bluuebunny/crossref_metadata_2025 huggingface dataset:
Favorable effect of ripasudil use on surgical outcomes of microhook ab interno trabeculotomy
Authors: Okuda Mina , Mori Sotaro , Ueda Kaori , Sakamoto Mari , Kusuhara Sentaro , Yamada-Nakanishi Yuko , Nakamura Makoto
Published: April 2023

Purpose

We have previously demonstrated that prolonged use of glaucoma medications was associated with a poor surgical outcome of ab interno trabeculotomy (µTLO). Given that almost all types of glaucoma eye drop either enhance the drainage through the uveoscleral pathway or reduce aqueous humor production, we hypothesized that prolonged use of these medications might cause disuse atrophy of the conventional pathway. In contrast, ripasudil increases the conventional outflow and eventually shows a favorable outcome of µTLO. This study aimed to evaluate the effect of ripasudil use on µTLO outcomes.

Method

The medical charts of 218 patients who underwent µTLO were analyzed retrospectively. We compared the 1-year outcome between ripasudil users versus nonusers by using propensity score matching. We set the covariates as age, sex, glaucoma types, preoperative intraocular pressure (IOP), the mean deviation values of visual field tests, the presence or absence of concomitant cataract surgery, trabecular meshwork incision range, the presence or absence of any glaucoma medication except ripasudil and duration of glaucoma medical therapy. Success was defined as a postoperative IOP between 5 and 21 mmHg, a ≥ 20% IOP reduction from baseline, and no additional glaucoma surgery at postoperative 1 year.

Result

Fifty-seven patients each were allocated to the ripasudil users or nonusers. The 1-year success rates were 74% in ripasudil users and 51% in nonusers (p = 0.01). Kaplan‒Meier survival curves also showed that the ripasudil users had a higher survival distribution (p = 0.01).

Conclusion

The patients who took ripasudil showed a favorable 1-year outcome of µTLO.
Two decades of gastric and gastroesophageal junction cancer surgery
Authors: Plum Patrick S. , Pamuk Aylin , Barutcu Atakan G. , Mallmann Christoph , Niesen Emanuel , Berlth Felix , Zander Thomas , Chon Seung-Hun , Moenig Stefan P. , Quaas Alexander , Bruns Christiane J. , Hoelscher Arnulf H. , Alakus Hakan
Published: April 2023

Purpose

Diagnosis and treatment of gastric and gastroesophageal junction cancer have undergone many critical changes during the last two decades. We addressed the question of how clinical reality outside of clinical trials has changed for gastric and gastroesophageal junction cancer patients in a European center for upper gastrointestinal surgery.

Methods

In this retrospective cohort study, patients undergoing (sub)total gastrectomy for gastric or gastroesophageal junction adenocarcinoma between 1996 and 2017 in a tertiary upper gastrointestinal center were included. The time was divided into a) before (1996–2006) (pre-CTx) and b) after (2006–2017) (CTx) the MAGIC trial. Data were comprehensively analyzed for demographics, tumor stage, perioperative treatment, surgery, histopathology, and survival rates (SR).

Results

737 patients (32% female) underwent gastrectomy, 255 patients in the pre-CTx era and 482 patients in the CTx era. The median age was 65 years and the median follow-up was 27.5 months for surviving patients. Around 16.9% of patients received neoadjuvant treatment in the pre-CTx era versus 46.3% in the CTx era. The 3-year survival rate (3-YSR) was 46.4% in the pre-CTx and 60.9% in the CTx era (p < 0.001). For pretreated patients, 3-YSR was 39.0% (pre-CTx) versus 55.3% (CTx) (p = 0.168). Survival rate (SR) for locally advanced tumor stages (cT3/cT4) was higher when neoadjuvant therapy was administered (3-YSR: 56.7% vs 40.6%; p = 0.022). There were no significant differences according to sex (p = 0.357), age (p = 0.379), pT category (p = 0.817), pN stage (p = 0.074), cM stage (p = 0.112), Laurén classification (p = 0.158), and SRs (3-YSR: 60.3% vs 59.4%; p = 0.898) between the MAGIC and FLOT regimens.

Conclusions

Survival rates have dramatically improved for gastric cancer patients during the last two decades. MAGIC and FLOT regimens showed similar results in the postsurgical follow-up.
The exposed Mule Creek vent deposits record the structure of a volcanic conduit during a hybrid explosive–effusive eruption
Authors: Unwin Holly E. , Tuffen Hugh , Wadsworth Fabian B. , Phillips Emrys R. , James Mike R. , Foster Annabelle , Kolzenburg Stephan , Castro Jonathan M. , Porritt Lucy A.
Published: April 2023

Silicic volcanic eruptions commonly begin with the explosive ejection of pyroclastic material, before transitioning to gentler effusion-dominated activity. Well-exposed dissected silicic systems are scarce and poorly studied, hindering the advances in our understanding of the explosive–effusive transition needed to improve interpretations of volcanic unrest and hazard forecasting. The Mule Creek vent (New Mexico, USA) is a dissected silicic conduit that records the processes controlling conduit formation and evolution, and the role tuffisites (fractures filled with variably welded pyroclasts) play in conduit dynamics. Here, we use decimeter-scale photo-mapping of lithostratigraphic units and thin section analysis to differentiate and interpret three dominant emplacement styles during vent evolution. First, there was repeated deposition and erosion of pyroclastic material at the conduit walls, recorded by erosive surfaces in pyroclastic breccia and agglomerates at the conduit margins. Second, sub-vertical domains of dense melt-dominated magma were emplaced and preserved as glass-dominated vitrophyre and brecciated vitrophyre, with the textural hallmarks of assembly from welding of pyroclasts. Finally, the sub-horizontal fracturing of previously deposited lithologies produced laterally cross-cutting tuffisites. The vent deposits track the widening and then narrowing of the conduit through time and reflect progressive insulation and generally higher temperatures towards the conduit center as pyroclasts accumulate. Welding of pyroclastic fill and the formation of dense vitrophyres towards the conduit center lowers deposit porosity and effective wall permeability. This drives localized gas pressure increases and results in gas-driven fracturing, generating tuffisites, which act as transient outgassing pathways. The structure of the Mule Creek vent records an explosive–effusive transition, constraining the processes controlling conduit evolution and aiding our interpretation of volcanic unrest.
Quantification of diffuse CO2 flux emission from the crater lagoon of Vila Franca do Campo Islet (São Miguel, Azores)
Authors: Andrade César , Zanon Vittorio , Viveiros Fátima , Cruz J Virgílio , Pimentel Adriano , Coutinho Rui
Published: April 2023

To investigate unexplored areas and apply methodologies suitable for monitoring volcanic activity, a pioneer study was undertaken in the crater lagoon of Vila Franca do Campo Islet to identify possible CO2degassing zones in the marine environment. This study was carried out using a floating accumulation chamber, which to the best of our knowledge, has only been applied to lacustrine environments.

A survey was carried out in the crater lagoon in August 2017, resulting in a total of 143 CO2flux measurements. Other parameters, such as water temperature, pH, electrical conductivity, and depth, were also determined at each measuring point, covering a study area of 0.02 km2. At one of the deepest sites with higher CO2flux values, water samples were collected at depth for determination of stable isotopic composition.

Water temperatures ranged between 21.0 and 27.0 °C, pH from 8.24 to 8.89, and electrical conductivity from 52.5 to 53.9 mS/cm. As expected, due to the marine water composition, sampled waters are of the Na-Cl type. CO2flux varied between 0.581 and 1.0 g m-2d-1(average = 2.967 g m-2d-1). A single CO2population, characterized by low CO2fluxes, points to a biogenic CO2origin (δ13C = −9.62‰). The estimated value for the total CO2emitted from the water surface is 0.05 t d-1. CO2flux measurements were also compared with the structural features that cross the tuff cone, but no clear relation was observed with fractures/faults.

This methodology should be applied to other coastal marine areas, especially where anomalous gas emissions have been reported.
New perspectives in pediatric dialysis technologies: the case for neonates and infants with acute kidney injury
Authors: Parolin Mattia , Ceschia Giovanni , Vidal Enrico
Published: April 2023

Advancements in pediatric dialysis generally rely on adaptation of technology originally developed for adults. However, in the last decade, particular attention has been paid to neonatal extracorporeal therapies for acute kidney care, an area in which technology has made giant strides in recent years. Peritoneal dialysis (PD) is the kidney replacement therapy (KRT) of choice in the youngest age group because of its simplicity and effectiveness. However, extracorporeal blood purification provides more rapid clearance of solutes and faster fluid removal. Hemodialysis (HD) and continuous KRT (CKRT) are thus the most used dialysis modalities for pediatric acute kidney injury (AKI) in developed countries. The utilization of extracorporeal dialysis for small children is associated with a series of clinical and technical challenges which have discouraged the use of CKRT in this population. The revolution in the management of AKI in newborns has started recently with the development of new CKRT machines for small infants. These new devices have a small extracorporeal volume that potentially prevents the use of blood to prime lines and dialyzer, allow a better volume control and the use of small-sized catheter without compromising the blood flow amount. Thanks to the development of new dedicated devices, we are currently dealing with a true “scientific revolution” in the management of neonates and infants who require an acute kidney support.
Repurposing drugs against Alzheimer’s disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD?
Authors: Leßmann Volkmar , Kartalou Georgia-Ioanna , Endres Thomas , Pawlitzki Marc , Gottmann Kurt
Published: April 2023

Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models and in humans suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals or in elderly humans before onset of disease symptoms. However, a pharmacological treatment that can reverse memory deficits in AD patients was thus far not identified. Importantly, AD disease-related dysfunctions have increasingly been associated with neuro-inflammatory mechanisms and searching for anti-inflammatory medication to treat AD seems promising. Like for other diseases, repurposing of FDA-approved drugs for treatment of AD is an ideally suited strategy to reduce the time to bring such medication into clinical practice. Of note, the sphingosine-1-phosphate analogue fingolimod (FTY720) was FDA-approved in 2010 for treatment of multiple sclerosis patients. It binds to the five different isoforms of Sphingosine-1-phosphate receptors (S1PRs) that are widely distributed across human organs. Interestingly, recent studies in five different mouse models of AD suggest that FTY720 treatment, even when starting after onset of AD symptoms, can reverse synaptic deficits and memory dysfunction in these AD mouse models. Furthermore, a very recent multi-omics study identified mutations in the sphingosine/ceramide pathway as a risk factor for sporadic AD, suggesting S1PRs as promising drug target in AD patients. Therefore, progressing with FDA-approved S1PR modulators into human clinical trials might pave the way for these potential disease modifying anti-AD drugs.
Optional projection under equivalent local martingale measures
Authors: Biagini Francesca , Mazzon Andrea , Perkkiö Ari-Pekka
Published: April 2023

We study optional projections of ${\mathbb{G}}$
G
-adapted strict local martingales on a smaller filtration ${\mathbb{F}}$
F
under changes of equivalent martingale measures. General results are provided as well as a detailed analysis of two specific examples given by the inverse Bessel process and a class of stochastic volatility models. This analysis contributes to clarify the absence of arbitrage opportunities of market models under restricted information.
Corrosion inhibition of magnesium alloy AZ31 in chloride-containing solutions by aqueous permanganate
Authors: Osipenko Maria A. , Kasach Aliaksandr A. , Adamiec Janusz , Zimowska Małgorzata , Kurilo Irina I. , Kharytonau Dzmitry S.
Published: April 2023

In this work, corrosion of the AZ31 magnesium alloy was examined in 0.05 M NaCl solutions containing 0.01–0.150 mol/dm3 of potassium permanganate as a corrosion inhibitor. A set of electrochemical impedance spectroscopy, linear sweep voltammetry, and hydrogen evolution measurements revealed high inhibitor effectiveness at relatively high (0.150 mol/dm3) KMnO4 concentrations. Based on data of energy-dispersive X-ray analysis, scanning electron microscopy, and Raman spectroscopy, a mechanism of the corrosion inhibition of AZ31 alloy by potassium permanganate in chloride-containing media was proposed.
Guess who? Evaluating individual acoustic monitoring for males and females of the Tawny Pipit, a migratory passerine bird with a simple song
Authors: Oñate-Casado Javier , Porteš Michal , Beran Václav , Petrusek Adam , Petrusková Tereza
Published: April 2023

Individual acoustic monitoring (IAM), based on the analysis of vocal cues, is particularly suitable for the identification and tracking of birds with temporally stable song or call characteristics. Unlike mark-recapture methods, IAM does not require the physical manipulation of individuals, which can have long-lasting behavioural effects. So far, IAM has usually focused on males, as singing females tend to be overlooked in temperate zones. Here, we evaluated the suitability of IAM for both sexes in an isolated population of the Tawny Pipit (Anthus campestris, Motacillidae), a migratory Palearctic species critically endangered in Central Europe, for which female singing has been occasionally documented. We confirmed that songs of all 101 studied individuals, both males and females, were individually distinct. Most individuals used only a single song type in their repertoires, with only three males using two. Of 45 ringed males (that could be unambiguously recognized visually), only two changed their song structure to some extent, either within or between seasons. Multiple individuals often sang structurally similar song types, which nevertheless consistently differed in minor characteristics; such differences were detectable by visual inspection and also affected quantitative analyses of song similarity. Songs sung by females did not have any apparent sex-specific characteristics. Unlike previously suggested, females did not adapt their vocalization to their breeding partner, and we presume their song is also temporally stable. Our findings support IAM as a reliable approach for studying the behaviour and ecology of this passerine species with a small repertoire and simple songs.
Probing the Impacts of Visual Context in Multimodal Entity Alignment
Authors: Wang Meng , Shi Yinghui , Yang Han , Zhang Ziheng , Lin Zhenxi , Zheng Yefeng
Published: April 2023

We study the problem of multimodal embedding-based entity alignment (EA) between different knowledge graphs. Recent works have attempted to incorporate images (visual context) to address EA in a multimodal view. While the benefits of multimodal information have been observed, its negative impacts are non-negligible as injecting images without constraints brings much noise. It also remains unknown under what circumstances or to what extent visual context is truly helpful to the task. In this work, we propose to learn entity representations from graph structures and visual context, and combine feature similarities to find alignments at the output level. On top of this, we explore a mechanism which utilizes classification techniques and entity types to remove potentially un-helpful images (visual noises) during alignment learning and inference. We conduct extensive experiments to examine this mechanism and provide thorough analysis about impacts of the visual modality on EA.
Food knowledge level among Tanzanian women of childbearing age: developing a score for the food knowledge questionnaire
Authors: Conti Maria Vittoria , Gnesi Marco , Mshanga Naelijwa , De Giuseppe Rachele , Giampieri Francesca , Cena Hellas
Published: April 2023

Food knowledge (FK) is one of the factors that contribute to malnutrition conditions in developing countries, together with food safety, food security and food access. FK is defined as ‘the competence to understand healthy nutrition concepts’; it impacts individuals’ life due to its relationship with food behaviour and eating habits. Therefore, acting on FK can represent a starting point for improving the health status of vulnerable populations. The authors present a total score of an FK questionnaire (FKQ) and its relation to the socio-demographic characteristics of a specific target population: Tanzanian women of childbearing age. The results of the manuscript complement evidence of construct validity of the FKQ by providing an algorithm to compute a total score as a measure of FK. The strength of this tool, and its score, lies in the fact that the questionnaire has been validated and is easy to administer.
Tornadoes’ Fastest Winds Howl Close to the Ground
Authors: Wilke Carolyn
Published: April 2023

Radar data from storm-tracking scientists reveal that twisters’ winds churn 30% faster near Earth’s surface than above 100 meters, where measurements usually are taken.
Comprehensive structural analysis reveals broad-spectrum neutralizing antibodies against SARS-CoV-2 Omicron variants
Authors: Chi Xiangyang , Xia Lingyun , Zhang Guanying , Chi Ximin , Huang Bangdong , Zhang Yuanyuan , Chen Zhengshan , Han Jin , Wu Liushu , Li Zeya , Sun Hancong , Huang Ping , Yu Changming , Chen Wei , Zhou Qiang
Published: April 2023

The pandemic of COVID-19 caused by SARS-CoV-2 continues to spread around the world. Mutant strains of SARS-CoV-2 are constantly emerging. At present, Omicron variants have become mainstream. In this work, we carried out a systematic and comprehensive analysis of the reported spike protein antibodies, counting the epitopes and genotypes of these antibodies. We further comprehensively analyzed the impact of Omicron mutations on antibody epitopes and classified these antibodies according to their binding patterns. We found that the epitopes of the H-RBD class antibodies were significantly less affected by Omicron mutations than other classes. Binding and virus neutralization experiments showed that such antibodies could effectively inhibit the immune escape of Omicron. Cryo-EM results showed that this class of antibodies utilized a conserved mechanism to neutralize SARS-CoV-2. Our results greatly help us deeply understand the impact of Omicron mutations. Meanwhile, it also provides guidance and insights for developing Omicron antibodies and vaccines.
2D carbon network arranged into high-order 3D nanotube arrays on a flexible microelectrode: integration into electrochemical microbiosensor devices for cancer detection
Authors: Sun Yimin , Dong Xulin , He Hu , Zhang Yan , Chi Kai , Xu Yun , Asif Muhammad , Yang Xuan , He Wenshan , Liao Kin , Xiao Fei
Published: April 2023

In this work, we develop a new type of mesoporous 2D N, B, and P codoped carbon network (NBP-CNW) arranged into high-order 3D nanotube arrays (NTAs), which are wrapped onto a flexible carbon fiber microelectrode, and this microelectrode is employed as a high-performance carbon-based nanocatalyst for electrochemical biosensing. The NBP-CNW-NTAs synthesized by a facile, controllable, ecofriendly and sustainable template strategy using ionic liquids as precursors possess a high structural stability, large surface area, abundant active sites, and effective charge transport pathways, which dramatically improve their electrocatalytic activity and durability in the redox reaction of cancer biomarker H2O2. Benefiting from these unique structural merits, superb electrochemical activity and good biocompatibility, the NBP-CNW-NTAs-modified microelectrode demonstrates excellent sensing performance toward H2O2 and is embedded in a homemade microfluidic electrochemical biosensor chip for the real-time tracking of H2O2 secreted from different live cancer cells with or without radiotherapy treatment, which provides a new strategy for distinguishing the types of cancer cells and evaluating the radiotherapeutic efficacy of cancer cells. Furthermore, the functional microelectrode is integrated into an implantable probe for the in situ detection of surgically resected human specimens to distinguish cancer tissues from normal tissues. These will be of vital significance for cancer diagnoses and therapy in clinical practice.
Data block decomposition and intelligent secure acquisition of microdata
Authors: Zhang Xiuquan , Shen Lin , Shi Kaiquan
Published: April 2023

P-sets (P stands for Packet) is a set model with dynamic characteristics, which is obtained by introducing dynamic characteristics into Cantor set and improving Cantor set. According to the fact that the characteristics of class I big data are completely consistent with the basic characteristics of P-sets, this paper gives research on theory and application on class I big data from the view of mathematics. Here we introduce Class I big data which need some new definitions of data block, microdata and data link. Based on these concepts, decomposition theorem of data block and microdata relation theorem are given, and then attribute reasoning theorem and microdata intelligent discovery and the intelligent secure acquisition algorithm of microdata are also proposed. By using these theoretical results, the applications of secure acquisition of microdata are presented. In summary, P-sets mathematical model provides a new theory and method for studying class I big data.
Atomistic modeling of the mechanical properties: the rise of machine learning interatomic potentials
Authors: Mortazavi Bohayra , Zhuang Xiaoying , Rabczuk Timon , Shapeev Alexander V.
Published: April 2023

This minireview highlights the superiority of machine learning interatomic potentials over the conventional empirical interatomic potentials and density functional theory calculations for the analysis of mechanical and failure responses.
Organosilica-based deformable nanopesticides with enhanced insecticidal activity prepared by flash nanoprecipitation
Authors: Ma Enguang , Fu Zhinan , Sun Liang , Chen Kai , Liu Zhiyong , Wei Zhong , Li Li , Guo Xuhong
Published: April 2023

A flash nanoprecipitation technique was developed for the construction of a novel type of deformable hollow organosilica nanoparticle for pesticide delivery.
A novel red AIE fluorescent probe for ratiometric detection of carbon monoxide in vitro and in vivo
Authors: Huang Shuai , Liu Xiaohui , Hou Jing , Liu Min , Luo Ting , Huang Xueyan , Chen Fei , Dong Jie , Zeng Wenbin
Published: April 2023

The first red AIE property fluorescent probe was used to detect endogenous and exogenous carbon monoxide.
Baukastenprinzip für eine moderne Ergotherapie – Betätigungsorientierung in der stationären Psychiatrie
Authors: Küppers Katrin , Schmid Markus
Published: April 2023

In der Psychiatrie haben Ergotherapeut*innen nur begrenzte Ressourcen für die inhaltliche Entwicklungsarbeit. Trotzdem ist eine differenzierte betätigungsorientierte Arbeit möglich, wie das Team der LVR-Klinik Viersen zeigt.
Lebensbegleitung in der pädiatrischen Palliativpflege – Entwicklung fördern und Begleitung ermöglichen bis zuletzt
Authors: Münstermann Uta
Published: April 2023

Wenn Kinder, Jugendliche und junge Erwachsene lebenslimitierend oder lebensbedrohlich erkrankt sind, beeinflussen die leidvollen Symptome nicht nur das Leben des Kindes, sondern den gesamten Familienalltag. Das Kind und seine Familie benötigen – entsprechend den daraus resultierenden Versorgungs- und Unterstützungsbedarfen – eine fachkompetente palliative Begleitung von der Diagnosestellung bis über den Tod hinaus 1
2. Basale Stimulation kann hier im Pflegeprozess handlungsleitend sein, um die Kinder zu fördern, die Eltern zu befähigen und die Familien zu begleiten.
Unexpected Severe Bocavirus Infections among Hospitalized Children during the COVID-19 Pandemic
Authors: Kara Yalcin , Kizil Mahmut Can , Arslanoglu Mehmet Ozgur , Kacmaz Ebru , Dalokay Nidai , Pala Ezgi , Kiral Eylem , Bozan Gürkan , Us Tercan , Kiliç Omer , Dinleyici Ener Cagri
Published: April 2023

Objective Acute respiratory tract infections are one of the leading causes of morbidity and mortality in children. Although human bocavirus (HBoV) infections are not as common as other seasonal respiratory viruses, children who are infected with HBoV are more likely to suffer from a variety of respiratory conditions, including the common cold, acute otitis media, asthma exacerbations, bronchiolitis pneumonia, some of the affected children require pediatric intensive care unit stay. Here, we aimed to evaluate pediatric bocavirus (HBoV) cases presenting with severe respiratory tract symptoms during the coronavirus disease 2019 (COVID-19) pandemic.

Methods This retrospective study evaluated the medical records of children diagnosed with respiratory infections, followed up at the Faculty of Medicine, Eskisehir Osmangazi University between September 2021 and March 2022. In this study, patients with HBoV identified using nasopharyngeal polymerase chain reaction (PCR) were considered positive. Cases were analyzed retrospectively for their clinical characteristics.

Results This study included 54 children (29 girls and 25 boys) with HBoV in nasopharyngeal PCR samples. The cases ranged in age from 1 month to 72 months (median 25 months). At the time of presentation, cough, fever, and respiratory distress were the most prevalent symptoms. Hyperinflation (48%), pneumonic consolidation (42%), and pneumothorax–pneumomediastinum (7%) were observed on the chest X-ray; 54% of the children required intensive care unit stay. The median length of hospitalization was 6 days. Bacterial coinfection was detected in 7 (17%) children, while HBoV and other viruses were present in 20 (37%) children; 57% of children received supplemental oxygen by mask, 24% high-flow nasal oxygen, 7% continuous positive airway pressure, and 9% invasive mechanical ventilation support. Antibiotics were given to 34 (63%) cases, and systemic steroid treatment was given to 41 (76%) cases. Chest tubes were inserted in three out of the four cases with pneumothorax–pneumomediastinum. All patients were recovered and were discharged from the hospital.

Conclusion The COVID-19 pandemic changed the epidemiology of seasonal respiratory viruses and the clinical course of the diseases. Although it usually causes mild symptoms, severe respiratory symptoms can lead to life-threatening illnesses requiring intensive care admission.
Plasma surface functionalization: A comprehensive review of advances in the quest for bioinstructive materials and interfaces
Authors: Zhianmanesh Masoud , Gilmour Aaron , Bilek Marcela M. M. , Akhavan Behnam
Published: April 2023

Surface biofunctionalization aims to create cell-instructive surfaces that control the behavior of cells and modulate cellular interactions by incorporating cell signaling moieties at the materials–biosystem interface. Despite advances in developing bioinert and biocompatible materials, blood clotting, inflammation, and cell death continue to be observed upon the contact of foreign materials with living tissues leading to the materials' rejection. Specific examples include the application of foreign materials in implantable devices (e.g., bone implants, antimicrobial surfaces, and cardiovascular stents), biosensors, drug delivery, and 3D-bioprinting. Biofunctionalization of materials to date has been predominantly realized using wet chemical approaches. However, the complexity of wet chemistry, toxicity of reactants, waste disposal issues, reaction time, poor reproducibility, and scalability drive a need for a paradigm shift from wet chemical approaches to dry methods of surface biofunctionalization. Plasma-based technologies that enable covalent surface immobilization of biomolecules have emerged as dry, reagent-free, and single-step alternatives for surface biofunctionalization. This review commences by highlighting the need for bioinstructive surfaces and coatings for various biomedical applications such as bone implants, antimicrobial surfaces, biosensors, and 3D-bioprinted structures, followed by a brief review of wet chemical approaches for developing biofunctionalized surfaces and biomimetic devices. We then provide a comprehensive review of the development of plasma-based technologies for biofunctionalization, highlighting the plasma–surface interactions and underpinning mechanisms of biomolecule immobilization.
Phylogeography of a salmonid fish, white-spotted charr (Salvelinus leucomaenis), in a historically non-glaciated region in the northwestern North Pacific
Authors: Yamamoto Shoichiro , Morita Kentaro , Kitano Satoshi , Tabata Ryoichi , Watanabe Katsutoshi , Maekawa Koji
Published: April 2023

The area around the Sea of Okhotsk and the Sea of Japan in the north-western North Pacific provides opportunities for studying the impact of climate oscillations on the evolutionary history of cold-temperate species independent of direct ice sheet development. We conducted a range-wide collection survey of white-spotted charr, Salvelinus leucomaenis, and integrated nuclear DNA and mitochondrial DNA (mtDNA) data to reveal the evolutionary history of this species. Phylogeographic analyses using genome-wide SNP data revealed the presence of five geographically distinct groups with slightly overlapping ranges. Of these, a northern group was widely distributed along the coast of the Sea of Okhotsk, the Sea of Japan and the northern region of Honshu Island, whereas the other four groups were only found on Honshu Island. The population structure of Honshu Island was largely divided into the Sea of Japan and Pacific Ocean groups by the mountain ranges running through the centre of Honshu Island, and was further subdivided by many geological factors, such as river capture and other vicariance processes. There was a discrepancy in the phylogeographic patterns between nuclear DNA and mtDNA, which was likely influenced by a complex population history that involved multiple dispersal and secondary contact events during several glacial-interglacial cycles.
Why Biblical Arguments for Abortion Fail
Authors: Miller Calum
Published: April 2023

While the traditional Christian teaching opposing abortion has been relatively unanimous until the twentieth century, it has been claimed in more recent decades that certain Biblical passages support the view that the fetus, or unborn child, has a lesser moral status than a born child, in a way that might support the permissibility of abortion. In this paper, I address the foremost three texts used to argue this point: Genesis 2:7; Exodus 21:22–25; and Numbers 5:11–31. I argue that interpreting the former in the literal way necessary to support abortion leads to untenable moral and exegetical conclusions, indeed straightforwardly contradicting other Biblical texts. I then demonstrate that the most plausible readings of the other passages—on textual and contextual grounds—do not support a lesser moral status, one of the passages plausibly even supporting full moral status, for the unborn child.
Application of the transfer learning method in multisource geophysical data fusion
Authors: Lv Pengfei , Xue Guoqiang , Chen Weiying , Song Wanting
Published: April 2023

Using multigeophysical exploration techniques is a common way for deep targets to be explored in complex survey areas. How to locate an unknown underground target using multiple datasets is a great challenge. The useful information in the multisource geophysical model can be extracted and fused with the help of data fusion, which also works well to correct the interpretation divergence brought on by expert experience, with image feature extraction being the key step in the fusion of the geophysical models. Traditionally, this method is often used for these kinds of geophysical images, but it significantly reduces the efficiency of feature extraction. As a result, we propose a novel method based on a transfer learning method to extract the features of multisource images. First, the ResNet50 network is used to extract the initial features of the images. Owing to the problems of feature redundancy and fuzzy features in initial features, Spearman and zero phase component analysis can be used to achieve feature reduction and enhancement, which can further improve the computational efficiency and fusion accuracy in fusion. Finally, the fusion image is obtained using fusion rules that we designed based on the current state. The algorithm's reliability is tested using field data from the Iliamna Volcano. The case study demonstrates the effectiveness of the proposed strategy, which also offers a novel way to locate subsurface targets.
A retrospective study of patients complaining of nontraumatic acute abdominal pain, admitted in the emergency department of an urban hospital in China
Authors: Luo Guanguan , Liu Qinqin , Zhang Zhongxiang , Jin Xiaoqing
Published: April 2023

Background

Nontraumatic acute abdominal pain (AAP) accounts for a large proportion of emergency department (ED) admissions. This study aimed to explore the underlying correlations among basic information, imaging examinations, and diagnoses.

Methods

A total of 7453 patients complaining of AAP, admitted to the ED of Zhongnan Hospital of Wuhan University, were enrolled in this retrospective study from January 1 to December 30, 2019. We collected the following information from the patients: sex, age, date of visit, pain location, nature of pain, level of severity, imaging (computed tomography, x-ray, and ultrasound), diagnosis, and outcomes (release from the hospital, transfer to another hospital, transfer to another department, observation room, hospitalization, or death).

Results

According to this study, AAP was more common in female than male. A total of 82.11% patients of AAP were in level 3 of severity, while 0.19% patients were in level 1. A total of 77.20% of the patients had undergone imaging. Swelling pain and colic are the 2 most common types of AAP. Nonspecific abdominal pain (NSAP) is the most common diagnosis. In the diagnosis of NSAP and gastroenteritis, female patients were more prevalent than male patients, but for renal colic, male patients were 3 times as many as female patients. Nonspecific abdominal pain, biliary colic, and cholecystitis are the 3 leading causes in patients 65 years or older. Nonspecific abdominal pain, renal colic, and gastroenteritis are the 3 leading causes of AAP in patients younger than 65 years.

Conclusion

With the help of imaging, clinicians can specify a diagnosis and perform corresponding treatment in most cases. However, making a precise diagnosis of AAP within a short period is still challenging. Further research should be conducted to seek safer and more effective techniques to streamline clinicians’ work.
Ferroptosis in hepatocellular carcinoma: from bench to bedside
Authors: Tang Daolin , Kroemer Guido , Kang Rui
Published: April 2023

The most widespread type of liver cancer, HCC, is associated with disabled cellular death pathways. Despite therapeutic advancements, resistance to current systemic treatments (including sorafenib) compromises the prognosis of patients with HCC, driving the search for agents that might target novel cell death pathways. Ferroptosis, a form of iron-mediated nonapoptotic cell death, has gained considerable attention as a potential target for cancer therapy, especially in HCC. The role of ferroptosis in HCC is complex and diverse. On one hand, ferroptosis can contribute to the progression of HCC through its involvement in both acute and chronic liver conditions. In contrast, having ferroptosis affect HCC cells might be desirable. This review examines the role of ferroptosis in HCC from cellular, animal, and human perspectives while examining its mechanisms, regulation, biomarkers, and clinical implications.
A review of reptile virus experimental infection studies
Authors: Wesson Jane P. , O'Dea Mark A. , Hyndman Timothy H.
Published: April 2023

Despite recent advances in molecular techniques, infection studies remain an important tool for biosecurity, veterinary and conservation medicines. Experimental infection studies are performed for many reasons: to investigate causal links between pathogens and disease, to study host species susceptibility, to study immune response to inoculation, to investigate pathogen transmission and to investigate methods for infection control. Experimental infection studies using viruses in reptiles have been conducted sporadically since at least the 1930s and this continues to be a fertile area of research. This review catalogues previously published research in the field. The key parameters of each study are tabulated, providing a summary of more than 100 experiments linked to their original publications. Common themes and trends within the data are discussed.
Dynamic structural adaptations enable the endobiotic predation ofbdellovibrio bacteriovorus
Authors: Kaplan Mohammed , Chang Yi-Wei , Oikonomou Catherine M. , Nicolas William J. , Jewett Andrew I. , Kreida Stefan , Dutka Przemysław , Rettberg Lee A. , Maggi Stefano , Jensen Grant J.
Published: April 2023

Bdellovibrio bacteriovorusis an endobiotic microbial predator that offers promise as a living antibiotic for its ability to kill Gram-negative bacteria, including human pathogens. Even after six decades of study, fundamental details of its predation cycle remain mysterious. Here, we used cryo-electron tomography to comprehensively image the lifecycle ofB. bacteriovorusat nanometer-scale resolution. In addition to providing the first high-resolution images of predation in a native (hydrated, unstained) state, we also discover several surprising features of the process, including novel macromolecular complexes involved in prey attachment/invasion and a flexible portal structure lining a hole in the prey peptidoglycan that tightly seals the prey outer membrane around the predator during entry. Unexpectedly, we find thatB. bacteriovorusdoes not shed its flagellum during invasion, but rather resorbs it into its periplasm for degradation. Finally, following replication and division in the bdelloplast, we observe a transient and extensive ribosomal lattice on the condensedB. bacteriovorusnucleoid.

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Multiplexed analysis of a single EV (MASEV) reveals unique biomarker
composition with diagnostic impact
Authors: Spitzberg Joshua , Ferguson Scott , Yang Katy , Peterson Hannah M. , Carlson Jonathan C.T. , Weissleder Ralph
Published: April 2023

Exosomes and extracellular vesicles (EV) are increasingly being explored as
circulating biomarkers, but their heterogenous composition will likely mandate
the development of single EV technologies. Highly multiplexed analyses of single
EVs have been challenging to implement beyond a few colors during spectral
sensing. We use a multiplexed analysis of the single EV technique (MASEV) to
interrogate thousands of individual EVs during 5 cycles of multi-channel
fluorescence staining for 15 EV biomarkers. Contrary to the common belief, we
show that i) several “ubiquitous” markers are much less common than believed;
ii) that multiple biomarkers concur in single vesicles but only in small
fractions, iii) that affinity purification can lead to loss of rare EV subtypes,
and iv) that deep profiling allows detailed analysis of EV potentially improving
the diagnostic content. These findings establish the potential of MASEV for
uncovering fundamental EV biology and heterogeneity and increasing diagnostic
specificity.

Abstract Figure

Graphical abstract

Multiplexed analysis of single EV (MASEV) allows robust
protein profiling at the single EV level, a prerequisite for
early cancer detection or organ of origin
determination.
Radiochemical Synthesis and Evaluation of 3-[11C]Methyl-4-aminopyridine in Rodents and Non-Human Primates for Imaging Potassium Channels in the CNS
Authors: Sun Yang , Guehl Nicolas J. , Zhou Yu-Peng , Takahashi Kazue , Belov Vasily , Dhaynaut Maeva , Moon Sung-Hyun , Fakhri Georges El , Normandin Marc D. , Brugarolas Pedro
Published: April 2023

Demyelination, the loss of the insulating sheath of neurons, causes failed or slowed neuronal conduction and contributes to the neurological symptoms in multiple sclerosis, traumatic brain and spinal cord injuries, stroke, and dementia. In demyelinated neurons, the axonal potassium channels Kv1.1 and Kv1.2, generally under the myelin sheath, become exposed and upregulated. Therefore, imaging these channels using positron emission tomography can provide valuable information for disease diagnosis and monitoring. Here, we describe the novel tracer for Kv1 channels [11C]3-methyl-4-aminopyridine ([11C]3Me4AP). [11C]3Me4AP was efficiently synthesized via Pd(0)-Cu(I) co-mediated Stille cross-coupling of a stannyl precursor containing a free amino group. Evaluation of its imaging properties in rats and nonhuman primates showed that [11C]3Me4AP has a moderate brain permeability and slow kinetics. Additional evaluation in monkeys showed that the tracer is metabolically stable and that a 1-tissue compartment model can accurately model the regional brain time-activity curves. Compared to the related tracers [18F]3-fluoro-4-aminopyridine ([18F]3F4AP) and [11C]3-methoxy-4-aminopyridine ([11C]3MeO4AP), [11C]3Me4AP shows lower initial brain uptake, which indicates reduced permeability to the blood-brain-barrier and slower kinetics, suggesting higher binding affinity consistent within vitrostudies. While the slow kinetics and strong binding affinity resulted in a tracer with less favorable properties for imaging the brain than its predecessors, these properties may make 3Me4AP useful as a therapeutic.
A genome-wide CRISPRi screen reveals a StkP-mediated connection between cell-wall integrity and competence inStreptococcus salivarius
Authors: Knoops Adrien , Waegemans Alexandra , Lamontagne Morgane , Decat Baptiste , Mignolet Johann , Veening Jan-Willem , Hols Pascal
Published: April 2023

Competence is one of the most efficient bacterial evolutionary and adaptative strategies by synchronizing production of antibacterial compounds and integration of DNA released by dead cells. In most streptococci, this tactic is orchestrated by the ComRS system, a pheromone communication device providing a sharp time window of activation in which only part of the population is responsive. Understanding how this developmental process integrates multiple inputs to fine-tune the adequate response is a long-standing question. However, essential genes involved in the regulation of ComRS have been challenging to study. In this work, we built a conditional mutant library using CRISPR-interference and performed three complementary screens to investigate competence genetic regulation in the human commensalStreptococus salivarius. We show that initiation of competence increases upon cell-wall impairment, suggesting a connection between cell envelope stress and competence activation. Notably, we report a key role for StkP, a serine-threonine kinase known to regulate cell-wall homeostasis. We show that StkP controls competence by a mechanism that reacts to peptidoglycan fragments. Together, our data suggest a key cell-wall sensing mechanism coupling competence to cell envelope integrity.

IMPORTANCE

Survival of human commensal streptococci in the digestive tract requires efficient strategies which must be tightly and collectively controlled for responding to competitive pressure and drastic environmental changes. In this context, the autocrine signaling system ComRS controlling competence for natural transformation and predation in salivarius streptococci could be seen as a multi-input device integrating a variety of environmental stimuli. In this work, we revealed novel positive and negative competence modulators by using a genome-wide CRISPR- interference strategy. Notably, we highlighted an unexpected connection between bacterial envelope integrity and competence activation that involves several cell-wall sensors. Together, these results showcase how commensal streptococci can fine-tune the pheromone-based competence system by responding to multiple inputs affecting their physiological status in order to calibrate an appropriate collective behavior.
Pharmacokinetic considerations for optimizing inhaled spray-dried pyrazinoic acid formulations
Authors: Yeshwante Shekhar B. , Hanafin Patrick , Miller Brittany K. , Rank Laura , Murcia Sebastian , Xander Christian , Annis Ayano , Baxter Victoria K. , Anderson Elizabeth J. , Jermain Brian , Konicki Robyn , Schmalstig Alan A. , Stewart Ian , Braunstein Miriam , Hickey Anthony J. , Rao Gauri G.
Published: April 2023

Tuberculosis (TB), caused byMycobacterium tuberculosis(Mtb), remains a leading cause of death with 1.6 million deaths worldwide reported in 2021. Oral pyrazinamide (PZA) is an integral part of anti-TB regimens, but its prolonged use has the potential to drive development of PZA resistantMtb. PZA is converted to the active moiety pyrazinoic acid (POA) by theMtbpyrazinamidase encoded bypncA, and mutations inpncAare associated with the majority of PZA resistance. Conventional oral and parenteral therapies may result in subtherapeutic exposure in the lung, hence direct pulmonary administration of POA may provide an approach to rescue PZA efficacy for treatingpncA-mutant PZA-resistantMtb.

The objectives of the current study were to i) develop novel dry powder POA formulations ii) assess their feasibility for pulmonary delivery using physicochemical characterization, iii) evaluate their pharmacokinetics (PK) in the guinea pig model and iv) develop a mechanism based pharmacokinetic model (MBM) usingin vivoPK data to select a formulation providing adequate exposure in epithelial lining fluid (ELF) and lung tissue.

We developed three POA formulations for pulmonary delivery and characterized their PK in plasma, ELF, and lung tissue following passive inhalation in guinea pigs. Additionally, the PK of POA following oral, intravenous and intratracheal administration was characterized in guinea pigs. The MBM was used to simultaneously model PK data following administration of POA and its formulations via the different routes. The MBM described POA PK well in plasma, ELF and lung tissue.

Physicochemical analyses and MBM predictions suggested that POA maltodextrin was the best among the three formulations and an excellent candidate for further development as it has: (i) the highest ELF-to-plasma exposure ratio (203) and lung tissue-to-plasma exposure ratio (30.4) compared with POA maltodextrin and leucine (75.7/16.2) and POA leucine salt (64.2/19.3); (ii) the highest concentration in ELF (CmacELF: 171 nM) within 15.5 minutes, correlating with a fast transfer into ELF after pulmonary administration (kPM: 22.6 1/h).

The data from the guinea pig allowed scaling, using the MBM to a human dose of POA maltodextrin powder demonstrating the potential feasibility of an inhaled product.

Table of Contents (TOC)/Abstract Graphic