bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of transcranial direct current stimulation on the glutamatergic pathway in the male rat hippocampus after experimental focal cerebral ischemia
Authors: Akçay Guven , Aslan Mutay , Kipmen Korgun Dijle , Çeker Tugçe , Akan Ezgi , Derin Narin
Published: October 2023

This study aimed to assess the focal cerebral ischemia‐induced changes in learning and memory together with glutamatergic pathway in rats and the effects of treatment of the animals with transcranial Direct Current Stimulation (tDCS). One hundred male rats were divided into five groups as sham, tDCS, Ischemia/Reperfusion (IR), IR + tDCS, and IR + E‐tDCS groups. Learning, memory, and locomotor activity functions were evaluated by behavioral experiments in rats. Glutamate and glutamine levels, alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionate receptor (AMPAR1), N‐Methyl‐D‐Aspartate receptors (NMDAR1 and NMDAR2A), vesicular glutamate transporter‐1 (VGLUT‐1), and excitatory amino acid transporters (EAAT1‐3) mRNA expressions in hippocampus tissues were measured. Ischemic areas were analyzed by TTC staining. The increase was observed in IR + tDCS, and IR + E‐tDCS groups compared to the IR group while a significant decrease was observed in IR group compared to the sham in the locomotor activity, learning, and memory tests. While glutamate and glutamine levels, AMPAR1, NMDAR1, NMDAR2A, VGLUT1, and EAAT1 mRNA expressions were significantly higher in IR group compared to the sham group, it was found to be significantly lower in IR + tDCS and IR + E‐tDCS groups compared to the IR group. EAAT2 and EAAT3 mRNA expressions were significantly higher in IR + tDCS and IR + E‐tDCS groups compared to the IR group. Ischemic areas were significantly decreased in IR + tDCS and IR + E‐tDCS groups compared to the IR group. Current results suggest that tDCS application after ischemia improves learning and memory disorders and these effects of tDCS may be provided through transporters that regulate glutamate levels.
Estimation of wheat crop production using multispectral information fusion
Authors: Jitendra  , Pant Triloki
Published: October 2023

BACKGROUND

The present work estimates the area and corresponding wheat crop production in the study area, which comprises the Etah region of Uttar Pradesh, India. For this purpose, multispectral images of multiple sensors, namely Sentinel‐2, Landsat‐8 and Landsat‐9 during the preharvest period, i.e. March for the years 2021 and 2022, were used. A multispectral information fusion approach was proposed, involving image classification as well as vegetation index‐based information extraction. For imposing information fusion, appropriate image bands were identified with the help of separability analysis followed by land cover classification for wheat crop class extraction. Support vector machine (SVM), artificial neural network (ANN) and maximum likelihood (ML) were used for classification, whereas normalized difference vegetation index (NDVI) and fractional vegetation cover (FVC) were used for index‐based crop area extraction.

RESULTS

A maximum accuracy of 98.34% was achieved for Sentinel‐2 data using ANN, whereas a minimum accuracy of 80.21% was achieved for Landsat‐9 using the ML classifier. The estimated area for Sentinel‐2 data for the year 2021 was 260 540 ha using ANN and 203 240 ha using ML, which is close to the reference data, i.e. 238 600 ha. SVM also showed good performance and calculated least error in estimated crop area for the year 2022 on Sentinel‐2 data. It calculated 8 408 490 tons of wheat for the same year.

CONCLUSION

The proposed method utilizes a single image per year for extraction of information supported by the ground truth data, which makes it a novel approach to information extraction for crop production monitoring. © 2023 Society of Chemical Industry.
Wharton's Jelly mesenchymal stromal cell‐derived extracellular vesicles promote nucleus pulposus cell anabolism in an in vitro 3D alginate‐bead culture model
Authors: Tilotta Veronica , Vadalà Gianluca , Ambrosio Luca , Di Giacomo Giuseppina , Cicione Claudia , Russo Fabrizio , Darinskas Adas , Papalia Rocco , Denaro Vincenzo
Published: October 2023

Background

Intradiscal transplantation of mesenchymal stromal cells (MSCs) has emerged as a promising therapy for intervertebral disc degeneration (IDD). However, the hostile microenvironment of the intervertebral disc (IVD) may compromise the survival of implanted cells. Interestingly, studies reported that paracrine factors, such as extracellular vesicles (EVs) released by MSCs, may regenerate the IVD. The aim of this study was to investigate the therapeutic effects of Wharton's Jelly MSC (WJ‐MSC)‐derived EVs on human nucleus pulposus cells (hNPCs) using an in vitro 3D alginate‐bead culture model.

Methods

After EV isolation and characterization, hNPCs isolated from surgical specimens were encapsulated in alginate beads and treated with 10, 50, and 100 μg/mL WJ‐MSC‐EVs. Cell proliferation and viability were assessed by flow cytometry and live/dead staining. Nitrite and glycosaminoglycan (GAG) content was evaluated through Griess and 1,9‐dimethylmethylene blue assays. hNPCs in alginate beads were paraffin‐embedded and stained for histological analysis (hematoxylin–eosin and Alcian blue) to assess extracellular matrix (ECM) composition. Gene expression levels of catabolic (MMP1, MMP13, ADAMTS5, IL6, NOS2), anabolic (ACAN), and hNPC marker (SOX9, KRT19) genes were analyzed through qPCR. Collagen type I and type II content was assessed with Western blot analysis.

Results

Treatment with WJ‐MSC‐EVs resulted in an increase in cell content and a decrease in cell death in degenerated hNPCs. Nitrite production was drastically reduced by EV treatment compared to the control. Furthermore, proteoglycan content was enhanced and confirmed by Alcian blue histological staining. EV stimulation attenuated ECM degradation and inflammation by suppressing catabolic and inflammatory gene expression levels. Additionally, NPC phenotypic marker genes were also maintained by the EV treatment.

Conclusions

WJ‐MSC‐derived EVs ameliorated hNPC growth and viability, and attenuated ECM degradation and oxidative stress, offering new opportunities for IVD regeneration as an attractive alternative strategy to cell therapy, which may be jeopardized by the harsh microenvironment of the IVD.
Preliminary Experience with 3‐Dimensional Exoscope‐Assisted Laryngoplasty
Authors: Sanuki Tetsuji , Takemoto Naoki , Sumiya Shogo , Iwasaki Shinichi
Published: October 2023

Objective

Laryngoplasty requires the manipulation of the vocal folds, which are not visible during the operation. The widespread use of this technique is limited by the need for adequate knowledge of anatomy, the small surgical field, and the high level of skill required for the procedure. An exoscope has been developed to provide a stereoscopic view similar to that of a microscope while using the same compact endoscopic tool. This study aimed to determine whether the three‐dimensional (3D) exoscopic surgical technique could be applied to laryngoplasty and explore its possibility to ultimately replace the current approach.

Methods

This was a retrospective case series analysis, which included 28 patients with hoarseness who underwent surgery with (Exoscope; n = 12) or without (Macrosurgery; n = 16) a 3D exoscope between July 2018 and February 2021. The feasibility of performing all surgical steps with the 3D exoscope was evaluated. The Exoscope and Macrosurgery groups were compared for surgical time, vocal function outcomes, and complications. Questionnaires were completed by medical staff regarding the usefulness of medical education.

Results

No intraoperative or postoperative complications occurred in either procedure. The operative time was similar in both groups. The vocal function outcomes were also comparable between the groups. Questionnaires revealed that the exoscope was useful in terms of sharing information on surgical procedures and anatomy, as well as functioning as an educational tool.

Conclusion

While this was a preliminary study, our results indicated that the exclusive use of the 3D exoscope was feasible for open approaches.

Level of Evidence

4 Laryngoscope, 134:1813–1819, 2024
Health Utility Score in Thai Patients with Chronic Rhinosinusitis: Pre‐ and Postoperative Analyses
Authors: Sangubol Melissa , Snidvongs Kornkiat , Lawpoolsri Saranath , Mongkolkul Kittichai , Kowatanamongkon Patlada , Chitsuthipakorn Wirach
Published: October 2023

Background

Endoscopic sinus surgery (ESS) can increase the health utility score (HUS) of patients with chronic rhinosinusitis (CRS) who require the surgery. HUS varies depending on the geographical or living environment. HUS in CRS has never been evaluated in Thailand. The objective of this study was to evaluate the HUS of Thai patients with CRS before and after ESS through multiple approaches.

Methods

Thai patients (age ≥ 18) with CRS scheduled for ESS were enrolled in this prospective study. The preoperative (baseline) demographics, 22‐items sinonasal outcome test, endoscopic score, and CT score were recorded. The HUS was evaluated using four methods: the EuroQoL‐5 Dimension‐5 level (EQ‐5D‐5L), Visual Analog Scale (VAS), Standard gamble (SG), and Time trade‐off (TTO); at baseline, three months and six months post‐operation.

Results

Data from 60 patients were analyzed. The mean baseline HUS scores by EQ‐5D‐5L, VAS, SG, and TTO were 0.75, 0.65, 0.79, and 0.85, respectively. The postoperative HUS significantly improved to 0.96, 0.91, 0.96, 0.97 at three months, and 0.97, 0.92, 0.97, and 0.98 at six months, respectively. ESS raised the HUS by 0.12–0.27 points. Among the four methods, VAS showed the lowest HUS at all time points.

Conclusion

The preoperative HUS in Thai patients with CRS generally increased to near‐perfect values after the ESS. The increase in HUS reflecting the improved general quality of life, was demonstrated at three and up to six months after ESS.

Level of Evidence

4 Laryngoscope, 134:2070–2076, 2024
Mapping grasslands' preservation potential: A case study from the northern Carpathians
Authors: Szczęch Mateusz , Kania Maciej , Loch Jan , Ostapowicz Katarzyna , Struś Paweł
Published: October 2023

The grasslands which are an important part of an ecosystem are endangered due to abandonment of traditional forms of land use. Preservation of biodiversity of semi‐natural grassland communities is of great importance, therefore it is important to identify threats and prepare a sustainable plan for their protection The goal of this study was to develop an approach to predict threatened grasslands hotspots, basing on multi‐factor machine learning analyses. The Gorce Mountains in the Polish Carpathians were chosen as a study area, as it is region partially protected by National Park, surrounded by villages with different socio‐economic conditions (agriculture or touristic oriented). The grasslands were identified and classified on Sentinel‐2 multispectral imagery. As lack of regular mowing of grasslands was found as main factor promoting forest succession. Therefore, in order to find endangered grasslands areas, support vector machines' algorithm was used to classify them in mowed and unmowed categories. Then the preservation potential of grasslands was modeled with the random forest method, based on the grasslands' mowing classification, digital terrain model, land‐use and population statistical data, and the historical forest extent. We found the grasslands above 750 m above sea level to be the most endangered. Also, the tourism activity and ongoing changes in employment structure from agriculture to services has had a negative influence on the grasslands preservation potential. On the other hand, the Gorce National Park's active grassland conservation by mowing and grazing was shown as a positive element in keeping with the high biodiversity of the area.
Seeking variety on the move: The effect of residential mobility on variety seeking
Authors: Cheng Jingran , Chi Yunjia , Bao Yuze
Published: October 2023

Given the widespread occurrence of residential mobility, it is interesting that people are seeking stability. However, the current research finds otherwise and sheds light on how mobility impacts consumers’ variety seeking. An analysis of national panel data and four studies show that consumers with residential mobility behave more variably. Specifically, residential mobility can encourage consumers to seek more variety by increasing their change‐seeking mindsets. Voluntariness of mobility moderates the positive effect of residential mobility on variety seeking. These results were proven using past moving experiences (an exploratory study, Studies 2 and 3) or by manipulating residential mobility (Studies 4 and 5). Our research reveals the causal relationship, underlying process, and moderation between residential mobility and variety seeking, helping enterprises manage variety‐seeking behaviors.
Lawsuit: Peace Corps denies assignments over outdated mental health concerns
Authors: Enos Gary
Published: October 2023

The Peace Corps has used fear‐based and speculative standards and ignored sound medical advice in denying volunteer assignments to numerous individuals with mental health disabilities, according to a federal class‐action complaint filed in Washington, D.C., late last month.
More than half of mental health therapists experience burnout
Authors: Canady Valerie A.
Published: October 2023

A comprehensive research study of more than 500 counselors, social workers, psychologists and other practitioners found that more than half have experienced burnout. Additionally, nearly half also said that their burnout has gotten worse since the first wave of COVID‐19.
Parties to Iowa child MH suit announce interim settlement
Authors: Enos Gary
Published: October 2023

Less than a year after advocates for children with mental health needs filed suit against Iowa officials over inadequacies in the state's Medicaid mental health services, the two sides have agreed to an interim settlement that could lead to a final resolution by next summer.
Microwave imaging for monitoring breast cancer treatment: A pilot study
Authors: Smith Katrin , Bourqui Jeremie , Wang Zefang , Besler Brendon , Lesiuk Mark , Roumeliotis Michael , Quirk Sarah , Grendarova Petra , Pinilla James , Price Sarah , Docktor Bobbie , Fear Elise
Published: October 2023

Background

Microwave imaging has been proposed for medical applications, creating maps related to water content of tissues. Breast imaging has emerged as a key application because the signals can be coupled directly into the breast and experience limited attenuation in fatty tissues. While the literature contains reports of tumor detection with microwave approaches, there is limited exploration of treatment monitoring.

Purpose

This study aims to detect treatment‐related changes in breast tissue with a low‐resolution microwave scanner.

Methods

Microwave scans of 15 patients undergoing treatment for early‐stage breast cancer are collected at up to 4 time points: after surgery (baseline), 6 weeks after accelerated partial breast radiation, as well as 1 and 2 years post‐treatment. Both the treated and untreated breast are scanned at each time point. The microwave scanner consists of planar transmit and receive arrays and uses signals from 0.1 to 10 GHz. The average microwave frequency properties (permittivity) are calculated for each scan to enable quantitative comparison. Baseline and 6‐week results are analyzed with a two‐way ANOVA with blocking.

Results

Consistent properties are observed for the untreated breast over time, similar to a previous study. Comparison of the scans of the treated and untreated breast suggests increased properties related to treatment, particularly at baseline and 6‐weeks following radiotherapy. Analysis of the average properties of the scans with ANOVA indicates statistically significant differences () in the treated and untreated breast at these time points.

Conclusions

Microwave imaging has the potential to track treatment‐related changes in breast tissues.
Exploring the Effects of Various Capping Agents on Zinc Sulfide Quantum Dot Characteristics and In‐vitro Fate
Authors: Montaseri Zohre , Tamaddon Ali Mohammad , Raee Mohammad Javad , Farvadi Fakhrossadat
Published: October 2023

The choice of capping agents used during the synthesis process of quantum dots (QDs) can significantly influence their fate and fundamental properties. Hence, choosing an appropriate capping agent is a critical step in both synthesis and biomedical application of QDs. In this research, ZnS QDs were synthesized via chemical precipitation process and three commonly employed capping agents, namely mercaptoethanol (ME), mercaptoacetic acid (MAA), and cysteamine (CA), were used to stabilize the QDs. This study was aimed to examine how these capping agents impact the physicochemical and optical characteristics of ZnS QDs, as well as their interactions with biological systems. The findings revealed that the capping agents had considerable effects on the behavior and properties of ZnS QDs. MAA‐QD exhibited superior crystal lattice, smaller size, and significant quantum yield (QY). In contrast, CA‐QDs demonstrated the lowest QY and the highest tendency for aggregation. ME‐QDs exhibited intermediate characteristics, along with an acceptable level of cytotoxicity, rapid uptake by cells, and efficient escape from lysosomes. Consequently, it is advisable to select capping agents in accordance with the specific objectives of the research.
14‐3‐3 protein inhibits CaMKK1 by blocking the kinase active site with its last two C‐terminal helices
Authors: Petrvalska Olivia , Honzejkova Karolina , Koupilova Nicola , Herman Petr , Obsilova Veronika , Obsil Tomas
Published: October 2023

Ca2+/CaM‐dependent protein kinase kinases 1 and 2 (CaMKK1 and CaMKK2) phosphorylate and enhance the catalytic activity of downstream kinases CaMKI, CaMKIV, and protein kinase B. Accordingly, CaMKK1 and CaMKK2 regulate key physiological and pathological processes, such as tumorigenesis, neuronal morphogenesis, synaptic plasticity, transcription factor activation, and cellular energy homeostasis, and promote cell survival. Both CaMKKs are partly inhibited by phosphorylation, which in turn triggers adaptor and scaffolding protein 14‐3‐3 binding. However, 14‐3‐3 binding only significantly affects CaMKK1 function. CaMKK2 activity remains almost unchanged after complex formation for reasons still unclear. Here, we aim at structurally characterizing CaMKK1:14‐3‐3 and CaMKK2:14‐3‐3 complexes by SAXS, H/D exchange coupled to MS, and fluorescence spectroscopy. The results revealed that complex formation suppresses the interaction of both phosphorylated CaMKKs with Ca2+/CaM and affects the structure of their kinase domains and autoinhibitory segments. But these effects are much stronger on CaMKK1 than on CaMKK2 because the CaMKK1:14‐3‐3γ complex has a more compact and rigid structure in which the active site of the kinase domain directly interacts with the last two C‐terminal helices of the 14‐3‐3γ protein, thereby inhibiting CaMKK1. In contrast, the CaMKK2:14‐3‐3 complex has a looser and more flexible structure, so 14‐3‐3 binding only negligibly affects the catalytic activity of CaMKK2. Therefore, Ca2+/CaM binding suppression and the interaction of the kinase active site of CaMKK1 with the last two C‐terminal helices of 14‐3‐3γ protein provide the structural basis for 14‐3‐3‐mediated CaMKK1 inhibition.
Highly Diastereoselective Synthesis of Multifunctionalized Dihydrofurans by a K3PO4‐Promoted Michael Addition‐Alkylation Reaction
Authors: Feng Juhua , Feng Jinxiang , Li Juanhong , Huang Ailin , Hu Haipeng , Yang Shengnan , Liu Kuan , Yue Guizhou
Published: October 2023

A simple and beneficial strategy for the construction of 2,3‐dihydrofurans from α‐bromochalcones and α‐substituted cyanoketones via Michael addition‐alkylation reaction has been realized. This transformation was well compatible with various α‐bromochalcones and α‐substituted cyanoketones, and the corresponding multifunctionalized 2,3‐dihydrofurans were obtained in up to 98 % yield. A highly diastereoselective variant of the reaction was also developed. Moreover, the reaction could be performed on gram‐scale.
Revealing the Mechano‐Electrochemical Coupling Behavior and Discharge Mechanism of Fluorinated Carbon Cathodes toward High‐Power Lithium Primary Batteries
Authors: Luo Zhenya , Luo Shun , Yang Mei , Mao Weiguo , Dai Cuiying , Pan Yong , Wu Dazhuan , Pan Junan , Ouyang Xiaoping
Published: October 2023

Unclear reaction mechanisms and unsatisfactory power performance hinder the further development of advanced lithium/fluorinated carbon (Li/CFx) batteries. Herein, the mechano‐electrochemical coupling behavior of a CFx cathode is investigated by in situ monitoring strain/stress using digital image correlation (DIC) techniques, electrochemical methods, and theoretical equations. The DIC monitoring results present the distribution and dynamic evolution of the plane strain and indicate strong dependence toward the material structure and discharge rate. The average plane principal strain of fully discharged 2D fluorinated graphene nanosheets (FGNSs) at 0.5 C is 0.50%, which is only 38.5% that of conventional bulk‐structure CFx. Furthermore, the superior structural stability of the FGNSs is demonstrated by the microstructure and component characterization before and after discharge. The plane stress evolution is calculated based on theoretical equations, and the contributions of electrochemical and mechanical factors are examined and discussed. Subsequently, a structure‐dependent three‐region discharge mechanism for CFx electrodes is proposed from a mechanical perspective. Additionally, the surface deformation of Li/FGNSs pouch cells formed during the discharge process is monitored using in situ DIC. This study reveals the discharge mechanism of Li/CFx batteries and facilitates the design of advanced CFx materials.
Nano–Bio Interactions: Biofilm‐Targeted Antibacterial Nanomaterials
Authors: Li Bo , Mao Jiahui , Wu Jiawei , Mao Kerou , Jia Yangrui , Chen Fulin , Liu Jing
Published: October 2023

Biofilm is a spatially organized community formed by the accumulation of both microorganisms and their secretions, leading to persistent and chronic infections because of high resistance toward conventional antibiotics. In view of the tunable physicochemical properties and the related unique biological behavior (e.g., size‐, shape‐, and surface charge‐dependent penetration, protein corona endowed targeting, catalytic‐ and electronic‐related oxidative stress, optical‐ and magnetic‐associated hyperthermia, etc.), nanomaterials‐based therapeutics are widely used for the treatment of biofilm‐associated infections. In this review, the biological characteristics of biofilm are introduced. And the nanomaterials‐based antibacterial strategies are further discussed via biofilm targeting, including preventing biofilm formation, enhancing biofilm penetration, disrupting the mature biofilm, and acting as drug delivery systems. In which, the interactions between biofilm and nanomaterials include mechanical disruption, electron transfer, enzymatic degradation, oxidative stress, and hyperthermia. Additionally, the current advances of nanomaterials for antibacterial nanomaterials by biofilm targeting are summarized. This review aims to present a complete vision of antibacterial nanomaterials–biofilm (nano–bio) interactions, paving the way for the future development and clinical translation of effective antibacterial nanomedicines.
Tracking Decomposition Layer Formation in Thin‐Film Si Electrodes via Thermogalvanic Profiles
Authors: Hubrechtsen Liese B. , De Taeye Louis L. , Vereecken Philippe M.
Published: October 2023

Si anodes are of great interest for next‐generation Li‐ion batteries due to their exceptional energy density. One of the problems hindering the adoption of this material is the presence of electrolyte decomposition reactions that result in capacity fade and Coulombic inefficiency. This work studies the influence of the decomposition layer in Si on its electrochemical performance using thermogalvanic profiling, a non‐destructive in operando technique. This is accomplished by comparing thermogalvanic profiles of uncoated thin‐film Si to those of lithium phosphorus oxynitride (LiPON)‐coated Si, in which decomposition reactions are inhibited. Through a combination with physico‐chemical methods including scanning electron microscopy and time‐of‐flight secondary ion mass spectrometry, the thermogalvanic profiles are found to contain signatures that reflect the nature of the decomposition layer. More specifically, this decomposition layer appears to gradually develop a passivating function during the first electrochemical cycles. Thermogalvanic profiles collected at later cycles indicate that this passivating behavior is eventually lost, causing the observed capacity degradation. The identification of a passivating regime in Si is highly relevant for the development of high‐capacity Li‐ion batteries. In addition, the use of thermogalvanic profiles to track the properties of decomposition layers could be of interest for monitoring the formation or degradation of battery cells.
Quality of life after endoscopic procedures for chronic pancreatitis: A multicentre study
Authors: Parhiala Mikael , Nøjgaard Camilla , Bartholdy Andreas , Waage Anne , Ignatavičius Povilas , Engjom Trond , Dimcevski Georg , Nordaas Ingrid Kvåle , Kalaitzakis Evangelos , Drewes Asbjørn M. , Hadi Amer , Olesen Søren S. , Poulsen Jakob L. , Laukkarinen Johanna ,   the Scandinavian Baltic Pancreatic Club
Published: October 2023

Background

Chronic Pancreatitis (CP) causes morphological changes in the pancreatic tissue, leading to complications and pain, which may require endoscopic interventions.

Objective

Our aim was to determine the frequency of endoscopic procedures (EP) in CP patients and to analyse pain and quality of life (QoL) in these patients after their EP.

Methods

This study included 1327 CP patients from the Scandinavian Baltic Pancreatic Club (SBPC) database including four countries and eight centres. We analysed patients undergoing EPs and gathered information on the EP, pancreatic function, pain, disease and duration. The EORTC C‐30 QoL questionnaire was gathered prospectively and multivariable analysis was conducted on independent parameters between the groups. The reference population had no interventions (n = 870).

Results

260 CP patients (22%) underwent EPs, median one year (range 0–39 years) after CP diagnosis. 68% were males. The median age was 59 (20–90) years. Most common aetiological factors were alcohol in 65% and smoking in 71%. Extracorporeal shock wave lithotripsy (ESWL) was used in 6% of the CP population and in 21% of the EP group. Biliary duct stenting was performed on 37% and pancreatic stenting was performed on 56% of the patients. There was no difference in pain patterns between patients who had pancreatic stenting and the reference population. The EP group had slightly better QoL (p = 0.047), functioning and fewer symptoms than the reference population, in the multivariable analysis there was no interaction effect analysis between the groups. The pancreatic stent group had better QoL and the same amount of pain than the reference group. The patients who needed later surgery (23%) had more pain (p = 0.043) and fatigue (p = 0.021).

Conclusions

One in five of the CP patients underwent EP. These patients scored higher on QoL responses and had better symptom scores. CP patients who had pancreatic stenting performed had the same pain patterns as the reference population. Randomised prospective trials are needed to determine the effect of endoscopy procedures on CP patients.
Time Trends in Human Milk Derived from WHO- and UNEP-Coordinated Exposure Studies, Chapter 2: DDT, Beta-HCH and HCB
Authors: Malisch Rainer , Hardebusch Björn , Lippold Ralf , van Leeuwen F. X. Rolaf , Moy Gerald , Tritscher Angelika , Šebková Kateřina , Klánová Jana , Kalina Jiří
Published: October 2023

Temporal trends of DDT (“DDT complex” as sum of p,p′-DDT, o,p′-DDT, p,p′-DDD and p,p′-DDE), beta-hexachlorocyclohexane (beta-HCH) and hexachlorobenzene (HCB) were assessed using pooled human milk samples from 44 countries from all United Nations Regional Groups based on their repeated participation in WHO/UNEP-coordinated exposure studies performed between 2000 and 2019. In contrast to a general estimation of time trends based on results from all countries, this is a more precise approach, because levels among countries are often highly variable. The primary objective of these temporal studies is to provide monitoring data for the effectiveness evaluation of the Stockholm Convention on Persistent Organic Pollutants (POPs).

For DDT, an overall decrease over 10 years between 50% and 80% was achieved in Africa, the Asia-Pacific region and in Latin America and the Caribbean region, and at a global level. Slightly lower decreases were observed in European countries because DDT was banned much earlier in these countries and only residual levels were depleting. Western European countries had the lowest median and the lowest maximum DDT concentrations. This is an indication that the decrease might be faster in regions with higher concentrations, compared to a slower decrease in less contaminated regions. The frequency distribution of the country-specific decrease (decrease rate constants) confirms these findings.

For beta-HCH, an overall decrease over 10 years between 50% and 98% was achieved in all UN regions and at a global level. Country-specific decreases vary in the low background range (below 5 μg beta-HCH/kg lipid). Regarding HCB, all countries from Africa and many countries from the Pacific Islands and Latin America and the Caribbean were in the range of a low background contamination below 5 μg/kg lipid resulting in a wide range of reduction rates. In contrast, in countries with HCB concentrations above 30 μg/kg lipid in previous rounds, overall decreases over 10 years between 50% and 85% were observed.

Therefore, the reduction rates should be seen also in context with the concentration range: A differentiation of levels above or in the range of the background contamination seems to be advised. If high levels are found, sources might be detected which could be eliminated. However, at low background levels, other factors, e.g. contamination of feed and food by air via long-range transport and subsequent bioaccumulation, cannot be influenced locally.
WHO- and UNEP-Coordinated Exposure Studies 2000–2019: Findings of Polychlorinated Biphenyls, Polychlorinated Dibenzo-p-Dioxins, and Polychlorinated Dibenzofurans
Authors: Malisch Rainer , Schächtele Alexander , van Leeuwen F. X. Rolaf , Moy Gerald , Tritscher Angelika
Published: October 2023

The concentrations of polychlorinated biphenyls (PCB), polychlorinated dibenzo-p-dioxins (PCDD), and polychlorinated dibenzofurans (PCDF) were determined in 232 pooled human milk samples from 82 countries from all United Nations regions participating in five exposure studies coordinated by the World Health Organization (WHO) and the United Nations Environment Programme (UNEP) between 2000 and 2019.

The highest concentrations of PCB were found in European countries. Countries of all other regions had considerably lower concentrations.

The highest median concentrations of toxic equivalents (TEQ) of PCDD/PCDF and dioxin-like PCB (expressed as WHO2005-TEQ) were found in Eastern and Western European countries, the widest variation in Africa. The median concentrations and maximum levels in the Pacific region and countries from Latin America and the Caribbean were at the lower end of the distribution. However, also time trends have to be considered for this overall picture for a period of 20 years.
Extrapolation is Not the Same as Interpolation
Authors: Wang Yuxuan , King Ross D.
Published: October 2023

We propose a new machine learning formulation designed specifically for extrapolation. The textbook way to apply machine learning to drug design is to learn a univariate function that when a drug (structure) is input, the function outputs a real number (the activity): F(drug) → activity. The PubMed server lists around twenty thousand papers doing this. However, experience in real-world drug design suggests that this formulation of the drug design problem is not quite correct. Specifically, what one is really interested in is extrapolation: predicting the activity of new drugs with higher activity than any existing ones. Our new formulation for extrapolation is based around learning a bivariate function that predicts the difference in activities of two drugs: F(drug1, drug2) → signed difference in activity. This formulation is general and potentially suitable for problems to find samples with target values beyond the target value range of the training set. We applied the formulation to work with support vector machines (SVMs), random forests (RFs), and Gradient Boosting Machines (XGBs). We compared the formulation with standard regression on thousands of drug design datasets, and hundreds of gene expression datasets. The test set extrapolation metrics use the concept of classification metrics to count the identification of extraordinary examples (with greater values than the training set), and top-performing examples (within the top 10% of the whole dataset). On these metrics our pairwise formulation vastly outperformed standard regression for SVMs, RFs, and XGBs. We expect this success to extrapolate to other extrapolation problems.
Gravitational capture of magnetic monopoles by primordial black holes in the early universe
Authors: Zhang Chen , Zhang Xin
Published: October 2023

Abstract

It is intriguing to ask whether the existence of primordial black holes (PBHs) in the early universe could significantly reduce the abundance of certain stable massive particles (SMP) via gravitational capture, after which the PBHs evaporate before BBN to avoid conflict with stringent bounds. For example, this mechanism is relevant to an alternative solution of the monopole problem proposed by Stojkovic and Freese, in which magnetic monopoles produced in the early universe are captured by PBHs, thus freeing inflation from having to occur during or after the corresponding phase transitions that produced the monopoles. In this work, we reanalyze the solution by modelling the capture process in the same way as the coexisting monopole annihilation. A subtle issue which is not handled properly in the previous literature is the choice of an effective capture cross section for diffusive capture. We model this aspect properly and justify our treatment. A monochromatic PBH mass function and a radiation-dominated era before PBH evaporation are assumed. We find that for Pati-Salam monopoles corresponding to a symmetry breaking scale between 1010 GeV and 1015 GeV, the capture rate is many orders of magnitude below what is needed to cause a significant reduction of the monopole density. Within our assumptions, we also find that the magnetic charge that is large enough to make an extremal magnetic black hole cosmologically stable cannot be obtained from magnetic charge fluctuation via monopole capture. The large magnetic charged required by cosmological stability can nevertheless be obtained from magnetic charge fluctuation at PBH formation, and if later the monopole abundance can be reduced significantly by some non-inflationary mechanism, long-lived near-extremal magnetic black holes of observational relevance might result.
Spinorial Representation of Submanifolds in a Product of Space Forms
Authors: Basilio Alicia , Bayard Pierre , Lawn Marie-Amélie , Roth Julien
Published: October 2023

We present a method giving a spinorial characterization of an immersion into a product of spaces of constant curvature. As a first application we obtain a proof using spinors of the fundamental theorem of immersion theory for such target spaces. We also study special cases: we recover previously known results concerning immersions in $$\mathbb {S}^2\times \mathbb {R}$$

S

2

×
R

and we obtain new spinorial characterizations of immersions in $$\mathbb {S}^2\times \mathbb {R}^2$$

S

2

×

R

2

and in $$\mathbb {H}^2\times \mathbb {R}.$$

H

2

×
R
.

We then study the theory of $$H=1/2$$

H
=
1
/
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surfaces in $$\mathbb {H}^2\times \mathbb {R}$$

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using this spinorial approach, obtain new proofs of some of its fundamental results and give a direct relation with the theory of $$H=1/2$$

H
=
1
/
2

surfaces in $$\mathbb {R}^{1,2}$$

R

1
,
2

.
Refinements of discrete and integral Jensen inequalities with Jensen’s gap
Authors: Horváth László
Published: October 2023

Motivated by a paper of Dragomir, we give new refinements for both discrete and integral Jensen inequalities using the Jensen’s gap. As applications, we give refinements of various inequalities verifiable by Jensen’s inequality. Topics covered: norms, quasi-arithmetic means, Hölder’s inequality andf-divergences in information theory.
Infiltrating macrophages amplify doxorubicin-induced cardiac damage: role of catecholamines
Authors: Gambardella Jessica , Santulli Gaetano , Fiordelisi Antonella , Cerasuolo Federica Andrea , Wang Xujun , Prevete Nella , Sommella Eduardo , Avvisato Roberta , Buonaiuto Antonietta , Altobelli Giovanna Giuseppina , Rinaldi Laura , Chiuso Francesco , Feliciello Antonio , Dal Piaz Fabrizio , Campiglia Pietro , Ciccarelli Michele , Morisco Carmine , Sadoshima Junichi , Iaccarino Guido , Sorriento Daniela
Published: October 2023

Background

The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, in the setup of heart failure in response to doxorubicin (Dox) is recently becoming of growing interest.

Objectives

The study aims to evaluate the role of macrophages in cardiac damage elicited by Dox treatment.

Methods

C57BL/6 mice were treated with one intraperitoneal injection of Dox (20 mg/kg) and followed up for 5 days by cardiac ultrasounds (CUS), histological, and flow cytometry evaluations. We also tested the impact of Dox in macrophage-depleted mice. Rat cardiomyoblasts were directly treated with Dox (D-Dox) or with a conditioned medium from cultured murine macrophages treated with Dox (M-Dox).

Results

In response to Dox, macrophage infiltration preceded cardiac damage. Macrophage depletion prevents Dox-induced damage, suggesting a key role of these cells in promoting cardiotoxicity. To evaluate the crosstalk between macrophages and cardiac cells in response to DOX, we compared the effects of D-Dox and M-Dox in vitro. Cell vitality was lower in cardiomyoblasts and apoptosis was higher in response to M-Dox compared with D-Dox. These events were linked to p53-induced mitochondria morphology, function, and autophagy alterations. We identify a mechanistic role of catecholamines released by Dox-activated macrophages that lead to mitochondrial apoptosis of cardiac cells through β-AR stimulation.

Conclusions

Our data indicate that crosstalk between macrophages and cardiac cells participates in cardiac damage in response to Dox.

Graphical abstract
Hodge-Elliptic Genera, K3 Surfaces and Enumerative Geometry
Authors: Cirafici Michele
Published: October 2023

K3 surfaces play a prominent role in string theory and algebraic geometry. The properties of their enumerative invariants have important consequences in black hole physics and in number theory. To a K3 surface, string theory associates an Elliptic genus, a certain partition function directly related to the theory of Jacobi modular forms. A multiplicative lift of the Elliptic genus produces another modular object, an Igusa cusp form, which is the generating function of BPS invariants of$$\textrm{K3} \times E$$K3×E. In this note, we will discuss a refinement of this chain of ideas. The Elliptic genus can be generalized to the so-called Hodge-Elliptic genus which is then related to the counting of refined BPS states of$$\textrm{K3} \times E$$K3×E. We show how such BPS invariants can be computed explicitly in terms of different versions of the Hodge-Elliptic genus, sometimes in closed form, and discuss some generalizations.
A characterization of consistent assessments using power sequences of strategy profiles
Authors: Dilmé Francesc
Published: October 2023

This paper provides a new characterization of belief consistency in extensive games. We show thatallconsistent assessments are supported by sequences of strategy profiles with the property that all actions with vanishing probability are played according to power functions of the sequence index. The result makes it simpler to prove or disprove that a given assessment is consistent, facilitating the use of sequential equilibria.
Influence of enzymatic clarification, filtration, and pasteurization on ellagitannin and anthocyanin content in raspberry juices
Authors: Sójka Michał , Nowakowska Aleksandra , Hejduk Agnieszka
Published: October 2023

The aim of the study was to investigate the effect of the enzymatic process of clarification, filtration, and pasteurization on the retention of ellagitannins in raspberry juices. Experiments were carried out to determine the influence of the enzymatic clarification and filtration of cloudy juice and the pasteurization of clear juice on the content of ellagitannins and anthocyanins typical for raspberry fruits, namely lambertianin C, sanguiin H-6, cyanidin-3-sophoroside, and cyanidin-3-rutinoside, in the final product. Enzymatic treatment was performed using the Rohapect 10L enzyme at the manufacturer’s recommended dose of 80 mg/L for 1 h at 45 °C. The process of cloudy juice filtration was carried out immediately after enzymatic treatment on a Hobrafilt type S40N filter medium enabling the retention of 5 μm particles. Due to the high retention of the main ellagitannins on the filtration barrier, the pasteurization process was carried out on juices fortified with the tested compounds. Pasteurization was carried out in four variants, using temperatures of 65 and 85 °C and pasteurization times of 20 and 60 s. The studies showed that the process of enzymatic clarification (1 h, 45 °C) did not significantly affect the content of ellagitannins or anthocyanins. The critical factor determining the content of the tested compounds was the filtration stage, which caused 100% retention of lambertianin C and 82% retention of sanguiin H-6 on the filtration barrier, as manifested by the low content of these substances in the filtered juice. The filtration process did not affect the content of anthocyanins. In addition, it was shown that regardless of the pasteurization conditions used, this process did not significantly affect the contents of lambertianin C, sanguiin H-6, or the tested anthocyanins.
Archeological wood conservation with selected organosilicon compounds studied by XFM and nanoindentation
Authors: Broda Magdalena , Jakes Joseph E. , Li Luxi , Antipova Olga A.
Published: October 2023

Waterlogged wood conservation is a complex and challenging task. Detailed knowledge about the interactions between the applied chemicals and wood is necessary to ensure the effective and safe conservation of wooden artifacts. The present research aims to determine the mechanism of dimensional stabilization of archeological wood by organosilicon compounds using the combination of synchrotron-based X-ray fluorescence microscopy (XFM) and nanoindentation. Archeological oak wood was treated with methyltrimethoxysilane, (3-mercaptopropyl)trimethoxysilane, or 1,3-bis-[(diethylamino)-3-(propoxy)propan-2-ol]-1,1,3,3-tetramethyldisiloxane, which in previous studies were found to be more effective than other organosilicons in stabilizing wood dimensions. The XFM and nanoindentation results showed that all three organosilicons infiltrated wood cell walls and enhanced their mechanical properties. The XFM also showed that part of the chemicals filled some void spaces like cell lumina. Based on the results obtained here and in our previous research, it is determined that the mechanism of archeological wood dimensional stabilization by organosilicon treatment is complex and likely involves both filling cell lumina and infiltration into cell walls where organosilicons interact with wood polymers.
Perceived spatial presence and body orientation affect the recall of out-of-sight places in an immersive sketching experiment
Authors: Grochulla Banafsheh , Mallot Hanspeter A.
Published: October 2023

The orientation of sketch maps of remote but familiar city squares produced from memory has been shown to depend on the distance and airline direction from the production site to the remembered square (position-dependent recall, Röhrich et al. in PLoS One 9(11): e112793, 2014). Here, we present a virtual reality version of the original experiment and additionally study the role of body orientation. Three main points can be made: First, “immersive sketching” is a novel and useful paradigm in which subjects sketch maps live on paper while being immersed in virtual reality. Second, the original effect of position-dependent recall was confirmed, indicating that the sense of being present at a particular location, even if generated in a virtual environment, suffices to bias the imagery of distant places. Finally, the orientation of the produced sketch maps depended also on the body orientation of the subjects. At each production site, body orientation was controlled by varying the position of the live feed in the virtual environment, such that subjects had to turn towards the prescribed direction. Position-dependent recall is strongest if subjects are aligned with the airline direction to the target and virtually goes away if they turn in the opposite direction. We conclude that the representation of out-of-sight target places depends on both the current airline direction to the target and the body orientation.
MDM2 amplification is rare in gastric cancer
Authors: Abdullazade Samir , Behrens Hans-Michael , Krüger Sandra , Haag Jochen , Röcken Christoph
Published: October 2023

The MDM2 proto-oncogene (MDM2) is a primary negative regulator of p53. The latter is frequently mutated in gastric cancer (GC). In the present study, we aimed to validate gene amplification, protein expression, and the putative tumor biological function of MDM2 in a well-characterized Western GC cohort. MDM2 amplification and protein expression were studied in a cohort of 327 GCs by fluorescence in situ hybridization (FISH) and immunohistochemistry. Gene amplification and protein expression were correlated with diverse clinicopathological patient characteristics including patient outcome. Immunohistochemically, 97 GCs (29.7%) were categorized as MDM2 positive and 230 GCs (70.3%) as negative. An amplification of MDM2 was found in 11 (3.4%) cases without evidence of intratumoral heterogeneity. Nine of these eleven (81.8%) cases showed MDM2 protein expression. MDM2 amplification correlated significantly with MDM2 protein expression (p < 0.001). On a case-by-case analysis, MDM2-amplified cases showed varied histological phenotypes and were most commonly microsatellite stable; EBV, HER2, and MET negative; and FGFR2 positive. A single case harbored both, MDM2 amplification and TP53 mutation. MDM2 amplification and MDM2 expression, respectively, did not correlate with overall or tumor-specific survival. Our targeted analysis of MDM2 in a well-characterized cohort of GC patients showed that MDM2 amplification is rare, of no specific histological phenotype, and may not be always mutually exclusive with TP53 mutations. Given the low number of cases, currently, no diagnostic or therapeutic recommendation related to MDM2 amplification can be given for GC of Western origin.