bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing a Sustainable, Circular Culinary System
Authors: Grèzes-Bürcher Sandra , Grèzes Vincent
Published: August 2023

The purpose of this paper is to design a sustainable, culinary system based on the principles of circular economy and systemic design integrating restaurants and hotels of a rural tourism region. The overall research question is: How can the current fruit and vegetable food system be transformed into a sustainable and circular culinary system creating benefits for all stakeholders? As the main aim of this exploratory study is to understand the challenges and experiences of the different actors involved in the current food network rather than measuring flows, the researchers adopt a qualitative approach based on the principles of systemic design. The authors conducted 15 semi-structured interviews with different actors along the value chain in the canton of Valais, Switzerland. The results show that among the factors needed to create a sustainable, circular local food network are a centralized distribution system, efficient transport, better food waste management, sensitization/education of different actors, and better promotion of regional food. The resulting model for a sustainable and circular culinary system includes a regional hub that coordinates the different material and relational flows, the transportation system, and promotional activities including a central marketplace platform. The results are of particular interest for policy strategies focusing on the promotion of regional food networks. In terms of practical applications, the study suggests different solutions to transform current food systems into circular, re-localized food networks that help valorize local food in rural tourism regions.
Neuroendocrine carcinoma of the cervix: A comprehensive clinicopathologic study and literature review
Authors: Zhang Xiaobo , Li Mingzhu , Zhang Guo , Shen Danhua
Published: August 2023

Aims

Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. This study aims to investigate the clinicopathological features and prognosis of NECC.

Methods

A retrospective analysis was conducted on twenty-one patients diagnosed with NECC between May 2008 and September 2021 ​at Peking University People's Hospital. The study involved histopathological examination, immunohistochemistry, ThinPrep cytology test (TCT), and high-risk HPV hybrid capture 2 (HC2) assay. Follow-up was conducted through telephone interviews and medical records for a range of 3–160 months, with an average follow-up period of 49.8 months.

Results

The average age of the patients was 48.6 years (range: 33–69 years). Seventeen patients were diagnosed with neuroendocrine carcinoma through biopsy. Nine cases underwent TCT and HC2 tests before biopsy, and TCT results of four cases showed high-grade squamous intraepithelial lesion (HSIL). High-risk HPV(HR-HPV) positive was detected in seven cases. The cancer cells exhibited consistent morphological features, including sparse cytoplasm, intensely stained nuclei, and extensive neoplastic necrosis. Thirteen cases were classified as pure NECC (61.9%), while eight cases were mixed types (38.1%). Three cases were associated with squamous cell carcinoma (SCC), and five cases were associated with adenocarcinoma. Prognosis varied significantly among these subtypes (p ​< ​0.05). The overall survival rate in the follow-up period was 66.7% (12/18).

Conclusions

NECC is an extremely rare and highly aggressive tumor with a poor prognosis, particularly in cases of mixed histology. It is strongly associated with HPV infection. TCT and HPV testing significantly enhance the detection rate before the biopsy. The diagnosis of NECC relies on histological and immunohistochemical examinations. This study provides valuable clinical observations on NECC and emphasizes the importance of early detection and accurate diagnosis for improved patient outcomes.
Learning to Lead in Early Childhood Education
Authors: Nuttall Joce , Reinertsen Anne B. , Armstrong-Read Arvay Hinemoa
Published: August 2023

Learning to Lead in Early Childhood Education makes a major new contribution to the educational leadership literature in early childhood education. Three sharply contrasting theoretical and methodological approaches are explained, each with an accompanying case study as a separate chapter. This allows readers to clearly see the relationship between theory, research, and practice, including theory-driven approaches to analysis. By drawing the case studies from three countries – Australia, Norway, and Aotearoa New Zealand, including one involving Indigenous participants – this book allows readers to learn about early childhood leadership policy and cultures in settings with different languages, histories, and national contexts. It will appeal to early childhood centre leaders, early childhood education and leadership academics, and post-graduate students in educational leadership interested in the potential of – and for – multiple approaches to leadership research and learning in early childhood education.
Data Modeling for the Sciences
Authors: Pressé Steve , Sgouralis Ioannis
Published: August 2023

With the increasing prevalence of big data and sparse data, and rapidly growing data-centric approaches to scientific research, students must develop effective data analysis skills at an early stage of their academic careers. This detailed guide to data modeling in the sciences is ideal for students and researchers keen to develop their understanding of probabilistic data modeling beyond the basics of p-values and fitting residuals. The textbook begins with basic probabilistic concepts, models of dynamical systems and likelihoods are then presented to build the foundation for Bayesian inference, Monte Carlo samplers and filtering. Modeling paradigms are then seamlessly developed, including mixture models, regression models, hidden Markov models, state-space models and Kalman filtering, continuous time processes and uniformization. The text is self-contained and includes practical examples and numerous exercises. This would be an excellent resource for courses on data analysis within the natural sciences, or as a reference text for self-study.
Encouraging Innovation
Authors: Reed Stephen K.
Published: August 2023

'Encouraging Innovation: Cognition, Education, and Implementation' is of interest to people who desire to become more innovative in their daily lives and careers. Part I discusses the cognitive and social skills required for innovation – reasoning, problem solving, creativity, group decision making, and collaborative problem solving. The second part discusses education – the development of cognitive skills and talent, application of relevant learning theories, methods and curricula for enhancing creativity, creativity across disciplines, and design education. Part III discusses the implementation of these skills in society – the transition from theory to practice, business innovation, social innovation, and organizational support. Whereas business innovation is related to commercialization, market demands, and profitability, social innovation addresses fulfilling social needs and public demands. Organizational support for innovation occurs at international, national, agency, and regional levels.
Characterizing infection prevention programs and urinary tract infection prevention practices in nursing homes: A mixed-methods study
Authors: Jones Karen M. , Krein Sarah L. , Mantey Julia , Harrod Molly , Mody Lona
Published: August 2023

Objective:

US policies require robust nursing home (NH) infection prevention and control (IPC) programs to ensure safe care. We assessed IPC resources and practices related to catheter and non–catheter-associated urinary tract infection (CAUTI and UTI) prevention among NHs.

Methods:

We conducted a mixed-methods study from April 2018 through November 2019. Quantitative surveys assessed NH IPC program resources, practices, and communication during resident transfer. Semistructured qualitative interviews focused on IPC programs, CAUTI and UTI prevention practices, and resident transfer processes. Using a matrix as an analytic tool, findings from the quantitative survey data were combined with the qualitative data in the form of a joint display.

Results:

Representatives from 51 NHs completed surveys; interviews were conducted with 13 participants from 7 NHs. Infection preventionists (IPs) had limited experience and/or additional roles, and in 36.7% of NHs, IPs had no specific IPC training. IP turnover was often mentioned during interviews. Most facilities were aware of their CAUTI and UTI rates and reported using prevention practices, such as hydration (85.7%) or nurse-initiated catheter discontinuation (65.3%). Qualitative interviewees confirmed use of these practices and expressed additional concerns about overuse of urine testing and antibiotics. Although transfer sheets were used by 84% to communicate about infections, the information received was described as suboptimal.

Conclusions:

NHs identified IP challenges related to turnover, limited education, and serving multiple roles. However, most NHs reported awareness of their CAUTI and UTI rates as well as their use of prevention practices. Importantly, we identified opportunities to enhance communication between NHs and hospitals to improve resident care and safety.
A Possible Case of Coccidioides Infection in a Thirteenth-Century Bolivian Mummy
Authors: Cilli Jacopo , Borrelli Lucia , D'Anastasio Ruggero , Soricelli Andrea , Capasso Luigi
Published: August 2023

Coccidioidomycosis is an infectious fungal disease endemic in Bolivia's Gran Chaco region that is caused by inspiration of the spores of Coccidiodes species. It is a respiratory pathology that can spread to the skeleton and produce diffuse lytic lesions in different parts of the body. This disease has rarely been described in historic populations, and we present here a new case of coccidioidomycosis in a mummified human individual. It corresponds to a female individual with an age at death of 25–35 years, dated to the Tiwanaku epoch of the thirteenth century AD. It was found inside a sepulchral cave near the city of Ulloma in western Bolivia. Radiographic examination shows numerous osseous lytic lesions with central cavitation concentrated on the cranial table and vertebral bodies. The observed condition could correspond to the secondary phase of coccidioidomycosis. This diagnosis is noteworthy because coccidioidomycosis was mainly described as a male work-related disease and has never been found in ancient western Bolivia.
Association between dam and calf measurements with overall and fetopelvic dystocia in Holstein heifers
Authors: Tsaousioti Angeliki , Praxitelous Anastasia , Kok Akke , Kiossis Evangelos , Boscos Constantinos , Tsousis Georgios
Published: August 2023

We investigated the relationship between dam's pelvic and calf's dimensions with dystocia due to fetopelvic disproportion in the Holstein breed and estimated risk factors and dystocia probability. For this purpose, external pelvic measurements were performed in 402 heifers 15 ± 11 (1–38) days ante-partum and specific conformation measurements were obtained from their calves 1.7 ± 1.2 post-partum. Dystocia was defined as the inability of the heifer to complete parturition spontaneously within 120 min after the appearance of the amnion with normal presentation, position and posture or as having definite obstetrical obstacles within 60 min. Overall and fetopelvic disproportion dystocia incidence was 10.4% and 5.2%, respectively. Heifer measurements mainly influenced overall dystocia, whereas calf conformation was related solely with fetopelvic dystocia. Specifically, heifers with a small pelvis (hip width <49.95 cm, pelvic inlet area <333.2 cm2, pelvic volume <7799.2 cm3) had 2.8 to 3.5 times greater incidence of overall dystocia (19.0–20.8%) compared to heifers with a larger pelvis (incidence of 7.0–7.6%). Regarding calf factors, sex (male calves), body weight, chest circumference and fetlock joint circumference significantly increased the odds of experiencing dystocia due to fetopelvic disproportion compared with female, lighter or smaller calves. In a backward elimination model with independent variables treated as continuous, an area under the ROC curve of 0.66 regarding the prediction of overall dystocia based on heifer pelvic length, and of 0.64 for the prediction of fetopelvic dystocia based on fetlock joint circumference was found. The combination of the two variables in one model improved the ROC area to 0.71 regarding dystocia due to fetopelvic disproportion, reaching acceptable level of discrimination. Our findings indicate that dystocia due to fetopelvic disproportion in heifers is mainly influenced by the fetal side. Additionally, the estimation of pelvic dimensions of the dam before parturition and specific conformation characteristics of the calf during parturition, especially fetlock joint circumference, could aid obstetricians and herdsmen regarding dystocia probability and parturition surveillance.
Contact force regulation in physical human-machine interaction based on model predictive control
Authors: Pacheco Quiñones Daniel , Paterna Maria , De Benedictis Carlo , Maffiodo Daniela , Franco Walter , Ferraresi Carlo
Published: August 2023

With increasing attention to physical human-machine interaction (pHMI), new control methods involving contact force regulation in collaborative and coexistence scenarios have spread in recent years. Thanks to its internal robustness, high dynamic performance, and capabilities to avoid constraint violations, a Model Predictive Control (MPC) action can pose a viable solution to manage the uncertainties involved in those applications. This paper uses an MPC-driven control method that aims to apply a well-defined and tunable force impulse on a human subject. After describing a general control design suitable to achieve this goal, a practical implementation of such a logic, based on an MPC controller, is shown. In particular, the physical interaction considered is the one occurring between the body of a patient and an external perturbation device in a dynamic posturography trial. The device prototype is presented in both its hardware architecture and software design. The MPC-based main control parameters are thus tuned inside hardware-in-the-loop and human-in-the-loop environments to get optimal behaviors. Finally, the device performance is analyzed to assess the MPC algorithm’s accuracy, repeatability, flexibility, and robustness concerning the several uncertainties due to the specific pHMI environment considered.
Trajectories, comorbidity, and risk factors for adolescent disordered eating and borderline personality disorder features
Authors: Lee Kirsty S. , Vaillancourt Tracy
Published: August 2023

Purpose:

Borderline personality disorder (BPD) and eating disorders are highly comorbid, but the shared course of symptoms and associated risks remain poorly understood. The aim of this study was to examine joint symptom trajectories, temporal precedence, risk factors, and population attributable fractions (PAFs) in a community sample of adolescents, using a developmental psychopathology and psychosocial framework.

Methods:

Across five years (age 14–18 years), adolescents (n = 544, 56% girls) reported on BPD features and disordered eating behavior. Sociodemographic, interpersonal, and clinical risks were assessed in childhood (age 10–13 years). We used a person-centered approach to examine latent class growth analyses, joint trajectory models, and calculated PAFs.

Results:

Three-class solutions were found for both disordered eating and BPD features (low, moderate, high), creating nine joint trajectories. High levels of disordered eating were a stronger indicator of high levels of BPD features than was the reverse. Girls and LGBTQ+ youth were most likely to be in a high symptom trajectory. Bullying perpetration and clinical hyperactivity were unique risks for BPD features. Bullying victimization contributed the largest PAF to disordered eating and BPD features.

Conclusion:

We identified several novel and clinically relevant findings related to temporality, risks, screening, and the treatment of adolescent eating problems and BPD.
Learning Goal Orientation and the Development of Perceived Employability of Young Workers
Authors: Grosemans Ilke , Houben Ellen , Kyndt Eva , De Cuyper Nele
Published: August 2023

Abstract: The current study probes the relation between learning and employability. First, we investigated the relationship between younger workers’ work-domain learning goal orientation and perceived employability and its development over time. This portrays an agentic view: Effort is expected to open up new opportunities. Second, we explored whether agency is equally strong for everyone by investigating whether having a higher education degree associated with this relationship. Latent growth analyses ( N = 792) demonstrated that work-domain learning goal orientation of younger workers only affected the initial value of perceived employability and only for workers without higher education degree. Furthermore, perceived employability of respondents without (vs. with) higher education degree started lower, but they seem to catch up over a 1-year period.
Heterogeneity‐Driven Localization and Weakening in Scaly Clays From a Fossil Accretionary Prism
Authors: Aretusini S. , Mittempergher S. , Remitti F. , Arletti R. , Polisi M. , De Paola N. , Tesei T.
Published: August 2023

In accretionary prisms, scaly clays structure might be the result of strain localization and weakening or strain delocalization and hardening. Therefore, it is not clear how they influence the mechanical behavior of the accretionary prism. Here, we investigate the effect of rock fabric on the mechanical properties of scaly clays sampled from a fossil accretionary prism in a range of pressure‐temperature conditions typical of burial within accretionary prisms. We performed triaxial experiments using a direct shear configuration on samples in which the natural scaly clay fabric and natural lithological boundaries were preserved, at confining pressures of 10–120 MPa and temperatures of 25–150°C. Samples with homogeneous composition and natural scaly fabrics display strain hardening behavior at all tested conditions. Shearing at high P‐T displays lower strength with respect to shearing at low P‐T. The samples containing a lithological contact display strain hardening at low P‐T and weakening at high P‐T conditions. After the experiments, the homogeneous samples show a distributed foliation and short, discontinuous shear surfaces at the contacts with the sample holder, while the samples including a contact developed a through‐going shear zone composed of a series of en‐echelon shear surfaces. A reduced smectite and water content is observed in the post‐deformation samples, suggesting that weakening may correlate with water release during dehydration reactions of clay minerals at 150°C. This shows how both dehydration reactions at high P‐T conditions and strain localization along lithological boundaries promote brittle behavior within scaly clays in subduction zones accretionary prisms.
The Lack of a QBO‐MJO Connection in Climate Models With a Nudged Stratosphere
Authors: Martin Zane K. , Simpson Isla R. , Lin Pu , Orbe Clara , Tang Qi , Caron Julie M. , Chen Chih‐Chieh , Kim Hyemi , Leung L. Ruby , Richter Jadwiga H. , Xie Shaocheng
Published: August 2023

The observed stratospheric quasi‐biennial oscillation (QBO) and the tropospheric Madden‐Julian oscillation (MJO) are strongly connected in boreal winter, with stronger MJO activity when lower‐stratospheric winds are easterly. However, the current generation of climate models with internally generated representations of the QBO and MJO do not simulate the observed QBO‐MJO connection, for reasons that remain unclear. This study builds on prior work exploring the QBO‐MJO link in climate models whose stratospheric winds are relaxed toward reanalysis, reducing stratospheric biases in the model and imposing a realistic QBO. A series of ensemble experiments are performed using four state‐of‐the‐art climate models capable of representing the MJO over the period 1980–2015, each with similar nudging in the stratosphere. In these four models, nudging leads to a good representation of QBO wind and temperature signals, however no model simulates the observed QBO‐MJO relationship. Biases in MJO vertical structure and cloud‐radiative feedbacks are investigated, but no conclusive model bias or mechanism is identified that explains the lack of a QBO‐MJO connection.
Early ascending growth is associated with maternal lipoprotein profile during mid and late pregnancy and in cord blood
Authors: Blanco Sequeiros Elina , Tuomaala Anna-Kaisa , Tabassum Rubina , Bergman Paula H. , Koivusalo Saila B. , Huvinen Emilia
Published: August 2023

Introduction

Intrauterine conditions and accelerating early growth are associated with childhood obesity. It is unknown, whether fetal programming affects the early growth and could alterations in the maternal-fetal metabolome be the mediating mechanism. Therefore, we aimed to assess the associations between maternal and cord blood metabolite profile and offspring early growth.

Methods

The RADIEL study recruited 724 women at high risk for gestational diabetes mellitus (GDM) BMI ≥ 30 kg/m2 and/or prior GDM) before or in early pregnancy. Blood samples were collected once in each trimester, and from cord. Metabolomics were analyzed by targeted nuclear magnetic resonance (NMR) technique. Following up on offsprings’ first 2 years growth, we discovered 3 distinct growth profiles (ascending n = 80, intermediate n = 346, and descending n = 146) by using latent class mixed models (lcmm).

Results

From the cohort of mother-child dyads with available growth profile data (n = 572), we have metabolomic data from 232 mothers from 1st trimester, 271 from 2nd trimester, 277 from 3rd trimester and 345 from cord blood. We have data on 220 metabolites in each trimester and 70 from cord blood. In each trimester of pregnancy, the mothers of the ascending group showed higher levels of VLDL and LDL particles, and lower levels of HDL particles (p < 0.05). When adjusted for gestational age, birth weight, sex, delivery mode, and maternal smoking, there was an association with ascending profile and 2nd trimester total cholesterol in HDL2, 3rd trimester total cholesterol in HDL2 and in HDL, VLDL size and ratio of triglycerides to phosphoglycerides (TG/PG ratio) in cord blood (p ≤ 0.002).

Conclusion

Ascending early growth was associated with lower maternal total cholesterol in HDL in 2nd and 3rd trimester, and higher VLDL size and more adverse TG/PG ratio in cord blood.

Clinical trial registration

ClinicalTrials.gov, http://www.clinicaltrials.com, NCT01698385.
Lipid saturation controls nuclear envelope function
Authors: Romanauska Anete , Köhler Alwin
Published: August 2023

The nuclear envelope (NE) is a spherical double membrane with elastic properties. How NE shape and elasticity are regulated by lipid chemistry is unknown. Here we discover lipid acyl chain unsaturation as essential for NE and nuclear pore complex (NPC) architecture and function. Increased lipid saturation rigidifies the NE and the endoplasmic reticulum into planar, polygonal membranes, which are fracture prone. These membranes exhibit a micron-scale segregation of lipids into ordered and disordered phases, excluding NPCs from the ordered phase. Balanced lipid saturation is required for NPC integrity, pore membrane curvature and nucleocytoplasmic transport. Oxygen deprivation amplifies the impact of saturated lipids, causing NE rigidification and rupture. Conversely, lipid droplets buffer saturated lipids to preserve NE architecture. Our study uncovers a fundamental link between lipid acyl chain structure and the integrity of the cell nucleus with implications for nuclear membrane malfunction in ischaemic tissues.
Programmable multispecific DNA-origami-based T-cell engagers
Authors: Wagenbauer Klaus F. , Pham Nhi , Gottschlich Adrian , Kick Benjamin , Kozina Viktorija , Frank Christopher , Trninic Daniela , Stömmer Pierre , Grünmeier Ruth , Carlini Emanuele , Tsiverioti Christina Angeliki , Kobold Sebastian , Funke Jonas J. , Dietz Hendrik
Published: August 2023

Multispecific antibodies have emerged as versatile therapeutic agents, and therefore, approaches to optimize and streamline their design and assembly are needed. Here we report on the modular and programmable assembly of IgG antibodies, F(ab) and scFv fragments on DNA origami nanocarriers. We screened 105 distinct quadruplet antibody variants in vitro for the ability to activate T cells in the presence of target cells. T-cell engagers were identified, which in vitro showed the specific and efficient T-cell-mediated lysis of five distinct target cell lines. We used these T-cell engagers to target and lyse tumour cells in vivo in a xenograft mouse tumour model. Our approach enables the rapid generation, screening and testing of bi- and multispecific antibodies to facilitate preclinical pharmaceutical development from in vitro discovery to in vivo proof of concept.
Single-molecule analysis of DNA base-stacking energetics using patterned DNA nanostructures
Authors: Banerjee Abhinav , Anand Micky , Kalita Simanta , Ganji Mahipal
Published: August 2023

The DNA double helix structure is stabilized by base-pairing and base-stacking interactions. However, a comprehensive understanding of dinucleotide base-stacking energetics is lacking. Here we combined multiplexed DNA-based point accumulation in nanoscale topography (DNA-PAINT) imaging with designer DNA nanostructures and measured the free energy of dinucleotide base stacking at the single-molecule level. Multiplexed imaging enabled us to extract the binding kinetics of an imager strand with and without additional dinucleotide stacking interactions. The DNA-PAINT data showed that a single additional dinucleotide base stacking results in up to 250-fold stabilization for the DNA duplex nanostructure. We found that the dinucleotide base-stacking energies vary from −0.95 ± 0.12 kcal mol−1 to −3.22 ± 0.04 kcal mol−1 for C|T and A|C base-stackings, respectively. We demonstrate the application of base-stacking energetics in designing DNA-PAINT probes for multiplexed super-resolution imaging, and efficient assembly of higher-order DNA nanostructures. Our results will aid in designing functional DNA nanostructures, and DNA and RNA aptamers, and facilitate better predictions of the local DNA structure.
Idecabtagene vicleucel for relapsed and refractory multiple myeloma: post hoc 18-month follow-up of a phase 1 trial
Authors: Lin Yi , Raje Noopur S. , Berdeja Jesús G. , Siegel David S. , Jagannath Sundar , Madduri Deepu , Liedtke Michaela , Rosenblatt Jacalyn , Maus Marcela V. , Massaro Monica , Petrocca Fabio , Yeri Ashish , Finney Olivia , Caia Andrea , Yang Zhihong , Martin Nathan , Campbell Timothy B. , Rytlewski Julie , Fuller Jaymes , Hege Kristen , Munshi Nikhil C. , Kochenderfer James N.
Published: August 2023

Idecabtagene vicleucel (ide-cel) is a B-cell-maturation antigen (BCMA)-directed chimeric antigen receptor T cell therapy. We performed a post hoc analysis of a single-arm phase 1 multicenter study in relapsed/refractory multiple myeloma (CRB-401) (n = 62; median follow-up, 18.1 months). The primary endpoint was safety outcomes, and secondary endpoints included overall response rate (ORR), complete response (CR) and very good partial response (VGPR). The study met its primary endpoint with low rates of grade 3/grade 4 cytokine release syndrome (6.5%) and neurotoxicity (1.6%). ORR was 75.8%; 64.5% achieved VGPR or better and 38.7% achieved CR or stringent CR. Among exploratory endpoints, median duration of response, progression-free survival (PFS) and overall survival were 10.3, 8.8 and 34.2 months, respectively, and ide-cel expansion in blood and bone marrow correlated with clinical efficacy and postinfusion reduction of soluble BCMA. Patients with PFS ≥ 18 months had more naive and less exhausted T cells in apheresis material and improved functional T cell phenotype in the drug product compared with those with less durable responses. These results confirm ide-cel safety, tolerability and efficacy and describe T cell qualities that correlate with durable response. Clinicaltrials.gov identifier : NCT02658929.
Orbitofrontal cortex control of striatum leads economic decision-making
Authors: Gore Felicity , Hernandez Melissa , Ramakrishnan Charu , Crow Ailey K. , Malenka Robert C. , Deisseroth Karl
Published: August 2023

Animals must continually evaluate stimuli in their environment to decide which opportunities to pursue, and in many cases these decisions can be understood in fundamentally economic terms. Although several brain regions have been individually implicated in these processes, the brain-wide mechanisms relating these regions in decision-making are unclear. Using an economic decision-making task adapted for rats, we find that neural activity in both of two connected brain regions, the ventrolateral orbitofrontal cortex (OFC) and the dorsomedial striatum (DMS), was required for economic decision-making. Relevant neural activity in both brain regions was strikingly similar, dominated by the spatial features of the decision-making process. However, the neural encoding of choice direction in OFC preceded that of DMS, and this temporal relationship was strongly correlated with choice accuracy. Furthermore, activity specifically in the OFC projection to the DMS was required for appropriate economic decision-making. These results demonstrate that choice information in the OFC is relayed to the DMS to lead accurate economic decision-making.
Molecular modelling and site-directed mutagenesis provide insight into saccharide pyruvylation by the Paenibacillus alvei CsaB enzyme
Authors: Stefanović Cordula , Hager-Mair Fiona F. , Breslmayr Erik , López-Guzmán Arturo , Lim Charlie , Blaukopf Markus , Kosma Paul , Oostenbrink Chris , Ludwig Roland , Schäffer Christina
Published: August 2023

Pyruvylation is a biologically versatile but mechanistically unexplored saccharide modification. 4,6-Ketal pyruvylated N-acetylmannosamine within bacterial secondary cell wall polymers serves as a cell wall anchoring epitope for proteins possessing a terminal S-layer homology domain trimer. The pyruvyltransferase CsaB from Paenibacillus alvei served as a model to investigate the structural basis of the pyruvyltransfer reaction by a combination of molecular modelling and site-directed mutagenesis together with an enzyme assay using phosphoenolpyruvate (PEP; donor) and synthetic β-D-ManNAc-(1 → 4)-α-D-GlcNAc-diphosphoryl-11-phenoxyundecyl (acceptor). CsaB protein structure modelling was done using Phyre2 and I-Tasser based on the partial crystal structure of the Schizosaccharomyces pombe pyruvyltransferase Pvg1p and by AlphaFold. The models informed the construction of twelve CsaB mutants targeted at plausible PEP and acceptor binding sites and KM and kcat values were determined to evaluate the mutants, indicating the importance of a loop region for catalysis. R148, H308 and K328 were found to be critical to PEP binding and insight into acceptor binding was obtained from an analysis of Y14 and F16 mutants, confirming the modelled binding sites and interactions predicted using Molecular Operating Environment. These data lay the basis for future mechanistic studies of saccharide pyruvylation as a novel target for interference with bacterial cell wall assembly.
Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management
Authors: Agu P. C. , Afiukwa C. A. , Orji O. U. , Ezeh E. M. , Ofoke I. H. , Ogbu C. O. , Ugwuja E. I. , Aja P. M.
Published: August 2023

Molecular docking is a computational technique that predicts the binding affinity of ligands to receptor proteins. Although it has potential uses in nutraceutical research, it has developed into a formidable tool for drug development. Bioactive substances called nutraceuticals are present in food sources and can be used in the management of diseases. Finding their molecular targets can help in the creation of disease-specific new therapies. The purpose of this review was to explore molecular docking's application to the study of dietary supplements and disease management. First, an overview of the fundamentals of molecular docking and the various software tools available for docking was presented. The limitations and difficulties of using molecular docking in nutraceutical research are also covered, including the reliability of scoring functions and the requirement for experimental validation. Additionally, there was a focus on the identification of molecular targets for nutraceuticals in numerous disease models, including those for sickle cell disease, cancer, cardiovascular, gut, reproductive, and neurodegenerative disorders. We further highlighted biochemistry pathways and models from recent studies that have revealed molecular mechanisms to pinpoint new nutraceuticals' effects on disease pathogenesis. It is convincingly true that molecular docking is a useful tool for identifying the molecular targets of nutraceuticals in the management of diseases. It may offer information about how nutraceuticals work and support the creation of new therapeutics. Therefore, molecular docking has a bright future in nutraceutical research and has a lot of potentials to lead to the creation of brand-new medicines for the treatment of disease.
Effect of caffeine and other xanthines on liver sinusoidal endothelial cell ultrastructure
Authors: Mao Hong , Szafranska Karolina , Kruse Larissa , Holte Christopher , Wolfson Deanna L. , Ahluwalia Balpreet Singh , Whitchurch Cynthia B. , Cole Louise , Lockwood Glen P. , Diekmann Robin , Le Couteur David , Cogger Victoria C. , McCourt Peter A. G.
Published: August 2023

Xanthines such as caffeine and theobromine are among the most consumed psychoactive stimulants in the world, either as natural components of coffee, tea and chocolate, or as added ingredients. The present study assessed if xanthines affect liver sinusoidal endothelial cells (LSEC). Cultured primary rat LSEC were challenged with xanthines at concentrations typically obtained from normal consumption of xanthine-containing beverages, food or medicines; and at higher concentrations below the in vitro toxic limit. The fenestrated morphology of LSEC were examined with scanning electron and structured illumination microscopy. All xanthine challenges had no toxic effects on LSEC ultrastructure as judged by LSEC fenestration morphology, or function as determined by endocytosis studies. All xanthines in high concentrations (150 μg/mL) increased fenestration frequency but at physiologically relevant concentrations, only theobromine (8 μg/mL) showed an effect. LSEC porosity was influenced only by high caffeine doses which also shifted the fenestration distribution towards smaller pores. Moreover, a dose-dependent increase in fenestration number was observed after caffeine treatment. If these compounds induce similar changes in vivo, age-related reduction of LSEC porosity can be reversed by oral treatment with theobromine or with other xanthines using targeted delivery.
Intelligent diagnostic model for malaria parasite detection and classification using imperative inception-based capsule neural networks
Authors: Madhu Golla , Mohamed Ali Wagdy , Kautish Sandeep , Shah Mohd Asif , Ali Irfan
Published: August 2023

Malaria is an acute fever sickness caused by the Plasmodium parasite and spread by infected Anopheles female mosquitoes. It causes catastrophic illness if left untreated for an extended period, and delaying exact treatment might result in the development of further complications. The most prevalent method now available for detecting malaria is the microscope. Under a microscope, blood smears are typically examined for malaria diagnosis. Despite its advantages, this method is time-consuming, subjective, and requires highly skilled personnel. Therefore, an automated malaria diagnosis system is imperative for ensuring accurate and efficient treatment. This research develops an innovative approach utilizing an urgent, inception-based capsule network to distinguish parasitized and uninfected cells from microscopic images. This diagnostic model incorporates neural networks based on Inception and Imperative Capsule networks. The inception block extracts rich characteristics from images of malaria cells using a pre-trained model, such as Inception V3, which facilitates efficient representation learning. Subsequently, the dynamic imperative capsule neural network detects malaria parasites in microscopic images by classifying them into parasitized and healthy cells, enabling the detection of malaria parasites. The experiment results demonstrate a significant improvement in malaria parasite recognition. Compared to traditional manual microscopy, the proposed system is more accurate and faster. Finally, this study demonstrates the need to provide robust and efficient diagnostic solutions by leveraging state-of-the-art technologies to combat malaria.
Molecular insights into recognition of GUCY2C by T-cell engaging bispecific antibody anti-GUCY2CxCD3
Authors: Rampuria Pragya , Mosyak Lidia , Root Adam R. , Svenson Kristine , Agostino Michael J. , LaVallie Edward R.
Published: August 2023

The intestinal epithelial receptor Guanylyl Cyclase C (GUCY2C) is a tumor-associated cell surface antigen expressed across gastrointestinal malignancies that can serve as an efficacious target for colorectal cancer immunotherapy. Here, we describe a yeast surface-display approach combined with an orthogonal peptide-based mapping strategy to identify the GUCY2C binding epitope of a novel anti-GUCY2CxCD3 bispecific antibody (BsAb) that recently advanced into the clinic for the treatment of cancer. The target epitope was localized to the N-terminal helix H2 of human GUCY2C, which enabled the determination of the crystal structure of the minimal GUCY2C epitope in complex with the anti-GUCY2C antibody domain. To understand if this minimal epitope covers the entire antibody binding region and to investigate the impact of epitope position on the antibody’s activity, we further determined the structure of this interaction in the context of the full-length extracellular domain (ECD) of GUCY2C. We found that this epitope is positioned on the protruding membrane-distal helical region of GUCY2C and that its specific location on the surface of GUCY2C dictates the close spatial proximity of the two antigen arms in a diabody arrangement essential to the tumor killing activity of GUCY2CxCD3 BsAb.
Development and analysis of a nano-triangular wave-shaped polarizer
Authors: Hokari Ryohei , Takakuwa Kyohei , Shiomoto Kengo , Kuwano Genki , Kurihara Kazuma
Published: August 2023

As society becomes smarter, advanced optical sensing and imaging technologies utilizing visible and near-infrared regions have become increasingly prevalent. Wire-grid polarizers, which are available for broadband electromagnetic waves, are effective in improving the signal-to-noise ratio of such optical systems and enabling more advanced object detection and analysis. However, to be implemented in everyday products, low-cost manufacturing methods must be developed while maintaining high-performance optical functions. To meet these requirements, we conducted an analysis of the geometry of wire-grid polarizers, and designed and developed a wire-grid polarizer with a nano-triangular wave-shaped structure that can be fabricated using general-purpose manufacturing equipment. Once the mould is prepared, this polarizer can be fabricated via nanoimprinting and metal deposition with a normal angle or electroless plating processes. The polarizer fabricated through electroless Ni plating achieves a transmittance of 40%, which is approximately 1.4 times higher than that achieved in a previous study using electroless Ni plating on a rectangular structure with the same period. In addition, the polarizer fabricated through normal angle Al deposition operates over a wide range of wavelengths from visible light to near-infrared, and achieves a polarization extinction ratio of 24 dB at a wavelength of 550 nm and a high transmittance of 81%. High-performance polarizers can be obtained through normal-angle deposition using general-purpose equipment in contrast to the oblique-angle deposition method employed in the manufacture of conventional rectangular structure-based wire-grid polarizers, thereby contributing to cost reduction and improved manufacturability.
Hybrid collagen–cellulose–Fe3O4@TiO2 magnetic bio-sponges derived from animal skin waste and Kenaf fibers for wastewater remediation
Authors: Assanvo E. F. , Nagaraj S. , Boa D. , Thanikaivelan P.
Published: August 2023

Water pollution from synthetic dyes and oil spills has a significant impact on the environment and living species. Here, we developed a low-cost, environmentally friendly and easily biodegradable magnetic hybrid bio-sponge nanocomposite from renewable resources such as collagen and cellulose (Kenaf fibre cellulose–collagen, KFCC). We loaded it with magnetic bimetallic Fe3O4@TiO2 (BFT) NPs to produce a photocatalyst material (KFCC-BFT) for the treatment of colored wastewater as well as a sorbent for oil–water separation. The characterization of the bimetallic BFT NPs by XRD, HRTEM and VSM showed the deposition of TiO2 particles onto the surface of Fe3O4 with lattice interlayers spacing of 0.24 and 0.33 nm for Fe3O4 and TiO2, respectively with ferromagnetic property. The UV–vis diffuse reflectance spectra result indicated that the band gap energy of bio-sponges decreases with the increase of the bimetallic moiety. The photocatalytic efficiency of the as-prepared magnetic hybrid bio-sponge in the degradation of crystal violet dye was up to 91.2% under visible light conditions and 86.6% under direct sunlight exposure. Furthermore, the magnetic hybrid bio-sponge was used to separate motor oil from water (> 99%) and had a high oil sorption capacity of 46.1 g/g. Investigation of the recyclability and reusability performance for 9 cycles revealed that the bio-sponge had a high sorption capacity for up to 5 cycles. Our results suggest that the bio-polymer-supported BFT hybrid nanocomposite is a cost-effective and easily biodegradable photocatalyst and has great potential for real-field environmental remediation applications.
Enhanced resolution and sensitivity acoustic-resolution photoacoustic microscopy with semi/unsupervised GANs
Authors: Le Thanh Dat , Min Jung-Joon , Lee Changho
Published: August 2023

Acoustic-resolution photoacoustic microscopy (AR-PAM) enables visualization of biological tissues at depths of several millimeters with superior optical absorption contrast. However, the lateral resolution and sensitivity of AR-PAM are generally lower than those of optical-resolution PAM (OR-PAM) owing to the intrinsic physical acoustic focusing mechanism. Here, we demonstrate a computational strategy with two generative adversarial networks (GANs) to perform semi/unsupervised reconstruction with high resolution and sensitivity in AR-PAM by maintaining its imaging capability at enhanced depths. The b-scan PAM images were prepared as paired (for semi-supervised conditional GAN) and unpaired (for unsupervised CycleGAN) groups for label-free reconstructed AR-PAM b-scan image generation and training. The semi/unsupervised GANs successfully improved resolution and sensitivity in a phantom and in vivo mouse ear test with ground truth. We also confirmed that GANs could enhance resolution and sensitivity of deep tissues without the ground truth.
Effects of preoperative sarcopenia-related parameters on the musculoskeletal and metabolic outcomes after bariatric surgery: a one-year longitudinal study in females
Authors: Crispim Carvalho Nara Nóbrega , Martins Vinícius José Baccin , Filho João Modesto , de Arruda Neta Adélia da Costa Pereira , Pimenta Flávia Cristina Fernandes , de Brito Alves José Luiz
Published: August 2023

Reduced muscle mass and/or strength are risk factors for metabolic and musculoskeletal impairment. The present study evaluated anthropometric, metabolic, and musculoskeletal outcomes in females with and without sarcopenic-obesity parameters who underwent bariatric surgery during a 1-year follow-up. A prospective, single-center cohort study was conducted in females with obesity undergoing preoperative evaluation for surgery. In the preoperative period, females were allocated into obesity with sarcopenic-obesity parameters (SOP group, n = 15) and without sarcopenic-obesity parameters (obesity group, n = 21). Sarcopenic obesity parameters were defined as lower appendicular skeletal mass adjusted for weight (ASM/wt) and/or low handgrip strength (HGS). Anthropometric, metabolic, and musculoskeletal parameters were assessed before surgery and at 3 months, 6 months, and a 1-year after bariatric surgery. Weight loss was similar between groups (p > 0.05). Weight, body mass index, fat mass, body fat percentage, skeletal muscle mass, fat-free mass, fat-free mass index, HGS were reduced in both groups during the 1-year follow-up (p < 0.05). However, when muscle mass and strength were analyzed relative to body size, an improvement after bariatric surgery was found in both groups (p < 0.05). Total cholesterol, LDL-c, triglycerides, fasting glucose, glycated hemoglobin, insulin, and insulin resistance were reduced in both groups during the 1-year follow-up (p < 0.05). In addition, HDL-c serum concentration increased in females with and without sarcopenic-obesity parameters over the 1-year follow-up (p < 0.05). Both groups had decreased bone mineral density (BMD) at all sites (lumbar spine, femoral neck, and total femur) over the 1-year follow-up (p < 0.05). The highest quartile of ASM/wt was positively associated with BMD variables in a longitudinal analysis, suggesting that preserved ASM/wt in pre-surgery may be beneficial for BMD after 1 year of bariatric surgery. The results showed that bariatric surgery promotes similar musculoskeletal and metabolic changes in females with preserved muscle mass and strength or in females with sarcopenia-related parameters.
Photocatalytically reactive surfaces for simultaneous water harvesting and treatment
Authors: Ghosh Ritwick , Baut Adrien , Belleri Giorgio , Kappl Michael , Butt Hans-Jürgen , Schutzius Thomas M.
Published: August 2023

Atmospheric water harvesting provides decentralized and sustainable supplies of fresh water in areas away from natural water resources. However, an important challenge is that water sources such as fog are subject to contamination from airborne pollutants, especially near population centres. Here we demonstrate a rationally designed system that can capture fog at high efficiency while simultaneously degrading organic pollutants. At the heart of our design is a wire mesh coated with anatase titanium dioxide nanoparticles embedded in a polymer matrix. Once activated by sunlight, the photoactive titanium dioxide layer decomposes organic molecules such as diesel, even in the absence of sunlight; moreover, the wettability of the mesh surface is engineered to enhance water extraction. In outdoor tests, the device can maintain a good fog harvesting performance as well as a water treatment efficiency of >85%. The continuous production of water with passive purification demonstrated in our study provides an energy-free solution to address water scarcity.
High resolution mass spectrometry of respiratory viruses: beyond MALDI-ToF instruments for next generation viral typing, subtyping, variant and sub-variant identification
Authors: Hoyle Joshua S. , Downard Kevin M.
Published: August 2023

Review of the ability of high resolution mass spectrometry to detect, type, subtype and distinguish variants and sub-variants in virus clinical specimens with high confidence.
Modern microelectronics and microfluidics on microneedles
Authors: Han Yanzhang , Li Jun , Chen Tingting , Gao Bingbing , Wang Huili
Published: August 2023

Possessing the attractive advantages of moderate invasiveness and high compliance, there is no doubt that microneedles (MNs) have been a gradually rising star in the field of medicine.