bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple Dietary Antioxidants Enhance the Efficacy of Standard and Experimental Cancer Therapies and Decrease Their Toxicity
Authors: Prasad Kedar N.
Published: November 2004

Cancer patients can be divided into 3 groups: those receiving standard or experimental therapy, those who have become unresponsive to these therapies, and those in remission at risk for recurrence or a second new cancer. While impressive progress in standard cancer therapy has been made, the value of this therapy in the management of solid tumors may have reached a plateau. At present, there is no strategy to reduce the risk of recurrence of the primary tumors or of a second cancer among survivors. Patients unresponsive to standard or experimental therapies have little option except for poor quality of life for the remainder of life. Therefore, additional approaches should be developed to improve the efficacy of current management of cancer. In this review, the author proposes that an active nutritional protocol that includes high doses of multiple dietary antioxidants and their derivatives (vitamin C, α-tocopheryl succinate, and natural β-carotene), but not endogenously made antioxidants (glutathione- and antioxidant enzyme-elevating agents), when administered as an adjunct to radiation therapy, chemotherapy, or experimental therapy, may improve its efficacy by increasing tumor response and decreasing toxicity. This nutritional protocol can also be used when patients become unresponsive to standard therapy or experimental therapy to improve quality of life and possibly increase the survival time. The authors also propose that after completion of standard therapy and/or experimental therapy, a maintenance nutritional protocol that contains lower doses of antioxidants and their derivatives, together with modification in diet and lifestyle, may reduce the risk of recurrence of the original tumor and development of a second cancer among survivors. Experimental data and limited human studies suggest that use of these nutritional approaches may improve oncologic outcomes and decrease toxicity. This review also discusses the reasons for the current debates regarding the use of antioxidants during radiation or chemotherapy.
SS-Wrapper: a package of wrapper applications for similarity searches on Linux clusters
Authors: Wang Chunlin , Lefkowitz Elliot J
Published: November 2004

Background

Large-scale sequence comparison is a powerful tool for biological inference in modern molecular biology. Comparing new sequences to those in annotated databases is a useful source of functional and structural information about these sequences. Using software such as the basic local alignment search tool (BLAST) or HMMPFAM to identify statistically significant matches between newly sequenced segments of genetic material and those in databases is an important task for most molecular biologists. Searching algorithms are intrinsically slow and data-intensive, especially in light of the rapid growth of biological sequence databases due to the emergence of high throughput DNA sequencing techniques. Thus, traditional bioinformatics tools are impractical on PCs and even on dedicated UNIX servers. To take advantage of larger databases and more reliable methods, high performance computation becomes necessary.

Results

We describe the implementation of SS-Wrapper (Similarity Search Wrapper), a package of wrapper applications that can parallelize similarity search applications on a Linux cluster. Our wrapper utilizes a query segmentation-search (QS-search) approach to parallelize sequence database search applications. It takes into consideration load balancing between each node on the cluster to maximize resource usage. QS-search is designed to wrap many different search tools, such as BLAST and HMMPFAM using the same interface. This implementation does not alter the original program, so newly obtained programs and program updates should be accommodated easily. Benchmark experiments using QS-search to optimize BLAST and HMMPFAM showed that QS-search accelerated the performance of these programs almost linearly in proportion to the number of CPUs used. We have also implemented a wrapper that utilizes a database segmentation approach (DS-BLAST) that provides a complementary solution for BLAST searches when the database is too large to fit into the memory of a single node.

Conclusions

Used together, QS-search and DS-BLAST provide a flexible solution to adapt sequential similarity searching applications in high performance computing environments. Their ease of use and their ability to wrap a variety of database search programs provide an analytical architecture to assist both the seasoned bioinformaticist and the wet-bench biologist.
Traumatic-event headaches
Authors: Haas David C
Published: November 2004

Background

Chronic headaches from head trauma and whiplash injury are well-known and common, but chronic headaches from other sorts of physical traumas are not recognized.

Methods

Specific information was obtained from the medical records of 15 consecutive patients with chronic headaches related to physically injurious traumatic events that did not include either head trauma or whiplash injury. The events and the physical injuries produced by them were noted. The headaches' development, characteristics, duration, frequency, and accompaniments were recorded, as were the patients' use of pain-alleviative drugs. From this latter information, the headaches were classified by the diagnostic criteria of the International Headache Society as though they were naturally-occurring headaches. The presence of other post-traumatic symptoms and litigation were also recorded.

Results

The intervals between the events and the onset of the headaches resembled those between head traumas or whiplash injuries and their subsequent headaches. The headaches themselves were, as a group, similar to those after head trauma and whiplash injury. Thirteen of the patients had chronic tension-type headache, two had migraine. The sustained bodily injuries were trivial or unidentifiable in nine patients. Fabrication of symptoms for financial remuneration was not evident in these patients of whom seven were not even seeking payments of any kind.

Conclusions

This study suggests that these hitherto unrecognized post-traumatic headaches constitute a class of headaches characterized by a relation to traumatic events affecting the body but not including head or whiplash traumas. The bodily injuries per se can be discounted as the cause of the headaches. So can fabrication of symptoms for financial remuneration. Altered mental states, not systematically evaluated here, were a possible cause of the headaches. The overall resemblance of these headaches to the headaches after head or whiplash traumas implies that these latter two headache types may likewise not be products of structural injuries.
Grouping of tooth surfaces by susceptibility to caries: a study in 5–16 year-old children
Authors: Batchelor Paul A , Sheiham Aubrey
Published: November 2004

Background

The decline in caries has slowed and this may be indicative of variation in the susceptibility of differing teeth to caries. This study tests the hypothesis that in children, there are groups of tooth sites that exhibit differences in caries susceptibility.

Methods

Probit analysis of caries data collected from a 4-year longitudinal study of 20,000 schoolchildren aged between 5 and 16 years in 10 differing locations in the United States.

Results

The development of dental caries within the mouth followed a fixed hierarchy indicating that tooth surfaces show variation in caries susceptibility. Certain teeth and tooth sites have similar susceptibilities and can be grouped, the sizes of the groups vary. The most susceptible group consists of six tooth surfaces: the buccal pits and occlusal fissured surfaces of the first molar teeth. The second group consisted of 12 sites on the second molar and premolar teeth. The group formed by the least susceptible sites included the largest number of tooth surfaces and consists of the majority of the lower anterior teeth and canines.

Conclusion

Variation in the caries susceptibility of tooth surfaces exists. Surfaces can be grouped according to caries susceptibility. An effect that reduces the cariogenic challenge of one of the sites within a group is likely to affect all the other sites within the particular group.
Within you, without you: HIV-1 Rev and RNA export
Authors: Dayton Andrew I
Published: November 2004

Nucleo-cytoplasmic transport of RNA is one of many cellular pathways whose illumination has progressed hand in hand with understanding of retroviral mechanisms. A recent paper in Cell reports the involvement of an RNA helicase in the pathway by which HIV exports partially spliced and unspliced RNA out of the nucleus. This suggests the ubiquity of RNA helicases in RNA export from the nucleus, and has novel mechanistic implications.
Immunity & Ageing: a new journal looking at ageing from an immunological point of view
Authors: Vasto Sonya , Caruso Calogero
Published: November 2004

In the elderly, many alterations of both innate and clonotypic immunity have been described. Alterations to the immune system in the elderly are generally viewed as a deterioration of immunity, leading to the use of the term immunosenescence. However, although many immunological parameters are often notably reduced in the elderly, retained function of both innate and clonotypic immunity in the elderly is tightly correlated to health status. Recognising the important role of the immune system in ageing, over the last few years, journals oriented towards gerontology and geriatric sciences have increasingly published articles dealing with the immunology of ageing, but a specialised journal in this area does not exist. Immunity & Ageing is a new Open Access, peer reviewed journal that aims to cover all the topics dealing with innate and clonotypic immunity which are relevant to ageing. The journal will provide an opportunity to focus on this topic, which is emerging as one of the critical mechanisms of ageing. Furthermore, as an online, Open Access journal, Immunity & Ageing will promote immediate accessibility to research, which is generally not possible for articles published in printed journals. We hope this forum, concentrating on the themes of ageing and immunology with a strong focus on human studies, will create a new perspective for viewing a world that is inevitably becoming older.
Americanisation and anti-Americanism at the periphery. Nicaragua and the Sandinistas
Authors: Ryan David
Published: November 2004

Anti-Americanism in Nicaragua arose from a dialectical relationship between US power and influence and opposition to it. The expressions of anti-Americanism were directed against American power and intervention and not towards some of the shared values such as liberty, self-determination
and democracy. The Sandinista revolution was largely successful because it coalessed around a ‘coalition of revulsion’ against the US client regime. It resisted both the US economic presence and its overbearing culture, attitudes, diplomacy and disproportionate influence. North
Americans were widely regarded as the champions of democracy, liberty and self-determination. When those narratives did not accord with the experience of those who encountered US power, and when that power was perceived as creating economic dependencies or supporting political authoritarianism
it fermented strong resentment. US attitudes further polarised the situation, giving rise to an identity politics based on caricature, exclusion, fundamental essences and intolerance.
Uniting a divided nation: Americanism and anti-Americanism in post-war Germany
Authors: Ickstadt Heinz
Published: November 2004

In the context of the Iraq war, ‘Anti-Americanism’ has become a European fact but also an instrument of political controversy, part of a simplifying argument of either/or. The essay probes into the various implications of European ‘Anti- Americanism’ and then
concentrates on German cultural history where the influence of American culture (‘Americanization’), after both wars, was fought by cultural nationalists on the right as well as on the left but was also embraced by those who wanted to break up rigid social and cultural structures
in the name of innovation and democracy. Resentment and ambivalence run deep but should not hide a basis of shared values as well as the new global fact of a mutual dependency which makes multilateralism a necessity.
Layers of anti-Americanism: Americanization, American unilateralism and anti-Americanism in a European perspective
Authors: Fabbrini Sergio
Published: November 2004

The American invasion of Iraq in the spring of 2003 brought to the surface of public debate among European elites a robust anti-Americanism. The reaction to US unilateralism has been nourished by a complex of fears. Two in particular. The first fear has to do with the presumed economic
and cultural Americanization of Europe. The second fear with the Americanization of the European political process. Both fears seem unjustified to a closer logical and empirical scrutiny. However, the overwhelming global power acquired by the US in the post Cold War era, and the unilateral
exercise of that power especially after September 11, 2001, fed the anti-American sentiment contributing to its most militant manifestation. Although anti-Americanism is deeply rooted in European political cultures and experiences, nevertheless its re-emergence has been greatly triggered by
American foreign policy strategy.
Under America’s sign: two nineteenthcentury British readings
Authors: Epstein James
Published: November 2004

Rather than emphasizing British anti-Americanism during the nineteenth century, ‘Under America’s sign: two nineteenth-century British readings’ examines the ways in which British attitudes to America and its culture reflect ambivalence about Britain’s own place
in the modern world. In order to illustrate how British identities were shaped in exchanges with America, the article concentrates on two texts: Charles Dickens’s American Notes for General Circulation (1842) and Charles Wentworth Dilke’s Greater Britain (1868). ‘America’
is thus seen as a space marked not by ‘otherness’ or sheer difference, but by the differences of proximity, in-between-ness, or kinship.
The current management of cervical cancer
Authors: Abu Jafaru I , Nunns David , Davies Quentin , Ireland David
Published: November 2004

Cervical cancer is a common cause of death worldwide. In the developed world, cervical cancer screening has successfully reduced the incidence of and mortality from the disease. Mortality remains high among developing nations. Over the past decade, there have been various developments in management strategies, based on currently available evidence. This review explores such evidence and recommends current management strategies, including fertilitysparing surgical options for early‐stage disease.
Childhood sexual abuse and subsequent gynaecological conditions
Authors: Kaliray Pavan , Drife James
Published: November 2004

Physical, sexual or emotional abuse in childhood occurs in all countries and social classes. Estimates of the prevalence of childhood sexual abuse among the general population vary from 7% to 38% but among gynaecological patients rates are generally between 15% and 20%. Rates are highest among women with chronic pelvic pain and those who have had gynaecological surgery. Childhood sexual abuse may cause adult depression, somatisation or neurological changes. Gynaecologists should remember that childhood sexual abuse is common. Empathic questioning about the possibility should be routinely included. Failure to do so may lead to inappropriate treatment, including unnecessary surgery. Women distressed by childhood sexual abuse should be offered appropriate referral.
Challenging the Royal College of Obstetricians and Gynaecologists to fulfil its international obligations
Authors: Saleh Wael F , Mossa Mohamed A
Published: November 2004

The international role of the RCOG could be expanded. We explore possible ways in which the RCOG could enhance its international role to place itself as the main international consultancy in women's health, and the benefits it might gain from this position.
Fair comment means fair assessment: how specialist trainees benefit from direct measurement of consumer opinion
Authors: Granik Sue
Published: November 2004

Direct measurement of consumer satisfaction with specialist trainees reduces the potential for unfairness inherent in the current system for assessing the quality of specialist trainee interaction with consumers. This article describes research undertaken by the Consumers' Forum to identify a fairer measure of consumer satisfaction for inclusion in the training assessment process. Three instruments for measuring consumer satisfaction were identified from peer‐reviewed journals and benchmarked against criteria including use in appraisal processes and congruence with consumer‐driven service quality dimensions. The Doctors Interpersonal Skills Questionnaire was selected as the Forum's preferred mechanism for measuring consumer opinion of specialist trainees.
Resummed spinning waveforms from five-point amplitudes
Authors: Brandhuber Andreas , Brown Graham R. , Chen Gang , Gowdy Joshua , Travaglini Gabriele
Published: February 2024

Abstract

We compute the classical tree-level five-point amplitude for the two-to-two scattering of spinning celestial objects with the emission of a graviton. Using this five-point amplitude, we then turn to the computation of the leading-order time-domain gravitational waveform. The method we describe is suitable for arbitrary values of classical spin of Kerr black holes and does not require any expansion in powers of the spin. In this paper we illustrate it in the simpler case of the scattering of one Kerr and one Schwarzschild black hole. An important ingredient of our calculation is a novel form of the Compton amplitude with spinning particles including contact terms derived from matching to black-hole perturbation theory calculations. This ensures that our waveform is valid up to at least fourth order in the spin. Our method can be applied immediately to generate improved waveforms once higher-order contact terms in the Compton amplitude become available. Finally, we show the formula for the gravitational memory to all orders in the spin, which is in agreement with our results.
Limits on dark matter annihilation from the shape of radio emission in M31
Authors: Weikert Mitchell J. , Buckley Matthew R.
Published: February 2024

Abstract

Well-motivated models of dark matter often result in a population of electrons and positrons within galaxies produced through dark matter annihilation — usually in association with gamma rays. As they diffuse through galactic magnetic fields, these e± produce synchrotron radio emission. The intensity and morphology of this signal depends on the properties of the interstellar medium through which the e± propagate. Using observations of the Andromeda Galaxy (M31) to construct a model of the gas, magnetic fields, and starlight, we set constraints on dark matter annihilation to $$ b\overline{b} $$
b

b
¯

using the morphology of 3.6 cm radio emission. As the emission signal at the center of M31 is very sensitive to the diffusion coefficient and dark matter profile, we base our limits on the differential flux in the region between 0.9 – 6.9 kpc from the center. We exclude annihilation cross sections ≳ 3 × 10−25 cm3/s in the mass range 10 – 500 GeV, with a maximum sensitivity of 7 × 10−26 cm3/s at 20 – 40 GeV. Though these limits are weaker than those found in previous studies of M31, they are robust to variations of the diffusion coefficient.
Equivariant Fusion Subcategories
Authors: Galindo César , Jones Corey
Published: February 2024

We provide a parameterization of all fusion subcategories of the equivariantization by a group action on a fusion category. As applications, we classify the Hopf subalgebras of a family of semisimple Hopf algebras of Kac-Paljutkin type and recover Naidu-Nikshych-Witherspoon classification of the fusion subcategories of the representation category of a twisted quantum double of a finite group.
Factors Impacting Survival After Transarterial Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: A Combined Analysis of the Prospective CIRT Studies
Authors: Reimer Peter , Vilgrain Valérie , Arnold Dirk , Balli Tugsan , Golfieri Rita , Loffroy Romaric , Mosconi Cristina , Ronot Maxime , Sengel Christian , Schaefer Niklaus , Maleux Geert , Munneke Graham , Peynircioglu Bora , Sangro Bruno , Kaufmann Nathalie , Urdaniz Maria , Pereira Helena , de Jong Niels , Helmberger Thomas
Published: February 2024

Purpose

Transarterial radioembolization (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). However, optimising the timing of TARE in relation to systemic therapies and patient selection remains challenging. We report here on the effectiveness, safety, and prognostic factors associated with TARE for ICC in a combined analysis of the prospective observational CIRT studies (NCT02305459 and NCT03256994).

Methods

A combined analysis of 174 unresectable ICC patients enrolled between 2015 and 2020 was performed. Patient characteristics and treatment-related data were collected at baseline; adverse events and time-to-event data (overall survival [OS], progression-free survival [PFS] and hepatic PFS) were collected at every follow-up visit. Log-rank tests and a multivariable Cox proportional hazard model were used to identify prognostic factors.

Results

Patients receiving a first-line strategy of TARE in addition to any systemic treatment had a median OS and PFS of 32.5 months and 11.3 months. Patients selected for first-line TARE alone showed a median OS and PFS of 16.2 months and 7.4 months, whereas TARE as 2nd or further treatment-line resulted in a median OS and PFS of 12 and 9.3 months (p = 0.0028), and 5.1 and 3.5 months (p = 0.0012), respectively. Partition model dosimetry was an independent predictor for better OS (HR 0.59 [95% CI 0.37–0.94], p = 0.0259). No extrahepatic disease, no ascites, and < 6.1 months from diagnosis to treatment were independent predictors for longer PFS.

Conclusion

This combined analysis indicates that in unresectable ICC, TARE in combination with any systemic treatment is a promising treatment option.

Level of evidence: level 3, Prospective observational

Graphic Abstract
Cardiovascular Events with the Use of Long-Acting Muscarinic Receptor Antagonists: An Analysis of the FAERS Database 2020–2023
Authors: Matera Maria Gabriella , Calzetta Luigino , Rogliani Paola , Hanania Nicola , Cazzola Mario
Published: February 2024

Purpose

This study aimed to examine reports of cardiovascular adverse events (CV AEs) observed in the real-world during treatment with aclidinium, tiotropium, glycopyrronium, and umeclidinium alone or in combination with a LABA and, in the context of triple therapy, with the addition of an ICS, and submitted to the food and drug administration adverse event reporting system (FAERS).

Methods

A retrospective disproportionality analysis was conducted utilizing CV AE reports submitted to the FAERS from January 2020 to 30 September 2023. Disproportionality was measured by calculating the reporting odds ratio.

Results

Compared with ipratropium, tiotropium was associated with fewer reports of CV AEs. Compared with tiotropium, other LAMAs were more likely to be associated with reports of CV AEs. Combinations of glycopyrronium with indacaterol or formoterol and umeclidinium with vilanterol significantly reduced reports of CV AEs compared with the respective LAMA. The addition of an ICS to these combinations further reduced the risk of CV AE reports.

Conclusion

Our study suggests that inhaled LAMAs are not free from cardiac AE risks. This risk may be more evident when the newer LAMAs are used, but it is generally significantly reduced when COPD patients are treated with dual bronchodilators or triple therapy. However, these results do not prove that LAMAs cause CV AEs, as FAERS data alone are not indicative of a drug’s safety profile. Given the frequency with which COPD and cardiovascular disease co-exist, a large study in the general population could shed light on this very important issue.
Impact of Temperature on the Performance of Plasma-Pulse Geo-Drilling (PPGD)
Authors: Ezzat Mohamed , Börner Jascha , Kammermann Benedikt , Rossi Edoardo , Adams Benjamin M. , Wittig Volker , Biela Jürgen , Schiegg Hans-Olivier , Vogler Daniel , Saar Martin O.
Published: February 2024

Advanced Geothermal Systems (AGS) may in principle be able to satisfy the global energy demand using standard continental-crust geothermal temperature gradients of 25–35$$^\circ$$∘C/km. However, conventional mechanical rotary drilling is still too expensive to cost-competitively provide the required borehole depths and lengths for AGS. This highlights the need for a new, cheaper drilling technology, such as Plasma-Pulse Geo-Drilling (PPGD), to improve the economic feasibility of AGS. PPGD is a rather new drilling method and is based on nanoseconds-long, high-voltage pulses to fracture the rock without mechanical abrasion. The absence of mechanical abrasion prolongs the bit lifetime, thereby increasing the penetration rate. Laboratory experiments under ambient-air conditions and comparative analyses (which assume drilling at a depth between 3.5 and 4.5 km) have shown that PPGD may reduce drilling costs by approximately 17–23%, compared to the costs of mechanical drilling, while further research and development are expected to reduce PPGD costs further. However, the performance of the PPGD process under deep wellbore conditions, i.e., at elevated temperatures as well as elevated lithostatic and hydrostatic pressures, has yet to be systematically tested. In this paper, we introduce a standard experiment parameter to examine the impact of deep wellbore conditions on PPGD performance, namely the productivity (the excavated rock volume per pulse) and the specific energy (the amount of energy required to drill a unit volume of rock). We employ these parameters to investigate the effect of temperature on PPGD performance, with temperatures increasing up to 80$$^\circ$$∘C, corresponding to a drilling depth of up to approximately 3 km.
Identification and characterization of endogenous biomarkers for hepatic vectorial transport (OATP1B3-P-gp) function using metabolomics with serum pharmacology
Authors: Jin Yong-wen , Ma Yan-rong , Zhang Ming-kang , Xia Wen-bin , Yuan Pei , Li Bo-xia , Wei Yu-hui , Wu Xin-an
Published: February 2024

The organic anion-transporting polypeptide 1B3 and P-glycoprotein (P-gp) provide efficient directional transport (OATP1B3-P-gp) from the blood to the bile that serves as a key determinant of hepatic disposition of the drug. Unfortunately, there is still a lack of effective means to evaluate the disposal ability mediated by transporters. The present study was designed to identify a suitable endogenous biomarker for the assessment of OATP1B3-P-gp function in the liver. We established stably transfected HEK293T-OATP1B3 and HEK293T-P-gp cell lines. Results showed that azelaic acid (AzA) was an endogenous substrate for OATP1B3 and P-gp using serum pharmacology combined with metabolomics. There is a good correlation between the serum concentration of AzA and probe drugs of rOATP1B3 and rP-gp when rats were treated with their inhibitors. Importantly, after 5-fluorouracil-induced rat liver injury, the relative mRNA level and expression of rOATP1B3 and rP-gp were markedly down-regulated in the liver, and the serum concentration of AzA was significantly increased. These observations suggest that AzA is an endogenous substrate of both OATP1B3 and P-gp, and may serve as a potential endogenous biomarker for the assessment of the function of OATP1B3-P-gp for the prediction of changes in the pharmacokinetics of drugs transported by OATP1B3-P-gp in liver disease states.
The Structure of Aisles and Co-aisles of t-Structures and Co-t-structures
Authors: Tattar Aran
Published: February 2024

Right triangulated categories can be thought of as triangulated categories whose shift functor is not an equivalence. We give intrinsic characterisations of when such categories are appearing as the (co-)aisle of a (co-)t-structure in an associated triangulated category. Along the way, we also give an interpretation of these structures in the language of extriangulated categories.
Power distance orientation alleviates the beneficial effects of empowering leadership on actors’ work engagement via negative affect and sleep quality
Authors: Kwan Ho Kwong , Chen Yang , Tang Guiyao , Zhang Xiaomeng , Le Jiaqi
Published: February 2024

Although many studies have explored the benefits of empowering leadership for followers, the beneficial effect of such behavior for actors who demonstrate empowering leadership has been overlooked. Applying conservation of resources theory, we propose and test a model that determines why and when empowering leadership benefits actors. We use an experience sampling survey to examine the effect of empowering leadership on actors’ daily work engagement. In particular, we focus on the moderating role of power distance orientation and the mediating roles of negative affect and sleep quality, which operate sequentially. The results based on responses from 160 supervisors in two Chinese organizations indicated that empowering leadership in the morning was negatively related to negative affect in the afternoon and positively related to sleep quality at night and next-day work engagement. The strength of this beneficial effect was moderated by power distance orientation, such that supervisors with a high degree of power distance orientation obtained fewer benefits from empowering leadership than those with a low degree of power distance orientation. The theoretical and practical implications of these findings for the leadership, affect, sleep, power distance, and conservation of resources literatures are discussed.
Clusterin: a marker and mediator of chemoresistance in colorectal cancer
Authors: Hlavca Sara , Chan Wing Hei , Engel Rebekah M. , Abud Helen E.
Published: February 2024

Intra-tumoural heterogeneity and cancer cell plasticity in colorectal cancer (CRC) have been key challenges to effective treatment for patients. It has been suggested that a subpopulation of LGR5-expressing cancer stem cells (CSCs) is responsible for driving tumour relapse and therapy resistance in CRC. However, studies have revealed that the LGR5+ve CSC population is highly sensitive to chemotherapy. It has been hypothesised that another subset of tumour cells can phenotypically revert to a stem-like state in response to chemotherapy treatment which replenishes the LGR5+ve CSC population and maintains tumour growth. Recently, a unique stem cell population marked by enriched clusterin (CLU) expression and termed the revival stem cell (RevSC) was identified in the regenerating murine intestine. This CLU-expressing cell population is quiescent during homeostasis but has the ability to survive and regenerate other stem cells upon injury. More recently, the CLU+ve signature has been implicated in several adverse outcomes in CRC, including chemotherapy resistance and poor patient survival; however, the mechanism behind this remains undetermined. In this review, we discuss recent insights on CLU in CRC and its roles in enhancing the plasticity of cells and further consider the implications of CLU as a prospective target for therapeutic intervention.
Deciphering the heterogeneity of neutrophil cells within circulation and the lung cancer microenvironment pre- and post-operation
Authors: Liu Fangming , Liu Xuanqi , Liu Yifei , Chen Dongsheng , Liu Xiaoxia , Qin Chuan , Song Yuanlin , Fang Hao , Wu Duojiao
Published: February 2024

Neutrophils play a crucial role in the immune system within tumor microenvironment. At present, numerous studies have explored the changes of neutrophils’ automatic killing effect and cellular communication with other immune cells under pathological conditions through single-cell sequencing. However, there remains a lack of definite conclusion about the identification criteria of neutrophil subgroups. Here, we collected tumor and para-carcinoma tissues, pre- and postoperative blood from patients with non-small cell lung cancer (NSCLC), and performed single-cell RNA (scRNA) sequencing to evaluate the distribution of neutrophil subgroups. We have developed a computational method of over expression rate (OER) to evaluate the specificity of neutrophil subgroups, in order to target gene panels with potential clinical application value. In addition, OER was used to evaluate specificity of neutrophil subsets in healthy people and patients with various diseases to further validate the feasibility of this evaluation system. As a result, we found the specificity of Neu_ c1_ IL1B and Neu_ c2_ cxcr4 (low) in postoperative blood has increased, while that of IL-7R + neutrophils has decreased, indicating that these groups of cells possibly differentiated or migrated to other subgroups in the state of lung cancer. In addition, seven gene panels (Neu_c3_CST7, RSAD2_Neu, S100A2/Pabpc1_Neu, ISG15/Ifit3_Neu, CD74_Neu, PTGS2/Actg1_Neu, SPP1_Neu) were high specific in all the four NSCLC-associated samples, meaning that changes in the percentage of these cell populations would have a high degree of confidence in assessing changes of disease status. In conclusion, combined consideration of the distribution characteristics of neutrophil subgroups could help evaluate the diagnosis and prognosis of NSCLC.

Graphical abstract

• An evaluation system based on OER was developed to assess the specificity of neutrophil subgroups

• Specificity of Neu_ c1_ IL1B, Neu_ c2_ cxcr4 (low) and IL-7R + neutrophils changed significantly between preoperative and postoperative blood

• 7 gene panels were high specific in all the four NSCLC-associated samples, meaning a high degree of confidence in assessing changes of these subgroups in various disease status
Revealing the structural behaviour of Brunelleschi’s Dome with machine learning techniques
Authors: Masini Stefano , Bacci Silvia , Cipollini Fabrizio , Bertaccini Bruno
Published: February 2024

The Brunelleschi’s Dome is one of the most iconic symbols of the Renaissance and is among the largest masonry domes ever constructed. Since the late 17th century, first masonry cracks appeared on the Dome, giving the start to a monitoring activity. In modern times, since 1988 a monitoring system comprised of 166 electronic sensors, including deformometers and thermometers, has been in operation, providing a valuable source of real-time data on the monument’s health status. With the deformometers taking measurements at least four times per day, a vast amount of data is now available to explore the potential of the latest Artificial Intelligence and Machine Learning techniques in the field of historical-architectural heritage conservation. The objective of this contribution is twofold. Firstly, for the first time ever, we aim to unveil the overall structural behaviour of the Dome as a whole, as well as that of its specific sections (known as webs). We achieve this by evaluating the effectiveness of certain dimensionality reduction techniques on the extensive daily detections generated by the monitoring system, while also accounting for fluctuations in temperature over time. Secondly, we estimate a number of recurrent and convolutional neural network models to verify their capability for medium- and long-term prediction of the structural evolution of the Dome. We believe this contribution is an important step forward in the protection and preservation of historical buildings, showing the utility of machine learning in a context in which these are still little used.
The role of education in innovation–migration nexus in Europe
Authors: Aldieri L. , Autiero G. , Nese A. , Vinci C. P.
Published: February 2024

Using panel data between 2012 and 2020, this research examines the relationship between the flows of low-skilled immigrants and innovation in the EU-15 group of nations and Switzerland. The empirical component is generated from a theoretical model that we construct. After addressing the potential endogeneity of the share of immigrants in the population, we find that regions with a relatively high immigrant population have a favorable impact on the generation of patent applications, whereas low-skilled immigrants have the reverse effects on innovation. Hence, the results are in line with the proposition in the theoretical section that lower-educated immigrants determine social decreasing returns in the economy.
In defence of object-given reasons
Authors: Vollmer Michael
Published: February 2024

One recurrent objection to the idea that the right kind of reasons for or against an attitude are object-given reasons for or against that attitude is that object-given reasons for or against belief and disbelief are incapable of explaining certain features of epistemic normativity. Prohibitive balancing, the behaviour of bare statistical evidence, information about future or easily available evidence, pragmatic and moral encroachment, as well as higher-order defeaters, are all said to be inexplicable in terms of those object-given reasons. In this paper, I provide a rebuttal to all these challenges by drawing attention to the object-given reasons for and against the third doxastic state, namely the suspension of judgement. First, I introduce an original picture of how suspension relates to belief and disbelief – as ways of being decided – which yields a novel weighing model of the corresponding reasons. Second, I demonstrate that this new take on doxastic deliberation can accommodate all five features of epistemic normativity. Finally, I extend the weighing model to cover practical deliberation and the suspension of intentions. The resulting theory provides an explanation of why epistemic and practical normativity differ in certain respects in terms of a significant difference between doxastic and conative suspension.
Investigating the Non-Linear Effects of Breach Parameters on a Dam Break Study
Authors: Marangoz Hasan Oğulcan , Anılan Tuğce , Karasu Servet
Published: February 2024

When settlements are located close to a dam, it is important to accurately predict the breach peak flow and the time to reach the peak. Therefore, the prediction of dam breach properties is essential in dam break studies. Dam breach parameters such as the breach side slope, final bottom width, final bottom elevation, weir coefficient, breach formation time, and initial elevation of reservoirs are the key variables for estimating the peak discharge during a dam break scenario. In this study, these six breach parameters were analyzed to investigate the impact of breach parameters on breach peak flow and the time to reach the peak. Thus, several scenarios were calculated and compared for Atasu Dam. The results revealed that the role of the initial water elevation, final bottom elevation, and breach development time had more of an impact on the breach peak flow and the time to reach the peak. In addition, the study indicated that the final bottom width and breach weir coefficient were less sensitive to both the peak discharge and peak discharge time. Furthermore, the analysis indicated that the breach side slope parameter had no major influence on the time to peak while also having an insignificant impact on the peak discharge. Understanding this breach mechanism provides a basis for relevant research in designating key parameters for dam break analysis. Thus, the results can contribute to decision making toward the design of flood mitigation and dam emergency action planning.
Geosite Recognition Based on Qualitative-Quantitative Assessment in the Light of Core Geological Features of a Mio-Pliocene Volcanic Arc Setting of the Coromandel Peninsula, New Zealand
Authors: Zakharovskyi Vladyslav , Németh Károly , Gravis Ilmars , Twemlow Chris
Published: February 2024

The far north part of Coromandel Peninsula can be considered a good place for geoeducation and geotourism, which is justified by the remnants of Miocene-Pleistocene volcanic integration with marine environment. These processes in collaboration with old Jurassic and quaternary sediments create a diverse geological and geomorphological constructions forming the abiotic environment of areas surrounding Port Jackson and Fletcher Bay. These two locations have been chosen as two main campsites of the north Coromandel Peninsula, which are maintained by the Department of Conservation (DOC) of Coromandel Peninsula. Hence, the campsites should be considered as main places for camping for the trips of different purposes. They provide an access costal way and/or trails leading to the main geologically important locations presenting some knowable features like Pinnacles and Sugar Loaf spread through the region. To highlight these locations of interests, “geosites,” we developed qualitative-quantitative assessment of geodiversity for geosite recognition based on 8-m DEM and 1:1250,000 scale geological map and QGIS (3.28 “Firenze”) software. The methodology utilizing 8-point evaluation system applied for geological formations of the studied region and its multiplication with morphological slope degree. The result of assessment has been expanded and justified with geological, cultural, and geomorphological database acquired from literature review and direct field trips of the studied areas. The conclusion demonstrates the main geological knowledge of recognized geosites together with description of drawbacks and possible obstacles for tourism and education in the region of the northern Coromandel Peninsula.
Healthy human skin Kelvin-Voigt fractional and spring-pot biomarkers reconstruction using torsional wave elastography
Authors: Almashakbeh Yousef , Shamimi Hirad , Faris Inas H. , Cortés José M. , Callejas Antonio , Rus Guillermo
Published: February 2024

This paper presents a novel method for reconstructing skin parameters using Probabilistic Inverse Problem (PIP) techniques and Torsional Wave Elastography (TWE) rheological modeling. A comprehensive examination was conducted to compare and analyze the theoretical, time-of-flight (TOF), and full-signal waveform (FSW) approaches. The objective was the identification of the most effective method for the estimation of mechanical parameters. Initially, the most appropriate rheological model for the simulation of skin tissue behavior was determined through the application and comparison of two models, spring pot (SP) and Kevin Voigt fractional derivative (KVFD). A numerical model was developed using the chosen rheological models. The collection of experimental data from 15 volunteers utilizing a TWE sensor was crucial for obtaining significant information for the reconstruction process. The study sample consisted of five male and ten female subjects ranging in age from 25 to 60 years. The procedure was performed on the ventral forearm region of the participants. The process of reconstructing skin tissue parameters was carried out using PIP techniques. The experimental findings were compared with the numerical results. The three methods considered (theoretical, TOF, FSW) have been used. The efficacy of TOF and FSW was then compared with theoretical method. The findings of the study demonstrate that the FSW and TOF techniques successfully reconstructed the parameters of the skin tissue in all of the models. The SP model’s the skin tissue $$\eta $$
η
values ranged from 8 to 12 $$Pa \cdot s$$

P
a
·
s

, as indicated by the TOF reconstruction parameters. $$\eta $$
η
values found by the KVFD model ranged from 4.1 to 9.3 $$Pa \cdot s$$

P
a
·
s

. The $$\mu $$
μ
values generated by the KVFD model range between 0.61 and 96.86 kPa. However, FSW parameters reveal that skin tissue $$\eta $$
η
values for the SP model ranged from 7.8 to 12 $$Pa \cdot s$$

P
a
·
s

. The KVFD model determined $$\eta $$
η
values between 6.3 and 9.5 $$Pa \cdot s$$

P
a
·
s

. The KVFD model presents $$\mu $$
μ
values ranging between 26.02 and 122.19 kPa. It is shown that the rheological model that best describes the nature of the skin is the SP model and its simplicity as it requires only two parameters, in contrast to the three parameters required by the KVFD model. Therefore, this work provides a valuable addition to the area of dermatology, with possible implications for clinical practice.
Variation type characterization of product Hardy spaces
Authors: Angeloni Laura , Liflyand Elijah , Vinti Gianluca
Published: February 2024

In the multidimensional Euclidean space, except the classical real Hardy space, there are numerous product ones. We associate with each of them a class of functions related to the known variations and new ones. Such a characterization is fulfilled by means of the integrability of the Fourier transform
Light Electric Vehicle Performance with Digital Twin Technology: A Comparison of Motor Types
Authors: Polat Abdurrahman Ozgur , Erden Bekir Cagri , Kul Seda , Nasiroglu Fehruleyl
Published: February 2024

Digital twin (DT) is proposed as a solution to reduce financial and time losses for vehicle manufacturers by streamlining the expensive and time-consuming processes of designing and implementing electric vehicle types and road assessments. The use of digital twins to monitor, evaluate, and optimize vehicle performance based on real-time road data is increasingly crucial in the DT concept. In this study, the digital twin of the CERYAN brand vehicle model has been employed to compare the performance of different motor types (PMSM, PMSM Brushless, BLDC/PMSM Brushless, and BLDC) in terms of energy consumption and acceleration at various inclination angles, utilizing real-time road data. According to the World Motorcycle Test Cycle (WMTC) standards, the motor type with the best performance parameters was determined as a PMSM brushless motor (5 kW). The main superior aspects of the proposed motor type are to achieve a 25% higher range than the BLDC Motor, 30% better grade ascending capability than the PMSM Motor, and 26% lower energy consumption than the PMSM brushless motor (6 kW).
Comparing the financial costs and carbon neutrality of polyester fibres produced from 100% bio-based PET, 100% recycled PET, or in combination
Authors: Berger Nathaniel J. , Pfeifer Christoph
Published: February 2024

The rise of fast fashion has led to challenges in sustainable production and recycling of polyester textile waste. Bio-based polyethylene terephthalate (bio-PET) and the enzymatic hydrolysis of PET textiles may offer two solutions for bio and circular clothing. This study designed and simulated scaled enzymatic hydrolysis of fossil PET into ethylene glycol (r-EG) and purified terephthalic acid (r-PTA), the production of bio-EG and bio-PTA from the wheat straw ethanol (EtOH) and corn stover isobutene (IBN), respectively, and the production of PET polyester textile fibres from these monomers. The research goal was to determine whether bio-PET, r-PET, or their mixture achieves better positive profitability and NPV2023 and carbon neutrality in textile fibres. The financial returns and carbon emissions for r-PET fibres with a bio-PET content of 0%, 20%, 40%, 60%, 80% to 100% was estimated for scenario 1 (a newly constructed plant), scenario 2 (no capital costs for the EtOH or IBN processes), and scenario 3 (no capital costs for the EtOH, IBN, and enzymatic hydrolysis processes). While scenario 1 was not able to generate positive net profits or NPV2023, scenarios 2 and 3 were able to attain financial sustainability when the bio-PET content was ≤ 40%. On the other hand, increasing the amount of bio-PET content in the polyester fibre from 0 to 100 wt.% decreased its carbon footprint from 2.99 to 0.46 kg CO2eq./kg of PET fibre.