bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Host Interactions with Engineered T-cell Micropharmacies
Authors: Bourne Christopher M. , Wallisch Patrick , Dacek Megan M. , Gardner Thomas J. , Pierre Stephanie , Vogt Kristen , Corless Broderick C. , Bah Mamadou A. , Romero-Pichardo Jesus E. , Charles Angel , Kurtz Keifer G. , Tan Derek S. , Scheinberg David A.
Published: July 2023

Abstract
Genetically engineered, cytotoxic, adoptively transferred T cells localize to antigen-positive cancer cells inside patients, but tumor heterogeneity and multiple immune escape mechanisms have prevented the eradication of most solid tumor types. More effective, multifunctional engineered T cells are in development to overcome the barriers to the treatment of solid tumors, but the interactions of these highly modified cells with the host are poorly understood. We previously engineered prodrug-activating enzymatic functions into chimeric antigen receptor (CAR) T cells, endowing them with a killing mechanism orthogonal to conventional T-cell cytotoxicity. These drug-delivering cells, termed Synthetic Enzyme-Armed KillER (SEAKER) cells, demonstrated efficacy in mouse lymphoma xenograft models. However, the interactions of an immunocompromised xenograft with such complex engineered T cells are distinct from those in an immunocompetent host, precluding an understanding of how these physiologic processes may affect the therapy. Herein, we expanded the repertoire of SEAKER cells to target solid-tumor melanomas in syngeneic mouse models using specific targeting with T-cell receptor (TCR)–engineered T cells. We demonstrate that SEAKER cells localized specifically to tumors, and activated bioactive prodrugs, despite host immune responses. We additionally show that TCR-engineered SEAKER cells were efficacious in immunocompetent hosts, demonstrating that the SEAKER platform is applicable to many adoptive cell therapies.
Table S1 from Activator protein-1 (AP-1) signaling inhibits the growth of Ewing sarcoma cells in response to DNA replication stress
Authors: Croushore Emma E. , Koppenhafer Stacia L. , Goss Kelli L. , Geary Elizabeth L. , Gordon David J.
Published: July 2023

Gene set enrichment analysis of genes up- and down-regulated in the EW8-RRM1-KO cells after removal of doxycycline.
Figure S2 from Activator protein-1 (AP-1) signaling inhibits the growth of Ewing sarcoma cells in response to DNA replication stress
Authors: Croushore Emma E. , Koppenhafer Stacia L. , Goss Kelli L. , Geary Elizabeth L. , Gordon David J.
Published: July 2023

Treatment of EW8-RRM1-KO cells with prexasertib.
Supplementary Movie 1 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade
Authors: Yadavilli Sapna , Waight Jeremy D , Brett Sara , Bi Meixia , Zhang Tianqian , Liu Yao-Bin , Ellis Catherine , Turner David C , Hahn Ashleigh , Shi Hong , Seestaller-Wehr Laura , Jing Junping , Xie Qing , Shaik Jafar Sadik , Ji Xiao , Gagnon Robert , Fieles William , Hook Laura , Grant Steven , Hopley Stephanie , DeYoung M. Phillip , Blackwell Christina , Chisamore Michael , Biddlecombe Robert , Figueroa David J , Hopson Christopher B , Srinivasan Roopa , Smothers James , Maio Michele , Rischin Danny , Olive Daniel , Paul Elaine , Mayes Patrick A. , Hoos Axel , Ballas Marc
Published: July 2023

Supplementary Movie 1
Supplementary Movie 1 Legend from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade
Authors: Yadavilli Sapna , Waight Jeremy D , Brett Sara , Bi Meixia , Zhang Tianqian , Liu Yao-Bin , Ellis Catherine , Turner David C , Hahn Ashleigh , Shi Hong , Seestaller-Wehr Laura , Jing Junping , Xie Qing , Shaik Jafar Sadik , Ji Xiao , Gagnon Robert , Fieles William , Hook Laura , Grant Steven , Hopley Stephanie , DeYoung M. Phillip , Blackwell Christina , Chisamore Michael , Biddlecombe Robert , Figueroa David J , Hopson Christopher B , Srinivasan Roopa , Smothers James , Maio Michele , Rischin Danny , Olive Daniel , Paul Elaine , Mayes Patrick A. , Hoos Axel , Ballas Marc
Published: July 2023

Expression dynamics and cellular localization of ICOS.
Supplementary Table S1 from LNS8801 inhibits Acute Myeloid Leukemia by inducing the production of reactive oxygen species and activating the endoplasmic reticulum stress pathway
Authors: Lee Inyoung , Doepner Miriam , Weissenrieder Jillian S , Majer Ariana D , Mercado Sophia , Estell Angela , Natale Christopher A , Sung Pamela J , Foskett J. Kevin , Carroll Martin , Ridky Todd W
Published: July 2023

Supplementary Table S1
Supplementary Figure 7 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade
Authors: Yadavilli Sapna , Waight Jeremy D , Brett Sara , Bi Meixia , Zhang Tianqian , Liu Yao-Bin , Ellis Catherine , Turner David C , Hahn Ashleigh , Shi Hong , Seestaller-Wehr Laura , Jing Junping , Xie Qing , Shaik Jafar Sadik , Ji Xiao , Gagnon Robert , Fieles William , Hook Laura , Grant Steven , Hopley Stephanie , DeYoung M. Phillip , Blackwell Christina , Chisamore Michael , Biddlecombe Robert , Figueroa David J , Hopson Christopher B , Srinivasan Roopa , Smothers James , Maio Michele , Rischin Danny , Olive Daniel , Paul Elaine , Mayes Patrick A. , Hoos Axel , Ballas Marc
Published: July 2023

Healthy human donor CD4+ T cells were pre-activated with antiCD3/CD28 for 48 hours and then re-stimulated with plate-bound anti-CD3 in the presence of increasing concentrations of soluble or plate-bound feladilimab or isotype control for 72 hours. IFNg levels were then assessed from cell-free supernatants using Meso Scale Discovery (MSD)-based detection.
Supplementary Figure S7 from LNS8801 inhibits Acute Myeloid Leukemia by inducing the production of reactive oxygen species and activating the endoplasmic reticulum stress pathway
Authors: Lee Inyoung , Doepner Miriam , Weissenrieder Jillian S , Majer Ariana D , Mercado Sophia , Estell Angela , Natale Christopher A , Sung Pamela J , Foskett J. Kevin , Carroll Martin , Ridky Todd W
Published: July 2023

Supplementary Figure S7. LNS8801-induced AML inhibition is independent of classical GPER signaling (A) Annexin V+ flow cytometry analysis of U937 cells treated with 250nM LNS8801, 10uM Forskolin, 100uM EPAC-specific cAMP (8-pCPT-2'-O-Me-cAMP), and 100uM PKA-specific cAMP (N6-benzoyl-cAMP). Cells were incubated for 24 hours. 3 replicates per condition were used. (B) Detection of intracellular calcium upon drug treatment via a spectrofluorimeter assay. Fura2-AM dye was used for detection. 25nM E2, 250nM LNS8801, 1uM Ionomycin, 2uM thapsigargin, and 100uM histamine were used. 3 replicates were used per condition.
Supplementary Figure S6 from LNS8801 inhibits Acute Myeloid Leukemia by inducing the production of reactive oxygen species and activating the endoplasmic reticulum stress pathway
Authors: Lee Inyoung , Doepner Miriam , Weissenrieder Jillian S , Majer Ariana D , Mercado Sophia , Estell Angela , Natale Christopher A , Sung Pamela J , Foskett J. Kevin , Carroll Martin , Ridky Todd W
Published: July 2023

Supplementary Figure S6. LNS8801 induces heterogeneous phosphorylation of CREB in AML (A) Western blot showing AML cell lines treated with either vehicle DMSO or 250nM LNS8801. Cells were treated for 30 minutes. pCREB quantification was normalized to CREB and Actin. (B) Western blots of primary AML samples treated with different doses of LNS8801. Cells were incubated for 1 hour. pCREB quantification was normalized to CREB and Actin.
Supplementary Figure S2 from LNS8801 inhibits Acute Myeloid Leukemia by inducing the production of reactive oxygen species and activating the endoplasmic reticulum stress pathway
Authors: Lee Inyoung , Doepner Miriam , Weissenrieder Jillian S , Majer Ariana D , Mercado Sophia , Estell Angela , Natale Christopher A , Sung Pamela J , Foskett J. Kevin , Carroll Martin , Ridky Todd W
Published: July 2023

Supplementary Figure S2. Human AML cell lines, primary MNC, and AML cells express GPER (A and B) Western blot of GPER expression in (A) AML cell lines, (B) normal mononuclear cells (MNC), and primary human AML samples. (C) Western blot of a primary AML sample treated with 250nM LNS8801 and/or 1uM G36. Cells were pretreated with G36 for 1 hour and treated with LNS8801 for 1 hour after pretreatment.
Supplementary Figure 2 from Activating Inducible T cell Co-stimulator (ICOS) yields anti-tumor activity alone and in combination with anti-PD-1 checkpoint blockade
Authors: Yadavilli Sapna , Waight Jeremy D , Brett Sara , Bi Meixia , Zhang Tianqian , Liu Yao-Bin , Ellis Catherine , Turner David C , Hahn Ashleigh , Shi Hong , Seestaller-Wehr Laura , Jing Junping , Xie Qing , Shaik Jafar Sadik , Ji Xiao , Gagnon Robert , Fieles William , Hook Laura , Grant Steven , Hopley Stephanie , DeYoung M. Phillip , Blackwell Christina , Chisamore Michael , Biddlecombe Robert , Figueroa David J , Hopson Christopher B , Srinivasan Roopa , Smothers James , Maio Michele , Rischin Danny , Olive Daniel , Paul Elaine , Mayes Patrick A. , Hoos Axel , Ballas Marc
Published: July 2023

Flow cytometry gating strategy for ICOS on individual T cell populations.
Supplementary Figure S1 from LNS8801 inhibits Acute Myeloid Leukemia by inducing the production of reactive oxygen species and activating the endoplasmic reticulum stress pathway
Authors: Lee Inyoung , Doepner Miriam , Weissenrieder Jillian S , Majer Ariana D , Mercado Sophia , Estell Angela , Natale Christopher A , Sung Pamela J , Foskett J. Kevin , Carroll Martin , Ridky Todd W
Published: July 2023

Supplementary Figure S1. AML cells are particularly sensitive to LNS8801 (A-F) Proliferation assay performed with (A) A375, (B) WM46, (C) Mel290, (D) PANC-1, (E) MiaPaca-2, and (F) U937 cells. Dotted line represents the number of cells seeded. Cells were treated with 250nM LNS8801 for 72 hours. 5 replicates were used per condition per cell line. P values were calculated via pairwise t-tests (*p=<0.05, **p=<0.01, ***p=<0.001, ****p=<0.0001).
Supplementary Figure S2 from A Th1-like CD4+ T-cell Cluster That Predicts Disease-free Survival in Early-stage Lung Cancer
Authors: Yanagihara Akitoshi , Yamasaki Satoshi , Hashimoto Kosuke , Taguchi Ryo , Umesaki Tetsuya , Imai Hisao , Kaira Kyoichi , Nitanda Hiroyuki , Sakaguchi Hirozo , Ishida Hironori , Kobayashi Kunihiko , Horimoto Katsuhisa , Kagamu Hiroshi
Published: July 2023

Fig. S2. Kaplan-Meier analysis of disease-free survival (DFS) in patients with stage Ⅰ-Ⅱ disease (A), epidermal growth factor receptor (EGFR) wild-type disease, and EGFR mutations (B) using the threshold of preoperative %Th7R in peripheral blood obtained by receiver operating characteristic curve analysis. Significance was tested using the log-rank (Mantel-Cox) test. Hazard ratio (HR) and 95% confidence interval (CI) were obtained by log-rank test.
FIGURE 4 from A Th1-like CD4+ T-cell Cluster That Predicts Disease-free Survival in Early-stage Lung Cancer
Authors: Yanagihara Akitoshi , Yamasaki Satoshi , Hashimoto Kosuke , Taguchi Ryo , Umesaki Tetsuya , Imai Hisao , Kaira Kyoichi , Nitanda Hiroyuki , Sakaguchi Hirozo , Ishida Hironori , Kobayashi Kunihiko , Horimoto Katsuhisa , Kagamu Hiroshi
Published: July 2023

CD4+ T-cell clusters in LNs. A, Cells from station #12 LNs close to lung cancer tissue were analyzed by mass cytometry as draining LNs, and cells from ipsilateral mediastinal LNs were analyzed as distant LNs (n = 20). Representative tSNE figures of gated CD4+CD3+ cells of lung cancer draining lymph node cells. B, Representative annotation of draining LN cells according to CXCR3, CCR4, CCR6, and FoxP3 expression. C, The percentages of Th and Treg clusters in draining LNs (dLN). D, CD62Llow CD4+ T-cell correlation between peripheral blood (PB) and draining LNs was analyzed. E, Correlation between the percentage of CD62Llow Th in PB and that of total Th in draining LNs was analyzed. F, The percentages of Th7R and Th1 between PB, draining LNs, and distant LNs were compared. Differences were tested using the mixed effects model (REML) followed by Tukey multiple comparison test.
FIGURE 1 from A Th1-like CD4+ T-cell Cluster That Predicts Disease-free Survival in Early-stage Lung Cancer
Authors: Yanagihara Akitoshi , Yamasaki Satoshi , Hashimoto Kosuke , Taguchi Ryo , Umesaki Tetsuya , Imai Hisao , Kaira Kyoichi , Nitanda Hiroyuki , Sakaguchi Hirozo , Ishida Hironori , Kobayashi Kunihiko , Horimoto Katsuhisa , Kagamu Hiroshi
Published: July 2023

CD4+ T-cell clusters predict DFS of patients with lung cancer after surgical resection. A, Peripheral blood T cells collected from patients with lung cancer before surgery were analyzed by mass cytometry. The percentage of CD62Llow CD4+ T cells and each Th cell type in the CD62Llow CD4+ T-cell subpopulation is shown for patients who relapsed by the last observation date and for those who did not relapse. Th types were determined by chemokine expression patterns, including CXCR3, CCR4, and CCR6. Unpaired Welch t test was used for statistical analysis. B, ROC curve analysis was performed to determine whether Th clusters in the CD62Llow CD4+ T-cell subpopulation could discriminate between relapsed and non-relapsed patients. Next, Kaplan–Meier analysis of DFS was performed using the threshold obtained from ROC analysis as the best likelihood ratio, or the median value was used as a threshold if ROC analysis showed no significance. Significance was tested by a log-rank (Mantel–Cox) test. The HR and 95% CI were obtained by the log-rank test.
TABLE 2 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: July 2023

Flow cytometry: Prostate cancer cell lines stained with stemness markers (CD44, CD133, and CD44/133) to determine the percent of CD44+, CD133+, and double-positive cells in prostate cancer subtypes
FIGURE 3 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: July 2023

Metronomic topotecan in combination with DTX showed potency against prostate cancer subtypes, ARLow/mCRPC/NEPC (PC-3, PC-3M, DU145) and ARLow/mCSPC/NEPCtaxane resistant (DUTXR) cells. Cytotoxicity: In vitro effect of metronomic and conventional administration of topotecan on prostate cancer cell lines was assessed. A, MTT assay: Cytotoxicity was measured following 72 hours of CONV-TOPO, CONV-DTX, METRO-TOPO, and the combination of CONV-DTX+METRO-TOPO treatment in PC-3, PC-3M, DU145, DUTXR cell lines using mitochondrial activity [3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] or the MTT assay. In all cell lines, METRO-TOPO (lower dose) reduced cell growth more compared with CONV (high dose) treatment at IC50/2. The greatest reduction in cell growth was observed following CONV-DTX + METRO-TOPO combination treatment in all prostate cancer cell lines tested (*, P ≤ 0.05). B, Apoptosis (caspase 3/7 assay): Levels of caspase 3/7 enzyme (a marker of apoptosis) activities measured followed CONV-TOPO, CONV-DTX, METRO-TOPO, and the combination of CONV-DTX + METRO-TOPO 72 hours treatment. Results showed significant increases in caspase 3/7 activity following each treatment compared with control. Results confirmed significantly greater treatment-induced apoptosis was observed for post-METRO-TOPO treatment compared with CONV-TOPO and DTX. The highest treatment-induced apoptosis was observed in combination with CONV-DTX+METRO-TOPO in all cell lines (*, P ≤ 0.05). C, Microscope images (Cytation5): Cell morphologic study reported micrographs of prostate cancer cells exposed to all dosing regimens showed decreases in cell density compared with control cells. Results showed that METRO-TOPO reduces higher cell density compared with CONV-TOPO and CONV-DTX. Highest cell death observed in CONV-DTX+METRO-TOPO combination treatment compared with CONV-TOPO, CONV-DTX, and METRO-TOPO single-drug treatment (*, P ≤ 0.05).
Data from Activator Protein-1 (AP-1) Signaling Inhibits the Growth of Ewing Sarcoma Cells in Response to DNA Replication Stress
Authors: Croushore Emma E. , Koppenhafer Stacia L. , Goss Kelli L. , Geary Elizabeth L. , Gordon David J.
Published: July 2023

Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in the synthesis of deoxyribonucleosides and is required for DNA replication. Multiple types of cancer, including Ewing sarcoma tumors, are sensitive to RNR inhibitors or a reduction in the levels of either the RRM1 or RRM2 subunits of RNR. However, the polypharmacology and off-target effects of RNR inhibitors have complicated the identification of the mechanisms that regulate sensitivity and resistance to this class of drugs. Consequently, we used a conditional knockout (CRISPR/Cas9) and rescue approach to target RRM1 in Ewing sarcoma cells and identified that loss of the RRM1 protein results in the upregulation of the expression of multiple members of the activator protein-1 (AP-1) transcription factor complex, including c-Jun and c-Fos, and downregulation of c-Myc. Notably, overexpression of c-Jun and c-Fos in Ewing sarcoma cells is sufficient to inhibit cell growth and downregulate the expression of the c-Myc oncogene. We also identified that the upregulation of AP-1 is mediated, in part, by SLFN11, which is a replication stress response protein that is expressed at high levels in Ewing sarcoma. In addition, small-molecule inhibitors of RNR, including gemcitabine, and histone deacetylase inhibitors, which reduce the level of the RRM1 protein, also activate AP-1 signaling and downregulate the level of c-Myc in Ewing sarcoma. Overall, these results provide novel insight into the critical pathways activated by loss of RNR activity and the mechanisms of action of inhibitors of RNR.
Significance:
RNR is the rate-limiting enzyme in the synthesis of deoxyribonucleotides. Although RNR is the target of multiple chemotherapy drugs, polypharmacology and off-target effects have complicated the identification of the precise mechanism of action of these drugs. In this work, using a knockout-rescue approach, we identified that inhibition of RNR upregulates AP-1 signaling and downregulates the level of c-Myc in Ewing sarcoma tumors.
Data from Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint Blockade
Authors: Yadavilli Sapna , Waight Jeremy D. , Brett Sara , Bi Meixia , Zhang Tianqian , Liu Yao-Bin , Ellis Catherine , Turner David C. , Hahn Ashleigh , Shi Hong , Seestaller-Wehr Laura , Jing Junping , Xie Qing , Shaik Jafar Sadik , Ji Xiao , Gagnon Robert , Fieles William , Hook Laura , Grant Steven , Hopley Stephanie , DeYoung M. Phillip , Blackwell Christina , Chisamore Michael , Biddlecombe Robert , Figueroa David J. , Hopson Christopher B. , Srinivasan Roopa , Smothers James , Maio Michele , Rischin Danny , Olive Daniel , Paul Elaine , Mayes Patrick A. , Hoos Axel , Ballas Marc
Published: July 2023

In recent years, there has been considerable interest in mAb-based induction of costimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet to translate to a meaningful clinical benefit. Inducible T-cell costimulator (ICOS) is a costimulatory receptor important for immune responses. Using a novel clinical-stage anti-ICOS immunoglobulin G4 mAb (feladilimab), which induces but does not deplete ICOS+ T cells and their rodent analogs, we provide an end-to-end evaluation of the antitumor potential of antibody-mediated ICOS costimulation alone and in combination with programmed cell death protein 1 (PD-1) blockade. We demonstrate, consistently, that ICOS is expressed in a range of cancers, and its induction can stimulate growth of antitumor reactive T cells. Furthermore, feladilimab, alone and with a PD-1 inhibitor, induced antitumor activity in mouse and humanized tumor models. In addition to nonclinical evaluation, we present three patient case studies from a first-time-in-human, phase I, open-label, dose-escalation and dose-expansion clinical trial (INDUCE-1; ClinicalTrials.gov: NCT02723955), evaluating feladilimab alone and in combination with pembrolizumab in patients with advanced solid tumors. Preliminary data showing clinical benefit in patients with cancer treated with feladilimab alone or in combination with pembrolizumab was reported previously; with example cases described here. Additional work is needed to further validate the translation to the clinic, which includes identifying select patient populations that will benefit from this therapeutic approach, and randomized data with survival endpoints to illustrate its potential, similar to that shown with CTLA-4 and PD-1 blocking antibodies.
Significance:
Stimulation of the T-cell activation marker ICOS with the anti-ICOS agonist mAb feladilimab, alone and in combination with PD-1 inhibition, induces antitumor activity across nonclinical models as well as select patients with advanced solid tumors.
Detergent-Compatible Amylases Produced by Fungal Species and Their Applications in Detergent Industry
Authors: Niyonzima Francois N. , Mahnashi Mater H. , Shaikh Ibrahim Ahmed , Mannasaheb Basheerahmed Abdulaziz , Ghoneim Mohammed M. , Asdaq Syed Mohammed Basheeruddin , Khan Aejaz Abdullatif , Nsanganwimana Florien , More Veena S. , Nuwayo Sincere I. , More Sunil S. , Vidya A. S.
Published: July 2023

Detergent enzymes are currently vital and important ingredients of modern powder and liquid detergents. They catalyze various biochemical processes intra-or extracellularly in the detergent industries. Microorganisms are the favored source of detergent compatible fungal amylases compared
to plant or animal sources. Detergents cannot be produced in the developed countries without a mixture of detergent enzymes supplementation because they are essential components in the detergent industries. In countries under development, various produced detergents do not have enzymes. Amylases,
proteases, pectinases, lipases, mannanases, and cellulases are generally the hydrolytic enzymes used in the detergent industries. They remove all soft, tough and stubborn starchy food, protein, pectin, fatty, mannane and cellulose-based stains attached to the various substrates like fabrics
or glassware. A number of review articles on detergent-compatible bacterial and fungal enzymes exists, but none specifically covers detergent-compatible fungal amylases. In the present review, production and aspects of detergent fungal amylases are discussed with an emphasis on the stability
of fungal amylases in the presence of detergent constituents. The article will help other worldwide research to study the properties of detergent pectinases and mannanases which are not extensively studied.
Investigating the association between serum ADAM/ADAMTS levels and bone mineral density by mendelian randomization study
Authors: Lv Xin , Lin Yuhong , Zhang Zhilei , Li Bo , Zeng Ziliang , Jiang Xu , Zhao Qiancheng , Li Wenpeng , Wang Zheyu , Yang Canchun , Yan Haolin , Wang Qiwei , Huang Renyuan , Hu Xumin , Gao Liangbin
Published: July 2023

Purpose

A Disintegrin and Metalloproteinase (ADAM) and A Disintegrin and Metalloproteinase with Thrombospondin Motif (ADAMTS) have been reported potentially involved in bone metabolism and related to bone mineral density. This Mendelian Randomization (MR) analysis was performed to determine whether there are causal associations of serum ADAM/ADAMTS with BMD in rid of confounders.

Methods

The genome-wide summary statistics of four site-specific BMD measurements were obtained from studies in individuals of European ancestry, including forearm (n = 8,143), femoral neck (n = 32,735), lumbar spine (n = 28,498) and heel (n = 426,824). The genetic instrumental variables for circulating levels of ADAM12, ADAM19, ADAM23, ADAMTS5 and ADAMTS6 were retrieved from the latest genome-wide association study of European ancestry (n = 5336 ~ 5367). The estimated causal effect was given by the Wald ratio for each variant, the inverse-variance weighted model was used as the primary approach to combine estimates from multiple instruments, and sensitivity analyses were conducted to assess the robustness of MR results. The Bonferroni-corrected significance was set at P < 0.0025 to account for multiple testing, and a lenient threshold P < 0.05 was considered to suggest a causal relationship.

Results

The causal effects of genetically predicted serum ADAM/ADAMTS levels on BMD measurements at forearm, femoral neck and lumbar spine were not statistically supported by MR analyses. Although causal effect of ADAMTS5 on heel BMD given by the primary MR analysis (β = -0.006, -0.010 to 0.002, P = 0.004) failed to reach Bonferroni-corrected significance, additional MR approaches and sensitivity analyses indicated a robust causal relationship.

Conclusion

Our study provided suggestive evidence for the causal effect of higher serum levels of ADAMTS5 on decreased heel BMD, while there was no supportive evidence for the associations of ADAM12, ADAM19, ADAM23, and ADAMTS6 with BMD at forearm, femoral neck and lumbar spine in Europeans.
Translation, cultural adaptation and evaluation of the psychometric properties of the Hamilton Anxiety Scale among a sample of Portuguese adult patients with mental health disorders
Authors: dos Santos Eugénia Raquel Pinheiro , Coelho Joana Catarina Ferreira , Ribeiro Isilda , Sampaio Francisco
Published: July 2023

Background

Only a few anxiety assessment tools that nurses may administer are validated forthe Portuguese population exist in the literature. Thus, this study aimed to translate and culturally adapt the Hamilton Anxiety Scale for the Portuguese population and assess its psychometric properties in a sample of adult people with mental health disorders.

Methods

This psychometric study uses a convenience sample of adult patients with mental health disorders.

Results

The confirmatory factor analysis confirmed the two factors of the original version of the tool. The internal consistency (Cronbach’s alpha) was high, at .92, as well as the inter-rater reliability (intraclass correlation coefficient) (.91).

Conclusions

The validity and reliability of the instrument are supported. However, the Hamilton Anxiety Scale should be used cautiously in the Portuguese population because the correlation with the “Anxiety State” subscale of the State-Trait Anxiety Inventory is not statistically significant.
A systematic review of the impact of the COVID-19 pandemic on the mental health of adolescents and young people with disabilities aged 15–29 years
Authors: Leung Xing Yu , Kavanagh Anne Marie , Quang Que Tien , Shields Marissa , Aitken Zoe
Published: July 2023

Background

The COVID-19 pandemic has exacerbated the psychological burden on young people around the world and may have disproportionately large impacts for young people with disabilities. This review aims to systematically review the quantitative evidence on the impact of the COVID-19 pandemic on the mental health of young people with disabilities and evaluate the quality of included studies.

Methods

A systematic search was conducted using 5 electronic databases. The quality of the studies was assessed using the SIGN risk of bias assessment tool. A narrative synthesis was performed to synthesize the results of included studies.

Results

The initial search yielded 1935 studies, of which two met the eligibility criteria, one longitudinal study and one cross-sectional study, both assessed to be of low quality. In the cross-sectional study, young people with intellectual and developmental disabilities self-reported an increase in mental health symptoms. The longitudinal study found no evidence of a change in mental health symptoms from pre-pandemic to during the pandemic among young people with autism spectrum disorder, although these individuals reported negative impacts of the COVID-19 pandemic on their emotional or mental health.

Conclusions

The findings of this review provide some weak evidence of a negative impact of the COVID-19 pandemic on the mental health of young people with disabilities. Importantly, the findings highlight the lack of research in this area. More research is needed to investigate the impact of the pandemic on the mental health of young disabled people, in order for governments to develop emergency preparedness plans to safeguard the well-being of this population.
Experiences of pain and pain management in advanced disease and serious illness for people from South Asian communities in Leeds and Bradford: a qualitative interview study
Authors: Clarke Gemma , Crooks Jodie , Bennett Michael I. , Mirza Zarina , OBE Ruby Bhatti , Nazar Wali , Mughal Rahila , Ahmed Shenaz
Published: July 2023

Background

Pain is a significant problem for many people with advanced disease or a serious illness. Culture and ethnicity can affect the experience and management of pain. However, there is limited research in South Asian communities in the UK on their experiences of pain. The aim of this study is to explore the experiences and attitudes of patients and family carers from South Asian communities about pain and its management within advanced disease or serious illness.

Methods

Qualitative thematic analysis based on descriptive phenomenology (Sundler et al. 2019). Qualitative semi-structured interviews with patients or family carers from South Asian communities (N = 15). Interviews were recorded, transcribed and analysed using an inductive approach. Public and Patient Involvement representatives from British South Asian communities were consulted for guidance.

Results

There were five key themes from the interviews: The importance of communication about pain with healthcare professionals; Concerns about taking pain medication; Personal resilience, privacy and self-management; Gender, culture and pain; Home pain management as struggle and frustration.

Conclusion

To improve pain management for people from South Asian communities with advanced disease or a serious illness, there are a number of important issues for healthcare professionals from palliative and primary care services to address. These include: greater awareness around people’s fears and concerns about pain medication; their potential use of alternative pain management strategies; and cultural issues such as resilience, privacy, dignity and gender roles. Effective communication between doctors, patients and family members could be improved by using a ‘cultural humility’ model; providing clear and accessible pain medication information; understanding and taking account of people with both low, and medium levels, of English language proficiency; and improving patient trust. Additionally, improvements to out of hours services could improve pain management for all patients managing their pain at home.
Improving cardiovascular health by replacing salt with low-sodium substitutes: a synthesis of existing evidence
Authors: Mohamed Areej , Ali-heybe Zundus , Hamer Oliver , Hill James
Published: July 2023

In this commentary, Areej Mohamed and colleagues critically appraise a Cochrane systematic review that synthesised the evidence for low-sodium salt substitutes as an intervention to improve health outcomes.
Key changes in the cardiovascular system during uncomplicated pregnancy, birth and the postnatal period: an overview
Authors: Maxwell Clare , Hudson Traci , Lotto Robyn
Published: July 2023

Clare Maxwell and colleagues provide an overview of the typical physiological changes that occur during and after pregnancy, and how these changes can lead to or exacerbate cardiovascular pathologies.
Summer poisoning hazards
Authors: Bates Nicola
Published: July 2023

There is a seasonal risk with some poisons and in the summer, when stinging insects and adders are more active, there is a risk of envenomation. Diagnosis of an adder bite may be missed in horses, as the biting event is rarely witnessed. Envenomation may result in local swelling and occasionally, systemic effects. Multiple bee stings are particularly hazardous as this can result in multi-organ involvement, which may be fatal. Grazing on some plants, such as ragwort or bracken, for a prolonged period can also result in poisoning as ragwort contains pyrrolizidine alkaloids which cause liver failure and bracken contains an enzyme that has an anti-thiamine effect, inducing thiamine deficiency. Photosensitisation following exposure to plants containing phototoxins and bright sunlight is also a risk in summer. Treatment of plant poisoning in horses is generally supportive and involves removing the plant, providing good quality food and supportive care. Thiamine supplementation may be required in severe cases of bracken poisoning. Animals should be protected from sunlight following exposure to a phototoxin, with supportive management of skin lesions. Management of adder bite is supportive with administration of adder antivenom. Multiple bee stings require aggressive supportive care.
Unraveling the Mystery of Parosteal Lipoma of the Distal Femur: A Rare Case Report
Authors: Sathiyaseelan Naveen , Meena Mahaveer , Jhanwar Purushottam
Published: July 2023

Introduction: Among all the primary bone tumors and all the type of lipomas, parosteal lipomas stand for <0.1% and 0.3%, respectively, which mostly consists of fully developed adipose tissue with or without a bony component. Patients with this tumor usually have bony lesions (59.2%), necessitating a differential diagnosis of malignant tumors. Case Report: Here, we analyze a case report of a 9-year-old boy, who developed a parosteal lipoma in the distal femur. A massive, well-defined, lobulated, mostly fat-intensity lesion of 10 cm by 6 cm by 8 cm was seen on an magnetic resonance imaging scan of the right distal femur. After the lump was removed, the pathologically reveals a parosteal lipoma without any malignant changes. Conclusion: Finally, it should be noted that parosteal lipomas are less common neoplasias with no known malignant potential. Since these tumors can be removed with mild impact to nearby structures, the lower limb’s functionality is kept intact. Keywords: Parosteal lipoma, distal femur, lipocytes, vastus medialis, case report.
Accurate modeling of ultrafast nonlinear pulse propagation in multimode gain fiber
Authors: Chen Yi-Hao , Haig Henry , Wu Yuhang , Ziegler Zachary , Wise Frank
Published: July 2023

The nonlinear propagation of picosecond or femtosecond optical pulses in multimode fiber amplifiers underlies a variety of intriguing physical phenomena as well as the potential for scaling sources of ultrashort pulses to higher powers. However, existing theoretical models of ultrashort-pulse amplification do not include some critical processes, and, as a result, they fail to capture basic features of experiments. We introduce a numerical model that combines steady-state rate equations with the unidirectional pulse propagation equation, incorporating dispersion, Kerr and Raman nonlinearities, and gain/loss-spectral effects in a mode-resolved treatment that is computationally efficient. This model allows investigation of spatiotemporal processes that are strongly affected by gain dynamics. Its capabilities are illustrated through examinations of amplification in few-mode gain fiber, multimode nonlinear amplification, and beam cleaning in a multimode fiber amplifier.
The burden of disabilities in Sidama National Regional State, Ethiopia: A cross-sectional, descriptive study
Authors: Tenaw Zelalem , Gari Taye , Gebretsadik Achamyelesh
Published: July 2023

Background

Assessing the burden and describing the status of people with disabilities is very essential. The previous studies conducted about the prevalence, causes, and types of disability in Ethiopia were inconsistent and disagreeable.

Objectives

To determine the prevalence, causes, and types of disabilities in Sidama National Regional State, Ethiopia.

Methods

A house-to-house census was carried out on a total of 39,842 households in 30 randomly selected kebeles of the Dale and Wonsho districts and Yirgalem city administration, Sidama National Regional State. The data were collected using structured and pretested questionnaires via the Kobo Collect application from May 01 to 30, 2022. The analysis was performed by STATA version 16 software. After cleaning and organizing, descriptive statistics were employed to characterize the study findings.

Results

In this study, people with disabilities aged one to 80 years old were included. The mean Standard Deviation (SD) age of people with disabilities in years was 31.95 (15.33). Of 228,814 people, 1,694 were people with disabilities in Dale and Wonsho districts and Yirgalem city administration, with a prevalence of 0.74% (95% CI: 0.72, 0.76). Of the causes of disability, 61% of the disabilities were due to illness, injury, and accidents. Extremity paralysis (35.4%), vision disability (20.13%), hearing disability (19.7%), walking disability (14.7%), and cognitive disabilities (7.7%) were the identified types of disabilities.

Conclusion

This study revealed that the burden of disability is considerable in Dale and Wonsho districts and Yirgalem city administration. The vast majority of disability causes could have been avoidable. As a result, developing and implementing various strategies to raise community awareness about the causes and preventive measures is critical.
A biochemical analysis of Black Soldier fly (Hermetia illucens) larval frass plant growth promoting activity
Authors: Green Terrence
Published: July 2023

Black Soldier fly (Hermetia illucens) larval (BSFL) frass was examined for its nutrient nitrogen, phosphate and potassium (N:P205:K2O), phytohormone and biogenic amine content, its plant growth promoting activity, and screened to test the hypothesis that bacteria characteristic of the genus Enterococcus (present in the biome of decaying catering waste and the larval gut) are excreted by BSFL in their frass. Frass plant growth promoting activity was measured by comparing the growth of winter wheat berry (Triticum aestivum) in frass treated soil to that of untreated (control) soil. The N:P205:K2O percent dry matter average, biogenic amine and phytohormone content of frass was determined by standard soil analysis, HPLC and HPLC/GC-MS methodologies, respectively. All were at too low of concentrations to account for its plant growth promoting activity. Frass added to soil induced a 11% increase in aerial mass and shoot length in treated plants over controls. Numerous colonies of Enterococci growing out on BEA (bile-esculin-agar) plates were detected in frass collected directly from larvae confirming the hypothesis that viable Enteroccoci are passing from the larval gut into their frass. Since a number of rhizobacteria, including Enterococci, have previously been identified as part of the larval gut biome, the passage of Enterococci from the larval gut into frass in the face of only trace N:P205:K2O percent dry matter averages, biogenic amine and phytohormone content is consistent with the hypothesis that Enterococci exhibiting rhizobacterial activity have a role in conferring to frass its plant growth promoting activity.
A short history of the successes and failures of the international climate change negotiations
Authors: Maslin Mark A. , Lang John , Harvey Fiona
Published: July 2023

The last 35 years have been a period of intense and continuous international negotiations to deal with climate change. During the same period of time humanity has doubled the amount of anthropogenic carbon dioxide in the atmosphere. There has, however, been progress and some notable successes in the negotiations. In 2015, at COP21 of the United Nations Framework Convention on Climate Change, 196 countries adopted the Paris Agreement stating that they would limit global temperatures to well below 2°C above pre-industrial levels and would pursue efforts to limit the temperature increase to 1.5°C above pre-industrial levels. The first review of the Paris Agreement was at COP26 in Glasgow with many countries pledging to go to net zero emissions by the middle of the century. But currently these pledges, if fulfilled, will only limit the global average temperature to between 2.4°C and 2.8°C. At COP27 in Egypt the core agreements from the Glasgow Climate Pact were maintained and countries finally agreed to set up a loss and damage facility – although details of who will provide the finance and who can claim are still be to be worked out. This article reviews the key moments in the history of international climate change negotiations and discusses what the key objectives are for future COP meetings.
Aktivnosti za preprečevanje osamljenosti starejših odraslih v domovih za starejše
Authors: Mlinar Reljić Nataša , Lavbič Mateja , Fekonja Zvonka , Kmetec Sergej
Published: July 2023

Uvod: Osamljenost je mednarodni problem javnega zdravja. Povzroča boleč in skrb vzbujajoč občutek čustvene ali socialne izolacije in je vzrok težavam, povezanim z duševnim zdravjem. Osamljenost je pogosto prisotna pri starejših odraslih, tudi pri tistih, ki bivajo v domovih za starejše. S pregledom literature želimo predstaviti aktivnosti in njihovo učinkovitost pri zmanjševanju osamljenosti pri starejših odraslih v domovihza starejše.Metode: Izvedli smo sistematični pregled znanstvene literature. Iskanje s ključnimi besedami v angleškem jeziku je potekalo v mednarodnih bazah podatkov: PubMed, CINAHL in SAGE. Za prikaz pregleda ter izbire vključenih člankov smo uporabili diagram poteka. Vključene članke smo kritično ocenili z orodjem Joanna Briggs Institutes in zbrane podatke analizirali po metodi tematske analize.Rezultati: V končno analizo je bilo vključenih 20 člankov. Oblikovali smo dve glavni temi. Prva tema »aktivnosti za preprečevanje osamljenosti« odraža dve podtemi: gibalne in družabne aktivnosti. Druga tema »vpliv aktivnosti na preprečevanje osamljenosti« prikazuje fizične, psihološke in socialne vplive aktivnosti na preprečevanje osamljenosti.Diskusija in zaključek: Pri zmanjševanju osamljenosti so najučinkovitejše vodene in usmerjene aktivnosti: telesne vadbe, umetniško ustvarjanje, vrtnarjenje, pogovorne skupine, pa tudi terapija smeha in obujanje spominov.
Animals are the homeless: A portrayal of sea ice dependent animals losing their natural habitat. A cognitive linguistics-oriented analysis of chosen climate change awareness raising campaigns
Authors: Majdzińska-Koczorowicz Aleksandra
Published: July 2023

The text aims at discussing the verbo-visual means of expression employed in three climate change-related campaigns in the context of their effectiveness. The chosen climate change awareness raising campaigns by two non-governmental organisations, EcoEduca and World Wide Fund for Nature Inc. (WWF), deal with the results of Arctic permafrost thaw resulting in the loss of sea ice dependent animals’ habitat. A cognitive linguistics oriented analysis refers to the theory of metaphor (Lakoff and Johnson 1980, Forceville 1996, Kövecses 2002, 2014), conceptual blending (Fauconnier and Turner 2003), and construal (Langacker 1987, 2008). The visual layer will also be described with reference to a grammar approach to visual communication (Kress and Van Leeuwen 1996, 2001, Machin 2010).
Application value of a nomogram model based on clinical and MRI features in predicting invasive placenta
Authors: Chen Junzhuo , Zhang Liwei , Cai Yan , Qin Haiyan , Hu Ping , Gao Chao , Hu Weizhuo , Sun Lei , Li Huan , Cao Shaodong
Published: July 2023

Purpose:

This study was aimed at investigating the value of a nomogram model based on clinical and MRI features in predicting the risk of invasive placenta.

Methods:

Clinical and imaging data for 162 pregnant women with suspected placenta accreta spectrum disorders (PASDs) were retrospectively analyzed; data for 122 cases were used as a derivation cohort, and data from 40 cases were used as a validation cohort. In the derivation cohort, multivariable logistic regression analyses were conducted to develop a model for predicting invasive placenta. The predictive model was validated in 40 pregnant women, the nomogram was constructed, and the predictive efficiency of the model was evaluated through receiver operating characteristic curve analysis.

Results:

Ten indicators—prior caesarean delivery, loss of the placental-myometrial interface, myometrial interruption, placental/uterine bulge, marked placental heterogeneity, T2-dark intraplacental bands, abnormal vascularization of the placental bed, intraplacental abnormal vascularization, cervical invasion and bladder invasion—significantly differed between invasive and non-invasive placenta (P<0.05). The independent risk factors for invasive placenta were placental/uterine bulge, loss of the placental-myometrial interface, marked placental heterogeneity and abnormal vascularization of the placental bed. The areas under the curve for the derivation cohort and validation cohort were 0.925 and 0.974, respectively, and the diagnostic coincidence rates were 87.7% and 90.0%, respectively.

Conclusion:

The nomogram model based on clinical and MRI features effectively predicts invasive placenta.
Photo-degradation of water borne acrylic coated modified and non-modified wood during artificial light exposure
Authors: Dekaa Manabendra , Petrič Marko
Published: July 2023

A series of experiments were carried out to investigate photo-degradation of thermally modified (at 210oC and minus 0.9 bars for two hours) and non-modified spruce wood [Picea abies L (Karst)], coated with transparent and semitransparent (with 3% pigment content) acrylic coatings during artificial UV light irradiation for 200 hours. Photo-degradation was evaluated in terms of colour changes throughout the irradiation period at an interval of 50 hours, along with IR and EPR spectroscopic study. One set of modified and non-modified woods was painted with coatings, while the other set was covered with free films made of coatings, just to simulate coated wood. The colour changes for both modified and non-modified wood samples without paint-coat or free film cover were comparable to that of wood samples with paint-coat and free film cover for transparent coat type, which indicated its ineffective-ness to prevent photo-degradation of wood underneath. However, the colour changes for both modified and non-modified wood samples with paint-coat and free film cover were much lower than those of samples without paint-coat or free film cover for semitransparent coat type, which might be due to hindrance of transmission of light energy through pigment to reach the underlying wood surface. On the other hand, whole substrate-coating system showed better photo-stability, when thermally modified wood was used as substrate. However, the colour changes of paint-coated and free-film covered samples for both modified and non modified woods might be due to colour changes of wood specimen underneath, because free films of both the coat types showed negligible colour change during UV irradiation.
The Interpersonal Relations in Deaf Children and Pupils
Authors: Georgieva Diyana
Published: July 2023

Interpersonal relationships occupy a central place in human life. People's willingness to interact is manifested in behavior, communication, social activities. An immanent characteristic of interpersonal relationships is their emotional basis, and the foundation – the primordial need for communication. Hearing children have sufficient capacity to accumulate experience in everyday communication. They form strategies for evaluating communication partners easily and promptly. In contrast, the limitation of social contacts and the specific assimilation of social experience in deaf children and pupils forms a peculiar picture of interpersonal relations, nuanced with a number of features in their construction to which this article is devoted.