bluuebunny/crossref_metadata_2025 huggingface dataset:
Traditional Vietnamese medicine Kovir capsule for non‐severe COVID‐19 patients: A phase III double‐blind randomized controlled trial
Authors: Loc Huynh Nguyen , Hoan Vu Minh , Vuong Nguyen Lam , Lan Truong Thi Ngoc , Huong Dinh Thi Lan , Hung Tran Quoc , Tuyen Nguyen Thanh , Quang Tran Minh , Dao Ly Minh
Published: February 2023

The number of COVID‐19 infections is still increasing with the omicron variant. Although vaccination has shown its effectiveness, efficacious treatments are still required. Kovir, a Vietnamese herbal medicine, has shown potential effects for non‐severe COVID‐19 patients in terms of symptom resolution and prevention of disease progression in previous studies. This phase‐3 trial evaluated the safety and efficacy of Kovir for non‐severe COVID‐19 adults. Participants were randomized to the Kovir (381 patients) or placebo (192 patients) groups. Outcomes were progression to severe/critical COVID‐19, a daily symptom score based on 11 pre‐defined symptoms, time to symptom resolution, a negative reverse transcription polymerase chain reaction, an EQ‐5D‐5L quality of life (QOL) score, and serious adverse events. Only one patient (in the placebo group) progressed to severe COVID‐19, thus we could not conclude the effect of Kovir on the prevention of disease progression. Kovir significantly reduced time to symptom resolution (median: 7 vs. 11 days, hazard ratio [95% confidence interval]: 2.03 [1.66–2.48]) compared to placebo. Kovir also increased the QOL score on days 7 and 14. No safety concerns were observed. To conclude, Kovir is safe and facilitates symptom relief for non‐severe COVID‐19 patients. We advocate using Kovir in the early phase of COVID‐19 for non‐severe adult patients.
Lz‐transform approach to evaluate reliability indices of multi‐state repairable weighted K‐out‐of‐n systems
Authors: Bisht Vaibhav , Singh S. B.
Published: February 2023

A multi‐state weightedK‐out‐of‐nsystem is of great importance in system engineering due to its generalized nature. In earlier studies, usually all the components of the multi‐state weightedK‐out‐of‐nsystem were considered to be in a steady state though we can encounter engineering systems where the components of this type of system can be dynamic in nature, that is, the states of components change over time. To deal with this situation, in the current study an algorithm, based on ‐transform is presented to determine the reliability indices of multi‐state weightedK‐out‐of‐nsystem in dynamic setup. The components of the system are assumed to follow Markov process and are repaired only when they are completely failed. In this proposed study reliability, availability, instantaneous mean expected performance, and performance deficiency are obtained for the considered system. Finally, a case study of the power system of warship is considered to apply and validate the proposed approach.
When biodiversity preservation meets biotechnology: The challenge of developing synthetic microbiota for resilient sustainable crop production
Authors: Fagorzi Camilla , Passeri Iacopo , Cangioli Lisa , Vaccaro Francesca , Mengoni Alessio
Published: February 2023

Agriculture needs to develop novel strategies and practices to meet the increasing global food demand, in an ecological and economical sustainable framework. The plant‐associated microbiota is gaining increasing attention as part of these strategies since it strongly contributes to plant health, nutrition, and resilience to environmental perturbations. However, plant domestication has brought to the reduction of the plant abilities to recruit a beneficial microbiota. It is becoming clear that successful use of the plant microbiota requires a multifaceted approach where microbiologist, geneticists, plant scientists, agronomists, and computational biologists can develop ways and solutions to modify both the plant microbiota and plant's ability to recruit it, directed to increase crop performances. Here, while briefly reviewing the state‐of‐the‐art in plant microbiota research, we focus the attention on the need to discover, understand and use the microbiota associated with wild relatives of crops and with neglected crops, which harbour the microbiota biodiversity needed for developing efficient bioinoculant solutions. In particular, we emphasize the convergence of in situ plant biodiversity preservation with microbiome preservation, which provides added value to nature and habitat conservation, as living collections of microbiome biodiversity. The heuristic value of bioinoculants (viz., synthetic communities) and the need of proper computational models to predict the outcome of their applications is also discussed toward a systems‐biology‐guided synthetic microbiota development.
Paraneoplastic Scleroderma in Kaposi's Sarcoma: Report of Two Cases
Authors: Oulad Ali Sara , Belcadi Jihane , Znati Kaoutar , Meziane Marieme , Ismaili Nadia , Benzekri Laila , Senouci Karima
Published: February 2023

Kaposi's sarcoma (KS) is a proliferative and multifocal disease with a double vascular and fibroblastic cell component, of mucocutaneous and visceral expression. It is a multifocal tumoral process, hyperplastic in nature without metastatic potential, induced by the human herpes virus 8 (HHV8). Paraneoplastic syndromes (PS) in KS are rare, with only a small number of cases reported and we have found no previous descriptions of a paraneoplastic scleroderma in KS in the literature. We report the cases of two patients with this atypical PS.
Nitrogen‐Doped Porous Nickel Molybdenum Phosphide Sheets for Efficient Seawater Splitting
Authors: Loomba Suraj , Khan Muhammad Waqas , Haris Muhammad , Mousavi Seyed Mahdi , Zavabeti Ali , Xu Kai , Tadich Anton , Thomsen Lars , McConville Christopher F. , Li Yongxiang , Walia Sumeet , Mahmood Nasir
Published: February 2023

Hydrogen is emerging as an alternative clean fuel; however, its dependency on freshwater will be a threat to a sustainable environment. Seawater, an unlimited source, can be an alternative, but its salt‐rich nature causes corrosion and introduces several competing reactions, hindering its use. To overcome these, a unique catalyst composed of porous sheets of nitrogen‐doped NiMo3P (N‐NiMo3P) having a sheet size of several microns is designed. The presence of large homogenous pores in the basal plane of these sheets makes them catalytically more active and ensures faster mass transfer. The introduction of N and Ni into MoP significantly tunes the electronic density of Mo, surface chemistry, and metal‐non‐metal bond lengths, optimizing surface energies, creating new active sites, and increasing electrical conductivity. The presence of metal‐nitrogen bonds and surface polyanions increases the stability and improves anti‐corrosive properties against chlorine chemistry. Ultimately, the N‐NiMo3P sheets show remarkable performance as it only requires overpotentials of 23 and 35 mV for hydrogen evolution reaction, and it catalyzes full water splitting at 1.52 and 1.55 V to achieve 10 mA cm−2 in 1 m KOH and seawater, respectively. Hence, structural and compositional control can make catalysts effective in realizing low‐cost hydrogen directly from seawater.
Qualitative and quantitative chemical characterization of spray‐dried extracts and the development of an innovative oral solid formulation from Lippia alba
Authors: de Almeida Maiara Prates , Silva Lorena Alves de Oliveira , Zimmermann Lara Almida , Bernardes Lilian Sibelle Campos , da Silva Marcelo Aparecido , da Silva Geraldo Alves , Amaral Juliano Geraldo , Gomes Angélica Ferraz , Leite Mateus Freire
Published: February 2023

A novel tablet formulation using Lippia alba was developed with spray‐dried extract leaf to obtain a product with anxiolytic properties. This work describes in silico study, extracting chemical qualitative and quantitative profiles, and the development and formulation of chemical‐physical characterization. A comprehensive understanding of L. alba oral dosage form components was obtained using a method based on high‐performance liquid chromatography coupled with a quadrupole time‐of‐flight mass spectrometer for the separation and characterization of L. alba tablets. Liquid chromatography‐tandem mass spectrometry analysis and Global Natural Product Social Molecular Networking allowed the identification of 36 compounds in the spray‐dried extract including flavonoids, iridoids, and phenylpropanoids glycosides. To determine biological markers, in silico analyzes were carried out with 15 compounds previously identified in this species. Acteoside was suggested as a biological marker, and the results of the Prediction of Activity Spectra for Substances pointed to a possible anxiolytic action. A quantitative method by high‐performance liquid chromatography‐diode array detection for Acteoside was also validated. The extract and formulation showed excellent flow characteristics, which favored the development of the formulation by direct compression. The tablets obtained were met for the quality control tests. Associating chemical strategies and technological development the novel tablet formulation could be used as a treatment for anxiolytic disorders.
Characteristics, properties, and analytical and bio‐analytical methods of enzalutamide: A review
Authors: Bondigalla Ramachandra , Challa Gangu Naidu , Yarraguntla Srinivasa Rao , Bandu Raju , Alla Subba Reddy
Published: February 2023

Enzalutamide is a potent second‐generation androgen receptor inhibitor that is used to treat metastatic castration‐resistant prostate cancer. It was developed by Medivation and Astellas and was approved by the Food and Drug Administration in 2012 under the brand name Xtandi. Enzalutamide has three major anticancer mechanisms, it inhibits the binding of androgens to the ligand‐binding domain of androgen receptors; inhibits nuclear translocation of androgen receptors; inhibits binding of androgen receptors to deoxyribonucleic acid. It demonstrates reduced expression of androgen receptor‐dependent genes, decreased prostate cancer cell proliferation, and induction of cancer cell death and tumor regression. As a result, patients with metastatic castration‐resistant prostate cancer have a higher chance of survival. Enzalutamide is very important in anticancer therapy, hence, it's necessary to compile all the analytical and bio‐analytical methods to monitor the bioequivalence, bioavailability, and therapeutic monitoring of a drug substance during the course of patient follow‐ups. Thus, this study presents a comprehensive review of the literature on characteristics, properties, and analytical and bio‐analytical methods in various matrices, including formulations, biological fluids, and drug delivery systems.
Effect of ECC layer thickness and reinforcement ratio on the load carrying capacity of steel‐reinforced composite beams
Authors: Arulanandam Preethy Mary , Kanakubo Toshiyuki , Singh S. B. , Sivasubramanian Madappa V. R.
Published: February 2023

The present study investigates the effect of Engineered Cementitious Composites (ECC) layer thickness against various reinforcement ratios on the flexural performance of reinforced ECC–concrete composite beams. In total, 20 reinforced composite beams are selected from the literature to predict their flexural response using Finite Element (FE) analysis. In addition to the FE analyses, a detailed analytical study is performed using the strain compatibility procedure to predict the flexural strength of ECC–concrete composite beams. The results from the FE analyses are compared against the experimental results and are found to show a close agreement. Using the validated FE models, detailed parametric studies are conducted to determine the effectiveness of different design parameters such as (a) ECC height replacement for a reinforcement ratio, (b) reinforcement ratio for an ECC height replacement, and (c) adequate reinforcement ratio for effective strengthening. The results of the parametric study show that the use of 0.4 ECC height replacement ratio and 1.70% steel reinforcement ratio exhibit better load‐carrying capacity in ECC–concrete composite beams. The effective tensile reinforcement ratio for the ECC–concrete composite beams from minimum to maximum varies in the range of 0.92%–1.85%, respectively. The moment capacities predicted from the section analysis is in good agreement with the experimental and numerical moment capacities.
Effect of terminal heat stress on osmolyte accumulation and gene expression during grain filling in bread wheat (Triticum aestivum L.)
Authors: Sihag Pooja , Kumar Upendra , Sagwal Vijeta , Kapoor Prexha , Singh Yogita , Mehla Sheetal , Balyan Priyanka , Mir Reazul Rouf , Varshney Rajeev K. , Singh Krishna Pal , Dhankher Om Parkash
Published: February 2023

The grain‐filling stage in Triticum aestivum (wheat) is highly vulnerable to increasing temperature as terminal heat stress diminishes grain quality and yield. To examine the mechanism of terminal heat tolerance, we performed the biochemical and gene expression analyses using two heat‐tolerant (WH730 and WH1218) and two heat‐sensitive (WH711 and WH157) wheat genotypes. We observed a significant increase in total soluble sugar (25%–47%), proline (7%–15%), and glycine betaine (GB) (22%–34%) contents in flag leaf, whereas a decrease in grain‐filling duration, 1000‐kernel weight (8%–25%), and grain yield per plant (11%–23%) was observed under the late‐sown compared to the timely sown. The maximum content of osmolytes, including total soluble sugar, proline, and GB, was observed in heat‐tolerant genotypes compared to heat‐sensitive genotypes. The expression of 10 heat‐responsive genes associated with heat shock proteins (sHsp‐1, Hsp17, and HsfA4), flavonoid biosynthesis (F3′‐1 and PAL), β‐glucan synthesis (CslF6 and CslH), and xyloglucan metabolism (XTH1, XTH2, and XTH5) was studied in flag leaf exposed to different heat treatments (34, 36, 38, and 40°C) at 15 days after anthesis by quantitative real‐time polymerase chain reaction. A significant increase in the relative fold expression of these genes with increasing temperature indicated their involvement in providing heat‐stress tolerance. The high differential expression of most of the genes in heat‐tolerant genotype “WH730” followed by “WH1218” indicates the high adaptability of these genotypes to heat stress compared to heat‐sensitive wheat genotypes. Based on the previous results, “WH730” performed better in terms of maximum osmolyte accumulation, grain yield, and gene expression under heat stress.
X‐ray computed microtomography time‐dependent analysis of sandwich bread in different storage conditions
Authors: de Lima João Carlos R. , de Araújo Olga M. O. , de Sá Silva Aline S. , Bastos Luan F. , Machado Alessandra S. , Oliveira Davi F. , Lopes Ricardo T.
Published: February 2023

Bread is one of the oldest foods of mankind, and among them, the sandwich bread is worldwide known and used. In this study we used the non‐destructive computed microtomography technique (microCT) to evaluate the behavior of bread structure over weeks after the production. In addition, the influence of the storage location of the sandwich bread, we performed a comparative analysis between storage at ambient temperature and refrigerated conditions. The analysis of the reconstructed images shows that the bread suffers loss of structure over the weeks. We also have found that keeping the bread refrigerated loses liquid, drying the bread, and thus increasing the loss of its structure. In addition, the porous structure of the bread was evaluated, and a complete characterization of the microstructural changes was performed over time.
Construction of the advanced flavin mononucleotide producers in the flavinogenic yeast Candida famata
Authors: Fedorovych Dariya V. , Tsyrulnyk Andriy O. , Ruchala Justyna , Sobchuk Svitlana M. , Dmytruk Kostyantyn V. , Fayura Lyubov R. , Sibirny Andriy A.
Published: February 2023

Flavin mononucleotide (FMN, riboflavin‐5′‐phosphate) is flavin coenzyme synthesized in all living organisms from riboflavin (vitamin B2) after phosphorylation in the reaction catalyzed by riboflavin kinase. FMN has several applications mostly as yellow colorant in food industry due to 200 times better water solubility as compared to riboflavin. Currently, FMN is produced by chemical phosphorylation of riboflavin, however, final product contains up to 25% of flavin impurities. Microbial overproducers of FMN are known, however, they accumulate this coenzyme in glucose medium. Current work shows that the recombinant strains of the flavinogenic yeast Candida famata with overexpressed FMN1 gene coding for riboflavin kinase in the recently isolated by us advanced riboflavin producers due to overexpression of the structural and regulatory genes of riboflavin synthesis and of the putative exporter of riboflavin from the cell, synthesized elevated amounts of FMN in the media not only with glucose but also in lactose and cheese whey. Activation of FMN accumulation on lactose and cheese whey was especially strong in the strains which expressed the gene of transcription activator SEF1 under control of the lactose‐induced LAC4 promoter. The accumulation of this coenzyme by the washed cells of the best recombinant strain achieved 540 mg/L in the cheese whey supplemented only with ammonium sulfate during 48 h in shake flask experiments.
No invariant perfect qubit codes
Authors: Mansuroglu Refik , Sahlmann Hanno
Published: February 2023

Abstract

Perfect tensors describe highly entangled quantum states that have attracted particular attention in the fields of quantum information theory and quantum gravity. In loop quantum gravity, the natural question arises whether SU(2) invariant tensors, which are fundamental ingredients of the basis states of spacetime, can also be perfect. In this work, we present a number of general constraints for the layout of such invariant perfect tensors (IPTs) and further describe a systematic and constructive approach to check the existence of an IPT of given valence. We apply our algorithm to show that no qubit encoding of valence 6 can be described by an IPT and close a gap to prove a no-go theorem for invariant perfect qubit encodings. We also provide two alternative proofs for the non-existence of 4-valent qubit IPTs which has been shown in [1, 2].
The two-loop eight-point amplitude in ABJM theory
Authors: He Song , Huang Yu-tin , Kuo Chia-Kai , Li Zhenjie
Published: February 2023

Abstract

In this paper, we present the two-loop correction to scattering amplitudes in three-dimensional $$ \mathcal{N} $$
N
= 6 Chern-Simons matter theory. We use the eight-point case as our main example, but the method generalizes to all multiplicities. The integrand is completely fixed by dual conformal symmetry, maximal cuts, constraints from soft-collinear behavior, and from the vanishing of odd-multiplicity amplitudes. After performing integrations with Higgs regularizations, the integrated results demonstrate that the infrared divergence is again identical to that of $$ \mathcal{N} $$
N
= 4 super Yang-Mills. After subtracting divergences, the finite part is dual conformal invariant, and respects various symmetries; it has uniform transcendentality weight two and exhibits a nice analytic structure.
Delicate windows into evaporating black holes
Authors: Craps Ben , Hernandez Juan , Khramtsov Mikhail , Knysh Maria
Published: February 2023

Abstract

We revisit the model of an AdS2 black hole in JT gravity evaporating into an external bath. We study when, and how much, information about the black hole interior can be accessed through different portions of the Hawking radiation collected in the bath, and we obtain the corresponding full quantitative Page curves. As a refinement of previous results, we describe the island phase transition for a semi-infinite segment of radiation in the bath, establishing access to the interior for times within the regime of applicability of the model. For finite-size segments in the bath, one needs to include the purifier of the black hole microscopic dual together with the radiation segment in order to access the interior information. We identify four scenarios of the entropy evolution in this case, including a possibility where the interior reconstruction window is temporarily interrupted. Analyzing the phase structure of the Page curve of a finite segment with length comparable to the Page time, we demonstrate that it is very sensitive to changes of the parameters of the model. We also discuss the evolution of the subregion complexity of the radiation during the black hole evaporation.
Noise-induced periodicity in a frustrated network of interacting diffusions
Authors: Marini Elisa , Andreis Luisa , Collet Francesca , Formentin Marco
Published: February 2023

We investigate the emergence of a collective periodic behavior in a frustrated network of interacting diffusions. Particles are divided into two communities depending on their mutual couplings. On the one hand, both intra-population interactions are positive; each particle wants to conform to the average position of the particles in its own community. On the other hand, inter-population interactions have different signs: the particles of one population want to conform to the average position of the particles of the other community, while the particles in the latter want to do the opposite. We show that this system features the phenomenon of noise-induced periodicity: in the infinite volume limit, in a certain range of interaction strengths, although the system has no periodic behavior in the zero-noise limit, a moderate amount of noise may generate an attractive periodic law.
Zukunftstrends und Einsatzmöglichkeiten digitaler Technologien in der settingbezogenen Prävention und Gesundheitsförderung – eine Delphi-Befragung
Authors: Stark Anna Lea , Albrecht Joanna , Dongas Eleana , Choroschun Katharina , Dockweiler Christoph
Published: February 2023

Hintergrund

Digitale Technologien zeigen ein hohes Nutzenpotenzial für die Gesundheitsförderung und Prävention, eine Analyse entlang der Planungs‑, Umsetzungs- und Evaluationsphasen von settingbasierter Gesundheitsförderung erfolgte bisher nicht. Auch ist noch unklar, inwiefern digitale Technologien Partizipation, Partnerschaften, Empowerment und Gerechtigkeit in Settings fördern.

Ziel

Die vorliegende Studie zielt auf die Erschließung künftiger Trends und Einsatzmöglichkeiten von Technologien entlang der Phasen settingbasierter Gesundheitsförderung in den nächsten 5 Jahren. Weiter wird der Technologieeinsatz zur Schaffung von Partizipation, Partnerschaften, Empowerment und Gerechtigkeit in Settings diskutiert und Unterschiede in Prognosen zwischen Expert*innen aus Wissenschaft und Praxis werden aufgezeigt.

Methode

Es erfolgte eine 2‑stufige webbasierte Delphi-Befragung von Expert*innen der settingbezogenen Gesundheitsförderung/Prävention. Offene Fragen wurden inhaltsanalytisch ausgewertet, geschlossene Fragen quantitativ.

Ergebnisse

Die digitale Transformation wird laut Expert*innen (N = 42, vollständige Teilnahme erste Befragungsrunde) in den nächsten 5 Jahren zunehmend Einzug in die verschiedenen Prozessphasen halten. Insbesondere Technologien zur Verhaltensänderung in Hybridformaten werden erwartet. Der Technologieeinsatz kann künftig einerseits zu mehr Partizipation, Partnerschaften, Empowerment und Gerechtigkeit in Settings führen, andererseits aber auch Exklusion und Ungerechtigkeit verstärken, wenn keine geeigneten Rahmenbedingungen vorliegen.

Diskussion

Es bedarf der Forschung zu verhältnispräventiven Technologien. Der Ausbau digitaler Kompetenzen und Infrastrukturen in Settings ist nötig, damit die Entwicklung gesundheitsfördernder Settings digital unterstützt werden kann.
Human–machine coordination in mixed traffic as a problem of Meaningful Human Control
Authors: Mecacci Giulio , Calvert Simeon C. , Santoni de Sio Filippo
Published: February 2023

The urban traffic environment is characterized by the presence of a highly differentiated pool of users, including vulnerable ones. This makes vehicle automation particularly difficult to implement, as a safe coordination among those users is hard to achieve in such an open scenario. Different strategies have been proposed to address these coordination issues, but all of them have been found to be costly for they negatively affect a range of human values (e.g. safety, democracy, accountability…). In this paper, we claim that the negative value impacts entailed by each of these strategies can be interpreted as lack of what we call Meaningful Human Control over different parts of a sociotechnical system. We argue that Meaningful Human Control theory provides the conceptual tools to reduce those unwanted consequences, and show how “designing for meaningful human control” constitutes a valid strategy to address coordination issues. Furthermore, we showcase a possible application of this framework in a highly dynamic urban scenario, aiming to safeguard important values such as safety, democracy, individual autonomy, and accountability. Our meaningful human control framework offers a perspective on coordination issues that allows to keep human actors in control while minimizing the active, operational role of the drivers. This approach makes ultimately possible to promote a safe and responsible transition to full automation.
Case Studies in the Assessment of Microbial Fitness: Seemingly Subtle Changes Can Have Major Effects on Phenotypic Outcomes
Authors: Worthan Sarah B. , McCarthy Robert D. P. , Behringer Megan G.
Published: February 2023

Following the completion of an adaptive evolution experiment, fitness evaluations are routinely conducted to assess the magnitude of adaptation. In doing so, proper consideration should be given when determining the appropriate methods as trade-offs may exist between accuracy and throughput. Here, we present three instances in which small changes in the framework or execution of fitness evaluations significantly impacted the outcomes. The first case illustrates that discrepancies in fitness conclusions can arise depending on the approach to evaluating fitness, the culture vessel used, and the sampling method. The second case reveals that variations in environmental conditions can occur associated with culture vessel material. Specifically, these subtle changes can greatly affect microbial physiology leading to changes in the culture pH and distorting fitness measurements. Finally, the last case reports that heterogeneity in CFU formation time can result in inaccurate fitness conclusions. Based on each case, considerations and recommendations are presented for future adaptive evolution experiments.
Loss of Heterozygosity and Its Importance in Evolution
Authors: Smukowski Heil Caiti
Published: February 2023

Loss of heterozygosity (LOH) is a mitotic recombination event that converts heterozygous loci to homozygous loci. This mutation event is widespread in organisms that have asexual reproduction like budding yeasts, and is also an important and frequent mutation event in tumorigenesis. Mutation accumulation studies have demonstrated that LOH occurs at a rate higher than the point mutation rate, and can impact large portions of the genome. Laboratory evolution experiments of heterozygous yeasts have revealed that LOH often unmasks beneficial recessive alleles that can confer large fitness advantages. Here, I highlight advances in understanding dominance, fitness, and phenotypes in laboratory evolved heterozygous yeast strains. I discuss best practices for detecting LOH in intraspecific and interspecific evolved clones and populations. Utilizing heterozygous strain backgrounds in laboratory evolution experiments offers an opportunity to advance our understanding of this important mutation type in shaping adaptation and genome evolution in wild, domesticated, and clinical populations.
Role of T cells in severe COVID-19 disease, protection, and long term immunity
Authors: Hermens Julia Maret , Kesmir Can
Published: February 2023

Infection with SARS-CoV-2 causes wide range of disease severities from asymptomatic to life-threatening disease. Understanding the contribution of immunological traits in immunity against SARS-CoV-2 and in protection against severe COVID-19 could result in effective measures to prevent development of severe disease. While the role of cytokines and antibodies has been thoroughly studied, this is not the case for T cells. In this review, the association between T cells and COVID-19 disease severity and protection upon reexposure is discussed. While infiltration of overactivated cytotoxic T cells might be harmful in the infected tissue, fast responding T cells are important in the protection against severe COVID-19. This protection could even be viable in the long term as long-living memory T cells seem to be stabilized and mutations do not appear to have a large impact on T cell responses. Thus, after vaccination and infections, memory T cells should be able to help prevent onset of severe disease for most cases. Considering this, it would be useful to add N or M proteins in vaccinations, alongside the S protein which is currently used, as this results in a broader T cell response.
Simulating cookiecutter shark bites with a 3D-printed jaw-dental model
Authors: Grace Mark A. , Huber Daniel , Travis Kevin , Doosey Michael H. , Ford Jonathan , Decker Summer , Mann Justin
Published: February 2023

Ectoparasitic cookiecutter sharks (Chondrichthyes: Squaliformes: Dalatiidae; Isistius) share common features for jaw and teeth structure, in particular, robust lower jaws and dignathic heterodonty (upper teeth crowns are more slender and shorter than the broader and longer lower teeth crowns). The jaws and teeth are well suited for feeding by excising a nearly symmetrical oval-flesh bite plug from a variety of prey species including marine mammals, fishes, and squids. There is considerable speculation regarding cookiecutter shark bite dynamics given that natural feeding behavior has not been observed. To elucidate cookiecutter shark bite dynamics, bites were experimentally simulated for the two cookiecutter shark species; the Cookiecutter Shark, Isistius brasiliensis (Quoy JRC, Gaimard, P (1824) Zoologie (3) Imprimerie royale) and the Largetooth Cookiecutter Shark, Isistius plutodus (Garrick JAF, Springer S (1964) Isistius plutodus, a new squaloid shark from the Gulf of Mexico. Copeia 678–682), using three-dimensional printed models of jaws with teeth. Bite simulations were conducted at standardized jaw bite-gape angles and ballistic gelatin was used to approximate prey flesh, from which aspect ratio analysis of bite wound geometrics was used to determine bite wound morphometrics for each species. The simulated bite experiment also was useful for assessing factors that potentially affect cookiecutter shark total length estimates when based on natural bite geometrics. In addition, the mechanics of producing experimental bites provide new insights related to the necessity for cookiecutter sharks to rotate their body to create nearly symmetrical oval bite wounds.
Scope actuation system for articulated laparoscopes
Authors: Abdurahiman Nihal , Khorasani Mohammad , Padhan Jhasketan , Baez Victor M. , Al-Ansari Abdulla , Tsiamyrtzis Panagiotis , Becker Aaron T. , Navkar Nikhil V.
Published: February 2023

Background

An articulated laparoscope comprises a rigid shaft with an articulated distal end to change the viewing direction. The articulation provides improved navigation of the operating field in confined spaces. Furthermore, incorporation of an actuation system tends to enhance the control of an articulated laparoscope.

Methods

A preliminary prototype of a scope actuation system to maneuver an off-the-shelf articulated laparoscope (EndoCAMaleon by Karl Storz, Germany) was developed. A user study was conducted to evaluate this prototype for the surgical paradigm of video-assisted thoracic surgery. In the study, the subjects maneuvered an articulated scope under two modes of operation: (a) actuated mode where an operating surgeon maneuvers the scope using the developed prototype and (b) manual mode where a surgical assistant directly maneuvers the scope. The actuated mode was further assessed for multiple configurations based on the orientation of the articulated scope at the incision.

Results

The data show the actuated mode scored better than the manual mode on all the measured performance parameters including (a) total duration to visualize a marked region, (a) duration for which scope focus shifts outside a predefined visualization region, and (c) number of times for which scope focus shifts outside a predefined visualization region. Among the different configurations tested using the actuated mode, no significant difference was observed.

Conclusions

The proposed articulated scope actuation system facilitates better navigation of an operative field as compared to a human assistant. Secondly, irrespective of the orientation in which an articulated scope’s shaft is inserted through an incision, the proposed actuation system can navigate and visualize the operative field.
Reallocating sedentary time to physical activity: effects on fatigue and quality of life in patients with breast cancer in the Phys-Can project
Authors: Mazzoni Anne-Sophie , Strandberg Emelie , Börjeson Sussanne , Sjövall Katarina , Berntsen Sveinung , Demmelmaier Ingrid , Nordin Karin
Published: February 2023

Purpose

We aimed to investigate the effects of reallocating sedentary time to an equal amount of light (LPA) or moderate-to-vigorous intensity physical activity (MVPA) on cancer-related fatigue and health-related quality of life (HRQoL) in patients with breast cancer. We also aimed to determine the daily amount of sedentary time needed to be reallocated to LPA or MVPA to produce minimal clinically important changes in these outcomes.

Methods

Pooled baseline data from three studies were used, including women with breast cancer who participated in the Phys-Can project. Fatigue was assessed with the Multidimensional Fatigue Inventory questionnaire (MFI; five dimensions, 4–20 scale) and HRQoL with the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30; 0–100 scale). Sedentary time and physical activity were measured with accelerometry. Isotemporal substitution modelling was used for the analyses.

Results

Overall, 436 participants (mean age 56 years, fatigue 11 [MFI], HRQoL 66 [EORTC QLQ-C30], LPA 254 min/day, MVPA 71 min/day) were included. Fatigue significantly decreased in two MFI dimensions when reallocating 30 min/day of sedentary time to LPA: reduced motivation and reduced activity (β =  − 0.21). Fatigue significantly decreased in three MFI dimensions when reallocating 30 min/day of sedentary time to MVPA: general fatigue (β =  − 0.34), physical fatigue (β =  − 0.47) and reduced activity (β =  − 0.48). To produce minimal clinically important changes in fatigue (− 2 points on MFI), the amount of sedentary time needed to be reallocated to LPA was ≈290 min/day and to MVPA was ≥ 125 min/day. No significant effects were observed on HRQoL when reallocating sedentary time to LPA or MVPA.

Conclusions

Our results suggest that reallocating sedentary time to LPA or MVPA has beneficial effects on cancer-related fatigue in patients with breast cancer, with MVPA having the greatest impact. In relatively healthy and physically active breast cancer populations, a large amount of time reallocation is needed to produce clinically important changes. Future studies are warranted to evaluate such effects in broader cancer populations.

Trial registration: NCT02473003 (10/10/2014) and NCT04586517 (14/10/2020).
Prediction of successful revision surgery for mesh-related complaints after inguinal hernia and pelvic organ prolapse repair
Authors: Van Rest K. L. C. , Gielen M. J. C. A. M. , Warmerdam L. M. , Kowalik C. R. , Roovers J. P. W. R. , Zwaans W. A. R.
Published: February 2023

Purpose

With this retrospective case series, we aim to identify predictors for reduction of pain after mesh revision surgery in patients operated for inguinal hernia or pelvic organ prolapse with a polypropylene implant. Identifying these predictors may aid surgeons to counsel patients and select appropriate candidates for mesh revision surgery.

Methods

Clinical records before and after mesh revision surgery from 221 patients with chronic postoperative inguinal pain (CPIP) and 59 patients with pain after pelvic organ prolapse (POP) surgery were collected at two experienced tertiary referral centers. Primary outcome was patient reported improvement of pain after revision surgery. A multivariable logistic regression model was used to specify predictors for pain reduction.

Results

The multivariable logistic regression was performed for each patient group separately. Patients with CPIP had higher chances of improvement of pain when time between mesh placement and mesh revision surgery was longer, with an OR of 1.19 per year. A turning point in chances of risks and benefits was demonstrated at 70 months, with improved outcomes for patients with revision surgery ≥ 70 months (OR 2.86). For POP patients, no statistically significant predictors for reduction of pain after (partial) removal surgery could be identified.

Conclusion

A longer duration of at least 70 months between implantation of inguinal mesh and revision surgery seems to give a higher chance on improvement of pain. Caregivers should not avoid surgery based on a longer duration of symptoms when an association between symptoms and the location of the mesh is found.
Constrained composite optimization and augmented Lagrangian methods
Authors: De Marchi Alberto , Jia Xiaoxi , Kanzow Christian , Mehlitz Patrick
Published: February 2023

We investigate finite-dimensional constrained structured optimization problems, featuring composite objective functions and set-membership constraints. Offering an expressive yet simple language, this problem class provides a modeling framework for a variety of applications. We study stationarity and regularity concepts, and propose a flexible augmented Lagrangian scheme. We provide a theoretical characterization of the algorithm and its asymptotic properties, deriving convergence results for fully nonconvex problems. It is demonstrated how the inner subproblems can be solved by off-the-shelf proximal methods, notwithstanding the possibility to adopt any solvers, insofar as they return approximate stationary points. Finally, we describe our matrix-free implementation of the proposed algorithm and test it numerically. Illustrative examples show the versatility of constrained composite programs as a modeling tool and expose difficulties arising in this vast problem class.
Supply chain integration in mass customization
Authors: Shen Bin , Zhang Jianing , Cheng Ming , Guo Shu , He Renlong
Published: February 2023

New technology such as 3D printing, robotic manufacturing, and the Internet of things can shorten the production time of mass customization (MC) products, enhance the self-design fun of consumers, and improve channel integration connectivity. In this study, we examine the impact of MC waiting time and self-design fun from the purchase of MC products on supply chain integration. We consider a supply chain consisting of one manufacturer, one retailer, and one customizer. The manufacturer produces and sells standardized products through the retailer, whereas the customizer sells customized products to consumers directly. The customizer can decide whether to integrate with the manufacturer (i.e., manufacturer–customizer integration) or with the retailer (i.e., retailer–customizer integration). We find that manufacturer–customizer integration can achieve a win–win–win outcome for all three supply chain members when the MC waiting time is within a moderate range and the probability of consumers being satisfied with the product quality is high, but retailer–customizer integration cannot achieve such an outcome, as the manufacturer will not be benefited if it does not participate in the integration. Furthermore, integration reduces the customizer’s investment in the level of self-design fun, which implies that the negative effect owing to the low level of self-design fun in the supply chain integration can be compensated by the competition mitigation effect owing to supply chain integration. With endogenized self-design fun, the achievability of a win–win–win outcome for all three supply chain members in the manufacturer–customizer integration will remain unchanged.
Sleep-Directed Hypnosis Improves Subjective Sleep Quality but not Extinction Memory After Exposure to Analog Trauma
Authors: Friesen Edith , Sopp M. Roxanne , Cordi Maren J. , Rasch Björn , Michael Tanja
Published: February 2023

Background

Evidence-based treatments of posttraumatic stress disorder (PTSD) aim to promote fear extinction learning. Post-learning sleep, particularly slow wave sleep (SWS), promotes memory consolidation and recall. Thus, boosting SWS might strengthen extinction recall. The current study investigated whether sleep-directed hypnosis designed to increase SWS and sleep quality improves extinction recall and reduces analog PTSD symptoms.

Method

In two subsamples (remote/laboratory), 211 healthy individuals underwent fear conditioning with a traumatic film clip. On the next evening, they underwent extinction training. Thereafter, the experimental group received sleep-directed hypnosis, whereas the control group listened to a control text. Extinction recall and generalization and film-related intrusions and rumination were assessed on the following morning.

Results

Subjective sleep quality declined following exposure to an aversive film. No group differences were found in SWS though exploratory analyses indicated less rapid eye movement sleep after hypnosis. After hypnosis, the experimental group reported improved sleep quality, whereas the control group showed a further deterioration. Hypnosis had no effects on extinction retention and generalization nor on analog intrusions and rumination.

Conclusion

The current results indicate that sleep-directed hypnosis may be beneficial for improving subjective sleep quality after trauma but not for enhancing extinction memory and reducing analog PTSD symptoms.
Stress-Related Exhaustion, Polygenic Cognitive Potential, and Cognitive Test Performance – A General Population Study
Authors: Ketvel Laila , Keltikangas-Järvinen Liisa , Pahkala Katja , Juonala Markus , Ahola-Olli Ari , Lehtimäki Terho , Viikari Jorma , Raitakari Olli , Rovio Suvi , Saarinen Aino
Published: February 2023

Background

We investigated whether stress-related exhaustion (chronic or short-term, and co-occurring with depression or not) is related to cognitive performance and whether polygenic cognitive potential modifies these associations.

Methods

The participants were from the Young Finns Study (N = 541–1273). Stress-related exhaustion was assessed using the Maastricht Questionnaire, depressive symptoms with the Beck Depression Inventory, and cognitive performance with subtests of the Cambridge Neuropsychological Test Automated Battery, measuring visuospatial learning, reaction time, sustained attention, and executive function. Cognitive performance and depression were assessed in 2011, and exhaustion in 2001, 2007, and 2011. A polygenic score for cognitive potential was calculated based on a GWAS on intelligence.

Results

High stress-related exhaustion, especially chronic, was associated with slower reaction time. Only clinical levels of depression were related to slower reaction time. Polygenic cognitive potential did not modify these associations. There were no differences in cognitive performance between individuals with co-occurring exhaustion and depression vs. those with only either condition.

Conclusion

Stress-related exhaustion, especially if chronic, seems to relate to slower reactions. Co-occurring exhaustion and depression may not have additive effects on cognitive performance. High polygenic cognitive potential may not protect from or predispose to harmful effects of exhaustion or depression on reaction time.
Progress on Levitating a Sphere in Cryogenic Fluids
Authors: Arrayás M. , Bettsworth F. , Haley R. P. , Schanen R. , Trueba J. L. , Uriarte C. , Zavjalov V. V. , Zmeev D. E.
Published: February 2023

We present the working prototype of a levitation system designed for investigation of flows in cryogenic helium fluids. The current device allows the levitation of a superconducting sphere and has several provisions made for allowing precise control over its motion. We report on progress in the detection and control systems of the prototype and demonstrate how uniform circular motion can be implemented.
A Dutch Study of Remarkable Recoveries After Prayer: How to Deal with Uncertainties of Explanation
Authors: Bendien Elena , Kruijthoff Dirk J. , van der Kooi Cornelis , Glas Gerrit , Abma Tineke
Published: February 2023

This article addresses cases of remarkable recoveries related to healing after prayer. We sought to investigate how people who experienced remarkable recoveries re-construct and give meaning to these experiences, and examine the role that epistemic frameworks available to them, play in this process. Basing ourselves on horizontal epistemology and using grounded theory, we conducted this qualitative empirical research in the Netherlands in 2016–2021. It draws on 14 in-depth interviews. These 14 cases were selected from a group of 27 cases, which were evaluated by a medical assessment team at the Amsterdam University Medical Centre. Each of the participants had experienced a remarkable recovery during or after prayer. The analysis of the interviews, which is based on the grounded theory approach, resulted in three overarching themes, placing possible explanations of the recoveries within (1) the medical discourse, (2) biographical discourse, and (3) a discourse of spiritual and religious transformation. Juxtaposition of these explanatory frameworks provides a way to understand better the transformative experience that underlies remarkable recoveries. Uncertainty regarding an explanation is a component of knowing and can facilitate a dialogue between various domains of knowledge.
Rectal use of levetiracetam: best practice report for a stepwise approach for sustainable off-label decision making and treatment
Authors: Rémi Constanze , Hermann Alina , Krull Elisabeth , Ockert-Schön Franziska , Rémi Jan
Published: February 2023

Off-label drug use is common practice in palliative care. It may pose a risk to the patient and benefit should outweigh harm. A decision and documentation aid for off-label use was developed to support practitioners in clinical practice off-label use. Using the example of the rectal administration of levetiracetam in three patient cases, the utilisation and benefits of the decision and documentation aid are presented and discussed. The rectal administration of levetiracetam clearly is an experimental treatment approach with little underlying evidence. To support and document the decision-making process for or against such an off-label use in clinical practice, it is helpful to have a structured approach in order to make this data comprehensible for a later point in time. Off-label use may be a permissible treatment alternative without underlying evidence, provided it takes place in a well-planned and well-monitored therapeutic setting and the benefits outweigh the potential risks.
A fast epigraph and hypograph-based approach for clustering functional data
Authors: Pulido Belén , Franco-Pereira Alba M. , Lillo Rosa E.
Published: February 2023

Clustering techniques for multivariate data are useful tools in Statistics that have been fully studied in the literature. However, there is limited literature on clustering methodologies for functional data. Our proposal consists of a clustering procedure for functional data using techniques for clustering multivariate data. The idea is to reduce a functional data problem into a multivariate one by applying the epigraph and hypograph indexes to the original curves and to their first and/or second derivatives. All the information given by the functional data is therefore transformed to the multivariate context, being informative enough for the usual multivariate clustering techniques to be efficient. The performance of this new methodology is evaluated through a simulation study and is also illustrated through real data sets. The results are compared to some other clustering procedures for functional data.