bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Crossroads of Cancer Epigenetics and Immune Checkpoint Therapy
Authors: Micevic Goran , Bosenberg Marcus W. , Yan Qin 
Published: November 2022

AbstractImmune checkpoint inhibitors (ICI) have significantly improved treatment outcomes for several types of cancer over the past decade, but significant challenges that limit wider effectiveness of current immunotherapies remain to be addressed. Certain “cold” tumor types, such as pancreatic cancer, exhibit very low response rates to ICI due to intrinsically low immunogenicity. In addition, many patients who initially respond to ICI lack a sustained response due to T-cell exhaustion. Several recent studies show that epigenetic modifiers, such as SETDB1 and LSD1, can play critical roles in regulating both tumor cell–intrinsic immunity and T-cell exhaustion. Here, we review the evidence showing that multiple epigenetic regulators silence the expression of endogenous antigens, and their loss induces viral mimicry responses bolstering the response of “cold” tumors to ICI in preclinical models. Similarly, a previously unappreciated role for epigenetic enzymes is emerging in the establishment and maintenance of stem-like T-cell populations that are critical mediators of response to ICI. Targeting the crossroads of epigenetics and immune checkpoint therapy has tremendous potential to improve antitumor immune responses and herald the next generation of sustained responses in immuno-oncology.
Gallium-68–labeled Peptide PET Quantifies Tumor Exposure of PD-L1 Therapeutics
Authors: Mishra Akhilesh , Kumar Dhiraj , Gupta Kuldeep , Lofland Gabriela , Sharma Ajay Kumar , Banka Dhanush S. , Hobbs Robert F. , Dannals Robert F. , Rowe Steven P. , Gabrielson Edward , Nimmagadda Sridhar 
Published: November 2022

Abstract

Purpose:
Immune checkpoint therapy (ICT) is currently ineffective in a majority of patients. Tumor drug exposure measurements can provide vital insights into mechanisms involved in the resistance of solid tumors to those therapeutics; however, tools to quantify in situ drug exposure are few. We have investigated the potential of programmed death-ligand 1 (PD-L1) pharmacodynamics, quantified using PET, to inform on the tumor exposure of anti–PD-L1 (aPD-L1) therapeutics.

Experimental Design:
To noninvasively quantify PD-L1 levels, we first developed a novel peptide-based gallium-68–labeled binder, [68Ga]Ga-DK223, and evaluated its in vivo distribution, pharmacokinetics, and PD-L1 specificity in preclinical models of triple-negative breast cancer and urothelial carcinoma with variable PD-L1 expression. We then quantified baseline and accessible PD-L1 levels in tumors as a noninvasive pharmacodynamic measure to assess tumor exposure to two aPD-L1 antibodies (avelumab and durvalumab).

Results:
DK223 exhibited a KD of 1.01±0.83 nmol/L for PD-L1 and inhibited the PD-1:PD-L1 interaction in a dose-dependent manner. [68Ga]Ga-DK223 provides high-contrast PET images within 60 minutes of administration and detects PD-L1 in an expression-dependent manner in xenograft models. PD-L1 pharmacodynamics measured using [68Ga]Ga-DK223-PET revealed that avelumab and durvalumab had similar exposure early during therapy, but only durvalumab exhibited sustained exposure at the tumor.

Conclusions:
[68Ga]Ga-DK223 detected variable PD-L1 levels and exhibited salient features required for clinical translation. [68Ga]Ga-DK223-PET could be useful for quantifying total PD-L1 levels at baseline and accessible PD-L1 levels during therapy to understand drug exposure at the tumor, thus supporting its use for guiding and optimizing ICT.
Dynamic Mutational Landscape of Cerebrospinal Fluid Circulating Tumor DNA and Predictors of Survival after Proton Craniospinal Irradiation for Leptomeningeal Metastases
Authors: Wijetunga N. Ari , Goglia Alexander G. , Weinhold Nils , Berger Michael F. , Cislo Michael , Higginson Daniel S. , Chabot Kiana , Osman Ahmed M. , Schaff Lauren , Pentsova Elena , Miller Alexandra M. , Powell Simon N. , Boire Adrienne , Yang Jonathan T. 
Published: November 2022

AbstractPurpose:Proton craniospinal irradiation (pCSI) is a promising treatment for patients with solid tumor leptomeningeal metastasis (LM). We hypothesize that genetic characteristics before and changes resulting after pCSI will reflect clinical response to pCSI. We analyzed the cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) from patients receiving pCSI for LM and explored genetic variations associated with response.Experimental Design:We subjected CSF from 14 patients with LM before and after pCSI to cell-free DNA sequencing using a targeted-sequencing panel. In parallel, plasma ctDNA and primary tumors were subjected to targeted sequencing. Variant allele frequency (VAF) and cancer cell fraction (CCF) were calculated; clonality of observed mutations was determined. Kaplan–Meier analysis was used to associate genomic changes with survival.Results:The median overall survival (OS) for the cohort was 9 months [interquartile range (IQR), 5–21 months]. We showed clonal evolution between tumor and ctDNA of the CSF and plasma with unique mutations identified by compartment. Higher CSF ctDNA mean VAF before pCSI (VAFpre) had worse OS (6 months for VAFpre ≥ 0.32 vs. 9 months for VAFpre &lt; 0.32; P = 0.05). Similarly, increased VAF after pCSI portended worse survival (6 vs. 18 months; P = 0.008). Higher mean CCF of subclonal mutations appearing after pCSI was associated with worse OS (8 vs. 17 months; P = 0.05).Conclusions:In patients with solid tumor LM undergoing pCSI, we found unique genomic profiles associated with pCSI through CSF ctDNA analyses. Patients with reduced genomic diversity within the leptomeningeal compartment demonstrated improved OS after pCSI suggesting that CSF ctDNA analysis may have use in predicting pCSI response.
Hate Speech: A Pragmatic Assessment of the European Court of Human Rights’ Jurisprudence
Authors: Sardo Alessio 
Published: November 2022

Abstract
This paper aims to offer a fresh start for addressing several conundrums relating to hate speech. The method of research combines a conceptual analysis with a possible model for evaluating the European Court of Human Rights’ (ECtHR) decisions on hate speech. First, drawing on a Gricean account of communication, the argument proposes a working definition of hate speech: hate speech is best understood as a public speech act, aimed at subordinating individuals, which causes harm to targeted groups. Second, the paper offers a taxonomy of the different forms of hate speech, based on their degree of explicitness and detachment from the speaker’s intentions. The most explicit forms of (harmful) hate speech – e.g., racial slurs, fighting words, or overtly sexist remarks – will be distinguished from implicit forms of (harmful) hate speech – e.g., innuendo, insinuation, and irony. Third, the author develops a categorical framework for hate speech that can be used as a standard for evaluating the jurisprudence of the ECtHR. The author also discusses three limitations of the model: a) the absence of a European consensus, b) puzzled speakers, and c) difficulty in determining harm.
Postscript: How long do Acari live? A survey of mite lifespans (part 2)
Authors: ZHANG ZHI-QIANG 
Published: November 2022

This is the second part of a survey of mite lifespans initiated last year (Zhang & Fan 2021). This series was launched to collect information on lifespan and related data across mite taxa, with the aim to stimulate more research on both the patterns and mechanisms of mite aging and lifespan (Zhang 2021). The first part covered lifespan and other life history data for Oribatida, Winterschmidtiidae, Eriophyoidea, Tydeidae, Anystidae, Cheyletidae and Blattisociidae (Zhang & Fan 2021). This part provides surveys of lifespan and related life history data for three major families: Tetranychidae (Li et al. 2022), Laelapidae (Zhang et al. 2022) and Phytoseiidae (Han et al. 2022). The third part in 2023 will complete this series.
Bio-efficacy of Tagetes minuta L. against Tetranychus truncatus Ehara (Prostigmata: Tetranychidae)
Authors: ASHISH V.V. , BHASKAR HASEENA , SREELATHA U. , DEEPTHY K.B. 
Published: November 2022

Tetranychus truncatus is the predominant species of spider mite infesting vegetable crops in Kerala (Bennur et al., 2015). The mite management in Kerala largely depends on the use of synthetic acaricides. However, extensive use of synthetic pesticides over decades has led to several adverse effects on environment and non-target organisms. Plants and plant-based products are receiving considerable attention worldwide for their utilization and applications in pest management. The Mexican marigold, Tagetes minuta L. (Asteraceae), has been reported to contain the chemicals 5-(3-buten-1-ynyl) 2, 2-bithienyl and alpha therthienyl, which have pesticidal properties (Morallo-Rejesus and Decena, 1982). A laboratory study was conducted to evaluate the efficacy of Tagetes minuta against the spider mite, Tetranychus truncatus. The solvent extracts (hexane, chloroform and water) of T. minuta were evaluated separately against eggs and gravid females of T. truncatus at five different concentrations viz., 0.025, 0.05, 0.1,0.15 and 0.2 per cent. To evaluate the ovicidal effect, ten gravid females were released on mulberry leaf bit (5×5 cm) placed in Petri plate lined with moistened cotton and allowed for egg laying. The adults were removed after 24 h and 25 eggs were retained per leaf bit. The solvent extracts were applied on the leaf bits with eggs using hand atomizer and observed for egg hatchability at 24, 48, 72 and 96 h of spraying and per cent mortality of egg was calculated. To evaluate the adulticidal activity, mulberry leaf bits were dipped in solvent extracts for 30 seconds, air dried and placed in a Petri plate lined with moistened cotton. Twenty-five gravid females were released to the leaf bit and adult mortality was recorded after 24, 48, 72, 96 and 120 h of treatment and per cent mortality was calculated. The extracts varied significantly in their ovicidal and adulticidal effects. Among the different extracts, 0.2 % hexane extract was found to be significantly superior in ovicidal activity over other treatments and recorded 100 per cent mortality at 120 h after treatment. This was followed by 0.15 and 0.1 per cent hexane extracts which recorded 81.33 and 53.33 per cent egg mortality, respectively. The hexane extracts 0.2 % and 0.15 % were found to be significantly superior over other treatments, recording 93.33 and 92 per cent adult mortality, respectively within 120 h of application. This was followed by 0.2 % chloroform and 0.1 % hexane extracts, recording 73.33 and 72.00 per cent mortality, respectively. These results indicate that Mexican marigold possess excellent acaricidal properties and the hexane and chloroform extracts of the plant can be explored for further utilization in the management of spider mites.
Topographic Trapping of the Leeuwin Current and Its Impact on the 2010/11 Ningaloo Niño
Authors: Feng Xue , Shinoda Toshiaki , Han Weiqing 
Published: November 2022

Abstract
Previous theoretical studies suggest that the topography along the west coast of Australia plays an important role in strengthening and trapping the Leeuwin Current (LC) at the coast. To isolate and quantify the effect of the continental shelf and slope on the LC and Ningaloo Niño, high-resolution (1/12°) ocean general circulation model experiments with different bottom topographies are performed. The “control” experiment uses a realistic bottom topography along the west coast of Australia, whereas the sensitivity (“no-shelf”) experiment uses a modified topography with no continental shelf and slope near the coast. The mean and variability of LC are realistically simulated in the control experiment. Compared to the control experiment, the strength of LC in the no-shelf experiment decreased by about 28%. The continental shelf influences the development of the 2010/11 Ningaloo Niño through modulating the LC variability: in August–October 2010 and January–February 2011, the LC in the control experiment is enhanced much more than that in the no-shelf experiment. As a result, the upper-50-m ocean temperature in the control experiment is about 26% warmer than the no-shelf experiment from September 2010 to March 2011. Different evolution of SST warming is also found in the two experiments. Comparisons of oceanic processes in the two experiments show that the shelf-slope topography can effectively trap the positive sea level anomaly at the coast in the control experiment while more Rossby waves radiate from the coast in the no-shelf experiment, resulting in a weaker LC.
Determinants of macrosomia among newborns delivered in northwest Ethiopia: a case–control study
Authors: Adugna Amanuel , Workineh Yinager , Tadesse Fikir , Alemnew Fentahun , Dessalegn Nigatu , Kindie Kassa 
Published: November 2022

Objective Macrosomia is associated with the risk of mortality and morbidity in neonates and their mothers. Despite the considerable public health effect of macrosomia, evidence on the determinants of macrosomia is limited in Northwest Ethiopia in general and in Amhara region in particular. Therefore, this study aimed to identify determinants of macrosomia among newborns delivered in referral hospitals in 2020 in Amhara region, Northwest Ethiopia. Methods A facility-based unmatched case-control study was conducted among 279 mothers and their newborns in Amhara region referral hospitals. Newborns weighing 4000 g and above and between 2500 and 3999 g were considered cases and controls, respectively. Bivariable and multivariable binary logistic regression were used to identify the determinants of macrosomia. Results In total, 273 of 279 mothers and their newborns (97.8% response rate) were included. The mean birth weights of cases and controls were 4312.97 ± 357.53 g and 3161.92 ± 452.12 g, respectively. Weight gain over pregnancy, antenatal follow up, physical activity during pregnancy, and neonate sex were the main determinants of macrosomia. Conclusion The main determinants of macrosomia were determined in this study. Government should place special emphasis on reducing the modifiable factors of macrosomia.
Is SARS-CoV-2 viral load a predictor of mortality in COVID-19 acute respiratory distress syndrome patients?
Authors: Dogan Lerzan , Allahverdiyeva Aytaj , Önel Mustafa , Meşe Sevim , Saka Ersin Esra , Anaklı İlkay , Sarıkaya Zeynep Tuğçe , Zengin Rehile , Gucyetmez Bulent , Yurtturan Uyar Neval , Özcan Perihan Ergin , Kocagöz Ayse Sesin , Uysal Hayriye Kırkoyun , Akinci İbrahim Ozkan , Ağaçfidan Ali 
Published: November 2022

Objective Viral load varies during infection and is higher during the initial stages of disease. Given the importance of the intensive care unit (ICU) in the late stages of COVID-19 infection, analyzing cycle threshold values to detect viral load upon ICU admission can be a clinically valuable tool for identifying patients with the highest mortality risk. Methods This was a retrospectively designed study. Patients older than 18 years who tested positive for SARS-CoV-2 PCR and had a PaO2/FiO2 ratio <200 were included in the study. The patient population was divided into two groups: survivors and non-survivors. Results Two hundred patients were included in the study. In non-survivors, age, relevant ICU admission scores, and procalcitonin levels were significantly higher whereas PaO2/FiO2 ratios and cycle threshold levels were significantly lower than in survivors. Conclusion Viral load at ICU admission has significant prognostic value. In combination with age, comorbidities, and severity scores, viral load may assist clinicians in identifying individuals who need more intensive monitoring. Increased awareness may improve outcomes by allowing the more effective monitoring and treatment of patients. More prospective studies are needed to determine how a high viral load worsens disease and how to avoid irreversible results.
Thromboelastography Parameters do not Discriminate for Thrombotic Events in Hospitalized Patients With COVID-19
Authors: Kartiko Susan , Koizumi Naoru , Yamane David , Sarani Babak , Siddique Abu B. , Levine Andrea R. , Jackson Amanda M. , Wieruszewski Patrick M. , Smischney Nathan J. , Khanna Ashish K. , Chow Jonathan H. ,   for the CRUSH COVID Investigators
Published: November 2022

Background Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state; leading to multiple sequelae. We sought to detect whether thromboelastography (TEG) parameters would be able to detect thromboembolic events in patients hospitalized with COVID-19. Methods We performed a retrospective multicenter case–control study of the Collaborative Research to Understand the Sequelae of Harm in COVID (CRUSH COVID) registry of 8 tertiary care level hospitals in the United States (US). This registry contains adult patients with COVID-19 hospitalized between March 2020 and September 2020. Results A total of 277 hospitalized COVID-19 patients were analyzed to determine whether conventional coagulation TEG parameters were associated with venous thromboembolic (VTE) and thrombotic events during hospitalization. A clotting index (CI) >3 was present in 45.8% of the population, consistent with a hypercoagulable state. Eighty-three percent of the patients had clot lysis at 30 min (LY30)  =  0, consistent with fibrinolysis shutdown, with a median of 0.1%. We did not find TEG parameters (LY30 area under the receiver operating characteristic [ROC] curve [AUC]  =  0.55, 95% CI: 0.44-0.65, P value  =  .32; alpha angle [α] AUC  =  0.58, 95% CI: 0.47-0.69, P value  =  .17; K time AUC  =  0.58, 95% CI: 0.46-0.69, P value  =  .67; maximum amplitude (MA) AUC  =  0.54, 95% CI: 0.44-0.64, P value  =  .47; reaction time [R time] AUC  =  0.53, 95% CI: 0.42-0.65, P value  =  .70) to be a good discriminator for VTE. We also did not find TEG parameters (LY30 AUC  =  0.51, 95% CI: 0.42-0.60, P value  =  .84; R time AUC  =  0.57, 95%CI: 0.48-0.67, P value .07; α AUC  =  0.59, 95%CI: 0.51-0.68, P value  =  .02; K time AUC  =  0.62, 95% CI: 0.53-0.70, P value  =  .07; MA AUC  =  0.65, 95% CI: 0.57-0.74, P value < .01) to be a good discriminator for thrombotic events. Conclusions In this retrospective multicenter cohort study, TEG in COVID-19 hospitalized patients may indicate a hypercoagulable state, however, its use in detecting VTE or thrombotic events is limited in this population.
Curve negotiation performance of a newly-designed medium and low speed maglev vehicle
Authors: Zhang Min , Yuan Cheng , Ma Weihua , Luo Shihui 
Published: November 2022

A newly-designed maglev vehicle, namely maglev vehicle with mid-mounted suspension (MVMS), with air-springs mounted at the middle of the levitation module, has removed the forced guidance device (FGD). However, there is a paucity of research in the curve negotiation performance of the vehicle without FGD. In order to evaluate the curve negotiation performance of MVMS, comparisons were carried out between two maglev vehicles, namely MVMS and the maglev vehicle with end-mounted suspension (MVES). The guidance modes and mechanisms of the two kinds of vehicles were introduced and their curve negotiation performances were analyzed and compared. First, the guidance mechanism of one levitation module on the curved rail was explicated. Second, the walking mechanisms of the two maglev vehicles were introduced, and the guidance mechanism of each vehicle was illustrated. Third, two dynamic models considering rail irregularities, curved rail, and levitation control were built. Finally, the dynamic performances of the two maglev vehicles on the curved rail with 100 m radius, 6° cross-slope angle, and 0.12°/m gradient of the transition curve and on the straight rail were analyzed. Results show that MVES fails to pass the given curved rail, while MVMS can pass it at the speed of 40 km/h. Moreover, on the curved rail, the electromagnet offset, current, and levitation force in MVES are all larger than those in MVMS. For instance, when the speed is 40 km/h, the maximum vertical and lateral electromagnet offsets of the former are about four and 1.6 times those of the latter, respectively, and the maximum current of the former is about 2 times that of the latter. On the straight rail, the mid-mounted suspension can effectively improve the ride stability of the cabin at each speed. Thus, MVMS has better guiding performance than MVES on curved rail and straight rail.
Investigating the survival of herpes simplex virus on toothbrushes and surrogate phallic devices
Authors: Suissa Chad A , Upadhyay Rista , Dabney Michael D , Mack Ricardo J , Masica Danielle , Margulies Barry J 
Published: November 2022

Background Herpes simplex virus-1 (HSV-1) is a member of the alphaherpesvirus (alphaherpesvirinae) subfamily, allowing it to affect a wide range of hosts. Herpes simplex virus-1 affects 3.7 billion people, or 67% of the population, under the age of 50. With a vast number of people infected by the virus, everyday objects are often contaminated with this agent. In this study we determined how long HSV-1 can remain viable on contaminated fomites. Methods Fomites were selected for their use near potentially contaminated orifices and variable frequency of sanitization. Toothbrushes and surrogate phallic devices (SPDs) were cut, sterilized, and contaminated. After contaminating the fomites, we collected samples over a 24 h period, then used plaque assays to determine viral titers at prescribed time points. Results The quantity of replication-competent virus present appears to decrease significantly 2 h post-contamination, then steadily declines over time, nearing zero at 24 h. Conclusions Our findings suggest that different surfaces influence HSV-1 survival. Proper cleaning must be performed for these types of fomites, especially if shared in an environment where someone with active genital or oral herpes lesions uses one of these fomites shortly after someone else.