bluuebunny/crossref_metadata_2025 huggingface dataset:
Shadow celestial amplitudes
Authors: Chang Chi-Ming , Cui Wei , Ma Wen-Jie , Shu Hongfei , Zou Hao
Published: February 2023

Abstract

We study scattering amplitudes in the shadow conformal primary basis, which satisfies the same defining properties as the original conformal primary basis and has many advantages over it. The shadow celestial amplitudes exhibit locality manifestly on the celestial sphere, and behave like correlation functions in conformal field theory under the operator product expansion (OPE) limit. We study the OPE limits for three-point shadow celestial amplitude, and general 2 → n − 2 shadow celestial amplitudes from a certain class of Feynman diagrams. In particular, we compute the conformal block expansion of the s-channel four-point shadow celestial amplitude of massless scalars at tree-level, and show that the expansion coefficients factorize as products of OPE coefficients.
A tale of two theories of gravity in asymptotically Anti-de Sitter spacetime
Authors: Durka Remigiusz , Kowalski-Glikman Jerzy
Published: February 2023

Abstract

We consider two BF formulations of the theory of gravity with a negative cosmological constant, of Plebanski and of MacDowell-Mansouri. Both give the standard Einstein equations in the bulk but differ in expressions of edge charges. We compute the asymptotic charges explicitly in both theories for AdS-Schwarzschild, AdS-Kerr, and AdS-Taub-NUT solutions. We find that while in the case of the Plebanski theory the charges are divergent, they are finite for MacDowell-Mansouri theory. Furthermore, we show that in the case of the arbitrary asymptotically AdS spacetimes, MacDowell-Mansouri asymptotic charges, action, and symplectic form are all finite. Therefore MacDowell-Mansouri theory of gravity in asymptotically AdS spaces does not need any counterterms.
Predictive and Prognostic Role of Tumor‐Infiltrating Lymphocytes in Patients with Advanced Breast Cancer Treated with Primary Systemic Therapy
Authors: Agarwal Gaurav , Vishvak Chanthar K. M. M. , Katiyar Shweta , Kumari Niraj , Krishnani Narendra , Sabaretnam M. , Chand Gyan , Mishra Anjali , Lal Punita
Published: February 2023

Introduction

Tumor‐infiltrating lymphocytes (TILs) are gaining recognition as an important immunological biomarker with therapeutic potential in breast cancer. In this cohort study conducted on patients with advanced breast cancer treated with primary systemic therapy (PST), the TILs concentration was correlated with response to PST and survival outcomes.

Methods

Patients with primary breast cancer treated with PST between 2016 and 2020 were included in this study, approved by IEC, and registered on ClinicalTrials.gov (NCT05250336). Tumor core biopsies obtained prior to starting treatment from 489 patients were assessed for the proportion of stromal TILs by standardized method and categorized into low (0–10% immune cells), intermediate (11–59%), and high (≥ 60%) TILs. TIL concentration and complete pathological response (pCR), disease‐free survival (DFS), and overall survival (OS) were correlated.

Results

Of the 489 patients, 372 matched the eligibility criteria for assessment of TILs and made the final study cohort. Among these, 135 were luminal, 129 HER2‐enriched, and 108 triple‐negative breast cancers (TNBC). Proportions of patients with high TILs were greater in TNBC (15.7%) and HER2‐enriched (9.3%), compared to luminal cancers (4.4%). High TIL concentration was correlated with higher pCR in all subtypes. A pCR was achieved in 33.3, 50, and 52.9% of high TIL patients in luminal, HER2‐enriched, and TNBC subtypes, respectively (p < 0.05). High TILs were linked to longer DFS and OS in TNBC and HER2‐enriched breast cancers.

Conclusion

In this first study of its kind from a low‐ and middle‐income country, high TILs concentration was found to be a predictor of response to PST across all breast cancer subtypes. TILs concentration was found predictive of better DFS and OS in TNBC and HER2‐enriched cancers. Prognostic role of TILs in luminal cancers was not so apparent.
Venetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States
Authors: Zeidan Amer M. , Pollyea Daniel A. , Borate Uma , Vasconcelos Alberto , Potluri Ravi , Rotter David , Kiendrebeogo Zephirin , Gaugler Lona , Prebet Thomas , Strocchia Maria , Bonifacio Gaetano , Chen Clara
Published: February 2023

Intensive chemotherapy (IC) is commonly used to achieve remission in patients with acute myeloid leukemia (AML). Venetoclax plus azacitidine (VEN-AZA) is FDA-approved to treat patients with AML aged ≥ 75 years or who are ineligible for IC. This retrospective analysis used de-identified electronic health records from the US-based Flatiron Health database from patients diagnosed 11/21/2018 to 10/31/2021 to compare treatment outcomes with VEN-AZA vs. IC. Patients were 1:1 propensity score-matched ($$N=276$$

N
=
276

). Assessments included rates of complete remission (CR) and hematopoietic stem cell transplant (HSCT), overall survival (OS), and relapse-free survival (RFS). CR and HSCT rates were higher with IC than with VEN-AZA (60.9% vs. 44.2% [P = 0.006] and 18.1% vs. 8.0% [P = 0.012], respectively). Median OS was 17.7 months in patients treated with IC and 11.3 months with VEN-AZA without censoring (P = 0.278) and 13.7 vs. 10.6 months, respectively, with censoring at HSCT (P = 0.584). Median RFS was 12.0 months in patients treated with IC vs. 9.5 months with VEN-AZA without censoring (P = 0.431) and 6.4 vs. 7.4 months, respectively, with censoring at HSCT (P = 0.444). No OS or RFS differences observed between the two arms reached statistical significance. Randomized controlled trials comparing the two approaches are warranted, as are novel approaches to reduce relapse rates following CR.
Experimental and DFT studies on the structural and optical properties of chitosan/polyvinyl pyrrolidone/ZnS nanocomposites
Authors: Abdelghany A. M. , Meikhail M. S. , Oraby A. H. , Aboelwafa M. A.
Published: February 2023

Chitosan/Polyvinyl pyrrolidone (CS/PVP) semi-natural polymeric blend involving gradient concentrations of ZnS nanoparticles (ZnS-NPS) was prepared via a simple casting method. In conjunction with computational density functional theory approaches (DFT), prepared samples were characterized by UV/Vis spectrophotometric studies and Fourier transform infrared measurements (FTIR) to take into account a detailed description of the different reaction mechanisms within the polymeric matrices. To conduct all calculations, the Becke three-parameter hybrid functional (B3LYP) correlation function used with the electron core potential basis set LANL2DZ was used. A detailed study of different reaction regimes was studied and reaction via Oxygen was observed to be preferred and compatible with that of the experimental data. UV/vis. Absorption experimental data were used to calculate the optical energy gap using the Mott-Davis equation and observed data was found to follow an indirect transition route.
Effect of environmental disturbances on crossflow instability
Authors: Placidi Marco , Ashworth Richard , Atkin Chris J. , Rolston Stephen
Published: February 2023

Wind tunnel experiments on the receptivity of three-dimensional boundary layers were performed in a range of freestream turbulence intensities, Tu, from 0.01%—the lowest level ever achieved in this type of work—up to 0.41%. This work confirms that for $$Tu=0.01\%$$

T
u
=
0.01
%

, and presumably below this level, the transition process is dominated by stationary modes. These are receptive to surface roughness and generate Type-I and Type-II secondary instabilities that eventually cause the transition to turbulence. The saturation amplitude of these stationary waves is highly sensitive to the level of environmental disturbances; the former is here recorded to be the highest in the literature, with the latter being the lowest. Travelling modes are still present; however, their influence on the transition process is marginal. At matched surface roughness levels, when the level of environmental disturbance is enhanced to $$Tu\ge 0.33\%$$

T
u
≥
0.33
%

, the travelling modes acquire more importance, strongly influencing the laminar/turbulent transition process, whilst the initial amplitude and growth of the stationary modes are hindered. For this level of Tu, is the interaction of steady and unsteady disturbances that produces highly amplified waves (Type-III), that quickly lead to nonlinear growth and anticipated turbulence. Finally, a simple rule of thumb is proposed, where the transition front was found to move forward by roughly $$10\%$$

10
%

chord for an increase in one order of magnitude in the Tu levels.

Graphical abstract
Outcomes of complex colorectal polyps managed by multi-disciplinary team strategies—a multi-centre observational study
Authors: Parker J. , Gupta S. , Shenbagaraj L. , Harborne P. , Ramaraj R. , Karandikar S. , Mottershead M. , Barbour J. , Mohammed N. , Lockett M. , Lyons A. , Vega R. , Torkington J. , Dolwani S.
Published: February 2023

Purpose

Team management strategies for complex colorectal polyps are recommended by professional guidelines. Multi-disciplinary meetings are used across the UK with limited information regarding their impact. The aim of this multi-centre observational study was to assess procedures and outcomes of patients managed using these approaches.

Method

This was a retrospective, observational study of patients managed by six UK sites. Information was collected regarding procedures and outcomes including length of stay, adverse events, readmissions and cancers.

Results

Two thousand one hundred ninety-two complex polyps in 2109 patients were analysed with increasing referrals annually. Most presented symptomatically and the mean polyp size was 32.1 mm. Primary interventions included endoscopic therapy (75.6%), conservative management (8.3%), colonic resection (8.1%), trans-anal surgery (6.8%) or combined procedures (1.1%). The number of primary colonic resections decreased over the study period without a reciprocal increase in secondary procedures or recurrence. Secondary procedures were required in 7.8%. The median length of stay for endoscopic procedures was 0 days with 77.5% completed as day cases. Median length of stay was 5 days for colonic resections. Overall adverse event and 30-day readmission rates were 9.0% and 3.3% respectively. Malignancy was identified in 8.8%. Benign polyp recurrence occurred in 13.1% with a median follow up of 30.4 months. Screening detected lesions were more likely to undergo bowel resection. Colonic resection was associated with longer stays, higher adverse events and more cancers on final histology.

Conclusion

Multi-disciplinary team management of complex polyps is safe and effective. Standardisation of organisation and quality monitoring is needed to continue positive effects on outcomes and services.
Makrozytäre Anämie und Polychondritis: VEXAS-Syndrom
Authors: Zeisbrich Markus , Schindler Viktoria , Krausz Máté , Proietti Michele , Mrovecova Pavla , Voll Reinhard E. , Glaser Cornelia , Röther Fabian , Warnatz Klaus , Venhoff Nils
Published: February 2023

Das VEXAS-Syndrom (Akronym für Vacuoles, E1 enzyme, X‑linked, Autoinflammatory, Somatic) wurde Ende 2020 erstmals beschrieben und verursacht durch eine erworbene Mutation auf dem X‑Chromosom ein autoinflammatorisches Syndrom vorwiegend bei Männern im höheren Lebensalter. Klinisch zeichnet sich das VEXAS-Syndrom durch ein Mischbild aus rheumatologischer Erkrankung mit separaten hämatologischen Pathologien aus, wobei besonders häufig eine Polychondritis und fast immer eine makrozytäre Anämie auftreten. Anhand dieser Kasuistik werden die diagnostischen Kernpunkte zur Erkennung des VEXAS-Syndroms demonstriert.
Management of acute periprosthetic knee infection: a comparison of arthroscopic and open debridement
Authors: Bartsch A. , Krenn P. , Lubberts B. , Morgenstern M. , Pagenstert G. , Clauss M.
Published: February 2023

Introduction

In acute periprosthetic knee infections, debridement and implant retention (DAIR) is the preferred treatment prior to one- and two-stage revisions. The aim of this study is to compare the outcomes of arthroscopic and open debridement of infected primary total knee arthroplasties (TKA).

Material and methods

We analyzed clinical, laboratory, and antibiotic treatment data, collected in patients with periprosthetic knee infection treated with DAIR at a Swiss Level 1 orthopedic and trauma center over a 10-year period between January 2005 and May 2015. Inclusion criteria were primary total knee arthroplasty and early postoperative or acute hematogenous periprosthetic joint infection (PJI). The primary endpoint was the need for further revision surgery due to persistent infection. The secondary endpoint was the prosthesis salvage in further infection surgeries.

Results

Forty-two patients with 44 acute or hematogenous periprosthetic knee infections were included. We recorded 20 recurrent infections (45%) in our study population: 10 (77%) out of 13 in the arthroscopic DAIR group and 10 (32%) out of 31 in the open DAIR group. Two-stage revision, meaning complete removal of the TKA, insertion of a spacer and replantation at a second stage, had to be performed in three patients treated initially arthroscopically (23%) and in six patients treated initially with an open surgical procedure (21%).

Conclusions

Open debridement for acute periprosthetic knee infection shows clear benefits in terms of infection eradication and prosthesis salvage compared to arthroscopic DAIR.
Radiological presence of vascular loops in the cerebellopontine angle region in patients with unilateral Ménière’s disease
Authors: Lei Ping , Xia Kaijun , Li Jing , Liu Yingzhao , Zhou Renhong , Liu Jingjing , Wang Hongchang , Zhou Yue , Leng Yangming , Liu Bo
Published: February 2023

Objective

The relationship between vascular compression of the vestibulocochlear nerve and audio-vestibular symptoms remains controversial. We aimed to examine the radiological features of vascular loops signs in cerebellopontine angle (CPA) and internal auditory canal (IAC) in patients with unilateral Ménière’s disease (MD).

Methods

One hundred and thirty-seven patients with unilateral definite MD and 69 control subjects (138 ears) were enrolled. All subjects received magnetic resonance imaging of CPA-IAC. The configuration of vascular loops in CPA-IAC, based on the Kazawa classification system, from MD-affected, non-affected and control ears were compared. The associations between imaging findings and Ménière’s stage, electrocochleogram (EcochG) and caloric test were analyzed.

Results

(1) Among the MD-affected ears, 6 cases (4.4%) were classified as Kazawa type IA, 27 cases (19.7%) as IB, 60 cases (43.8%) as IIA, and 44 cases (32.1%) as IIB. No significant interaural difference in the distribution of Kazawa's types was found ($${x}^{2}$$

x

2

= 4.737, p = 0.578) in unilateral MD patients. (2) The distribution of Kazawa's types were not significantly different between the MD-affected ears and the control subjects ($${x}^{2}$$

x

2

= 2.876, p = 0.411). (3) No relationship was found between Kazawa staging of the MD-affected ear and Ménière’s stage (H = 2.679, p = 0.444), EcochG ($${x}^{2}$$

x

2

= 0.827, p = 0.867) and caloric test ($${x}^{2}$$

x

2

= 4.116, p = 0.248).

Conclusions

In patients with unilateral MD, the configuration of vascular loops in CPA-IAC region, measured by Kazawa criteria, did not correlate with the laterality, clinical stage, the results of EcochG and caloric test, suggesting that vascular loops may be natural anatomical variations for patients with MD.
A critical appraisal of the ISGLS definition of biliary leakage after liver resection
Authors: Sliwinski Svenja , Heil Jan , Franz Josephine , El Youzouri Hanan , Heise Michael , Bechstein Wolf O. , Schnitzbauer Andreas A.
Published: February 2023

Purpose

The International Study Group of Liver Surgery (ISGLS) defined post-hepatectomy biliary leakage as drain/serum bilirubin ratio > 3 at day 3 or the interventional/surgical revision due to biliary peritonitis. We investigated the definition’s applicability.

Methods

A retrospective evaluation of all liver resections over a 6-year period was performed. ROC analyses were performed for drain/serum bilirubin ratios on days 1, 2, and 3 including grade A to C (analysis I) and grade B and C biliary leakages (analysis II) to test specific cutoff values.

Results

A total of 576 patients were included. One hundred nine (18.9%) postoperative bile leakages occurred (19.6% of the whole population grade A, 16.5% grade B/C). Areas under the curve (AUC) for analysis I were 0.841 (day 1), 0.846 (day 2), and 0.734 (day 3). The highest sensitivity (78% on day 1/77% on day 2) and specificity (78% on day 1/79% on day 2) in analysis I were obtained for a drain/serum bilirubin ratio of 2.0. AUCs for analysis II were similar: 0.788 (day 1), 0.791 (day 2), and 0.650 (day 3). The highest sensitivity (73% on day 1/71% on day 2) and specificity (74% on day 1/76% on day 2) in analysis II were detected for a drain/serum bilirubin ratio of 2.0 on postoperative day 2.

Conclusion

Biliary leakages should be defined if the drain/serum bilirubin ratio is > 2.0 on postoperative day 2.
Efficacy of auriculotherapy in the control of pain, edema, and trismus following surgical extraction of the lower third molars: a split-mouth, randomized, placebo-controlled, and triple-blind study
Authors: Vaira Luigi Angelo , Massaiu Andrea , Massaiu Giuseppe , Salzano Giovanni , Maglitto Fabio , Lechien Jerome R. , Biglio Andrea , Visaloco Giulio , Piombino Pasquale , Biglioli Federico , De Riu Giacomo
Published: February 2023

Background

The aim of this split-mouth, randomized, placebo-controlled, and triple-blind study was to evaluate whether auriculotherapy had any effect on the post-operative course after the extraction of third molars in terms of the control of pain, edema, and trismus.

Materials and methods

The study included 42 patients (84 teeth) who had undergone a surgical extraction of the lower third molars. In each patient, the two extractions were randomly assigned to two study groups. In the therapy group, the patients underwent auriculotherapy with vaccaria seeds applied with patches in 6 ear points. In the control group, the patches were applied, without seeds, to the same ear points. After the extraction, the patients were asked to stimulate the ear points three times a day and whenever they felt pain. The patients were asked to keep a diary in which they assessed their pain by means of the Visual Analog Scale (VAS) for 8 days. Edema and trismus were assessed 1, 2, 3, and 8 days after surgery.

Results

The differences between the two groups were statistically significant at the 12-h control (auriculotherapy group (AG) VAS 5.5 [IQR 4.25–6.75], placebo group (PG) VAS 6 [IQR 5–8], p = 0.040), after 24 h (AG VAS 5 [IQR 4–6], PG VAS 6 [IQR 4.25–7], p = 0.024), after 2 days (AG VAS 4 [IQR 3–5], PG VAS 4.5 [IQR 4–6], p = 0.044), and after 3 days (AG VAS 3 [IQR 0–5], PG VAS 4 [IQR 3–5], p = 0.024). Throughout the observation period, the AG took a significantly lower number of painkillers than the PG (AG 6 [IQR 4.25–7]; PG 8 [IQR 8–9], p < 0.001). There were no significant differences in the levels of edema and trismus between the two groups throughout the observation period.

Conclusions

On the basis of the results of the present study, auriculotherapy can be considered as a cost-effective adjuvant pain reliever treatment in patients undergoing an extraction of the lower third molars.
Economic and environmental impact of electric vehicles production in Indonesia
Authors: Pirmana Viktor , Alisjahbana Armida Salsiah , Yusuf Arief Anshory , Hoekstra Rutger , Tukker Arnold
Published: February 2023

The use of fossil fuel-based vehicles may gradually be replaced by electric vehicles in the future. The trend indicates that the number of users of electric vehicles, especially electric cars, continues to increase. Indonesia is well-positioned to take advantage of this opportunity as it has the world’s largest nickel reserves, an essential raw material for making electric vehicle batteries (EVB). The study examines the economic and environmental implications if Indonesia were to successfully set up electric vehicle (EV) production rather than exporting such raw materials overseas. We use an input–output model to estimate electric vehicle production’s economic and environmental impacts in Indonesia. This study assumes that nickel, which is usually exported, is absorbed by domestic economic activities, including being used in manufacturing batteries and electric vehicles in Indonesia. Our estimates include direct and indirect output, value-added, and employment changes. The same model is also used to estimate changes in emissions’ environmental costs. It is evident from the results that batteries and EV production are economically beneficial. Additional value-added is Rp. 100.57 trillion, 1.5% of GDP in 2010. At the same time, 538,658 additional jobs were created, which is about a 0.5% increase. Lastly, EV production will have extra external costs of emissions, around Rp. 2.23 trillion, or an increase of about 0.6%. Based on these findings, it is concluded that electric vehicle production increases productivity, gross value-added, and job creation with a relatively small impact on the environment. A limitation of this study is that we assumed EVs were produced for export only, and we did not assume a reduction in economic activities in the supply chain of conventional vehicles.

Graphical Abstract

Economic and Environmental Impact of Electric Vehicles Production in Indonesia.
Is there a role for microbiome-based approach in common variable immunodeficiency?
Authors: Poto Remo , laniro Gianluca , de Paulis Amato , Spadaro Giuseppe , Marone Gianni , Gasbarrini Antonio , Varricchi Gilda
Published: February 2023

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.
Potential use of Sargassum muticum as source of plant biostimulants after three different drying methods
Authors: Baltrusch K. , Flórez-Fernández N. , Illera M. , Torres M. D. , López-Mosquera M. E. , Domínguez H.
Published: February 2023

Seaweed derived biostimulants are gaining attention as an important tool in sustainable agriculture. This offers a unique opportunity to alleviate the environmental impact ofSargassum muticum(Ochrophyta, Phaeophyceae) as an invasive species by finding new applications for its biomass. In this sense, incorporating green extraction technologies is fundamental to ensure environmental-friendly goals. This research was initiated in an attempt to contribute to an integral valorization system ofS. muticumbiomass, exploring the biostimulant potential of the solubles obtained from pressed solids, through an autohydrolysis treatment. In addition, we compared the effect of three different liquid phase drying techniques (spray-drying, freeze-drying and convective air-drying). Low stress drying techniques as spray-drying showed better conservation of bioactive compounds and biostimulant potential. A bioassay withNastrium officinaleshowed no phytotoxic effects despite high electric conductivity in most of the extracts and concentrations. Dried extracts showed mainly an amorphous structure but occasional crystal formation when spray-dried at low temperatures (Tout = 50 ºC) and after convective air drying (T = 40 ºC). Significant increases in root development were achieved at a concentration of 5 mg L−1of spray-dried extracts and 50 mg L−1in case of freeze-dried extracts. Munoo-Liisa vitality index showed best results with 50 mg L−1of freeze-dried extracts. This study provides important information about the influence of different drying techniques on the physicochemical properties and biostimulant potential ofS. muticumaqueous extracts and contributes to the integral valorization of its biomass.
Role of Superconducting Materials in the Endeavor to Stop Climate Change and Reach Sustainable Development
Authors: Muralidhar M. , Srikanth A. Sai , Pinmangkorn S. , Santosh M. , Milos J.
Published: February 2023

Progress in the mass production of newly developed bulk (Gd0.33Y0.13Er0.53)Ba2Cu3Oy “(Gd,Y,Er)123” and MgB2 systems is presented. Two batches of (Gd,Y,Er)123 pellets of 20 mm diameter and 7 mm thick were prepared in air by an infiltration growth “IG” process. Trapped field distribution profiles of fully grown bulk samples clearly showed that all samples were single-grain and the trapped field values were more than 0.5 T at 77 K, 1.3 mm above top surface. The best bulk exhibited the trapped field value of 0.63 T at 77 K. Ultra-sonication technique was employed for refining precursors of both (Gd,Y,Er)211 and boron. TEM studies revealed that boron powder subjected to ultrasonication was refined up to nanoscale. The micron-sized particles were reduced to nanoscale, which led to improvement of critical current by up to 36% in bulk MgB2 at 20 K and self-field. This progress in fabrication of high-performance LREBa2Cu3Oy and MgB2 superconducting bulks further promotes commercialization of superconductors’ production as a mode of sustainable technology.
Lipid Nanoparticles for Nucleic Acid Delivery to Endothelial Cells
Authors: Liu Gary W. , Guzman Edward B. , Menon Nandita , Langer Robert S.
Published: February 2023

Endothelial cells play critical roles in circulatory homeostasis and are also the gateway to the major organs of the body. Dysfunction, injury, and gene expression profiles of these cells can cause, or are caused by, prevalent chronic diseases such as diabetes, cardiovascular disease, and cancer. Modulation of gene expression within endothelial cells could therefore be therapeutically strategic in treating longstanding disease challenges. Lipid nanoparticles (LNP) have emerged as potent, scalable, and tunable carrier systems for delivering nucleic acids, making them attractive vehicles for gene delivery to endothelial cells. Here, we discuss the functions of endothelial cells and highlight some receptors that are upregulated during health and disease. Examples and applications of DNA, mRNA, circRNA, saRNA, siRNA, shRNA, miRNA, and ASO delivery to endothelial cells and their targets are reviewed, as well as LNP composition and morphology, formulation strategies, target proteins, and biomechanical factors that modulate endothelial cell targeting. Finally, we discuss FDA-approved LNPs as well as LNPs that have been tested in clinical trials and their challenges, and provide some perspectives as to how to surmount those challenges.
Thai stakeholders’ awareness and perceptions of the patient adverse event reporting system for herbal medicines: a qualitative study
Authors: Worakunphanich Wiwan , Suwankesawong Wimon , Youngkong Sitaporn , Thavorncharoensap Montarat , Anderson Claire , Toh Li Shean
Published: February 2023

Background

In Thailand, the consumption of herbal medicines has been increasing. Adverse events (AEs) of herbal medicines have been identified through the spontaneous reporting system. However, the number of patients reporting AEs of herbal medicines remains limited.

Aim

To explore the awareness and perceptions about the patient reporting system and to explore attitudes towards safety of herbal medicines, experiences, and intention to report AEs of herbal medicines.

Method

Semi-structured in-depth interviews were conducted with stakeholders (patients, community pharmacists, village health volunteers, and consumers who had experienced submitting a complaint about health products to the Consumers Foundation). Additionally, a focus group discussion was held with stakeholders (academics, herbal medicine manufacturers, healthcare professionals, policy maker who was responsible for promoting the use of herbal medicines, pharmacovigilance staff, patient, and representative from patient organisations). The data were audio recorded, transcribed verbatim and analysed using thematic analysis.

Results

Fifty participants were interviewed and the focus group discussion included 12 participants. Patients had positive attitudes towards the safety of herbal medicines. Lack of awareness of the patient reporting system was identified. Nevertheless, all stakeholders acknowledged the importance of the safety monitoring of herbal medicines and indicated a willingness to report AEs via the patient reporting system in the future. A simple reporting system, a variety of reporting channels, the provision of feedback, and providing rewards would motivate patients to report AEs.

Conclusion

Although there is a lack of awareness, this provides a great opportunity to improve patient AE reporting system for herbal medicines in Thailand.
Randomized Trial of a Sexual Health Video Intervention for Black and Hispanic Adolescent Females
Authors: Jenner Eric , Walsh Sarah , Henley Catherine , Demby Hilary , Leger Rebekah , Falk Gretchen
Published: February 2023

Despite significant declines, adolescent birth rates in the USA are higher than other industrialized countries, with black and Hispanic youth disproportionately affected. This study assessed the efficacy of a single-session, entertainment-education sexual health video intervention for these populations. Using an individual-level randomized controlled trial, 1770 18- to 19-year-old black and Hispanic females were assigned to watch Plan A (n = 886) or a control video (n = 884) prior to a sexual reproductive health (SRH) visit. Participants self-reported data at baseline and 3 months post-baseline. Within an intent-to-treat framework, we estimated the average causal effect of assignment to Plan A on three confirmatory and five exploratory outcomes. We found that individuals assigned to Plan A had higher contraceptive knowledge, may be more likely to get sexually transmitted infection (STI) testing, and may have elevated HIV/STI risk perceptions 3 months post-video. Although we found no difference in long-acting reversible contraception (LARC) use nor frequency of condomless sex in the full sample, we did observe that first-time SRH visitors assigned to Plan A had a higher probability of using LARC than those in the control group. This study demonstrates that Plan A is a low-burden, inexpensive, and highly scalable video intervention for black and Hispanic adolescent females that has significant and borderline significant effects on protective sexual health behaviors and important antecedents. It adds to the evidence base of effective teen pregnancy prevention programs and the limited set of rigorous and causal studies investigating the effectiveness of entertainment-education interventions on sexual risk reduction. Registered in ClinicalTrials.gov (NCT03238313) on August 3, 2017.
Microtargeting, Dogwhistles, and Deliberative Democracy
Authors: Howdle Giles
Published: February 2023

‘Dogwhistles’ and microtargeted political advertisements are objects of widespread moral and political concern. With a few notable exceptions in the case of dogwhistles (and none in the case of microtargeting) moral criticism of these speech act types generally focuses on problematiccontent—that a dogwhistle is, for instance, racist, or a microtargeted advertisement misleading. I argue that these practices areadditionallymorally wrongful on content-neutral grounds—regardless of their content. My argument proceeds from a deliberative conception of democracy according to which only a vote which follows from anadequate deliberative processconfers democratic legitimacy on its results. I claim that both dogwhistles and microtargeting threaten to prevent adequate democratic deliberation from taking place, and therefore that these practices are anti-democratic and, additionally, morally impermissible. I then discuss potential objections and how my argument relates to existing work.
An anisotropic damage–permeability model for hydraulic fracturing in hard rock
Authors: Liao Jianxing , Wang Hong , Mehmood Faisal , Cheng Cao , Hou Zhengmeng
Published: February 2023

Hydraulic fracturing is the most efficient method to exploit valued geothermal energy trapped in low-permeable hard rock, e.g. granite. Most research on the hydraulic fracturing has focused on its application in shale gas and oil. However, the hydraulic fracturing performs differently in geothermal reservoir, as the rock properties are quite different. In this work, an anisotropic damage–permeability model is developed on the fundament of continuum theory to study the hydraulic fracturing of hard rock in geothermal reservoir. The plastic-hardening and damage-softening behaviours are considered in this model. A cubic law is adopted to characterize the damage enhanced permeability. Its directional information is converted from damage tensor, while the effect of compression stress on permeability is isotropic and characterized by an impact factor. The newly developed model is calibrated and validated by a series of stress–strain curve, damage and axial permeability from triaxial tests on granite. In the application to cyclic fracturing test at Aspö Hard Rock Laboratory, the capacity of newly developed model is proven by good matching of measured injection pressure, permeability, etc. The results show clearly that the fracture is mostly activated by tensile failure in this case. Moreover, the stimulated fracture will be closed during flow back and re-activated in subsequent re-fracturing. If the fracture from previous fracturing is not re-activated completely, no new fractures will be created in current re-fracturing, and the damage amasses continuously due to repeated re-activation of closed fracture during re-fracturing.
Brain water content in sudden unexpected infant death
Authors: Eidahl Johanna Marie Lundesgaard , Rognum Torleiv Ole , Stray-Pedersen Arne , Opdal Siri Hauge
Published: February 2023

The extensive and rapid development of the human brain during the first years of life complicates the postmortem diagnosis of brain edema in infancy. The aim of this study was to describe brain water content, the brain weight/body weight ratio, and the brain weight/head circumference ratio throughout the first years of life. Furthermore, we examined the relationship between these parameters and rs2075575 in the AQP4 gene. Our hypothesis was that dysregulated water homeostasis might be a risk factor for sudden infant death syndrome (SIDS), which may be reflected by increased water content in the brain. The study included 90 subjects with sudden unexpected death < 4 years of age: 22 cases of sudden infant death syndrome, 11 cases of sudden unexplained death in childhood, 47 cases of death due to disease, and 10 cases of accident/violent death. Brain water content, brain weight/body weight ratio, and brain weight/head circumference ratio were investigated according to corrected age, diagnosis group, attempt to resuscitate, and presence of brain edema. We found that brain water content and brain weight/body weight ratio were significantly reduced with increasing age, while brain weight/head circumference were increased. Brain weight/head circumference was correlated with brain water content. Cases with brain edema had a significantly higher brain weight/head circumference than the non-edematous cases. No differences were found between the diagnosis groups for any of the investigated parameters. In summary, the findings contribute to the current body of knowledge regarding brain growth during the first months of life.
Mechanism of Molecular Activity of Yolkin—a Polypeptide Complex Derived from Hen Egg Yolk—in PC12 Cells and Immortalized Hippocampal Precursor Cells H19-7
Authors: Kazana Wioletta , Jakubczyk Dominika , Siednienko Jakub , Zambrowicz Aleksandra , Macała Józefa , Zabłocka Agnieszka
Published: February 2023

Food-derived bioactive peptides able to regulate neuronal function have been intensively searched and studied for their potential therapeutic application. Our previous study showed that a polypeptide complex yolkin, isolated from hen egg yolk as a fraction accompanying immunoglobulin Y (IgY), improved memory and cognitive functions in rats. However, the mechanism activated by the yolkin is not explained. The goal of the present study was to examine what molecular mechanism regulating brain-derived neurotrophic factor (BDNF) expression is activated by the yolkin complex, using in vitro models of PC12 cell line and fetal rat hippocampal cell line H19-7. It was shown that yolkin increased the proliferative activity of rat hippocampal precursor cells H19-7 cells and upregulated the expression/production of BDNF in a cyclic adenosine monophosphate (cAMP)-response element-binding protein (CREB)-dependent manner. Additionally the upregulation of carboxypeptidase E/neurotrophic factor–α1 (CPE/(NF-α1) expression was shown. It was also determined that upregulation of CREB phosphorylation by yolkin is dependent on cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) signaling pathway activation. Moreover, the impact of yolkin on the level of intracellular Ca2+, nitric oxide, and activation of extracellular signal-regulated kinases 1/2 (ERK 1/2 kinase) was excluded. These results emphasize that yolkin can act comprehensively and in many directions and may participate in the regulation of neurons’ survival and activity. Therefore, it seems that the yolkin specimen can be used in the future as a safe, bioavailable, natural nutraceutical helping to improve the cognition of older people.
Optimal portfolios with sustainable assets: aspects for life insurers
Authors: Korn Ralf , Nurkanovic Ajla
Published: February 2023

Since August 2022 customers have to be asked if they are interested in sustainable investment when entering a pension contract. Hence, the provider has to be prepared to offer suitable investment opportunities. Further, the provider has to manage the new risks and chances of those assets in the whole portfolio. We therefore especially look at possible consequences for optimal portfolio decisions of a life insurer and suggest modeling approaches for the evolution of the demand and the sustainability ratings for sustainable assets. We will solve various portfolio problems under sustainability constraints explicitly and suggest further research topics. As a special feature for a life insurer, we particularly look at the role of the actuarial reserve fund and the annual declaration of its return.
Tribochemical synthesis of functionalized covalent organic frameworks for anti-wear and friction reduction
Authors: Zhang Xiaozhi , Lu Qi , Yan Yaojie , Zhang Tingting , Liu Shujuan , Cai Meirong , Ye Qian , Zhou Feng , Liu Weimin
Published: February 2023

Tribochemistry can be defined as a field dealing with the chemical reactions occurring in the friction zone, capable of catalyzing mechanical and physico-chemical changes in the friction contact area, facilitating the formation of tribo-films, which is also an efficient approach to fabricate novel innovative materials. In this paper, we report the successful synthesis of the silicon oil (SO)-functionalized covalent organic frameworks (COFs) prepared via the tribochemical method when subjected to the reciprocating friction; during the friction process, the rich aldehyde-terminated COFs can bond with amino SO via the Schiff base reaction between aldehyde group and amino group to obtain the desired functionalized COFs (SO@COF-LZU1). The tribochemical reaction progress was tracked through in-situ monitoring of the friction coefficient and the operating conditions during the entire friction process. Noticeably, the friction coefficient continued to decrease until it finally stabilized as the reaction progressed, which revealed the formation of a protective tribo-film. Herein, an approximate tribochemical model was presented, wherein the reaction mechanism was investigated and analyzed by employing structural analysis techniques like magic angle spinning nuclear magnetic resonance (MAS NMR), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). Furthermore, the tribochemical-induced SO@COF-LZU1 exhibited remarkable tribological performance with a low friction coefficient of 0.1 and 95.5% reduction in wear volume when used as additives of 500SN base oil. The prime focus of our research was on the preparation and functionalization of COF materials via tribochemical reactions, unraveling a new avenue for the rational design and preparation of functional materials.
Cause meno frequenti di aumento del TSH
Authors: Dell’Acqua Marco , Persani Luca
Published: February 2023

Sommario

La misurazione del TSH circolante rappresenta il marcatore più solido e accurato nella valutazione delle disfunzioni tiroidee, capace di rivelare anche disfunzioni tiroidee lievi o subcliniche. Per questo motivo, diverse linee guida e società scientifiche raccomandano la strategia del TSH riflesso per il depistaggio delle disfunzioni tiroidee nella popolazione. Tale raccomandazione è stata recepita largamente da diverse amministrazioni sanitarie nazionali e regionali. L’ipotiroidismo primario di origine autoimmune rappresenta la forma di disfunzione tiroidea largamente più frequente nella popolazione e si accompagna classicamente a variabili elevazioni del TSH. Questa rassegna illustra alcune delle cause meno frequenti di aumento del TSH circolante (interferenze analitiche, come il macroTSH, resistenza al TSH, ipotiroidismo da consumo, refrattarietà al trattamento sostitutivo) evidenziando quando sospettarne la presenza, come diagnosticarle e le insidie che possono rappresentare nel trattamento dei pazienti affetti.
Stability criteria for Bayesian calibration of reservoir sedimentation models
Authors: Mouris Kilian , Acuna Espinoza Eduardo , Schwindt Sebastian , Mohammadi Farid , Haun Stefan , Wieprecht Silke , Oladyshkin Sergey
Published: February 2023

Modeling reservoir sedimentation is particularly challenging due to the simultaneous simulation of shallow shores, tributary deltas, and deep waters. The shallow upstream parts of reservoirs, where deltaic avulsion and erosion processes occur, compete with the validity of modeling assumptions used to simulate the deposition of fine sediments in deep waters. We investigate how complex numerical models can be calibrated to accurately predict reservoir sedimentation in the presence of competing model simplifications and identify the importance of calibration parameters for prioritization in measurement campaigns. This study applies Bayesian calibration, a supervised learning technique using surrogate-assisted Bayesian inversion with a Gaussian Process Emulator to calibrate a two-dimensional (2d) hydro-morphodynamic model for simulating sedimentation processes in a reservoir in Albania. Four calibration parameters were fitted to obtain the statistically best possible simulation of bed level changes between 2016 and 2019 through two differently constraining data scenarios. One scenario included measurements from the entire upstream half of the reservoir. Another scenario only included measurements in the geospatially valid range of the numerical model. Model accuracy parameters, Bayesian model evidence, and the variability of the four calibration parameters indicate that Bayesian calibration only converges toward physically meaningful parameter combinations when the calibration nodes are in the valid range of the numerical model. The Bayesian approach also allowed for a comparison of multiple parameters and found that the dry bulk density of the deposited sediments is the most important factor for calibration.
Networks of climate change: connecting causes and consequences
Authors: Holme Petter , Rocha Juan C.
Published: February 2023

Understanding the causes and consequences of, and devising countermeasures to, global warming is a profoundly complex problem. Network representations are sometimes the only way forward, and sometimes able to reduce the complexity of the original problem. Networks are both necessary and natural elements of climate science. Furthermore, networks form a mathematical foundation for a multitude of computational and analytical techniques. We are only beginning to see the benefits of this connection between the sciences of climate change and network science. In this review, we cover the wide spectrum of network applications in the climate-change literature—what they represent, how they are analyzed, and what insights they bring. We also discuss network data, tools, and problems yet to be explored.
Update of sentinel lymph node mapping assessment in endometrial cancer
Authors: Kim Se Ik , Kim Jae-Weon
Published: February 2023

Endometrial cancer is the most common gynecologic malignancy in developed countries. Pathologic confirmation of lymph node metastasis is important for risk stratification and the administration of adjuvant treatments. Therefore, comprehensive, systematic lymphadenectomy has been routinely performed but has been associated with various morbidities. Meanwhile, the concept of sentinel lymph node (SLN) mapping and biopsy has emerged and is now accepted as an alternative to conventional systematic lymphadenectomy in early-stage endometrial cancer. For better management of endometrial cancer, we conducted a literature review to summarize the role and diagnostic accuracy of the SLN mapping strategy in endometrial cancer. Evidence from the monumental and recent literature and ongoing clinical trials will be introduced.
Coevolutionary strategies at the collective level for improved generalism
Authors: Grudniewski Przemyslaw Andrzej , Sobey Adam James
Published: February 2023

In many complex practical optimization cases, the dominant characteristics of the problem are often not known prior. Therefore, there is a need to develop general solvers as it is not always possible to tailor a specialized approach to each application. The previously developed multilevel selection genetic algorithm (MLSGA) already shows good performance on a range of problems due to its diversity-first approach, which is rare among evolutionary algorithms. To increase the generality of its performance, this paper proposes utilization of multiple distinct evolutionary strategies simultaneously, similarly to algorithm selection, but with coevolutionary mechanisms between the subpopulations. This distinctive approach to coevolution provides less regular communication between subpopulations with competition between collectives rather than individuals. This encourages the collectives to act more independently creating a unique subregional search, leading to the development of coevolutionary MLSGA (cMLSGA). To test this methodology, nine genetic algorithms are selected to generate several variants of cMLSGA, which incorporates these approaches at the individual level. The mechanisms are tested on 100 different functions and benchmarked against the 9 state-of-the-art competitors to evaluate the generality of each approach. The results show that the diversity divergence in the principles of working of the selected coevolutionary approaches is more important than their individual performances. The proposed methodology has the most uniform performance on the divergent problem types, from across the tested state of the art, leading to an algorithm more likely to solve complex problems with limited knowledge about the search space, but is outperformed by more specialized solvers on simpler benchmarking studies.