bluuebunny/crossref_metadata_2025_split huggingface dataset:
Keeping it simple: the value of mortality prediction after trauma with basic indices like the Reverse Shock Index multiplied by Glasgow Coma Scale
Authors: Frieler Sven , Lefering Rolf , Gerstmeyer Julius , Drotleff Niklas , Schildhauer Thomas A , Waydhas Christian , Hamsen Uwe 
Published: June 2022

BackgroundIdentification of trauma patients at significant risk of death in the prehospital setting is challenging. The prediction probability of basic indices like vital signs, Shock Index (SI), SI multiplied by age (SIA) or the GCS is limited and more complex scores are not feasible on-scene. The Reverse SI multiplied by GCS score (rSIG) has been proposed as a triage tool to identify trauma patients with an increased risk of dying at EDs. Age adjustment (rSIG/A) displayed no advantage.We aim to (1) validate the accuracy of the rSIG in predicting death or early transfusion in a large trauma registry population, and (2) determine if the rSIG is valid for evaluation of trauma patients in the prehospital setting.Methods70 829 trauma patients were retrieved from the TraumaRegister DGU database (time period between 2008 and 2017). The area under the receiver operating characteristic curve (AUROC) was calculated to measure the ability of SI, SIA, rSIG and rSIG divided by age (rSIG/A) to predict in-hospital mortality from data at the time of hospital arrival and solely from prehospital data.ResultsThe rSIG at time of hospital admission was not sufficiently predictive for clinical decision-making. However, rSIG calculated solely from prehospital data accurately predicted risk of death. Using prehospital data, the AUROC for mortality of rSIG/A was the highest (0.85; CI: 0.85 to 0.86), followed by rSIG (0.76; CI: 0.75 to 0.77), SIA (0.71; CI: 0.70 to 0.71) and SI (0.48; CI: 0.47 to 0.49).ConclusionThe prehospital rSIG/A can be a useful adjunct for the prehospital evaluation of trauma patients and their allocation to trauma centres or trauma team activation. However, we could not confirm that the rSIG at hospital admission is a reliable tool for risk stratification.
Prognostic impact of follow-up pulmonary vascular resistance in pulmonary arterial hypertension
Authors: Suzuki Sho , Asano Ryotaro , Aoki Tatsuo , Nakayama Sayuri , Ueda Jin , Tsuji Akihiro , Noguchi Teruo , Ogo Takeshi 
Published: June 2022

ObjectivePulmonary arterial hypertension (PAH), caused by pulmonary artery remodelling and increased pulmonary vascular resistance (PVR) due to an unknown mechanism, is an intractable disease with a poor prognosis. The recent development of PAH-specific treatment medications may allow for higher PVR reduction than previously achieved. This study aimed to identify the prognostic significance of follow-up PVR levels achieved shortly after the initiation of targeted treatment in patients with idiopathic/heritable pulmonary arterial hypertension (I/H-PAH).MethodsWe analysed the data of all patients with I/H-PAH admitted to our hospital between 1998 and 2019. We collected data at baseline and during the first invasive haemodynamic evaluation. The primary outcome was death or lung transplantation.ResultsOf the 133 treatment-naïve patients enrolled in this study, 47 experienced adverse events during a median follow-up period of 6.4 (IQR 3.5–11.5) years. The median time interval to first follow-up from diagnosis was 162 (IQR 117–253) days. Incidence of the primary outcome was significantly lower in patients who achieved low PVR at follow-up. Of risk factors evaluated at follow-up, the multivariate Cox regression analysis revealed PVR as an independent predictor of the primary outcome (HR 1.103, 95% CI 1.029 to 1.183; p=0.006). The results were consistent across risk profiles according to the simplified risk stratification recommended by the European Society of Cardiology and European Respiratory Society guidelines.ConclusionFollow-up PVR was an independent predictor of transplant-free survival in patients with I/H-PAH. Evaluation of haemodynamic status shortly after initiating treatment may help predict long-term prognosis.
The compact mitogenome of Ceratocystiopsis pallidobrunnea
Authors: Wai Alvan , Hausner Georg 
Published: June 2022

Ceratocystiopsis is a fungal genus that has been assigned to the Ophiostomatales, fungi known for their association with various bark beetles and other arthropods. The mitochondrial genome of Ceratocystiopsis pallidobrunnea has been characterized and compared with other members of the genus Ceratocystiopsis and Ophiostomatales. At 29 022 bp, the mitogenome of C. pallidobrunnea is the smallest reported so far for this genus. Gene arrangement was observed to be conserved for this group of fungi, and mitogenome variation appears to be mostly due to the absence and presence of introns. The long-term goal is to apply mitogenomes to resolve taxonomic issues within the Ophiostomatales and within the various genera that comprise the Ophiostomataceae.
Effects of Occupational Therapy Program Based on Active Meditation on Hair Cortisol Levels in Undergraduate Healthcare Students
Authors: Espinosa Alejandra , Morrison Rodolfo , Gonzalez Diego , Jamardo Juan , Fortuna Federico , Díaz Carmen-Paz , Gutiérrez Pamela , Frías Carla , Soto Paula , González Alejandra , Mella Sandra , Fabre Bibiana 
Published: June 2022

Context. Meditation incorporation helps to fight against disorders such as depression, stress, and anxiety. Specifically, few studies have studied Osho’s Active Meditation on young people, but observed evidence using passive meditation shows that it could improve stress well-management, emotional control, and other mental unhealthy conditions. Goal. The present study pointed to evaluate the results of an occupational therapy program centered on active meditation on hair cortisol concentration in a sample of undergraduate healthcare students. Methods. Undergraduate students from the University of Chile’s health careers were divided at random into control (

n
=
7

) and treated groups (

n
=
15

). The treated group participated in an active meditation program once a week for three months. This treatment included different techniques such as Chakra Sounds, Nataraj, Mandala, Kundalini, Devavani, Gourishankar, and Nadabrahma. Hair samples were taken before and after the treatment period to measure cortisol. Results. The control group increased cortisol level

168.9
±
76.8

pg/mg compared with initial levels. The treated group shows a decrease of initial cortisol values in

28.5
±
12.8

pg/mg after meditation protocol application. Conclusions. Blending active meditation in students’ daily routine through occupational therapy intervention might prevent undergraduate students’ stress in healthcare careers.
Identification of Effective and Nonpromiscuous Antidiabetic Drug Molecules from Penicillium Species
Authors: Saleem Shahzad , Bibi Shabana , Yousafi Qudsia , Hassan Tehzeem , Khan Muhammad Saad , Hasan Mohammad Mehedi , Chopra Hitesh , Moustafa Mahmoud , Al-Shehri Mohammed , Khalid Mohammad , Kabra Atul 
Published: June 2022

Diabetes mellitus (DM) is a very common metabolic disorder/disease. The deterioration of β-cells by autoimmune system is the hallmark of this disease. Thioredoxin-Interacting Protein (TXNIP) is responsible for β-cells degradation by T-cells in the pancreas. This protein had been declared a good drug target for controlling DM. Lots of side effects have been reported as a result of long-time consumption of conventional antidiabetic drugs. The development of new and effective drugs with the minimal side effects needs time. TXNIP was selected as a target for Computer-Aided Drug Design. The antidiabetic fungal metabolite compounds were selected from the literature. The compounds were screened for their drug-likeness properties by DruLiTo and DataWarior tools. Twenty-two drug-like fungal compounds were subjected to Quantitative Structure-Activity Relationship (QSAR) analysis by using CheS-Mapper 2.0. The lowest (0.01) activity cliff was found for three compounds: Pinazaphilone A, Pinazaphilone B, and Chermesinone A. The highest value for apol (81.76) was shown by Asperphenamate, while Albonoursin and Sterenin L showed highest score (40.66) for bpol. The lowest value (0.46) for fractional molecular frame (FMF) was calculated for Pinazaphilone A and Pinazaphilone B. TPSA for Pinazaphilone A and Pinazaphilone B was 130.51 Å2.

log

P
<
5

was observed for all the twenty-two compounds. Molecular docking of fungal compounds with TXNIP was done by AutoDock Vina. The binding energy for complexes ranged between −9.2 and −4.6 kcal/mol. Four complexes, TXNIP-Pinazaphilone A, TXNIP-Pinazaphilone B, TXNIP-Asperphenamate, and TXNIP-Sterenin L, were selected for MD simulation to find out the best lead molecule. Only one complex, TXNIP-Pinazaphilone B, showed a stable conformation throughout the 80 ns run of MD simulation. Pinazaphilone B derived from the Penicillium species fungi was selected as the lead molecule for development of antidiabetic drug having the least side effects.
Characterization of programmed cell death 4 in multiple human cancers reveals a novel enhancer of drug sensitivity
Authors: Jansen Aaron P. , Camalier Corinne E. , Stark Cristi , Colburn Nancy H. 
Published: June 2022

AbstractProgrammed cell death 4 (Pdcd4), originally identified as an inhibitor of murine cellular transformation, inhibits protein synthesis by directly interacting with eukaryotic initiation factor 4A (eIF4A) of the translation initiation complex. The relevance of Pdcd4 to a broad range of human cancers derived from multiple tissue sites is unknown. Protein expression patterns from the National Cancer Institute drug-screening panel of 60 human cancer cells (NCI60) were analyzed by Western blot methods and revealed frequent reduction of Pdcd4 protein levels in renal-, lung-, and glia-derived tumors. Greater than mean Pdcd4 protein levels correlated with the antitumor activity of geldanamycin and tamoxifen. Stable expression of antisense PDCD4 significantly reduced the sensitivity of MCF-7 breast cancer cells to geldanamycin and to tamoxifen. Sensitivity to geldanamycin significantly increased in UO-31 renal cancer cells expressing sense PDCD4 cDNA. Increased geldanamycin sensitivity was accompanied by enhanced cell cycle arrest and apoptosis. One primary mode of inactivation of Pdcd4 in human cancers appears to involve down-regulated expression, and this down-regulation causes a decreased sensitivity to geldanamycin cytotoxicity. Thus, up-regulating Pdcd4 expression may be promising for geldanamycin-based combination therapy.
Gene expression correlating with response to paclitaxel in ovarian carcinoma xenografts
Authors: Bani Maria Rosa , Nicoletti Maria Ines , Alkharouf Nawal W. , Ghilardi Carmen , Petersen David , Erba Eugenio , Sausville Edward A. , Liu Edison T. , Giavazzi Raffaella 
Published: June 2022

Abstract
We have investigated gene expression profiles of human ovarian carcinomas in vivo during Taxol® (paclitaxel) treatment and observed a difference in expression. Nude mice bearing 1A9 or 1A9PTX22 xenografts were given 60 mg/kg of paclitaxel. Therapeutic efficacy was achieved for 1A9, while 1A9PTX22 did not respond. Tumor tissues harvested 4 and 24 h after treatment were evaluated by cDNA microarray against untreated tumors. Paclitaxel caused the modulation of more genes in 1A9 than in 1A9PTX22 tumors, in accordance to their therapeutic response. Most gene expression alterations were detected 24 h after paclitaxel administration and affected genes involved in various biological functions including cell cycle regulation and cell proliferation (CDC2, CDKN1A, PLAB, and TOP2A), apoptosis (BNIP3 and PIG8), signal transduction and transcriptional regulation (ARF1, ATF2, FOS, GNA11, HDAC3, MADH2, SLUG, and SPRY4), fatty acid biosynthesis and sterol metabolism (FDPS, IDI1, LIPA, and SC5D), and IFN-mediated signaling (G1P3, IFI16, IFI27, IFITM1, and ISG15). The modulation of two representative genes, CDKN1A and TOP2A, was validated by Northern analyses on a panel of seven ovarian carcinoma xenograft models undergoing treatment with paclitaxel. We found that the changes in expression level of these genes was strictly associated with the responsiveness to paclitaxel. Our study shows the feasibility of obtaining gene expression profiles of xenografted tumor models as a result of drug exposure. This in turn might provide insights related to the drugs' action in vivo that will anticipate the response to treatment manifested by tumors and could be the basis for novel approaches to molecular pharmacodynamics.
Effects of the proteasome inhibitor ritonavir on glioma growth in vitro and in vivo
Authors: Laurent Nathalie , de Boüard Sophie , Guillamo Jean-Sébastien , Christov Christo , Zini Roland , Jouault Hélène , Andre Patrice , Lotteau Vincent , Peschanski Marc 
Published: June 2022

Abstract
Glioblastoma is a therapeutic challenge as a highly infiltrative, proliferative, and resistant tumor. Among novel therapeutic approaches, proteasome inhibition is very promising in controlling cell cycle and inducing apoptosis. This study investigated the effect of ritonavir, a protease inhibitor of the HIV and a proteasome modulator, on glioma cells. The hypothesis was that proteasome modulation, mainly by only inhibiting proteasome chymotrypsin-like activity, could be sufficient to control tumor progression. The experiments were done on a human glioblastoma-derived GL15 cell line and a rat nitrosourea-induced gliosarcoma 9L cell line. Culturing conditions included monolayer cultures, transplantations into brain slices, and transplantations into rat striata. The study demonstrates that ritonavir, by inhibiting the chymotrypsin-like activity of the proteasome, has cytostatic and cytotoxic effects on glioma cells, and can induce resistances in vitro. Ritonavir was unable to control tumor growth in vivo, likely because the therapeutic dose was not reached in the tumor in vivo. Nevertheless, ritonavir might also be beneficial, by decreasing tumor infiltration, in the reduction of the deleterious peritumor edema in glioblastoma.
Novel peptide ligands for integrin α4β1 overexpressed in cancer cells
Authors: Mikawa Masahito , Wang Henry , Guo Linlang , Liu Ruiwu , Marik Jan , Takada Yoshikazu , Lam Kit , Lau Derick 
Published: June 2022

Abstract
Using the “one-bead one-peptide” combinatorial technology, a library of random cyclic octapeptides and nonapeptides, consisting of natural and unnatural amino acids, was synthesized on polystyrene beads. This library was used to screen for peptides that promoted attachment and proliferation of bronchioloalveolar carcinoma cells (H1650), employing a “cell growth on bead” assay. Consensus peptide sequences of cNleDXXXXc and cXNleDXXXXc (where Nle is norleucine) were identified. With alanine scanning and site-directed deletion, a typical ligand consisted of a motif of -NleDI/V/Nle- with two flanking cysteines. These peptide ligands were specific for promoting cell attachment of the H1650 cells and the cells of lymphoid cancers (Jurkat and Raji) but not other selected human cell lines of lung cancer and fibroblast. In an antibody blocking assay, integrin α4β1, which was overexpressed in H1650, Jurkat, and Raji, was identified as a putative receptor for these peptide ligands. Using Chinese hamster ovary cells transfected with either wild-type or mutant integrin α4, a critical binding site for these peptides was localized to the glycine residue at position 190 of integrin α4.
Caspase-mediated apoptosis and caspase-independent cell death induced by irofulven in prostate cancer cells
Authors: Liang Huiyun , Salinas Richard A. , Leal Belinda Z. , Kosakowska-Cholody Teresa , Michejda Christopher J. , Waters Stephen J. , Herman Terence S. , Woynarowski Jan M. , Woynarowska Barbara A. 
Published: June 2022

Abstract
Irofulven (hydroxymethylacylfulvene) is a novel antitumor drug, which acts by alkylating cellular macromolecular targets. The drug is a potent inducer of apoptosis in various types of tumor cells, whereas it is nonapoptotic in normal cells. This study defined molecular responses to irofulven involving mitochondrial dysfunction and leading to death of prostate tumor LNCaP-Pro5 cells. Irofulven caused early (2–5 hours) translocation of the proapoptotic Bax from cytosol to mitochondria followed by the dissipation of mitochondrial membrane potential and cytochrome c release at 4 to 12 hours. These effects preceded caspase activation and during the first 6 hours were not affected by caspase inhibitors. Processing of caspase-9 initiated the caspase cascade at ∼6 hours and progressed over time. The activation of the caspase cascade provided a positive feedback loop that enhanced Bcl-2-independent translocation and cytochrome c release. General and specific caspase inhibitors abrogated irofulven-induced apoptotic DNA fragmentation with the following order of potency: pan-caspase ≥ caspase-9 &gt; caspase-8/6 &gt; caspase-2 &gt; caspase-3/7 &gt; caspase-1/4. Abrogation of caspase-mediated DNA fragmentation failed to salvage irofulven-treated cells from growth inhibition and loss of viability, demonstrating a substantial contribution of a caspase-independent cell death. Monobromobimane, an inhibitor of alternative caspase-independent apoptotic pathway that is mediated by mitochondrial permeability transition, antagonized both apoptosis, measured as phosphatidylserine externalization, and cytotoxicity of irofulven. Collectively, the results indicate that irofulven-induced signaling is integrated at the level of mitochondrial dysfunction. The induction of both caspase-dependent and caspase-independent death pathways is consistent with pleiotropic effects of irofulven, which include targeting of cellular DNA and proteins.
Antiadhesive antibodies targeting E-cadherin sensitize multicellular tumor spheroids to chemotherapy in vitro
Authors: Green Shane K. , Francia Giulio , Isidoro Ciro , Kerbel Robert S. 
Published: June 2022

Abstract
Multicellular resistance, a subtype of therapeutic resistance manifested in cancer cells grown as three-dimensional multicellular masses, such as spheroids in vitro and solid tumors in vivo, occurs with respect to a variety of anticancer treatment strategies including chemotherapy, ionizing radiation, and even host-mediated antibody-dependent cellular cytotoxicity. Previous studies from our laboratory have shown that multicellular resistance to chemotherapy demonstrated by aggregates of EMT-6 murine mammary carcinoma cells can be overcome by using hyaluronidase to disrupt intercellular adhesive interactions and associated patterns of protein expression. In this proof of principle study, we explored the concept of antiadhesive chemosensitization in the context of human cancer cells by using a monoclonal antibody to disrupt E-cadherin-mediated cell-cell interactions in multicellular spheroids of HT29 human colorectal adenocarcinoma. In so doing, we found that disruption of E-cadherin-mediated adhesion sensitizes multicellular spheroids of HT29 in vitro to treatment with 5-fluorouracil, paclitaxel, vinblastine, and etoposide but not cisplatin. Furthermore, we have found that antibody-mediated blockage of E-cadherin function leads to decreased expression and activity of protein kinase C α and β1, both of which have previously been implicated in chemoresistance exhibited by HT29 cells; however, we have found that the chemosensitization effects of the anti-E-cadherin antibody are independent of its influence on protein kinase C β1.
Regulation of Vinca alkaloid-induced apoptosis by NF-κB/IκB pathway in human tumor cells
Authors: Huang Yi , Fang Yong , Wu Jinmin , Dziadyk Jennifer M. , Zhu Xueming , Sui Meihua , Fan Weimin 
Published: June 2022

Abstract
Antimicrotubule Vinca alkaloids, such as vinblastine and vincristine, interfere with the dynamics of microtubules and have shown significant cell killing activity in a variety of tumor cells through induction of apoptosis. The mechanism by which Vinca alkaloids induce apoptosis is not entirely clear. In this study, we found that glucocorticoids inhibit Vinca alkaloid-induced apoptosis without affecting G2-M arrest in human breast cancer BCap37 cells and human epidermoid tumor KB cells, suggesting that Vinca alkaloid-induced apoptosis may occur via a pathway independent of cell cycle arrest. Further analyses indicated that Vinca alkaloids cause significant degradation of IκBα, which in turn results in nuclear factor-κB (NF-κB) activation. Transfection of antisense IκBα in BCap37 cells sensitizes Vinca alkaloid-induced apoptosis. Moreover, in vitro kinase assays show that the activity of IκB kinase (IKK) was activated by Vinca alkaloids and was not affected by glucocorticoids. Stable transfection of dominant-negative deletional mutant IκBα, which is insensitive to IKK-mediated phosphorylation and degradation, resulted in the inhibition of Vinca alkaloid-induced NF-κB activation and reduced sensitivity of tumor cells to Vinca alkaloid-induced apoptosis. These findings suggest that the NF-κB/IκB signaling pathway may contribute to the mediation of Vinca alkaloid-induced apoptosis in human tumor cells.
The proteasome inhibitor bortezomib synergizes with gemcitabine to block the growth of human 253JB-V bladder tumors in vivo
Authors: Kamat Ashish M. , Karashima Takashi , Davis Darren W. , Lashinger Laura , Bar-Eli Menashe , Millikan Randall , Shen Yu , Dinney Colin P. N. , McConkey David J. 
Published: June 2022

Abstract
Bortezomib (PS-341, Velcade) is a dipeptidyl boronic acid inhibitor of the 20S proteasome that was developed as a therapeutic agent for cancer. Here, we investigated the effects of bortezomib on the growth of human 253JB-V bladder cancer cells. Although the drug did not stimulate significant increases in levels of apoptosis, it inhibited cell growth in a concentration-dependent fashion and augmented the growth inhibitory effects of gemcitabine in vitro. These effects were associated with accumulation of p53 and p21 and suppression of cyclin-dependent kinase 2 activity. Bortezomib also inhibited secretion of the proangiogenic factors matrix metalloproteinase-9, interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF). In vivo studies with 253JB-V tumors growing in nude mice demonstrated that bortezomib (1 mg/kg) did not inhibit tumor growth when it was delivered as a single agent, although it reduced tumor microvessel density and inhibited expression of VEGF and IL-8. However, combination therapy with bortezomib plus gemcitabine produced synergistic tumor growth inhibition associated with strong suppression of tumor cell proliferation. Together, our results demonstrate that bortezomib has significant antiproliferative activity in aggressive bladder cancer cells, which is best exploited within the context of combination chemotherapy.