bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting the Antifungal Activity of Carbon Dots against Candida albicans Biofilm Formation by Tailoring Their Surface Functional Groups
Authors: Sturabotti Elisa , Camilli Alessandro , Georgian Moldoveanu Vyali , Bonincontro Graziana , Simonetti Giovanna , Valletta Alessio , Serangeli Ilaria , Miranda Elena , Amato Francesco , Giacomo Marrani Andrea , Migneco Luisa Maria , Sennato Simona , Simonis Beatrice , Vetica Fabrizio , Leonelli Francesca
Published: December 2023

Carbon dots (CDs) are an emerging class of carbon nanoparticles, which for their characteristics have found applications in many fields such as catalysis, materials and biomedicine. Within this context, the application of CDs as antibacterial agents has received much attention in very recent years, while their use as antifungal nanoparticles has been scarcely investigated. Here we report a systematic investigation of the surface functional groups of CDs to study their influence on these nanoparticles’ against Candida albicans. Three classes of CDs have been synthesised and fully characterized. A thorough in vitro and in vivo biological screening against C. albicans was performed to test their antifungal, antiadhesion and antibiofilm formation activities. Moreover, the interaction with C. albicans cells was investigated by microscopic analysis. Our results evidence how the presence of a positively polarised surface results crucial for the internalization into COS‐7 cells. Positively charged nanoparticles were also able to inhibit adhesion and biofilm formation, to interact with the cellular membrane of C. albicans, and to increase the survival of G. mellonella infected larvae after the injection with positive nanoparticles. The antifungal activity of CDs and their extremely low toxicity may represent a new strategy to combat infections sustained by C.albicans.
Sichere Sanierung von Tanklagern
Authors: Gieseler Jens
Published: December 2023

Unternehmen, die große Tanks vorhalten, müssen diese Anlagen alle zehn Jahre sanieren und auf den neusten technischen Stand bringen. Jeder Tank ist anders und mit vielen Besonderheiten ausgestattet. Sicherheit, Arbeits‐ und Umweltschutz haben im Gerüstbau für die Sanierung höchste Prioriät, was bei Gemeinhardt Service mit dem SCCP‐Zertifikat belegt wird.
Effiziente Überwachung von Kondensatableitern
Authors: Lambrecht Maren , Schoene Jens
Published: December 2023

Manuelle Inspektionen von Kondensatableitern sind eine bekannte Herausforderung in der Industrie. Weil sie oft auf jährliche Intervalle beschränkt sind, kann die dadurch verzögerte Fehlererkennung aufgrund signifikanter Ausfallraten von Kondensatableitern zu erheblichen Energieverlusten und unnötigen CO2‐Emissionen führen. Blockierte Kondensatableiter können wiederum Sicherheitsrisiken und Produktionsausfälle zur Folge haben. Industrie 4.0‐Technologie hat schon länger die Art und Weise revolutioniert, wie industrielle Anlagen betrieben werden. Das IIoT‐basierte System Loctite Pulse Smart Steam Trap bietet eine kontinuierliche überwachung mit deutlich reduzierter Detektionszeit.
Sicherheit durch Sichtbarkeit
Authors: Wenderoth Sarah , Schug Benedikt
Published: December 2023

Ein Indikator auf Suprapartikel‐Basis kann die Anwesenheit von Wasserstoff schnell und kostengünstig erkennbar machen. Ein zweistufiger Farbumschlag zeigt die Wasserstoffexposition oder Leckage an. Der Farbindikator wurde in der Zusammenarbeit zwischen dem Fraunhofer‐Institut für Silicatforschung ISC und der Friedrich‐Alexander‐Universität entwickelt.
Nanomedicine in chemistry education: Targeted drug delivery with polymer nanoparticles
Authors: Fruntke Antonia , Behnke Mira , Dietel Elisabeth , Vollrath Antje , Schubert Ulrich S. , Wilke Timm
Published: December 2023

In diesem Beitrag werden zwei Versuchsreihen zum Thema Nanomedizin für die Oberstufe und Schülerlabore präsentiert. Es wird das Prinzip der „Nanocarrier“ vorgestellt, die genutzt werden können, um Wirkstoffe zielgerichtet zu Organen und infiziertem Gewebe zu transportieren. Dadurch können lokal eine höhere Wirkstoffdosis erreicht und gleichzeitig Nebenwirkungen minimiert werden. Die Versuchsreihen umfassen alle relevanten Schritte von (1) der Wahl bzw. der Synthese der Polymere über (2) die Formulierung und Beladung mit fluoreszierenden Modellsubstanzen bis zu (3) dem zielgerichteten Abbau der Nanocarrier durch Esterspaltung und der Freisetzung der Modellsubstanz. Alle Experimente können als Schülerversuche mit einfachen Geräten aus dem Schullabor innerhalb von einer Doppelstunde durchgeführt werden. Inhaltlich können die Lehrplanthemen „Nano“ und „Polymere“ ideal miteinander vernetzt und zahlreiche klassische Inhalte des Chemieunterrichts (Polymerisation, Polarität, Esterbildung, ‐spaltung, Carbonsäuren, …) anhand eines attraktiven und motivierenden Kontextes eingeführt oder gefestigt werden.
Dispersed Nickel Phosphide Cocatalyst on Nb2O5 Ultrathin Nanosheets to Boost Photocatalytic CO2 Reduction
Authors: Wang Zijian , Li Mengdie , Xiao Mingjiao , Wei Yanze , Yu Ranbo , Wang Zumin
Published: December 2023

Photocatalytic CO2 reduction holds great promise to solve energy shortage and global warming. Nb2O5 has demonstrated superiority in CO2 activation and selectivity regulation, but suffers from poor light absorption ability and fast carrier recombination. To tackle these problems, we designed and synthesized ultrathin Nb2O5 nanosheets which were decorated with tiny NiP nanoparticles as cocatalyst. In this way, light absorption range broadened, carrier migration distance reduced, charge transfer resistance decreased, and surface reaction kinetics promoted. Consequently, the as‐prepared NiP/Nb2O5 showed notably enhanced activity (148.7 μmol ⋅ g−1) and selectivity (82.1 %) towards CO, as well as remarkable stability. This work paves the way for cheap and earth abundant alternatives as cocatalysts and deepens the understanding of their functions in CO2 photoreduction.
Spin Polarization: A New Frontier in Efficient Photocatalysis for Environmental Purification and Energy Conversion
Authors: Zhao Zhiyong , Zhang Tao , Yue Shuai , Wang Pengfei , Bao Yueping , Zhan Sihui
Published: December 2023

As a promising strategy to improve photocatalytic efficiency, spin polarization has attracted enormous attention in recent years, which could be involved in various steps of photoreaction. The Pauli repulsion principle and the spin selection rule dictate that the behavior of two electrons in a spatial eigenstate is based on their spin states, and this fact opens up a new avenue for manipulating photocatalytic efficiency. In this review, recent advances in modulating the photocatalytic activity with spin polarization are systematically summarized. Fundamental insights into the influence of spin‐polarization effects on photon absorption, carrier separation, and migration, and the behaviors of reaction‐related substances from the photon uptake to reactant desorption are highlighted and discussed in detail, and various photocatalytic applications for environmental purification and energy conversion are presented. This review is expected to deliver a timely overview of the recent developments in spin‐polarization‐modulated photocatalysis for environmental purification and energy conversion in terms of their practical applications.
General dental practitioners' fees for root canal treatment, coronal restoration and follow‐on treatment in the adult population in Sweden: A 10‐year follow‐up of data from the Swedish Dental Register
Authors: Wigsten Emma , Fransson Helena , Isberg Per‐Erik ,   EndoReCo, Dawson Victoria S.
Published: December 2023

Objectives

To analyze the accumulated fees connected with root filling, permanent coronal restoration and follow‐on treatment charged by Swedish dentists over a 10–11‐year follow‐up period. Furthermore, analyzing these fees with reference to the type of restoration, tooth group, and the root‐filled teeth which survived compared to those requiring extraction.

Material and Methods

In 2009, the data register of the Swedish Social Insurance Agency recorded a total of 215,611 teeth as root‐filled. The accumulated fees for each tooth encompassed the following interventions: initial root filling, coronal restorations, and follow‐up treatments during the designated period. The outcomes were analyzed using descriptive and analytic statistics, including t tests and one‐way analysis of variance. The fees are presented in Euros (€1 = SEK 8.94).

Results

The total accumulated fees for root fillings amounted to 72 million Euros: the mean fee per root filled tooth was €333.6. The total mean fee over a 10–11‐year period, comprising root canal treatment, coronal restorations, and any follow‐up treatments, was €923.4. Root‐filled teeth with indirect restorations presented a higher mean fee (€1 279.3) compared to those with direct restorations (€829.4) or those without specified restorations (€832.7; p < .001). Moreover, molars presented a significantly higher mean fee (€966.4) compared to premolars (€882.8) and anterior teeth (€891.3; p < .001). Lastly, the mean fee for extracted teeth was €1225.3, which was higher compared to those who survived the follow‐up period (€848.0; p < .001).

Conclusions

Fees charged by general dental practitioners for root‐filled teeth accumulate over time, probably due to the need for further treatment of the tooth. The total mean fee was significantly higher for molars and root‐filled teeth with indirect restorations. However, an analysis of the total costs would require prospective clinical cost‐effectiveness studies.
Cultivar and environmental impacts on protein and mineral concentrations in peas (Pisum sativum L.)
Authors: Franck William , Chen Chengci , Franck Sooyoung , Mohammed Yesuf Assen , Abdelhamid Magdi T. , Miller Perry , Carr Patrick M. , Lamb Peggy , Torrion Jessica , Khan Qasim , McVay Kent
Published: December 2023

Pea (Pisum sativum L.) grain contains abundant protein, starch, and minerals. However, there are obstacles to growing peas that achieve consistently high protein and mineral concentrations. Seven pea cultivars were planted at seven locations with contrasting soils and environmental factors to evaluate the genetic and environmental effects on pea yield and quality. Correlations and principal component analyses (PCA) were performed to correlate pea grain yield and protein with mineral concentrations in pea grain and soil. Significant cultivar × location interactions were observed on pea grain yield but not on pea grain protein concentration. Some cultivars demonstrated more sensitivity to the environment than others in terms of grain yield potential and stability. The lack of a cultivar × location interaction for pea grain protein concentration indicates consistent genetic control of this quality parameter. Although there was a negative relationship between pea grain yield and protein concentration at the cultivar level at each environment, this correlation became weaker while pooling the data from all environments (site‐years) due to the confounding effect from environments. Pea grain mineral concentrations were significantly affected by cultivar and location, but location generally affected the mineral levels more than cultivar. Grain mineral nutrients, especially macronutrients, were highly correlated with soil minerals. The three distinct clusters formed in the PCA indicate mega environments that determine pea grain yield and quality, and understanding the mega environments in combination with improved soil fertility management may represent the most effective means of increasing pea grain yield, protein, and targeted mineral levels.
Donor‐Acceptor Conjugated Acetylenic Polymers for High‐Performance Bifunctional Photoelectrodes
Authors: Borrelli Mino , An Yun , Querebillo Christine Joy , Morag Ahiud , Neumann Christof , Turchanin Andrey , Sun Hanjun , Kuc Agnieszka , Weidinger Inez M. , Feng Xinliang
Published: December 2023

Due to the drastic required thermodynamical requirements, a photoelectrode material that can function as both a photocathode and a photoanode remains elusive. In this work, we demonstrate for the first time that, under simulated solar light and without co‐catalysts, donor‐acceptor conjugated acetylenic polymers (CAPs) exhibit both impressive oxygen evolution (OER) and hydrogen evolution (HER) photocurrents in alkaline and neutral medium, respectively. In particular, poly(2,4,6‐tris(4‐ethynylphenyl)‐1,3,5‐triazine) (pTET) provides a benchmark OER photocurrent density of ~200 μA cm−2 at 1.23 V vs. reversible hydrogen electrode (RHE) at pH 13 and a remarkable HER photocurrent density of ~190 μA cm−2 at 0.3 V vs. RHE at pH 6.8. By combining theoretical investigations and electrochemical‐operando Resonance Raman spectroscopy, we show that the OER proceeds with two different mechanisms, with the electron‐depleted triple bonds acting as single‐site OER in combination with the C4‐C5 atoms of the phenyl rings as dual sites. The HER, instead, occurs via an electron transfer from the tri‐acetylenic linkages to the triazine rings, which act as the HER active sites. This work represents a novel application of organic‐based materials and contributes to the development of high‐performance photoelectrochemical catalysts for the solar fuels’ generation.
Elevated Id2 expression causes defective meiosis and spermatogenesis in mice
Authors: He Zhen , Yan Rong‐Ge , Shang Qin‐Bang , Yang Qi‐En
Published: December 2023

Background

Inhibitors of DNA binding (ID) proteins mainly inhibit gene expression and regulate cell fate decisions by interacting with E‐proteins. All four ID proteins (ID1–4) are present in the testis, and ID4 has a particularly important role in spermatogonial stem cell fate determination. Several lines of evidence indicate that ID proteins are involved in meiosis; however, functional experiments have not been conducted to validate this observation.

Results

In this study, we report that ID2 is enriched in spermatocytes and that forced ID2 expression in germ cells causes defects in spermatogenesis. A detailed analysis demonstrated that Id2 overexpression (Id2 OE) decreased the total number of spermatogonia and changed the dynamics of meiosis progression. Specifically, spermatocytes were enriched in the zygotene stage, and the proportion of pachytene spermatocytes was significantly decreased, indicating defects in the zygotene–pachytene transition. The number of MLH1‐positive foci per cell was decreased in pachytene spermatocytes from Id2 OE testes, suggesting abnormalities in recombination. Transcriptome analysis revealed that forced Id2 expression changed the expression of a list of genes mainly associated with meiosis and spermatid development.

Conclusions

ID2 protein is expressed in spermatocytes, and its genetic ablation in the germline does not affect spermatogenesis, likely due to genetic compensation of its family members. However, forced Id2 expression changes meiosis progression and causes defects in spermiogenesis. These data provide important evidence that ID proteins play pivotal roles in male meiosis and spermatid development.
Rectal sensitivity correlated with gastrointestinal‐mediated glucose disposal, but not the incretin effect
Authors: Meling Sondre , Tjora Erling , Eichele Heike , Nedergaard Rasmus B. , Knop Filip K. , Ejskjaer Niels , Carlsen Siri , Njølstad Pål R. , Brock Christina , Søfteland Eirik
Published: December 2023

Objective

The mechanisms behind the diminished incretin effect in type 2 diabetes are uncertain, but impaired vagal transmission has been suggested. We aimed to investigate the association between the incretin effect and autonomic neuropathy, and the degree of dysglycaemia and duration of diabetes.

Design and Methods

For a cross‐sectional study, we included participants with either longstanding type 2 diabetes, recent onset, untreated diabetes and controls without diabetes matched for age, sex and body mass index. Autonomic nerve function was assessed with cardiovascular reflex tests, heart rate variability and sudomotor function. Visceral afferent nerves in the gut were tested performing rapid rectal balloon distention. An oral glucose tolerance test and an intravenous isoglycaemic glucose infusion were performed to calculate the incretin effect and gastrointestinal‐mediated glucose disposal (GIGD).

Results

Sixty‐five participants were recruited. Participants with diabetes had rectal hyposensitivity for earliest sensation (3.7 ± 1.1 kPa in longstanding, 4.0 ± 1.3 in early), compared to controls (3.0 ± 0.9 kPa), p = .005. Rectal hyposensitivity for earliest sensation was not associated with the incretin effect (rho = −0.204, p = .106), but an association was found with GIGD (rho −0.341, p = .005). Incretin effect and GIGD were correlated with all glucose values, HbA1c and duration of diabetes.

Conclusions

Rectal hyposensitivity was uncovered in both longstanding and early type 2 diabetes, and was not associated with the incretin effect, but with GIGD, implying a potential link between visceral neuropathy and gastrointestinal handling of glucose. Both the incretin effect and GIGD were associated with the degree of dysglycaemia and the duration of diabetes.

Previously Published

Some of the data have previously been published and presented as a poster on the American Diabetes Association 83rd Scientific Sessions: Meling et al; 1658‐P: Rectal Hyposensitivity, a Potential Marker of Enteric Autonomic Nerve Dysfunction, Is Significantly Associated with Gastrointestinally Mediated Glucose Disposal in Persons with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 1658–P. https://doi.org/10.2337/db23‐1658‐P.
European Society of Cardiology guidelines and 1 year outcomes of acute heart failure treatment in Central Asia and Europe
Authors: Abdurashidova Tamila , Müller Martin , Schukraft Sara , Soborun Nisha , Pitta‐Gros Barbara , Kikoïne John , Lu Henri , Chazymova Zalina , Dzhorupbekova Kanzaada , Beishenkulov Medet , Tzimas Georgios , Kirsch Matthias , Vollenweider Peter , Mean Marie , Monney Pierre , Hullin Roger
Published: December 2023

Aims

Outcomes reported for patients with hospitalization for acute heart failure (AHF) treatment vary worldwide. Ethnicity‐associated characteristics may explain this observation. This observational study compares characteristics and 1‐year outcomes of Kyrgyz and Swiss AHF patients against the background of European Society of Cardiology guidelines‐based cardiovascular care established in both countries.

Methods and results

The primary endpoint was 1 year all‐cause mortality (ACM); the secondary endpoint was 1 year ACM or HF‐related rehospitalization. A total of 538 Kyrgyz and 537 Swiss AHF patients were included. Kyrgyz patients were younger (64.0 vs. 83.0 years, P < 0.001); ischaemic or rheumatic heart disease and chronic obstructive pulmonary disease were more prevalent (always P < 0.001). In Swiss patients, smoking, dyslipidaemia, hypertension, and atrial flutter/fibrillation were more frequent (always P ≤ 0.035); moreover, left ventricular ejection fraction (LVEF) was higher (47% vs. 36%; P < 0.001), and >mild aortic stenosis was more prevalent (P < 0.001). Other valvular pathologies were more prevalent in Kyrgyz patients (P < 0.001). At discharge, more Swiss patients were on vasodilatory treatment (P < 0.006), while mineralocorticoid receptor antagonists (P = 0.001), beta‐blockers (P = 0.001), or loop diuretics (P < 0.001) were less often prescribed. In Kyrgyz patients, unadjusted odds for the primary and secondary endpoints were lower [odds ratio (OR) 0.68, 95% confidence interval (CI): 0.51–0.90, P = 0.008; OR 0.72, 95% CI: 0.56–0.91, P = 0.006, respectively]. After adjustment for age and LVEF, no difference remained (primary endpoint: OR 1.03, 95% CI: 0.71–1.49, P = 0.894; secondary endpoint: OR 0.82, 95% CI: 0.60–1.12, P = 0.206).

Conclusions

On the background of identical guidelines, age‐ and LVEF‐adjusted outcomes were not different between Central Asian and Western European AHF patients despite of large ethnical disparity.
Prostaglandin E₂ impacts multiple stages of the natural killer cell antitumor immune response
Authors: Patterson Chloe , Hazime Khodor S. , Zelenay Santiago , Davis Daniel M.
Published: December 2023

Tumor immune escape is a major factor contributing to cancer progression and unresponsiveness to cancer therapies. Tumors can produce prostaglandin E2 (PGE2), an inflammatory mediator that directly acts on Natural killer (NK) cells to inhibit antitumor immunity. However, precisely how PGE2 influences NK cell tumor‐restraining functions remains unclear. Here, we report that following PGE₂ treatment, human NK cells exhibited altered expression of specific activating receptors and a reduced ability to degranulate and kill cancer targets. Transcriptional analysis uncovered that PGE₂ also differentially modulated the expression of chemokine receptors by NK cells, inhibiting CXCR3 but increasing CXCR4. Consistent with this, PGE₂‐treated NK cells exhibited decreased migration to CXCL10 but increased ability to migrate toward CXCL12. Using live cell imaging, we showed that in the presence of PGE2, NK cells were slower and less likely to kill cancer target cells following conjugation. Imaging the sequential stages of NK cell killing revealed that PGE₂ impaired NK cell polarization, but not the re‐organization of synaptic actin or the release of perforin itself. Together, these findings demonstrate that PGE₂ affects multiple but select NK cell functions. Understanding how cancer cells subvert NK cells is necessary to more effectively harness the cancer‐inhibitory function of NK cells in treatments.
Bridging upstream and downstream for improved adenovirus 5 bioprocess
Authors: Petrović Koshmak Ivana , Jug Hana , Vrabec Katja , Mavri Ana , Novak Valentina , Dekleva Petra , Fujs Veronika , Leskovec Maja , Štrancar Aleš
Published: December 2023

Adenoviruses are well‐known viral vectors that have been previously used in gene therapy and as a vaccine‐delivery vehicle for humans and animals. During the COVID‐19 pandemic, it gained renewed attention, but at the same time, it raised concerns due to side effects observed with some of the resulting vaccines administered to patients. It has been indicated that these side effects might be attributed to impurities present in the final product. Therefore, constant enhancement of the vaccine purity and further improvement of impurity detection methods are needed. In this work, we showcase an example of industry‐relevant adenovirus bioprocess optimization. Our data show the effect of upstream parameters on the bioburden introduced to the downstream process. We provide an example of process optimization using a combination of the PATfix analytical method, ddPCR, infectivity, total DNA, and total protein analyses to optimize cell density, multiplicity of infection, and length of production. Additionally, we provide data illustrating the robustness of the convective interaction media quaternary amine monolithic chromatography step. This anion exchange strategy was shown to remove over 99% of protein and DNA impurities, including those unable to be addressed by tangential flow filtration, while maintaining high adenovirus recoveries.
Investigating the Performance of Newly Designed Benzothiophene‐4,8‐Dione‐Based Dyes for Dye‐Sensitized Solar Cells
Authors: Hassan Abrar U. , Li Yuchuan
Published: December 2023

This research analyzes newly designed benzo1,2‐b:4,5‐b'dithiophene‐4,8‐dione‐based electron–hole transport dyes (BDD1‐BDD5), focusing mainly on their electronic and photovoltaic parameters. The calculations are performed using density functional theory with the M‐06X/6‐31G+(d,p) level of theory. Their highest occupied molecular orbital energies (EHOMO) range from −5.46 to −2.58 eV, while their lowest occupied molecular orbital energies (ELUMO) to range from −0.32 to −1.31 eV, with energy gaps (Egaps) of 2.67 to −5.88 eV. Their photovoltaic parameters show light harvesting efficiency (LHE) ranging from 0.84 to 0.93 eV, open‐circuit voltage (Voc) ranging from 0.88 to 1.45 eV, fill factor (FF) ranging from 0.883 to 0.9117, short‐circuit current (Jsc) ranging from 29.22 to 37.71 mA cm−2, and maximum incident power (Pmax) ranging from 24.01 to 39.92 W with maximum absorbance (λmax) ranging from 390 to 557 nm. Their range of global chemical reactivity parameters, such as ionization potential (IP, 2.58–5.46 eV), electron affinity (EA, −0.25–0.32 eV), electronegativity (x, 1.25–2.61 eV), global hardness (η, 1.33–2.94 eV), electrophilicity index (0.17–0.38 eV), and softness (σ, 0.18–0.45 eV), provides insights into the stability, reactivity, electron transfer capabilities, and planarity of molecules. Their natural bond orbital analysis reveals transitions with perturbation energies ranging from 0.34 to 30.85 K cal mol−1. These findings provide valuable insights into their properties and potential applications, particularly in photovoltaics as organic dyes.
Optimization of spicy red pepper paste (Awaze) formulation by D‐optimal mixture design
Authors: Kefale Biadge , Delele Mulugeta Admasu , Fanta Solomon Workneh , Abate Solomon
Published: December 2023

The aim of this study was to produce spicy red pepper paste (Awaze) by addition of various sources of antioxidant, mineral, and fiber and optimize better processing methods of the paste. For this purpose, D‐optimal mixture design was used, Awaze considering color value (a*), antioxidant content, mineral content, fiber content, chewiness, and viscosity of the paste as the main parameters. Various properties of the optimized formulation were evaluated. The optimal formulation contained 65.66% red pepper, 10% garlic, 19.08% red onion, and 5.25% ginger. In the optimized formulation, the redness value (a*) increased by more than 3.12 times compared to the control with the average antioxidant activity (44.6%). The optimal formulation had a higher fiber content, chewiness, and viscosity value compared to control which is probably related to the ingredient proportion difference. Due to the higher nutritional and processing quality obtained, this formulation can be suggested for commercial and household producers as a guide to manufacture Awaze. The results obtained indicate that it is possible to production of Awaze with high nutritional value and improved processing quality by utilizing a blend of red pepper, garlic, red onion, and ginger. Therefore, this formulation stands as a viable recommendation for both commercial enterprises and household producers due to its demonstrated ability to yield Awaze with enhanced nutritional content and superior processing quality.
High‐dose vitamin D supplementation in patients with COVID‐19: A meta‐analysis of randomized controlled trials
Authors: Zhong Zhaoshuang , Zhao Long , Zhao Yan , Xia Shuyue
Published: December 2023

The efficacy of administering high doses of vitamin D to patients diagnosed with COVID‐19 remains uncertain. We conducted a comprehensive search across multiple databases (PubMed, EMBASE, Cochrane Library, and ISI Web of Science) from inception until August 2022, with no limitations on language, to locate randomized controlled trials (RCTs) that investigated the impact of high‐dose vitamin D supplementation (defined as a single dose of ≥100,000 IU or daily dose of ≥10,000 IU reaching a total dose of ≥100,000 IU) on COVID‐19 patients. Risk ratios (RR) with 95% confidence intervals (CI) and weighted mean differences (WMD) with 95% CI were calculated. Our meta‐analysis included 5 RCTs with a total of 834 patients. High‐dose vitamin D supplementation did not show any significant benefits for mortality (I2 = 0.0%, p = .670; RR 1.092, 95% CI 0.685–1.742, p = .711) or intensive care unit (ICU) admission (I2 = 0.0%, p = .519; RR 0.707, 95% CI 0.454–1.102, p = .126) in COVID‐19 patients compared to the control group. However, it was found to be safe and well‐tolerated (I2 = 0.0%, p = .887; RR 1.218, 95% CI 0.930–1.594, p = .151). Subgroup analysis also showed no benefits in overall mortality, including for patients with vitamin D deficiency (I2 = 0.0%, p = .452; RR 2.441, 95% CI 0.448–13.312, p = .303) or compared to the placebo (I2 = 0.0%, p = .673; RR 1.666, 95% CI 0.711–3.902, p = .240). Our research indicates that there is no evidence to support the efficacy of high‐dose vitamin D supplementation in improving clinical outcomes among individuals with COVID‐19, in line with previous studies focused on contexts including rickets. Considering the limitations of the study, additional research may be required.
The role of the primary sensorimotor system in generalized epilepsy: Evidence from the cerebello–cerebral functional integration
Authors: Chen Junxia , Jiang Sisi , Lu Bao , Liao Jiangyan , Yang Zhihuan , Li Hechun , Pei Haonan , Li Jianfu , Iturria‐Medina Yasser , Yao Dezhong , Luo Cheng
Published: December 2023

The interaction between cerebellum and cerebrum participates widely in function from motor processing to high‐level cognitive and affective processing. Because of the motor symptom, idiopathic generalized epilepsy (IGE) patients with generalized tonic–clonic seizure have been recognized to associate with motor abnormalities, but the functional interaction in the cerebello–cerebral circuit is still poorly understood. Resting‐state functional magnetic resonance imaging data were collected for 101 IGE patients and 106 healthy controls. The voxel‐based functional connectivity (FC) between cerebral cortex and the cerebellum was contacted. The functional gradient and independent components analysis were applied to evaluate cerebello–cerebral functional integration on the voxel‐based FC. Cerebellar motor components were further linked to cerebellar gradient. Results revealed cerebellar motor functional modules were closely related to cerebral motor components. The altered mapping of cerebral motor components to cerebellum was observed in motor module in patients with IGE. In addition, patients also showed compression in cerebello–cerebral functional gradient between motor and cognition modules. Interestingly, the contribution of the motor components to the gradient was unbalanced between bilateral primary sensorimotor components in patients: the increase was observed in cerebellar cognitive module for the dominant hemisphere primary sensorimotor, but the decrease was found in the cerebellar cognitive module for the nondominant hemisphere primary sensorimotor. The present findings suggest that the cerebral primary motor system affects the hierarchical architecture of cerebellum, and substantially contributes to the functional integration evidence to understand the motor functional abnormality in IGE patients.
HPV‐negative head and neck cancers with adverse pathological features carry specific molecular changes that are associated with survival
Authors: Kim Hugh Andrew Jinwook , Zeng Peter Y. F. , Cecchini Matthew , Shaikh Mushfiq Hassan , Laxague Francisco , Deng Xiaoxiao , Jarycki Laura , Ryan Sarah Elizabeth Belle , Dawson Alice , Liu Mu Han , Palma David A. , Patel Krupal , Mundi Neil , Barrett John W. , Mymryk Joe S. , Boutros Paul C. , Nichols Anthony C.
Published: December 2023

Background

Adverse pathological features following surgery in head and neck squamous cell carcinoma (HNSCC) are strongly associated with survival and guide adjuvant therapy. We investigated molecular changes associated with these features.

Methods

We downloaded data from the Cancer Genome Atlas and Cancer Proteome Atlas HNSCC cohorts. We compared tumors positive versus negative for perineural invasion (PNI), lymphovascular invasion (LVI), extracapsular spread (ECS), and positive margins (PSM), with multivariable analysis.

Results

All pathological features were associated with poor survival, as were the following molecular changes: low cyclin E1 (HR = 1.7) and high PKC‐alpha (HR = 1.8) in tumors with PNI; six of 13 protein abundance changes with LVI; greater tumor hypoxia and high Raptor (HR = 2.0) and Rictor (HR = 1.6) with ECS; and low p38 (HR = 2.3), high fibronectin (HR = 1.6), low annexin A1 (HR = 3.1), and high caspase‐9 (HR = 1.6) abundances with PSM.

Conclusions

Pathological features in HNSCC carry specific molecular changes that may explain their poor prognostic associations.
Decreased fetal movements: Report from the International Stillbirth Alliance conference workshop
Authors: Bradford Billie F. , Hayes Dexter J. L. , Damhuis Stefanie , Shub Alexis , Akselsson Anna , Radestad Ingela , Heazell Alexander E. P. , Flenady Vicki , Gordijn Sanne J.
Published: December 2023

Maternal reports of decreased fetal movement (DFM) are a common reason to present to maternity care and are associated with stillbirth and other adverse outcomes. Promoting awareness of fetal movements and prompt assessment of DFM has been recommended to reduce stillbirths. However, evidence to guide clinical management of such presentations is limited. Educational approaches to increasing awareness of fetal movements in pregnant women and maternity care providers with the aim of reducing stillbirths have recently been evaluated in a several large clinical trials internationally. The International Stillbirth Alliance Virtual Conference in Sydney 2021 provided an opportunity for international experts in fetal movements to share reports on the findings of fetal movement awareness trials, consider evidence for biological mechanisms linking DFM and fetal death, appraise approaches to clinical assessment of DFM, and highlight research priorities in this area. Following this workshop summaries of the sessions prepared by the authors provide an overview of understandings of fetal movements in maternity care at the current time and highlights future directions in fetal movement research.
Legislation expanding pharmacist scope of practice to furnish Human Immunodeficiency Virus pre‐exposure prophylaxis: A content analysis
Authors: Cocohoba Jennifer , Tweedie Lauren , Frank Michael , McElya Brad , Witt Ed
Published: December 2023

Introduction

Approximately 1.2 million persons in the United States have indications for human immunodeficiency virus (HIV) pre‐exposure prophylaxis (PrEP) yet utilization remains low. Alternative models for PrEP access, such as community pharmacy programs where pharmacists may prescribe and dispense HIV PrEP medications, may help improve rates of utilization. Individual states have begun to pass laws governing expanded pharmacist practice for provision of PrEP.

Methods

An internet search was conducted from January 2022 to June 2023 to identify United States legislative bills which support the independent provision of PrEP by pharmacists. A content analysis was conducted of the bill text to conceptualize key components, compare these across states, and hypothesize implications for implementation and pharmacy practice.

Results

Twelve states (Arkansas, California, Colorado, Nevada, Utah, New Mexico, Virginia, Oregon, Illinois, Maine, Rhode Island, and Connecticut) with legislation supporting pharmacist‐furnished HIV PrEP were identified. Content analysis revealed differences in required pharmacist training, conditions for furnishing PrEP, total amount of PrEP permitted for dispensing, and discussions of pharmacist‐provided laboratory testing and reimbursement.

Conclusion

Pharmacist‐furnished PrEP is rapidly gaining support as a means to expand access to HIV prevention tools. State‐to‐state differences in legislation will have an impact on implementation and scalability of these models. It will be important to observe states that were early adopters of this type of legislation and who experienced challenges in implementing such programs in order to refine the new legislation being presented in other states.
Sleep duration and cardiorespiratory fitness in adolescents: Longitudinal analysis from the LabMed study
Authors: Sousa‐Sá Eduarda , Fonseca Ana Paula , Lopes Luís , Abreu Sandra , Moreira Carla , Agostinis‐Sobrinho César , Oliveira André , Azevedo Carolina , Santos Rute
Published: December 2023

Purpose

We aimed to investigate longitudinal associations between sleep duration and cardiorespiratory fitness, in adolescents.

Methods

Sleep duration was self‐reported and cardiorespiratory fitness was assessed by the 20 m shuttle run test, both at baseline and follow‐up (2‐year follow‐up). Participants were 734 Northern Portuguese adolescents (349 girls), aged 14.6 ± 1.8 years, from the LabMed study.

Results

Significant decreases were found between baseline and follow‐up for sleep duration, whereas for cardiorespiratory fitness there was an increase. Adolescents with short sleep duration at baseline had lower cardiorespiratory fitness at follow‐up, comparing to those meeting the sleep guidelines (odds ratio [OR] = 0.506, 95% confidence interval [CI]: 0.326–0.785; p = .002 for whole week; OR = 0.597, 95% CI: 0.407–0.875; p = .008 for weekdays). Girls who were short sleepers at baseline had lower odds of having a healthy cardiorespiratory fitness at follow‐up, comparing to those meeting the sleep guidelines (OR = 0.311, 95% CI: 0.158–0.613; p < .001 for whole week; OR = 0.469, 95% CI: 0.262–0.838; p = .011 for weekdays). No significant associations between sleep duration and cardiorespiratory fitness were found for boys.

Discussion

There was a significant longitudinal association between short sleep duration and lower cardiorespiratory fitness levels, particularly in girls. Future interventions targeting adolescents' sleep duration should acknowledge behavioral differences between genders, as well as different behaviors adopted by boys ang girls, specifically on weekends.
Effects of CYP2D6 *10 and *41 Variants in Healthy Chinese Men on the Pharmacokinetics of Dapoxetine
Authors: Wang Zhipeng , Gao Yuan , Ji Xingfang , Wu Tong , Pu Libin , Qiu Wen
Published: December 2023

Dapoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat premature ejaculation (PE), and is mainly metabolized by CYP2D6, CYP3A4, and flavin‐containing monooxygenase 1. The purpose of the study was to evaluate the effect of CYP2D6 polymorphism on the pharmacokinetics of dapoxetine in healthy Chinese men. Thirty‐nine subjects who received a single oral dose of 30 mg dapoxetine hydrochloride were classified based on their CYP2D6 genotype: *1/*1 (n = 9), *1/*41 (n = 1), *1/*10 (n = 12), *10/*41 (n = 3), or *10/*10 (n = 14). The difference in pharmacokinetic parameters between different genotype groups was analyzed and then scored according to the activity score system. Compared with the wild‐type subjects of CYP2D6 *1/*1, the peak plasma concentration (Cmax) and the area under the plasma drug concentration‐time curve (AUCinf) of dapoxetine in the *10/*10 and *10/*41 groups were notably increased (P ≤ .05). Significant differences in Cmax, AUC, volume of distribution/bioavailability (V/F) and clearance/bioavailability (CL/F) were observed among dapoxetine activity score groups (P ≤ .05). The AUCinf was increased significantly (154% and 89.73%, P ≤ .05) and the Cmax was increased significantly (73.45% and 42.67%, P ≤ .05) in CYP2D6 *10/*41 subjects, compared with CYP2D6 *1/*1 and *1/*10 subjects. The results obtained indicated that CYP2D6 *10 and *41 polymorphisms have significant effects on the pharmacokinetic properties of dapoxetine.
DBC1 maintains skeletal muscle integrity by enhancing myogenesis and preventing myofibre wasting
Authors: Liang Na , He Jia , Yan Jiaqi , Han Xueying , Zhang Xiaoqian , Niu Yamei , Sha Wuga , Li Jun
Published: December 2023

Background

Skeletal muscle atrophy, particularly ageing‐related muscular atrophy such as sarcopenia, is a significant health concern. Despite its prevalence, the underlying mechanisms remain poorly understood, and specific approved medications are currently unavailable. Deleted in breast cancer 1 (DBC1) is a well‐known regulator of senescence, metabolism or apoptosis. Recent reports suggest that DBC1 may also potentially regulate muscle function, as mice lacking DBC1 exhibit weakness and limpness. However, the function of DBC1 in skeletal muscle and its associated molecular mechanisms remain unknown, thus prompting the focus of this study.

Methods

Tibialis anterior (TA) muscle‐specific DBC1 knockdown C57BL/6J male mice were generated through a single injection of 2.00 E + 11 vg of adeno‐associated virus 9 delivering single‐guide RNA for DBC1. Grip strength and endurance were assessed 2 months later, followed by skeletal muscle harvest. Muscle atrophy model was generated by cast immobilization of the mouse hindlimb for 2 weeks. Molecular markers of atrophy were probed in muscles upon termination. Cardiotoxin (CTX) was injected in TA muscles of DBC1 knockdown mice, and muscle regeneration was assessed by immunohistochemistry, quantitative PCR and western blotting. DBC1 knockdown C2C12 cells and myotubes were investigated using immunofluorescence staining, Seahorse, immunohistology, fluorescence‐activated cell sorting and RNA‐sequencing analyses.

Results

DBC1 knockdown in skeletal muscle of young mice led to signatures of muscle atrophy, including a 28% reduction in muscle grip force (P = 0.023), a 54.4% reduction in running distance (P = 0.002), a 14.3% reduction in muscle mass (P = 0.007) and significantly smaller myofibre cross‐sectional areas (P < 0.0001). DBC1 levels decrease in age‐related or limb immobilization‐induced atrophic mouse muscles and overexpress DBC1‐attenuated atrophic phenotypes in these mice. Muscle regeneration was hampered in mice with CTX‐induced muscle injury by DBC1 knockdown, as evidenced by reductions in myofibre cross‐sectional areas of regenerating myofibres with centralized nuclei (P < 0.0001), percentages of MyoG+ nuclei (P < 0.0001) and fusion index (P < 0.0001). DBC1 transcriptionally regulated mouse double minute 2 (MDM2), which mediated ubiquitination and degradation of forkhead box O3 (FOXO3). Increased FOXO3 proteins hampered myogenesis in DBC1 knockdown satellite cells by compromising around 50% of mitochondrial functions (P < 0.001) and exacerbated atrophy in DBC1 knockdown myofibres by activating the ubiquitin–proteasome and autophagy–lysosome pathways.

Conclusions

DBC1 is essential in maintaining skeletal muscle integrity by protecting against myofibres wasting and enhancing muscle regeneration via FOXO3. This research highlights the significance of DBC1 for healthy skeletal muscle function and its connection to muscular atrophy.
Atomic force microscopy in disease‐related studies: Exploring tissue and cell mechanics
Authors: Liu Shuaiyuan , Han Yibo , Kong Lingwen , Wang Guixue , Ye Zhiyi
Published: December 2023

Despite significant progress in human medicine, certain diseases remain challenging to promptly diagnose and treat. Hence, the imperative lies in the development of more exhaustive criteria and tools. Tissue and cellular mechanics exhibit distinctive traits in both normal and pathological states, suggesting that “force” represents a promising and distinctive target for disease diagnosis and treatment. Atomic force microscopy (AFM) holds great promise as a prospective clinical medical device due to its capability to concurrently assess surface morphology and mechanical characteristics of biological specimens within a physiological setting. This review presents a comprehensive examination of the operational principles of AFM and diverse mechanical models, focusing on its applications in investigating tissue and cellular mechanics associated with prevalent diseases. The findings from these studies lay a solid groundwork for potential clinical implementations of AFM.

Research Highlights

By examining the surface morphology and assessing tissue and cellular mechanics of biological specimens in a physiological setting, AFM shows promise as a clinical device to diagnose and treat challenging diseases.
Natural male hybrid common shrews with a very long chromosomal multivalent at meiosis appear not to be completely sterile
Authors: Matveevsky Sergey N. , Kolomiets Oxana L. , Shchipanov Nikolay A. , Pavlova Svetlana V.
Published: December 2023

Among 36 known chromosomal hybrid zones of the common shrew Sorex araneus, the Moscow–Seliger hybrid zone is of special interest because inter‐racial complex heterozygotes (F1 hybrids) produce the longest meiotic configuration, consisting of 11 chromosomes with monobrachial homology (undecavalent or chain‐of‐eleven: CXI). Different studies suggest that such a multivalent may negatively affect meiotic progression and in general should significantly reduce fertility of hybrids. In this work, by immunocytochemical and electron microscopy methods, we investigated for the first time chromosome synapsis, recombination and meiotic silencing in pachytene spermatocytes of natural inter‐racial heterozygous shrew males carrying CXI configurations. Despite some abnormalities detected in spermatocytes, such as associations of chromosomes, stretched centromeres, and the absence of recombination nodules in some arms of the multivalent, a large number of morphologically normal spermatozoa were observed. Possible low stringency of pachytene checkpoints may mean that even very long meiotic configurations do not cause complete sterility of such complex inter‐racial heterozygotes.
Akkermansia muciniphila might improve anti‐PD‐1 therapy against HCC by changing host bile acid metabolism
Authors: Lan Xiucai , Ma Jiaming , Huang Zhipeng , Xu Yuzhen , Hu Yaomin
Published: December 2023

PD‐1 monoclonal antibodies (mAb) have demonstrated remarkable efficacy in a variety of cancers, including Hepatocellular carcinoma (HCC). However, the patient response rates remain suboptimal, and a significant proportion of initial responders may develop resistance to this therapeutic approach. Akkermansia muciniphila (AKK), a microorganism implicated in multiple human diseases, has been reported to be more abundant in patients who exhibit favorable responses to PD‐1mAb. However, the underlying mechanism has yet to be elucidated. In our study, we found that AKK could enhance the efficacy of PD‐1mAb against HCC in a tumor‐bearing mouse model. It promotes HCC tumor cells apoptosis and raise the CD8+T proportion in the tumor microenvironment. Additionally, AKK downregulates PD‐L1 expression in tumor cells. Furthermore, the analysis of metabonomics demonstrates that AKK induces alterations in the host's bile acid metabolism, leading to a significant increase in serum TUDCA levels. Considering the immunosuppresive roles of TUDCA in HCC development, it is plausible to speculate that AKK may reinforce the immunotherapy of PD‐1mAb against HCC through its impact on bile acid metabolism.