bluuebunny/crossref_metadata_2025_split huggingface dataset:
The global return on investment from preventing and treating adolescent mental disorders and suicide: a modelling study
Authors: Stelmach Rachel , Kocher Erica L , Kataria Ishu , Jackson-Morris Angela Mary , Saxena Shekhar , Nugent Rachel 
Published: June 2022

IntroductionDespite the high burden of mental disorders among adolescents and the potentially lifelong consequences of these conditions, access to mental health services remains insufficient for adolescents in low-income and middle-income countries. We conducted an economic modelling study to quantify the potential costs and benefits of mental health interventions to prevent or treat anxiety, depression, bipolar disorder, and suicide among adolescents.MethodsWe developed a Markov model that followed cohorts of adolescents (ages 10–19) from 36 countries to assess the impact of addressing anxiety, depression, bipolar disorder, and suicide during adolescence on health and non-health outcomes through their lives. We estimated the costs of interventions using an ingredients-based approach and modelled impacts on education and employment and the resulting economic, morbidity, and mortality benefits.ResultsImplementing the selected interventions offers a return on investment of 23.6 and a cost of $102.9 per disability adjusted life year (DALY) averted over 80 years. The high return on investment and low cost per DALY averted is observed across regions and country income levels, with the highest return on investment arising from treating mild depression with group-based cognitive behavioural therapy, prevention of suicide attempts among high-risk adolescents, and universal prevention of combined anxiety and depression in low-income and lower-middle income countries.ConclusionsThe high return on investment and low cost per DALY averted suggests the importance and value of addressing mental disorders among adolescents worldwide. Intervening to prevent and treat these mental disorders even only during adolescence can have lifelong health and economic benefits.
Increase in serum choline levels predicts for improved progression-free survival (PFS) in patients with advanced cancers receiving pembrolizumab
Authors: Watson Geoffrey Alan , Sanz-Garcia Enrique , Zhang Wen-Jiang , Liu Zhihui Amy , Yang SY Cindy , Wang Ben , Liu Shaofeng , Kubli Shawn , Berman Hal , Pfister Thomas , Genta Sofia , Spreafico Anna , Hansen Aaron R , Bedard Philippe L , Lheureux Stephanie , Abdul Razak Albiruni , Cescon Dave , Butler Marcus O , Xu Wei , Mak Tak W , Siu Lillian L , Chen Eric 
Published: June 2022

BackgroundRecent studies have demonstrated that T cells can induce vasodilation in a choline-acetyltransferase dependent manner, leading to an increase in T cell migration to infected tissues in response to viral infection, but its role in cancer is unclear. Choline acetyltransferase catalyzes the production of acetylcholine from choline and acetyl-CoA, however, acetylcholine is challenging to quantify due to its extremely short half-life while choline is stable. This study aims to correlate serum choline levels in patients with advanced solid tumors receiving pembrolizumab with treatment outcomes.MethodsBlood samples were collected at baseline and at week 7 (pre-cycle 3) in patients treated with pembrolizumab in the INvestigator-initiated Phase 2 Study of Pembrolizumab Immunological Response Evaluation phase II trial (NCT02644369). Samples were analyzed for choline and circulating tumor DNA (ctDNA). Multivariable Cox models were used to assess the association between choline and overall survival (OS) and progression-free survival (PFS) when including ΔctDNAC3(the change in ctDNA from baseline to cycle 3), cohort, PD-L1 expression and tumor mutation burden (TMB). An independent validation cohort from the LIBERATE study (NCT03702309) included patients on early phase trials treated with a PD-1 inhibitor.ResultsA total of 106 pts were included in the analysis. With a median follow-up of 12.6 months, median PFS and OS were 1.9 and 13.7 months, respectively. An increase in serum choline level at week 7 compared with baseline (ΔcholineC3) in 81 pts was significantly associated with a better PFS (aHR 0.48, 95% CI 0.28 to 0.83, p=0.009), and a trend toward a better OS (aHR 0.64, 95% CI 0.37 to 1.12, p=0.119). A combination of ΔctDNAC3and ΔcholineC3was prognostic for both OS and PFS. Multivariable analyses show ΔcholineC3was a prognostic factor for PFS independent of ΔctDNAC3, cohort, PD-L1 and TMB. In the independent validation cohort (n=51), an increase in serum choline at cycle 2 was associated with a trend to improved PFS.ConclusionsThis is the first exploratory report of serum choline levels in pan-cancer patients receiving pembrolizumab. The association between improved PFS and ΔcholineC3suggests a possible role for the cholinergic system in the regulation of antitumor immunity. Further pre-clinical and clinical studies are required to validate this finding.Trial registration numberNCT03702309.
Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study
Authors: Tiu Bruce C , Zubiri Leyre , Iheke James , Pahalyants Vartan , Theodosakis Nicholas , Ugwu-Dike Pearl , Seo Jayhyun , Tang Kimberly , Sise Meghan E , Sullivan Ryan , Naidoo Jarushka , Mooradian Meghan J , Semenov Yevgeniy R , Reynolds Kerry L 
Published: June 2022

BackgroundImmune checkpoint inhibitors (ICIs) have improved survival and are increasingly used for non-small cell lung cancer. However, use may be limited by immune-related adverse events such as checkpoint-inhibitor pneumonitis (CIP). Literature estimates for CIP incidence are inconsistent. Real-world adherence to guidelines, clinical course, and healthcare utilization in the treatment of CIP has not been described in large cohorts.MethodsA combined claims and electronic health record database (TriNetX) was used to identify 13,113 patients with lung cancer treated with programmed cell death receptor/ligand 1 (PD-1/PD-L1) inhibitors, and a propensity score-matched control cohort treated with chemotherapy or targeted therapies. The attributable risk of CIP was calculated in the first 12 months after therapy by comparing the incidence of diagnosis codes for pneumonitis/pneumonia between cohorts. Cases of CIP, identified by the most specific code for drug-induced respiratory conditions, were further analyzed for medication usage, rates of diagnostic bronchoscopy, ICI discontinuation rates, and usage of hospital services compared with patients receiving PD-1/PD-L1 inhibitors who did not develop CIP.ResultsThe attributable risk of pneumonitis to PD-1/PD-L1 inhibitors was 2.49% (95% CI, 1.50% to 3.47%). Median time to onset in the CIP subcohort was 3.9 months (IQR, 2.1–7.3 months). Steroid and antibiotic use increased dramatically after a pneumonitis diagnosis, and 70.2% of patients permanently discontinued ICI therapy. Compared with controls, patients with CIP had more than a threefold increased risk of needing critical care (relative risk 3.59, 95% CI, 2.31 to 5.57) and an increased risk of mortality (HR 2.34, 95% CI, 1.47 to 3.71).ConclusionsIn a large claims-based analysis, PD-1/PD-L1 inhibitors increase the risk of pneumonitis in patients with lung cancer by 2.49%. Cases of CIP are associated with high healthcare utilization, discontinuation of ICIs, and mortality.
Endovascular treatment of intracranial aneurysms using the Derivo Embolization Device: a multicenter experience
Authors: Chagas Lourenço Galileu , Dantas François , Silva e Carvalho Tiago , Firmino Róberti Uili Rodrigues , Quesado Filgueiras Filho Marcelo , Tosello Renato Tavares , José Leão Cláudio , Leo Piske Ronie , Zenóbio Darwich Rogério 
Published: June 2022

BackgroundFlow diversion is the first-line treatment for several types of intracranial aneurysms. We report on a large series of patients treated with the Derivo Embolization Device who underwent a 1-year angiographic control follow-up.MethodsWe performed a multicenter retrospective analysis of prospectively collected data, designed to evaluate the clinical and angiographic results of treatment of intracranial aneurysms with the Derivo Flow Diverter. The primary endpoint was complete occlusion of the aneurysm within 12 months, which was evaluated using DSA. The secondary endpoint was the absence of any serious adverse events. Univariate and multivariate logistic regression analyses were performed to analyze the data.ResultsThe study was conducted from December 2016 to September 2019 and enrolled 127 patients with 177 intracranial aneurysms, treated at three different centers. Efficacy at 6 months was 70.1% (122/174) for total occlusion and 87.3% (152/174) for favorable occlusion and, at 12 months, it was 83.3% (145/174) for total occlusion and 97.7% (170/174) for favorable occlusion. Regarding safety concerns, 97.6% (124/127) of patients did not experience severe adverse effects during the follow-up period of 12 months, and there was no procedure-related mortality.ConclusionsThe Derivo Embolization Device, achieving a total occlusion rate of 83.3% and a favorable occlusion rate of 97.7% in a 1-year angiographic control study of 174 aneurysms with minor morbidity and no intervention-related mortality, is a safe and effective treatment for intracranial aneurysms.
Dual microcatheter and coil/balloon pressure cooker technique for transvenous embolization of cerebrospinal fluid-venous fistulas
Authors: Parizadeh Donna , Vasconcelos Antonio H C , Miller David A , Fermo Olga P , Huynh Thien J 
Published: June 2022

Cerebrospinal fluid-venous fistula is increasingly recognized as a cause of spontaneous intracranial hypotension.1 Transvenous embolization is emerging as an efficacious minimally invasive treatment.2–4 The procedure aims to embolize paraspinal and foraminal veins draining the fistula; however, complete embolization may be challenging as numerous small venous tributaries at the foraminal venous plexus, including dorsal muscular branches, may serve as additional routes of cerebrospinal fluid egress.5 To ensure curative embolization, we adopted a dual microcatheter pressure cooker technique, previously used for treatment of brain arteriovenous malformations.6 This allows improved control of embolic material reflux and greater chance of complete embolization of the site of the fistula and all potential venous tributaries. Video 1 demonstrates this technique employed in a typical case using Onyx (Medtronic, Minnesota, USA) to embolize a cerebrospinal fluid-venous fistula at the left L1 neural foramen.Video 1Technical video demonstrating dual-microcatheter and coil/balloon pressure cooker technique.
Effect of suprainguinal fascia iliaca compartment block on postoperative opioid consumption and functional recovery in posterolateral-approached total hip arthroplasty: a single-blind randomized controlled trial
Authors: Carella Michele , Beck Florian , Piette Nicolas , Denys Sébastien , Kurth William , Lecoq Jean-Pierre , Bonhomme Vincent L 
Published: June 2022

IntroductionPosterolateral-approached total hip arthroplasty (PLTHA) is followed by moderate to severe postoperative pain. Suprainguinal fascia iliaca compartment block (SFICB) has been proposed as a promising analgesia technique.MethodsData from 86 patients scheduled for PLTHA with spinal anesthesia were analyzed in this prospective randomized controlled trial. Patients were randomly divided into two groups of 43 patients each. As opposed to the control group (group C), ropivacaine group (group R) received additional SFICB using 40 mL of 0.375% ropivacaine. As primary endpoint, blind observers noted total morphine consumption at postoperative 48 hours. Secondary endpoints were pain at rest and mobilization on 0–10 Numeric Rating Scale (rest and dynamic NRS) at fixed time points (1 hour and 6 hours after surgery, and at day 1 and day 2 at 8:00, 13:00 and 18:00 hours), walking performance at day 1 and day 2; postoperative complications including morphine-related side effects or orthostatic intolerance symptoms such as dizziness, nausea, blurred vision or vasovagal syncope.ResultsA 48-hour morphine consumption (mg; median (IQR)) was significantly lower in group R than in group C (11 (8.5–15.5)) vs 26 (21–33.5), p<0001), as well as incidence of morphine-related side effects such as nausea at day 1 (p=0.04) and day 2 (p<0.01). Rest and dynamic NRS were globally significantly lower in group R than in group C (p<0.01). Group R showed less orthostatic intolerance at day 1 (p<0.001) and day 2 (p<0.01) and better functional walking performance at day 1 (<0.001) and day 2 (<0.001).DiscussionIn PLTHA, SFICB provides opioid sparing, improved postoperative pain control, and enhanced functional recovery.Trial registration numberNCT04574479.
Comparison of postoperative analgesic effects of posterior quadratus lumborum block and intrathecal morphine in laparoscopic donor hepatectomy: a prospective randomized non-inferiority clinical trial
Authors: Lee Seungwon , Kang Ryung A , Kim Gaab Soo , Gwak Mi Sook , Choi Gyu-Seong , Kim Jong Man , Ko Justin Sangwook 
Published: June 2022

BackgroundPosterior quadratus lumborum block (QLB) and intrathecal morphine are accepted analgesic strategies in laparoscopic liver resection, but their effects have not been compared after laparoscopic donor hepatectomy. This study was planned to perform this comparison.MethodsFifty-six donors were randomized to receive bilateral posterior (QLB2, 20 mL of 0.375% ropivacaine on each side, 150 mg total) or preoperative injection of 0.4 mg morphine sulfate intrathecally. Primary outcome was resting pain score at 24 hour postsurgery. Secondary outcomes included cumulative opioid consumption and recovery parameters. Serial plasma ropivacaine concentrations were measured in QLB group. Only the outcome assessor was properly blinded.ResultsMean resting pain score at 24-hour postsurgery was 4.19±1.66 in QLB group (n=27) and 3.07±1.41 in intrathecal morphine group (n=27, p=0.04). Mean difference (QLB group-intrathecal morphine group) was 1.11 (95% CI 0.27 to 1.95), and the upper limit of CI was higher than prespecified non-inferiority margin (δ=1), indicating an inferior effect of QLB. Cumulative opioid consumption was significantly higher in QLB group at 24 hours and 48 hours postsurgery. QLB group exhibited lower incidence of postoperative pruritus at all time points, and there were no differences in other recovery outcomes. All measured ropivacaine concentrations were below the threshold for systemic toxicity (4.3 µg/mL).ConclusionsBilateral posterior QLB elicited higher resting pain scores at 24-hour after laparoscopic donor hepatectomy than intrathecal morphine and did not meet the definition of non-inferiority.Trial registration numberKCT0005360.
The global transformation of geomorphology
Authors: Goudie Andrew S. , Burt Tim P. , Viles Heather A. 
Published: June 2022

Abstract

This chapter reviews the various developments in geomorphology in terms of institutions, journals, textbooks, research stations, etc. Among the institutions discussed are the Binghamton Geomorphology Symposium, the Geological Society of America Quaternary Geology and Geomorphology Division, the Association of American Geographers Geomorphology Specialty Group, the British Geomorphological Research Group, the IGU Commission on Measurements, Theory and Application in Geomorphology (COMTAG), the International Association of Geomorphologists, the European Geosciences Union (EGU), the American Geophysical Union (AGU), the International Quaternary Association, and the International Conference on Aeolian Research. Many countries established their own national bodies. A number of new journals appeared, including
Catena
,
Earth Surface Processes and Landforms
,
Géomorphologie
, and
Geomorphology
. In addition, during the closing decades of the twentieth century there was a proliferation of textbooks in geomorphology. One development was that geomorphological research was promoted by the establishment of research stations. These permitted long-term monitoring and provided bases for sustained investigations. The study of fluvial processes was much encouraged in the United States at USDA Forest Service research basins (known as ‘watersheds’ in the USA) such as the Hubbard Brook Experimental Forest (New Hampshire), Coweeta Hydrologic Laboratory (North Carolina) and the H.J. Andrews Experimental Forest (Oregon). The Royal Geographical Society (with the Institute of British Geographers) organized ambitious research projects in collaboration with host nations. Various US government departments supported much geomorphological research in various parts of the world. Some European countries fostered overseas geomorphological research and created missions. Notable was the work of ORSTOM (Office de la Recherche Scientifique et Technique Outre-mer) in former francophone colonies. In the post-war years, and as independence approached and then occurred, new universities were established in Africa. These employed expatriate geomorphologists and also trained up a new generation of indigenous scholars. The decades since the 1960s have been a period of space exploration and the development of remote sensing. This has had important implications for geomorphology. The period also saw the onset of the digital age and the beginning of the World Wide Web's influence on teaching and research. Applied research became increasingly important. A major cause for international and cross-disciplinary co-operation during the period was the emergence of geoarchaeology. Finally, since the 1950s, an increasing number of women have made important contributions to the discipline.
Abstract 1008: Cell density-related variability in chemotherapeutic resistance patterns in human cancer cells
Authors: Brown Thomas , Punyamurtula Ujwal , Strandberg Jill , El-Deiry Wafik S. 
Published: June 2022

Abstract
Assessment of chemosensitivity and resistance varies with cancer cell of origin, drug and culture conditions. However, it is also not uncommon to find multiple different IC50 values for the same chemotherapeutic treatments acting on the same tumor cell lines. The aim of this research was to investigate this discrepancy in phenotypes and elucidate relevant variables that influence them. We assessed chemosensivity as a function of tumor cell density by plating TOV-21G ovarian, HT29 colorectal, and U2OS osteosarcoma cell lines in 96-well plates at various seeding densities per well and treated them with various concentrations of cisplatin, 5-fluorouracil (5-FU), and etoposide, respectively. CellTiter Glo assays were performed at 72 hours of treatment to determine IC50. Cisplatin IC50 for TOV-21G cells plated at 50,000, 20,000, 10,000, 5,000, 2,000, 1,000, and 500 cells/well were 12.00 μM, 5.47 μM, 3.16 μM, 2.45 μM, 2.54 μM, 2.83 μM, and 2.66 μM, respectively. Etoposide IC50 for U2OS cells plated at the same seeding densities were 6.50 μM, 5.19 μM, 3.23 μM, 2.98 μM, 2.49 μM, 2.13 μM, and 1.88 μM, respectively. IC50 values for HT29 cells treated with 5-FU at 2,000, 1,000, and 500 cells/well were 35.89 μM, 19.74 μM, and 13.42 μM, respectively. TOV-21G, U2OS, and HT29 cells all showed differences in IC50 values depending on cell plating density. TOV-21G and U2OS cells both showed a gradual decrease and plateau in IC50 as the cancer cell density decreased from 50,000 cells/well to 500 cells/well. HT29 cells displayed a sharper IC50 decrease as the cell density decreased from 2,000 cells/well to 500 cells/well. Our experiments demonstrate that IC50 values are not static at 72 hours and that tumor cell density is an important variable in influencing observed tumor resistance to traditionally effective drugs. As the density of cancer cells increases, the cells develop more resistance to the associated chemotherapy and require higher quantities of drug to achieve the same level of growth inhibition. We are currently exploring underlying molecular mechanisms that may influence these changes in IC50 including cell survival signaling proteins, cell-cell contact or growth factors that may influence cell density-related chemoresistance.
Citation Format: Thomas Brown, Ujwal Punyamurtula, Jill Strandberg, Wafik S. El-Deiry. Cell density-related variability in chemotherapeutic resistance patterns in human cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1008.
Abstract 1037: Targeting the RBM38-EIF4E complex to increase wild-type p53 as a novel cancer therapeutic strategy
Authors: Lucchesi Chris August , Zhang Jin , Chen Xinbin 
Published: June 2022

Abstract
To date, dysregulation of more than 450 RNA-binding proteins (RBPs) across a multitude of cancers has been implicated in tumorigenesis and chemoresistance. In fact, emerging evidence suggests RBPs are principal modulators of every hallmark of cancer progression. Functionally, RBPs are believed to modulate the stability, localization, and translation of transcripts encoding for virtually all known oncogenes and tumor suppressor genes. Consequently, aberrant expression of RBPs may contribute to the malignant transformation of cancer cells through enhancing the expression of oncogenes or decreasing the expression of tumors suppressor genes, such as TP53. As a potent transcription factor, TP53 is a leading regulator of numerous signaling pathways involved in tumor suppression. While mutation or deletion of TP53 contributes to tumorigenesis in more than half of all human cancers, suppression of wild-type TP53 expression also drives tumorigenesis. Thus far, multiple RBPs have been implicated in the repression of wild-type TP53, such as RNA-binding motif protein 38 (RBM38). Specifically, RBM38 interacts with eukaryotic translation initiation factor 4E (EIF4E) on the TP53 transcript, preventing EIF4E from binding to TP53 m7G cap, thus inhibiting TP53 translation. We previously demonstrated that Pep8, an 8 amino acid peptide derived from RBM38, disrupts the RBM38-EIF4E complex enhancing TP53 expression. Moreover, Pep8 alone or in combination with doxorubicin, significantly decreased tumor xenograft growth. As activation of wild-type TP53 by targeting non-genetic mechanisms that inhibit TP53 expression is a promising therapeutic tactic for malignancies that carry wild-type TP53, we are developing more efficacious Pep8 derivatives as a novel therapeutic approach for cancers that express wild-type TP53.
Citation Format: Chris August Lucchesi, Jin Zhang, Xinbin Chen. Targeting the RBM38-EIF4E complex to increase wild-type p53 as a novel cancer therapeutic strategy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1037.