bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR14: Defining isoform-specific roles for AKTs in BRAFV600E-driven melanoma
Authors: Farrell Jaymes , Pietruska Jodie , McRee Siobhan , Tsichlis Philip , Hinds Philip 
Published: June 2022

Abstract
The PI3K/AKT pathway is frequently dysregulated in cutaneous melanoma and impacts both tumor aggression and resistance to BRAFV600E/K inhibitors. While current clinical approaches to AKT inhibition are severely limited by the toxicity of pan-AKT inhibitors, selective inhibition of individual AKT isoforms (AKT1, AKT2, or AKT3) remains an attractive, if yet unattainable, approach. A critical gap in our understanding concerns how the three highly homologous yet functionally distinct AKT isoforms contribute to melanomagenesis and treatment response. To address this question, we are employing RNAi and gene editing approaches to interrogate the effect of selective suppression or CRISPR/Cas9-mediated deletion of each isoform in vitro, as well as the impact of AKT isoform loss on 1) the growth of melanoma xenografts and 2) the development of spontaneous tumors in a melanoma-prone mouse model. In addition, we are interrogating tumor-promoting functions of AKT isoform-selective substrates recently identified in a phospho-proteomic screen of mouse fibroblasts, a system that allows us to identify downstream actionable targets that may mediate the effects of AKT isoforms in tumorigenesis. Broadly, we are focusing on the importance of AKTs in tumor cell growth, metastasis, and response to inhibitors of BRAFV600E/K or CDK4/6. We find that loss of AKT1 impacts growth of BRAF mutant human melanoma cells both in vitro and in vivo. Additionally, AKT1 appears to play an isoform-specific role in response to pharmacologic CDK4/6 inhibition, impacting transcriptional and morphologic changes typically associated with permanent cell cycle arrest. In contrast, loss of AKT2 has a minimal impact on melanoma cell growth or response to CDK4/6 inhibition, but severely limits the development of metastatic disease, potentially through a combination of impaired seeding at the metastatic site and defects in glycolysis. While AKT3 loss does not appreciably impact the above-mentioned cellular phenotypes, the protumorigenic role of AKT3 may involve activation of broadly-acting neutral proteases previously implicated in cell cycle progression, cell migration, and CDK5 regulation. Taken together, we provide evidence for distinct roles for AKT isoforms in several aspects of the tumorigenic process as well as response to current therapies. Future studies will focus on identification and targeting of the relevant downstream mediators of these phenotypes.
This abstract is also being presented as Poster A16.
Citation Format: Jaymes Farrell, Jodie Pietruska, Siobhan McRee, Philip Tsichlis, Philip Hinds. Defining isoform-specific roles for AKTs in BRAFV600E-driven melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr PR14.
Improving SpellChecking: an effective Ad-Hoc probabilistic lexical measure for general typos
Authors: Gueddah Hicham , Nejja Mohamed , Iazzi Said , Yousfi Abdellah , Aouragh Si Lhoussain 
Published: June 2022

<p>Since the era of learning to write by human beings, mistakes made in typing words have occupied a privileged place in linguistic studies, integrating new disciplines into school curricula such as spelling and dictation. According to exhaustive studies that we have done in the field of spellchecking errors made in typing Arabic texts, very few research works that deal with typographical errors specifically caused by the insertion or missing of the blank-space in words. On the other hand, spelling correction software remains ineffective for handling this type of errors. Failure to process errors due to the insertion/missing of blankspace between and in words leads and brings us back to situations of ambiguity and incomprehension of the meaning of the typed text. To remedy this limitation of correction, we propose in this article an ad-hoc probabilistic method which is based jointly on two approaches. The first approach treats the errors due to deletion or missing of blank-space between or inside words, while the second puts emphasis in correcting space insertion errors in a word of course in addition to other kinds of elementary editing errors (addition, deletion, permutation of characters). Our new approach combines edit distance with n-gram language models to correct the errors already mentioned. Our new approach gave an accuracy rate that reaches 98,14% for missing blank-space errors (noted MBSE) and 89,5% for insertion blank-dpace errors (noted IBSE), which gives an average correction rate of around 95,26%. These results are very encouraging and show the interest and the importance of our approach.</p>
Modeling and simulation of electro-hydraulic telescopic elevator system controlled by programmable logic controller
Authors: Al-Had Istabraq Hassan Abed , Mohammed Farag Mahel , Mohammed Jamal A.-K. 
Published: June 2022

Traditional hydraulic <span>cylinders are widely used in industry as load lifting tools. There is difficulty in employing these cylinders in narrow installation space like building elevators as well as they require a long working stroke, so solving this problem requires using the telescopic hydraulic cylinder instead. This cylinder is a unique hydraulic cylinder design that uses a sequence of decreasing diameters to create a long operating stroke in a compact-retracted form. In this work, the Auto Station software is used to build a telescopic hydraulic cylinder model that includes hydraulic elements such as double-acting hydraulic telescopic cylinders, pump, valves, pipeline, and filter, as well as electrical parts such as programmable logic controller (PLC), push-bottoms, and position sensors. The proposed model is operated by a PLC controller and has three floors with an overall height of around 300 cm for lifting a 100 kg payload. The accuracy and validity of this model in lifting big weights were demonstrated by the analytical findings of characteristic curves for cylinder position and velocity. This model can be used a basic reference to analyze and construct hydraulic cylinders with any number of stages. The findings of simulations reveal that a quick change in pressure due to phase change causes multi-phase vibration.</span>
Health State Utility Values in People With Stroke: A Systematic Review and Meta‐Analysis
Authors: Joundi Raed A. , Adekanye Joel , Leung Alexander A. , Ronksley Paul , Smith Eric E. , Rebchuk Alexander D. , Field Thalia S. , Hill Michael D. , Wilton Stephen B. , Bresee Lauren C. 
Published: June 2022

Background
Health state utility values are commonly used to provide summary measures of health‐related quality of life in studies of stroke. Contemporaneous summaries are needed as a benchmark to contextualize future observational studies and inform the effectiveness of interventions aimed at improving post‐stroke quality of life.

Methods and Results

We conducted a systematic search of the literature using Medline, EMBASE, and Web of Science from January 1995 until October 2020 using search terms for stroke, health‐related quality of life, and indirect health utility metrics. We calculated pooled estimates of health utility values for EQ‐5D‐3L, EQ‐5D‐5L, AQoL, HUI2, HUI3, 15D, and SF‐6D using random effects models. For the EQ‐5D‐3L we conducted stratified meta‐analyses and meta‐regression by key subgroups. We screened 14 251 abstracts and 111 studies met our inclusion criteria (sample size range 11 to 12 447). EQ‐5D‐3L was reported in 78% of studies (study n=87; patient n=56 976). The pooled estimate for EQ‐5D‐3L at ≥3 months following stroke was 0.65 (95% CI, 0.63–0.67), which was ≈20% below population norms. There was high heterogeneity (I
2
>90%) between studies, and estimates differed by study size, case definition of stroke, and country of study. Women, older individuals, those with hemorrhagic stroke, and patients prior to discharge had lower pooled EQ‐5D‐3L estimates.

Conclusions
Pooled estimates of health utility for stroke survivors were substantially below population averages. We provide reference values for health utility in stroke to support future clinical and economic studies and identify subgroups with lower healthy utility.

Registration

URL:
https://www.crd.york.ac.uk/prospero/
. Unique Identifier: CRD42020215942.
What Explains Caste-based Wage Inequalities and Earning Gaps in the Indian Labour Market? Theil and Oaxaca Decomposition Analysis
Authors: Gupta Pallavi , Kothe Satyanarayan 
Published: June 2022

Caste-based wage discrimination can counteract the development process. This article uses two distinct estimation methods to examine earning gaps between forward castes also referred to as ‘general category’ workers and traditionally disadvantaged or ‘backward caste’ workers in the Indian labour market. First, we interpret the inequality indicator of the Theil index and decompose Theil to show within and between-group inequalities. Second, a Threefold Oaxaca Decomposition is employed to break earnings differentials into components of endowment, coefficient and interaction. Earning gaps are examined separately in urban and rural divisions. Within-group inequalities are found larger than between groups across variables, with a higher overall inequality for forward castes. Wage differentials are substantially greater for urban areas and favour FC. A high endowment implies pre-market discrimination in human capital investments such as nutrition and education. Policymakers should first invest in basic quality education and simultaneously expand postgraduate diploma opportunities, subsequently increasing participation in the labour force for traditionally disadvantaged in disciplines and occupations where forward castes have long dominated. JEL Codes: J01, J08, J15, J30, J31, J71
Socioeconomic differences associated with consumption of a plant-based diet: Results from the national health and nutrition examination survey
Authors: Gonzalgo Mia R. , Nackeeran Sirpi , Mouzannar Ali , Blachman-Braun Ruben 
Published: June 2022

Background A plant-based diet (PBD) has been associated with potential health benefits, but factors that may affect access to and consumption of a PBD are not well defined. Aim To determine the association between socioeconomic status and plant-based dietary consumption among participants enrolled in the National Health and Nutrition Examination Survey (NHANES). Methods This was a cross-sectional study using data obtained from the NHANES database. The following covariates were assessed: age, sex, race/ethnicity, educational level, marital status, smoking status, physical activity, alcohol use, history of diabetes, and hypertension. Socioeconomic status was categorized according to poverty-income ratio (PIR). Food frequency questionnaires were used to calculate previously validated plant-based diet index (PDI) and healthful plant-based diet index (hPDI). Multivariable-adjusted logistic regression was performed to determine the association between PIR, clinical, demographic, and plant-based diet indices. Results A total of 5037 participants were in the final analytic sample. Median age of participants was 51 ± 18.5 years. Overall PDI and hPDI were 50 [46–54] and 52 [47–57], respectively. Median PDI index was significantly different among PIR groups (PDI, p = 0.018; hPDI, p < 0.001). On multivariable analysis, participants in the poorest socioeconomic group (PIR ≤ 130%) were more likely to have lower consumption of a healthful PBD (hPDI). Conclusion Lower socioeconomic status (PIR ≤ 130%) was associated with decreased consumption of a healthful plant-based diet. These data suggest that socioeconomic disparities may limit consumption of healthier food and contribute to the high prevalence of adverse health conditions that exist in certain population groups.
Inadequate human resources, equipment and training: A qualitative assessment of the objectives of the NUHELP end-of-life care programme in the context of the COVID-19 pandemic
Authors: Mota Romero Emilio , Puente Fernández Daniel , Rodríguez Pertíñez Carmen , Árbol Fernández Gema , Moreno Guerrero Socorro , Montoya Juárez Rafael 
Published: June 2022

Background: The COVID-19 pandemic had a particularly severe impact on nursing homes, exposing numerous pre-existing deficiencies in end-of-life care. Aim: To describe how the COVID-19 pandemic affected nursing home and primary care professionals’ attempts to achieve the objectives of a pre-existing end-of-life programme and to explore their personal experiences of end-of-life care in these facilities. Design: A qualitative descriptive study using thematic analysis. Setting/participants: Twenty semi-structured interviews were conducted from March to November 2020 with professionals from nursing homes and primary care facilities who participated in the development of the NUHELP programme. Results: Six main themes were identified: (1) Comprehensive assessments of residents at the homes were not conducted due to excessive workload and high staff turnover. (2) New technologies and changes to professional roles were used to meet relatives’ needs for information. Residents only received information when they requested it. (3) Advance care planning was not carried out and was limited to potential hospital transfer. (4) Arrangements were made to allow relatives to spend time with residents during their final moments, but complicated grief among relatives and professionals is anticipated. (5) Management of complexity varied depending on the degree of coordination with primary care facilities. (6) Nursing home professionals felt abandoned, with a lack of human resources, equipment and training. Conclusions: The pandemic cast light on existing shortcomings in nursing homes in terms of comprehensive assessments, communication, decision making, grief management and palliative care complexity. Nursing homes need more human, material and training resources, as well as improved coordination with the public healthcare system.
Usefulness of subtraction images for accurate diagnosis of pituitary microadenomas in dynamic contrast-enhanced magnetic resonance imaging
Authors: Taheri Morteza Sanei , Ghomi Zahra , Mirshahi Reza , Moradpour Moein , Niroomand Mahtab , Yarmohamadi Parsa , Zeidabadi Hamideh 
Published: June 2022

Background Dynamic contrast-enhanced magnetic resonance imaging (MRI) is the modality of choice for the diagnosis of pituitary microadenomas; however, it may be associated with a relatively high false-negative rate, especially in small lesions. Purpose To evaluate the usefulness of subtraction images for enhancing the visual detection of pituitary microadenomas. Material and Methods In total, 50 patients with clinically established diagnosis hyperprolactinemia, acromegaly, and Cushing's disease were enrolled. Ten patients referred for brain MRI for reasons other than pituitary abnormality were selected as control group. Routine dynamic MRI of the pituitary gland and obtained subtraction MRI scans were scrutinized separately on different sessions by an experienced radiologist blinded to the study design and patient's data. The investigator's opinion on the presence or absence of a lesion and lesion size were collected. Results In patients with pituitary microadenoma, dynamic MRI images were reported positive in 42 (84%) patients and negative in 8 (16%). Subtraction images were described as positive in all patients (100%)—including all patients with negative dynamic MRI—and the difference was statistically significant ( P=0.016). Undetected lesions on dynamic MRI had a mean size of 2.84 ± 1.79 mm (median= 2.20 mm, interquartile range=1.62–4.62 mm) and a significant inverse correlation was noted between lesion size and negative report of dynamic MRI ( P=0.018). Brain MRI scans in the control group were reported negative for pituitary microadenoma in both dynamic contrast-enhanced and subtraction images. Conclusion Subtraction images can successfully identify all lesions detectable with conventional dynamic MRI as well as improving visualization of lesions undetected on dynamic MRI, especially in small lesions.
Correlation between C-reactive protein/albumin ratio and prognosis in patients with lung adenocarcinoma
Authors: Jia-min Zheng , Wei Dai , Ye Lu , Xiang-tao Pan 
Published: June 2022

Objective This study was performed to examine the relationship between the C-reactive protein/albumin ratio (CAR) and the prognosis of patients with lung adenocarcinoma and thus provide a reference for evaluating the prognosis of lung adenocarcinoma. Methods The clinical data of 130 patients with lung adenocarcinoma were retrospectively collected and analyzed. The patients’ overall survival (OS) time was calculated, and the factors affecting OS were statistically analyzed. Results The CAR was correlated with sex, clinical stage, brain metastasis, S100 calcium-binding protein B (S100B), interleukin 17, myelin basic protein, squamous cell carcinoma antigen (SCC-Ag), and the lymphocyte count. The median OS was significantly shorter in the high- than low-CAR group (18 vs. 64 months, respectively). The CAR, clinical stage, brain metastasis, S100B, interleukin 17, SCC-Ag, C-reactive protein, albumin, and neutrophil count affected the OS of patients with lung adenocarcinoma. The CAR and clinical stage were independent risk factors for a poor prognosis in patients with lung adenocarcinoma. Conclusions The CAR and clinical stage are independent risk factors for OS in patients with lung adenocarcinoma.
Minimally invasive ureterolysis and intraperitonealization of ureter for idiopathic retroperitoneal fibrosis; single center analysis of an erratic disease
Authors: Batra Vikram Shah , Singh Mahendra , Kathuria Sachin , Jain Saurabh , Rasool Shahnawaz , Gupta Manu , Pandey Himanshu , Sharma Ajay 
Published: June 2022

Introduction Idiopathic retroperitoneal fibrosis is a known cause of obstructive uropathy. Ureterolysis is done when medical management fails or the presentation is at an advanced stage. Conventionally ureterolysis without omental wrap has been considered incomplete. Our Institute has experience of laparoscopic or robotic ureterolysis with intraperitonealization of the ureter alone and no other adjunctive procedure. This study retrospectively assesses the result of the procedure with patients presenting with varying severity of disease. Methods From 2008, all patients who underwent laparoscopic or robotic ureterolysis were analyzed retrospectively for pre-operative management, operative findings, and post operative outcomes. Results We operated and released nine renal units in seven patients. Two of the nine cases were performed robotically completely and the rest was performed by laparoscopic approach. Median follow up was 60 months. All patients documented resolution of symptoms. The mean post-operative creatinine at 1 year was significantly decreased to 1.47 ± 0.49 mg/dl in comparison to preoperative creatinine ( p < 0.05). The postoperative mean ESR decreased significantly from a preoperative value of 58.2 ± 19.41 mm to 15.8 ± 17.23. The nuclear scan revealed unobstructed drainage and radiological imaging revealed resolution of hydronephrosis and fibrosis in all. The mean GFR on the nuclear scan after 3 and 12 months of surgery was 36.3 ± 4.33 and 40 ± 3.77, respectively. Thus, there was significant increase noted in GFR at 3 and 12 months in comparison to preoperative GFR ( p < 0.05). Conclusion Laparoscopic/robotic ureterolysis with intraperitonealization alone is secure and durable procedure for idiopathic retroperitoneal fibrosis needing surgical release.
Adverse Hemodynamic Effects of Dexmedetomidine in Critically Ill Elderly Adults
Authors: Ingebrigtson Megan , Miller James T. 
Published: June 2022

Background: Dexmedetomidine is a currently recommended first-line sedative agent for critically ill patients requiring mechanical ventilation. Recent trials demonstrated no difference in clinical outcomes between patients treated with dexmedetomidine vs usual care, but significantly more hemodynamic adverse effects in the dexmedetomidine group. One subgroup analysis suggested a 90-day mortality benefit in elderly patients, but no distinction was made between groups regarding age when reporting adverse effects. Given potential decreased baroreceptor function in the elderly, adverse hemodynamic effects of dexmedetomidine may impact them more. Objective: To assess the incidence of adverse hemodynamic effects of dexmedetomidine in elderly ICU patients compared to other sedative agents to clarify the role of dexmedetomidine in this patient population. Methods: This was a single-center, retrospective study including mechanically ventilated elderly patients requiring sedative agents for ≥12 hours. The primary outcome evaluated was composite end point of incidence of bradycardia and hypotension. Secondary outcomes included incidence of each adverse event individually, hospital and ICU length of stay, and duration of mechanical ventilation. Results: There was no difference in adverse events between the two groups (58.7% vs 74.1% in the dexmedetomidine vs usual care groups, P =.074). There was no difference in hospital or ICU length of stay. Patients in the dexmedetomidine group were on the ventilator longer than patients in the usual care group with a median of 6 vs 3 days, respectively ( P = 0.004). Conclusion: In this single-center, retrospective study dexmedetomidine had a similar incidence of adverse events in elderly patients compare to the usual care group.
A Study of Sick Newborn for Inborn Error of Metabolism by Tandem Mass Spectrometry
Authors: Bhautara Rahul , Agarwal Kamlesh Kumar , Gupta Ashok , Goyal Manisha , Kapoor Seema 
Published: June 2022

Introduction: Inborn errors of metabolism (IEM) form a large class of genetic diseases involving congenital disorders of metabolism. In most disorders, problems arise due to the accumulation of various toxic substances. Although some IEMs are harmless (benign), many can cause significant handicaps. Screening for IEMs among newborns not only prevents premature death and permanent neurological damage but also helps in planning prenatal diagnosis in future pregnancies. Tandem mass spectrometry (TMS) is an effective diagnostic technique and has been proposed as a means to realize this aim. Therefore, this study was planned to screen the sick newborns for inborn error of metabolism by TMS and to diagnose IEM as early as possible to minimize morbidity and mortality in sick/high-risk neonates. Material and Methods: This hospital-based descriptive diagnostic study was conducted in the Department of Pediatrics, SPMCHI, SMS Medical College, Jaipur from June 2017 to May 2018. The study population included indoor 90 patients with age up to 28 days of life who were enrolled after applying exclusion criteria. All data were collected and analyzed with the help of suitable statistical parameters. Results: Out of 90 cases enrolled, 66 were of normal birth weight and 24 were of low-birth weight neonates and all positive subjects were low birth weight. Out of 90 neonates, 7 (7.8%) were positive for IEM and 83 (92.2%) were negative for IEM. Out of 7 positive, 3 (42.8%) had maple syrup urine disease, 2 (28.6%) had methylmalonic acidemia and 2 (28.6%) had carnitine palmitoyl transferase type 1 deficiency/mitochondrial myopathy. Out of 90, 26 (28.9%) were positive and 64 (71.1%) were negative for hypoglycemia. Out of 7 cases of IEM, 6 (85.7%) were positive and 1 (14.3%) was negative for hypoglycemia. Conclusion: Screening helps in early diagnosis and initiation of treatment. Early treatment and rehabilitation to the child with IEM prevent premature death and permanent neurological disability.