bluuebunny/crossref_metadata_2025 huggingface dataset:
Reciprocal transplants reveal asymmetric local adaptation of Himalayan Rhododendron approaching elevational range limit
Authors: Mainali Kumar , Adhikari Subodh , Shrestha Sushila , Singer Michael C. , White Joseph , Parmesan Camille
Published: July 2023

As plant species expand their upper limits of distribution under current warming, some retain both traditional climate space and biotic environment while others encounter novel conditions. The latter is the case for Rhododendron campanulatum, a woody shrub that grows both above and below treeline at our study site in the Eastern Himalayas where a very conspicuous, stable treeline was defined by a nearly contiguous canopy of tall Abies spectabilis trees, many of which are over a century old. Prior work showed that treeline had remained static in this region while R. campanulatum expanded its elevational range limit. We tested local adaptation of R. campanulatum by performing reciprocal transplants between the species' current elevational range limit (4023 m above sea level [asl]) and just above treeline (3876 m asl). Contrary to expectation, the coldest temperatures of late winter and early mid‐spring were experienced by plants at the lower elevation: R. campanulatum at species' limit (upper site) were covered by snow for a longer period (40 more days) and escaped the coldest temperatures suffered by conspecifics at treeline (lower site). The harsher spring conditions at treeline likely explain why leaves were smaller at treeline (15.3 cm2) than at species limit (21.3 cm2). Contrary to results from equivalent studies in other regions, survival was reduced more by downslope than by upslope movement, again potentially due to extreme cold temperatures observed at treeline in spring. Upslope transplantation had no effect on mortality, but mortality of species limit saplings transplanted downslope was three times higher than that of residents at both sites. A general expectation is that locals should survive better than foreign transplants, but survival of locals and immigrants at our species limit site was identical. However, those species limit saplings that survived the transplant to treeline grew faster than both locals at treeline and the transplants at species limit. Overall, we found asymmetric adaptation: Compared with treeline saplings, those at species limit (147 m above treeline) were more tolerant of extremes in the growing season but less tolerant of extremes in winter and early mid‐spring, displaying local adaptation in a more complex manner than simply home advantage, and complicating predictions about impacts of future regional climate change.
Optimization of jujube peel pigment multivesicular liposome formulation and evaluation of the protective effect on UVB‐induced photodamage
Authors: Liu Zhiming , Zheng Ying , Yue Bowen , Luo Yali , Cao Zhaoxin , Su Jingyi , Wang Xinyu , Zhang Yan , Zhang Yifei , Wang Bingxue , Cheng Xiaoliang , Zhou Zhiyong , Ge Xuemei
Published: July 2023

Jujube peel pigment (JP), an ideal natural water‐soluble pigment extracted from jujube peel, mainly consists of flavonoids and possesses a wide range of physiological activities. In this study, JP‐loaded multivesicular liposomes (JP‐MVL) were prepared using the double emulsification method. JP‐MVL was characterized, and its encapsulation efficiency was determined using the UV‐Vis method. Furthermore, the release behavior and antioxidant capacity of JP‐MVL were evaluated in vitro. The results displayed in the structure of JP‐MVL were spherical with internal vesicles; the average particle size of JP‐MVL was 5.63 μm, and the zeta potential was −69.50 mV. Analysis of the release results indicated that the best‐fitting models in PBS (Phosphate buffered saline pH 7.4) and 0.9% NaCl were the Higuchi and first‐order kinetic models, respectively. The cytotoxicity of JP‐MVL at the appropriate concentrations was negligible and had a good protective effect against UVB‐induced photodamage.
Deconstructing Eurocentrism in skin pigmentation research via the incorporation of diverse populations and theoretical perspectives
Authors: Pryor Yemko , Lindo John
Published: July 2023

The evolution of skin pigmentation has been shaped by numerous biological and cultural shifts throughout human history. Vitamin D is considered a driver of depigmentation evolution in humans, given the deleterious health effects associated with vitamin D deficiency, which is often shaped by cultural factors. New advancements in genomics and epigenomics have opened the door to a deeper exploration of skin pigmentation evolution in both contemporary and ancient populations. Data from ancient Europeans has offered great context to the spread of depigmentation alleles via the evaluation of migration events and cultural shifts that occurred during the Neolithic. However, novel insights can further be gained via the inclusion of diverse ancient and contemporary populations. Here we present on how potential biases and limitations in skin pigmentation research can be overcome with the integration of interdisciplinary data that includes both cultural and biological elements, which have shaped the evolutionary history of skin pigmentation in humans.
Harvesting the volatility smile in a large emerging market: A Dynamic Nelson–Siegel approach
Authors: Kumar Sudarshan , Agarwalla Sobhesh Kumar , Varma Jayanth R. , Virmani Vineet
Published: July 2023

While there is a large literature on modeling volatility smile in options markets, most such studies are eventually focused on the forecasting performance of the model parameters and not on the applicability of the models in a trading environment. Drawing on the analogy of volatility smile like a term structure in the context of interest rates in fixed‐income markets, we evaluate the performance of the Dynamic Nelson–Siegel (DNS) approach to modeling the dynamics of volatility smile in a trading environment against competing alternatives. Using model‐based mispricing as our sorting criterion, and deploying a trading strategy of going long the options in the upper deciles and going short the options in the lower deciles, we show that dynamic models consistently outperform their static counterparts, with the worst dynamic model outperforming the best static model in terms of the percentage of mean returns from the trading portfolios and the Sharpe ratio. Specifically, we find that the DNS model consistently outperforms all other competing specifications on most of our selected criteria.
Refined cytogenetic IPSS‐R evaluation by the use of SNP array in a cohort of 290 MDS patients
Authors: Scarpelli Ilaria , Stalder Valérie Beyer , Tsilimidos Gerasimos , Rapakko Katrin , Costanza Mariangela , Blum Sabine , Schoumans Jacqueline
Published: July 2023

Genetic testing plays a central role in myelodysplastic neoplasms (MDS) diagnosis, prognosis, and therapeutic decisions. The widely applied cytogenetic revised international prognostic scoring system (IPSS‐R) was based on chromosome banding analysis (CBA). However, subsequently developed genetic methodologies, such as single nucleotide polymorphism (SNP) array, demonstrated to be a valid alternative test for MDS. SNP array is, in fact, able to detect the majority of MDS‐associated cytogenetic aberrations, by providing further genomic information due to its higher resolution. In this study, 290 samples from individuals with a confirmed or suspected diagnosis of MDS were tested by both CBA and SNP array, in order to evaluate and compare their cytogenetic IPSS‐R score in the largest MDS cohort reported so far. A concordant or better refined cytogenetic IPSS‐R array‐based score was obtained for 95% of cases (277). Therefore, this study confirms the effective applicability of SNP array toward the cytogenetic IPSS‐R evaluation and consequently, toward the molecular international prognostic scoring system for MDS (IPSS‐M) assessment, which ensures an improved MDS risk stratification refinement. Considering the advent of additional genetic technologies interrogating the whole genome with increased resolutions, counting cytogenetic abnormalities based on their size may result in a simplistic approach. On the contrary, assessing overall genomic complexity may provide additional crucial information. Independently of the technology used, genetic results should indeed aim at ensuring a highly refined stratification for MDS patients.
Current status of sinonasal cancer survivorship care
Authors: Han Albert Y. , Nader Marc‐Elie , Lam Keng , Su Shirley Y.
Published: July 2023

Sinonasal cancer is a heterogeneous orphan disease of diverse histologies, each with distinct clinical, oncologic, and toxicity profiles. Because of the comparative rarity of these cancers, sinonasal cancers are treated as a grouped diagnosis despite their clinical and biological heterogeneity. Multimodality treatment with a combination of surgery, chemotherapy, and/or radiotherapy is the standard‐of‐care for advanced‐stage patients but there are few surveillance or follow‐up practice guidelines or formalized survivorship care pathways. A scoping literature review was conducted via PubMed, EMBASE, and Google Scholar. A total of 112 studies were included, which were grouped along the following topics: surveillance, second primary tumors, quality of life, and symptom burden. Sinonasal cancer tends to exhibit a higher rate of local failure and occur in a delayed fashion compared to mucosal malignancies of the head and neck. Moreover, the site of failure and time‐varying risk of recurrence is histology‐specific. Following multimodality treatment of the skull base, patients may experience endocrine, visual, auditory, sinonasal, olfactory, and neurocognitive deficits, as well as psychosocial impairments that impact multiple physical and neuropsychological domains, resulting in diminished quality of life. Sinonasal cancer patients would benefit from tailored, histology‐specific survivorship programs to address the recurrence, second primary, and functional impairments resulting from disease and treatment toxicity.
BAG3: An enticing therapeutic target for idiopathic pulmonary fibrosis
Authors: Chillappagari Shashipavan , Guenther Andreas , Mahavadi Poornima
Published: July 2023

Idiopathic pulmonary fibrosis (IPF) is a dreadful and fatal disease of unknown etiology, for which no cure exists. Autophagy, a lysosomal cellular surveillance pathway is insufficiently activated in both alveolar epithelial type II cells and fibroblasts of IPF patient lungs. Fine‐tuning this pathway may result in the degradation of the accumulated cargo and influence cell fate. Based on our previous data, we here present our view on modulating autophagy via a unique co‐chaperone, namely Bcl2‐associated athanogene3 (BAG3) in IPF and discuss about how repurposing drugs that modulate this pathway may emerge as a promising novel therapeutic approach for IPF.
Totally symmetric quasigroups of order 16
Authors: Ginsberg Hy
Published: July 2023

We present the number of totally symmetric quasigroups (equivalently, totally symmetric Latin squares) of order 16, as well as the number of isomorphism classes of such objects. Totally symmetric quasigroups of orders up to and including 16 that are (respectively) medial, idempotent, and unipotent are also enumerated.
Patterns of morphological variation and ecological correlates in the skull of vipers (Serpentes: Viperidae)
Authors: Carrasco Paola A. , Prystupczuk Lilen , Koch Claudia , González Germán A. , Leynaud Gerardo C. , Grazziotin Felipe G.
Published: July 2023

The skull of vipers is a highly kinetic anatomical structure involved in envenomating and consuming of prey. Morphological knowledge about the viperid skull is based on studies on some groups of species, but information on its variation within the whole family and its functional morphology is still scarce. In this study, we aimed to explore variation in skull morphology among species of the three subfamilies of Viperidae, and test whether that variation correlates with macrohabitat and diet. We performed quantitative analyses of the viperid skull based on broad taxonomic sampling and two methodological approaches: linear and geometric morphometrics. The results of both approaches showed that much of the variation lies in differences of shape and relative size of the premaxilla, the nasals, the frontals, and the parietals. The results indicated that phylogeny and size influence the shape of the skull, but we also found evidence of morphological differentiation between arboreal and terrestrial species and in species with mammal specialist diet. Our findings imply that, besides evolutionary allometry and phylogenetic signal, demands of particular diets coupled with use of certain habitats have in part shaped morphological evolution of the viperid skull.
The impact of body mass index on oncoplastic breast surgery: A multicenter analysis
Authors: De La Cruz Ku Gabriel , Camarlinghi Madison , Mallouh Michael P. , Torres‐Roman J. Smith , Linshaw David , Persing Sarah M. , Nardello Salvatore , Chatterjee Abhishek
Published: July 2023

Background

Obesity has nearly tripled in the last 50 years. During the last decades, oncoplastic breast surgery has become an important choice in the surgical treatment of breast cancer. An association exists between higher body mass index (BMI) and wound complications for major operations, but there is scarce literature on oncoplastic surgery. Hence, our aim was to compare the complication rates among patients who underwent oncoplastic surgery, stratified by BMI.

Methods

Patient data were analyzed from the National Surgical Quality Improvement Program database (NSQIP) for oncoplastic breast procedures (2005–2020). Patients were stratified according to World Health Organization obesity classifications. Multivariate logistic regression was performed to assess risk factors for complications (overall, operative, and wound‐related).

Results

From a total of 6887 patients who underwent oncoplastic surgery, 4229 patients were nonobese, 1380 had Class 1 obesity (BMI: 30 to <35 kg/m2), 737 Class 2 obesity (BMI: 35 to <40 kg/m2), and 541 Class 3 obesity (BMI: ≥ 40 kg/m2). Greater operative time was found according to higher BMI (p < 0.001). Multivariate analysis adjusted for baseline characteristics showed that patients with obesity Class 2 (odds ratio [OR] = 1.51, 95% confidence interval [CI]: 1.03–2.23, p = 0.037) and 3 (OR = 1.87, 95% CI 1.24–2.83, p = 0.003) had increased risk of overall and wound complications compared with Nonobese patients. Comparing obese with nonobese patients, there were no differences in rates of deep SSI, organ/space SSI, pneumonia, reintubation, pulmonary embolism, deep vein thrombosis, urinary tract infection, stroke, bleeding, postoperative sepsis, length of stay, and readmission.

Conclusions

Oncoplastic surgery is a safe procedure for most patients. However, caution should be exercised when performing oncoplastic surgery for patients with Class 2 or 3 obesity (BMI ≥ 35 kg/m2), given there was a higher rate of overall and wound‐specific complications, compared with patients who were not obese or had Class 1 obesity.
Hypotensive Levels on Endoscopic Sinus Surgery Visibility: A Randomized Non‐Inferiority Trial
Authors: Zhang Kangda , Wang Lichun , Qi Feng , Meng Tao
Published: July 2023

Objective

Optimization of endoscopic sinus surgery (ESS) conditions is a common focus of interest for otolaryngologists and anesthesiologists. Relying on hypotension alone to achieve a bloodless field may not without risks. We sought to determine whether ESS is feasible in the context of moderate hypotension.

Methods

This randomized non‐inferiority trial enrolled 96 adult patients who were to undergo ESS. The patients were divided into two groups: Controlled hypotension group (n = 48, MAP reduction to 55–65 mmHg, minimum of 60% of baseline blood pressure) or Individualized hypotension group (n = 48, MAP reduction to 75–80% of baseline blood pressure). All participants were placed in 10° reverse Trendelenburg position during ESS, and cottonoid patties dammed with epinephrine was recommended to clear the operative field of bleeding. The two groups were compared according to Boezaart grading scale (BS) score, estimated blood loss, blood loss rate, arterial lactate level and postoperative recovery.

Results

Both levels of intraoperative hypotension (62.2 ± 2.3 mmHg vs. 74.0 ± 2.8 mmHg) provided acceptable surgical conditions with no difference in mean BS scores [2.00 (1.88–2.33) vs. 2.00 (1.85–2.45), p = 0.926]. The 95% CI for median value differences in mean BS scores is lower than the preset non‐inferiority margin. There were no differences in blood loss rate and estimated blood loss between two groups (p > 0.05) Postoperative arterial lactate and Ramsay sedation scores were significantly different between the two groups (p < 0.05).

Conclusions

In ESS, both levels of intraoperative hypotension, combined with position adjustment and low‐concentration adrenaline to constrict nasal mucosal blood vessels, provided acceptable surgical conditions.

Level of Evidence

2 Laryngoscope, 134:569–576, 2024
Predicting Acoustic Hearing Preservation Following Cochlear Implant Surgery Using Machine Learning
Authors: Zeitler Daniel M , Buchlak Quinlan D , Ramasundara Savindi , Farrokhi Farrokh , Esmaili Nazanin
Published: July 2023

Objectives

The aim of the study was to train and test supervised machine‐learning classifiers to predict acoustic hearing preservation after CI using preoperative clinical data.

Study Design

Retrospective predictive modeling study of prospectively collected single‐institution CI dataset.

Methods

One hundred and seventy‐five patients from a REDCap database including 761 patients >18 years who underwent CI and had audiometric testing preoperatively and one month after surgery were included. The primary outcome variable was the lowest quartile change in acoustic hearing at one month after CI using various formulae (standard pure tone average, SPTA; low‐frequency PTA, LFPTA). Analysis involved applying multivariate logistic regression to detect statistical associations and training and testing supervised learning classifiers. Classifier performance was assessed with numerous metrics including area under the receiver operating characteristic curve (AUC) and Matthews correlation coefficient (MCC).

Results

Lowest quartile change (indicating hearing preservation) in SPTA was positively associated with a history of meningitis, preoperative LFPTA, and preoperative SPTA. Lowest quartile change in SPTA was negatively associated with sudden hearing loss, noise exposure, aural fullness, and abnormal anatomy. Lowest quartile change in LFPTA was positively associated with preoperative LFPTA. Lowest quartile change in LFPTA was negatively associated with tobacco use. Random forest demonstrated the highest mean classification performance on the validation dataset when predicting each of the outcome variables.

Conclusions

Machine learning demonstrated utility for predicting preservation of residual acoustic hearing in patients undergoing CI surgery, and the detected associations facilitated the interpretation of our machine‐learning models. The models and statistical associations together may be used to facilitate improvements in shared clinical decision‐making and patient outcomes.

Level of Evidence

3 Laryngoscope, 134:926–936, 2024
m6A reader YTHDF3 triggers the progression of hepatocellular carcinoma through the YTHDF3/m6A‐EGFR/STAT3 axis and EMT
Authors: Hu Bowen , Gao Jie , Shi Jihua , Wen Peihao , Guo Wenzhi , Zhang Shuijun
Published: July 2023

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of tumor‐related deaths worldwide. N6‐methyladenosine (m6A) mediates RNA metabolism in tumor biology. However, the regulatory role of YTHDF3, an m6A reader, in HCC progression and its underlying mechanisms remains unclear. Therefore, this study aims to investigate the oncogenic effect of YTHDF3 on HCC progression via the epigenetic regulation of m6A‐modified mRNAs. The expression levels of YTHDF3 in HCC tissues and matched adjacent liver tissues were detected using western blot analysis, immunohistochemistry, and quantitative real‐time polymerase chain reaction. The function of YTHDF3 in HCC progression and its underlying mechanisms have been studied both in vitro and in vivo. YTHDF3 expression was significantly higher in HCC tissues than in paracancerous liver tissues. YTHDF3 was also significantly upregulated in HCC with microvascular invasion (MVI) compared to that in HCC without MVI. YTHDF3 overexpression facilitated the proliferation, invasion, and migration of HCC cells both in vitro and in vivo. However, the YTHDF3 knockdown resulted in an inverse trend. Mechanistically, YTHDF3 enhanced the translation and stability of the m6A‐modified epidermal growth factor receptor (EGFR) mRNA, which activated the downstream EGFR/signal transducer and activator of transcription 3 (STAT3) and epithelial‐mesenchymal transition (EMT) oncogenic pathways. YTHDF3 enhanced the stability and translation of m6A‐modified EGFR mRNA and stimulated HCC progression via the YTHDF3/m6A‐EGFR/STAT3 and EMT pathways. These findings reveal that YTHDF3 plays a significant role in regulating HCC progression, suggesting a promising and novel target for HCC treatment.
LKB1 loss promotes colorectal cancer cell metastasis through regulating TNIK expression and actin cytoskeleton remodeling
Authors: Hu Guanghui , Huang Ning , Zhang Jing , Zhang Die , Wang Shuren , Zhang Yuanyuan , Wang Liming , Du Yingxi , Kuang Shuwen , Ma Kai , Zhu Hongxia , Xu Ningzhi , Liu Mei
Published: July 2023

Colorectal cancer (CRC) is one of the most common malignant tumors. Approximately 5%–6% of CRC cases are associated with hereditary CRC syndromes, including the Peutz–Jeghers syndrome (PJS). Liver kinase B1 (LKB1), also known as STK11, is the major gene responsible for PJS. LKB1 heterozygotic deficiency is involved in intestinal polyps in mice, while the mechanism of LKB1 in CRC remains elusive. In this study, we generated LKB1 knockout (KO) CRC cell lines by using CRISPR‐Cas9. LKB1 KO promoted CRC cell motility in vitro and tumor metastases in vivo. LKB1 attenuated expression of TRAF2 and NCK‐interacting protein kinase (TNIK) as accessed by RNA‐seq and western blots, and similar suppression was also detected in the tumor tissues of azoxymethane/dextran sodium sulfate‐induced intestinal‐specific LKB1‐KO mice. LKB1 repressed TNIK expression through its kinase activity. Moreover, attenuating TNIK by shRNA inhibited cell migration and invasion of CRC cells. LKB1 loss‐induced high metastatic potential of CRC cells was depended on TNIK upregulation. Furthermore, TNIK interacted with ARHGAP29 and further affected actin cytoskeleton remodeling. Taken together, LKB1 deficiency promoted CRC cell metastasis via TNIK upregulation and subsequently mediated cytoskeleton remodeling. These results suggest that LKB1‐TNIK axis may play a crucial role in CRC progression.
Some results for a system of NLS arising in optical materials with χ3 nonlinear response
Authors: Zhang Guoqing , Duan Yingxin
Published: July 2023

In this paper, we investigate the nonlinear Schödinger equations with cubic interactions, arising in nonlinear optics. To begin, we prove the existence results for normalized ground state solutions in the subcritical case and
‐supercritical case, respectively. Our proofs relies on the Concentration‐compactness principle, Pohozaev manifold, and rearrangement technique. Then, we establish the nonexistence of normalized ground state solutions in the
‐critical case by finding that there exists a threshold. In addition, based on the existence of the normalized solutions, we also establish the blow‐up results by using localized virial estimates as well as a new blow‐up criterion which is related to normalized solutions.
Pretreatment information–aided automatic segmentation for online magnetic resonance imaging‐guided prostate radiotherapy
Authors: Yang Bining , Liu Yuxiang , Zhu Ji , Lu Ningning , Dai Jianrong , Men Kuo
Published: July 2023

Background

It is necessary to contour regions of interest (ROIs) for online magnetic resonance imaging (MRI)‐guided adaptive radiotherapy (MRIgART). These updated contours are used for online replanning to obtain maximum dosimetric benefits. Contouring can be accomplished using deformable image registration (DIR) and deep learning (DL)‐based autosegmentation methods. However, these methods may require considerable manual editing and thus prolong treatment time.

Purpose

The present study aimed to improve autosegmentation performance by integrating patients’ pretreatment information in a DL‐based segmentation algorithm. It is expected to improve the efficiency of current MRIgART process.

Methods

Forty patients with prostate cancer were enrolled retrospectively. The online adaptive MR images, patient‐specific planning computed tomography (CT), and contours in CT were used for segmentation. The deformable registration of planning CT and MR images was performed first to obtain a deformable CT and corresponding contours. A novel DL network, which can integrate such patient‐specific information (deformable CT and corresponding contours) into the segmentation task of MR images was designed. We performed a four‐fold cross‐validation for the DL models. The proposed method was compared with DIR and DL methods on segmentation of prostate cancer. The ROIs included the clinical target volume (CTV), bladder, rectum, left femur head, and right femur head. Dosimetric parameters of automatically generated ROIs were evaluated using a clinical treatment planning system.

Results

The proposed method enhanced the segmentation accuracy of conventional procedures. Its mean value of the dice similarity coefficient (93.5%) over the five ROIs was higher than both DIR (87.5%) and DL (87.2%). The number of patients (n = 40) that required major editing using DIR, DL, and our method were 12, 18, and 7 (CTV); 17, 4, and 1 (bladder); 8, 11, and 5 (rectum); 2, 4, and 1 (left femur head); and 3, 7, and 1 (right femur head), respectively. The Spearman rank correlation coefficient of dosimetry parameters between the proposed method and ground truth was 0.972 ± 0.040, higher than that of DIR (0.897 ± 0.098) and DL (0.871 ± 0.134).

Conclusion

This study proposed a novel method that integrates patient‐specific pretreatment information into DL‐based segmentation algorithm. It outperformed baseline methods, thereby improving the efficiency and segmentation accuracy in adaptive radiotherapy.
Efficient numerical strategies for an implicit volume fraction transfer scheme for single crystal plasticity including twinning and secondary plasticity on the example of magnesium
Authors: Dittmann Jan , Wulfinghoff Stephan
Published: July 2023

In this work an efficient algorithm for a fully implicit single crystal plasticity routine including twinning and secondary plasticity is presented and implemented for the example of magnesium. The material model uses the volume fraction transfer scheme for the evolution of twinning, that is, plastic slip in newly formed twins (“secondary plasticity”) is resolved. This is considered particularly important, if the volume fractions of some twins reach the order of magnitude of the parent phase. However the resolution of secondary plasticity also implies a large number of unknowns, which is significantly reduced by a newly proposed algorithm. For magnesium a hardening model based on basal, prismatic, pyramidal a and pyramidal c+a slip modes as well as a tension and a compression twinning mode and yields a total of 18 slip systems and 12 twinning systems. As a special feature of the proposed algorithm, the total amount of 246 unknowns, due to simultaneous slip in the parent phase and the twinned phases, is reduced to only 31 unknowns. Additionally, thermodynamic consistency is ensured by including the second law with the Clausius–Duhem equation, which considers the change of free energy upon twinning as an additional driving force for twinning. Further, the setup of the time discrete nonlinear equation system using midpoint rule, as well as the analytical solution of the algorithmic tangent are given in detail. Finally, the implemented model is tested in finite element simulations and compared to single‐ and polycrystal compression and tension experiments.
Encouraging adherence in adolescents with asthma using financial incentives: An RCT
Authors: Keyser Heather H. De , Brinton John T. , Bothwell Samantha , Camacho Megan , Kempe Allison , Szefler Stanley J.
Published: July 2023

Background

Medication adherence in adolescents remains a significant management challenge and innovative strategies are needed to improve medication adherence. Financial incentives have been used to improve outcomes for health behaviors among adults, but have not been well‐studied among adolescents. The objective of this study was to test if a modest financial incentive improved medication adherence in adolescents with asthma compared with a control group.

Methods

Participants were randomized to either control (electronic medication monitoring [EMM] with App reminders/feedback for 4 months) or intervention (EMM + $1 per day for perfect medication adherence for 3 months [maximum $84] followed by 1 month of EMM only). A repeated measures mixed model, with a first order autoregressive correlation structure between errors, was used to test the null hypothesis for an interaction of treatment group and week.

Results

Fifty‐two participants were enrolled, and 48 completed primary analysis. Mean adherence rates declined in both groups over time, and there was no significant difference in the change in adherence rates between the groups (F‐statistic = 0.72, ndf = 15, ddf = 625, p = 0.76). Adherence rates (during the 12 weeks when incentives were given) declined from 80% to 64% in the control group, and from 90% to 58% in the incentive group. There was no significant change in the slope of decline in the incentives group in the month following payment discontinuation.

Conclusion

A modest financial incentive did not lead to significantly different medication adherence rates in adolescents with asthma who were receiving a monitoring and reminder intervention. Further study is needed to determine viable interventions to optimize medication use in this group.
Development of a multiscale mechanistic modeling framework integrating differential cellular kinetics of CAR T‐cell subsets and immunophenotypes in cancer patients
Authors: Salem Ahmed M. , Mugundu Ganesh M. , Singh Aman P.
Published: July 2023

Chimeric antigen receptor (CAR) T‐cell subsets and immunophenotypic composition of the pre‐infusion product, as well as their longitudinal changes following infusion, are expected to affect CAR T‐cell expansion, persistence, and clinical outcomes. Herein, we sequentially evolved our previously described cellular kinetic‐pharmacodynamic (CK‐PD) model to incorporate CAR T‐cell product‐associated attributes by utilizing published preclinical and clinical datasets from two affinity variants (FMC63 and CAT19 scFv) anti‐CD19 CAR T‐cells. In step 1, a unified cell‐level PD model was used to simultaneously characterize the in vitro killing datasets of two CAR T‐cells against CD19+ cell lines at varying effector:target ratios. In step 2, an augmented CK‐PD model for anti‐CD19 CAR T‐cells was developed, by integrating CK dataset(s) from two bioanalytical measurements (quantitative polymerase chain reaction and flow cytometry) in patients with cancer. The model described the differential in vivo expansion properties of CAR T‐cell subsets. The estimated expansion rate constant was ~1.12‐fold higher for CAR+CD8+ cells in comparison to CAR+CD4+ T‐cells. In step 3, the model was extended to characterize the disposition of four immunophenotypic populations of CAR T‐cells, including stem‐cell memory, central memory, effector memory, and effector cells. The model adequately characterized the longitudinal changes in immunophenotypes post anti‐CD19 CAR T‐cell infusion in pediatric patients with acute lymphocytic leukemia. Polyclonality in the pre‐infusion product was identified as a categorical covariate influencing differentiation of immunophenotypes. In the future, this model could be leveraged a priori toward optimizing the composition of CAR T‐cell infusion product, and further understand the CK‐PD relationship in patients.
Deep‐learning based segmentation of ultrasound adipose image for liposuction
Authors: Cai Ruxin , Liu Yanzhen , Sun Zhibin , Wang Yuneng , Wang Yu , Li Facheng , Jiang Haiyue
Published: July 2023

Background

To develop an automatic and reliable ultrasonic visual system for robot‐ or computer‐assisted liposuction, we examined the use of deep learning for the segmentation of adipose ultrasound images in clinical and educational settings.

Methods

To segment adipose layers, it is proposed to use an Attention Skip‐Convolutions ResU‐Net (Attention SCResU‐Net) consisting of SC residual blocks, attention gates and U‐Net architecture. Transfer learning is utilised to compensate for the deficiency of clinical data. The Bama pig and clinical human adipose ultrasound image datasets are utilized, respectively.

Results

The final model obtains a Dice of 99.06 ± 0.95% and an ASD of 0.19 ± 0.18 mm on clinical datasets, outperforming other methods. By fine‐tuning the eight deepest layers, accurate and stable segmentation results are obtained.

Conclusions

The new deep‐learning method achieves the accurate and automatic segmentation of adipose ultrasound images in real‐time, thereby enhancing the safety of liposuction and enabling novice surgeons to better control the cannula.
Cyano‐Regulated Organic Polymers for Highly Efficient Photocatalytic H2O2 Production in Various Actual Water Bodies
Authors: Chu Chengcheng , Yao Ducheng , Chen Zhong , Liu Xinru , Huang Qisu , Li Qiuju , Mao Shun
Published: July 2023

Photocatalytic production of H2O2 has drawn significant attention in recent years, but the yield rate of current photocatalytic systems is still unsatisfactory. Moreover, the presence of various components in actual water bodies will consume the photogenerated charges and deactivate the catalyst, severely limiting the real applications of photocatalytic H2O2 production. Herein, a cyano‐modified polymer photocatalyst is synthesized by Knoevenagel condensation with subsequent thermal polymerization. The introduction of cyano group and sulfer (S), oxygen (O) elements modulates the microstructure and energy band of the polymer catalyst, and the cyano group sites can effectively adsorb and activate O2, realizing the generation of H2O2 in the two‐step single‐electron oxygen reduction process. The reported system achieves high H2O2 generation rate up to 1119.2 µmol g−1 h−1 in various water bodies including tap water, river water, seawater, and secondary effluent. This simple and readily available catalyst demonstrates good anti‐interference performance and pH adaptability in photocatalytic H2O2 production in actual water bodies, and its photodegradation and sterilization applications are also demonstrated. This study offers new insights in developing polymer catalysts for efficient photocatalytic production of H2O2 in various water bodies for practical application.
Scoparone attenuates glioma progression and improves the toxicity of temozolomide by suppressing RhoA/ROCK1 signaling
Authors: Zhou Yuhao , Han Zhenying , Zhao Zilong , Zhang Jianning
Published: July 2023

Background

Glioma, a type of malignant brain tumor, has become a challenging health issue globally in recent years.

Methods

In this study, we investigated the potential therapeutic role of scoparone in glioma and the underlying mechanism. Initially, transcriptome sequencing was conducted to identify genes that exhibited differential expression in glioma cells treated with scoparone compared to untreated cells. Subsequently, the impact of scoparone on the proliferation, migration, and invasion of glioma cells was assessed in vitro using a range of assays including cell viability, colony formation, wound healing, and transwell assays. Moreover, the apoptotic effects of scoparone on glioma cells were evaluated through flow cytometry and western blot analysis. Furthermore, we established a glioma xenograft mouse model to assess the in vivo antitumor activity of scoparone. Lastly, by integrating transcriptome analysis, we endeavored to unravel the molecular mechanisms underlying the observed antitumor effects of scoparone by examining the expression levels of RhoA/ROCK1 signaling pathway components using western blot analysis and qRT‐PCR.

Results

Our transcriptome sequencing results revealed that scoparone significantly downregulated RhoA/ROCK1 signaling in glioma cells. Furthermore, scoparone treatment inhibited glioma cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. Moreover, scoparone reduced tumor growth and prolonged survival in a glioma xenograft mouse model, and improved the toxicity of temozolomide. Finally, our results showed that the antitumor effects of scoparone were mediated by the suppression of RhoA/ROCK1 signaling.

Conclusion

Scoparone could be a promising therapeutic agent for glioma by suppressing RhoA/ROCK1 signaling. These findings pave the way for future research endeavors aimed at the development and optimization of scoparone‐based therapeutic strategies.
The role of hydropedology when aiming for the United Nations Sustainable Development Goals
Authors: Bouma Johan
Published: July 2023

Soil physics defines soil water, air, and temperature regimes that are crucial for agricultural production, the quality of water resources, and waste management. Positioning such activities in the context of the United Nations Sustainable Development Goals (SDGs) will provide a valuable link to the international policy arena and should also include consideration of other SDGs dealing with climate change, biodiversity preservation, and soil health, thereby covering aspects of SDG 2 (zero hunger), SDG3 (good health and wellbeing), SDG6 (clean water and sanitation), SDG13 (climate action), and SDG15 (life on land). Combined expertise of soil physicists and pedologists in hydropedology offers a basic soil package, to be completed by soil chemists and biologists, to interdisciplinary teams studying ecosystem services in line with SDGs. Soils not being isotropic and homogeneous, pedology offers descriptions of soil heterogeneity, requiring innovative measuring methods. Digital mapping significantly improves the quality of traditional soil maps by being more quantitative at lower cost. Socioeconomic conditions are important elements of sustainable development as is recognized by the soil security concept, distinguishing soil connectivity with users and soil codification, linking soil with the policy arena. The latter has been successfully achieved in South Africa. Innovative, “applied” interdisciplinary research is needed to develop operational methods, assessing ecosystem services that are relatively of low cost, simple, and transparent, allowing acceptance by critical stakeholders. Modern proximal sensing techniques offer a promising perspective. An exploratory case study of a Dutch: “Living Lab” is referred to as an example of such an “applied” interdisciplinary approach.
Toward Holistic Digital Material Description During Press-Hardening
Authors: Wesselmecking Sebastian , Ackermann Marc , Blankart Charline , Wang Jing , Brasche Frederike , Plum Tobias , Qin Siyuan , Pütz Felix , Münstermann Sebastian , Broeckmann Christoph , Hirt Gerhard , Ulrich Krupp
Published: July 2023

Press hardening of manganese-boron steels is one of the most widely used production processes for high-strength automotive components. The low residual formability of these parts is a decisive disadvantage. The low formability originates from a strong, but brittle martensitic microstructure transformed during quenching in the press-hardening tool. In contrast, medium manganese steels (MMnS) contain high fractions of ductile retained austenite improving press-hardened parts toward promising candidates for crash-relevant car body components. Disadvantages include a more complex alloy design, a highly sensitive production process, and more demanding requirements on the tool due to higher strength during press-hardening.

A detailed description of the entire production process along the process chain including the material and the press-hardening tool is important for tailoring the properties. Combined information is required to enable a precise control of the production process and its influences on the final properties of the part. Maximum economic use of the material is achieved by digitally describing MMnS as well as the tool along the entire process chain (casting, forging, hot rolling, cold rolling, galvanizing and press hardening including Q&P). To link the process steps and to describe the changes of the material, a new material database structure (idCarl) was developed. All production parameters are recorded and processed as a digital material twin. Ultimately, deviations occurring during production process can be deduced from in-line data analysis and counteracted. These can then be counteracted by adapted process control and the product can be brought back into the required parameter field of properties. Clear identification of the component and the used material allows conclusions about steps responsible for errors in the production process that become apparent during use.
Digital Shadows: Infrastructuring the Internet of Production
Authors: van der Aalst Wil M. P. , Jarke Matthias , Koren István , Quix Christoph
Published: July 2023

Digitization in the field of production is fragmented in very different domains, ranging from materials to production technology to process and business models. Each domain comes with specialized knowledge, often incorporated into mathematical models. This heterogeneity makes it hard to naively exploit advances in data-driven machine learning that could facilitate situation adaptation and experience transfer. Innovative combinations of model-driven and data-driven solutions must be invented but also made comparable and interoperable to avoid ending up in information silos. In future World Wide Labs (WWLs), experiences can be shared, aggregated, and used for innovation. WWLs will be complex, evolving socio-technical networks of interconnected devices, software, data stores, and humans as users and contributors of expert knowledge and feedback. Integrating a large number of research labs, engineering, and production sites requires a capable cross-domain Internet of Production (IoP) infrastructure. The IoP project claims Digital Shadows (DSs) to offer a shared conceptual foundation for infrastructuring the IoP. In engineering, DSs were introduced as the data provision link to Digital Twins, whereas in computer science, DSs generalize the well-established concept of database views. In this chapter, we elaborate on the roles of DSs in infrastructuring the IoP from three perspectives: analytic functionality, conceptual organization, and technical networking. As an example where an integrative DS-like approach is already highly successful, we showcase the approach and infrastructure of the process mining field.
Challenges for Participation and Empowerment. Six Youth Dialogue Projects in Comparative Perspective
Authors: Treimer Swantje , Lorenz Astrid
Published: July 2023

Youth work aimed at empowering people to be active citizens is demanding in organisational and didactic terms, and because of diverse contexts and EU perceptions which have to be respected. This chapter compares the practical challenges encountered by organisers of six youth dialogue projects in post-socialist regions of the European Union funded by Erasmus+ in 2019. It identifies typical challenges, including varying attitudes toward the EU and EU citizenship, a low interest in politics, challenging living conditions, underdeveloped youth work opportunities in remote rural areas, the difficulties in reaching a target group, the unstable motivation of young people, a lack of prior knowledge, no systematic consideration of the youth dialogue results by decision-makers, the unclear long-term effects of the projects and problems with funding. It also discusses the findings in light of previous studies on youth work and European citizenship that did not specifically focus on our region of interest.
A Building Block of an Overall Strategy for Political Education: Decide on Europe
Authors: Tadzhetdinova Amaliia , Gutzer Grete
Published: July 2023

This chapter deals with the Erasmus+ funded project Decide on Europe and how it was established as a transnational project between the Czech Republic and Slovakia to teach and inform secondary school students about European policy and the possibilities to participate in youth initiatives. Furthermore, challenges and problems, such as being able to reach out to students from rural areas, but also success factors, for example being able to be involved in a well-known project, with more and more participants each time, are addressed to provide an informative overview regarding the project.
Even Successful Projects Must End? Lessons Learned from the Project The Best Is Yet to Come
Authors: Bockelmann Henrieke , Samstag Svenja
Published: July 2023

This chapter reports about the transnational youth project The Best is yet to Come and the processes and challenges the organisers faced when creating a voice for young people from rural areas. The project also aimed at preparing a “European Rural Youth Parliament”, which brings together young people from different European countries to discuss and exchange ideas on life in rural areas. It was funded within the EU’s Erasmus+ framework. The chapter presents the framework conditions for such a project, as well as the benefits of involving youth. The sustainability of such and similar projects is critically considered, with an additional focus on network building and administrative processes. The chapter reveals that even if young people are enthusiastic and interested in creating a common European youth voice in rural areas, the structures to support these ambitions might not be sufficient to involve them systematically and can be strengthened.
Perspectives for Digital Participation in Rural Areas: Evidence from German Regions
Authors: Stein Veronika , Pentzold Christian
Published: July 2023

The shortcomings of top-down policies for rural development underscore the importance of local potentials and the role of citizens who are perceived as taking a more active role in shaping the future of rural areas. The engagement of the local population is facilitated by digitally-supported forms of civic participation. These technological services, in particular, should reach younger target groups. This shift toward citizen-centred approaches in rural development is manifested on the EU level in programs like LEADER, as well as in country-specific or regional initiatives. In our contribution, we draw on three case studies from Germany in order to make suggestions for local actors on how to foster citizen participation in a ‘smart’ way.
EU Citizenship and the Young People in the Peripheral Areas of East Central Europe: Three Recommendations for Research on Citizenship
Authors: Karolewski Ireneusz Paweł
Published: July 2023

EU citizenship is a specific case of citizenship, which transnationally expands nation-state citizenship by focusing on cross-border mobility and transnational participation rights. The chapter argues that the key issue with EU citizenship remains the equality of status, especially when it comes to young people in peripheral areas of East Central Europe. The chapter sketches some key issues of citizenship research including EU citizenship. It also problematizes them concerning peripheral (especially rural) areas and young citizens. Against this backdrop, it formulates three recommendations for the research on citizenship, specifically EU citizenship with regard to rural areas in East Central Europe. The recommendations focus on (1) the difference between urban and rural citizenship, (2) direct social rights, and (3) the EU citizenship as nested and enacted citizenship.