bluuebunny/crossref_metadata_2025 huggingface dataset:
Brick wall diagrams as a completely integrable system
Authors: Kade Moritz , Staudacher Matthias
Published: January 2024

We study the free energy of an integrable, planar, chiral and non-unitary four-dimensional Yukawa theory, the bi-fermion fishnet theory discovered by Pittelli and Preti. The typical Feynman-diagrams of this model are of regular “brick-wall”-type, replacing the regular square lattices of standard fishnet theory. We adapt A. B. Zamolodchikov’s powerful classic computation of the thermodynamic free energy of fishnet graphs to the brick-wall case in a transparent fashion, and find the result in closed form. Finally, we briefly discuss two further candidate integrable models in three and six dimensions related to the brick wall model.
Two-loop coefficient functions in deeply virtual Compton scattering: flavor-singlet axial-vector and transversity case
Authors: Ji Yao , Schoenleber J.
Published: January 2024

Abstract

We calculate the two-loop flavor-singlet axial-vector and gluon transversity coefficient functions for deeply virtual Compton scattering in QCD. We observe interesting properties regarding the transcendentality of the transversity coefficient function. Our results complete the calculation of the full next-to-next-to-leading order coefficient function in deeply virtual Compton scattering. Numerically, the two-loop corrections in the axial-vector and transversity channel are comparable to their vector counterpart at moderate skewness parameter ξ and hence indispensable for analyzing the upcoming high-precision data from the Electron-Ion Collider.
Mitochondrial oxidative damage reprograms lipid metabolism of renal tubular epithelial cells in the diabetic kidney
Authors: Hou Yanjuan , Tan Enxue , Shi Honghong , Ren Xiayu , Wan Xing , Wu Wenjie , Chen Yiliang , Niu Hiumin , Zhu Guozhen , Li Jing , Li Yafeng , Wang Lihua
Published: January 2024

The functional and structural changes in the proximal tubule play an important role in the occurrence and development of diabetic kidney disease (DKD). Diabetes-induced metabolic changes, including lipid metabolism reprogramming, are reported to lead to changes in the state of tubular epithelial cells (TECs), and among all the disturbances in metabolism, mitochondria serve as central regulators. Mitochondrial dysfunction, accompanied by increased production of mitochondrial reactive oxygen species (mtROS), is considered one of the primary factors causing diabetic tubular injury. Most studies have discussed how altered metabolic flux drives mitochondrial oxidative stress during DKD. In the present study, we focused on targeting mitochondrial damage as an upstream factor in metabolic abnormalities under diabetic conditions in TECs. Using SS31, a tetrapeptide that protects the mitochondrial cristae structure, we demonstrated that mitochondrial oxidative damage contributes to TEC injury and lipid peroxidation caused by lipid accumulation. Mitochondria protected using SS31 significantly reversed the decreased expression of key enzymes and regulators of fatty acid oxidation (FAO), but had no obvious effect on major glucose metabolic rate-limiting enzymes. Mitochondrial oxidative stress facilitated renal Sphingosine-1-phosphate (S1P) deposition and SS31 limited the elevated Acer1, S1pr1 and SPHK1 activity, and the decreased Spns2 expression. These data suggest a role of mitochondrial oxidative damage in unbalanced lipid metabolism, including lipid droplet (LD) formulation, lipid peroxidation, and impaired FAO and sphingolipid homeostasis in DKD. An in vitro study demonstrated that high glucose drove elevated expression of cytosolic phospholipase A2 (cPLA2), which, in turn, was responsible for the altered lipid metabolism, including LD generation and S1P accumulation, in HK-2 cells. A mitochondria-targeted antioxidant inhibited the activation of cPLA2f isoforms. Taken together, these findings identify mechanistic links between mitochondrial oxidative metabolism and reprogrammed lipid metabolism in diabetic TECs, and provide further evidence for the nephroprotective effects of SS31 via influencing metabolic pathways.
On the profinite rigidity of free and surface groups
Authors: Morales Ismael
Published: January 2024

Let S be either a free group or the fundamental group of a closed hyperbolic surface. We show that if G is a finitely generated residually-p group with the same pro-p completion as S, then two-generated subgroups of G are free. This generalises (and gives a new proof of) the analogous result of Baumslag for parafree groups. Our argument relies on the following new ingredient: if G is a residually-(torsion-free nilpotent) group and $$H\le G$$

H
≤
G

is a virtually polycyclic subgroup, then H is nilpotent and the pro-p topology of G induces on H its full pro-p topology. Then we study applications to profinite rigidity. Remeslennikov conjectured that a finitely generated residually finite G with profinite completion $${\hat{G}}\cong {\hat{S}}$$

G
^

≅

S
^

is necessarily $$G\cong S$$

G
≅
S

. We confirm this when G belongs to a class of groups $${\mathcal {H}_\textbf{ab}}$$

H
ab

that has a finite abelian hierarchy starting with finitely generated residually free groups. This strengthens a previous result of Wilton that relies on the hyperbolicity assumption. Lastly, we prove that the group $$S\times \mathbb {Z}^n$$

S
×

Z

n

is profinitely rigid within finitely generated residually free groups.
Exploring Winegrowers’ Behaviours and Ecological Impacts Under Climate Change and Policy Scenarios—Examples from Three European Winegrowing Regions
Authors: Chen Yang , Möth Stefan , Winter Silvia , Willemen Louise , Schwarz Nina
Published: January 2024

Viticulture is an example of a socio-ecological system that poses serious challenges for sustainable soil management and pesticide use, with various interactions between winegrowers’ decision-making and ecological consequences. This study introduces an agent-based model (ABM) on winegrowers’ decision on inter-row management and pesticide use. The ABM builds upon an empirical study of winegrowers’ decision-making in European viticultural landscapes and has been built for three case study regions: Leithaberg (Austria), Palatinate (Germany) and Târnave (Romania). The ABM allows for analysing potential effects of policy instruments including mandatory vegetation cover in the inter-rows, the reduction of fungicide use and ban of insecticides against Lobesia botrana. The effects of policies differ between the case study regions, indicating how important the local context is for effective policies. For example, policies aiming at higher inter-row vegetation cover had the strongest effects on vegetation cover, landscape aesthetics and soil loss in Târnave since many vineyards are currently intensively tilled and there exist no policies supporting inter-row vegetation cover in Romania.
Efficient In Vitro Platform for Multiplication, Acclimatization, and Deliver of High-NaCl-Tolerant Clones of the Halophyte Arthrocaulon macrostachyum
Authors: Jurado-Mañogil Carmen , Díaz-Vivancos Pedro , Hernández José A. , Piqueras Abel , Barba-Espín Gregorio
Published: January 2024

Halophytes are species able to grow and complete their life cycle under NaCl concentrations above 0.2 M. In a context of growing population and uncertain agricultural food sustainability, there is an interest on halophytes as potential source of food and fodder. However, scarce research has addressed in vitro propagation of halophytes as a tool for study, conservation, and propagation of elite germplasm. In this study, an efficient method for micropropagation of the succulent and salt accumulator halophyte Arthrocaulon macrostachyum has been established for the first time, using shoot tips from in vitro-germinated plant material. During shoot multiplication stage, superior genotypes were selected from explants grown in high strength and NaCl content medium and subsequently rooted and acclimatized to ex vitro conditions. A comprehensive characterization including determination of oxidative stress, photosynthesis performance, and mineral nutrient contents was done. This research gains insight into the physiological and biochemical characterization of halophytes during micropropagation and provides a solid platform for the production of elite A. macrostachyum germplasm for ulterior uses.
Two-stage laparoscopic transversus abdominis plane block as an equivalent alternative to thoracic epidural anaesthesia in bowel resection—an explorative cohort study
Authors: Kaufmann M. , Orth V. , Dorwarth T.-J. , Benrath J. , Gerber B. , Ghezel-Ahmadi D. , Reißfelder C. , Herrle F.
Published: January 2024

Purpose

We evaluated the effect of the two-stage laparoscopic transversus abdominis plane block (TS-L-TAPB) in comparison to thoracic epidural anaesthesia (TEA) and a one-stage L-TAPB (OS-L-TAPB) in patients who underwent elective laparoscopic bowel resection.

Methods

We compared a TS-L-TAPB (266 mg bupivacaine), which was performed bilaterally at the beginning and end of surgery, with two retrospective cohorts. These were patients who had undergone a TEA (ropivacaine/sufentanil) or an OS-L-TAPB (200 mg ropivacaine) at the beginning of surgery. Oral and i.v. opiate requirements were documented over the first 3 postoperative days (POD).

Results

Patients were divided into three groups TEA (n = 23), OS-L-TAPB (n = 75), and TS-L-TAPB (n = 49). By the evening of the third POD, patients with a TEA had a higher cumulative opiate requirement with a median of 45.625 mg [0; 202.5] than patients in the OS-L-TAPB group at 10 mg [0; 245.625] and the TS-L-TAPB group at 5.625 mg [0; 215.625] (p = 0.1438). One hour after arrival in the recovery room, significantly more patients in the TEA group (100%) did not need oral and i.v. opioids than in the TS-L-TAPB (78%) and OS-L-TAPB groups (68%) (p = 0.0067).This was without clinical relevance however as the median in all groups was 0 mg. On the third POD, patients in the TEA group had a significantly higher median oral and i.v. opioid dose at 40 mg [0; 80] than the TS-L-TAPB and OS-L-TAPB groups, both at 0 mg [0; 80] (p = 0.0009).

Conclusion

The TS-L-TAP showed statistically significant and clinically meaningful benefits over TEA and OS-L-TAP in reducing postoperative opiate requirements.
Autologous microfragmented adipose tissue treatment of knee osteoarthritis demonstrates effectiveness in 68% of patients at 4-year follow-up
Authors: Onorato Francesco , Rucci Massimiliano , Alessio-Mazzola Mattia , Bistolfi Alessandro , Castagnoli Carlotta , Formica Matteo , Ferracini Riccardo
Published: January 2024

Background

Adipose tissue-derived stem cells are an interesting therapeutic option for early knee osteoarthritis (OA) treatment due to their high plasticity, easiness of harvesting and rapidity of administration. The aim of this study was to evaluate the medium-term effectiveness and safety of Microfragmented Autologous Fat Tissue (MFAT) injection treatment at 4-year follow-up and to investigate potential correlations among patients’ pre-treatment clinical condition and clinical outcomes to identify possible predicting factors for procedure success or failure.

Patients and methods

This is a prospective trial enrolling 46 patients with diagnosis of symptomatic knee OA and failure of previous conservative measures who underwent diagnostic arthroscopy and single autologous MFAT injection between June 2017 and July 2018. Patients were assessed with repeated clinical scoring systems at baseline, 6 months, 1 and 4 years after surgery. The evaluation included demographic characteristics, arthroscopic findings, and stem cell number from injected tissue.

Results

No major complications were reported during follow-up period and there was a significant increase of Lysholm knee score from baseline value of 61.7 ± 13.8 to 79.5 ± 16.9 at 4 years (p < 0.001). The WOMAC score increased from a baseline value of 66.5 ± 14.7 to 82.8 ± 15.7 at 4 years (p < 0.001) and there was a significant decrease of VAS pain score from baseline value of 6.3 ± 1.5 to 3.5 ± 2.6 at 4-year follow-up (p < 0.001). ROM improved significantly from 118.4 ± 2.6 to 122.5 ± 2.5 at 12 months (p < 0.001), but did not improve at 4 years (p > 0.05). 15 patients (32.6%) were considered treatment failures, because they required secondary surgery, further injection therapy or experienced symptoms persistence. Patient with synovitis had 75% failure rate, although synovitis did not result as a statistically significant factor influencing clinical outcome up to 4-year follow-up (p = 0.058). Age, cartilage defects severity, BMI, concomitant procedures, and stem cell number from injected MFAT did not show any significant correlation with the results.

Conclusions

MFAT intra-articular injection is a safe procedure with positive improvements up to 4-year follow-up in patients with early knee OA. These findings suggest MFAT could be a minimally invasive treatment of early knee OA with durable benefits at mid-term evaluation.

Trial registration

IRB number ID-3522.
Treatment of cartilage defects in the patellofemoral joint with matrix-associated autologous chondrocyte implantation effectively improves pain, function, and radiological outcomes after 5–7 years
Authors: Eichinger Martin , Henninger Benjamin , Petry Benjamin , Schuster Philipp , Herbst Elmar , Wagner Moritz , Rosenberger Ralf , Mayr Raul
Published: January 2024

Introduction

The aim of the present study was to evaluate midterm outcomes 5–7 years after matrix-associated autologous chondrocyte implantation (MACI) in the patellofemoral joint.

Materials and methods

Twenty-six patients who had undergone MACI using the Novocart® 3D scaffold were prospectively evaluated. Clinical outcomes were determined by measuring the 36-Item Short-Form Health Survey (SF-36) and International Knee Documentation Committee (IKDC) scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) values preoperatively and 3, 6, and 12 months, and a mean of 6 years postoperatively. At the final follow-up, the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was evaluated.

Results

Twenty-two patients with 23 focal cartilage defects (19 patella and four trochlea) were available for the final follow-up. The mean defect size was 4.0 ± 1.9 cm2 (range 2.4–9.4 cm2). All clinical outcome scores improved significantly until 5–7 years after MACI (SF-36 score, 61.2 ± 19.6 to 83.2 ± 11.6; P = 0.001; IKDC score, 47.5 ± 20.6 to 74.7 ± 15.5; P < 0.001; and WOMAC, 29.8 ± 15.7 to 8.2 ± 10.3; P < 0.001). The mean MOCART score was 76.0 ± 11.0 at the final follow-up. Nineteen of the 22 patients (86.4%) were satisfied with the outcomes after 5–7 years and responded that they would undergo the procedure again.

Conclusion

MACI in the patellofemoral joint demonstrated good midterm clinical results with a significant reduction in pain, improvement in function, and high patient satisfaction. These clinical findings are supported by radiological evidence from MOCART scores.

Level of evidence

IV–case series.
The effects of an interdisciplinary employment program on paid employment and mental health among persons with severe mental disorders
Authors: Hijdra R. W. , Robroek S. J. W. , Sadigh Y. , Burdorf A. , Schuring M.
Published: January 2024

Purpose

This study evaluates the effects of the interdisciplinary employment program ‘Work As Best Care (WABC)’ on employment participation and mental health of persons with severe mental disorders.

Methods

WABC is a ‘work first’ employment program for unemployed persons with severe mental disorders in which employment professionals work closely together with mental health professionals. In a longitudinal non-randomized controlled study, participants of WABC (n = 35) are compared with participants of the control group (n = 37), who received regular employment support. Participants were followed for 1 year and filled out questionnaires on individual characteristics and health at baseline, after 6 and 12 months. This information was enriched with monthly register data on employment status from 2015 until 2020. Difference-in-differences analyses were performed to investigate changes in employment participation among participants of WABC and the control group. A generalized linear mixed-effects model was used to compare changes in mental health (measured on 0–100 scale) between the two groups.

Results

Before WABC, employment participation was 22.0%points lower among participants of WABC compared to the control group. After starting WABC, employment participation increased with 15.3%points per year among participants of WABC, compared to 5.6%points in the control group. Among all participants of WABC, no change in mental health was found (β 1.0, 95% CI − 3.4; 5.5). Only female participants of WABC showed a significant change in mental health (β 8.0, 95% CI 2.6; 13.4).

Conclusion

To enhance employment participation of persons with severe mental disorders, an interdisciplinary ‘work-first’ approach in which professionals of employment services and mental health services work in close collaboration, is of paramount importance.
A century of exercise physiology: effects of muscle contraction and exercise on skeletal muscle Na+,K+-ATPase, Na+ and K+ ions, and on plasma K+ concentration—historical developments
Authors: McKenna Michael J. , Renaud Jean-Marc , Ørtenblad Niels , Overgaard Kristian
Published: January 2024

This historical review traces key discoveries regarding K+ and Na+ ions in skeletal muscle at rest and with exercise, including contents and concentrations, Na+,K+-ATPase (NKA) and exercise effects on plasma [K+] in humans. Following initial measures in 1896 of muscle contents in various species, including humans, electrical stimulation of animal muscle showed K+ loss and gains in Na+, Cl− and H20, then subsequently bidirectional muscle K+ and Na+ fluxes. After NKA discovery in 1957, methods were developed to quantify muscle NKA activity via rates of ATP hydrolysis, Na+/K+ radioisotope fluxes, [3H]-ouabain binding and phosphatase activity. Since then, it became clear that NKA plays a central role in Na+/K+ homeostasis and that NKA content and activity are regulated by muscle contractions and numerous hormones. During intense exercise in humans, muscle intracellular [K+] falls by 21 mM (range − 13 to − 39 mM), interstitial [K+] increases to 12–13 mM, and plasma [K+] rises to 6–8 mM, whilst post-exercise plasma [K+] falls rapidly, reflecting increased muscle NKA activity. Contractions were shown to increase NKA activity in proportion to activation frequency in animal intact muscle preparations. In human muscle, [3H]-ouabain-binding content fully quantifies NKA content, whilst the method mainly detects α2 isoforms in rats. Acute or chronic exercise affects human muscle K+, NKA content, activity, isoforms and phospholemman (FXYD1). Numerous hormones, pharmacological and dietary interventions, altered acid–base or redox states, exercise training and physical inactivity modulate plasma [K+] during exercise. Finally, historical research approaches largely excluded female participants and typically used very small sample sizes.
Central nervous system tumours in neonates: what should the neonatologist know?
Authors: Toniutti Maristella , Sasso Annalisa Lo , Carai Andrea , Colafati Giovanna Stefania , Piccirilli Eleonora , Del Baldo Giada , Mastronuzzi Angela
Published: January 2024

Central nervous system (CNS) tumours in neonates are relatively rare and present differently when compared with those occurring later in childhood in terms of aetiology, clinical features, location, histology and prognosis. The clinical presentation is extremely variable. Even if the most frequent clinical sign is a macrocephaly, there are many other non-specific symptoms associated. The prognosis is usually poor with overall survival of less than 30%. Surgery continues to be the primary treatment for neonatal CNS tumours, aiming for a gross total resection, directly correlated with prognosis and the overall outcome. The chemotherapy is the only adjuvant therapy whereas the radiotherapy is avoided under three years of age because of the severe sequelae. Hence the importance of molecular characterization of these neoplasms in order to improve the accuracy of the diagnosis and identify new therapeutic targets. The aim of this review is to describe the main characteristics of these tumours and the recent advances in their treatment in order to recognize these pathologies in the prenatal period and create a multidisciplinary team providing the best possible treatment while minimising the risk of long-term complications. Neonatologists play a key role in the early detection, diagnostic evaluation, management and supportive care of these neonates.

  Conclusion: The aim of this review is to describe the main characteristics of these tumours and the recent advances in their treatment in order to ensure the essential knowledge that will help the neonatologist identify them and create a multidisciplinary team providing the best possible treatment while minimising the risk of long-term complications.

What is Known:• Neonatal CNS tumours are relatively rare and their early identification is important to identify the best diagnostic-therapeutic management.• Surgery is the main treatment of neonatal CNS tumours. The extent of surgical resection directly correlates with prognosis and outcome.

What is New:• Predisposing conditions such as Cancer Predisposition Syndromes must be considered.• Targeted drugs and other therapeutic strategies can be identified through molecular characterization
Looking inside the lab: a systematic literature review of economic experiments in health service provision
Authors: Finocchiaro Castro Massimo , Guccio Calogero , Romeo Domenica
Published: January 2024

Experimental economics is, nowadays, a well-established approach to investigate agents’ behavior under economic incentives. In the last decade, a fast-growing number of studies have focused on the application of experimental methodology to health policy issues. The results of that stream of literature have been intriguing and strongly policy oriented. However, those findings are scattered between different health-related topics, making it difficult to grasp the overall state-of-the-art. Hence, to make the main contributions understandable at a glance, we conduct a systematic literature review of laboratory experiments on the supply of health services. Of the 1248 articles retrieved from 2011, 56 articles published in peer-review journals have met our inclusion criteria. Thus, we have described the experimental designs of each of the selected papers and we have classified them according to their main area of interest.
Engagement and accessibility tools for pro-environmental action on air quality: the SOCIO-BEE paradigm
Authors: Atutxa Ekhi , Garcia-Torres Sofia , Kyfonidis Charalampos , Karanassos Dimitrios , Kopsacheilis Evangelos , Tsita Christina , Casado-Mansilla Diego , Emvoliadis Alexandros , Angelis Georgios , López-de-Ipiña Diego , Puerta Maite , Drosou Anastasios , Tzovaras Dimitrios
Published: January 2024

The involvement of citizens and all stakeholders is crucial in tackling environmental and social matters. This, addressing equity and diversity issues, although challenging, is a necessary condition for achieving positive outcomes and ensuring that no one is left behind. To help ease this challenge, this work presents a systematic approach to ensure inclusive participation and leverage non-technical and technical elements to maximise stakeholder engagement in scientific activities to successfully address sustainability concerns. For that, it builds on the interim results of the H2020 SOCIO-BEE project, a Citizen science (CS) proposal to reduce air pollution through inclusive community engagement and social innovation. As part of an interdisciplinary CS project, an abductive systematic combining methodology was employed, which allowed for dialogue and collaboration between theory and practice throughout the whole process, during which separate groups of experts and potential end-users were involved. The article presents (i) the stakeholder engagement strategy codified in the SOCIO-BEE toolkit as a robust, actionable and inclusive foundation of engagement to CS activities; and (ii) the digital platform UX that allows setting up campaigns for measurements and assignment to citizens, incorporating the requirements for flexibility, accessibility, limited digital literacy, inclusion and legal and ethical considerations. Their combination and mutual interaction aim to leverage the pros of CS and technology whilst reducing their cons to ensure the four pillars of applicability, scalability, actionability, and inclusion. This is supported by the presented hybrid model which combines physical and virtual spaces and individual and collective action.
Eye tracking-based evaluation of accessible and usable interactive systems: tool set of guidelines and methodological issues
Authors: Molina Ana I. , Arroyo Yoel , Lacave Carmen , Redondo Miguel A. , Bravo Crescencio , Ortega Manuel
Published: January 2024

This paper describes some fundamentals and challenges in using eye tracking for the assessment of usability and accessibility in the fields in Human–Computer Interaction and Educational Computing. This technique has great potential since it allows considering human factors and individual differences in these areas. This non-invasive method, of physiological nature, allows to know, in an objective way, the visual behavior of the users when facing a user interface or educational material, allowing to infer conclusions related to psychological processes, such as attention or cognitive load. The purpose of this work is to propose a tool set of guidelines and measures, as well as a methodological approach, to be used in eye tracking assessments. This proposal is based on and validated by the authors’ previous experience and results in the application of this technique.
A Model for Low-Frequency, Anisotropic Wind Fluctuations and Coherences in the Marine Atmosphere
Authors: Syed Abdul Haseeb , Mann Jakob
Published: January 2024

To assess dynamic loads, large offshore wind turbines need detailed and reliable statistical information on the inflow turbulence. We present a model that includes low frequencies down to $$\sim 1$$

∼
1

hr$$^{-1}$$

-
1

using the observed $$S(f) \propto f^{-5/3}$$

S

(
f
)

∝

f

-
5
/
3

in that range. The presented model contains a parameter representing the anisotropy of the two-dimensional, incompressible turbulence, and it assumes the low-frequency fluctuations to be homogeneous in the vertical direction. Combined with a three-dimensional model for the smaller scales, the model can predict correlations between different points. We have validated the model against two offshore wind data sets: a nacelle-mounted, forward-looking Doppler lidar with four beams at the Hywind Scotland offshore wind farm and sonic anemometer measurements at the FINO1 research platform in the North Sea. One-point auto spectra and two-point cross spectra were calculated after splitting the data into different atmospheric stability classes. The relative strength of the 2D low-frequency fluctuations to the 3D fluctuations was higher under stable conditions. The combined 2D+3D model was able to fit the measured spectra with good accuracy and could then predict the two-point cross spectra, co-coherences, and phase angles between wind fluctuations at different lateral and vertical separations. Good agreement was found between the measured and predicted values, albeit with exceptions. The model can generate stochastic wind fields for investigating wake meandering in wind farms or dynamic loads on floating wind turbines.
Treatment patterns of patients with HR+/HER2- metastatic breast cancer receiving CDK4/6 inhibitor-based regimens: a cohort study in the French nationwide healthcare database
Authors: Read Stephanie H. , Quignot Nadia , Kapso-Kapnang Raissa , Comerford Erin , Zheng Ying , Gainford Corona , Sasane Medha , Vataire Anne-Lise , Delzongle Laure , Bidard Francois-Clement
Published: January 2024

Purpose

To assess real-world treatment patterns in patients diagnosed with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC) who received cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with an aromatase inhibitor (AI) or fulvestrant at first line.

Methods

Patient characteristics, treatment history, and outcomes data were extracted from the French ‘Système National des Données de Santé’ (SNDS) database for patients diagnosed with HR+/HER2- mBC between January 2014 and June 2019 and who received combination therapy with a CDK4/6 inhibitor and endocrine therapy. Kaplan-Meier methodology was used to assess time to next treatment (TTNT) and time to treatment discontinuation (TTTD).

Results

The cohort comprised 6061 patients including 4032 patients who received CDK4/6 inhibitors + AIs and 2029 patients who received CDK4/6 inhibitors + fulvestrant. Median follow-up was 13.5 months (IQR 9.5–18.1). The median TTTD of first line treatment with CDK4/6 inhibitors + AIs and CDK4/6 inhibitors + fulvestrant was 17.3 months (95% CI 16.8–17.9) and 9.7 months (95% CI 9.0–10.2), respectively. Chemotherapy was the most common second line therapy. Median TTTD of subsequent treatment lines was progressively shorter following first line treatment with CDK4/6 inhibitors + AIs (2nd line: 4.6 months (95% CI 4.4–4.9) and with CDK4/6 inhibitors + fulvestrant (2nd line: 4.7 months (95% CI 4.3–5.1). TTNT was longer than TTTD across lines of therapy.

Conclusion

This real-world analysis confirms the effectiveness of CDK4/6 inhibitor-based regimens in French patients and highlights the frequent use of chemotherapy as second line therapy.
A portable low-cost device to quantify advective gas fluxes from mofettes into the lower atmosphere: First application to Starzach mofettes (Germany)
Authors: Büchau Yann Georg , Leven Carsten , Bange Jens
Published: January 2024

In this study, we introduce a portable low-cost device for in situ gas emission measurement from focused point sources of CO2, such as mofettes. We assess the individual sensors’ precision with calibration experiments and perform an independent verification of the system’s ability to measure gas flow rates in the range of liters per second. The results from one week of continuous CO2 flow observation from a wet mofette at the Starzach site is presented and correlated with the ambient meteorological dynamics. In the observed period, the gas flow rate of the examined mofette exhibits a dominant cycle of around four seconds that is linked to the gas rising upwards through a water column. We find the examined mofette to have a daily emission of 465 kg ±16 %. Furthermore, two events were observed that increased the flow rate abruptly by around 25 % within only a few minutes and a decaying period of 24 hours. These types of events were previously observed by others at the same site but dismissed as measurement errors. We discuss these events as a hydrogeological phenomenon similar to cold-water geyser eruptions. For meteorological events like the passages of high pressure fronts with steep changes in atmospheric pressure, we do not see a significant correlation between atmospheric parameters and the rate of gas exhalation in our one-week time frame, suggesting that on short timescales the atmospheric pumping effect plays a minor role for wet mofettes at the Starzach site.
Oxali-palladium nanoparticle synthesis, characterization, protein binding, and apoptosis induction in colorectal cancer cells
Authors: Golestannezhad Nasim , Divsalar Adeleh , Badalkhani-Khamseh Farideh , Rasouli Milad , Seyedarabi Arefeh , Ghalandari Behafarid , Ding Xianting , Goli Fatemeh , Bekeschus Sander , Movahedi Ali Akbar Moosavi , Moghadam Mahboube Eslami
Published: January 2024

This paper focuses on the synthesis of nano-oxali-palladium coated with turmeric extract (PdNPs) using a green chemistry technique based on the reduction in the Pd (II) complex by phytochemicals inherent in turmeric extract. PdNPs were examined and characterized using Field Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS), Fourier Transform Infrared (FTIR), and Atomic Force Microscopy (AFM). Using different spectroscopic and molecular dynamics simulations, a protein-binding analysis of the produced nanoparticle was conducted by observing its interaction with human serum albumin (HSA). Lastly, the cytotoxic effects and apoptotic processes of PdNPs were studied against the HCT116 human colorectal cell line using the MTT assay and flow cytometry tests. According to the findings, PdNPs with spherical and homogenous morphology and a size smaller than 100 nm were generated. In addition, they can induce apoptosis in colorectal cancer cells in a dose-dependent manner with a lower Cc50 (78 µL) than cisplatin and free oxali-palladium against HCT116 cells. The thermodynamic characteristics of protein binding of nanoparticles with HSA demonstrated that PdNPs had a great capacity for quenching and interacting with HSA through hydrophobic forces. In addition, molecular dynamics simulations revealed that free oxali-palladium and PdNP attach to the same area of HSA via non-covalent interactions. It is conceivable to indicate that the synthesized PdNPs are a potential candidate for the construction of novel, nature-based anticancer treatments with fewer side effects and a high level of eco-friendliness.

Graphical Abstract
Dexamethasone release from hyaluronic acid microparticle and proanthocyanidin-gelatin hydrogel in sciatic tissue regeneration
Authors: Javanmardi Kazem , Shahbazi Hamideh , Soltani Hekmat Ava , Khanmohammadi Mehdi , Goodarzi Arash
Published: January 2024

Biodegradable microparticles are useful vehicles for the controlled release of bioactive molecules in drug delivery, tissue engineering and biopharmaceutical applications. We developed dexamethasone (Dex) encapsulation into tyramine-substituted hyaluronic acid microparticles (Dex-HA-Tyr Mp) mediated by horseradish peroxidase (HRP) crosslinking using a microfluidic device and infollowing crosslinked gelatin (Gela) with proanthocyanidin (PA) as a semi-confined bed hydrogel for the repair of sciatic tissue injury. It was found that the simultaneous use of Dex-HA-Tyr Mp and cross-linked Gela-PA hydrogel improved the physical properties of the hydrogel, including mechanical strength and degradability. The designed composite also provided a sustained release system for Dex delivery to the surrounding sites, demonstrating the applicability of the fabricated hydrogel composite for sciatic nerve tissue engineering and regeneration. The encapsulated cells were viable and showed adequate growth ability and morphogenesis during prolonged incubation in Gela-PA/HA-Tyr Mp hydrogel compared to control conditions. Interestingly, histological analysis revealed a significant increase in the number of axons in the injured sciatic nerve following treatment with Dex-HA-Tyr Mp and injectable Gela-PA hydrogel compared to other control groups. In conclusion, the results demonstrated that fabricated Dex-loaded MPs and injectable hydrogel from biomimetic components are suitable systems for sustained delivery of Dex with adequate biocompatibility and the approach may have potential therapeutic applications in peripheral nerve regeneration.

Graphical Abstract
Universal Biomaterial-on-Chip: a versatile platform for evaluating cellular responses on diverse biomaterial substrates
Authors: Atif Abdul Raouf , Aramesh Morteza , Carter Sarah-Sophia , Tenje Maria , Mestres Gemma
Published: January 2024

Microfluidics has emerged as a promising approach for assessing cellular behavior in vitro, providing more physiologically relevant cell culture environments with dynamic flow and shear stresses. This study introduces the Universal Biomaterial-on-Chip (UBoC) device, which enables the evaluation of cell response on diverse biomaterial substrates in a 3D-printed microfluidic device. The UBoC platform offers mechanical stimulation of the cells and monitoring of their response on diverse biomaterials, enabling qualitative and quantitative in vitro analysis both on- and off-chip. Cell adhesion and proliferation were assessed to evaluate the biocompatibility of materials with different physical properties, while mechanical stimulation was performed to investigate shear-dependent calcium signaling in pre-osteoblasts. Moreover, the applicability of the UBoC platform in creating more complex in vitro models by culturing multiple cell types was demonstrated, establishing a dynamic multicellular environment to investigate cellular interfaces and their significance in biological processes. Overall, the UBoC presents an adaptable tool for in vitro evaluation of cellular behavior, offering opportunities for studying various biomaterials and cell interactions in microfluidic environments.

Graphical Abstract
Thermodynamic and structural change of Cu-13.5Al-4Ni shape memory alloy aged under different pressures for equal times
Authors: Balo Ş. Nevin , Manguri Hawbir Swara Ahmed
Published: January 2024

In this study, Cu-13.5Al-4Ni shape memory alloy (mass %) was tested. The alloy samples, at different pressures, were aged for an equal period of 5 min. The physical properties of Cu-13.5Al-4Ni alloy samples aged for an equal period were investigated. Differential scanning calorimetry (DSC) was used to investigate the impact on thermodynamic parameters. The differential thermal analysis (TG/DTA) measurements were made to obtain the ordered-disordered phase transformations from room temperature to 1200 °C. X-ray diffraction (XRD) and optic microscope observation were used to examine the microstructure. Microhardness measurements were performed on alloy samples aged for an equal period. The physical properties of the samples aged at different pressures for an equal period were compared to the measurement results of the homogenous sample.
Which factors determine adaptation to drought amongst farmers in Northern Thailand? Investigating farmers’ appraisals of risk and adaptation and their exposure to drought information communications as determinants of their adaptive responses
Authors: Sutcliffe Chloe , Holman Ian , Goodwin Daniel , Salmoral Gloria , Pardthaisong Liwa , Visessri Supattra , Ekkawatpanit Chaiwat , Rey Dolores
Published: January 2024

Drought communications constitute an important source of learning about climate risks and responses that can assist adaptation decision-making amongst those whose livelihoods are threatened by drought. This paper applies Protection Motivation Theory to explore associations between drought communications and attitudes towards drought risk and adaptation amongst farmers in Northern Thailand. The analysis reveals links between drought communications, farmers’ adaptation appraisal, and their adaptation decisions, whilst links with risk appraisal are minimal. The results highlight positive feedbacks between adaptation experience and appraisal and reveal a weak negative relationship between risk appraisal and adaptation appraisal. The findings imply benefits to framing drought communications in terms of the efficacy and attainability of suitable adaptations, rather than simply highlighting drought risks or providing drought warnings, to best enable farmers to build drought resilience.
Performance evaluation of mpeg-5 part 2 (lcevc): impact of packet loss
Authors: Roberts George , Adeyemi-Ejeye Anthony
Published: January 2024

This paper presents an evaluation of the latest MPEG-5 Part 2 Low Complexity Enhancement Video Coding (LCEVC) for video streaming applications using best effort protocols. LCEVC is a new video standard by MPEG, which enhances any base codec through an additional low bitrate stream, improving both video compression efficiency and and transmission. However, there is an interplay between packetization, packet loss visibility, choice of codec and video quality, which implies that prior studies with other codecs may be not as relevant. The contributions of this paper is, therefore in twofold: It evaluates the compression performance of LCEVC and then the impact of packet loss on its video quality when compared to H.264 and HEVC.The results from this evaluation suggest that, regarding compression, LCEVC outperformed its base codecs, overall in terms average encoding bitrate savings when using the constant rate factor (CRF) rate control. For example at a CRF of 19, the average encoding bitrate was reduced by  18.7% and 15.8% when compared with the base H.264 and HEVC codecs respectively. Furthermore, LCEVC produced better visual quality across the packet loss range compared to its base codecs and the quality only started to decrease once packet loss exceeded 0.8-1%, and decreases at a slower pace compared to its equivalent base codecs. This suggests that the LCEVC enhancement layer also provides error concealment. The results presented in this paper will be of interest to those considering the LCEVC standard and expected video quality in error-prone environments
Facet analysis in data envelopment analysis: some pitfalls of the CRS models
Authors: Olesen O. B. , Petersen N. C.
Published: January 2024

The nonparametric estimator of the Extended Facet reference technology for the Constant Returns to Scale case has attracted some attention, because the associated production frontier by construction does only include strongly efficient faces of maximal dimension, or strongly efficient faces that are part of such strongly efficient faces of maximal dimension. The strongly efficient faces of maximal dimension are denoted Full Dimensional Efficient Facets (FDEFs). The identification of such strongly efficient facets is facilitated by removing all inefficient and all strongly efficient but not extreme efficient DMUs from the estimation procedure of the technology set. Any face that i) is passing through the origin and with (s + m − 1) linear independent extreme efficient observed DMUs positioned on it and ii) with a normal vector with strict positive (strict negative) output (input) components, is a FDEF, where s (m) is the number of outputs (inputs). It is, however, not correct that every face that satisfies only i) is a FDEF. We denote a face (a subface) that satisfies only condition i) but not condition ii) for an AP-face (an AP-subface). It is proved that a radial projection of any output input combination in the estimated EXFA technology set is positioned on the strongly efficient frontier if and only if i) no AP-(sub)faces exist, ii) a regulaty condition RC1 is satisfied and only dual multiplier constraints corresponding to extreme efficient DMUs are included in the estimation. A test for the fulfillment of the condition that no AP-(sub)faces exist is provided.
On the importance of data encoding in quantum Boltzmann methods
Authors: Schalkers Merel A. , Möller Matthias
Published: January 2024

In recent years, quantum Boltzmann methods have gained more and more interest as they might provide a viable path toward solving fluid dynamics problems on quantum computers once this emerging compute technology has matured and fault-tolerant many-qubit systems become available. The major challenge in developing a start-to-end quantum algorithm for the Boltzmann equation consists in encoding relevant data efficiently in quantum bits (qubits) and formulating the streaming, collision and reflection steps as one comprehensive unitary operation. The current literature on quantum Boltzmann methods mostly proposes data encodings and quantum primitives for individual phases of the pipeline, assuming that they can be combined to a full algorithm. In this paper, we disprove this assumption by showing that for encodings commonly discussed in the literature, either the collision or the streaming step cannot be unitary. Building on this landmark result, we propose a novel encoding in which the number of qubits used to encode the velocity depends on the number of time steps one wishes to simulate, with the upper bound depending on the total number of grid points. In light of the non-unitarity result established for existing encodings, our encoding method is to the best of our knowledge the only one currently known that can be used for a start-to-end quantum Boltzmann solver where both the collision and the streaming step are implemented as a unitary operation.
Associations between the EQ-5D-5L and exacerbations of chronic obstructive pulmonary disease in the ETHOS trial
Authors: Jackson Dan , Jenkins Martin , de Nigris Enrico , Purkayastha Debasree , Patel Mehul , Ouwens Mario
Published: January 2024

Purpose

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with deteriorating health and health-related quality of life (HRQoL) among people with COPD during and after events. HRQoL data are key to evaluating treatment cost-effectiveness and informing reimbursement decisions in COPD. EuroQoL 5-dimension 5-level (EQ-5D-5L) utility scores, based on various HRQoL measures, are used in economic evaluations of pharmacotherapy. These analyses estimated associations between EQ-5D-5L utility scores and exacerbations (new and previous) in patients with moderate-to-very severe COPD.

Methods

Longitudinal mixed models for repeated measures (MMRM), adjusted for time and treatment, were conducted using data from the ETHOS study (NCT02465567); models regressed EQ-5D-5L on current and past exacerbations that occurred during the study, adjusting for other patient reported outcomes and clinical factors.

Results

Based on the simplest covariate adjusted model (adjusted for current exacerbations and number of previous exacerbations during the study), a current moderate exacerbation was associated with an EQ-5D-5L disutility of 0.055 (95% confidence interval: 0.048, 0.062) with an additional disutility of 0.035 (0.014, 0.055) if the exacerbation was severe. After resolving, each prior exacerbation was associated with a disutility that persisted for the remainder of the study (moderate exacerbation, 0.014 [0.011, 0.016]; further disutility for severe exacerbation, 0.011 [0.003, 0.018]).

Conclusion

An EQ-5D-5L disutility of 0.090 was associated with a current severe exacerbation in ETHOS. Our findings suggest incorporating the effects of current, recently resolved, and cumulative exacerbations into economic models when estimating benefits and costs of COPD pharmacotherapy, as exacerbations have both acute and persistent effects.
Gender diversity at entrepreneurial firm IPOs: responding to changing societal norms
Authors: Kenney Martin , Patton Donald , Terjesen Siri
Published: January 2024

Recently, the lack of diversity in startup leadership has been criticized by public figures and institutional investors as a signal of inadequate governance. And yet, little is known about the historical changes in gender diversity in entrepreneurial firms. Using a unique database of the gender composition in all entrepreneurial firm IPOs from 1990 to 2020 in the USA, we examine these changes. The IPO is a particularly interesting moment in an entrepreneurial firm’s evolution, as governance evolves from a private firm directed by venture capitalists, with their beliefs about what a good management team is, into a public firm with owners who are institutional investors with potentially different goals and beliefs. Grounded in signaling theory, our expectation is that the changes in public investors’ view of proper governance will result in changes in the gender in personnel added immediately prior to the IPO and that IPO teams will be more diverse than Early Teams when the firm was younger and controlled by its private investors. We suggest that the private investors such as venture capitalists have different mental models of what “good” members or top management and the board of directors are. We expect these models are particularly influential in the digital technologies where a “tech bros” model is dominant, and thus there is little “space” for women leaders, particularly in contrast to the university research-based biotechnology industry, which has not experienced such direct criticism. We find support for our propositions, and also document an increase in women directors and top management team members over time.