bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial and enzymatic changes in cigar tobacco leaves during air-curing and fermentation
Authors: Zhang Qing , Kong Guanghui , Zhao Gaokun , Liu Jun , Jin Honggang , Li Zhihua , Zhang Guanghai , Liu Tao
Published: July 2023

Metabolic enzyme activity and microbial composition of the air-curing and fermentation processes determine the quality of cigar tobacco leaves (CTLs). In this study, we reveal the evolution of the dominant microorganisms and microbial community structure at different stages of the air-curing and fermentation processes of CTLs. The results showed that the changes in metabolic enzymes occurred mainly during the air-curing phase, with polyphenol oxidase (PPO) being the most active at the browning phase. Pseudomonas, Bacteroides, Vibrio, Monographella, Bipolaris, and Aspergillus were the key microorganisms in the air-curing and fermentation processes. Principal coordinate analysis revealed significant separation of microbial communities between the air-curing and fermentation phases. Redundancy analysis showed that bacteria such as Proteobacteria, Firmicutes, Bacteroidota, and Acidobacteriota and fungi such as Ascomycota and Basidiomycota were correlated with enzyme activity and temperature and humidity. Bacteria mainly act in sugar metabolism, lipid metabolism, and amino acid metabolism, while fungi mainly degrade lignin, cellulose, and pectin through saprophytic action. Spearman correlation network analysis showed that Firmicutes, Proteobacteria, and Actinobacteria were the key bacterial taxa, while Dothideomycetes, Sordariomycetes, and Eurotiomycetes were the key fungal taxa. This research provides the basis for improving the quality of cigars by improving the air-curing and fermentation processes.

Key points

• Changes in POD and PPO activity control the color change of CTLs at the air-curing stage.

• Monographella, Aspergillus, Pseudomonas, and Vibrio play an important role in air-curing and fermentation.

• Environmental temperature and humidity mainly affect the fermentation process, whereas bacteria such as Proteobacteria, Firmicutes, Bacteroidota, and Acidobacteriota and fungi such as Ascomycota and Basidiomycota are associated with enzyme activity and temperature and humidity.

Graphical Abstract
The prognostic significance of microsatellite instability in colorectal cancer: a Swedish multi-center study
Authors: Rantanen Petri , Keränen Anne , Barot Shabane , Ghazi Sam , Liljegren Annelie , Nordenvall Caroline , Lindblom Annika , Lindforss Ulrik
Published: July 2023

Purpose

About 10 to 15% of patients with sporadic colorectal cancer display mutations in DNA mismatch repair (MMR) genes shown as microsatellite instability (MSI). Previous reports of colorectal cancer (CRC) indicate a better prognosis for patients with MSI tumors compared to patients with microsatellite stable (MSS) tumors. In this study, our aim was to investigate whether MSI is an independent prognostic factor in CRC.

Patients and methods

Patients with stage I–III colorectal cancer and subject to curative surgery during 2002–2006 in the Swedish low-risk colorectal cancer study group cohort were eligible for inclusion. Deficient MMR (dMMR) status was analyzed by immunohistochemistry (IHC) and/or by MSI testing with polymerase chain reaction (PCR). Prognostic follow-up and treatment data were retrieved from patient records. Statistical analyses to assess MSI-status and prognosis were done using logistic regression and survival analyses using the Kaplan-Meier method and Cox regression hazards models adjusted for age, sex, stage, comorbidity, and tumor location.

Results

In total, 463 patients were included, MSI high tumors were present in 66 patients (14%), and the remaining 397 were MSS/MSI low. Within 6 years, distant recurrences were present in 9.1% and 20.2% (P = 0.049), and death occurred in 25.8% and 31.5% in MSI and MSS patients, respectively. There was no statistically significant difference in overall mortality (HR 0.80, 95% CI 0.46–1.38), relapse-free survival (HR 0.82, 95% CI 0.50–1.36), or cancer-specific mortality (HR 1.60, 95% CI 0.73–3.51).

Conclusion

Despite distant metastases being less common in patients with MSI, there was no association between MSI and overall, relapse-free, or cancer-specific survival.
Evaluating ChatGPT as an adjunct for the multidisciplinary tumor board decision-making in primary breast cancer cases
Authors: Lukac Stefan , Dayan Davut , Fink Visnja , Leinert Elena , Hartkopf Andreas , Veselinovic Kristina , Janni Wolfgang , Rack Brigitte , Pfister Kerstin , Heitmeir Benedikt , Ebner Florian
Published: July 2023

Background

As the available information about breast cancer is growing every day, the decision-making process for the therapy is getting more complex. ChatGPT as a transformer-based language model possesses the ability to write scientific articles and pass medical exams. But is it able to support the multidisciplinary tumor board (MDT) in the planning of the therapy of patients with breast cancer?

Material and Methods

We performed a pilot study on 10 consecutive cases of breast cancer patients discussed in MDT at our department in January 2023. Included were patients with a primary diagnosis of early breast cancer. The recommendation of MDT was compared with the recommendation of the ChatGPT for particular patients and the clinical score of the agreement was calculated.

Results

Results showed that ChatGPT provided mostly general answers regarding chemotherapy, breast surgery, radiation therapy, chemotherapy, and antibody therapy. It was able to identify risk factors for hereditary breast cancer and point out the elderly patient indicated for chemotherapy to evaluate the cost/benefit effect. ChatGPT wrongly identified the patient with Her2 1 + and 2 + (FISH negative) as in need of therapy with an antibody and called endocrine therapy “hormonal treatment”.

Conclusions

Support of artificial intelligence by finding individualized and personalized therapy for our patients in the time of rapidly expanding amount of information is looking for the ways in the clinical routine. ChatGPT has the potential to find its spot in clinical medicine, but the current version is not able to provide specific recommendations for the therapy of patients with primary breast cancer.
Incidence of venous thromboembolism following head and neck surgery
Authors: Albertsen Ida E. , Lyhne Nina M. , Larsen Torben B. , Nielsen Peter B.
Published: July 2023

Purpose

Venous thromboembolism (VTE) is associated with significant morbidity and mortality in patients undergoing surgery, but conflicting data exist on VTE risk in patients undergoing head and neck surgery for malignant and non-malignant conditions. Our aim was to examine the risk of VTE among patients with and without cancer undergoing head and neck surgery.

Methods

We conducted a nationwide cohort study to examine the risk of VTE among patients with an otolaryngological diagnosis using data from the Danish National Patient Register between 2010 and 2018. Analyses were stratified by cancer and anatomical areas of the surgical procedure.

Results

In total, 116,953 patients were included of whom 10% (n = 12,083) had active cancer. After 3 months, 1.2% of the patients with cancer and 0.3% of the patients without cancer experienced VTE, respectively. For patients undergoing mouth/throat surgery, 0.8% with cancer and 0.2% without cancer had VTE, respectively. After nose/sinuses surgery 0.7% and 0.2%, respectively. No patients experienced VTE after ear surgery; and after endoscopies the numbers were 1.3% and 0.6% respectively.

Conclusions

While the minority of patients undergoing head and neck surgery develop VTE postoperatively, the risk increases among those with cancer. To support clinical decision making on anticoagulation, risk stratification tools could be further developed to recognize this hazard in patients with cancer undergoing head and neck surgery.
Evaluation of myotonometry for myotonia, muscle stiffness and elasticity in neuromuscular disorders
Authors: Lukas Katharina , Gutschmidt Kristina , Schoser Benedikt , Wenninger Stephan
Published: July 2023

Neuromuscular disorders show extremely varied expressions of different symptoms and the involvement of muscles. Non-invasively, myotonia and muscle stiffness are challenging to measure objectively. Our study aims to test myotonia, elasticity, and stiffness in various neuromuscular diseases and to provide reference values for different neuromuscular disease groups using a novel handheld non-invasive myometer device MyotonPRO®. We conducted a monocentric blinded cross-sectional study in patients with a set of distinct neuromuscular diseases (NCT04411732, date of registration June 2, 2020). Fifty-two patients in five groups and 21 healthy subjects were enrolled. We evaluated motor function (6-min walk test, handheld dynamometry, Medical Research Council (MRC) Scale) and used ultrasound imaging to assess muscle tissue (Heckmatt scale). We measured muscle stiffness, frequency, decrement, creep, or relaxation using myotonometry with the device MyotonPRO®. Statistically, all values were calculated using the t test and Mann–Whitney U test. No differences were found in comparing the results of myotonometry between healthy and diseased probands. Furthermore, we did not find significant results in all five disease groups regarding myotonometry correlating with muscle strength or ultrasound imaging results. In summary, the myometer MyotonPRO® could not identify significant differences between healthy individuals and neuromuscular patients in our patient collective. Additionally, this device could not distinguish between the five different groups of disorders displaying increased stiffness or decreased muscle tone due to muscle atrophy. In contrast, classic standard muscle tests could clearly decipher healthy controls and neuromuscular patients.
The role of diagnostic, prognostic, and predictive biomarkers in the management of early pancreatic cancer
Authors: Maloney Sarah , Clarke Stephen J. , Sahni Sumit , Hudson Amanda , Colvin Emily , Mittal Anubhav , Samra Jaswinder , Pavlakis Nick
Published: July 2023

Despite modern advances in cancer medicine, pancreatic cancer survival remains unchanged at just 12%. For the small proportion of patients diagnosed with ‘early’ (upfront or borderline resectable) disease, recurrences are common, and many recur soon after surgery. Whilst chemotherapy has been shown to increase survival in this cohort, the morbidity of surgery renders many candidates unsuitable for adjuvant treatment. Due to this, and the success of upfront chemotherapy in the advanced setting, use of neoadjuvant chemotherapy has been introduced in patients with upfront or borderline resectable disease. Randomized controlled trials have been conducted to compare upfront surgery to neoadjuvant chemotherapy in this patient cohort, opinions on the ideal upfront treatment approach are divided. This lack of consensus has highlighted the need for biomarkers to assist in clinical decision making. This review analyses the potential diagnostic, prognostic and predictive biomarkers that may assist in the diagnosis and management of early (upfront and borderline resectable) pancreatic cancer.
CUSUM learning curves: what they can and can’t tell us
Authors: Lin Peng-Lin , Zheng Feibi , Shin Minkyung , Liu Xi , Oh Daniel , D’Attilio Daniel
Published: July 2023

Introduction

There has been increased interest in assessing the surgeon learning curve for new skill acquisition. While there is no consensus around the best methodology, one of the most frequently used learning curve assessments in the surgical literature is the cumulative sum curve (CUSUM) of operative time. To demonstrate the limitations of this methodology, we assessed the CUSUM of console time across cohorts of surgeons with differing case acquisition rates while varying the total number of cases used to calculate the CUSUM.

Methods

We compared the CUSUM curves of the average console times of surgeons who completed their first 20 robotic-assisted (RAS) cases in 13, 26, 39, and 52 weeks, respectively, for their first 50 and 100 cases, respectively. This analysis was performed for prostatectomy (1094 surgeons), malignant hysterectomy (737 surgeons), and inguinal hernia (1486 surgeons).

Results

In all procedures, the CUSUM curve of the cohort of surgeons who completed their first 20 procedures in 13 weeks demonstrated a lower slope than cohorts of surgeons with slower case acquisition rates. The case number at which the peak of the CUSUM curve occurs uniformly increases when the total number of cases used in generation of the CUSUM chart changes from 50 to 100 cases.

Conclusion

The CUSUM analyses of these three procedures suggests that surgeons with fast initial case acquisition rates have less variability in their operative times over the course of their learning curve. The peak of the CUSUM curve, which is often used in surgical learning curve literature to denote “proficiency” is predictably influenced by the total number of procedures evaluated, suggesting that defining the peak as the point at which a surgeon has overcome the learning curve is subject to routine bias. The CUSUM peak, by itself, is an insufficient measure of “conquering the learning curve.”
A critical review of the material properties guiding the clinician’s choice of root canal sealers
Authors: Cardinali F. , Camilleri J.
Published: July 2023

Objectives

The introduction of hydraulic cement sealers has increased the popularity of single cone obturation where the chemistry and properties of hydraulic cement sealers are crucial. This article has investigated the materials present on the market by reviewing the chemistry aiming at understanding whether these materials are optimized or have been tested appropriately.

Methodology

A market search on materials called bioceramic and hydraulic sealers was undertaken. The safety data sheet and manufacturer details for every material were searched and the components were checked. The literature was searched for information about the properties of these materials based on their composition.

Results

The safety data sheets and manufacturer details were imprecise with some manufacturers providing little detail on composition. From the publications reviewed, it is apparent that the materials used clinically are not optimized, and there is little evidence that the material chemistry and presentation aid the clinical technique in any way.

Conclusions

There has been a rapid increase in materials identifying as bioceramics on the market. These materials have diverse chemistries, and some of the constituents are not declared. This may affect the clinical performance of these materials.

Clinical significance

Smart materials developed on the clinical need which are appropriately tested are necessary for a paradigm shift in root canal obturation. It is important to use reputable materials that have been adequately researched in clinical practice.
Choline chloride-acetic acid mixture as a medium for the investigation of the electrochemical processes
Authors: Połomski Damian , Chotkowski Maciej
Published: July 2023

Physicochemical properties of a liquid mixture containing choline chloride (ChCl) and acetic acid (AA) with a molar ratio of 1:2 were analyzed to determine its suitability for electrochemical studies. Viscosity, ionic conductivity, and density values as well as the width of the electrochemical window of the ChCl:AA mixture show that this liquid can be used as a supporting electrolyte in electrochemical studies. This was confirmed by the results of electrochemical studies on a model red-ox system of o-tolidine. Additional electrochemical tests revealed the dissolution of solid Pt in ChCl:FA. The ChCl:AA solution was also used as a background electrolyte in preliminary studies on the electrochemical reduction of pertechnetates. Cyclic voltammetry and UV-Vis spectroscopy experiments reveal a multi-path process which leads to the formation of Tc(IV or III) ionic species.
Potentiometry, chemical equilibria, and flow injection analysis—three important topics taught with one experimental setup
Authors: Kahlert Heike , Meyer Gabriele , Albrecht Anja
Published: July 2023

In general, concepts such as chemical equilibria and classical analytical chemistry, as well as instrumental methods such as potentiometry and flow injection analysis (FIA), are taught separately in the curricula of chemistry-related degree programs. However, FIA provides an opportunity to connect all of these important topics. This article shows how simple experiments can be used to link the fundamentals of FIA and potentiometry to the fundamentals of chemical equilibria and teach them in a sustainable way. The experiments were designed for undergraduate environmental science students with basic knowledge of chemical equilibria and classical analytical chemistry and minimal knowledge of electrochemistry. However, they can also be integrated into various courses on instrumental analysis in chemistry-related degree programs.
Environmental impact of process constrained topology optimization design on automotive component’ life
Authors: Borda Francesco , La Rosa Angela Daniela , Filice Luigino , Gagliardi Francesco
Published: July 2023

The components’ lightweighting has been pursued, especially in the transport industry, for greenhouse gas reduction. Topology optimization, being able to allocate the material within a provided design space, is a mathematical method that can support the design of lightweight components, preserving, at the same time, their mechanical performances. In this paper, a standard shape of a component, specifically an automotive bracket, was topology optimized by estimating the impacts of the new designs from an eco-friendly point of view. A subtractive, an additive and a casting manufacturing process were considered as possible manufacturing routes achieving an optimized geometry of the component for each of them. The topology optimizations were performed considering each processes’ peculiarities, introduced as constraints. Same strength for a given set of loads and boundary conditions was the target of each analysis. The component’s lightening can be considered environmentally friendly just after assessing the impacts associated with all the stages of the product’ life cycle. Indeed, each phase of the product’ life cycle can be affected, differently, by the performed topology optimization taking into account the peculiarities of the employed manufacturing process. The overall considerations on the most environmentally safe strategies can, therefore, change according to the specificities of the optimized shapes. The topology optimization showed its utmost potentiality, from a sustainable point of view, if applied to additive manufacturing techniques for the advantages arisen by the capability to manufacture complex shapes benefiting also of reduction time process owing to less material to be deposited.
Inferring the territoriality of Upper Palaeolithic hunter-gatherer’s groups settled at Cueva del Gato 2 (Épila, Zaragoza)
Authors: Sánchez de la Torre Marta , Jiménez Ruiz Luis , Gratuze Bernard , Duarte Elsa , Blasco María Fernanda , Rodanés José María
Published: July 2023

In recent decades, the development of different analytical procedures applied to the study of archaeological lithic remains has allowed us to approach the territoriality of past societies. The application of geochemical tools has improved the study of lithic raw materials, allowing direct connections between archaeological samples and specific geological formations. In a similar way, the incorporation of GIS tools to the study of past mobility and territoriality has allowed to define which could have been the most probable routes used by past groups to stock up on rocks. In this paper, we present the results obtained after the geochemical study by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) of lithic cherts found at Upper Palaeolithic human occupations at Cueva del Gato 2 (Épila, Zaragoza, Spain) as well as the least cost path routes obtained after GIS analyses. The Cueva del Gato 2 archaeological site is a large cave placed in the first foothills of the Iberian System, close to the Middle Ebro Basin, in Eastern Iberia. The archaeological work has revealed a long sequence of occupation with archaeological levels from the Bronze Age, the Ancient Neolithic and the Upper Palaeolithic. In this paper, we have focused on the study of level II, which has been dated in the range 21,000–23,000 cal BP. Results have demonstrated that past human groups from the Last Glacial Maximum knew and frequented the Sierra de Lanaja – Montes de Castejón lacustrine chert sources, outcropping in the Middle Ebro Basin.
A new insight into the evolution of the Qatar Arch to recognize faults and a new gas field
Authors: Daneshvar Mohammad Reza Mansouri , Mansouri-Daneshvar Parviz , Moussavi-Harami Reza , Gharaie Mohamad Hosein Mahmudy , Mahboubi Asadollah , Khanehbad Mohammad , Feizie Amir , Ebrahimi Majid , Sadeghi Ali
Published: July 2023

Despite the previous interpretations of the evolutionary scenarios of the Qatar Arch, the present study aimed to present a new complementary scenario to lay out the probable effects of another basement fault, corresponding to the physical shape of the Arch. A remote sensing study was carried out based on geological and geophysical data interpretations, obtained from some national and international databases, including GIS-based global geology data of Harvard University, the free-air gravity anomaly data from the World Gravity Map (WGM), and the airborne geophysical project of the National Geosciences Database of Iran (NGDIR). Results revealed that offshore extrapolation of the Trans Arabian-Bostaneh Fault (TABF) lineament through the morphological boundary of Hauterivian–Barremian (HB) formations and the offshore extrapolation of the Kazerun fault could produce a new complementary model for the Qatar Arch evolution. Based on the particular shape of the Arch (i.e., narrowing and uplifting to the south influenced by the Kazerun basement fault and the rotation of TABF), we can propose that these faults crossed each other after the Barremian age, created a particular shape of the Qatar Arch, and influenced beneath the Fars hinterland. The obtained geophysical gravity data also showed a good match between structural units and faults with maximum values corresponding to the Qatar Arch and minimum values relating to the thick sediment field in the Fars region. In conclusion, the present study contributes to a new proposition about exploring the possible faults and a new gas field situated in the interior territory of Iran. All of these interpretations will provide a new insight to improve the extant knowledge in the geology and petroleum evolution of the study area, such as the Plate tectonic events and the creation of possible reservoirs in future.
Practical implications of tumor proximity to landmark vessels in minimally invasive radical antegrade modular pancreatosplenectomy
Authors: Kauffmann Emanuele Federico , Napoli Niccolò , Di Dato Armando , Salamone Alice , Ginesini Michael , Gianfaldoni Cesare , Viti Virginia , Amorese Gabriella , Cappelli Carla , Vistoli Fabio , Boggi Ugo
Published: July 2023

Careful preoperative planning is key in minimally invasive radical antegrade modular pancreatosplenectomy (MI-RAMPS). This retrospective study aims to show the practical implications of computed tomography distance between the right margin of the tumor and either the left margin of the spleno-mesenteric confluence (d-SMC) or the gastroduodenal artery (d-GDA). Between January 2011 and June 2022, 48 minimally invasive RAMPS were performed for either pancreatic cancer or malignant intraductal mucinous papillary neoplasms. Two procedures were converted to open surgery (4.3%). Mean tumor size was 31.1 ± 14.7 mm. Mean d-SMC was 21.5 ± 18.5 mm. Mean d-GDA was 41.2 ± 23.2 mm. A vein resection was performed in 10 patients (20.8%) and the pancreatic neck could not be divided by an endoscopic stapler in 19 operations (43.1%). In patients requiring a vein resection, mean d-SMC was 10 mm (1.5–15.5) compared to 18 mm (10–37) in those without vein resection (p = 0.01). The cut-off of d-SMC to perform a vein resection was 17 mm (AUC 0.75). Mean d-GDA was 26 mm (19–39) mm when an endoscopic stapler could not be used to divide the pancreas, and 46 mm (30–65) when the neck of the pancreas was stapled (p = 0.01). The cut-off of d-GDA to safely pass an endoscopic stapler behind the neck of the pancreas was 43 mm (AUC 0.75). Computed tomography d-SMC and d-GDA are key measurements when planning for MI-RAMPS.
High-speed laser cladding of chromium carbide reinforced Ni-based coatings
Authors: Tuominen Jari , Kiviö Jouko , Balusson Clara , Raami Lassi , Vihinen Jorma , Peura Pasi
Published: July 2023

Fusion-bonded and low-diluted overlay welded coatings are frequently very thick (>1mm). High-speed laser cladding is a novel process capable of producing thin fusion-bonded and low-diluted coatings with high coverage rates and low heat input. In this study, for the first time, high-speed laser cladding was used to fabricate relatively thin Ni-based coatings reinforced with chromium carbides onto low-alloy structural and quenched and tempered steels. Obtained coatings were characterized with X-ray diffraction (XRD), optical (OM), and scanning electron microscopy (SEM), as well as electron backscatter diffraction (EBSD). Mechanical and wear properties were tested with Vickers microhardness measurements and three-body dry-sand rubber wheel abrasion tests (RWAT). It was shown that high-speed laser cladding produces 0.2–0.3-mm-thick coatings, which consist of ultrafine-substructured hypereutectic M7C3 structures reinforced with coarser primary Cr3C2 particles. Coatings with hardness up to 1300 HV0.05 exhibited high wear resistance in low-stress three-body abrasion. Coatings developed can be used as alternatives for hard-chrome plated coatings.
Heterogeneity in regional changes in body composition induced by androgen deprivation therapy in prostate cancer patients: potential impact on bone health—the BLADE study
Authors: Dalla Volta A. , Palumbo C. , Zamboni S. , Mazziotti G. , Triggiani L. , Zamparini M. , Maffezzoni F. , Rinaudo L. , Bergamini M. , Di Meo N. , Caramella I. , Valcamonico F. , Borghetti P. , Guerini A. , Farina D. , Antonelli A. , Simeone C. , Berruti A.
Published: July 2023

Background

It is not clear whether changes in body composition induced by androgen deprivation therapy (ADT) in prostate cancer (PC) patients are uniform or vary in the different body districts and whether regional lean body mass (LBM) and fat body mass (FBM) could have an impact on bone health.

Objective

To prospectively evaluate the regional changes in LBM and FBM in PC patients submitted to degarelix; to explore the relationship of regional body composition and bone mineral density (BMD) and bone turnover markers.

Design, setting, and participants

29 consecutive non metastatic PC patients enrolled from 2017 to 2019. FBM, LBM and bone mineral density (BMD) evaluated by dual-energy x-ray absorptiometry (DXA) at baseline and after 12-month of ADT. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) assessed at baseline, 6 and 12 months.

Intervention

All patients underwent degarelix administration.

Outcome measurements and statistical analysis

T-test or sign test and Pearson or Spearman test for continuous variables were used when indicated.

Results and limitations

Median percent increase in FBM ranged from + 14.5% in trunk to + 25.4% in the left leg after degarelix. LBM changes varied from + 2% in the trunk to − 4.9% in the right arm. LBM in both arms and legs and their variations after degarelix directly correlated with ALP and inversely correlated with CTX. Lean mass of limbs, trunk and legs significantly correlated with BMD of the hip, lean mass of the trunk significantly correlated with spine BMD. These are post-hoc analysis of a prospective study and this is the main limitation.

Conclusions

an heterogeneous change in body composition among body district is observed after ADT and bone turnover is influenced by lean mass and its variation. A supervised physical activity is crucial to maintain general physical performance and preserving bone health.
Non-line-of-sight target tracking with improved recurrent extreme learning machine
Authors: Yang Xiaofeng
Published: July 2023

Target tracking provides important location-based services in many applications. The main challenge of target tracking is to combat the severe degradation problem in Non-Line-of-Sight (NLOS) scenario. Most Deep Learning algorithms available in literature to address this issue belong to batch learning with high complexity. This paper proposes a novel online sequential learning algorithm, Improved Recurrent Extreme Learning Machine (IRELM), to solve the NLOS target tracking problem as a position series prediction task. IRELM is able to train Recurrent Neural Network (RNN) inputs one-by-one and adaptively update the input weight, hidden weight, feedback weight and output weight. Extensive simulations and experiments prove the superior tracking performance and feasible complexity of IRELM over the state-of-the-art Deep Learning methods.
Quantum Metropolis Solver: a quantum walks approach to optimization problems
Authors: Campos Roberto , Casares P. A. M. , Martin-Delgado M. A.
Published: July 2023

The efficient resolution of optimization problems is one of the key issues in today’s industry. This task relies mainly on classical algorithms that present scalability problems and processing limitations. Quantum computing has emerged to challenge these types of problems. In this paper, we focus on the Metropolis-Hastings quantum algorithm, which is based on quantum walks. We use this algorithm to build a quantum software tool called Quantum Metropolis Solver (QMS). We validate QMS with the N-Queen problem to show a potential quantum advantage in an example that can be easily extrapolated to an Artificial Intelligence domain. We carry out different simulations to validate the performance of QMS and its configuration.
Navigating fairness measures and trade-offs
Authors: Buijsman Stefan
Published: July 2023

To monitor and prevent bias in AI systems, we can use a wide range of (statistical) fairness measures. However, it is mathematically impossible to optimize all of these measures at the same time. In addition, optimizing a fairness measure often greatly reduces the accuracy of the system (Kozodoi et al., Eur J Oper Res 297:1083–1094, 2022). As a result, we need a substantive theory that informs us how to make these decisions and for what reasons. I show that by using Rawls’ notion of justice as fairness, we can create a basis for navigating fairness measures and the accuracy trade-off. In particular, this leads to a principled choice focusing on both the most vulnerable groups and the type of fairness measure that has the biggest impact on that group. This also helps to close part of the gap between philosophical accounts of distributive justice and the fairness literature that has been observed by (Kuppler et al. Distributive justice and fairness metrics in automated decision-making: How much overlap is there? arXiv preprint arXiv:2105.01441, 2021), and to operationalise the value of fairness.
Mind the Governance Gaps: Harmful Corporate Strategies Leading to Avoidance of Responsibility and Civil Society Counter-Strategies
Authors: Booth Katharine
Published: July 2023

The ‘Mind the Gap’ project has created a toolkit for civil society to hold companies to account for their adverse impacts. The toolkit sets out two distinct but interlinked frameworks: harmful corporate strategies resulting in the avoidance of responsibility for adverse impacts, and civil society counter-strategies to overcome these harmful strategies. Both frameworks capture the unique experiences of the Mind the Gap project’s global consortium partners and civil society actors focused on corporate accountability. The project responds to a need to close governance gaps that arise in the context of the current global economic system. It is only by identifying and understanding harmful corporate strategies that civil society can effectively advocate for corporate accountability and the closure of governance gaps.
Endogenous Popularity: How Perceptions of Support Affect the Popularity of Authoritarian Regimes
Authors: BUCKLEY NOAH , MARQUARDT KYLE L. , REUTER ORA JOHN , TERTYTCHNAYA KATERINA
Published: July 2023

Being popular makes it easier for dictators to govern. A growing body of scholarship therefore focuses on the factors that influence authoritarian popularity. However, it is possible that the perception of popularity itself affects incumbent approval in autocracies. We use framing experiments embedded in four surveys in Russia to examine this phenomenon. These experiments reveal that manipulating information—and thereby perceptions—about Russian President Vladimir Putin’s popularity can significantly affect respondents’ support for him. Additional analyses, which rely on a novel combination of framing and list experiments, indicate that these changes in support are not due to preference falsification, but are in fact genuine. This study has implications for research on support for authoritarian leaders and defection cascades in nondemocratic regimes.
Helicon and lower hybrid current drive comparisons in tokamak geometry
Authors: Catto Peter J. , Zhou Muni
Published: July 2023

The parallel current driven by applied helicon waves is evaluated in tokamak geometry along with the radio frequency (rf) power absorbed by the passing electrons. The results are compared with the corresponding expressions for lower hybrid current drive. The efficiency of both current drive schemes is found to be the same for any single wave frequency, single mode number limit. The evaluation of the parallel currents is performed using an adjoint technique. Tokamak geometry is retained by using an eigenfunction expansion appropriate for a transit averaged long mean free path treatment of electrons making correlated poloidal passes through the applied rf fields.
ON POSSIBLE VALUES OF THE INTERIOR ANGLE BETWEEN INTERMEDIATE SUBALGEBRAS
Authors: GUPTA VED PRAKASH , SHARMA DEEPIKA
Published: July 2023

We show that all values in the interval
$[0,{\pi }/{2}]$
can be attained as interior angles between intermediate subalgebras (as introduced by Bakshi and the first named author [‘Lattice of intermediate subalgebras’, J. Lond. Math. Soc. (2)104(2) (2021), 2082–2127]) of a certain inclusion of simple unital
$C^*$
-algebras. We also calculate the interior angles between intermediate crossed product subalgebras of any inclusion of crossed product algebras corresponding to any action of a countable discrete group and its subgroups on a unital
$C^*$
-algebra.
Cell segmentation in images without structural fluorescent labels
Authors: Zyss Daniel , Ribeiro Susana A. , Ludlam Mary J. C. , Walter Thomas , Fehri Amin
Published: July 2023

High-content screening (HCS) provides an excellent tool to understand the mechanism of action of drugs on disease-relevant model systems. Careful selection of fluorescent labels (FLs) is crucial for successful HCS assay development. HCS assays typically comprise (a) FLs containing biological information of interest, and (b) additional structural FLs enabling instance segmentation for downstream analysis. However, the limited number of available fluorescence microscopy imaging channels restricts the degree to which these FLs can be experimentally multiplexed. In this article, we present a segmentation workflow that overcomes the dependency on structural FLs for image segmentation, typically freeing two fluorescence microscopy channels for biologically relevant FLs. It consists in extracting structural information encoded within readouts that are primarily biological, by fine-tuning pre-trained state-of-the-art generalist cell segmentation models for different combinations of individual FLs, and aggregating the respective segmentation results together. Using annotated datasets that we provide, we confirm our methodology offers improvements in performance and robustness across several segmentation aggregation strategies and image acquisition methods, over different cell lines and various FLs. It thus enables the biological information content of HCS assays to be maximized without compromising the robustness and accuracy of computational single-cell profiling.
Severe COVID-19 associated hyperglycemia is caused by beta cell dysfunction: a prospective cohort study
Authors: Gojda Jan , Koudelková Kateřina , Ouřadová Anna , Lang Alexander , Krbcová Magdaléna , Gvozdeva Alexandra , Šebo Viktor , Slagmolen Lotte , Potočková Jana , Tůma Petr , Rossmeislová Lenka , Anděl Michal , Karpe Fredrik , Schlesinger Sabrina
Published: July 2023

Background

COVID-19, an infectious disease caused by SARS-CoV-2, was shown to be associated with an increased risk of new-onset diabetes. Mechanisms contributing to the development of hyperglycemia are still unclear. We aimed to study whether hyperglycemia is related to insulin resistance and/or beta cell dysfunction.

Materials and methods

Survivors of severe COVID-19 but without a known history of diabetes were examined at baseline (T0) and after 3 (T3) and 6 (T6) months: corticosteroids use, indirect calorimetry, and OGTT. Insulin response and sensitivity (IS) were expressed as insulinogenic (IGI), disposition (DI), and Matsuda insulin sensitivity index (ISI). Resting energy expenditure (REE) and respiratory quotient (RQ) was calculated from the gas exchange and nitrogen losses.

Results

26 patients (out of 37) with complete outcome data were included in the analysis (age ~59.0 years; BMI ~ 30.4, 35% women). Patients were hypermetabolic at T0 (30.3 ± 4.0 kcal/kg lean mass/day, ~120% predicted) but REE declined over 6 months (ΔT6-T0 mean dif. T6-T0 (95% CI): −5.4 (−6.8, −4.1) kcal/kg FFM/day, p < 0.0001). 17 patients at T0 and 13 patients at T6 had hyperglycemia. None of the patients had positive islet autoantibodies. Insulin sensitivity in T0 was similarly low in hyperglycemic (H) and normoglycemic patients (N) (T0 ISIH = 3.12 ± 1.23, ISIN = 3.47 ± 1.78, p = 0.44), whereas insulin response was lower in the H group (DIH = 3.05 ± 1.79 vs DIN = 8.40 ± 5.42, p = 0.003). Over 6 months ISI (ΔT6-T0 mean dif. T6-T0 for ISI (95% CI): 1.84 (0.45, 3.24), p = 0.01)) increased in the H group only.

Conclusions

Patients with severe COVID-19 had increased REE and insulin resistance during the acute phase due to the infection and corticosteroid use, but these effects do not persist during the follow-up period. Only patients with insufficient insulin response developed hyperglycemia, indicating that beta cell dysfunction, rather than insulin resistance, was responsible for its occurrence.
BCKDK regulates breast cancer cell adhesion and tumor metastasis by inhibiting TRIM21 ubiquitinate talin1
Authors: Xu Chunlan , Yang Kunao , Xuan Zuodong , Li Jinxin , Liu Yankuo , Zhao Yue , Zheng Zeyuan , Bai Yang , Shi Zhiyuan , Shao Chen , Zhang Lei , Sun Huimin
Published: July 2023

Breast cancer is the most common malignant cancer in women worldwide. Cancer metastasis is the major cause of cancer-related deaths. BCKDK is associated with various diseases, including proliferation, migration, and invasion in multiple types of human cancers. However, the relevance of BCKDK to the development and progression of breast cancers and its function is unclear. This study found that BCKDK was overexpressed in breast cancer, associated with poor prognosis, and implicated in tumor metastasis. The downregulation of BCKDK expression inhibited the migration of human breast cancer cells in vitro and diminished lung metastasis in vivo. BCKDK perturbed the cadherin-catenin complex at the adherens junctions (AJs) and assembled focal adhesions (FAs) onto the extracellular matrix, thereby promoting the directed migration of breast cancer cells. We observed that BCKDK acted as a conserved regulator of the ubiquitination of cytoskeletal protein talin1 and the activation of the FAK/MAPK pathway. Further studies revealed that BCKDK inhibited the binding of talin1 to E3 ubiquitin ligase-TRIM21, leading to the decreased ubiquitination/degradation of talin1. In conclusion, identifying BCKDK as a biomarker for breast cancer metastasis facilitated further research on diagnostic biomarkers. Elucidating the mechanism by which BCKDK exerted its biological effect could provide a new theoretical basis for developing new markers for breast cancer metastasis and contribute to developing new therapies for the clinical treatment of breast cancer patients.
NEDD8-activating enzyme inhibition potentiates the anti-myeloma activity of natural killer cells
Authors: Petillo Sara , Sproviero Elena , Loconte Luisa , Cuollo Lorenzo , Zingoni Alessandra , Molfetta Rosa , Fionda Cinzia , Soriani Alessandra , Cerboni Cristina , Petrucci Maria Teresa , Fazio Francesca , Paolini Rossella , Santoni Angela , Cippitelli Marco
Published: July 2023

Natural Killer (NK) cells act as important regulators in the development and progression of hematological malignancies and their suppressor activity against Multiple Myeloma (MM) cells has been confirmed in many studies. Significant changes in the distribution of NK cell subsets and dysfunctions of NK cell effector activities were described in MM patients and correlated with disease staging. Thus, restoring or enhancing the functionality of these effectors for the treatment of MM represents a critical need. Neddylation is a post-translational modification that adds a ubiquitin-like molecule, NEDD8, to the substrate protein. One of the outcomes is the activation of the Cullin Ring Ligases (CRLs), a class of ubiquitin-ligases that controls the degradation of about 20% of proteasome-regulated proteins. Overactivation of CRLs has been described in cancer and can lead to tumor growth and progression. Thus, targeting neddylation represents an attractive approach for cancer treatment. Our group has recently described how pharmacologic inhibition of neddylation increases the expression of the NKG2D activating receptor ligands, MICA and MICB, in MM cells, making these cells more susceptible to NK cell degranulation and killing. Here, we extended our investigation to the direct role of neddylation on NK cell effector functions exerted against MM. We observed that inhibition of neddylation enhanced NK cell-mediated degranulation and killing against MM cells and improved Daratumumab/Elotuzumab-mediated response. Mechanistically, inhibition of neddylation increased the expression of Rac1 and RhoA GTPases in NK cells, critical mediators for an efficient degranulation at the immunological synapse of cytotoxic lymphocytes, and augmented the levels of F-actin and perforin polarization in NK cells contacting target cells. Moreover, inhibition of neddylation partially abrogated TGFβ-mediated repression of NK cell effector activity. This study describes the role of neddylation on NK cell effector functions and highlights the positive immunomodulatory effects achieved by the inhibition of this pathway in MM.
Bcl-2 family inhibitors sensitize human cancer models to therapy
Authors: Valentini Elisabetta , Di Martile Marta , Brignone Matteo , Di Caprio Marica , Manni Isabella , Chiappa Michela , Sergio Ilaria , Chiacchiarini Martina , Bazzichetto Chiara , Conciatori Fabiana , D’Aguanno Simona , D’Angelo Carmen , Ragno Rino , Russillo Michelangelo , Colotti Gianni , Marchesi Francesco , Bellone Maria Laura , Dal Piaz Fabrizio , Felli Maria Pia , Damia Giovanna , Del Bufalo Donatella
Published: July 2023

BH3 mimetics, targeting the Bcl-2 family anti-apoptotic proteins, represent a promising therapeutic opportunity in cancers. ABT-199, the first specific Bcl-2 inhibitor, was approved by FDA for the treatment of several hematological malignancies. We have recently discovered IS21, a novel pan BH3 mimetic with preclinical antitumor activity in several tumor types. Here, we evaluated the efficacy of IS21 and other BH3 mimetics, both as single agents and combined with the currently used antineoplastic agents in T-cell acute lymphoblastic leukemia, ovarian cancer, and melanoma. IS21 was found to be active in T-cell acute lymphoblastic leukemia, melanoma, lung, pancreatic, and ovarian cancer cell lines. Bcl-xL and Mcl-1 protein levels predicted IS21 sensitivity in melanoma and ovarian cancer, respectively. Exploring IS21 mechanism of action, we found that IS21 activity depends on the presence of BAX and BAK proteins: complexes between Bcl-2 and Bcl-xL proteins and their main binding partners were reduced after IS21 treatment. In combination experiments, BH3 mimetics sensitized leukemia cells to chemotherapy, ovarian cancer cells and melanoma models to PARP and MAPK inhibitors, respectively. We showed that this enhancing effect was related to the potentiation of the apoptotic pathway, both in hematologic and solid tumors. In conclusion, our data suggest the use of inhibitors of anti-apoptotic proteins as a therapeutic strategy to enhance the efficacy of anticancer treatment.
ZHX2 deficiency enriches hybrid MET cells through regulating E-cadherin expression
Authors: He Yan , Zhang Qimin , Chen Yuanhong , Wu Yingjian , Quan Yuan , Chen Weihua , Yao Jing , Zhang Peijing
Published: July 2023

Growing evidence indicates that the epithelial to mesenchymal (E/M) hybrid state plays a key role in tumorigenesis. Importantly, a hybrid mesenchymal to epithelial transition (MET) state in which individual cells express both epithelial and mesenchymal markers was recently identified in vivo, further strengthening the bonds between the hybrid EMT state and cancer progression. However, the role and the molecular mechanisms by which the hybrid MET state is maintained in triple-negative breast cancer cells (TNBC) remain elusive. Here, we find that loss of ZHX2 expression results in the hybrid MET phenotype in mesenchymal TNBC cells. Mechanistically, through directly binding to the CDH1 promoter, depletion of ZHX2 specifically reactivates expression of CDH1 encoding E-cadherin, an epithelial marker that is crucial for maintaining epithelial phenotype. Functionally, loss of ZHX2 expression enriches the hybrid MET cells and inhibits the migration and dissemination of TNBC cells or organoids, which could be reversed by restoration of E-cadherin. Moreover, depletion of ZHX2 suppresses lung metastasis in preclinical models of TNBC. In patients with TNBC, ZHX2 expression was amplified and negatively correlated with the expression of E-cadherin. These findings suggest that loss of ZHX2 promotes the hybrid MET state to impair TNBC progression.