bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II study of sitravatinib in combination with tislelizumab in patients with advanced biliary tract cancer who have failed to at least 1 prior systemic treatment: Trial in progress.
Authors: Oh Do-Youn , Kim Jin Won , Chon Hongjae , Lee Choong-kun , Kim Ji-Won , Kang Beodeul , Choi Hye Jin , Park Se Jun , Yoon Jeesun , Lee Myung Ah
Published: January 2022

TPS490

Background: In biliary tract cancer (BTC), there was a positive association of overall survival (OS) with high levels of tumor-infiltrating CD4+, CD8+, and Foxp3+ T lymphocytes, whereas increases in PD-1+/CD8+ tumor-infiltrating lymphocytes had a negative association with OS (Tariq NU et al. 2018). Therefore, immune-modulating treatment can be promising option to overcome a dismal prognosis in BTC patients. However, immune checkpoint inhibitor (ICI) monotherapy, including tislelizumab (anti-PD-1 monoclonal antibody), has a modest effect in advanced BTC (Desai J et al. 2020). Thus, several combination strategies to improve the anti-tumor effect of ICI are being conducted. Anti-angiogenic agent in combination with ICI is one of the promising strategies in which anti-angiogenic agent induced improved anti-tumor immune responses by increasing tumor antigen presentation and promoting lymphocyte infiltration and migration (Song Y et al. 2020). However, this combination have not been widely tested in BTC patients. Sitravatinib is a potent inhibitor of multiple receptor tyrosine kinases including Axl, MER, MET, KIT, FLT3, RET, VEGFR1-3, PDGFRα, which targets are expressed in a number of immune cell types and promote an immunosuppressive tumor microenvironment. This study aim to evaluate the efficacy of the combination strategy of sitravatinib with tislelizumab in advanced BTC and to reveal the immune-modulation through the combination of ICI and antiangiogenic agents. Methods: This study is an open-label, phase 2 study to evaluate the efficacy of sitravatinib and tislelizumab combination treatment in advanced BTC patients who have failed to first-line chemotherapy. Eligible patients have histologically proven BTC (including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer, and ampulla of Vater cancer) and have failed one prior systemic chemotherapy. Patients who have previously received ICI can be enrolled. However, patients who have experienced unacceptable toxicity during prior ICI treatment are excluded. All patients will receive sitravatinib 120mg orally once daily in combination with tislelizumab 200mg intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is disease control rate, with key secondary endpoints including overall response rate, progression-free survival, overall survival, and safety. For evaluating metabolic response, 18F-FDG PET-CT scan will be performed before treatment and at the first response evaluation. Tissue biopsies will be conducted three times in total: screening, the first response evaluation, and disease progression. Blood samples are being collected every cycles for translational biomarker studies. Clinical trial information: NCT04727996.
Pivotal phase III COMPOSE trial will compare 177Lu-edotreotide with best standard of care for well-differentiated aggressive grade 2 and grade 3 gastroenteropancreatic neuroendocrine tumors.
Authors: Halfdanarson Thorvardur Ragnar , Reidy Diane Lauren , Vijayvergia Namrata , Halperin Daniel M. , Goldstein Grace , Kong Grace , Michael Michael , Leyden Simone , Grozinsky-Glasberg Simona , Sorbye Halfdan , Oberg Kjell E. , Sierras Cristina , Harris Philip
Published: January 2022

TPS514

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs), which represent approximately 70% of NETs, frequently develop metastatic disease with limited treatment options. Current standard therapies for well-differentiated high grade 2 and grade 3 GEP-NETs include cytoreductive procedures, somatostatin analogues, molecular targeted therapies (everolimus or sunitinib), chemotherapy and peptide receptor radionuclide therapy (PRRT), with no specified sequence of use. PRRT may stabilize disease and induce objective tumor responses. This treatment uses radiolabeled somatostatin analogues to selectively target somatostatin receptor expressing (SSTR+) tumor cells. 177Lu-edotreotide is an innovative radiolabeled somatostatin analogue with a favorable safety profile and promising efficacy. Retrospective data in metastatic GEP-NETs treated with two or more 177Lu-edotreotide cycles demonstrated a progression free survival (PFS) of at least 30 months. The currently recruiting Phase III COMPETE trial compares the efficacy and safety of 177Lu-edotreotide, versus everolimus, in grade 1 and grade 2 GEP-NETs. Methods: COMPOSE (NCT04919226) is a prospective, randomized, controlled, open-label, multi-center Phase III study, in patients with well-differentiated high grade 2 and grade 3 (Ki-67 index 15−55%), SSTR+, GEP-NETs. This trial is to evaluate the efficacy, safety and patient-reported outcomes of first- or second-line treatment with 177Lu-edotreotide PRRT compared to best standard of care. It aims to randomize 202 patients 1:1 to a defined number of cycles of 177Lu-edotreotide or an active comparator (either chemotherapy [CAPTEM or FOLFOX] or everolimus, according to investigator´s choice). The primary endpoint is PFS, assessed every 12 weeks until disease progression (RECIST v1.1), or death, whichever occurs earlier. Secondary outcomes include overall survival, assessed up to 2 years after disease progression. Study recruitment for COMPOSE commenced in September 2021. It is expected that COMPOSE will inform optimal treatment options for patients with well-differentiated high grade 2 and grade 3 SSTR+ GEP-NETs, including for first-line therapy. Clinical trial information: NCT04919226.
PANOVA-3: A phase 3 study of tumor treating fields (TTFields) with gemcitabine and nab-paclitaxel (GnP) for front-line treatment of locally advanced pancreatic adenocarcinoma.
Authors: Picozzi Vincent J. , Macarulla Teresa , Philip Philip A. , Becerra Carlos Roberto , Dragovich Tomislav
Published: January 2022

TPS629

Background: Tumor Treating Fields (TTFields) are a non-invasive, loco-regional antimitotic therapy approved for the treatment of glioblastoma and malignant pleural mesothelioma. TTFields (150–200 kHz) are delivered via arrays placed on the skin surrounding the tumor site. In vitro, TTFields (150 kHz), with or without chemotherapy, had antiproliferative and anticlonogenic effects on pancreatic cancer cells. The Phase 2 PANOVA study (NCT01971281) demonstrated the safety and preliminary efficacy of TTFields combined with nab-paclitaxel and gemcitabine (GnP) in both metastatic and locally advanced pancreatic adenocarcinoma (LAPC). Methods: The Phase 3 PANOVA-3 trial (NCT03377491) will evaluate the efficacy and safety of adding TTFields to GnP in a larger group of patients with LAPC. This prospective, randomized trial is currently enrolling 556 patients with unresectable LAPC (per National Comprehensive Cancer Network guidelines), Eastern Cooperative Oncology Group performance status of 0-2, and no prior progression or treatment. Patients will be randomized 1:1 to receive TTFields plus GnP or to GnP alone, stratified by performance status and geographical region. A recent protocol amendment included the use of a smaller, more light-weight (reduced from 6 to 2.7 lbs.) TTFields device. Standard doses of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) will be administered on days 1, 8, and 15 of a 28-day cycle. TTFields (150 kHz) will be delivered ≥ 18 h/day until local disease progression per Response Evaluation Criteria In Solid Tumors Criteria V1.1. Follow-up visits will be conducted every 4 weeks; a computed tomography scan of the chest and abdomen will be performed every 8 weeks. After local disease progression, patients will be followed for survival on a monthly basis. The primary endpoint is overall survival (OS). Secondary endpoints include progression free survival (PFS), local PFS, objective response rate, 1 year survival rate, pain- and puncture-free survival rate, rate of resectability, quality of life, and toxicity. The sample size calculation used a log-rank test comparing time to event in patients treated with TTFields plus GnP with control patients on gemcitabine alone. PANOVA-3 is designed to detect a hazard ratio of 0.75 in OS. Type I error is set to 0.05 (2-sided) and power to 80%. Study locations in Austria, Belgium, Canada, Croatia, Czech Republic, France, Germany, Hong Kong, Hungary, Israel, Italy, Poland, Spain, Switzerland, and the US are currently recruiting. Clinical trial information: NCT03377491.
State Regulation and Hospital Community Benefit Spending in Medicaid Expansion States
Authors: Sun Qingqing , Spreen Thomas Luke
Published: January 2022

Context: Previous studies show that nonprofit hospital spending on charity care declined in Medicaid expansion states. We test whether state community benefit regulations mitigated the decline in charity care spending.

Methods: We use a fixed effects model to evaluate the association between state regulations and nonprofit hospital community benefit spending and its subcategories as a share of total expenses in Medicaid expansion states. We obtained community benefit spending data from the Internal Revenue Service Form 990 Schedule H filings of 1,738 hospitals in 44 states and the District of Columbia from 2010 to 2017. We determine the stringency of state regulations by comparing the provisions of state and federal requirements based on regulation information compiled by the Hilltop Institute.

Findings: State minimum community benefit requirements are associated with increased community benefit and charity care spending by nonprofit hospitals in Medicaid expansion states.

Conclusions: States that imposed minimum community benefit requirements on nonprofit hospitals did not experience a decline in charity care spending after Medicaid expansion. The results suggest state minimum community benefit rules may expand the provision of community benefit and charitable care spending.
Lipid-driven CFTR clustering is impaired in cystic fibrosis and restored by corrector drugs
Authors: Abu-Arish Asmahan , Pandžić Elvis , Luo Yishan , Sato Yukiko , Turner Mark J. , Wiseman Paul W. , Hanrahan John W.
Published: January 2022

Membrane proteins often cluster in nanoscale membrane domains (lipid rafts) that coalesce into ceramide-rich platforms during cell stress, however the clustering mechanisms remain uncertain. The cystic fibrosis transmembrane conductance regulator (CFTR), which is mutated in cystic fibrosis (CF), forms clusters that are cholesterol dependent and become incorporated into long-lived platforms during hormonal stimulation. We report here that clustering does not involve known tethering interactions of CFTR with PDZ domain proteins, filamin A or the actin cytoskeleton. It also does not require CFTR palmitoylation but is critically dependent on membrane lipid order and is induced by detergents that increase the phase separation of membrane lipids. Clustering and integration of CFTR into ceramide-rich platforms are abolished by the disease mutations F508del and S13F and rescued by the CFTR modulators elexacaftor plus tezacaftor. These results indicate CF therapeutics that correct mutant protein folding restore both trafficking and normal lipid interactions in the plasma membrane.

This article has an associated First Person interview with the first author of the paper.
Digital Literacy in the Networked Educational Space
Authors: Shevchenko G. , Brynza S. , Kalashnikova A.
Published: January 2022

The modern digital world dictates its own trends and laws, against the background of which there is a change in the ways of thinking, highly qualified personnel are in demand, the preparation of which seems to be an urgent pedagogical task. Education is actively discussing the problem of the formation and development of digital literacy. Particular attention is paid to its components, aimed at developing the potential of the student on the basis of network interaction. In this regard, the theoretical foundations of digital literacy deserve detailed consideration, revealing the content of the concept of digital competence, as well as highlighting the criteria for achieving it.
Powieść Jana Rompskiego Wurvanô spjéva jako metafora projektu narodowego Zrzeszyńców
Authors: Jabłoński Artur
Published: January 2022

W 1943 roku kaszubski pisarz Jan Rompski napisał powieść zatytułowanąWurvanô spjéva, którą można odczytać jako metaforę projektu narodowegoskierowanego do Kaszubów, stworzonego przez inteligencki krąg przyjaciółw realiach II Rzeczypospolitej lat 30. XX wieku. Jan Rompski był współzałożycielem i ideologiem grupy ideowo-literackiej Zrzeszyńców, która kontynuowała tradycje ruchu kaszubskiego, swoimi korzeniami sięgającego pierwszej połowy XIX stulecia. Niniejszy artykuł jest próbą odpowiedzi na pytanie, co stanowiło filary projektu Zrzeszyńców, a także jakie były jego podstawowe założenia, mające pomóc w kreacji wyobrażenia narodu, którego przedstawicielami się czuli. Należało się również przyjrzeć, jak Jan Rompski przeniósł owe założenia na karty powieści Wurvanô spjéva. Analizując powieść i teksty publicystyczne Zrzeszyńców, posłużyłem się metodą krytycznej analizy dyskursu. Jeśli naród to zbiór elementów połączony jakimiś więzami, to tym, co spaja Kaszubów, są: język, kultura i polityka.
Murray Rothbard, Anarchist
Authors: Block Walter E.
Published: January 2022

This essay is in honor of Murray N. Rothbard. He made many important, nay, exquisite contributions to belles letters, not limited to economics, history, philosophy, sociology; even to movie reviews of all things. The present essay is an attempt to honor him by making the case for free market anarchism, the thesis that ran through most of his intellect output.
Enlightenment and Social Progress – Back to the Enlightenment
Authors: Stachoň Marek
Published: January 2022

The world today operates in a highly fragmented manner and in constant motion. The question of social progress is tempered. Morality does not determine the direction of social development and social interest. Scientific schematizing of our social reality and education is done intentionally in order to achieve maximum profits and success in the sciences, whose justification is questionable under the influence of meeting the requirements of the time. It is therefore necessary to review the issue and return to the roots of reflection on the meaning of enlightenment and progress, hence the Enlightenment. Kant and Rousseau are very specific philosophers within the Enlightenment. In many issues they are different from the other philosophers of the Enlightenment. In many ways Kant overcomes the Enlightenment and both think about the question of social progress differently from their contemporaries.
Disolución Matrimonial: la Ruptura de Matrimonios del mismo Sexo en Andalucía.
Authors: Jimenez-Cabello Jose
Published: January 2022

Tras diversos intentos de regulación de los matrimonios de personas del mismo por parte de algunas comunidades autónomas, la Ley 13/2005 supuso el reconocimiento de este tipo de uniones. La misma situó a España como uno de los países pioneros en reconocer este tipo de matrimonios. Este texto aborda la evolución de los divorcios de matrimonios compuestos por personas del mismo sexo, y diversos aspectos destacados, en uno de los territorios donde más enlaces se producen: Andalucía. El método empleado es cuantitativo, aplicando un análisis descriptivo mediante la utilización de la Estadística de Nulidades, Separaciones y Divorcios (ENSD, 2012-2018). Las principales conclusiones extraídas son que los divorcios de este tipo de matrimonios han ido aumentando de forma paulatina a lo largo del periodo analizado. La mayoría de estos divorcios se caracterizan por ser consensuados. Los matrimonios tienen, en su mayoría, una duración de 5 años o más y están compuestos esencialmente por cónyuges de nacionalidad española. Por último, dos tercios de los divorcios ocurren en parejas sin hijos menores.
Regularized Aggregation of One-Off Probability Predictions
Authors: Satopää Ville A.
Published: January 2022

How much can rational people really disagree? If we can understand the limits of such disagreement, can we remove noise by labeling excess disagreement as irrational and then construct a group belief based on everyone's rational beliefs? Based on this idea, “Regularized Aggregation of One-Off Probability Predictions” by Satopää proposes a Bayesian aggregator that requires no user intervention and can be computed efficiently even for a large number of one-off probability predictions. To illustrate, the aggregator is evaluated on predictions collected during a four-year forecasting tournament sponsored by the U.S. intelligence community. The aggregator improves the squared error (a.k.a., the Brier score) of simple averaging by around 20% and other commonly used aggregators by 10%−25%. This advantage stems almost exclusively from improved calibration. An R package called braggR implements the method and is available on CRAN.
Hepatitis B, Hepatitis C and Liver Disease: A Review for the Dental Practitioner
Authors: Macpherson Iain , Brennan Paul N , Dillon John F
Published: January 2022

The prevalence of chronic liver disease continues to rise, and important causes include viral infections, such as hepatitis B and hepatitis C. Both of these viruses can be contracted by healthcare workers through an inoculation injury and can lead to liver cirrhosis and cancer. In addition, chronic liver disease can result in disorders of liver function, including coagulopathy and abnormal metabolism of drugs widely used in dentistry. This article reviews current prevalence, transmission rates and treatment of hepatitis B and hepatitis C, as well as particular considerations for dental patients with liver disease.

CPD/Clinical Relevance: Viral hepatitis remains a risk to all healthcare workers, and patients with liver disease provide various challenges when providing dental treatment.
Hereditary Angioedema Type I Triggered by Dental Treatment: A Case Report and Review of the Literature
Authors: Jagatiya Yashoda , Yogarajah Sangeetha , Monteiro Luis , Carey Barbara , Albuquerque Rui
Published: January 2022

Type 1 hereditary angioedema (HAE) is a rare genetic condition characterized by recurrent episodes of oedema caused by a deficiency of C1-esterase inhibitor (C1-INH). A 29-year-old male presented to the oral medicine department at Guy's Hospital, London, with lip swelling following crown preparation and impressions. Haematological investigations showed reduced levels of complement C4 (0.02 g/L; reference range 0.1–0.4 g/L) and C1-INH function was <31% (reference range 85–99%). Immunology confirmed the diagnosis of type 1 HAE, with a de novo mutation. This case highlights how a detailed medical history and multidisciplinary teamwork ensure the correct diagnosis and management.

CPD/Clinical Relevance: To demonstrate the various dental triggers, relevant signs and symptoms, and management options for patients diagnosed with hereditary angioedema to allow for effective decision-making in a primary dental setting.
Polarimetric photoluminescence microscope for strain imaging on semiconductor devices
Authors: Schaub Emmanuel , Ahammou Brahim , Landesman Jean-Pierre
Published: January 2022

Anisotropic strain induces a partial linear polarization of the photo-luminescence (PL) emitted by cubic semiconductor crystals such as GaAs or InP. This paper thus presents a polarimetric PL microscope dedicated to the characterization of semiconductor devices. The anisotropic strain is quantified through the determination of the degree of linear polarization (DOLP) of the PL and the angle of this partial linear polarization. We illustrate the possibilities of this tool by mapping the anisotropic strain generated in GaAs by the presence of a stressor film at its surface, that is, a microstructure defined in a dielectric thin film (SiNx) that has been deposited with a built-in stress and shaped into a narrow stripe by lithography and etching. Our setup shows a DOLP resolution as low as

4.5
×

10

−
4

on GaAs.
Insight into band structures for out-of-plane propagation of a 2D dispersive photonic crystal: the dispersive photonic crystal iterative method
Authors: Valenzuela-Sau J. D. , García-Llamas Raúl
Published: January 2022

A study of the band structures of a two-dimensional dispersive photonic crystal for out-of-plane propagation along with the dispersive photonic crystal iterative method are presented. In these calculations, the proposed method uses the plane wave expansion method as the foundation. The photonic crystal is a square array of circular cross-sectional dispersive MgO Lorentz single-pole rods. The band structures were calculated starting at the high symmetry points

Γ

, X, and M as a function of the oblique component of the propagation wave vector. The method used is discussed in detail, and a simple equation is presented for straightforward analytical calculations of points of the frequency bands in the transparency window, where the dielectric constant equals that of vacuum.
Manifestation of the anisotropic properties of the molecular J-aggregate shell in the optical spectra of plexcitonic nanoparticles
Authors: Kondorskiy A. D. , Moritaka S. S. , Lebedev V. S.
Published: January 2022

The theoretical studies of light absorption and scattering spectra of the plexcitonic two-layer triangular nanoprisms and three-layer nanospheres are reported. The optical properties of such metal-organic core–shell and core–double-shell nanostructures were previously explained within the framework of pure isotropic models for describing their outer excitonic shell. In this work, we show that the anisotropy of the excitonic shell permittivity can drastically affect the optical spectra of such hybrid nanostructures. This fact is confirmed by directly comparing our theory with some available experimental data, which cannot be treated using conventional isotropic shell models. We have analyzed the influence of the shell anisotropy on the optical spectra and proposed a type of hybrid nanostructure that seems the most convenient for experimental observation of the effects associated with the anisotropy of the excitonic shell. A strong dependence of the anisotropic properties of the J-aggregate shell on the material of the intermediate spacer layer is demonstrated. This allows proposing a new way to effectively control the optical properties of metal-organic nanostructures by selecting the spacer material. Our results extend the understanding of physical effects in optics of plexcitonic nanostructures to more complex systems with the anisotropic and multi-excitonic properties of their molecular aggregate shell.
Compact MZI modulators on thin film Z-cut lithium niobate
Authors: Hassanien Ahmed E. , Ghoname Amr O. , Chow Edmond , Goddard Lynford L. , Gong Songbin
Published: January 2022

In this paper, we designed, implemented, and characterized compact Mach-Zehnder interferometer-based electro-optic modulators. The modulator utilizes spiral-shaped optical waveguides on Z-cut lithium niobate and the preeminent electro-optic effect which is applied using top and bottom electrodes. Optical waveguides are made of rib etched lithium niobate waveguides with bottom silicon oxide cladding, while SU8 polymer covers the top and sides of the rib waveguides. The proposed implementation resulted in low optical losses < 1.3 dB/cm. Moreover, we achieved compact modulators that fit 0.286 cm and 2 cm long optical waveguides in 110 µm × 110 µm and 300 µm × 300 µm areas, respectively. For single arm modulation, the modulators achieved a VπL of 7.4 V.cm and 6.4 V.cm and 3-dB bandwidths of 9.3 GHz and 2.05 GHz, respectively. Push-pull modulation is expected to cut these VπL in half. The proposed configuration avoids traveling wave modulation complexities and represents a key development towards miniature and highly integrated photonic circuits.
Third-order optical nonlinearities of exfoliated Bi2Te3 nanoparticle films in UV, visible and near-infrared ranges measured by tunable femtosecond pulses
Authors: Kim Vyacheslav V. , Bundulis Arturs , Popov Viktor S. , Lavrentyev Nikolay A. , Lizunova Anna A. , Shuklov Ivan A. , Ponomarenko Vladimir P. , Grube Jurgis , Ganeev Rashid A.
Published: January 2022

We characterize the nonlinear optical properties of synthesized Bi2Te3 nanoparticle-contained thin films using the tunable femtosecond laser in the spectral range of 400–1000 nm. These nanoparticles possess a strong saturable absorption and positive nonlinear refraction (−6.8×10−5 cm W−1 in the case of 500 nm, 150 fs probe pulses, and 3×10−10 cm2 W−1 in the case of 400 nm, 150 fs probe pulses, respectively). The spectral, intensity, and temporal variation of saturable absorption and nonlinear refraction of the thin films containing exfoliated Bi2Te3 nanoparticles are discussed.
Substrate-wave-induced antireflection in metasurfaces
Authors: Ko Y. H. , Magnusson R.
Published: January 2022

We address the antireflection (AR) properties of periodic surfaces, or metasurfaces, supporting substrate waves. The work is motivated by recent literature where AR bands formed by substrate-wave propagation are incorrectly attributed to Mie scattering. In contrast, as clearly shown here, substrate-wave generation with corresponding AR signatures is a diffractive effect due to a periodic lattice and is not due to particle scattering as in Mie resonance. Treating both 1D and 2D surfaces, we demonstrate a clear quantitative connection between major AR loci and corresponding total substrate transmittance loci via maps in period versus wavelength. As shown, this holds for fully dispersed, lossy surfaces as well. The results presented here serve to elucidate the physical properties of periodic metasurfaces placed on substrates admitting propagating diffraction orders and may inform the design and implementation of grating-based AR structures.
Dynamic spectroscopic imaging ellipsometry
Authors: Kim Daesuk , Dembele Vamara , Choi Sukhyun , Hwang Gukhyeon , Kheiryzadehkhanghah Saeid , Joo Chulmin , Magnusson Robert
Published: January 2022

A dynamic spectroscopic imaging ellipsometer (DSIE) employing a monolithic polarizing interferometer is described. The proposed DSIE system can provide spatio-spectral ellipsometric phase map data Δ(λ, x) dynamically at a speed of 30 Hz. We demonstrate the ultrafast mapping capability of the spectroscopic ellipsometer by measuring a patterned 8-inch full wafer with a spatial resolution of less than 50 × 50 µm2 in an hour.
A noncanonical chaperone interacts with drug efflux pumps during their assembly into bacterial outer membranes
Authors: Stubenrauch Christopher J. , Bamert Rebecca S. , Wang Jiawei , Lithgow Trevor
Published: January 2022

Bacteria have membrane-spanning efflux pumps to secrete toxic compounds ranging from heavy metal ions to organic chemicals, including antibiotic drugs. The overall architecture of these efflux pumps is highly conserved: with an inner membrane energy-transducing subunit coupled via an adaptor protein to an outer membrane conduit subunit that enables toxic compounds to be expelled into the environment. Here, we map the distribution of efflux pumps across bacterial lineages to show these proteins are more widespread than previously recognised. Complex phylogenetics support the concept that gene cassettes encoding the subunits for these pumps are commonly acquired by horizontal gene transfer. Using TolC as a model protein, we demonstrate that assembly of conduit subunits into the outer membrane uses the chaperone TAM to physically organise the membrane-embedded staves of the conduit subunit of the efflux pump. The characteristics of this assembly pathway have impact for the acquisition of efflux pumps across bacterial species and for the development of new antimicrobial compounds that inhibit efflux pump function.
Higher-level phylogeny of Chrysomelidae based on expanded sampling of mitogenomes
Authors: Zhang Heng , Song Nan , Yin Xinming
Published: January 2022

Chrysomelidae is one of the most diverse lineages of beetles. The classification and phylogeny of Chrysomelidae have been contentious. In this study, we obtained 16 new mitogenome sequences by using next-generation sequencing. Combined with the published mitogenomes, we inferred the phylogenetic relationships of Chrysomelidae. Different data recoding strategies and substitution models were applied to phylogenetic reconstruction. In the Maximum likelihood analyses under the homogeneous model, Dayhoff recoding allowed for the improved phylogenetic resolution due to the decreased level of heterogeneous sequence divergence. Bayesian inference under the heterogeneous model yielded generally well resolved subfamily relationships. The present mitogenome data strongly supported Chrysomelidae as a monophyletic group. Consistent with previous work, we found three major subfamily clades within Chrysomelidae. However, the pattern of the “sagrine” clade plus the “eumolpine” clade being sister to the “chrysomeline” clade contrasted with the prior study. The placement of the genusSynetawith regards to these three clades was ambiguous. Relationships recovered suggested several major chrysomelid lineages, including: (1) Bruchinae in the “sagrine” clade; (2) Donaciinae + Criocerinae; (3) Spilopyrinae + (Cassidinae + (Eumolpinae + (Lamprosomatinae + Cryptocephalinae))); (4) Chrysomelinae + (Alticinae + Galerucinae). Results also suggested the placement ofTimarchaoutside the major Chrysomelinae.
Circlize package in R and Analytic Hierarchy Process (AHP): Contribution values of ABCDE and AGL6 genes in the context of floral organ development
Authors: Shen Gangxu , Wang Wei-Lung
Published: January 2022

The morphological diversity of floral organs can largely be attributed to functional divergence in the MADS-box gene family. Nonetheless, research based on the ABCDE model has yet to conclusively determine whether the AGAMOUS-LIKE 6 (AGL6) subgroup has a direct influence on floral organ development. In the current study, the ABCDE model was used to quantify the contributions of ABCDE and AGL6 genes in the emergence of floral organs. We determined that the flower formation contribution values of the ABCDE and AGL6 genes were as follows: A gene, 0.192; B gene, 0.231; CD gene, 0.192; E gene, 0.385; and AGL6, 0.077. As AGL6 does not directly influence floral structure formation, the contribution value of AGL6 to flower formation was low. Furthermore, the gradient values of the floral organs were as follows: sepals, 0.572; petals, 1.606; stamens, 2.409; and carpels, 2.288. We also performed detailed analysis of the ABCDE and AGL6 genes using the Circlize package in R. Our results suggest that these genes likely emerged in one of two orders: 1) B genes→CD genes→AGL6→E genes→A genes; or 2) B genes→CD genes→AGL6/E genes→A genes. We use the analytic hierarchy process (AHP) to prove the contribution values and gradient values of floral organs. This is the first study to understand the contribution values of ABCDE and AGL6 genes using the AHP and the Circlize package in R.
Molecular mechanism of inhibitory effects of melatonin on prostate cancer cell proliferation, migration and invasion
Authors: Nyamsambuu Altannavch , Khan Md. Asaduzzaman , Zhou Xi , Chen Han-Chun
Published: January 2022

The increasing incidence of prostate cancer (PCa) indicates an urgent need for the development of new effective drug therapy. There are limited options to treat the PCa, this study tried to determine a new therapy option for this acute cancer. Androgen-independent PCa cell lines PC3 and DU145 were treated with different melatonin concentrations (0.1~3.5 mM) for 1~3 days and assessed cell migration, cell invasion, cycle arrest in G0/G1 phase as well as apoptosis. We utilized RNA-seq technology to analyze the transcriptional misregulation pathways in DU145 prostate cancer cell line with melatonin (0.5 mM) treatment. Data revealed 20031 genes were up and down-regulated, there were 271 genes that differentially expressed: 97 up-regulated (P<0.05) and 174 down-regulated (P<0.05) genes. Furthermore, RNA-seq results manifested that the melatonin treatment led to a significant increase in the expression levels of HPGD, IL2Rβ, NGFR, however, IGFBP3 and IL6 (P <0.05) had decreased expression levels. The immunoblot assay revealed the expression of IL2Rβ and NGFR genes was up-regulated, qPCR confirmed the gene expression of HPGD and IL2RB were also up-regulated in Du145 cells. Consequently, we probed mechanisms that generate kinetic patterns of NF-κB-dependent gene expression in PCa cells responding to a NF-κB-activation, the significant results were indicated by the inhibition of the NF-kB pathway via IL2Rβ actions. Based on our investigation, it could be concluded that melatonin is a chemotherapeutic molecule against PCa and provides a new idea for clinical therapy of PCa.
Lives saved and lost in the first six month of the US COVID-19 pandemic: A retrospective cost-benefit analysis
Authors: Yakusheva Olga , van den Broek-Altenburg Eline , Brekke Gayle , Atherly Adam
Published: January 2022

In the beginning of the COVID-19 US epidemic in March 2020, sweeping lockdowns and other aggressive measures were put in place and retained in many states until end of August of 2020; the ensuing economic downturn has led many to question the wisdom of the early COVID-19 policy measures in the US. This study’s objective was to evaluate the cost and benefit of the US COVID-19-mitigating policy intervention during the first six month of the pandemic in terms of COVID-19 mortality potentially averted, versus mortality potentially attributable to the economic downturn. We conducted a synthesis-based retrospective cost-benefit analysis of the full complex of US federal, state, and local COVID-19-mitigating measures, including lockdowns and all other COVID-19-mitigating measures, against the counterfactual scenario involving no public health intervention. We derived parameter estimates from a rapid review and synthesis of recent epidemiologic studies and economic literature on regulation-attributable mortality. According to our estimates, the policy intervention saved 866,350–1,711,150 lives (4,886,214–9,650,886 quality-adjusted life-years), while mortality attributable to the economic downturn was 57,922–245,055 lives (2,093,811–8,858,444 life-years). We conclude that the number of lives saved by the spring-summer lockdowns and other COVID-19-mitigation was greater than the number of lives potentially lost due to the economic downturn. However, the net impact on quality-adjusted life expectancy is ambiguous.
Repercussions of the COVID-19 pandemic on health professionals in the state of Rio de Janeiro / Brazil
Authors: Camacho Karla Gonçalves , Gomes Junior Saint Clair dos Santos , Reis Adriana Teixeira , Junqueira-Marinho Maria de Fátima , França Luiz Carlos Moraes , Abramov Dimitri Marques , de Azevedo Zina Maria Almeida , Moreira Maria Elisabeth Lopes , de Vasconcelos Zilton Farias Meira , Salú Margarida dos Santos , da Silva Milene Lucio , Castro Barbara da Silveira Madeira de , Rodrigues Juliana Martins , Pereira Cláudia Dayube , Werner Junior Jairo , Bastos Junior Rossy Moreira , Caixeta Daniella Mancino da Luz , Moore Daniella Campelo Batalha Cox
Published: January 2022

Brazil has been severely affected by the COVID-19 pandemic. The high numbers of confirmed cases and deaths have continued unabated since the first reported case, with no flattening or downward turn in the curve. In this context, healthcare workers have been exposed uninterruptedly to stress factors throughout a year of the pandemic. The study´s aim was to identify and analyze healthcare workers´ perceptions of their feelings and concerns that have surfaced in responding to the pandemic. Method: This was a cross-sectional online qualitative survey study of 554 healthcare personnel working in the state of Rio de Janeiro during the COVID-19 pandemic. Recruitment occurred from July 20 to September 30, 2020, using an online survey, preceded byfree informed consent term. Data were analyzed with the Iramuteq software. Results: Through a dendrogram, the words with the highest chi-square were highlighted and grouped into four classes: healthcare workers´ fear of falling ill to COVID-19 and infecting their family members; work/labor issues; feelings of powerlessness and need for public policies for government action; and fatigue and burnout in the pandemic. Each word class was also illustrated by a similarity tree. Conclusion: The study revealed healthcare workers´ exacerbated fear of infection and transmission of COVID-19 to their family members, besides financial losses and feelings of powerlessness and abandonment.
Correlation coefficient local capping REMD adaptive filtering method for laser interference signal
Authors: Wu Junfeng , Chen Hanyu , Li Xu , Kang Guohua , Lu Yuangang
Published: January 2022

Considering the issue of noise reduction associated with Laser Doppler Interference (LDI) signal, the paper presented a correlation coefficient local capping robust empirical mode decomposition (REMD) filter algorithm for LDI laser sensor that enables more robust reconstruction of the displacement information from an LDI signal. The performance of the algorithm is studied, and it is shown that the algorithm is capable of removing high-frequency noise. Useful information can be extracted more easily by this method, and the Hilbert phase unwrapping displacement reconstructions method based on this algorithm has been experimentally validated. The experimental results show that the proposed method can improve the frequency separation performance in experiments, and is robust against noise interference.
Authors submission guidelines, a survey of pediatric dentistry journals regarding ethical issues
Authors: Walia Tarun , Kalra Gauri , Mathur Vijay Prakash , Dhillon Jatinder Kaur
Published: January 2022

Objective

To assess the pattern of instructions regarding the ethical requirements given to authors in various Pediatric Dental Journals.

Material & methods

A cross-sectional survey of ‘instructions for authors,’ for analysis of guidelines on ethical processes, was done. Instructions to authors in journals of pediatric dentistry across the globe were reviewed for guidelines with regards to fourteen key ethical issues. Descriptive statistics were used, and results were expressed in percentages as well as numbers.

Results

Of the 18journals of pediatric dentistry, all 14 ethical issues were covered by the instructions to authors in only three journals with only 50% of these providing clarity about authorship using ICMJE guidelines. Furthermore, COI declaration was found to be present as mandatory in about 44% of the journals. 38.9% of the sampled journals mentioned guidelines on research misconduct, publication issues such as plagiarism, overlapping/fragmented publications, and availability of raw research data from authors. Guidelines on handling of complaints about editorial team was provided to authors by slightly over 33% of the selected pediatric dentistry titles while handling of complaints about authors and reviewers were mentioned in 16.7%and 55.6% of the journals respectively.

Conclusion

A significant proportion of Journals of Pediatric Dentistry did not provide adequate instructions to authors regarding ethical issues.
Validation of a Computerized Adaptive Test Suicide Scale (CAT-SS) among United States Military Veterans
Authors: Brenner Lisa A. , Betthauser Lisa M. , Penzenik Molly , Bahraini Nazanin , Gibbons Robert D.
Published: January 2022

To validate the Computerized Adaptive Test Suicide Scale (CAT-SS), Veterans completed measures at baseline (n = 305), and 6- (n = 249), and 12-months (n = 185), including the CAT-SS (median items 11, duration of administration 107 seconds) and the Columbia-Suicide Severity Rating Scale (C-SSRS). Logistic regression was used to relate CAT-SS scores (baseline) to C-SSRS assessed outcomes (active ideation with plan and intent; attempt; interrupted, aborted or self-interrupted attempt, or preparatory acts or behaviors; all outcomes combined). A mixed-effects logistic regression model was used to evaluate the relationship between the lagged CAT-SS scores and outcomes (6- and 12-months). The baseline CAT-SS demonstrated predictive accuracy for all outcomes at 6-months, and similar results were found for baseline and all outcomes at and through 12-months. Longitudinal analysis revealed for every 10-point change in the CAT-SS there was a 50–77% increase in the likelihood of suicide-related outcomes. The CAT-SS demonstrated added value when compared to current suicide risk prediction practices.
A systematic review of artificial reefs as platforms for coral reef research and conservation
Authors: Higgins Emily , Metaxas Anna , Scheibling Robert E.
Published: January 2022

Artificial reefs (ARs) have been used on coral reefs for ecological research, conservation, and socio-cultural purposes since the 1980s. We examined spatio-temporal patterns in AR deployment in tropical and subtropical coral reefs (up to 35° latitude) and evaluated their efficacy in meeting conservation objectives, using a systematic review of the scientific literature. Most deployments (136 studies) were in the North Atlantic and Central Indo-Pacific in 1980s – 2000s, with a pronounced shift to the Western Indo-Pacific in 2010s. Use of ARs in reef restoration or stressor mitigation increased markedly in response to accelerating coral decline over the last 2 decades. Studies that evaluated success in meeting conservation objectives (n = 51) commonly reported increasing fish abundance (55%), enhancing habitat quantity (31%) or coral cover (27%), and conserving target species (24%). Other objectives included stressor mitigation (22%), provision of coral nursery habitat (14%) or source populations (2%) and addressing socio-cultural and economic values (16%). Fish (55% of studies) and coral (53%) were the most commonly monitored taxa. Success in achieving conservation objectives was reported in 33 studies. Success rates were highest for provision of nursery habitat and increasing coral cover (each 71%). Increasing fish abundance or habitat quantity, mitigating environmental impacts, and attaining socio-cultural objectives were moderately successful (60–64%); conservation of target species was the least successful (42%). Failure in achieving objectives commonly was attributed to poor AR design or disruption by large-scale bleaching events. The scale of ARs generally was too small (m2 –10s m2) to address regional losses in coral cover, and study duration too short (< 5 years) to adequately assess ecologically relevant trends in coral cover and community composition. ARs are mostly likely to aid in reef conservation and restoration by providing nursery habitat for target species or recruitment substrate for corals and other organisms. Promoting local socio-cultural values also has potential for regional or global impact by increasing awareness of coral reef decline, if prioritized and properly monitored.
Susceptibility to disease (tropical theileriosis) is associated with differential expression of host genes that possess motifs recognised by a pathogen DNA binding protein
Authors: Larcombe Stephen D. , Capewell Paul , Jensen Kirsty , Weir William , Kinnaird Jane , Glass Elizabeth J. , Shiels Brian R.
Published: January 2022

Background

Knowledge of factors that influence the outcome of infection are crucial for determining the risk of severe disease and requires the characterisation of pathogen-host interactions that have evolved to confer variable susceptibility to infection. Cattle infected by Theileria annulata show a wide range in disease severity. Native (Bos indicus) Sahiwal cattle are tolerant to infection, whereas exotic (Bos taurus) Holstein cattle are susceptible to acute disease.

Methodology/Principal findings

We used RNA-seq to assess whether Theileria infected cell lines from Sahiwal cattle display a different transcriptome profile compared to Holstein and screened for altered expression of parasite factors that could generate differences in host cell gene expression.

Significant differences (<0.1 FDR) in the expression level of a large number (2211) of bovine genes were identified, with enrichment of genes associated with Type I IFN, cholesterol biosynthesis, oncogenesis and parasite infection. A screen for parasite factors found limited evidence for differential expression. However, the number and location of DNA motifs bound by the TashAT2 factor (TA20095) were found to differ between the genomes of B. indicus vs. B. taurus, and divergent motif patterns were identified in infection-associated genes differentially expressed between Sahiwal and Holstein infected cells.

Conclusions/Significance

We conclude that divergent pathogen-host molecular interactions that influence chromatin architecture of the infected cell are a major determinant in the generation of gene expression differences linked to disease susceptibility.
Establishing a comprehensive list of mental health-related services and resource use items in Austria: A national-level, cross-sectoral country report for the PECUNIA project
Authors: Fischer Claudia , Mayer Susanne , Perić Nataša , Simon Judit ,   on behalf of the PECUNIA Group
Published: January 2022

Background

A comprehensive, comparable assessment of the economic disease burden and the value of relevant care forms a major challenge in the case of mental diseases. This study aimed to inform the development of a resource use measurement (RUM) instrument and harmonized reference unit costs valid for multi-sectoral and multi-national cost assessments for mental health diseases as part of the European PECUNIA project.

Methods

An iterative, multi-methods approach was applied. Systematic literature reviews appended with national grey literature searches in six European countries were conducted to generate preliminary, literature-based, international, mental health-related service and resource use lists for all investigated sectors in 2018. As part of a multi-national expert survey, these lists were reviewed by 18 Austrian sector-specific experts regarding the clarity, relevance, comprehensiveness and availability in the Austrian context.

Results

Out of 295 items included in the preliminary, international, sector-specific lists (health and social care—201 items, criminal justice—35 items, education—39 items; patient, family and informal care—20 items), a total of 261 items and descriptions (88%) were considered clear by all experts. 42 items (14%) were considered not existing in Austria, and 111 items (38%) were prioritized regarding their relevance in the national context. Thirteen additional items (4%) were suggested to be added to accommodate for Austria-specific features of the individual sectors. Major typological difficulties based on item names were observed.

Conclusions

The identified country-specific variations and general typological bias and their potential contributions to service and resource use cost variations across countries and sectors call for further systematic investigation. Next, PECUNIA will develop internationally harmonized and comparable definitions of the listed items and their units of analysis based on a new conceptual multi-sectoral costing framework. The developed lists will require consolidation and further prioritization for the development of a patient-reported RUM instrument and consequent reference unit cost valuation.