increase their original regional income, both in the economic, demographic and tourism sectors.
Pivotal Role of Duplex Ultrasonography on Arteriovenous Fistula for Hemodialysis Access
Authors: Firdaus Achmad Jauhar , Kurnianingsih Novi
Published: July 2024

The global incidence of end-stage renal disease (ESRD) is rising, amounting to more than 800 million individuals are suffered, in line with the rise of the number of patients undergoing hemodialysis as treatment modalities. Hemodialysis requires vascular access, and the arteriovenous fistula (AVF) access is considered the most ideal vascular access option due to its long-term patency and low complication rate compared to other access options. However, up to one-third of hospital admissions for ESRD patients are caused by AVF dysfunction, which is also one of the main causes of morbidity and mortality in ESRD patients. AVF creation requires careful pre- and post-operative evaluation to ensure the vascular access maturation and patency. While the latest guidelines have not explicitly emphasized the role of vascular mapping and surveillance, routine duplex ultrasonography before and after AVF creation procedures holds great potential advantages to ensure the success of AV access for hemodialysis.
Diagnosis and Management of Upper Gastrointestinal Bleeding in Long-Term NSAID Users : Case Report
Authors: Haitsam Muhamad Haitsam , Wardhani Shinta , Yudha Fakhmi
Published: July 2024

Upper gastrointestinal bleeding is one of the most frequently encountered emergency cases. For most general practitioners, diagnosing and providing initial management is a challenge in itself. Upper gastrointestinal bleeding is divided into variceal and non-variceal bleeding. Clinical symptoms that can be found include hematemesis or melena. Patients with melena tend to have lower hemoglobin (Hb) levels than hematemesis because clinical manifestations appear more slowly. Drug Induced NSAIDs are also one of the etiologies that can cause upper gastrointestinal bleeding. Endoscopy is the gold standard for diagnosis, but not all health facilities are able to perform it.
     This case reported a 66-years-old male patient came to the emergency room with complaints of blackish stools with a soft, sticky consistency for 6 days, accompanied by weakness, dizziness, nausea in the stomach and disruption of daily activities. The patient has a history of taking over-the-counter NSAIDs long term to relieve his knee pain. On physical examination, hepatomegaly and splenomegaly were not found and the patient’s hemodynamics is stable. On laboratory examination, Hb was found to be 3.4 g/dl. It was suspected that there was upper gastrointestinal bleeding, then received therapy in the form of PPI injections, antiemetic injections and planned PRC transfusion.
O homem e o equilíbrio ecológico regional na Amazônia brasileira
Authors: Penteado Antonio Rocha
Published: July 2024

In this research the author demonstrates that it is possible to occupy the Amazonia cautiously, throughout a colonization process which would not damage the ecological conditions of the region. Starting from the point that the population of the Amazónia is a small one and that is distributed in the region in great dispersion, according to hydrographic net, the author calls the attention to the consequent problems of the exploitation of vegetal coai and to the exploitation of woods, to the capture of the sylvan animais, to the fishing in the rivers and lakes, getting to modern occupation based on immigration and agriculture in one of the most favorable areas of Amazonia, because of its localization near to the city of Belem, were a great consuming market would be available, the Bragantina Region of the State of Para. Further, the author presents more recent enterprises such as Jari S/A., Pirelli and Good-Year and their exemples, and the enterprise of Tomé-Acu and Paragominas, correlating them with facts that were studied by the author in Tropical África. The main problem to face, is of man himself, who doesn’t still have a colonizing mentality. Concludes exemplefying that the fixation of man to the soil depends mainly on several items of cultural order and that the ecological defense of Amazonia is connected with the behavior of researchers, who in direct connection with the geographer, the economist, the sanitarist, the pedologist, etc., should always have a forest engenier among them in order to have structured a colonization process which shall avoid the transformation of the Amazónia into another desert created by man.
Fontes manuscritas do "Comércio Livre"
Authors: Dias Manuel Nunes
Published: July 2024

In the second half of the XVIIIth century the economic relations between Spain and West Indians suffered changes in its structure. It was the “Free Commerce” system that started the changes of the “Unic Port” rule and at the same time made possible the continuity of the Spanish merchantilism. Beside Seville and Cadiz thirty seven other ports began to operate throughout transoceanic routes and so increasing the circulation of mechandises in the Metrópoles and Colony. This article provides a guide to the archives of manuscript sources on “Free Commerce”. They are of great importance for Portuary History, and available in many archives of Spain and America, such as: “Archivo General de índias”, in Seville; “Archivo Histórico Nacional” in Madrid; “Archivo Provincial de Guipuzcoa”; “Archivo de Simancas”; “Manuscritos da Biblioteca Nacional de Madrid”; “Museo Naval de Madrid”; “Archivo General de La Nacion”, in Caracas; “Archivo General de la Nacion”, in Buenos Aires.
Apolipoprotein B: Bridging the Gap Between Evidence and Clinical Practice
Authors: De Oliveira-Gomes Diana , Joshi Parag H. , Peterson Eric D. , Rohatgi Anand , Khera Amit , Navar Ann Marie
Published: July 2024

Despite data suggesting that apolipoprotein B (apoB) measurement outperforms low-density lipoprotein cholesterol level measurement in predicting atherosclerotic cardiovascular disease risk, apoB measurement has not become widely adopted into routine clinical practice. One barrier for use of apoB measurement is lack of consistent guidance for clinicians on how to interpret and apply apoB results in clinical context. Whereas guidelines have often provided clear low-density lipoprotein cholesterol targets or triggers to initiate treatment change, consistent targets for apoB are lacking. In this review, we synthesize existing data regarding the epidemiology of apoB by comparing guideline recommendations regarding use of apoB measurement, describing population percentiles of apoB relative to low-density lipoprotein cholesterol levels, summarizing studies of discordance between low-density lipoprotein cholesterol and apoB levels, and evaluating apoB levels in clinical trials of lipid-lowering therapy to guide potential treatment targets. We propose evidence-guided apoB thresholds for use in cholesterol management and clinical care.
Discovery of four new Chinese species of Jacobsonina Hebard, 1929 and Blattella Caudell, 1903 (Blaberoidea: Blattellidae)
Authors: YAO WEN-WEN , LI QIAN-QIAN , LI LIN-WEI , WANG ZONG-QING , CHE YAN-LI
Published: July 2024

In this study, specimens of Blattellidae collected in China in recent years are analyzed by combining molecular data and morphological characters, and four new species of Jacobsonina and Blattella are described, Jacobsonina plicata Yao & Che, sp. nov., Jacobsonina subapiculata Yao & Che, sp. nov., Jacobsonina ericonvexa Yao & Che, sp. nov., and Blattella punctoria Yao & Che, sp. nov. Photographs of all new species and the key to Chinese Jacobsonina are also included.
Two anomalous new species of Rhagovelia (Heteroptera: Veliidae) from southern New Guinea
Authors: POLHEMUS DAN A.
Published: July 2024

Two new species of Rhagovelia are described from southern New Guinea: R. kiunga from the Fly River basin of Papua New Guinea, and R. timikana from the Iweka River basin of Indonesian New Guinea. These species are placed in a newly defined R. kiunga species group on the basis of shared distinctive morphological character states. Photographic figures of the dorsal habitus in both sexes and other key morphological characters are provided for both species, along with line drawings of the male parameres and a distribution map.
Track Deflection of Typhoon Chanthu (2021) near Taiwan as Investigated Using a High-Resolution Global Model
Authors: Chi Ya-Shin , Huang Ching-Yuang , Skamarock William C.
Published: July 2024

The Model for Prediction Across Scales (MPAS) with variable resolution (60–15–1 km) is used to investigate the track deflection of Typhoon Chanthu (2021) near Taiwan. Chanthu exhibited a rightward track deflection as it approached southeast Taiwan and underwent a leftward deflection when moving northward offshore of northeast Taiwan. Numerical experiments are conducted to identify the physical processes for the track deflection. The rightward deflection of the northbound typhoon is induced by the recirculating flow resulting from the effect of Taiwan’s topography. A wavenumber-1 potential vorticity (PV) budget analysis indicates that horizontal PV advection dominates the earlier rightward deflection, while the later leftward deflection is mainly in response to stronger asymmetric cloud heating at low levels at the offshore quadrant of the typhoon. A pair of cyclonic and anticyclonic gyres in the wavenumber-1 flow difference is induced by Taiwan’s topography. These rotate counterclockwise to drive the track deflection, most often in westbound typhoons. Idealized WRF simulations are also conducted to explore the track deflection under different northbound conditions. The simulations confirm the track deflection mechanism with similar PV dynamics to the MPAS simulations for Chanthu and illustrate the variabilities of the track deflection for different steering conditions and vortex origins. The rightward deflection of northbound typhoons is essentially determined by a reduced ratio of R/LE, where R is the vortex size and LE is the effective length of the mountain range.
Gut fungi of black-necked cranes (Grus nigricollis) respond to dietary changes during wintering
Authors: Li Wenhao , Cheng Lijun , He Xin , He Guiwen , Liu Yutong , Sang Zhenglin , Wang Yuanjian , Shao Mingcui , Xiong Tingsong , Xu Huailiang , Zhao Junsong
Published: July 2024

Background

Migratory birds exhibit heterogeneity in foraging strategies during wintering to cope with environmental and migratory pressures, and gut bacteria respond to changes in host diet. However, less is known about the dynamics of diet and gut fungi during the wintering period in black-necked cranes (Grus nigricollis).

Results

In this work, we performed amplicon sequencing of the trnL-P6 loop and ITS1 regions to characterize the dietary composition and gut fungal composition of black-necked cranes during wintering. Results indicated that during the wintering period, the plant-based diet of black-necked cranes mainly consisted of families Poaceae, Solanaceae, and Polygonaceae. Among them, the abundance of Solanaceae, Polygonaceae, Fabaceae, and Caryophyllaceae was significantly higher in the late wintering period, which also led to a more even consumption of various food types by black-necked cranes during this period. The diversity of gut fungal communities and the abundance of core fungi were more conserved during the wintering period, primarily dominated by Ascomycota and Basidiomycota. LEfSe analysis (P < 0.05, LDA > 2) found that Pyxidiophora, Pseudopeziza, Sporormiella, Geotrichum, and Papiliotrema were significantly enriched in early winter, Ramularia and Dendryphion were significantly enriched in mid-winter, Barnettozyma was significantly abundant in late winter, and Pleuroascus was significantly abundant in late winter. Finally, mantel test revealed a significant correlation between winter diet and gut fungal.

Conclusions

This study revealed the dynamic changes in the food composition and gut fungal community of black-necked cranes during wintering in Dashanbao. In the late wintering period, their response to environmental and migratory pressures was to broaden their diet, increase the intake of non-preferred foods, and promote a more balanced consumption ratio of various foods. Balanced food composition played an important role in stabilizing the structure of the gut fungal community. While gut fungal effectively enhanced the host’s food utilization rate, they may also faced potential risks of introducing pathogenic fungi. Additionally, we recongnized the limitations of fecal testing in studying the composition of animal gut fungal, as it cannot effectively distinguished between fungal taxa from food or soil inadvertently ingested and intestines. Future research on functions such as cultivation and metagenomics may further elucidate the role of fungi in the gut ecosystem.
Helicobacter Pylori infection in children with inflammatory bowel disease: a prospective multicenter study
Authors: Dilaghi Emanuele , Felici Enrico , Lahner Edith , Pilozzi Emanuela , Furio Silvia , Lucchini Livia , Quatrale Giovanna , Piccirillo Marisa , Parisi Pasquale , Curto Sara , Annibale Bruno , Ferretti Alessandro , Mennini Maurizio , Persechino Severino , Di Nardo Giovanni
Published: July 2024

Background

The relationship between Helicobacter-pylori(Hp)infection and inflammatory-bowel-disease(IBD) in pediatric-patients remains controversial. We aimed to assess the Hp-infection occurrence in newly-diagnosed pediatric-patients with IBD compared to no-IBD patients. Additionally, we aimed to examine differences in clinical-activity-index(CAI) and endoscopic-severity-score(ESS)between IBD-patients with and without Hp-infection, at baseline and at 1-year-follow-up(FU), after eradication-therapy(ET).

Methods

IBD diagnosis was based on Porto-criteria, and all patients underwent gastroscopy at baseline and 1-year FU. For Crohn's-disease(CD) and ulcerative colitis(UC), IBD-CAI and -ESS were classified using PCDAI/SES-CD and PUCAI/UCEIS, respectively.

Results

76 IBD-patients were included in the study[35 F(46.1%),median-age 12(range 2–17)]. CD and UC were diagnosed in 29(38.2%) and 45(59.2%)patients, respectively, and unclassified-IBD in two(2.6%)patients. Non-IBD patients were 148[71 F(48.0%),median-age 12(range 1–17)]. Hp-infection at baseline was reported in 7(9.2%) and 18(12.2%)IBD and non-IBD patients, respectively(p = 0.5065).

The 7 IBD patients with Hp infection were compared to 69 IBD patients without Hp-infection at baseline evaluation, and no significant differences were reported considering CAI and ESS in these two groups.

At 1-year FU, after ET, IBD patients with Hp infection improved, both for CAI and ESS, but statistical significance was not reached.

Conclusion

The occurrence of Hp-infection did not differ between IBD and no-IBD patients. No differences in CAI or ESS were observed at the diagnosis, and after ET no worsening of CAI or ESS was noted at one-year FU, between Hp-positive and -negative IBD patients.
Analysis of serum peptidome profiles of non-metastatic and metastatic feline mammary carcinoma using liquid chromatography-tandem mass spectrometry
Authors: Paphussaro Weejarin , Roytrakul Sittiruk , Phaonakrop Narumon , Buthasane Wannapol , Rungsipipat Anudep , Tharasanit Theerawat , Suriyaphol Gunnaporn
Published: July 2024

Background

Feline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection is essential for preventing local and distant metastasis, thereby improving overall survival rates. While acquiring molecular data before surgery offers significant potential benefits, the current protein biomarkers for monitoring disease progression in non-metastatic FMC (NmFMC) and metastatic FMC (mFMC) are limited. The objective of this study was to investigate the serum peptidome profiles of NmFMC and mFMC using liquid chromatography-tandem mass spectrometry. A cross-sectional study was conducted to compare serum peptidome profiles in 13 NmFMC, 23 mFMC and 18 healthy cats. The liquid chromatography-tandem mass spectrometry analysis was performed on non-trypsinized samples.

Results

Out of a total of 8284 expressed proteins observed, several proteins were found to be associated with human breast cancer. In NmFMC, distinctive protein expressions encompassed double-stranded RNA-binding protein Staufen homolog 2 (STAU2), associated with cell proliferation, along with bromodomain adjacent to zinc finger domain 2A (BAZ2A) and gamma-aminobutyric acid type A receptor subunit epsilon (GABRE), identified as potential treatment targets. Paradoxically, positive prognostic markers emerged, such as complement C1q like 3 (C1QL3) and erythrocyte membrane protein band 4.1 (EPB41 or 4.1R). Within the mFMC group, overexpressed proteins associated with poor prognosis were exhibited, including B-cell lymphoma 6 transcription repressor (BCL6), thioredoxin reductase 3 (TXNRD3) and ceruloplasmin (CP). Meanwhile, the presence of POU class 5 homeobox (POU5F1 or OCT4) and laminin subunit alpha 1 (LAMA1), reported as metastatic biomarkers, was noted.

Conclusion

The presence of both pro- and anti-proliferative proteins was observed, potentially indicating a distinctive characteristic of NmFMC. Conversely, proteins associated with poor prognosis and metastasis were noted in the mFMC group.
The role and application of small extracellular vesicles in glioma
Authors: Yang Zhihao , Wu HaoYuan , Wang ZhiWei , Bian ErBao , Zhao Bing
Published: July 2024

Small extracellular vesicles (sEVs) are cell-derived, nanometer-sized particles enclosed by a lipid bilayer. All kinds of biological molecules, including proteins, DNA fragments, RNA, lipids, and metabolites, can be selectively loaded into sEVs and transmitted to recipient cells that are near and distant. Growing shreds of evidence show the significant biological function and the clinical significance of sEVs in cancers. Numerous recent studies have validated that sEVs play an important role in tumor progression and can be utilized to diagnose, stage, grading, and monitor early tumors. In addition, sEVs have also served as drug delivery nanocarriers and cancer vaccines. Although it is still infancy, the field of basic and translational research based on sEVs has grown rapidly. In this review, we summarize the latest research on sEVs in gliomas, including their role in the malignant biological function of gliomas, and the potential of sEVs in non-invasive diagnostic and therapeutic approaches, i.e., as nanocarriers for drug or gene delivery and cancer vaccines.
The survival prediction of advanced colorectal cancer received neoadjuvant therapy—a study of SEER database
Authors: Han Zhuo , Yang Haicheng , Qiao Qing , Wu Tao , He Xianli , Wang Nan
Published: July 2024

Purpose

The aim of study was to screen factors associated with the overall survival of colorectal cancer patients with lymph nodes metastasis who received neoadjuvant therapy and construct a nomogram model.

Methods

All enrolled subjects of the SEER database were randomly assigned to the training and testing group in a ratio of 3:2. The patients of Tangdu Hospital were seemed as validation group. Univariate cox regression analysis, lasso regression and random forest survival were used to screen variables related to the survival of advanced CRC patients received neoadjuvant therapy in the training group. Area under curves were adopted to evaluate the 1,3,5-year prediction value of the optimal model in three cohorts. Calibration curves were drawn to observe the prediction accuracy of the nomogram model. Decision curve analysis was used to assess the potential clinical value of the nomogram model.

Results

A total of 1833 subjects were enrolled in this study. After random allocation, 1055 cases of the SEER database served as the training group, 704 cases as the testing group and 74 patients from our center as the external validation group. Variables were screened by univariate cox regression used to construct a nomogram survival prediction model, including M, age, chemotherapy, CEA, perineural invasion, tumor size, LODDS, liver metastasis and radiation. The AUCs of the model for predicting 1-year OS in the training group, testing and validation group were 0.765 (0.703,0.827), 0.772 (0.697,0.847) and 0.742 (0.601,0.883), predicting 3-year OS were 0.761 (0.725,0.780), 0.742 (0.699,0.785), 0.733 (0.560,0.905) and 5-year OS were 0.742 (0.711,0.773), 0.746 (0.709,0.783), 0.838 (0.670,0.980), respectively. The calibration curves showed the difference between prediction probability of the model and the actual survival was not significant in three cohorts and the decision curve analysis revealed the practice clinical application value. And the prediction value of model was better for young CRC than older CRC patients.

Conclusion

A nomogram model including LODDS for the prognosis of advanced CRC received neoadjuvant therapy was constructed and verified based on the SEER database and single center practice. The accuracy and potential clinical application value of the model performed well, and the model had better predictive value for EOCRC than LOCRC.
The 5Cs of positive youth development: their impact on symptoms of depression, anxiety, stress, and emotional distress in Chilean adolescents
Authors: Marín-Gutiérrez Mauricio , Caqueo-Urízar Alejandra , Castillo-Francino Jenifer , Escobar-Soler Carolang
Published: July 2024

Effective approaches to addressing mental health challenges faced by adolescents require a deep understanding of the factors contributing to optimal development, well-being, and prosperity. From the perspective of Positive Youth Development (PYD), this study proposes to examine the relationship between the 5Cs of PYD (Competence, Confidence, Connection, Character, and Caring) and symptoms of depression, anxiety, stress, and emotional distress among Chilean adolescents. A quantitative, cross-sectional, non-experimental study was conducted with 425 adolescents (ages 12 to 19, M = 14.95, SD = 1.81) from three Chilean cities: Arica (23%), Alto Hospicio (32%), and Iquique (46%). Data analysis included the use of confirmatory factor analysis (CFA) and structural equation modeling (SEM). The results indicate that two of the 5Cs, Confidence and Connection, have a significant negative direct effect on the four evaluated criterion indicators. These findings contribute to the literature on positive youth development in Latin America and underscore the importance of fostering confidence and connection in interventions aimed at promoting the mental health of adolescents in Chile and in similar contexts.