bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I study of mesenchymal stem cell (MSC)-derived exosomes with KRASG12D siRNA in patients with metastatic pancreatic cancer harboring a KRASG12D mutation.
Authors: Surana Rishi , LeBleu Valerie S. , Lee J. Jack , Smaglo Brandon George , Zhao Dan , Lee Michael Sangmin , Wolff Robert A. , Overman Michael J. , Mendt Mayela C. , McAndrews Kathleen M. , Yang Sujuan , Rezvani Katy , Kalluri Raghu , Maitra Anirban , Shpall Elizabeth J. , Pant Shubham 
Published: January 2022

TPS633 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with few effective therapeutic options. Over 90% of patients with PDAC harbor activating mutations in KRAS, a known oncogenic driver of tumor growth, cancer cell survival and metastasis thus making for an attractive therapeutic target. However, targeting the most common KRAS mutations in pancreatic cancer (KRASG12D and KRASG12V) remains a pharmacological challenge. Exosomes are extracellular nano-vesicles that are efficiently internalized by target cells and are under investigation as a drug-delivery vehicle for various therapeutic payloads, including nucleic acids such as small interfering RNA (siRNA). Previously published pre-clinical data demonstrate effective delivery of exosomes loaded with siRNA targeting KRASG12D leading to tumor control in various murine models of PDAC. Methods: This is a single arm, single institution, phase I trial evaluating treatment with KRASG12D-siRNA loaded exosomes. Large-scale production of KRASG12D-siRNA loaded exosomes from mesenchymal stromal cells will be performed at the MD Anderson Cancer Center using pre-specified GMP-compliant protocols. The primary endpoints of this study are to determine a maximum tolerated dose (MTD) of KRASG12D-loaded exosomes and to identify dose-limiting toxicities (DLT). Key secondary endpoints include the pharmacokinetics of circulating exosomes, overall response rate, disease control rate (defined as partial responses and patients with stable disease), median progression-free survival (PFS) and median overall survival (OS). Key inclusion criteria include histologically confirmed metastatic pancreatic ductal adenocarcinoma, documented progression on one or more lines of systemic therapy, and documented presence of a KRASG12D mutation. Selected correlative studies include measurement of circulating siRNA and KRASG12D DNA using PCR. This trial will enroll up to 28 patients and will follow a 3+3 design for dose escalation. This trial is actively accruing and has enrolled six patients at the time of submission. Clinical trial information: NCT03608631.
CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer
Authors: Shepherd Jonathan H. , Ballman Karla , Polley Mei-Yin C. , Campbell Jordan D. , Fan Cheng , Selitsky Sara , Fernandez-Martinez Aranzazu , Parker Joel S. , Hoadley Katherine A. , Hu Zhiyuan , Li Yan , Soloway Matthew G. , Spears Patricia A. , Singh Baljit , Tolaney Sara M. , Somlo George , Port Elisa R. , Ma Cynthia , Kuzma Charles , Mamounas Eleftherios , Golshan Mehra , Bellon Jennifer R. , Collyar Deborah , Hahn Olwen M. , Hudis Clifford A. , Winer Eric P. , Partridge Ann , Hyslop Terry , Carey Lisa A. , Perou Charles M. , Sikov William M. 
Published: January 2022

PURPOSE CALGB 40603 ( NCT00861705 ), a 2 × 2 randomized phase II trial, demonstrated that adding carboplatin or bevacizumab to weekly paclitaxel (wP) followed by doxorubicin and cyclophosphamide significantly increased the pathologic complete response (pCR) rate in stage II-III triple-negative breast cancer. We now report long-term outcomes (LTOs) and correlative science end points. PATIENTS AND METHODS The Kaplan-Meier method was used to estimate LTOs in 443 patients who initiated study treatment. Log-rank tests and Cox proportional hazards models evaluated the impact of clinical characteristics, pathologic response, calculated residual cancer burden (RCB) in patients with residual disease (RD), treatment assignment, and dose delivery during wP on LTOs, including event-free survival (EFS). Genomic predictors of treatment response and outcomes were assessed on pretreatment tumor samples by mRNA sequencing. RESULTS Among baseline characteristics, only the clinical stage was associated with LTOs. At a median follow-up of 7.9 years, LTOs were not significantly improved with either carboplatin or bevacizumab, overall or in patients with basal-like subtype cancers by genomic analysis. Patients with pCR (n = 205, 46.3%) had significantly higher 5-year EFS (85.5% v 56.6%, log-rank P < .0001) and overall survival (87.9% v 63.4%, P < .0001) rates compared with patients with RD, even those with RCB class I. Among clinical and genomic features, evidence of immune activation, including tumor-infiltrating lymphocytes and low B-cell receptor evenness, was associated with pCR and improved EFS. CONCLUSION Despite higher pCR rates, neither carboplatin nor bevacizumab appeared to improve LTOs although the study was not powered to assess these secondary end points. pCR was associated with superior LTOs even when compared with minimal RD. Markers of immune activation in pretreatment tumor biopsies were independently associated with higher pCR rates and improved survival.
H1-Antihistamines Reduce the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus, Hepatitis C Virus, or Dual Hepatitis B Virus-Hepatitis C Virus Infection
Authors: Shen Yu-Chuan , Hsu Hui-Ching , Lin Tzu-Min , Chang Yu-Sheng , Hu Li-Fang , Chen Lung-Fang , Lin Sheng-Hong , Kuo Pei-I. , Chen Wei-Sheng , Lin Yi-Chun , Chen Jin-Hua , Liang Yu-Chih , Chang Chi-Ching 
Published: January 2022

PURPOSE H1-antihistamines (AHs) may exert protective effects against cancer. This study investigated the association of AH use with the risk of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or dual HBV-HCV virus infection. MATERIALS AND METHODS Patients with HBV, HCV, or dual HBV-HCV infection were enrolled from Taiwan's National Health Insurance Research Database and examined for the period from January 1, 2006, to December 31, 2015. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the association between AH use and HCC risk. RESULTS We included patients with HBV infection (n = 521,071), HCV (n = 169,159), and dual HBV-HCV (n = 39,016). Patients with HBV, HCV, or dual virus infection who used AHs exhibited significantly lower risk of HCC relative to patients who did not use AH, with their adjusted hazard ratio being 0.489 (95% CI, 0.455 to 0.524), 0.484 (95% CI, 0.450 to 0.522), and 0.469 (95% CI, 0.416 to 0.529), respectively. Furthermore, there was a dose-response relationship between AH use and the risk of HCC in the HBV cohort. The adjusted hazard ratios were 0.597 (95% CI, 0.530 to 0.674), 0.528 (0.465 to 0.600), 0.470 (0.416 to 0.531), and 0.407 (0.362 to 0.457) for AH use of 28-42, 43-63, 64-119, and ≥ 120 cumulative defined daily doses, respectively, relative to no AH use. Additionally, there was also a dose-response relationship between AH use and the risk of HCC in the HCV and dual HBV-HCV cohorts. CONCLUSION AH use may reduce the risk for HCC among patients with HBV, HCV, or dual infection in a dose-dependent manner. Further mechanistic research is needed.
Hydroxychloroquine for COVID-19: Variation in Regional Political Preferences Predicted New Prescriptions after President Trump's Endorsement
Authors: Madanay Farrah , McDevitt Ryan C. , Ubel Peter A. 
Published: January 2022

Abstract
Context: On March 19, 2020, President Donald Trump endorsed using hydroxychloroquine for COVID-19 treatment despite inconclusive evidence of the drug's effectiveness. This study sought to understand the influence of political preferences on prescription uptake by quantifying the relationship between a geographic area's partisan leaning and hydroxychloroquine prescription rates following Trump's endorsement.
Methods: We analyzed hydroxychloroquine prescriptions filled in 205 continental US designated market areas (DMAs) between March 1, 2018, and July 31, 2020, and the percentage of votes for Donald Trump in the 2016 presidential election in each DMA. We estimated associations by using an empirical strategy resembling a difference-in-differences estimation.
Findings: Before President Trump's endorsement, mean weekly hydroxychloroquine prescription rates were similar across DMAs with the highest and lowest Trump vote percentages (0.56 and 0.49 scripts per 100,000). After Trump's endorsement, although both high- and low-Trump-supportive DMAs experienced sharp increases in weekly hydroxychloroquine prescription rates, results indicated a 1-percentage-point increase in share of Trump votes was associated with 0.013, or 2%, more weekly hydroxychloroquine prescriptions per 100,000 people (b = 0.013, t = 2.20, p = .028).
Conclusion: President Trump's endorsement of an untested therapy influenced prescribing behavior, especially when that endorsement aligned with communities' political leanings.
How Do Medicaid Agencies Improve Substance Use Treatment Benefits? Lessons from Three States' 1115 Waiver Experiences
Authors: Crable Erika , Jones David K. , Walley Alexander Y. , Hicks Jacqueline Milton , Benintendi Allyn , Drainoni Mari-Lynn 
Published: January 2022

Abstract
Context: In 2015, the Centers for Medicare and Medicaid Services (CMS) urged state Medicaid programs to use 1115 waiver demonstrations to expand substance use treatment benefits. We analyzed four critical points in states' decision-making processes before expanding benefits.
Methods: We conducted qualitative cross-case comparison of three states that were early adopters of the 1115 waiver request. We conducted 44 interviews with key informants from CMS, Medicaid, and other state agencies, providers, and managed care organizations.
Findings: Policy makers expanded substance use treatment in response to “fragmented” care systems and unsustainable funding streams. Medicaid staff had mixed preferences for implementing new benefits via 1115 waivers or state plan amendments. The 1115 waiver process enabled states to provide coverage for residential benefits, but state plan amendments made other services permanent parts of the benefit. Medicaid agencies relied on interorganizational networks to identify evidence-based practices. Medicaid staff secured legislative support for reform by focusing on program integrity concerns and downstream effects of substance use rather than Medicaid beneficiaries' needs.
Conclusions: Decision-making processes were influenced by Medicaid agency characteristics and interorganizational partnerships, not federal executive branch influence. Lessons from early-adopter states provide a road map for other state Medicaid agencies considering similar reform.
PCTAIRE1 promotes mitotic progression and resistance against antimitotic and apoptotic signals
Authors: Gillani Syed Qaaifah , Reshi Irfana , Nabi Nusrat , Un Nisa Misbah , Sarwar Zarka , Bhat Sameer , Roberts Thomas M. , Higgins Jonathan M. G. , Andrabi Shaida 
Published: January 2022

ABSTRACT
PCTAIRE1 (also known as CDK16) is a serine-threonine kinase implicated in physiological processes like neuronal development, vesicle trafficking, spermatogenesis and cell proliferation. However, its exact role in cell division remains unclear. In this study, using a library screening approach, we identified PCTAIRE1 among several candidates that resisted mitotic arrest and mitotic cell death induced by polyomavirus small T (PolST) expression in mammalian cells. Our study showed that PCTAIRE1 is a mitotic kinase that localizes at centrosomes during G2 and at spindle poles as the cells enter mitosis, and then at the midbody during cytokinesis. We also report that PCTAIRE1 protein levels fluctuate through the cell cycle and reach their peak at mitosis, during which there is an increase in PCTAIRE1 phosphorylation as well. Interestingly, knockdown of PCTAIRE1 resulted in aberrant mitosis by interfering with spindle assembly and chromosome segregation. Further, we found that PCTAIRE1 promotes resistance of cancer cells to antimitotic drugs, and this underscores the significance of PCTAIRE1 as a potential drug target for overcoming chemotherapeutic resistance. Taken together, these studies establish PCTAIRE1 as a critical mediator of mitotic progression and highlight its role in chemotherapeutic resistance.
This article has an associated First Person interview with the first author of the paper.
Prevalence and factors associated with anemia among children under five years of age in Rombo district, Kilimanjaro region, Northern Tanzania
Authors: Mboya Innocent B. , Mamseri Redempta , Leyaro Beatrice J. , George Johnston , Msuya Sia E. , Mgongo Melina 
Published: January 2022

Background: Anemia is a severe public health problem affecting more than half of children under five years of age in low-, middle- and high-income countries. The study aimed to determine the prevalence and factors associated with anemia among children under five years of age in northern Tanzania. Methods: This community-based cross-sectional study was conducted in Rombo district, Kilimanjaro region, northern Tanzania, in April 2016. Multistage sampling technique was used to select a total of 602 consenting mothers and their children aged 6-59 months and interviewed using a questionnaire. Data were analyzed using Stata version 15.1. We used generalized linear models (binomial family and logit link function) with a robust variance estimator to determine factors associated with anemia. Results: Prevalence of anemia was 37.9%, and it was significantly higher among children aged 6-23 months (48.3%) compared to those aged 24-59 months (28.5%). There were no significant differences in anemia prevalence by sex of the child. Adjusted for other factors, children aged 6-23 months had over two times higher odds of being anemic (OR=2.47, 95% CI 1.73, 3.53, p<0.001) compared to those aged 24-59 months. No significant association was found between maternal and nutritional characteristics with anemia among children in this study. Conclusion: Prevalence of anemia was lower than the national and regional estimates, and it still constitutes a significant public health problem, especially among children aged 6-23 months. The study recommends iron supplementation, food fortification, dietary diversification, and management of childhood illnesses interventions for mothers and children under two years.
Anomalous energy consumption detection using a Naïve Bayes approach
Authors: Lim Jia Yan , Tan Wooi-Nee , Tan Yi-Fei 
Published: January 2022

Background: Industrial energy management has emerged as an important component in monitoring energy consumption particularly with the recent trend of migrating towards IR 4.0. The capability to detect anomalies is essential as it serves as a precautionary step for real-time response to mitigate the maximum demand penalty. The purpose of this research was to develop a high accuracy anomalies detection algorithm to identify anomalies in the energy consumption data recorded by a smart meter. Methods: The proposed algorithm utilized supervised and unsupervised machine learning techniques, namely Isolation Forest and Gaussian Naïve Bayes. The data were first labeled by using Isolation Forest to categorize them into normal and abnormal groups. This was followed by Gaussian Naïve Bayes to classify and predict the anomalies of the smart meter reading. Results: These machine learning techniques showed significant accuracy in predicting the anomalies in smart meter readings. The data used were simulated data collected in less than a month with 30-minute reading intervals. The data were divided into testing and validation sets according to a ratio of 7:3. The balanced accuracy score in predicting anomalies for each different smart meter was above 89%. The average precision, average recall and average F1 score for the normal data were 98%, 99% and 98%, respectively. Whereas the corresponding scores for the abnormal data set were 95%, 90% and 92%. Conclusions: The proposed algorithm is a hybrid approach based on Isolation Forest and Gaussian Naïve Bayes and it provided satisfactory accuracy in anomaly electricity consumption detection based on smart meter readings. The study presents a quick and simple method for categorizing energy consumption data as normal or abnormal, which assists in automatically labelling vast datasets of energy consumption readings. The proposed approach establishes a fundamental framework for predicting the occurrence of anomalies in the industrial energy management system.
Scjentystyczna szkoła filozofii marksistowskiej w Polsce i rewizjonizm
Authors: Winczewski Damian Michał 
Published: January 2022

Celem artykułu była omówienie scjentystycznej filozofii marksistowskiej w Polsce jako jednej z odmian szerokiego nurtu rewizjonizmu w marksizmie. Zrekonstruowano jej główne cele i założenia, które można odczytać jako modernizację materializmu dialektycznego w duchu krytycznego realizmu i krytycznego racjonalizmu. Osiągnięcia scjentystycznego marksizmu porównano z perspektywą marksizmu humanistycznego, uchodzącego w Polsce za główną odmianę marksistowskiego rewizjonizmu. Jak się okazuje, tezy polskich scjentystów odpierają większość zarzutów stawianych przez rewizjonistycznych marksistów materializmowi dialektycznemu. Zarówno marksistowska filozofia naukowa, jak i marksistowska teoria społeczna mogą istnieć równolegle. Oba nurty padły jednak ofiarą degeneracji politycznej systemu socjalistycznego.
‘Peroxide-free’ Bleaching: Should we be Worried?
Authors: Mudhar Onkar 
Published: January 2022

An increase in patient awareness and education has seen the demand for cosmetic dentistry rise. The use of social media applications such as Instagram provide patients with a plethora of information on procedures, such as direct composite bonding, veneers of different types and the align, bleach and bond protocol. When using social media applications, it is common to see advertisements for ‘peroxide-free’ gels, from a range of brands, many of which ‘influencers’ and celebrities are paid to endorse. These direct-to-consumer products allow the patient to bypass the traditional method of speaking to their dental practitioner. This coupled with the reach that some of these companies possess on social media platforms means that patients could be putting their future dental health at risk. This article outlines the risks involved in the use of ‘peroxide-free’ bleaching gels, which are becoming increasingly popular among patients. Furthermore, the article also outlines the potential pitfalls associated when ‘peroxide-free’ gels are used in conjunction with other unregulated dental products such as ‘charcoal toothpastes’ and ‘direct-to-consumer aligners’ CPD/Clinical Relevance: This article aims to help clinicians to recognize and discuss the dangers associated with unregulated whitening products and direct-to-consumer orthodontics with patients.
Osteoradionecrosis in the Current Era of Radiation Treatment
Authors: Patel Vinod , Fenlon Michael , Silvio Lucy Di , McGurk Mark 
Published: January 2022

Osteoradionecrosis (ORN) is a late complication of radiotherapy treatment for head and neck cancer. In the past two decades there have been significant changes in the mode by which radiation is delivered and it was assumed this would lead to a reduction, or even elimination, of this complication. Paradoxically, ORN rates may have risen. This article provides a summary of the current understanding and approach to ORN. CPD/Clinical Relevance: Those who have had radiotherapy carry a life-long risk of developing osteoradionecrosis, and it is important that the dental team are aware of this.
Impact of Systemic Disease on Non-surgical Endodontic Treatment Outcomes
Authors: Salem Basma , McKenna Gerry , Quilligan Graham 
Published: January 2022

Interactions between systemic and oral diseases have been investigated in many contexts. This is a narrative review discussing the impact of several systemic diseases, including cardiovascular disease and diabetes mellitus, on non-surgical endodontic treatment outcomes. There is currently a lack of conclusive evidence to support links between systemic disease and endodontic outcomes. Further high-quality research is needed for systemic disease to be reliably considered a prognostic factor. CPD/Clinical Relevance: If systemic disease is found to impact upon non-surgical endodontic treatment outcomes, dentists could learn essential information regarding the prognosis of endodontic treatment by looking at a patient's medical history.
Developing your Video Consultation Skills
Authors: Chia Matthew 
Published: January 2022

The principle of the video consultation is to provide safe, effective, evidence based care and advice that your patients require. This article guides dental clinicians in the use of video consultations by adapting their current communication skills and developing new ones. It covers guiding principles, selection of cases and patients, systematic preparation, communication, using technology, sharing information and importance of practice. The challenges of using video consultations and how to overcome these are discussed. Being able to use video consultations confidently and professionally is rewarding for the clinician and beneficial for the patient. Evolving communication skills to accomplish this will ultimately improve the quality of patient care and enhance personal job satisfaction. CPD/Clinical Relevance: There is a need for dental professionals to develop and adapt their communication skills to using video consultations.
Orthodontic rescue of a case of bilaterally ectopic canines causing root resorption of central and lateral incisors
Authors: Solanki Bhavin , Flett Andrew 
Published: January 2022

A 14-year-old medically fit and well patient presented with bilaterally ectopic maxillary canines resorbing the central and lateral incisors. It is relatively rare that both maxillary ectopic canines cause resorption to the central and lateral incisors. Treatment options discussed with the patient are explored as well as case management and how potential complications were minimized. A good result was achieved at the end of the treatment, despite the complex nature of this case. CPD/Clinical Relevance: To demonstrate how a patient with bilaterally ectopic canines resorbing central and lateral incisors can be managed. This is clinically relevant to orthodontists and GDPs.
Interceptive correction of a deranged occlusion
Authors: Conville Robert M , Flett Andrew 
Published: January 2022

Infra-occluded deciduous molars can pose a great challenge to clinicians. The management and treatment of a severely infra-occluded tooth often requires a multidisciplinary team (MDT) approach. This case report demonstrates the effective management of a 7-year-old girl who presented with a severely infra-occluded maxillary deciduous second molar. It highlights the importance of early diagnosis and appropriate intervention to help prevent further disruption to a patient's occlusal development. Following removal of the submerging deciduous molar, an upper sectional (2x4) fixed appliance was used to recreate sufficient space for the developing premolars and correct the occlusal discrepancies caused as a result of the infra-occlusion. CPD/Clinical Relevance: A novel approach to managing an infra-occluded deciduous molar and correcting the associated space loss due to its submergence is described and the benefits of early MDT intervention are highlighted.