bluuebunny/crossref_metadata_2025_split huggingface dataset:
Head-to-head comparison of composite and individual biomarkers to predict clinical benefit to PD-1 blockade in non-small cell lung cancer
Authors: Hummelink Karlijn , van der Noort Vincent , Muller Mirte , Schouten Robert D. , van den Heuvel Michel M. , Thommen Daniela S. , Smit Egbert F. , Meijer Gerrit A. , Monkhorst Kim 
Published: July 2024

Background
The efficacy of PD-1 blocking agents in advanced NSCLC has shown prolonged effectiveness, but only in a minority of patients. Multiple biomarkers have been explored to predict treatment benefit, yet their combined performance remains inadequately examined. In this study, we assessed the combined predictive performance of multiple biomarkers in NSCLC patients treated with nivolumab.

Methods
Pretreatment samples from 135 patients receiving nivolumab were used to evaluate the predictive performance of CD8 tumor-infiltrating lymphocytes (TILs), intratumoral (IT) localization of CD8 TILs, PD-1 high expressing TILs (PD1T TILs), CD3 TILs, CD20 B-cells, tertiary lymphoid structures (TLS), PD-L1 tumor proportion score (TPS) and the Tumor Inflammation score (TIS). Patients were randomly assigned to a training (n = 55) and validation cohort (n = 80). The primary outcome measure was Disease Control at 6 months (DC 6m) and the secondary outcome measure was DC at 12 months (DC 12m).

Results
In the validation cohort, the two best performing composite biomarkers (i.e. CD8+IT-CD8 and CD3+IT-CD8) demonstrated similar or lower sensitivity (64% and 83%) and NPV (76% and 85%) compared to individual biomarkers PD-1T TILs and TIS (sensitivity: 72% and 83%, NPV: 86% and 84%) for DC 6m, respectively. Additionally, at 12 months, both selected composite biomarkers (CD8+IT-CD8 and CD8+TIS) demonstrated inferior predictive performance compared to PD-1T TILs and TIS alone. PD-1T TILs and TIS showed high sensitivity (86% and 100%) and NPV (95% and 100%) for DC 12m. PD-1T TILs could more accurately discriminate patients with no long-term benefit, as specificity was substantially higher compared to TIS (74% versus 39%).

Conclusion
Composite biomarkers did not show improved predictive performance compared to PD-1T TILs and TIS alone for both the 6- and 12-month endpoints. PD-1T TILs and TIS identified patients with DC 12m with high sensitivity. Patients with no long-term benefit to PD-1 blockade were most accurately identified by PD-1T TILs.
Bridging the divide: addressing discrepancies between clinical guidelines, policy guidelines, and biomarker utilization
Authors: Horgan Denis , Hofman Paul , Buttner Reinhard , Rieß Olaf , Lugowska Iwona , Dube France , Singh Jaya , Nadal Ernest , Stokłosa Tomasz , Sīviņa Elīna , Van der Buckle Marc , Mosoiu Silvia , Bertolaccini Luca , Girard Nicolas , Meerbeeck Jan Van , Omar Imran , Capoluongo Ettore D. , Bielack Stefan , Hills Tanya , Baldwin David , Subbiah Vivek 
Published: July 2024

Abstract

Objectives
This paper aims to identify and address gaps in cancer treatment and diagnosis within European health services, focusing specifically on discrepancies between clinical guidelines and policy guidelines. It seeks to highlight how the underutilization of advanced diagnostic techniques recommended by medical societies contributes to missed opportunities for improving patient outcomes.

Methods
A comprehensive analysis was conducted across multiple European countries to assess the compliance and integration of clinical guidelines with the availability of advanced diagnostic technologies. Secondary data related to clinical and policy guidelines in cancer care were collected and analyzed. Key indicators of adoption and utilization of next-generation sequencing and liquid biopsy were examined to evaluate their impact on health service efficiency and patient care.

Results
The analysis revealed significant discrepancies between the recommendations of medical societies regarding advanced diagnostic techniques and their adoption in health policy decisions across Europe. Country-specific assessments indicated varying levels of alignment between clinical guidelines and the availability of advanced diagnostics. These findings underscored missed opportunities for optimizing patient care and health service efficiency through better alignment and integration of clinical guidelines with policy decisions.

Conclusions
This study concludes that there is a critical need for health policy decision-makers to prioritize the adoption of clinical guidelines in resource allocation and health service organization. Greater attention to the recommendations of medical societies regarding advanced diagnostic techniques could significantly enhance diagnostic accuracy, treatment efficacy, and overall patient outcomes in cancer care. The paper advocates for policy reforms that acknowledge and leverage the potential benefits of advanced diagnostics in improving health service performance and patient-centered care across Europe.
Why Did Plato not Write the ‘Unwritten Doctrine’? Some Preliminary Remarks
Authors: Ferber Rafael 
Published: July 2024

Abstract
This article asks the question “Why did Plato not write the ‘unwritten doctrine’?” and answers it by citing a combination of two obstacles. The first derives from the limitations of the episteme available to an embodied soul about the essence of the good. Even if the dialectician has access to some kind of knowledge, the mismatch between the unchanging essence of the good and the precarious logoi which aim to identify it (and allow others some measure of access to it) can never fully be overcome. At best, Socrates (or Plato) can lead souls to an incomplete account of it: It is possible that even the most expert dialectician can only have a claim to knowledge, but no absolute certainty. Another obstacle lies in the audience or readership itself: No shortcut to understanding is possible, and yet a mere written presentation, which is all they have, is just such a shortcut, and so represents an empty promise. In memory of Charles H. Kahn (1928–2023), a letter of his from September 5, 1989, concerning the question “Why did Plato not write the ‘unwritten doctrine’?” is published, along with some comments.
Nachweis der Varietätenkette anhand historischer Patientenbriefe
Authors: Schiegg Markus 
Published: July 2024

Zusammenfassung
Die Varietätenkette bildet ein zentrales Konzept der Varietätenlinguistik und modelliert gerichtete Affinitäten zwischen den drei Varietätendimensionen der Diatopik, Diastratik und Diaphasik. Diese weisen jeweils eine interne Skalierung auf, deren Abstufungen in gerichteter Beziehung zueinander stehen und dabei auch am konzeptionellen Kontinuum der Nähe- und Distanzsprachlichkeit ‚hängen‘ (vgl. Koch & Oesterreicher 1994: 595). Die Varietätenkette wurde weitgehend intuitiv postuliert, allerdings nie an einem größeren Sprachkorpus empirisch überprüft. Dieser Beitrag belegt an einem Korpus von 191 süddeutschen Briefen des 19. und frühen 20. Jahrhunderts, geschrieben von Patientinnen und Patienten der psychiatrischen Anstalt Kaufbeuren-Irsee, die klaren Zusammenhänge zwischen den Varietätendimensionen sowie Nähe- und Distanzsprachlichkeit.
Simulative analysis of carrier suppressed return to zero based symmetrical compensated optical link
Authors: Singh Manjit , Sarangal Himali , Singh Butta , Kour Satveer , Kaur Pawandeep 
Published: July 2024

Abstract
Optical communication systems provide high data rates to fulfil users’ demands. In addition, the modulation format is essential to the system’s transmission quality and spectral efficiency. Furthermore, the effects of chromatic dispersion, which impair the performance and quality of transmitted signals, are mitigated using dispersion compensation techniques. In optical communication systems, dispersion compensation techniques are essential for preserving signal quality, increasing transmission distances, improving system performance, and offering network designers flexibility. These methods seek to improve signal quality and enable transmission at longer distances by reducing or eliminating the distortion brought on by dispersion. This paper uses a symmetrical compensation technique to analyze the performance of the CSRZ modulation format-based optical communication system. The research is conducted within a communication range of 150–350 km. The system is evaluated in terms of input power, filter order, and filter depth. The results indicate that the proposed system performed better at an input power of 4 dBm using a third-order filter and 60 dB filter depth.
Evaluating the effectiveness of various diversity and combining techniques on an RF-FSO link
Authors: Joshi Hardik , Gupta Shilpi 
Published: July 2024

Abstract
Diversity and combining is one of the robust techniques to mitigate multi-path fading in RF links and turbulence-induced scintillation in FSO links. This article evaluates the effect of different diversity and combining techniques on outage and BER performance of decode and forward RF-FSO link. We have utilized diversity and combining techniques over source to relay RF link and/or relay to destination FSO link. The selection combining, transmit antenna selection, maximal ratio combining, and maximum ratio transmission schemes are considered. The Monte-Carlo simulation results of outage probability and bit error rate are compared by considering different parameters affecting link quality like the strength of atmospheric turbulence, pointing error, FSO link detection scheme, RF link fading strength, diversity order, etc. It is found that configurations like SIMO-SISO, MISO-SISO, SISO-SIMO, and SISO-MISO, where diversity is applied in either source to relay link or relay to destination link, are improving the overall link performance provided that diversity is applied at the link experiencing stronger fading compared to another link. The link configurations SIMO-MISO or MISO-SIMO also improve the link performance and it can achieve BER of 10−5 at less than 15 dB SNR in favourable link conditions.
A combination of DST precoder and ICF based-methods for PAPR suppression in OFDM signal
Authors: Yadav Ajay Kumar 
Published: July 2024

Abstract
One well-known demerit of orthogonal frequency division multiplexing (OFDM) is its high peak-to-average power ratio (PAPR) which limits the efficiency of high-power amplifier (HPA) and also destroys its bit error rate (BER) performance. Hence, a method based on grouping of discrete sine transform (DST) precoder and iterative clipping and filtering (ICF) is proposed to reduce PAPR in this article. The DST precoder reduces PAPR to certain level by changing phase of the signal. Moreover, the ICF technique is also implemented in DST based-OFDM signal for additional minimization of PAPR. Therefore, the proposed method (DST-ICF) preserves BER performance also from other existing methods. At complementary cumulative distribution function (CCDF) = 10−3, the simulation results indicate the proposed technique that minimizes PAPR with iteration values (I = 1, I = 2, and I = 3) to 6.37 dB, 5.29 dB, and 4.81 dB respectively. Moreover, at same BER, the E

b
/N
0 of proposed technique with iteration value (I = 3) is achieved by 9.75 dB for quadrature phase shift keying (QPSK).
“Silence is the best answer for a bully”: an exploration of humour techniques in selected Nigerian newspaper political cartoons
Authors: Osisanwo Ayo , Atoloye Lekan 
Published: July 2024

Abstract
Newspaper political cartoons, known for their satirical nature, employ semiotic and linguistic techniques to comment on or criticise political leaders and events humorously. While previous studies on Nigerian newspaper political cartoons have focused on ideological issues and discourse frames, little attention has been given to the linguistic investigation of semiotic humour techniques in these cartoons. This study, therefore, investigates these humour techniques, utilising Salvatore Attardo and Victor Raskin’s General Theory of Verbal Humour (GTVH) as the framework within a descriptive design. Three newspapers – Punch, The Guardian, and Daily Trust – were purposively selected for their regular publication of cartoons, criticising Nigeria’s politics. Eleven political cartoons were purposively selected for their semiotic and humorous depictions of Nigeria’s politics, and subjected to linguistic analysis. Six semiotic humour techniques were identified in the cartoons: exaggeration, humorous metaphor, distortion of formulaic expressions, neologism, innovative collocation, and sarcasm. These techniques were employed to satirise three governance issues in Nigeria – misgovernance, corruption and insecurity.
Asymmetric dumbbell dimers simultaneously supporting quasi-bound states in continuum and anapole modes for terahertz biosensing
Authors: Feng Jixin , Wang Xianghui , Shi Weinan , Ma Liang , Ji Yunyun , Fan Fei , Chang Shengjiang 
Published: July 2024

Abstract
Multi-resonant metasurfaces are of great significance in the applications of multi-band nanophotonics. Here, we propose a novel metasurface design scheme for simultaneously supporting quasi-bound states in continuum (QBIC) and other resonant modes, in which QBIC resonance is generated by mirror or rotational symmetry breaking in oligomers while other resonant modes can be simultaneously excited by rationally designing the shapes of meta-atoms within oligomers. As an example, the simultaneous excitation of QBIC and anapole modes are demonstrated in a dimer metasurface composed of asymmetric dumbbell-shaped apertures. Based on the far-field multipole decomposition and near-field electromagnetic field distributions, the origin mechanisms of QBIC and anapole mode are elucidated. The symmetry breaking of dumbbell-shaped dimer results in QBIC. Within a certain asymmetric variation range, the contributions of toroidal dipole moment and electric dipole moment with approximately equal magnitudes remain dominant, which allows the anapole mode to always present. The effectiveness of the proposed design scheme is further confirmed by the experimental results identical with the evolutions of numerical simulation. In terahertz biosensing experiments, the anapole mode exhibits a higher sensitivity of 271.3 GHz (nmol/μl)−1, whereas the QBIC can achieve a lower detection limit of 0.015 nmol/μl and expands the detection range by almost an order of magnitude. Our findings are beneficial to designing multi-resonant metasurfaces with different resonance modes and promote the corresponding applications in the fields of biosensing, lasers, filtering, and nonlinearity.
Analytical investigation of convective phenomena with nonlinearity characteristics in nanostratified liquid film above an inclined extended sheet
Authors: Yasmin Humaira 
Published: July 2024

Abstract
This work focuses on the time-variant convective thin-film nanoliquid fluid flow and heat transfer over a stretching, inclined surface under the effect of magnetism for different energy technologies for sustainability. It is crucial to understand how solid materials can be treated with thin films while focusing on the actual ability to improve the body surface features for infiltration, shock resistance, rigidness, brightness, dispersal, absorption, or electrical efficiency. All of these improvements are invaluable, especially in the field of nanotechnology. As with any mass and thermal transport phenomena, the study breaks down important factors such as thermophoresis and Brownian movement, in an attempt to improve the energetic balance and lessen fuel consumption. Utilizing the mathematical model of the temporal evolution on the liquid film flow characteristics over an inclined surface, we obtain a system of nonlinear partial differential equations and convert it to a system of coupled ordinary differential equations appropriately. Finally, the results of the model problem computational analysis are produced using the Laplace Adomian decomposition method (LADM) and are shown both quantitatively and visually. During the flow analysis, the impact of specific flow parameters such as the magnetic, Brownian, and thermophoresis parameters are examined and found to be highly significant. Furthermore, it is found that the effects of (

M

M

) and (Nt) factors on (

F

F

), (

Φ

\Phi

), and (

ϕ

\phi

) lead to decreased conduction. Conversely, the thermal gradient within the liquid films rises in proportion to the (Nb) factor. This research is distinguished from similar attempts made in the past in terms of thin-film nanoliquid flow from inclined planes and application of LADM approach toward modeling. The findings have provided tangible use in coming up with new methods of cooling electronics gadgets, energy harvesting for solar energy, and eco-friendly industrial processes.
Method development for multielement determination of halogens and sulfur in teas
Authors: Mesko Marcia F. , Costa Larissa C. A. , Cerqueira Jenifer H. , Balbinot Fernanda P. , Rondan Filipe S. 
Published: July 2024

Abstract
Microwave-induced combustion was evaluated as a sample preparation method for several types of tea (black, green, lemon balm, boldo, and mint) for further determination of bromine, chlorine, fluorine, iodine, and sulfur by ion chromatography. Parameters such as the sample mass efficiently decomposed and the most suitable absorbing solution (ultrapure water and 25, 50, 100, and 150 mmol L−1 NH4OH) were evaluated, considering the characteristics of the analytes and the determination technique used. The maximum sample mass possible to be decomposed was 900 mg of milled tea in the form of pellets, and the absorbing solution chosen was 100 mmol L−1 NH4OH, which provided suitable stabilization of the analytes (recoveries between 95 % and 103 %). To assess the accuracy of the proposed method, a certified reference material (BCR 060, aquatic plant) was analyzed. Agreements with the certified values ranged from 101 % to 107 %. The proposed method was used to analyze tea samples and the concentrations ranged from 549 to 2,549 mg kg−1 for chlorine, 223 to 828 mg kg−1 for fluorine, and 786 to 4,023 mg kg−1 for sulfur; bromine and iodine concentrations were below the limits of quantification (42 and 80 mg kg−1, respectively) in all evaluated samples.
Erprobung einer miniaturisierten Infrarotspektroskopie zur Messung von Alterungseffekten in Öl
Authors: Uebel Julian , Stiemcke Yvo , Huber Maximilian E. , Rheinländer Carl , Thielen Stefan , Koch Oliver , Wehn Norbert , Seewig Jörg 
Published: July 2024

Kurzfassung
In diesem Artikel wird ein Ansatz zur Ölzustandsüberwachung mit dem Ziel vorgestellt, in Zukunft Veränderungen in den Eigenschaften von Schmierölen zu messen. Die Messung ermöglicht eine automatisierte Überwachung des Schmierstoffs und es können somit Maßnahmen der prädiktiven Instanthaltung eingeleitet und Beschädigungen der Maschinen vermieden werden. Um eine möglichst breite Masse an unterschiedlichen Maschinen mit Ölschmierung und auch Bestandsmaschinen überwachen zu können, soll die Sensorik in einen handelsüblichen Radialwellendichtring (RWDR) integrierbar sein. Zur Messung der Alterungseffekte wird eine Kombination aus Infrarot-(IR-)LED und -Fotodiode eingesetzt. In dieser ersten Iterationsstufe wird die Sensorik so ausgelegt, dass eine Sensitivität bezüglich des Rußgehalts im Öl besteht. Mit dem Aufbau ist es bei niedrigen Rußkonzentrationen möglich den Rußgehalt mit einer mittleren Messabweichung von 0,0026 Ma-% zu ermitteln. Vorgestellt werden die ersten Messergebnisse und Berechnungen der Rußkonzentration in Schmierstoffproben, sowie der Messaufbau und die Modellierung des Sensorverhaltens.
Reproductive Ageing: Declining translational capacity as a potential driver for oocyte meiotic instability
Authors: Danielson Katie J , Judson Kayla L , Greenblatt Ethan J 
Published: July 2024

In Brief
This point of view article focuses on the potential contribution of defects in protein synthesis (translation) to the incidence of oocyte meiotic failure. We discuss the potential cause of diminished oocyte translation during aging and the impact of these deficits on the function of the meiotic spindle.

Abstract
Errors during female meiosis lead to embryonic aneuploidy and miscarriage and occur with increasing frequency during aging. The underlying molecular changes that drive female meiotic instability remain a subject of debate. Developing oocytes undergo a tremendous increase in cytoplasmic volume over several months of follicle development and rely on long-lived mRNAs and ribosomes accumulated during this growth phase for subsequent meiotic maturation. In this point of view article, we discuss how the unique reliance on stores of long-lived mRNAs and ribosomes may represent an Achilles' heel for oocyte function and how alterations that reduce the translational capacity of oocytes could be a factor significantly contributing to female infertility. Understanding these mechanisms could lead to new therapeutic strategies to improve fertility outcomes.
Variability of the groundwater regime on the background of сhanges in snow storage (by the example of the Prioksko-Terrasny Reserve)
Authors: Китаев Л.М. , Аблеева В.А. 
Published: July 2024

На основе данных экспериментальных наблюдений 1999–2021 гг. на примере характерных участков Приокско-Террасного заповедника уточнена степень влияния снегонакопления на динамику глубины залегания уровней грунтовых вод c учетом изменчивости приземной температуры воздуха и осадков. Проведена оценка пространственной неоднородности сезонных и многолетних изменений метеорологических характеристик и глубины залегания уровня грунтовых вод. Регрессионный анализ показал наличие значимого влияния снегозапасов на многолетнюю динамику глубины залегания грунтовых вод как в снежный период (декабрь–апрель), так и во время их максимального подъема (май–июль) – при малой значимости влияния приземной температуры воздуха холодного периода, продолжительности оттепелей и их суммы положительных температур. Полученные закономерности могут быть использованы для уточнения особенностей региональных процессов водообмена и модельных алгоритмов соответствующего направления исследований.
Based on observation data on typical areas of the Prioksko-Terrasny Reserve for 1999–2021, the influence of snow accumulation on the dynamics of the groundwater level was clarified with due account for the variability in air temperature and precipitation. An assessment of the spatial heterogeneity of seasonal and long-term variability in meteorological characteristics and the groundwater level was made. A regression analysis demonstrated that the snow storage has a significant influence on the long-term dynamics of the groundwater level during both the snowy season (December–April) and the maximum rise of the groundwater level (May–July). The effects of the air temperature of the cold season, duration of thaws, and the accumulated positive air temperatures during them on the groundwater level were statistically insignificant. The obtained conclusions complement the results of studies of the relationship between the variability of snow cover characteristics and the depth of groundwater under the conditions of modern meteorological regime and can be used to specify regional features of water exchange processes.
A kutatásalapú tanulás helye a felsőoktatásban: kiváltság vagy a bevonás eszköze
Authors: Sass Judit Gabriella 
Published: July 2024

A tanulmány a 21. századi készségigényekre reflektálni tudó, kutatásalapú tanulás
hazai felsőoktatási tapasztalatait vizsgálja a nem természettudományi
oktatásban. Áttekinti a kutatásalapú tanulás fogalmát, valamint néhány példát a
gyakorlatból. Bemutatja a kapcsolódó alapkérdéseket (irányítás helye, kutatás
szerepe) és az alkalmazás feltételeit.
A vizsgálat a kutatásalapú tanulás alkalmazásának céljait és akadályait tárja fel
módszertani központvezetők és oktatók tematikus interjúival. Az interjúk
tartalomelemzése alapján felvázolhatók a „kutatásalapú tanulás” értelmezései:
kutatási folyamat- és tehetséggondozás-hangsúly, a kommunikációs készségek
fejlesztendő területei és az intézményi támogatás lehetséges beavatkozási
pontjai.