bluuebunny/crossref_metadata_2025 huggingface dataset:
Connected bikeability in London: Which localities are better connected by bike and does this matter?
Authors: Beecham Roger , Yang Yuanxuan , Tait Caroline , Lovelace Robin
Published: March 2023

Bikeability, the extent to which a route network enables cycling for everyday travel, is a frequently cited theme for increasing and diversifying cycling uptake and therefore one that attracts much research attention. Indexes designed to quantify bikeability typically generate a single bikeability value for a single locality. Important to transport planners making and evaluating infrastructure decisions, however, is how well-connected by bike are pairs of localities. For this, it is necessary to estimate the bikeability of plausible routes connecting different parts of a city. We approximate routes for all origin-destination trips cycled in the London Cycle Hire Scheme for 2018 and estimate the bikeability of each route, linking to the newly released London Cycle Infrastructure Database. We then divide the area of inner London covered by the bikeshare scheme into ‘villages’ and profile how bikeability varies for trips connecting those villages – we call this connected bikeability. Our bikeability scores vary geographically with certain localities in London better connected by bike than others. A key finding is that higher levels of connected bikeability are conferred to origin-destination village pairs of strategic importance, aligning with the stated ambition of recent cycling infrastructure interventions. The geography of connected bikeability maps to the commuting needs of London’s workers and we find some evidence that connected bikeability has a positive association with observed cycling activity, especially so when studying patterns of cycling to job-rich villages.
The shape-retention and heat-tolerant elastic helix based on azobenzene-polyimide supramolecular assembly
Authors: Li Shuangwen , Cui Yongsheng , Jia Shuai , Lin Song , Gong Lan , An Haoran , Sun Yanrong , Xu Linan
Published: March 2023

Helical structures are ubiquitous in natural and engineered systems across multiple length scales, while they often exhibit nearly uniform radius and pitch. Utilization of biomimetic structure design to develop stretchable and robust 3D helical structures that are shape-preserving and heat-tolerant is of great interest. Herein, we devise flexible 3D helixes by supramolecular self-assembly and high voltage electric field orientation of molecular chains. The 3D helixes not only inherit buffering mechanics with exceptional shape-retention ability against cyclic stretching but also exhibit excellent heat-resistant quality. The results of the experimental tests confirm that the helix can recover its original shape without obvious residual strain and basically withstand after 2000 cycles under force loading of 10 cN. Such robust biomimetic materials hold great prospects in the fields of artificial muscles, wearable materials, and so on.
RNA splicing factor Rbm25 underlies heterogeneous preleukemic clonal expansion in mice
Authors: Bramlett Charles , Eerdeng Jiya , Jiang Du , Lee Yeachan , Garcia Ivon , Vergel-Rodriguez Mary C , Condie Patrick , Nogalska Anna , Lu Rong
Published: March 2023

Clonal expansion sets the stage for cancer genesis by allowing for the accumulation of molecular alterations. While genetic mutations that induce clonal expansion and malignancy, such as Tet2, have been identified, these mutations are also frequently found in healthy individuals. Here, we tracked preleukemic clonal expansion using genetic barcoding in an inducible Tet2 knockout mouse model and found that only a small fraction of hematopoietic stem cells (HSCs) expanded excessively upon Tet2 knockout. These overexpanded HSCs expressed significantly lower levels of genes associated with leukemia and RNA splicing compared to non-overexpanded Tet2 knockout HSCs. Knocking down Rbm25, an identified RNA splicing factor, accelerated the expansion of Tet2-knockout hematopoietic cells in vitro and in vivo. Our data suggest that mutations of an epigenetic factor Tet2 induces variability in the expression of an RNA splicing factor Rbm25, which subsequently drives heterogeneous preleukemic clonal expansion. This heterogeneous clonal expansion could contribute to the variable disease risks across individuals.
Molecular associations of response to the new-generation BTK inhibitor zanubrutinib in marginal zone lymphoma
Authors: Tatarczuch Maciej , Waltham Mark , Shortt Jake , Polekhina Galina , Hawkes Eliza A. , Ho Shir-Jing , Trotman Judith , Brasacchio Daniella , Co Melannie , Li Jessica , Ramakrishnan Vanitha , Dunne Karin , Opat Stephen S. , Gregory Gareth P.
Published: March 2023

Using tissue whole exome sequencing (WES) and circulating tumor cell–free DNA (ctDNA), this Australasian Leukaemia & Lymphoma Group translational study sought to characterize primary and acquired molecular determinants of response and resistance of marginal zone lymphoma (MZL) to zanubrutinib for patients treated in the MAGNOLIA clinical trial. WES was performed on baseline tumor samples obtained from 18 patients. For 7 patients, ctDNA sequence was interrogated using a bespoke hybrid-capture next-generation sequencing assay for 48 targeted genes. Somatic mutations were correlated with objective response data and survival analysis using Fisher exact test and Kaplan-Meier (log-rank) method, respectively. Baseline WES identified mutations in 33 of 48 (69%) prioritized genes. NF-κB, NOTCH, or B-cell receptor (BCR) pathway genes were implicated in samples from 16 of 18 patients (89%). KMT2D mutations (n = 11) were most common, followed by FAT1 (n = 9), NOTCH1, NOTCH2, TNFAIP3 (n = 5), and MYD88 (n = 4) mutations. MYD88 or TNFAIP3 mutations correlated with improved progression-free survival (PFS). KMT2D mutations trended to worse PFS. Acquired resistance mutations PLCG2 (R665W/R742P) and BTK (C481Y/C481F) were detected in 2 patients whose disease progressed. A BTK E41K noncatalytic activating mutation was identified before treatment in 1 patient who was zanubrutinib-refractory. MYD88, TNFAIP3, and KMT2D mutations correlate with PFS in patients with relapsed/refractory MZL treated with zanubrutinib. Detection of acquired BTK and PLCG2 mutations in ctDNA while on therapy is feasible and may herald clinical disease progression. This trial was registered at https://anzctr.org.au/ as #ACTRN12619000024145.
Genome Scan of Rice Landrace Populations Collected Across Time Revealed Climate Changes’ Selective Footprints in the Genes Network Regulating Flowering Time
Authors: Ahmadi Nourollah , Barry Mamadou Billo , Frouin Julien , de Navascués Miguel , Toure Mamadou Aminata
Published: March 2023

Analyses of the genetic bases of plant adaptation to climate changes, using genome-scan approaches, are often conducted on natural populations, under hypothesis of out-crossing reproductive regime. We report here on a study based on diachronic sampling (1980 and 2011) of the autogamous crop species, Oryza sativa and Oryza glaberrima, in the tropical forest and the Sudanian savannah of West Africa. First, using historical meteorological data we confirmed changes in temperatures (+ 1 °C on average) and rainfall regime (less predictable and reduced amount) in the target areas. Second, phenotyping the populations for phenology, we observed significantly earlier heading time in the 2010 samples. Third, implementing two genome-scan methods (one of which specially developed for selfing species) on genotyping by sequencing genotypic data of the two populations, we detected 31 independent selection footprints. Gene ontology analysis detected significant enrichment of these selection footprints in genes involved in reproductive processes. Some of them bore known heading time QTLs and genes, including OsGI, Hd1 and OsphyB. This rapid adaptive evolution, originated from subtle changes in the standing variation in genetic network regulating heading time, did not translate into predominance of multilocus genotypes, as it is often the case in selfing plants, and into notable selective sweeps. The high adaptive potential observed results from the multiline genetic structure of the rice landraces, and the rather large and imbricated genetic diversity of the rice meta-population at the farm, the village and the region levels, that hosted the adaptive variants in multiple genetic backgrounds before the advent of the environmental selective pressure. Our results illustrate the evolution of in situ diversity through processes of human and natural selection, and provide a model for rice breeding and cultivars deployment strategies aiming resilience to climate changes. It also calls for further development of population genetic models for adaptation of plant populations to environmental changes. To our best knowledge, this is the first study dealing with climate-changes’ selective footprint in crops.
Validation with single-step SNPBLUP shows that evaluations can continue using a single mean of genotyped individuals, even with multiple breeds
Authors: Aldridge Michael , Vandenplas Jeremie , Duenk Pascal , Henshall John , Hawken Rachel , Calus Mario
Published: March 2023

Background

In genomic prediction, it is common to centre the genotypes of single nucleotide polymorphisms based on the allele frequencies in the current population, rather than those in the base generation. The mean breeding value of non-genotyped animals is conditional on the mean performance of genotyped relatives, but can be corrected by fitting the mean performance of genotyped individuals as a fixed regression. The associated covariate vector has been referred to as a ‘J-factor’, which if fitted as a fixed effect can improve the accuracy and dispersion bias of sire genomic estimated breeding values (GEBV). To date, this has only been performed on populations with a single breed. Here, we investigated whether there was any benefit in fitting a separate J-factor for each breed in a three-way crossbred population, and in using pedigree-based expected or genome-based estimated breed fractions to define the J-factors.

Results

For body weight at 7 days, dispersion bias decreased when fitting multiple J-factors, but only with a low proportion of genotyped individuals with selective genotyping. On average, the mean regression coefficients of validation records on those of GEBV increased with one J-factor compared to none, and further increased with multiple J-factors. However, for body weight at 35 days this was not observed. The accuracy of GEBV remained unchanged regardless of the J-factor method used. Differences between the J-factor methods were limited with correlations approaching 1 for the estimated covariate vector, the estimated coefficients of the regression on the J-factors, and the GEBV.

Conclusions

Based on our results and in the particular design analysed here, i.e. all the animals with phenotype are of the same type of crossbreds, fitting a single J-factor should be sufficient, to reduce dispersion bias. Fitting multiple J-factors may reduce dispersion bias further but this depends on the trait and genotyping rate. For the crossbred population analysed, fitting multiple J-factors has no adverse consequences and if this is done, it does not matter if the breed fractions used are based on the pedigree-expectation or the genomic estimates. Finally, when GEBV are estimated from crossbred data, any observed bias can potentially be reduced by including a straightforward regression on actual breed proportions.
The association between anticholinergic burden and mobility: a systematic review and meta-analyses
Authors: Phutietsile Geofrey O. , Fotaki Nikoletta , Jamieson Hamish A. , Nishtala Prasad S.
Published: March 2023

Background

As people age, they accumulate several health conditions, requiring the use of multiple medications (polypharmacy) to treat them. One of the challenges with polypharmacy is the associated increase in anticholinergic exposure to older adults. In addition, several studies suggest an association between anticholinergic burden and declining physical function in older adults.

Objective/Purpose

This systematic review aimed to synthesise data from published studies regarding the association between anticholinergic burden and mobility. The studies were critically appraised for the strength of their evidence.

Methods

A systematic literature search was conducted across five electronic databases, EMBASE, CINAHL, PSYCHINFO, Cochrane CENTRAL and MEDLINE, from inception to December 2021, to identify studies on the association of anticholinergic burden with mobility. The search was performed following a strategy that converted concepts in the PECO elements into search terms, focusing on terms most likely to be found in the title and abstracts of the studies. For observational studies, the risk of bias was assessed using the Newcastle Ottawa Scale, and the Cochrane risk of bias tool was used for randomised trials. The GRADE criteria was used to rate confidence in evidence and conclusions. For the meta-analyses, we explored the heterogeneity using the Q test and I2 test and the publication bias using the funnel plot and Egger’s regression test. The meta-analyses were performed using Jeffreys’s Amazing Statistics Program (JASP).

Results

Sixteen studies satisfied the inclusion criteria from an initial 496 studies. Fifteen studies identified a significant negative association of anticholinergic burden with mobility measures. One study did not find an association between anticholinergic intervention and mobility measures. Five studies included in the meta-analyses showed that anticholinergic burden significantly decreased walking speed (0.079 m/s ± 0.035 MD ± SE,95% CI: 0.010 to 0.149, p = 0.026), whilst a meta-analysis of four studies showed that anticholinergic burden significantly decreased physical function as measured by three variations of the Instrumental Activities of Daily Living (IADL) instrument 0.27 ± 0.12 (SMD ± SE,95% CI: 0.03 to 0.52), p = 0.027. The results of both meta-analyses had an I2 statistic of 99% for study heterogeneity. Egger’s test did not reveal publication bias.

Conclusion

There is consensus in published literature suggesting a clear association between anticholinergic burden and mobility. Consideration of cognitive anticholinergic effects may be important in interpreting results regarding the association of anticholinergic burden and mobility as anticholinergic drugs may affect mobility through cognitive effects.
Histological endometrial dating: a reliable tool for personalized frozen-thawed embryo transfer in patients with repeated implantation failure in natural cycles
Authors: Li Yuan , Wen Quan , Hu Jing , Liao Jingnan , Fan Xiangxiu , Chen Huijun , Zhao Qi , Lu Guang-Xiu , Lin Ge , Gong Fei
Published: March 2023

Objective

To evaluate the clinical availability and stability of histological endometrial dating as a tool for personalized frozen-thawed embryo transfer (pFET) in patients with repeated implantation failure (RIF) in natural cycles.

Methods

A total of 1245 RIF patients were recruited to the present study. All of the patients received an endometrial dating evaluation on day 7 post-ovulation (PO + 7) to guide their first pFET. The second and third pFETs were executed according to histological examination (again employing biopsy) or by reference to previous results. Subsequent pregnancy outcomes for all of the cycles were ultimately tracked.

Results

The out-of-phase rate for RIF patients was 32.4% (404/1245) and the expected dating rate (the probability of the expected endometrial dating aligning with repeat biopsy) for endometrial dating reevaluation was as high as 94.3% (50/53). The clinical pregnancy rates of first, second, and third pFETs were 65.3%, 50.0%, and 44.4%, respectively; and the cumulative clinical pregnancy rate attained 74.9% after three transfers. Endometrial dating reevaluations met expectations with more than a 2-year duration in three cases and elicited favorable clinical outcomes.

Conclusion

We validated the relatively high stability of the histological endometrial dating platform—including the out-of-phase rate and the expected dating rate of reevaluation in patients with RIF—by expanding the sample size. The pFET, based on histological endometrial dating, was of acceptable clinical value and was worthy of promotion in patients with unexplained RIF.
Etanercept for patients with juvenile idiopathic arthritis: drug levels and influence of concomitant methotrexate: observational study
Authors: Levälampi Tiina , Kärki Johanna , Rebane Katariina , Vähäsalo Paula , Malin Merja , Kröger Liisa , Grönlund Minna-Maija , Backström Maria , Pohjankoski Heini , Kautiainen Hannu , Jokiranta Sakari , Aalto Kristiina
Published: March 2023

Background

Etanercept (ETN) is widely used tumour necrosis factor (TNF) blocker in the treatment of juvenile idiopathic arthritis (JIA) when traditional synthetic disease modifying antirheumatic drug (sDMARD) therapy is not sufficient. There is limited information about the effects of methotrexate (MTX) on serum ETN concentration in children with JIA. We aimed to investigate whether ETN dose and concomitant MTX would effect ETN serum trough levels in JIA patients, and whether concomitant MTX have an influence on the clinical response in patients with JIA receiving ETN.

Methods

In this study, we collected the medical record data of 180 JIA patients from eight Finnish pediatric rheumatological centres. All these patients were treated with ETN monotherapy or combination therapy with DMARD. To evaluate the ETN concentrations, blood samples of the patients were collected between injections right before the subsequent drug. Free ETN level was measured from serum.

Results

Ninety-seven (54%) of the patients used concomitant MTX, and 83 (46%) received either ETN monotherapy or used sDMARDs other than MTX. A significant correlation was noted between ETN dose and drug level [r = 0.45 (95% CI: 0.33–0.56)]. The ETN dose and serum drug level were correlated (p = 0.030) in both subgroups – in MTX group [r = 0.35 (95% CI: 0.14–0.52)] and in non-MTX group [r = 0.54 (95% CI: 0.39–0.67)].

Conclusion

In the present study, we found that concomitant MTX had no effect on serum ETN concentration or on clinical response. In addition, a significant correlation was detected between ETN dose and ETN concentration.
Comparing dislocation rates by approach following elective primary dual mobility total hip arthroplasty: a systematic review
Authors: Butler Justin T. , Stegelmann Samuel D. , Butler Johnathon L. , Bullock Matthew , M. Miller Richard
Published: March 2023

Background

Dual mobility components can be implanted during total hip arthroplasty (THA) for primary osteoarthritis via a direct anterior approach (DAA), anterolateral approach (ALA), direct lateral approach (DLA), or posterior/posterolateral approach (PLA). This review compares dual mobility hip dislocation rates using these approaches for elective primary THA.

Methods

PubMed, Embase, and Cochrane databases were systematically searched for articles published after January 1, 2006 that reported dislocation rates for adult patients after primary THA with dual mobility implants. Articles were excluded if they reported revision procedures, nonelective THA for femoral neck fractures, acetabular defects requiring supplemental implants, prior surgery, or ≤ 5 patients. The primary outcome was hip dislocation rate. Secondary outcomes included infection, Harris Hip Score (HHS), and Postel-Merle d’Aubigné (PMA) score.

Results

After screening 542 articles, 63 met inclusion criteria. Due to study heterogeneity, we did not perform a meta-analysis. Eight studies reported DAA, 5 reported ALA, 6 reported the DLA, and 56 reported PLA. Study size ranged from 41 to 2,601 patients. Mean follow-up time ranged from 6 months to 25 years. Rates of infection and dislocation were low; 80% of ALA, 87.5% of DAA, 100% of DLA, and 82.1% of PLA studies reported zero postoperative dislocations. Studies reporting postoperative HHS and PMA scores showed considerable improvement for all approaches.

Conclusions

Patients undergoing primary THA with dual mobility implants rarely experience postoperative dislocation, regardless of surgical approach. Additional studies directly comparing DAA, ALA, DLA, and PLA are needed to confirm these findings.
Effects of climate and plant functional types on forest above-ground biomass accumulation
Authors: Chen Xia , Luo Mingyu , Larjavaara Markku
Published: March 2023

Background

Forest above-ground biomass (AGB) accumulation is widely considered an important tool for mitigating climate change. However, the general pattern of forest AGB accumulation associated with age and climate gradients across various forest functional types at a global scale have remained unclear. In this study, we compiled a global AGB data set and applied a Bayesian statistical model to reveal the age-related dynamics of forest AGB accumulation, and to quantify the effects of mean annual temperature and annual precipitation on the initial AGB accumulation rate and on the saturated AGB characterizing the limit to AGB accumulation.

Results

The results of the study suggest that mean annual temperature has a significant positive effect on the initial AGB accumulation rate in needleleaf evergreen forest, and a negative effect in broadleaf deciduous forest; whereas annual precipitation has a positive effect in broadleaf deciduous forest, and negative effect in broadleaf evergreen forest. The positive effect of mean annual temperature on the saturated AGB in broadleaf evergreen forest is greater than in broadleaf deciduous forest; annual precipitation has a greater negative effect on the saturated AGB in deciduous forests than in evergreen forests. Additionally, the difference of AGB accumulation rate across four forest functional types is closely correlated with the forest development stage at a given climate.

Conclusions

The contrasting responses of AGB accumulation rate to mean annual temperature and precipitation across four forest functional types emphasizes the importance of incorporating the complexity of forest types into the models which are used in planning climate change mitigation. This study also highlights the high potential for further AGB growth in existing evergreen forests.
PHQ-9, CES-D, health insurance data—who is identified with depression? A Population-based study in persons with diabetes
Authors: Linnenkamp Ute , Gontscharuk Veronika , Ogurtsova Katherine , Brüne Manuela , Chernyak Nadezda , Kvitkina Tatjana , Arend Werner , Schmitz-Losem Imke , Kruse Johannes , Hermanns Norbert , Kulzer Bernd , Evers Silvia M. A. A. , Hiligsmann Mickaël , Hoffmann Barbara , Icks Andrea , Andrich Silke
Published: March 2023

Aims

Several instruments are used to identify depression among patients with diabetes and have been compared for their test criteria, but, not for the overlaps and differences, for example, in the sociodemographic and clinical characteristics of the individuals identified with different instruments.

Methods

We conducted a cross-sectional survey among a random sample of a statutory health insurance (SHI) (n = 1,579) with diabetes and linked it with longitudinal SHI data. Depression symptoms were identified using either the Centre for Epidemiological Studies Depression (CES-D) scale or the Patient Health Questionnaire-9 (PHQ-9), and a depressive disorder was identified with a diagnosis in SHI data, resulting in 8 possible groups. Groups were compared using a multinomial logistic model.

Results

In total 33·0% of our analysis sample were identified with depression by at least one method. 5·0% were identified with depression by all methods. Multinomial logistic analysis showed that identification through SHI data only compared to the group with no depression was associated with gender (women). Identification through at least SHI data was associated with taking antidepressants and previous depression. Health related quality of life, especially the mental summary score was associated with depression but not when identified through SHI data only.

Conclusion

The methods overlapped less than expected. We did not find a clear pattern between methods used and characteristics of individuals identified. However, we found first indications that the choice of method is related to specific underlying characteristics in the identified population. These findings need to be confirmed by further studies with larger study samples.
Supratentorial CNS-PNETs in children; a Swedish population-based study with molecular re-evaluation and long-term follow-up
Authors: Schepke Elizabeth , Löfgren Maja , Pietsch Torsten , Kling Teresia , Nordborg Claes , Olsson Bontell Thomas , Holm Stefan , Öberg Anders , Nyman Per , Eliasson-Hofvander Marie , Sabel Magnus , Lannering Birgitta , Carén Helena
Published: March 2023

Background

Molecular analyses have shown that tumours diagnosed as supratentorial primitive neuro-ectodermal tumours of the central nervous system (CNS-PNETs) in the past represent a heterogenous group of rare childhood tumours including high-grade gliomas (HGG), ependymomas, atypical teratoid/rhabdoid tumours (AT/RT), CNS neuroblastoma with forkhead box R2 (FOXR2) activation and embryonal tumour with multi-layered rosettes (ETMR). All these tumour types are rare and long-term clinical follow-up data are sparse. We retrospectively re-evaluated all children (0–18 years old) diagnosed with a CNS-PNET in Sweden during 1984–2015 and collected clinical data.

Methods

In total, 88 supratentorial CNS-PNETs were identified in the Swedish Childhood Cancer Registry and from these formalin-fixed paraffin-embedded tumour material was available for 71 patients. These tumours were histopathologically re-evaluated and, in addition, analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier.

Results

The most frequent tumour types, after histopathological re-evaluation, were HGG (35%) followed by AT/RT (11%), CNS NB-FOXR2 (10%) and ETMR (8%). DNA methylation profiling could further divide the tumours into specific subtypes and with a high accuracy classify these rare embryonal tumours. The 5 and 10-year overall survival (OS) for the whole CNS-PNET cohort was 45% ± 12% and 42% ± 12%, respectively. However, the different groups of tumour types identified after re-evaluation displayed very variable survival patterns, with a poor outcome for HGG and ETMR patients with 5-year OS 20% ± 16% and 33% ± 35%, respectively. On the contrary, high PFS and OS was observed for patients with CNS NB-FOXR2 (5-year 100% for both). Survival rates remained stable even after 15-years of follow-up.

Conclusions

Our findings demonstrate, in a national based setting, the molecular heterogeneity of these tumours and show that DNA methylation profiling of these tumours provides an indispensable tool in distinguishing these rare tumours. Long-term follow-up data confirms previous findings with a favourable outcome for CNS NB-FOXR2 tumours and poor chances of survival for ETMR and HGG.
Superior protective effects of PGE2 priming mesenchymal stem cells against LPS-induced acute lung injury (ALI) through macrophage immunomodulation
Authors: Hezam Kamal , Wang Chen , Fu Enze , Zhou Manqian , Liu Yue , Wang Hui , Zhu Lihong , Han Zhibo , Han Zhong-Chao , Chang Ying , Li Zongjin
Published: March 2023

Background

Mesenchymal stem cells (MSCs) have demonstrated remarkable therapeutic promise for acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS). MSC secretomes contain various immunoregulatory mediators that modulate both innate and adaptive immune responses. Priming MSCs has been widely considered to boost their therapeutic efficacy for a variety of diseases. Prostaglandin E2 (PGE2) plays a vital role in physiological processes that mediate the regeneration of injured organs.

Methods

This work utilized PGE2 to prime MSCs and investigated their therapeutic potential in ALI models. MSCs were obtained from human placental tissue. MSCs were transduced with firefly luciferase (Fluc)/eGFP fusion protein for real-time monitoring of MSC migration. Comprehensive genomic analyses explored the therapeutic effects and molecular mechanisms of PGE2-primed MSCs in LPS-induced ALI models.

Results

Our results demonstrated that PGE2-MSCs effectively ameliorated lung injury and decreased total cell numbers, neutrophils, macrophages, and protein levels in bronchoalveolar lavage fluid (BALF). Meanwhile, treating ALI mice with PGE2-MSCs dramatically reduced histopathological changes and proinflammatory cytokines while increasing anti-inflammatory cytokines. Furthermore, our findings supported that PGE2 priming improved the therapeutic efficacy of MSCs through M2 macrophage polarization.

Conclusion

PGE2-MSC therapy significantly reduced the severity of LPS-induced ALI in mice by modulating macrophage polarization and cytokine production. This strategy boosts the therapeutic efficacy of MSCs in cell-based ALI therapy.
CT-free quantitative SPECT for automatic evaluation of %thyroid uptake based on deep-learning
Authors: Kwon Kyounghyoun , Hwang Donghwi , Oh Dongkyu , Kim Ji Hye , Yoo Jihyung , Lee Jae Sung , Lee Won Woo
Published: March 2023

Purpose

Quantitative thyroid single-photon emission computed tomography/computed tomography (SPECT/CT) requires computed tomography (CT)-based attenuation correction and manual thyroid segmentation on CT for %thyroid uptake measurements. Here, we aimed to develop a deep-learning-based CT-free quantitative thyroid SPECT that can generate an attenuation map (μ-map) and automatically segment the thyroid.

Methods

Quantitative thyroid SPECT/CT data (n = 650) were retrospectively analyzed. Typical 3D U-Nets were used for the μ-map generation and automatic thyroid segmentation. Primary emission and scattering SPECTs were inputted to generate a μ-map, and the original μ-map from CT was labeled (268 and 30 for training and validation, respectively). The generated μ-map and primary emission SPECT were inputted for the automatic thyroid segmentation, and the manual thyroid segmentation was labeled (280 and 36 for training and validation, respectively). Other thyroid SPECT/CT (n = 36) and salivary SPECT/CT (n = 29) were employed for verification.

Results

The synthetic μ-map demonstrated a strong correlation (R2 = 0.972) and minimum error (mean square error = 0.936 × 10−4, %normalized mean absolute error = 0.999%) of attenuation coefficients when compared to the ground truth (n = 30). Compared to manual segmentation, the automatic thyroid segmentation was excellent with a Dice similarity coefficient of 0.767, minimal thyroid volume difference of − 0.72 mL, and a short 95% Hausdorff distance of 9.416 mm (n = 36). Additionally, %thyroid uptake by synthetic μ-map and automatic thyroid segmentation (CT-free SPECT) was similar to that by the original μ-map and manual thyroid segmentation (SPECT/CT) (3.772 ± 5.735% vs. 3.682 ± 5.516%, p = 0.1090) (n = 36). Furthermore, the synthetic μ-map generation and automatic thyroid segmentation were successfully performed in the salivary SPECT/CT using the deep-learning algorithms trained by thyroid SPECT/CT (n = 29).

Conclusion

CT-free quantitative SPECT for automatic evaluation of %thyroid uptake can be realized by deep-learning.
Exposure to environmental chemicals and cancer risk: epidemiological evidence from Japanese studies
Authors: Iwasaki Motoki , Itoh Hiroaki , Sawada Norie , Tsugane Shoichiro
Published: March 2023

Exposure to certain chemicals in the environment may contribute to the risk of developing cancer. Although cancer risk from environmental chemical exposure among general populations is considered low compared to that in occupational settings, many people may nevertheless be chronically exposed to relatively low levels of environmental chemicals which vary by such various factors as residential area, lifestyle, and dietary habits. It is therefore necessary to assess population-specific exposure levels and examine their association with cancer risk. Here, we reviewed epidemiological evidence on cancer risk and exposure to dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFASs), cadmium, arsenic, and acrylamide. Japanese are widely exposed to these chemicals, mainly through the diet, and an association with increased cancer risk is suspected. Epidemiological evidence from Japanese studies to date does not support a positive association between blood concentrations of DDT, HCH, PCBs, and PFASs and risk of breast or prostate cancer. We established assessment methods for dietary intake of cadmium, arsenic, and acrylamide using a food frequency questionnaire. Overall, dietary intakes of cadmium, arsenic, and acrylamide were not significantly associated with increased risk of total cancer and major cancer sites in the Japan Public Health Center-based Prospective Study. However, statistically significant positive associations were observed between dietary cadmium intake and risk of estrogen receptor-positive breast cancer among postmenopausal women, and dietary arsenic intake and risk of lung cancer among male smokers. In addition, studies using biomarkers as exposure assessment revealed statistically significant positive associations between urinary cadmium concentration and risk of breast cancer, and between ratio of hemoglobin adducts of acrylamide and glycidamide and risk of breast cancer. Epidemiological studies of general populations in Japan are limited and further evidence is required. In particular, studies of the association of organochlorine and organofluorine compounds with risk of cancer sites other than breast and prostate cancer are warranted, as are large prospective studies of the association between biomarkers of exposure and risk of cancer.
Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study
Authors: de Braud Filippo , Dooms Christophe , Heist Rebecca S. , Lebbe Celeste , Wermke Martin , Gazzah Anas , Schadendorf Dirk , Rutkowski Piotr , Wolf Jürgen , Ascierto Paolo A. , Gil-Bazo Ignacio , Kato Shumei , Wolodarski Maria , McKean Meredith , Muñoz Couselo Eva , Sebastian Martin , Santoro Armando , Cooke Vesselina , Manganelli Luca , Wan Kitty , Gaur Anil , Kim Jaeyeon , Caponigro Giordano , Couillebault Xuân-Mai , Evans Helen , Campbell Catarina D. , Basu Sumit , Moschetta Michele , Daud Adil
Published: March 2023

PURPOSE

No approved targeted therapy for the treatment of patients with neuroblastoma RAS viral (v-ras) oncogene homolog ( NRAS)–mutant melanoma is currently available.

PATIENTS AND METHODS

In this phase Ib escalation/expansion study (ClinicalTrials.gov identifier: NCT02974725 ), the safety, tolerability, and preliminary antitumor activity of naporafenib (LXH254), a BRAF/CRAF protein kinases inhibitor, were explored in combination with trametinib in patients with advanced/metastatic KRAS- or BRAF-mutant non–small-cell lung cancer (escalation arm) or NRAS-mutant melanoma (escalation and expansion arms).

RESULTS

Thirty-six and 30 patients were enrolled in escalation and expansion, respectively. During escalation, six patients reported grade ≥3 dose-limiting toxicities, including dermatitis acneiform (n = 2), maculopapular rash (n = 2), increased lipase (n = 1), and Stevens-Johnson syndrome (n = 1). The recommended doses for expansion were naporafenib 200 mg twice a day plus trametinib 1 mg once daily and naporafenib 400 mg twice a day plus trametinib 0.5 mg once daily. During expansion, all 30 patients experienced a treatment-related adverse event, the most common being rash (80%, n = 24), blood creatine phosphokinase increased, diarrhea, and nausea (30%, n = 9 each). In expansion, the objective response rate, median duration of response, and median progression-free survival were 46.7% (95% CI, 21.3 to 73.4; 7 of 15 patients), 3.75 (95% CI, 1.97 to not estimable [NE]) months, and 5.52 months, respectively, in patients treated with naporafenib 200 mg twice a day plus trametinib 1 mg once daily, and 13.3% (95% CI, 1.7 to 40.5; 2 of 15 patients), 3.75 (95% CI, 2.04 to NE) months, and 4.21 months, respectively, in patients treated with naporafenib 400 mg twice a day plus trametinib 0.5 mg once daily.

CONCLUSION

Naporafenib plus trametinib showed promising preliminary antitumor activity in patients with NRAS-mutant melanoma. Prophylactic strategies aimed to lower the incidence of skin-related events are under investigation.
Green Walls: Everyday Ecofascism and the Politics of Proximity
Authors: Anson April , Banerjee Anindita
Published: March 2023

QAnon's rallying cry of “the storm” on January 6 and thereafter articulates a structural taxonomy of planetary scale and apocalyptic eschatology that pervades the environmental imaginaries of contemporary fascism. While they become visible only in times of emergency and states of exception, this essay argues that equal attention needs to be paid to expressions and operations of ecofascism in the mundane places and practices of everyday life. Expanding beyond the geographic and historical specificities of Nazism and its transatlantic dialogue with North American settler colonialism, this essay theorizes everyday ecofascism as an oiko-logics and oiko-nomics across borders, a transversal condition of deeply globalized, inextricably interconnected structures and systems.
Effect of carbon nanoparticle addition on epoxy cure
Authors: Δημόπουλος Αθανάσιος
Published: March 2023

Η διατριβή αναφέρεται σε μελέτες κινητικής και μεταβολής της θερμοκρασίας υαλώδους μετάπτωσης τριών εμπορικών συστημάτων εποξειδικής ρητίνης: MY 750/ HY 5922 (Vantico), MTM 44 -1 (ACG) και 8552 (Hexcel Composites). Η έρευνα διεξήχθη με τη χρήση Διαφορικής Θερμιδομετρίας Σάρωσης (DSC) και Διαμόρφωσης Θερμοκρασίας DSC (TMDSC). Κατάλληλα φαινομενολογικά μοντέλα κινητικής κατασκευάστηκαν για να προβλέψουν τον βαθμό αντίδρασης ως συνάρτηση του προφίλ θερμοκρασίας/χρόνου. Η εγκυρότητα της υπέρθεσης δυναμικών και ισοθερμικών πειραματικών δεδομένων επιβεβαιώθηκε. Ρεολογικές μετρήσεις πραγματοποιήθηκαν προκειμένου να προσδιοριστεί η περιοχή ζελατινοποίησης κάτω από δεδομένες συνθήκες. Η μεθοδολογία μοντελοποίησης επικυρώθηκε λαμβάνοντας μέρος σε μια διεθνή άσκηση Round-Robin με επικεφαλής το Πανεπιστήμιο της Βρετανικής Κολομβίας (Καναδάς).Τα αποτελέσματα της ενσωμάτωσης νανοσωματιδίων άνθρακα στην κινητική αντίδρασης και η αύξηση της θερμοκρασίας υαλώδους μετάπτωσης για δύο από τα εποξειδικά συστήματα μελετήθηκαν επίσης. Τα μοντέλα κινητικής αναπτύχθηκαν για νανοσύνθετα υλικά που περιέχουν εμπορικούς νανοσωλήνες άνθρακα πολλαπλών τοιχωμάτων και έγινε άμεση σύγκριση με τα μοντέλα των συστημάτων σκέτης ρητίνης. Η πρόοδος της θερμοκρασίας υαλώδους μετάπτωσης φαίνεται να επηρεάζεται στα αρχικά στάδια της αντίδρασης. Μελετήθηκε η κατάσταση της διασποράς των νανοσωματιδίων προκειμένου να συσχετιστούν με τις παρατηρούμενες επιδράσεις στην αντίδραση και στη μορφολογία των αντιδρώντων δειγμάτων. Η παρουσία συστάδων νανοσωλήνων άνθρακα φαίνεται να έχει επίδραση στον διαχωρισμό φάσεων στο σύστημα ρητίνης MTM 44-1. Ως πιθανή βιομηχανική εφαρμογή αυτής της μελέτης, οι οπτικές ίνες χρησιμοποιήθηκαν ως τεχνική παρακολούθησης της αντίδρασης σε απευθείας σύνδεση. Διαπιστώθηκε μία καλή συσχέτιση μεταξύ των μετρούμενων μεταβολών του δείκτη διάθλασης κατά τη διάρκεια της αντίδρασης και της απόδοσης της αντίδρασης που προβλέπεται από τα παραπάνω μοντέλα, για τα σκέτα συστήματα ρητίνης και τα νανοσύνθετά τους.
Formulation and in vitro evaluation of meloxicam as a self-microemulsifying drug delivery system
Authors: Muhammed Saja Abdulkareem , Al-Kinani Khalid Kadhem
Published: March 2023

Background: The nonsteroidal anti-inflammatory medication meloxicam (MLX) belongs to the oxicam family and is used to reduce inflammation and pain. The aim of this study was to improve MLX's dispersibility and stability by producing it as a liquid self-microemulsifying drug delivery system since it is practically insoluble in water.

Methods: Five different formulations were made by adjusting the amounts of propylene glycol, Transcutol P, Tween 80, and oleic acid oil and establishing a pseudo-ternary diagram in ratios of 1:1, 1:2, 1:3, 1:4, and 3:4, respectively. All of the prepared formulations were tested for a variety of properties, including thermodynamic stability, polydispersity index, particle size distributions, dilution resistance, drug contents, dispersibility, in vitro solubility of the drug, and emulsification time.

Results: F5 was chosen as the optimal MLX liquid self-microemulsion due to its higher drug content (99.8%), greater in vitro release (100% at 40 min), smaller droplet size (63 nm), lower polydispersity index (PDI) value (0.3), and higher stability (a zeta potential of -81 mV).

Conclusions: According to the data provided here, the self-microemulsifying drug delivery system is the most practical method for improving the dispersibility and stability of MLX.
Measuring Benefits from New Products in Markets with Information Frictions
Authors: Morozov Ilya
Published: March 2023

I study how much consumers benefit from new products in markets with information frictions. I analyze new products in the U.S. hard drive market, which is characterized by ample product innovation. Using unique click-stream data, I measure the magnitude of two frictions, category consideration and costly search, and show that both play a crucial role in shaping consumer demand. To estimate consumer surplus from new products, I develop a search model that captures both frictions and propose a novel Bayesian estimation method to recover its parameters. I then show that ignoring information frictions leads researchers to underestimate the consumer surplus from new hard drives because it appears that consumers do not value the combinations of attributes these hard drives offer. Partly eliminating frictions, through marketing efforts or market-wide transparency initiatives, can help consumers to more fully internalize the benefits of new product launches.

This paper was accepted by Matthew Shum, marketing.

Supplemental Material: The data files and online appendices are available at https://doi.org/10.1287/mnsc.2023.4729 .
Analysis of a WDM system with a modified duobinary modulation scheme in an optical network using EDFA
Authors: Janakiraman Vidhya , Michael Margarat , Britto Elizabeth Caroline
Published: March 2023

Advanced modulation format is a promising solution to accomplish improved bandwidth exploitation for quality transmission in optical networks. This paper proposes a modified duobinary modulation in an optical communication network, and the proposed system is compared with the preceding modulation scheme of duobinary modulation without a precoder and duobinary modulation with a precoder. Ideally, two or more signals are transmitted over single-mode fiber using a multiplexing method. Hence, wavelength division multiplexing (WDM) using an erbium-doped fiber amplifier (EDFA) as an active optical network is utilized to improve the quality factor and reduce the effect of intersymbol interference in optical networks. The performance of the proposed system is analyzed for parameters such as quality factor, bit error rate, and extinction ratio using OptiSystem 14 software.
High-resolution astronomical spectrograph design method with a single echelle grating
Authors: Kukushkin Dmitrii E. , Sazonenko Dmitrii A. , Valyavin Gennady G. , Bakholdin Alexey V.
Published: March 2023

The paper presents a method for calculation of the main paraxial and
energy parameters of a high-resolution astronomical spectrograph with
a single echelle grating in a wide spectral range, without
cross-dispersion elements. We consider two variants of the system
design, namely, with a fixed grating (spectrograph) and with a movable
grating (monochromator). Based on the analysis of the spectral
resolution dependence on the echelle grating characteristics and the
collimated beam diameter, the limits of the achievable maximum
spectral resolution of the system are determined. The results obtained
in this work can simplify the choice of the starting point for
spectrograph designing. As an example of the presented method
application design of the spectrograph for the Large Solar
Telescope-coronagraph LST-3, operating in the spectral range of
390–900 nm, with spectral resolving power of R=200,000 and minimum diffraction efficiency of
the echelle grating I
g
>0.68, is considered.
Photoacoustic imaging with limited sampling: a review of machine learning approaches
Authors: Wang Ruofan , Zhu Jing , Xia Jun , Yao Junjie , Shi Junhui , Li Chiye
Published: March 2023

Photoacoustic imaging combines high optical absorption contrast and deep acoustic penetration, and can reveal structural, molecular, and functional information about biological tissue non-invasively. Due to practical restrictions, photoacoustic imaging systems often face various challenges, such as complex system configuration, long imaging time, and/or less-than-ideal image quality, which collectively hinder their clinical application. Machine learning has been applied to improve photoacoustic imaging and mitigate the otherwise strict requirements in system setup and data acquisition. In contrast to the previous reviews of learned methods in photoacoustic computed tomography (PACT), this review focuses on the application of machine learning approaches to address the limited spatial sampling problems in photoacoustic imaging, specifically the limited view and undersampling issues. We summarize the relevant PACT works based on their training data, workflow, and model architecture. Notably, we also introduce the recent limited sampling works on the other major implementation of photoacoustic imaging, i.e., photoacoustic microscopy (PAM). With machine learning-based processing, photoacoustic imaging can achieve improved image quality with modest spatial sampling, presenting great potential for low-cost and user-friendly clinical applications.
In vivo longitudinal 920 nm two-photon intravital kidney imaging of a dynamic 2,8-DHA crystal formation and tubular deterioration in the adenine-induced chronic kidney disease mouse model
Authors: Choi Jieun , Choi Min-Sun , Jeon Jehwi , Moon Jieun , Lee Jingu , Kong Eunji , Lucia Stephani Edwina , Hong Sujung , Lee Ji-Hye , Lee Eun Young , Kim Pilhan
Published: March 2023

Chronic kidney disease (CKD) is one of the most common renal diseases manifested by gradual loss of kidney function with no symptoms in the early stage. The underlying mechanism in the pathogenesis of CKD with various causes such as high blood pressure, diabetes, high cholesterol, and kidney infection is not well understood. In vivo longitudinal repetitive cellular-level observation of the kidney of the CKD animal model can provide novel insights to diagnose and treat the CKD by visualizing the dynamically changing pathophysiology of CKD with its progression over time. In this study, using two-photon intravital microscopy with a single 920 nm fixed-wavelength fs-pulsed laser, we longitudinally and repetitively observed the kidney of an adenine diet-induced CKD mouse model for 30 days. Interestingly, we could successfully visualize the 2,8-dihydroxyadenine (2,8-DHA) crystal formation with a second-harmonics generation (SHG) signal and the morphological deterioration of renal tubules with autofluorescence using a single 920 nm two-photon excitation. The longitudinal in vivo two-photon imaging results of increasing 2,8-DHA crystals and decreasing tubular area ratio visualized by SHG and autofluorescence signal, respectively, were highly correlated with the CKD progression monitored by a blood test showing increased cystatin C and blood urea nitrogen (BUN) levels over time. This result suggests the potential of label-free second-harmonics generation crystal imaging as a novel optical technique for in vivo CKD progression monitoring.