bluuebunny/crossref_metadata_2025 huggingface dataset:
Berberine nanostructures attenuate ß-catenin, a key component of epithelial mesenchymal transition in lung adenocarcinoma
Authors: Malyla Vamshikrishna , De Rubis Gabriele , Paudel Keshav Raj , Chellappan Dinesh Kumar , Hansbro Nicole G. , Hansbro Philip M. , Dua Kamal
Published: June 2023

Lung cancer (LC) is the leading cause of cancer-related deaths globally. It accounts for more than 1.9 million cases each year due to its complex and poorly understood molecular mechanisms that result in unregulated cell proliferation and metastasis. β-Catenin is a developmentally active protein that controls cell proliferation, metastasis, polarity and cell fate during homeostasis and aids in cancer progression via epithelial–mesenchymal transition. Therefore, inhibition of the β-catenin pathway could attenuate the progression of LC. Berberine, an isoquinoline alkaloid which is known for its anti-cancer and anti-inflammatory properties, demonstrates poor solubility and bioavailability. In our study, we have encapsulated berberine into liquid crystalline nanoparticles to improve its physiochemical functions and studied if these nanoparticles target the β-catenin pathway to inhibit the human lung adenocarcinoma cell line (A549) at both gene and protein levels. We observed for the first time that berberine liquid crystalline nanoparticles at 5 µM significantly attenuate the expression of the β-catenin gene and protein. The interaction between berberine and β-catenin was further validated by molecular simulation studies. Targeting β-catenin with berberine nanoparticles represents a promising strategy for the management of lung cancer progression.
Comparison of quantitative FDG-PET and MRI in anti-LGI1 autoimmune encephalitis
Authors: Sadaghiani Mohammad S. , Roman Samantha , Diaz-Arias Luisa A. , Habis Ralph , Venkatesan Arun , Probasco John C. , Solnes Lilja B.
Published: June 2023

Objectives

Anti-leucine glioma-inactivated protein 1 (anti-LGI1) autoimmune encephalitis (AE) presents as subacute memory loss, behavioral changes, and seizures. Diagnosis and treatment delays can result in long term sequelae, including cognitive impairment. 18F-FDG PET/CT may be more sensitive than MRI in patients with AE. Our objective was to determine if anti-LGI1 is associated with a distinct pattern of FDG uptake and whether this pattern persists following treatment.

Methods

Nineteen18F-FDG PET/CT brain scans (13 pre-treatment, 6 convalescent phase) for 13 patients with anti-LGI1 were studied using NeuroQ™ and CortexID™. The sensitivity of the PET images was compared to MRI. The Z scores of 47 brain regions between the pre-treatment and next available follow-up images during convalescence were compared.

Results

All 18F-FDG PET/CT scans demonstrated abnormal FDG uptake, while only 6 (42.9%) pre-treatment brain MRIs were abnormal. The pre-treatment scans demonstrated hypermetabolism in the bilateral medial temporal cortices, basal ganglia, brain stem, and cerebellum and hypometabolism in bilateral medial and mid frontal, cingulate, and parietotemporal cortices. Overall, the brain uptake during convalescence showed improvement of the Z scores towards 0 or normalization of previous hypometabolic activity in medial frontal cortex, inferior frontal cortex, Broca’s region, parietotemporal cortex, and posterior cingulate cortex and previous hypermetabolic activity in medial temporal cortices, caudate, midbrain, pons and cerebellum.

Conclusions

Brain FDG uptake was more commonly abnormal than MRI in the pre-treatment phase of anti-LGI1, and patterns of dysmetabolism differed in the pre-treatment and convalescent phases. These findings may expedite the diagnosis, treatment, and monitoring of anti-LGI1 patients.
Habitat quality affects the social organization in mouse lemurs (Microcebus griseorufus)
Authors: Abel Christoph , Giertz Peggy , Ratovonamana Yedidya R. , Püttker Thomas , Rakotondranary S. Jacques , Scheel Bettina M. , Lenz Tobias L. , Ganzhorn Jörg U.
Published: June 2023

Species can either maintain a certain social organization in different habitats or show different social organizations in similar habitats. The reasons underlying this variability are not always clear but might have consequences for population dynamics, especially under changing environmental conditions. Among mammals, the primate genus Microcebus lives in small groups of closely related females, derived from female philopatry and dispersed males, as illustrated by the well-studied Microcebus murinus. Here, we studied the genetic structure of a population of the congeneric Microcebus griseorufus, inhabiting three adjacent habitats with different resource availabilities. In order to learn more about the plasticity of the species’ social organization under these different conditions, we analyzed the spatial arrangement of mitochondrial haplotypes of 122 individuals. The study revealed high haplotype diversity and a pronounced difference in spatial distribution between the sexes. Females exhibited spatial aggregation of haplotypes, suggesting a system of female philopatry and matrilines, similar to M. murinus. Male haplotypes were dispersed, and males were more likely to carry rare haplotypes, indicating higher dispersal activity. These findings hint towards the unity of the social organization across the genus Microcebus, suggesting a phylogenetic origin of the social organization. Yet, with decreasing resources, the clustering of female haplotypes declined and approached a random distribution in the marginal habitat, with cluster sizes correlating with resource availability as predicted by the socioecological model. Our study supports the notion that social organization is shaped by both phylogenetic origin and ecological conditions, at least in these small primates.

Significance statement

Impacts of habitat degradation are mostly described in terms of changes in population densities in relation to the reduction of resources. This neglects the possible effects of altered social organizations due to declining resources or population densities. Using a genetic sampling of three subpopulations of mouse lemurs in Madagascar along a gradient of food availability up to the limit of the species’ ecological tolerance, we show that their social organization consisting of spatial clusters of closely related females and overdispersed males converges towards random spatial distributions of both sexes with declining food availability.
Lobectomy Versus Sublobar Resection in Simultaneous Bilateral Thoracoscopic Lung Resection
Authors: Liu Yu‐Wei , Wu Ming‐Ho , Kao Chieh‐Ni , Chiang Hung‐Hsing , Lee Jui‐Ying , Li Hsien‐Pin , Chang Po‐Chih , Chou Andre , Chou Shah‐Hwa
Published: June 2023

Background

Simultaneous bilateral thoracoscopic lung resection (SBTLR) has been shown to be a feasible and efficacious approach for a wide range of pulmonary conditions. Our aim was to evaluate the impact of different procedures on surgical outcomes in patients receiving SBTLR.

Methods

Between 2012 and 2021, 207 patients with bilateral lung neoplasms who underwent SBTLR were retrospectively reviewed. Fifty‐one patients received ipsilateral plus contralateral lobectomy or sublobectomy (lobar group), whilst 156 patients received bilateral sublobectomy (sublobar group). Propensity scores were calculated and matched. Perioperative and clinicopathologic outcomes were compared.

Results

The lobar group had a greater mean age (64.5 vs. 60.0 years, p = 0.008), longer operative time (254 vs. 205 min, p < 0.001), and more blood loss (74 vs. 46 ml,p < 0.001). The sublobar group had fewer complications (6.4 vs. 19.6%, p = 0.006), shorter hospital stay (4.8 vs. 7.4 days, p < 0.001), and lower hospital costs (p = 0.03). Among 50 pairs of matched groups, significant differences were found only in operative time, hospital stay, and costs. Maximum tumor size and pathological features differed significantly before and after matching (all p < 0.05), with the lobar group consistently demonstrating a larger main tumor (median, 2.5 cm) and a higher percentage of primary lung cancer (84%). Multivariate logistic regression analysis showed that a longer operative time was the factor associated with more complications (OR: 1.01; 95% CI 1.00–1.02, p = 0.002).

Conclusions

With regard to SBTLR, our data suggests that sublobectomy may reduce the prolonged recovery, hospital costs, and complications incurred by lobectomy, without compromising oncological outcomes.
Measurement of the turbulent heat fluxes in mixed convection using combined stereoscopic PIV and PIT
Authors: Mommert Michael , Niehaus Konstantin , Schiepel Daniel , Schmeling Daniel , Wagner Claus
Published: June 2023

The results of simultaneous measurements of velocity and temperature fields in a turbulent mixed convection airflow are analyzed and discussed. To access local temperature and velocity fields in airflows, we present a combination of stereoscopic particle image velocimetry and particle image thermometry. The obtained flow fields make it possible to determine the local convective heat fluxes, thus giving insight into the dynamics of plumes and Taylor–Görtler-like vortices. The evaluated mean local heat fluxes further reveal that the main convection roll transports a substantial amount of heat along the cooling plate and back to the heated bottom plate. Yet, the associated mean turbulent heat fluxes remain positive as they are dominated by the correlation of the temperature and the vertical velocity component. More specifically, a statistical analysis of the local heat flux distribution reveals that Taylor–Görtler-like vortices lead to more skewed distributions of the turbulent convective heat fluxes than plumes.

Graphical abstract
Incidence and associated morbidity of sarcopenia in non-malignant small and large bowel anastomosis: propensity score-matched analysis
Authors: Traeger Luke , Bedrikovetski Sergei , Nguyen Thuy-My , Moore James W. , Sammour Tarik
Published: June 2023

Purpose

Sarcopenia is a prognostic factor for poor outcomes in colorectal cancer, but data are scarce in colorectal surgery for benign conditions where patients could benefit from a deferral of surgery to enter a prehabilitation programme. We assessed the incidence of sarcopenia and complications in patients with benign colorectal disease.

Methods

Patients who underwent elective non-malignant colorectal surgery during 2018–2022 were retrospectively identified. The cross-sectional psoas area was calculated using computed tomography (CT) imaging mid-3rd lumbar vertebrae. Sarcopenia was determined using gender-specific cut-offs. The primary outcome was complications measured by the comprehensive complication index (CCI).

Results

Of 188 patients identified, 39 (20.7%) were sarcopenic. Patients diagnosed with sarcopenia were older (63 vs. 58 years, p = 0.047) and had a reduced BMI (24.7 vs. 27.38 kg/m2, p = 0.001). Sarcopenic patients had more complications (82.1 vs. 64.4%, p = 0.036), and CCI was statistically but not clinically higher (20.9 vs. 20.9, p = 0.047). On univariate linear regression analysis, age ≥ 65 years old, ASA grade ≥ 3, active smokers, sarcopenia, and preoperative anaemia were predictive of CCI. Propensity score-matched analysis was performed, matching 78 cases to remove selection bias, which demonstrated sarcopenia had no impact on postoperative complications. On multivariate analysis, age (p = 0.022), smoking (p = 0.005), and preoperative anaemia (p = 0.008) remained predictive of CCI.

Conclusion

Sarcopenia is prevalent in one-fifth of patients undergoing benign colorectal surgery. Taking advantage of the longer preoperative waiting periods, sarcopenia could be explored as a target for prehabilitation programmes to improve outcomes.
MRI surveillance after translabyrinthine vestibular schwannoma resection and cochlear implantation: is it feasible?
Authors: Dahm Valerie , Schwarz-Nemec Ursula , Arnoldner Michael A. , Liepins Rudolfs , Auinger Alice B. , Matula Christian , Arnoldner Christoph
Published: June 2023

Purpose

Cochlear implantation in patients with vestibular schwannomas is of increasing importance and interest. Two remaining challenges are the assessment of conduction of the cochlear nerve and the possibility of postoperative surveillance with magnetic resonance imaging. The aim of the current study was to assess follow-up imaging and determine the visibility of the internal auditory canal after vestibular schwannoma resection and cochlear implantation as well as in patients with persistent vestibular schwannomas and cochlear implants in place. Visibility of the internal auditory canal, cerebellopontine angle, and labyrinth were evaluated and graded.

Methods

For this retrospective study, 15 MR examinations of 13 patients after translabyrinthine vestibular schwannoma resection and ipsilateral cochlear implantation were included. All patients had been implanted with an MED-EL cochlear implant. Magnetic resonance imaging was carried out on a 1.5T device. All patients were prepped according to the manufacturer’s recommendations.

Results

All 15 examinations were carried out without any adverse event during imaging, such as pain, magnet dislocation, or malfunction. The internal auditory canal and the cerebellopontine angle were sufficiently visible in all cases to allow for vestibular schwannoma follow-up.

Conclusion

Magnetic resonance imaging surveillance of the internal auditory canal following vestibular schwannoma resection and cochlear implantation is feasible and safe with modern implants with a 1.5T magnetic resonance imaging device using metal artifact reduction sequences. Necessary follow-up imaging should not be a contraindication for cochlear implantation in patients with vestibular schwannomas.
Validity and reliability of the Niigata PPPD Questionnaire in a Western population
Authors: Castillejos-Carrasco-Muñoz Rodrigo , Peinado-Rubia Ana Belén , Lérida-Ortega Miguel Ángel , Ibáñez-Vera Alfonso Javier , Tapia-Toca María Cruz , Lomas-Vega Rafael
Published: June 2023

Purpose

To analyze the psychometric properties of the Niigata Questionnaire (NPQ) for use in a European population with persistent postural-perceptual dizziness (PPPD).

Methods

Observational study included 140 patients with different vestibular conditions. Construct validity, internal consistency and concurrent validity were analyzed. Intra-class correlation coefficient (ICC), standard error of measurement (SEM) and minimal detectable change (MDC) were calculated. Receiver operating characteristic (ROC) curve was used to test diagnostic values.

Results

Of the 140 patients, 47 had a diagnosis of PPPD. Factorial analysis showed a single-factor structure and concurrent validity analysis showed strong correlations with other instruments. Cronbach alpha coefficients of 0.938 for the total score, 0.869 for the standing and gait subscale, 0.803 for the subscale of movements and 0.852 for the visual stimulation subscale were obtained. The reproducibility was substantial except for the standing subscale, which could be considered moderate. For the standing, movement and visual stimulation subscales and for the total score, the SEM was 3.27, 2.41, 2.50 and 6.63, respectively, and the MDC was 6.40, 4.72, 4.91 and 12.99, respectively. The NPQ total score showed an area under the curve (AUC) of 0.661, a sensitivity of 72.34 and a specificity of 55.91 for discriminating between PPPD and other vestibular disorders.

Conclusions

The NPQ is feasible for use in a Western population and presents a uni-factorial structure, high internal consistency and strong correlation with other instruments. The reliability can be considered substantial. The NPQ has low accuracy in discriminating between subjects with or without PPPD.
Real-world patient-reported outcomes and concordance between patient and physician reporting of side effects across lines of therapy in multiple myeloma within the USA
Authors: Ribbands Amanda , Boytsov Natalie , Bailey Abigail , Gorsh Boris , Luke Emily , Lambert Annabel
Published: June 2023

Purpose

We aimed to explore patient-reported outcomes (PROs) and patient and physician concordance of side effects perception across lines of therapy (LOT) in multiple myeloma (MM) within the United States of America (USA).

Methods

Data were drawn from the Adelphi Real World MM III Disease Specific Programme™, a point-in-time survey of hemato-oncologists/hematologists and their patients with MM conducted in the USA between August 2020 and July 2021. Physicians reported patient characteristics and side effects. Patients reported side-effect bother and health-related quality of life (HRQoL) using validated PRO tools (European Organisation for the Research and Treatment of Cancer Quality of Life Core Questionnaire/-MM Module [EORTC QLQ-C30/-MY20], EQ-5D-3L and Functional Assessment of Cancer Therapy—General Population physical item 5). Descriptive, linear regression and concordance analyses were performed.

Results

Records from 63 physicians and 132 patients with MM were analyzed. EORTC QLQ-C30/-MY20 and EQ-5D-3L scores were consistent across LOTs. Scores tended to be worse with higher side-effect bother; patients “very much” bothered by side effects had lower median (interquartile range) global health status scores (33.3 [25.0–50.0]) than those “not at all” bothered (79.2 [66.7–83.3]). Patient and physician concordance on side-effect reporting was poor to fair. Patients frequently reported fatigue and nausea as bothersome side effects.

Conclusion

HRQoL of patients with MM was worse with greater side-effect bother. Discordant patient and physician reporting of side effects indicated a need for improved communication during management of MM.
Late Alpine multistage exhumation of the northwestern Rhodope Metamorphic Complex (northern Rila Mountains, Bulgaria)
Authors: Kounov Alexandre , Gerdjikov Ianko , Antić Milorad D. , Georgiev Neven , Spikings Richard A.
Published: June 2023

The Rhodope crystalline massif is an Alpine metamorphic complex exposed across several mountain ranges in southern Bulgaria and northern Greece which has experienced a complex history including continental collision, partial subduction and syn-metamorphic nappe stacking followed by syn- to post-contractional extension. We present new40Ar/39Ar and fission-track data from samples taken from both sides of the North Rhodopean Detachment that were combined with detailed structural studies to investigate the tectonothermal evolution of the northern Rila Mountains. A migmatite from the hanging wall of the North Rhodopean Detachment yields a40Ar/39Ar muscovite age of 100.79 ± 0.55 Ma, a zircon fission-track age of 38.6 ± 1.9 Ma, and an apatite fission-track age of 21.4 ± 1.5 Ma. A biotite schist from the footwall of the detachment yields40Ar/39Ar biotite age of 34.90 ± 0.15 Ma, and zircon and apatite fission-track ages of 35.6 ± 5.6 and 13.3 ± 1.1 Ma, respectively. Our new data give evidence of a multistage exhumation of the study area. Late Early Cretaceous (~ 101 ± 0.6 Ma) cooling of the Variscan high-grade metamorphic basement through 440–400 °C was caused by either erosion of the emplacing thrust sheet, or post-contractional denudation. Fast exhumation along the North Rhodopean Extensional System drove a pulse of increased tectonic denudation and cooling during the Eocene (39–35 Ma). Exhumation of the rocks in the northern part of the Rila Mountains below 110 ± 10 °C during the middle–late Miocene was associated with displacement along a system of normal faults.
The Nobel Prize of Physiology or Medicine, 1923: controversies on the discovery of the antidiabetic hormone
Authors: de Leiva-Hidalgo Alberto , de Leiva-Pérez Alejandra
Published: June 2023

Aims

To analyze the main contributions to the discovery of the antidiabetic hormone in the period between 1889, the year in which Oskar Minkowski demonstrated that complete pancreatectomy in dogs caused diabetes, and the year 1923, the date in which the clinical use of insulin was consolidated. A main objective has been to review the controversies that followed the Nobel Prize and to outline the role of the priority rule in Science.

Methods

We have considered the priority rule defined by Robert Merton in 1957, which takes into account the date of acceptance of the report of a discovery in an accredited scientific journal and/or the granting of a patent, complemented by the criteria set out by Ronald Vale and Anthony Hyman (2016) regarding the transfer of information to the scientific community and its validation by it. The awarding of the Nobel Prize in Physiology or Medicine in October 1923 has represented a frame of reference. The claims and disputes regarding the prioritization of the contributions of the main researchers in the organotherapy of diabetes have been analyzed through the study of their scientific production and the debate generated in academic institutions.

Main results and conclusions

(1) According to the criteria of Merton, Vale and Hyman, the priority of the discovery of the antidiabetic hormone corresponds to the investigations developed in Europe by E. Gley (1900), GL Zülzer (1908) and NC Paulescu (1920). (2) The active principle of the pancreatic extracts developed by Zülzer (acomatol), Paulescu (pancreina) and Banting and Best (insulin) was the same. (3) JB Collip succeeded in isolating the active ingredient from the pancreatic extract in January 1922, eliminating impurities to the point of enabling its use in the clinic. (4) In 1972, the Nobel Foundation modified the purpose of the 1923 Physiology or Medicine award to Banting and Macleod by introducing a new wording: "the credit for having produced the pancreatic hormone in a practical available form" (instead of “for the discovery of insulin”).
A report of short-term aversive conditioning on a wolf documented through telemetry
Authors: Zanni Michele , Brivio Francesca , Berzi Duccio , Calderola Sonia , Luccarini Siriano , Costanzi Liliana , Dartora Fabio , Apollonio Marco
Published: June 2023

Predation by large predators on livestock is one of the main concerns in species conservation as it elicits prompt and effective retaliations. Therefore, conflict mitigation is essential to ensure long-term coexistence of predators with humans. We performed aversive conditioning (AC) with rubber bullets on one collared wolf that had become particularly bold toward a transhumant shepherd and had preyed on livestock. By exploiting the unique fine-resolution location data available before and after the AC event, alongside careful retrospective field investigations, we were able to analyse the effects of AC on wolf behaviour. Our study revealed that after just a single AC event, the wolf modified its spatial and predatory behaviour: the wolf changed its use of space by increasing distance from humans and ceased to attack farms in the following 2 months; actually, the only livestock preyed after AC was represented by a sheep and two goats lost by shepherds that had left alpine pastures. This study represents a first step to increase knowledge on AC effect on the wolf. Additional researchers are encouraged to conduct and publish findings on this topic in order to provide a useful and widely tested array of tools to promote wolf conservation in human-dominated landscapes.
Comprehensive Analysis of TICRR in Hepatocellular Carcinoma Based on Bioinformatics Analysis
Authors: Chen Jing-Jing , Zhang Lu-Lu , Liu Zhen , Men Wan Qi , Chen Fang , Shen Jilu
Published: June 2023

Hepatocellular carcinoma (HCC) is one of the leading cause of cancer-associated death in the world. However, due to the complexity of HCC, it is urgent for us to find a reliable and accurate biomarker for HCC gene therapy.TopBP1-interacting checkpoint and replication regulator (TICRR), known as Treslin in vertebrate and sld3 in yeast, is involved in the tumorigenesis, progression, matastasis, diagnosis, and predicting prognosis of HCC. Disappointingly, the mechanism of TICRR expression in HCC is still not described in detail and requires further analysis. In this study, TCGA (www.tcga-data.nci.nih.gov/tcga/) datasets and GEO (www.ncbi.nlm.nih.gov/geo) datasets were used to analyze the expression of TICRR in HCC, the relevance of TICRR mRNA expression and clinicopathological characteristics in patients with HCC, and the relationship between TICRR expression and immune infiltration level in Patients with HCC. Based on MethSurv database, the impact of TICRR in patients with HCC was investigated. In addition, GO/KEGG enrichment analysis of TICRR co-expression was performed using the R package. TICRR was found drastically highly expressed in a variety of cancer types including HCC.ROC curve analysis showed that TICRR had higher accuracy in predicting HCC compared with AFP. The expression level of TICRR was marked positively correlated with tumor stage and prognosis in Patients with HCC.GO/KEGG enrichment analysis showed that TICRR was associated with cell division and cell cycle as well as p53 signaling pathway. In addition, patients with high TICRR methylation of cg05841809, cg09403165, and cg03312532 CpG sites were significantly correlated with poor prognosis of HCC. This study demonstrated that increased TICRR expression in HCC might play an important role in the tumorigenesis, progression, diagnosis, and predicting prognosis of HCC. Therefore, TICRR might be used as a promising diagnostic and prognostic biomarker for HCC gene therapy.
A Cognitive Load Theory Approach to Defining and Measuring Task Complexity Through Element Interactivity
Authors: Chen Ouhao , Paas Fred , Sweller John
Published: June 2023

Educational researchers have been confronted with a multitude of definitions of task complexity and a lack of consensus on how to measure it. Using a cognitive load theory-based perspective, we argue that the task complexity that learners experience is based on element interactivity. Element interactivity can be determined by simultaneously considering the structure of the information being processed and the knowledge held in long-term memory of the person processing the information. Although the structure of information in a learning task can easily be quantified by counting the number of interacting information elements, knowledge held in long-term memory can only be estimated using teacher judgment or knowledge tests. In this paper, we describe the different perspectives on task complexity and present some concrete examples from cognitive load research on how to estimate the levels of element interactivity determining intrinsic and extraneous cognitive load. The theoretical and practical implications of the cognitive load perspective of task complexity for instructional design are discussed.
Optimizing treatment of brain metastases in an era of novel systemic treatments: a single center consecutive series
Authors: van Schie P. , Rijksen B. L. T. , Bot M. , Wiersma T. , Merckel L. G. , Brandsma D. , Compter A. , de Witt Hamer P. C. , Post R. , Borst G. R.
Published: June 2023

Background

The multidisciplinary management of patients with brain metastases consists of surgical resection, radiation treatment and systemic treatment. Tailoring and timing these treatment modalities is challenging. This study presents real-world data from consecutively treated patients and assesses the impact of all treatment strategies and their relation with survival. The aim is to provide new insights to improve multidisciplinary decisions towards individualized treatment strategies in patients with brain metastases.

Methods

A retrospective consecutive cohort study was performed. Patients with brain metastases were included between June 2018 and May 2020. Brain metastases of small cell lung carcinoma were excluded. Overall survival was analyzed in multivariable models.

Results

676 patients were included in the study, 596 (88%) received radiotherapy, 41 (6%) awaited the effect of newly started or switched systemic treatment and 39 (6%) received best supportive care. Overall survival in the stereotactic radiotherapy group was 14 months (IQR 5–32) and 32 months (IQR 11–43) in patients who started or switched systemic treatment and initially did not receive radiotherapy. In patients with brain metastases without options for local or systemic treatment best supportive care was provided, these patients had an overall survival of 0 months (IQR 0–1). Options for systemic treatment, Karnofsky Performance Score ≥ 70 and breast cancer were prognostic for a longer overall survival, while progressive extracranial metastases and whole-brain-radiotherapy were prognostic for shorter overall survival.

Conclusions

Assessing prognosis in light of systemic treatment options is crucial after the diagnosis of brain metastasis for the consideration of radiotherapy versus best supportive care.

Graphical Abstract
Evolutionary diversity of proton and water channels on the oxidizing side of photosystem II and their relevance to function
Authors: Hussein Rana , Ibrahim Mohamed , Bhowmick Asmit , Simon Philipp S. , Bogacz Isabel , Doyle Margaret D. , Dobbek Holger , Zouni Athina , Messinger Johannes , Yachandra Vittal K. , Kern Jan F. , Yano Junko
Published: June 2023

One of the reasons for the high efficiency and selectivity of biological catalysts arise from their ability to control the pathways of substrates and products using protein channels, and by modulating the transport in the channels using the interaction with the protein residues and the water/hydrogen-bonding network. This process is clearly demonstrated in Photosystem II (PS II), where its light-driven water oxidation reaction catalyzed by the Mn4CaO5 cluster occurs deep inside the protein complex and thus requires the transport of two water molecules to and four protons from the metal center to the bulk water. Based on the recent advances in structural studies of PS II from X-ray crystallography and cryo-electron microscopy, in this review we compare the channels that have been proposed to facilitate this mass transport in cyanobacteria, red and green algae, diatoms, and higher plants. The three major channels (O1, O4, and Cl1 channels) are present in all species investigated; however, some differences exist in the reported structures that arise from the different composition and arrangement of membrane extrinsic subunits between the species. Among the three channels, the Cl1 channel, including the proton gate, is the most conserved among all photosynthetic species. We also found at least one branch for the O1 channel in all organisms, extending all the way from Ca/O1 via the ‘water wheel’ to the lumen. However, the extending path after the water wheel varies between most species. The O4 channel is, like the Cl1 channel, highly conserved among all species while having different orientations at the end of the path near the bulk. The comparison suggests that the previously proposed functionality of the channels in T. vestitus (Ibrahim et al., Proc Natl Acad Sci USA 117:12624–12635, 2020; Hussein et al., Nat Commun 12:6531, 2021) is conserved through the species, i.e. the O1-like channel is used for substrate water intake, and the tighter Cl1 and O4 channels for proton release. The comparison does not eliminate the potential role of O4 channel as a water intake channel. However, the highly ordered hydrogen-bonded water wire connected to the Mn4CaO5 cluster via the O4 may strongly suggest that it functions in proton release, especially during the S0 → S1 transition (Saito et al., Nat Commun 6:8488, 2015; Kern et al., Nature 563:421–425, 2018; Ibrahim et al., Proc Natl Acad Sci USA 117:12624–12635, 2020; Sakashita et al., Phys Chem Chem Phys 22:15831–15841, 2020; Hussein et al., Nat Commun 12:6531, 2021).
Multinomial Logistic Factor Regression for Multi-source Functional Block-wise Missing Data
Authors: Du Xiuli , Jiang Xiaohu , Lin Jinguan ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: June 2023

Multi-source functional block-wise missing data arise more commonly in medical care recently with the rapid development of big data and medical technology, hence there is an urgent need to develop efficient dimension reduction to extract important information for classification under such data. However, most existing methods for classification problems consider high-dimensional data as covariates. In the paper, we propose a novel multinomial imputed-factor Logistic regression model with multi-source functional block-wise missing data as covariates. Our main contribution is to establishing two multinomial factor regression models by using the imputed multi-source functional principal component scores and imputed canonical scores as covariates, respectively, where the missing factors are imputed by both the conditional mean imputation and the multiple block-wise imputation approaches. Specifically, the univariate FPCA is carried out for the observable data of each data source firstly to obtain the univariate principal component scores and the eigenfunctions. Then, the block-wise missing univariate principal component scores instead of the block-wise missing functional data are imputed by the conditional mean imputation method and the multiple block-wise imputation method, respectively. After that, based on the imputed univariate factors, the multi-source principal component scores are constructed by using the relationship between the multi-source principal component scores and the univariate principal component scores; and at the same time, the canonical scores are obtained by the multiple-set canonial correlation analysis. Finally, the multinomial imputed-factor Logistic regression model is established with the multi-source principal component scores or the canonical scores as factors. Numerical simulations and real data analysis on ADNI data show the proposed method works well.
Induction of apoptosis, oxidative stress, hormonal, and histological alterations in the reproductive system of thiamethoxam-exposed female rats
Authors: El-Din Marwa Alaa El-Din Sarry , Ghareeb Abd El-Wahab El , El-Garawani Islam M. , El-Rahman Heba Ali Abd
Published: June 2023

The present study aimed to investigate the oral toxic effects of 1/10 LD50 and 1/5 LD50 of thiamethoxam (TMX), a neonicotinoid insecticide, on the reproductive system of female Wistar rats. Thirty female rats were divided into three groups and supplied orally with either; saline solution, 1/10 LD50 of TMX (156 mg/kg) or 1/5 LD50 of TMX (312 mg/kg). The daily administration was extended for 30 days. Investigating the parameters of oxidative stress, hormonal levels, histopathological alterations, and the apoptotic markers (P53, BAX, BCL-2, and caspase-3) was performed in the uterus and ovary of rats. Results showed significant changes in the body weight gain, and relative weight of the left and right ovaries and uterus. Moreover, luteinizing hormone (LH), estradiol (ED), and progesterone (PG) serum levels were not significantly altered following TMX oral administration. The level of follicle-stimulating hormone in the TMX-exposed group (156 mg/kg) was significantly increased; however, a significant decrease was observed in TMX-exposed animals (312 mg/kg). TMX induced significant oxidative stress in exposed groups by reducing the activities of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT), and elevating malondialdehyde (MDA) levels. Following hematoxylin and eosin staining, the microscopic examination revealed deteriorated luteal cells with vacuolation in the corpus luteum, a follicle containing a degenerated oocyte and degeneration/necrosis of the circular muscle layer with a high rate of apoptotic cells in TMX-exposed animals. TMX induced transcriptional alterations in apoptosis-related genes shifting towards the activation of the intrinsic apoptotic pathway. Collectively, results suggest the toxic effect of the TMX on the reproductive health of female Wistar rats.
APEX1 Nuclease and Redox Functions are Both Essential for Adult Mouse Hematopoietic Stem and Progenitor Cells
Authors: Zaunz Samantha , De Smedt Jonathan , Lauwereins Lukas , Cleuren Lana , Laffeber Charlie , Bajaj Manmohan , Lebbink Joyce H. G. , Marteijn Jurgen A. , De Keersmaecker Kim , Verfaillie Catherine
Published: June 2023

Self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) are carefully controlled by extrinsic and intrinsic factors, to ensure the lifelong process of hematopoiesis. Apurinic/apyrimidinic endonuclease 1 (APEX1) is a multifunctional protein implicated in DNA repair and transcriptional regulation. Although previous studies have emphasized the necessity of studying APEX1 in a lineage-specific context and its role in progenitor differentiation, no studies have assessed the role of APEX1, nor its two enzymatic domains, in supporting adult HSPC function. In this study, we demonstrated that complete loss of APEX1 from murine bone marrow HSPCs (induced by CRISPR/Cas9) caused severe hematopoietic failure following transplantation, as well as a HSPC expansion defect in culture conditions maintaining in vivo HSC functionality. Using specific inhibitors against either the nuclease or redox domains of APEX1 in combination with single cell transcriptomics (CITE-seq), we found that both APEX1 nuclease and redox domains are regulating mouse HSPCs, but through distinct underlying transcriptional changes. Inhibition of the APEX1 nuclease function resulted in loss of HSPCs accompanied by early activation of differentiation programs and enhanced lineage commitment. By contrast, inhibition of the APEX1 redox function significantly downregulated interferon-stimulated genes and regulons in expanding HSPCs and their progeny, resulting in dysfunctional megakaryocyte-biased HSPCs, as well as loss of monocytes and lymphoid progenitor cells. In conclusion, we demonstrate that APEX1 is a key regulator for adult regenerative hematopoiesis, and that the APEX1 nuclease and redox domains differently impact proliferating HSPCs.

Graphical Abstract
Seasonality and mobility of Epipaleolithic groups in the north-east of the Iberian Peninsula: tooth wear analysis of ungulates from Balma del Gai
Authors: Duñó-Iglesias Paulo , Rivals Florent , Lloveras Lluís , Nadal Jordi
Published: June 2023

The aim of this work is to provide evidence about the mobility of hunter-gatherer groups from the north-east of the Iberian Peninsula during the Epipaleolithic, more specifically, those from the Balma del Gai site (Moià, Barcelona, Spain). To do so, a study of the dental meso- and microwear of ungulates hunted by the groups that occupied the Balma del Gai site during the Epipaleolithic was carried out with two main objectives. First, we aimed to determine the diet of the hunted ungulates to reconstruct the habitat in which they lived in the areas near the site through the comparison of the dental microwear patterns with those of extant populations of directly related taxa that inhabited different regions. Second, we aimed to study the variability in the diet of the hunted ungulates to determine the durations of the occupations, and therefore, to characterize the mobility model (forager vs. collector) of the hunter-gatherer groups at Balma del Gai during the Epipaleolithic. The results indicate that the rock shelter was occupied on a seasonal basis. The browsing dietary traits of the red deer at the time of death combined with archaeological evidence suggest that the occupation took place during late summer and especially autumn. This points to a forager mobility pattern for the hunter-gatherer groups of Balma del Gai that could have been present throughout other contemporary human groups of the Mediterranean coast and pre-coastal area.
Equivalent characterizations of martingale Hardy–Lorentz spaces with variable exponents
Authors: Weisz Ferenc
Published: June 2023

We prove that under the log-Hölder continuity condition of the variable exponent $$p(\cdot )$$

p
(
·
)

, a new type of maximal operators, $$U_{\gamma ,s}$$

U

γ
,
s

is bounded from the variable martingale Hardy–Lorentz space $$H_{p(\cdot ),q}$$

H

p
(
·
)
,
q

to $$L_{p(\cdot ),q}$$

L

p
(
·
)
,
q

, whenever $$0<p_-\le p_+ <\infty $$

0
<

p
-

≤

p
+

<
∞

, $$0<q \le \infty $$

0
<
q
≤
∞

, $$0<\gamma ,s<\infty $$

0
<
γ
,
s
<
∞

and $$1/p_- - 1/p_+ < \gamma +s$$

1
/

p
-

-
1
/

p
+

<
γ
+
s

. Moreover, the operator $$U_{\gamma ,s}$$

U

γ
,
s

generates equivalent quasi-norms on the Hardy–Lorentz spaces $$H_{p(\cdot ),q}$$

H

p
(
·
)
,
q

.
Design-oriented study on target station for spallation neutron source at KOMAC
Authors: Lee Pilsoo , Kang Namwoo , Jang Yongsik
Published: June 2023

A neutron-production target system, composed of targets, moderators, reflectors, and shielding, has been conceptually designed for the future MW-class spallation neutron source based on a high-intensity proton accelerator at KOMAC. For targetry, we tentatively adopted a fixed-metal target concept; tantalum-clad tungsten plates in a water-cooled target shroud made of stainless steel. In the thermal analysis and stress calculations using ANSYS, the von Mises stress was found to exceed the yield stress of SS316L at the edges of the structure for a 500-kW proton beam on target. Relatively high stress at edges seems to be a stress concentration that could be reduced by minor design modifications. Preliminary calculation results for a conservative design of target shielding show that radiation dose after the outermost shielding could be lower than 10 $$\upmu$$
μ
Sv/h in a 500-kW operation condition, implying that the design could be optimized to reduce construction costs without loss of shielding performance.
Facial Attractiveness, but not Facial Masculinity, is Used as a Cue to Paternal Involvement in Fathers
Authors: Bartlome Ronja I. , Lee Anthony J.
Published: June 2023

Purpose

Facial femininity in men is purportedly used as a cue by women as a signal of paternal involvement. However, evidence for this claim is questionable. Previous findings have shown that paternal involvement is linked to testosterone, but have not investigated facial masculinity directly, while other studies have found that facial masculinity is negatively associated with perceptions of paternal involvement but do not assess the accuracy of this judgement. Here, we assess whether facial masculinity in men is used as a cue to paternal involvement, and whether this cue is accurate.

Methods

We collected facial photographs of 259 men (156 of which were fathers) who also completed self-report measures of paternal involvement. Facial images were then rated by a separate group of raters on facial masculinity, attractiveness, and perceived paternal involvement. Shape sexual dimorphism was also calculated from the images using geometric morphometrics.

Results

We found that facial masculinity was not associated with perceptions of paternal involvement, nor was it related with self-reported paternal involvement. Interestingly, facial attractiveness was negatively associated with perceptions of paternal involvement, and we found partial evidence that facial attractiveness was also negatively associated with self-reported paternal involvement.

Conclusion

These findings challenge the hypothesis that sexual dimorphism is used as a cue to paternal involvement, and perhaps indicate that facial attractiveness is more important for this judgement instead.
PtNi-W/C with Atomically Dispersed Tungsten Sites Toward Boosted ORR in Proton Exchange Membrane Fuel Cell Devices
Authors: Wang Huawei , Gao Jialong , Chen Changli , Zhao Wei , Zhang Zihou , Li Dong , Chen Ying , Wang Chenyue , Zhu Cheng , Ke Xiaoxing , Pei Jiajing , Dong Juncai , Chen Qi , Jin Haibo , Chai Maorong , Li Yujing
Published: June 2023

The performance of proton exchange membrane fuel cells is heavily dependent on the microstructure of electrode catalyst especially at low catalyst loadings. This work shows a hybrid electrocatalyst consisting of PtNi-W alloy nanocrystals loaded on carbon surface with atomically dispersed W sites by a two-step straightforward method. Single-atomic W can be found on the carbon surface, which can form protonic acid sites and establish an extended proton transport network at the catalyst surface. When implemented in membrane electrode assembly as cathode at ultra-low loading of 0.05 mgPt cm−2, the peak power density of the cell is enhanced by 64.4% compared to that with the commercial Pt/C catalyst. The theoretical calculation suggests that the single-atomic W possesses a favorable energetics toward the formation of *OOH whereby the intermediates can be efficiently converted and further reduced to water, revealing a interfacial cascade catalysis facilitated by the single-atomic W. This work highlights a novel functional hybrid electrocatalyst design from the atomic level that enables to solve the bottle-neck issues at device level.
Criminal Careers of Burglars and Robbers in the Netherlands
Authors: Kros Mathijs , Piersma Tjeerd W. , Beijersbergen Karin A.
Published: June 2023

This paper investigates criminal career characteristics and trajectories of domestic burglars, residential and commercial robbers, and street robbers in the Netherlands. We used longitudinal data which includes the criminal cases from 1997 until 2020 for all people of 12 years or older. We studied all 89,062 offenders that had at least one criminal case in the period between 2002 and 2004. Semiparametric group trajectory models were used to cluster these offenders into groups with similar criminal careers. Our results suggest that in order to predict who will follow the career path of a life-course persistent offender, it is important to distinguish between specific groups of offenders. Life-course persistent offenders are found amongst domestic burglars, residential and commercial robbers, and street robbers, but not amongst offenders of other types of crime. Furthermore, the size of the group of life-course persistent offenders varies between the domestic burglars, residential and commercial robbers, and street robbers and is largest for domestic burglars. Other criminal career characteristics, such as age of onset, age of termination, duration, and specialisation, are also compared between offender groups.
Numerical modeling of near-wellbore diverter bridging in hydraulic fracturing
Authors: Luo Bo , Han Yanhui , Wong George K.
Published: June 2023

In this work, we used a particle transport model integrated into the fluid solver in FLAC to simulate the transport of particles in the near-wellbore region inside a hydraulic fracture. Complex flow behaviors, including divergent flow near the fracture entrance and detouring flow around diverter packs, can be captured in this coupling system. In the numerical implementation, the coupled fluid flow and particle transport are realized by updating the fracture permeability, particle concentration, and velocities of fluid and particles in each time step. Simulation results indicate that the final shape of the particle bridging zone at the near-wellbore region is determined by the flow-driven and settling-driven particle transport. A continuous bridging band initially forms at the bottom region of the fracture, then the fluid-driven particles move upwards to block the top region of the fracture. Lastly, a V-shaped bridging band is formed inside the fracture. It is observed that high initial particle concentration and large particle size result in the creation of a small-scale bridging band near the injection entrance, which promotes the rapid growth of the closed bridging band and high-pressure buildup.