bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma: NEO-Nal-IRI study.
Authors: Rogers Sherise C. , Lee Ji-Hyun , Ramnaraign Brian Hemendra , Hitchcock Kathryn , Hughes Steven J. , Turk Anita Ahmed , Russell Karen Bullock , El-Far Ahmad , Thomas Ryan M. , Fabregas Jesus C. , Sahin Ilyas , Allegra Carmen Joseph , DeRemer David L. , George Thomas J.
Published: January 2022

TPS619

Background: Neoadjuvant treatment for potentially curable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given pre-op. Liposomal irinotecan injection (Nal-IRI) in combination with 5FU/LV is FDA approved with a well-tolerated safety profile in relapsed, refractory metastatic PDAC. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen (NALIRIFOX) and to demonstrate safe and effective neoadjuvant delivery. Methods: This phase 2, open-label, multicenter single-arm study focuses on patients (pts) with operable PDAC without metastatic disease. Other key eligibility criteria include age ≥18 years, resectability confirmed by multiD GI tumor board (resectable vs. borderline), adequate cardiac, renal, hepatic function and ECOG performance status of 0 to 1. Pts receive NALIRIFOX regimen as per the table every 2 weeks for four months followed by disease reassessment. Pts who remain surgical candidates will undergo surgical resection within 4 to 8 weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in pre-op setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life during treatment as measured by the NCI validated FACT-G scale. Exploratory ctDNA and stool microbiome analyses are also planned. Enrollment continues to a maximum of 28 evaluable pts to demonstrate a reduction in historical 30-day post-op complication rate. Clinical trial information: NCT03483038. [Table: see text]
A phase 1/2 study to evaluate the safety, tolerability, and preliminary efficacy of GP-2250 in combination with gemcitabine for advanced or metastatic pancreatic adenocarcinoma.
Authors: Kasi Anup , Iglesias Jose Luis
Published: January 2022

TPS620

Background: GP-2250 is a metabolic enzyme inhibitor that selectively induces oxidative stress, mitochondrial dysfunction, and apoptosis in cancer cells by inhibiting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and limiting aerobic glycolysis, an essential process for energy production in cancer cells. In vitro, increasing concentrations of GP-2250 induced proportional dose-response effects in 5 different pancreatic cancer cell lines (Buchholtz BMC Cancer 2017). Patient-derived pancreatic xenograft studies in mice demonstrated tumor growth inhibition with GP-2250 monotherapy (Braumann J Clin Oncol 2020). In combination with gemcitabine, a synergistic effect was shown with greater inhibition of pancreatic tumor growth than with either gemcitabine or GP-2250 alone. These findings support the assessment of the therapeutic potential of GP-2250 in combination with gemcitabine in patients with pancreatic cancer. Methods: This open-label phase 1/2 trial will evaluate the safety and tolerability of escalating doses of GP-2250 and the preliminary efficacy of GP-2250 in combination with gemcitabine in patients with advanced unresectable or metastatic pancreatic adenocarcinoma who have progressed on prior treatment with FOLFIRINOX chemotherapy. In phase 1, Bayesian Optimal Interval design will be used for GP-2250 dose escalation. The dose-limiting toxicity (DLT)–assessment period will be 5 weeks at each dose level (starting dose 250 mg once weekly intravenously), consisting of a 1-week run-in period with GP-2250 monotherapy, followed by a full cycle of GP-2250 plus standard dose and schedule of gemcitabine. Single patient cohorts (100% dose escalation between cohorts) will be enrolled until the occurrence of the first DLT (or cohort 4 if no DLTs occur in cohorts 1−3), after which, cohorts will be expanded to 3 patients with 35%−45% dose escalations between cohorts. Patients will receive treatment until disease progression or development of unacceptable toxicity. Primary study endpoints include safety and tolerability of GP-2250, tumor response (RECIST 1.1), disease control rate (complete response, partial response, stable disease), and duration of response. Pharmacokinetics, incidence and severity of laboratory abnormalities and treatment-emergent adverse events, progression-free survival, and overall survival will also be assessed. As of September 2021, 19 patients have been enrolled. Following completion of the phase 1/2 trial, a phase 3 first-line maintenance study will be initiated. This study is funded by Geistlich Pharma AG. Clinical trial information: NCT03854110. Clinical trial information: NCT03854110.
Phase Ib/II trial of siltuximab and spartalizumab in patients in metastatic pancreatic cancer.
Authors: Akce Mehmet , Shaib Walid Labib , Diab Maria , Alese Olatunji B. , Wu Christina , Thomas Sunisha , Greene Emily , Herting Cameron , Lesinski Gregory B. , El-Rayes Bassel F.
Published: January 2022

TPS626

Background: Interleukin-6 (IL-6) is associated with carcinogenesis, immune suppression, and poor prognosis in pancreatic adenocarcinoma (PDAC). Preclinical data demonstrated dual inhibition of IL-6 and (programmed death ligand-1) PD-L1 facilitates CD8+ T cell migration into pancreatic tumors and was effective in controlling tumor growth in syngeneic and genetically engineered PDAC mouse models. Siltuximab is a chimeric monoclonal antibody which targets the IL-6 molecule specifically and spartalizumab is a high-affinity ligand-blocking humanized IgG4 antibody against the PD-1 receptor. Based on this preclinical rationale, we developed a phase Ib/II trial to determine the recommended phase II dose (RP2D), evaluate the safety, toxicity profile, preliminary antitumor activity, and immunogenicity of the siltuximab and spartalizumab in patients with previously treated metastatic PDAC. Methods: The phase Ib trial design is standard 3+3. Primary endpoint is to determine RP2D. Siltuximab is administered intravenously (IV) in three dose levels of 6 mg/kg (DL1), 11 mg/kg (DL2), 9 mg/kg (only if 2 DLTs observed on DL2) every 3 weeks with spartalizumab at 300 mg IV every 3 weeks. Eligible patients must have stage IV PDAC who have failed at least one prior therapy age ≥18 years, ECOG PS 0-1, no prior anti PD-1 or anti-PD-L1 agent. After RP2D is established, an expansion phase will enroll 24 patients with PDAC. Pre and on-treatment biopsy will be performed in 24 patients in the expansion cohort for correlative analysis. Pre-treatment and on-treatment peripheral blood samples will be collected from all patients. In the expansion phase patients will receive initial cycle (every 3 weeks) treatment with either spartalizumab or spartalizumab plus siltuximab and then starting cycle 2 all patients receive the combination following the on-treatment research biopsy. This design will enable us to evaluate the immunological effects of spartalizumab alone versus the combination in the tumor microenvironment and peripheral blood. This study was activated in January 2020 and to date 12 patients were enrolled in dose escalation phase. The dose expansion phase has recently started accrual. Clinical trial information: NCT04191421.
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

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

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

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.
Οι διάκονοι και η διακονία του λόγου στη Σερβική Εκκλησία κατά τον 19ο και 20ο αιώνα
Authors: Στάντσιτς Νίκολα
Published: January 2022

Στα πλαίσια της παρούσας διδακτορικής διατριβής μελετήθηκε τη διακονία του λόγου στη Σερβική Εκκλησία στον 19ο και 20ο αιώνα. Έτσι, κατέγραψα τις προσωπικότητες εκείνες (18 ιεροκήρυκες) οι οποίες ασχολούνταν με τη διακονία του λόγου, το ιστορικό πλαίσιο στο οποίο δρούσαν, τον βίο, τη θεολογία και τα ομιλητικά τους έργα, ώστε να εντοπίσω τη θεματολογία των ομιλιών τους. Για μια καλύτερη εικόνα των παραπάνω πρόσθεσα κάποια στοιχεία μέσα από περιοδικά της Σερβικής Εκκλησίας, τα οποία σχετίζονται με τη διακονία του λόγου. Εξετάστηκαν οι επιρροές, τα ρεύματα οποία επηρέασαν τη διακονία του λόγου της Σερβικής Εκκλησίας. Επίσης, εντοπίστηκαν συγκυρίες των ιεροκηρύκων, η αλλαγή του κηρυκτικού παραδείγματος σε αυτούς τους δυο αιώνες. Στον 19ο αιώνα παρατηρείται μια επιρροή σχολαστικής θεολογίας, η οποία τονίζει υπερβολικά την ηθική. Στον 20ο αιώνα αυτό το κηρυκτικό παράδειγμα αλλάζει και βλέπουμε ένα αγιοπατερικό κήρυγμα, κυρίως από τους δυο κορυφαίους ιεροκήρυκες της Σερβικής Εκκλησίας, του Αγίου Νικολάου Βελιμίροβιτς και του Οσίου Ιουστίνου Πόποβιτς. Δυο βασικά χαρακτηριστικά της διακονίας του λόγου της Σερβικής Εκκλησίας είναι: η χριστολογία του Αγίου Νικολάου Βελιμίροβιτς και του Οσίου Ιουστίνου Πόποβιτς και η αίσθηση του σερβικού λαού για τη δικαιοσύνη οποία πηγάζετε από την διαθήκη του Κοσόβου. Αυτή η διατριβή ανοίγει μια καινούρια σελίδα στη διακονία του λόγου της Σερβικής Εκκλησίας επειδή προσφέρει θέματα για επόμενες διατριβές και μελέτες αυτού του τομέα.
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.
Monitoring the readiness of leaders and teachers of educational organizations for inclusive education
Authors: Manuylova V. , Guseynova A.
Published: January 2022

The article highlights the issues of determining and developing special conditions in educational institutions of different levels of education for children with disabilities. The results of studying the state of readiness of leaders and teachers of educational organizations for inclusive education are presented. Based on the results of the monitoring, conclusions were drawn and key problems of staffing of educational organizations were identified, personnel shortages of each educational organization were identified and directions for the development of management and pedagogical teams on the organization and implementation of inclusive education were described.
Kontekst socjologiczny historyczno-filozoficznych badań ideologii liberalizmu Mykoły Konrada
Authors: Sheremeta Oksana
Published: January 2022

Mykoła (Mikołaj) Konrad (1876-1941) - duchowny greckokatolicki, doktor teologii i filozofii, ukraiński historyk filozofii. Pisemne dziedzictwo myśliciela, oprócz badań nad historią filozofii, stanowią prace poświęcone ideologiom, w szczególności liberalizmowi, którego wizję Konrad przedstawił w dziele Główne kierunki najnowszej socjologii. Część pierwsza. Liberalizm (Lwów: Edycja "Bohosloviyi ", Cz. 21, 1936). W celu zbadania poglądów ojca Konrada na liberalizm w odpowiednim kontekście religijno-filozoficznym konieczne było ustalenie, dlaczego myśliciel rozważał tę tradycję myśli politycznej w kontekście socjologii. Ważne było porównanie poglądów Konrada z poglądami znanych mu myślicieli katolickich. W wyniku badań ustalono, że definicja i wizja rozwoju socjologii u M. Konrada i europejskich filozofów-neotomistów A. Uszenicznika, A. Roszkowskiego, A. Szymańskiego, W. Cathreina, Y. Biederlyaka są podobne. Ich źródłem są społeczna i etyczna nauki Kościoła Katolickiego zbudowane na zasadach neotomizmu. One określiły przedmiot i zadania socjologii katolickiej, mającej na celu rozwiązywanie problemów społecznych, które rodziły potrzebę studiowania ideologii. Dlatego rozpatrywanie liberalizmu przez M. Konrada w ramach socjologii było całkiem słuszne. Kolejnym zadaniem jest zbadanie, jakie było rozumienie socjologii u myśliciela ukraińskiego i jaki wpływ wywarł na niego kontekst socjologiczny.
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.
Educacion... Mirando al futuro, abriendo horizontes
Authors: US Facultad de Ciencias de la Educación
Published: January 2022

La presente obra surge a raíz de la idea propuesta por el Sr. Rector de la Universidad de Sevilla en el Acto de Apertura del 25 Aniversario de la Facultad de Ciencias de la Educación el pasado año. En dicho acto, se planteó la posibilidad de editar un libro homenaje que sirviera como hito en la memoria de nuestra Facultad. Hubiera sido previsible plasmar la idea en formato narrativo y/o gráfico, donde se hiciera una recopilación de relatos y fotos cedidas por personas que han formado parte de la vida del Centro. En la línea de querer señalar la efeméride, desde el Equipo Decanal consideramos otra manera de hacer homenaje a los 25 años ya vividos, mirando hacia adelante, partiendo del ahora. Así, las imágenes que ofrecemos forman parte de la exposición permanente Educación Engloba. En todas ellas aparecen personas que forman parte y dan vida a la comunidad universitaria de nuestra Facultad. Las/os espectadoras/es podrán coparticipar de la esencia de nuestras/os compañeras/os, que aparecen por orden alfabético de su nombre. El nombre por el que nos damos a conocer y nos conocen. Es una forma de acercarnos a los demás tal y como sentimos la Educación. En una conversación de pasillo, en una clase participativa, en unas jornadas que enriquecen nuestra formación Las aportaciones de cada protagonista hacen referencia a cómo entienden la Educación de ahora en adelante, mirando a futuro.
Códigos Emergentes de "Dadvertising": Representaciones Paternas con Enfoque Equitativo.
Authors: Morales-Vivanco Verónica , Gallardo-Echenique Eliana
Published: January 2022

Este estudio analizó los códigos de dadvertising asociados a la equidad de género. El dadvertising es un tipo de publicidad paternal que promueve representaciones cercanas y multifacéticas de los hombres en su rol de padre dentro del hogar. Al ser una tendencia emergente, no hay suficientes estudios enfocados en construir mensajes publicitarios empáticos e inclusivos dirigido a los padres. Se adoptó una metodología cualitativa para analizar el spot “Más tiempo para crecer” de la marca bancaria Interbank. Se realizaron entrevistas semiestructuradas a 15 padres de familia peruanos de 25 a 39 años de edad. Como resultado, los códigos de dadvertising asociados a la equidad de género en el spot son: protección, satisfacción, compañerismo, empoderamiento emocional, valores de equidad, expresión emocional y equilibrio trabajo-familia. Estos códigos contribuyen a la construcción de un discurso publicitario alejado de estereotipos tradicionales, para generar una identificación y actitud positiva de marca con los padres de familia.
Democracia: Hitos y Retos.
Authors: Díaz-Cano Eduardo , Tardivo Giuliano
Published: January 2022

La democracia tiene tras de sí una larga historia, pero todavía no se ha constituido de forma plena y completa, presentando importantes fisuras entre lo que se espera de ella y cómo se ha puesto en práctica. Este trabajo se interesa por las formas de democracia y sus titubeos históricos desde Mesopotamia hasta Silicon Valley, pasando por el resurgir de la Revolución Francesa y sus efectos. El objetivo es analizar cómo se ha materializado la democracia en diferentes épocas con casos que ilustran estas variaciones. Se utiliza el método histórico-comparativo y la recogida de datos consiste en recabar indicios de “democracia” desde la Antigüedad hasta nuestros días, mediante revisión bibliográfica de las aportaciones de autores de diversas especialidades. Los resultados son diversos y la introducción de la democracia coincide históricamente como respuesta a situaciones contradictorias y negativas para gran parte de la población. Se concluye que tampoco en el siglo XXI la democracia lo ha conseguido y, si bien sigue siendo el mejor instrumento, los desafíos siguen presentes y la misma idea resulta ser cuestionada en un mundo de democracias.
‘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.
Management of lower incisor extraction cases. Part 2: problems and solutions when choosing extraction
Authors: Scholey John , Visram Semina , Patel Yatisha A
Published: January 2022

In part one of this series we described situations where extracting a lower incisor could provide a useful alternative to premolar extractions, in addition to solutions for treatment planning certain types of cases. In part two, we look at some of the problems caused by opting to extract a lower incisor and how they may be overcome.

CPD/Clinical Relevance: Part two of this series aims to guide clinicians on potential pitfalls of lower incisor extraction treatment plans and how these can be avoided.
Biogas Production with Beef Cattle Manure and Wastewater from Hydraulic Fracturing
Authors: Campbell Terra N. , Rhoades Marty B. , Parker David B. , Blaser Brock C.
Published: January 2022

Highlights

Hydraulic fracking wastewater is evaluated as a possible alternative to freshwater in combination with beef cattle manure for bio-methane generation by anaerobic digestion (AD).

Optimum conditions for AD with fracking wastewater remain unknown, but differ from AD with freshwater.

Contrary to AD with freshwater, biogas production with fracking wastewater increased with lower MC.

Abstract. Wastewater from hydraulic fracturing (HF) and manure from beef cattle production are two of the largest waste streams in the Texas Panhandle. The objective of this study was to evaluate the potential of generating biogas, a renewable natural gas, from the combination of HF wastewater and beef manure through anaerobic digestion (AD) at varying moisture contents. In a laboratory study, substrate combinations of manure mixed with produced and flowback water (PFW), well water (WW), and a 50/50 mixture of PFW and WW were evaluated at four moisture contents (MC; 65%, 70%, 80%, and 90%). Beef manure was harvested from the West Texas A&M University research feedlot. The PFW was collected from a HF operation in the Texas Panhandle. The combinations of manure and WW at 90% MC yielded the greatest amount of biogas and methane (CH4). The greatest amount of biogas and CH4 with the combination of manure and PFW was produced at 65% MC. This combination produced 57% less biogas than the optimum CH4-producing WW treatment. Diluting PFW with WW produced amounts of CH4 comparable to WW at 80% MC. While there is potential to generate biogas and methane with PFW and manure, more research is needed to isolate the CH4-inhibiting constituents in PFW. Keywords: Anaerobic digestion, Manure, Methane, Produced and flowback water.
Single-carrier 800 Gbit/s and 1.2 Tbit/s Transmission Using 96 GBaud Commercial Optoelectronic Components
Authors: Qiang ZHENG , Hong YANG , Longbao WANG , Zhuopeng XIAO , Huijian ZHANG
Published: January 2022

Using commercial optoelectronic components we experimentally demonstrate an 800 Gbit/s/lambda system with 96 GBaud 32QAM. The BER floor is 9e-5 and the receiver sensitivity is -20.7 dBm, which may support several DCI applications.
Neural Architecture Search-enabled Deep Reinforcement Learning for Slice Deployment in a Converged Optical- Wireless Access Network
Authors: Wang Ruikun , Zhang Jiawei , Gu Zhiqun , Chen Zhuo , Ji Yuefeng
Published: January 2022

We propose a neural architecture search-enabled deep reinforcement learning (NAS- DRL) for RAN slice deployment in a converged optical-wireless access network. Simulation results validate its superiority in resources saving and DRL retaining times.
Data-effective and Accurate EDFA Gain Prediction Black-box Model
Authors: Zhang Mingming , Li Yuqi , Li Weihao , Chen Junda , Chen Yizhao , Tang Ming
Published: January 2022

An EDFA gain prediction model is proposed. With a small size of experimental data, the spectral gain root-mean-squared-error of the model is 0.1756 dB.
Spirally rotating particles with structured beams generated by phase-shifted zone plates
Authors: Rafighdoost Jila , Li Xing , Zhou Yuan , Zhou Meiling , Li Manman , Yan Shaohui , Yao Baoli
Published: January 2022

The emerging field of structured beams has led to optical manipulation with tremendous progress. Beyond various methods for structured beams, we use phase-shifted zone plates known as beam-shaping diffractive optical elements to generate beams whose phase exclusively or both phase and intensity are twisted along a curve. These beams can trap and guide particles on open curved trajectories for continuous motion, not necessarily requiring a closed symmetric intensity distribution. We show the feasibility and versatility of the proposed method as a promising technique in optical manipulation in which the trajectory of the spiral rotation and the rate of rotation of trapped particles can be controlled.
Smartphone-based corneal topography with null-screens
Authors: Huerta-Carranza Oliver , Campos-García Manuel , Moreno-Oliva Victor Ivan , Aguirre-Aguirre Daniel , Pérez-Lomelí Juan Salvador
Published: January 2022

To measure the shape of the fast corneal surface of the human eye, we propose the design and characterization of a compact corneal topographer using the capabilities of a smartphone. The performance evaluation of the compact corneal topographer includes the calculation and compensation of the distortion introduced by the smartphone lens used to acquire the images and the evaluation of a reference surface. To demonstrate the feasibility of our proposal, we performed surface topography measurements on some human corneas and compared the results with those obtained by a commercial corneal topographer. We showed that the results obtained with our algorithms were consistent with other methods that analyze the corneal surface.
Utilizing the temporal superresolution approach in an optical parametric synthesizer to generate multi-TW sub-4-fs light pulses
Authors: Muschet A. A. , De Andres A. , Fischer P. , Salh R. , Veisz L.
Published: January 2022

The Fourier-transform limit achieved by a linear spectral phase is the typical optimum by the generation of ultrashort light pulses. It provides the highest possible intensity, however, not the shortest full width at half maximum of the pulse duration, which is relevant for many experiments. The approach for achieving shorter pulses than the original Fourier limit is termed temporal superresolution. We demonstrate this approach by shaping the spectral phase of light from an optical parametric chirped pulse amplifier and generate sub-Fourier limited pulses. We also realize it in a simpler way by controlling only the amplitude of the spectrum, producing a shorter Fourier-limited duration. Furthermore, we apply this technique to an optical parametric synthesizer and generate multi-TW sub-4-fs light pulses. This light source is a promising tool for generating intense and isolated attosecond light and electron pulses.
Theoretical analysis of the role of complex transition dipole phase in XUV transient-absorption probing of charge migration
Authors: Kobayashi Yuki , Neumark Daniel M. , Leone Stephen R.
Published: January 2022

We theoretically investigate the role of complex dipole phase in the attosecond probing of charge migration. The iodobromoacetylene ion (ICCBr+) is considered as an example, in which one can probe charge migration by accessing both the iodine and bromine ends of the molecule with different spectral windows of an extreme-ultraviolet (XUV) pulse. The analytical expression for transient absorption shows that the site-specific information of charge migration is encoded in the complex phase of cross dipole products for XUV transitions between the I-4d and Br-3d spectral windows. Ab-initio quantum chemistry calculations on ICCBr+ reveal that there is a constant π phase difference between the I-4d and Br-3d transient-absorption spectral windows, irrespective of the fine-structure energy splittings. Transient absorption spectra are simulated with a multistate model including the complex dipole phase, and the results correctly reconstruct the charge-migration dynamics via the quantum beats in the two element spectral windows, exhibiting out-of-phase oscillations.