bluuebunny/crossref_metadata_2025 huggingface dataset:
Interrelationships between Skin Structure, Function, and Microbiome of Pregnant Females and Their Newborns: Study Protocol for a Prospective Cohort Study
Authors: Wilborn Doris , Kottner Jan , Hillmann Kathrin , Xu Sa , Konietschke Frank , Blume-Peytavi Ulrike
Published: November 2021

Background. Pregnancy leads to several skin changes, but evidence about structural and functional skin changes is scarce. Findings on skin structure and function in children in their first year reveal rapid skin maturation, but evidence indicates that in particular, water holding and transport mechanisms are different from adults. Important questions include whether maternal cutaneous properties predict infant skin condition, and if so, how. This is especially relevant for the skin’s microbiome because it closely interacts with the host and is assumed to play a role in many skin diseases. Therefore, the study objective is to explore characteristics of skin and hair of pregnant women and their newborns during pregnancy and in the first six months after delivery and their associations. Methods. The study has an observational longitudinal design. We are recruiting pregnant females between 18 and 45 years using advertisement campaigns in waiting areas of gynecologists and hospital’s outpatient services. A final sample size of n = 100 women is the target. We perform noninvasive, standardized skin, hair, and skin microbiome measurements. We establish the baseline visit during pregnancy until at the latest four weeks before delivery. We schedule follow-up visits four weeks and six months after birth for mothers and their newborns. We will calculate descriptive statistical methods using frequencies and associations over time depending on scale levels of the measurements. Discussion. The majority of previous studies that have investigated infants’ skin microbiome and its associations used cross-sectional designs and focused on selected characteristics in small samples. In our longitudinal study, we will characterize a broad range of individual and environmental characteristics of mothers and their newborns to evaluate interrelationships with skin parameters and their changes over time. Considering the combination of these multiple variables and levels will allow for a deeper understanding of the complex interrelationship of the newborn’s skin maturation. This trial is registered with ClinicalTrials.gov (Identifier: NCT04759924).
Path Optimization of Joint Delivery Mode of Trucks and UAVs
Authors: Cao Qingkui , Zhang Xuefei , Ren Xiangyang
Published: November 2021

With the development of e-commerce and information technology, new modes of distribution are emerging. A new type of distribution tool, UAV (unmanned aerial vehicle), has entered into the public’s field of vision. In the background of growing e-commerce, this paper proposes a new delivery mode of joint delivery of trucks and UAVs which particularly has been popular in recent years, with the advantages of prompt delivery, low cost, and independence from terrain restrictions, while traditional transportation tools such as trucks have more advantages in terms of flight distance and load capacity. Therefore, the joint delivery mode of trucks and UAVs proposed in this paper can well realize the complementary advantages of trucks and UAVs in the distribution process and consequently optimize the distribution process. Moreover, the growing e-commerce promotes customers’ higher needs for delivery efficiency and the integrity of the delivered goods which urges companies to pay more attention to customers’ satisfaction. This paper analyzes the joint delivery mode of trucks and UAVs, aims to minimize total delivery cost and maximize customer satisfaction, and builds a multiobjective optimization model for joint delivery. Furthermore, an improved ant colony algorithm is proposed in order to solve the mode in this paper. In order to effectively avoid prematurity of the ant colony algorithm, the limited pheromone concentration and the classification idea of the artificial bee colony algorithm are introduced to improve the ant colony algorithm. Finally, some experiments are simulated by MATLAB software, and the comparison shows that the joint delivery of trucks and UAVs has more advantages, and the improved ant colony algorithm is more efficient than the traditional ant colony.
Fuzzy Set Qualitative Comparative Analysis (fsQCA) Applied to the Driving Mechanism of Total Factor Productivity Growth
Authors: Diao Qibo , Liu Yuanchun
Published: November 2021

With the gradual improvement of fuzzy set qualitative comparative analysis (fsQCA), it is introduced into more and more fields to analyze practical problems. This paper calculates the total factor productivity index and analyzes its development trend based on relevant economic development theories and China’s inter-provincial panel data from 1999 to 2019. We use the fsQCA method to study the interaction of factors influencing total productivity in various regions. Two specific paths to improve total factor productivity are obtained, which provide a reference for different areas to improve total factor productivity according to local conditions.
Design, Implementation, and Evaluation of an Information System to Enhance Road Safety Level for Pedestrians in China
Authors: Huang Hanjing , Liu Luosha , Fu Zhiyong , Zhang Yichi , Zhang Jun , Tsai Yuehlin , Guo Li , Rau Pei-Luen Patrick
Published: November 2021

Pedestrians’ unsafe behavior is one of the most critical factors causing traffic incidents in China. The primary objective of this study is to explore the cause of pedestrians’ unsafe behavior and provide possible solutions. We interviewed pedestrians and experts to investigate pedestrians’ unsafe behaviors. Results from interviews indicated that pedestrians were likely to exhibit unsafe behavior at intersections owing to use of smartphones, reluctance to obey the rules, and unawareness of risk. According to the experts, attracting the attention of pedestrians and guiding them to exhibit safe behaviors can improve their safety. Based on these results, we designed “LookMe,” which is a multimedia information system placed at the intersections, to guide pedestrians across the road and improve their experience of waiting in traffic. The results of user tests indicated that pedestrians had relatively high acceptance of LookMe. Moreover, participants wanted to see diverse multimedia information on the screen of LookMe such as news, videos, maps, and traffic information. Findings from this study can be useful in understanding why Chinese pedestrians exhibit unsafe behaviors and proposing effective solutions to enhance their safety.
Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia
Authors: Malani Disha , Kumar Ashwini , Brück Oscar , Kontro Mika , Yadav Bhagwan , Hellesøy Monica , Kuusanmäki Heikki , Dufva Olli , Kankainen Matti , Eldfors Samuli , Potdar Swapnil , Saarela Jani , Turunen Laura , Parsons Alun , Västrik Imre , Kivinen Katja , Saarela Janna , Räty Riikka , Lehto Minna , Wolf Maija , Gjertsen Bjorn Tore , Mustjoki Satu , Aittokallio Tero , Wennerberg Krister , Heckman Caroline A. , Kallioniemi Olli , Porkka Kimmo
Published: November 2021

We generated ex vivo drug-response and multiomics profiling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, and functional data for application in clinical treatment decisions. Actionable drugs were found for 97% of patients with AML, and the recommendations were clinically implemented in 37 relapsed or refractory patients. We report a 59% objective response rate for the individually tailored therapies, including 13 complete responses, as well as bridging five patients with AML to allogeneic hematopoietic stem cell transplantation. Data integration across all cases enabled the identification of drug response biomarkers, such as the association of IL15 overexpression with resistance to FLT3 inhibitors. Integration of molecular profiling and large-scale drug response data across many patients will enable continuous improvement of the FPMTB recommendations, providing a paradigm for individualized implementation of functional precision cancer medicine.

Significance:

Oncogenomics data can guide clinical treatment decisions, but often such data are neither actionable nor predictive. Functional ex vivo drug testing contributes significant additional, clinically actionable therapeutic insights for individual patients with AML. Such data can be generated in four days, enabling rapid translation through FPMTB.

See related commentary by Letai, p. 290.

This article is highlighted in the In This Issue feature, p. 275
The Long Noncoding RNA-H19 Mediates the Progression of Fibrosis from Acute Kidney Injury to Chronic Kidney Disease by Regulating the miR-196a/Wnt/β-Catenin Signaling
Authors: Dong Xiangnan , Cao Rui , Li Qiang , Yin Lianghong
Published: November 2021

Introduction: Long noncoding RNAs (lncRNAs) have been reported to be involved in the occurrence and development of various diseases. This study was to investigate the role of lncRNA-H19 in the transition from acute kidney injury (AKI) to chronic kidney disease (CKD) and its underlying mechanism. Methods: Bilateral renal pedicle ischemia-reperfusion injury (IRI) was used to establish the IRI-AKI model in C57BL/6 mice. The expression levels of lncRNA-H19, miR-196a-5p, α-SMA, collagen I, Wnt1, and β-catenin in mouse kidney tissues and fibroblasts were determined by quantitative real-time PCR and Western blotting. The degree of renal fibrosis was evaluated by hematoxylin and eosin staining. The interaction between lncRNA-H19 and miR-196a-5p was verified by bioinformatics analysis and luciferase reporter assay. Immunohistochemistry and immunofluorescence were used to evaluate the expression of α-SMA and collagen I in kidney tissues and fibroblasts of mice. Results: lncRNA-H19 is upregulated, and miR-196a-5p is downregulated in kidney tissues of IRI mice. Moreover, miR-196a-5p is a direct target of lncRNA-H19. lncRNA-H19 overexpression promotes kidney fibrosis and activates fibroblasts during AKI-CKD development, while miR-196a-5p overexpression reversed these effects in vitro. Furthermore, lncRNA-H19 overexpression significantly upregulates Wnt1 and β-catenin expression in kidney tissues and fibroblasts of IRI mice, while miR-196a-5p overexpression downregulates Wnt1 and β-catenin expression in kidney tissues and fibroblasts of IRI mice. Conclusion: lncRNA-H19 induces kidney fibrosis during AKI-CKD by regulating the miR-196a-5p/Wnt/β-catenin signaling pathway.
Living with Ulcerative Colitis in Japan: Biologic Persistence and Health-Care Resource Use
Authors: Bargo Danielle , Tritton Theo , Cappelleri Joseph C. , DiBonaventura Marco , Smith Timothy W. , Tsuchiya Takanori , Gardiner Sean , Modesto Irene , Holbrook Tim , Bluff Daniel , Kobayashi Taku
Published: November 2021

Objective: The aim of the study was to improve understanding of adherence and persistence to biologics, and their association with health-care resource utilization (HCRU), in Japanese patients with moderate to severe ulcerative colitis (UC). Methods: Data were from Medical Data Vision, a secondary care administrative database. A retrospective, longitudinal cohort analysis was conducted of data from UC patients initiating biologic therapy between August 2013 and July 2016. Data collected for 2 years prior (baseline) and 2 years after (follow-up) the index date were evaluated. Patients completing biologic induction were identified, and adherence/persistence to biologic therapy calculated. HCRU, steroid, and immunosuppressant use during baseline and follow-up were assessed. Biologic switching during the follow-up was evaluated. Descriptive statistics (e.g., means and proportions) were obtained and inferential analyses (from Student’s t tests, Fisher’s exact tests, χ2 tests, the Cox proportional hazard model, and negative binomial regression) were performed. Results: The analysis included 649 patients (adalimumab: 265; infliximab: 384). Biologic induction was completed by 80% of patients. Adherence to adalimumab was higher than that to infliximab (p < 0.001). Persistence at 6, 12, 18, and 24 months was higher with infliximab than with adalimumab (p < 0.05). Overall, gastroenterology outpatient visits increased, and hospitalization frequency and duration decreased, from baseline to follow-up. UC-related hospitalizations were fewer and shorter, and endoscopies fewer, in persistent than in nonpersistent patients, although persistent patients made more outpatient visits than nonpersistent patients. Hospitalization duration was lower in persistent than nonpersistent patients. Approximately 50% of patients received an immunosuppressant during biologic therapy; 5% received a concomitant steroid during biologic therapy. Overall, 17% and 3% of patients, respectively, received 2nd line and 3rd line biologics. Conclusions: Poor biologic persistence was associated with increased non-medication-associated HCRU. Effective treatments with high persistence levels and limited associated HCRU are needed in UC.
Dynamics of Circulating miR-122 Predict Liver Cancer and Mortality in Japanese Patients with Histopathologically Confirmed NAFLD and Severe Fibrosis Stage
Authors: Akuta Norio , Kawamura Yusuke , Suzuki Fumitaka , Saitoh Satoshi , Arase Yasuji , Muraishi Nozomu , Fujiyama Shunichiro , Sezaki Hitomi , Hosaka Tetsuya , Kobayashi Masahiro , Kobayashi Mariko , Suzuki Yoshiyuki , Ikeda Kenji , Kumada Hiromitsu
Published: November 2021

Introduction: It is unclear whether the relationships between changes in fibrosis and circulating microRNA-122 (miR-122) dynamics might influence the prognosis of nonalcoholic fatty liver disease (NAFLD). Methods: This study investigates the impact of serum miR-122 dynamics and histological changes on the incidence of liver cancer and mortality in 81 Japanese NAFLD patients who underwent serial liver biopsies. The median interval between the first and second liver biopsies was 2.9 years. Results: The fibrosis stage scores indicated progression, no change, and improvement (a decrease of one point or more) in 21.0%, 56.8%, and 22.2% of the patients, respectively. There were 64 patients in the high-risk group who had no improvement in stage scores. Among these, the miR-122 levels were significantly lower in 7 patients with liver cancer than those of the 54 patients who had no liver cancer at the second liver biopsy. The cumulative rates of liver cancer were significantly higher in cases with miR-122 ratios <0.5 (serum miR-122 level at second biopsy to that at first biopsy) than those with ratios ≥0.5. The cumulative survival rates in cases with miR-122 ratios <0.5 tended to be lower than those with ratios ≥0.5. Of the 64 high-risk patients, 39 indicated stage 2 or greater (severe fibrosis stage) at the first liver biopsy and also showed similar results of cumulative liver cancer and survival rates. Conclusions: Longitudinal examination of serial liver biopsies indicated that the circulating miR-122 dynamics might be useful in predicting the prognosis for NAFLD patients with severe fibrosis stage and no improvement of the stage scores.
A Case of Multiple Liver Metastases after Surgery in Elderly HER2-Positive Breast Cancer in Which Anastrozole + Trastuzumab Was Ineffective but T-DM1 Was Effective
Authors: Shidahara Tomohiro , Ohsumi Shozo , Miyoshi Yuichiro , Takahashi Mina , Takashima Seiki , Aogi Kenjiro , Teramoto Norihiro
Published: November 2021

Chemotherapy is often difficult to treat human epidermal growth factor receptor 2 (HER2)-positive metastatic recurrent breast cancer in the elderly, and no standard treatment has been established at this point. We experienced a case in which trastuzumab (Tmab) + anastrozole (ANA) was ineffective (progressive disease; PD) in elderly HER2-positive breast cancer with postoperative multiple liver metastases, but T-DM1 was significantly effective (complete response; CR), and treatment could be continued safely. An 82-year-old woman was referred to our department with a right breast mass. A close examination revealed right breast cancer cT1bN0M0 cStage I, and total mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological result was pT1bN0M0 pStage I (luminal HER2 type). The patient was elderly and had no adjuvant treatment after the operation. Approximately 2 years after the operation, multiple liver metastases were observed, and treatment with ANA and Tmab was started. Four months later, MRI showed that the number of multiple liver metastases increased. The patient was diagnosed with PD, and the anti-HER2 drug was changed from trastuzumab to trastuzumab emtansine (T-DM1). The dose was reduced due to vomiting (grade 3). Two months later, MRI showed that the multiple liver metastases shrank and became obscure after 5 months. After that, T-DM1 was continued, and the disease did not worsen. In elderly people with difficulty in administering chemotherapy, T-DM1 may have a safe and sufficient therapeutic effect by adjusting the dose and managing side effects appropriately.
Risk Factors Associated with Falls among Nursing Home Residents: A Case-Control Study
Authors: Imaginário Cristina , Martins Teresa , Araújo Fátima , Rocha Magda , Machado Paulo Puga
Published: November 2021

Introduction: To identify factors predictive of falls and enable appropriate management of fall risk it is necessary to understand the behaviour and health conditions of older adults living in nursing homes. Objective: This study had two main objectives. The first was to find significant predictors for falls in older adults living in nursing homes. The second main goal was to build a predictive model to find the best predictors for falls. Methods: Out of 56 nursing homes with the same legal statute, 25 agreed to participate. The sample was randomly selected and only the independent or slight/moderately dependent participants were included in the study (n = 325). Results: There was a mean of 1.47 ± 0.99 falls (range from 1 to 7) per resident in nursing homes. By using the t test and odds ratio analysis, ten factors related to falls were identified. Through the binary logistic regression, a model was tested identifying four robust predictors: static balance, resorting to emergency services, polypharmacy, and an independent self-care profile. Conclusions: The present study replicated the main results of contemporary research on the risk factors of falls. More importantly, it suggests that the self-care profile model should be taken into account in future studies and early interventions. It is crucial to implement preventive measures consistent with safer environments and to establish an individual plan for integrated activities according to older adults’ health needs.
Critical Steps for Human Gut Exfoliome RNA Profiling Analysis Using Non-Invasive Stool Samples
Authors: Sánchez-Campillo María , Pastor-Fajardo María Teresa , Sabater-Molina María , López-Andreo María José , Larqué Elvira
Published: November 2021

Introduction: Dietary exposure and drug treatments influence gut cellular pathways and hence growth and potentially even the gut-brain-microbiome axis. Since eukaryotic mRNA presents poly-A sequence that distinguishes them from the prokaryotes mRNA, we could analyze the gene expression of human gut cells using exfoliated gut cells available in stool samples. However, the impact of the critical steps of these non-invasive methods must be analyzed. Methods: We tested prokaryote contamination in all the steps of different procedures to analyze human exfoliome by microarrays and the influence of the fecal sampling collection process. Results: The least bacterial contamination was found using RNA amplified with oligo dT from the GeneChip 3′ IVT Pico Reagent Kit or using RNA purified by both Oligotex® + oligo dT. RNAlater® collection of feces affects the microarray results compared to directly frozen fecal samples, although both methods produce similar cDNA quality. Conclusion: This technique is a potential non-invasive diagnostic tool that can be applied to larger studies to quantify intestinal gene expression in humans with non-invasive samples, but samples should always be collected and analyzed under the same procedure.
Carotid Plaques From Symptomatic Patients With Mild Stenosis Is Associated With Intraplaque Hemorrhage
Authors: Nardi Valentina , Benson John , Bois Melanie C. , Saba Luca , Larson Anthony S. , Özcan Ilke , Ahmad Ali , Morse David W. , Meyer Fredric B. , Brinjikji Waleed , Lanzino Giuseppe , Lerman Lilach O. , Savastano Luis E. , Lerman Amir
Published: November 2021

Carotid plaque vulnerability features beyond the degree of stenosis may play a key role in the pathogenesis and recurrence of ischemic cerebrovascular events.

This study sought to compare intraplaque hemorrhage (IPH) as a marker of plaque vulnerability in symptomatic patients with mild (<50%), moderate (50%–69%), and severe (≥70%) carotid artery stenosis.

We included patients who experienced ischemic cerebrovascular events with no other identifiable sources and underwent carotid endarterectomy for mild (n=32), moderate (n=47), and severe (n=58) carotid artery stenosis. The degree of stenosis and imaging hallmarks were assessed by computed tomography angiography or magnetic resonance angiography. Plaque specimens were stained with hematoxylin and eosin and Movat pentachrome staining.

Carotid plaques of patients with mild stenosis had a higher extent of IPH (%) on tissue analysis compared with patients with moderate (mild, 15.7% [interquartile range, 7.8%–26.7%]; moderate, 3.9% [0.0%–9.2%];
P
<0.001) and severe carotid artery stenosis (mild, 15.7% [interquartile range, 7.8%–26.7%]; severe, 2.5% [interquartile range, 0.0%–11.2%];
P
<0.001). When considering the degree of carotid artery stenosis as a continuous variable, a lower lumen narrowing was associated with higher extent of IPH (
P
<0.001; R, −0.329).

Our major finding is the association of IPH with mild carotid artery stenosis based on histological analysis. The current study may suggest that IPH potentially plays a role in the mechanism of stroke in patients with nonobstructive carotid stenosis.
Czech Litigation on Systematic Detention of Asylum Seekers: Ripple Effects across Europe
Authors: Moraru Madalina , Janků Linda
Published: November 2021

This article investigates the development of national litigation against the Czech Republic’s governmental policy to detain asylum seekers under the Dublin III Regulation, as a means to address the so-called refugee crisis. The outcome of this litigation has been the preliminary ruling of the Court of Justice of the European Union in the Al Chodor case, which has been praised for enhancing domestic standards of protection of asylum seekers and returnees’ right to liberty across the EU. The article demonstrates that this preliminary ruling has been a catalyst for domestic legislative and jurisprudential reforms across the EU, improving to a certain extent the protection of the right to liberty of asylum seekers. However, it is argued that in the Czech Republic the case has not initiated a change in the legislation, nor has it reduced the systematic use of asylum detention. The article identifies some important legal, political and social factors from within and beyond courtrooms that have contributed to this ambiguous outcome of the Czech litigation. It concludes by identifying circumstances that need to be taken into account when using the preliminary reference procedure as a tool for strategic litigation.
The „Niemands“ – Heimatlose Ausländer in Mannheim
Authors: Alexopoulou Maria
Published: November 2021

Heimatloser Ausländer (homeless foreigner) was a status granted to Displaced Persons, who were mostly slave or foreign workers during the Third Reich. How did local authorities and the population in Mannheim – an industrial ‘migration-city’– deal with these first ‘Ausländer’ of the Federal Republic of Germany?

This article outlines how local authorities managed housing for dp s and later homeless foreigners and how their concerns were treated with at the Ausländerbehörde (foreigners office). It also looks into the reactions and attitudes of the population mirrored in local/regional administrative files and press coverage.

The self-denomination as Niemands (nobodies), originating from sociologist and Mannheim based son of dp s, Stanislaus Stepień, expresses the history of a group of migrants who have been mostly forgotten after serving as projection surfaces and transmission objects for racial knowledge about the ‘migrant Other’ and ‘the German’.
New species of flea-toad, genus Brachycephalus (Anura: Brachycephalidae) from the Atlantic Forest of Espírito Santo, Brazil
Authors: ALMEIDA-SILVA DIEGO , SILVA-SOARES THIAGO , RODRIGUES MIGUEL TREFAUT , VERDADE VANESSA KRUTH
Published: November 2021

We describe a new species of dull-colored flea-toad, genus Brachycephalus, from the Atlantic Forest of Caparaó mountains in southeastern Brazil. The new species is characterized by its diminutive size, “leptodactyliform” body, brownish color with an inverted V-shaped dark mark on dorsum, skin smooth, hyperossification and dorsal shield absent, linea masculinea absent, Fingers I and IV vestigial, Toe I externally absent, Toe II reduced but functional, Toes III and IV with pointed tips, Toe V vestigial, and ventral color uniformly brown. It is a leaf litter dweller, known only from type locality in the humid forests on the eastern slopes of Parque Nacional do Caparaó mountains, a protected area in the states of Espírito Santo and Minas Gerais, southeastern Brazil. It is the third flea-toad occurring in the state of Espírito Santo recovered as sister to all other Brachycephalus distributed from the state of São Paulo northward in the Atlantic Forest.
The Effects of Signaling-Selective Parathyroid Hormone Analogs on Osteoporotic Osteocyte Apoptosis
Authors: Song Meng-Sheng , Yu Xiao , Rong Peng-Ze , Pang Qing-Jiang
Published: November 2021

Objectives: To compare the effects of signaling-selective parathyroid hormone analogs [G1, R19]hPTH(1–28) [GR(1–28)] and [G1, R19]hPTH(1–34) [GR(1–34)] on osteoporotic osteocyte apoptosis, and to explore the mechanism of the anti-osteoporotic difference.
Methods: The osteoporosis model was established in eighty adult female C57BL/6 mice aged 12 weeks. The mice were subcutaneously administered with GR(1–28) and GR(1–34) 5 days per week for 8 weeks. Bilateral femur samples were collected at 4 and 8 weeks, and micro-computed
tomography (CT), H&E staining and immunohistochemical staining analyses were performed. Results: From micro-CT analysis, GR(1–34) increased proximal femoral bone mineral density (BMD) and relative bone volume (BV/TV), which was higher than GR(1–28) did. In addition,
more trabecular number (Tb.N), thinner trabecular thickness (Tb.Th) and wider trabecular separation (Tb.Sp) were measured at week 8 using GR(1–34). From H&E and immunohistochemical staining, a stronger apoptosis inhibition was induced by GR(1–34) with more Bcl-2 secretion
but less Bax expression, as opposed to GR(1–28). Conclusions: GR(1–34) shows better anti-osteoporotic effects than GR(1–28), which appears to be attributed to the activation of the PLC-independent PKC signaling pathway triggered by the former, inhibiting osteocyte
apoptosis through up-regulation of Bcl-2 and down-regulation of Bax to increase bone mass and improving trabecular bone microstructure to enhance bone quality by reducing trabecular number, increasing trabecular thickness and trabecular space.
A Parameterization of Slantwise Convection in the WRF Model
Authors: Chen Ting-Chen , Yau Man-Kong , Kirshbaum Daniel J.
Published: November 2021

In this study, we introduce a parameterization scheme for slantwise convection (SC) to be considered for models that are too coarse to resolve slantwise convection explicitly (with a horizontal grid spacing coarser than 15 km or less). This SC scheme operates in a locally defined 2D cross section perpendicular to the deep-layer-averaged thermal wind. It applies momentum tendency to adjust the environment toward slantwise neutrality with a prescribed adjustment time scale. Condensational heating and the associated moisture loss are also considered. To evaluate the added value of the SC scheme, we implement it in the Weather Research and Forecasting (WRF) Model to supplement the existing cumulus parameterization schemes for upright convection and test for two different numerical setups: a 2D idealized, unforced release of conditional symmetric instability (CSI) in an initially conditionally stable environment, and a 3D real-data precipitation event containing both CSI and conditional instability along the cold front of a cyclonic storm near the United Kingdom. Both test cases show significant improvements for the coarse-gridded (40-km) simulations when parameterizing slantwise convection. Compared to the 40-km simulations with only the upright convection scheme, the counterparts with the additional SC scheme exhibit a larger extent of CSI neutralization, generate a stronger grid-resolved slantwise circulation, and produce greater amounts of precipitation, all in better agreement with the corresponding fine-gridded reference simulations. Given the importance of slantwise convection in midlatitude weather systems, our results suggest that there exist potential benefits of parameterizing slantwise convection in general circulation models.
Examining the Kinematic Structures within which Lightning Flashes Are Initiated Using a Cloud-Resolving Model
Authors: Salinas Vicente , Bruning Eric C. , Mansell Edward R.
Published: November 2021

Lightning is frequently initiated within the convective regions of thunderstorms, and so flash rates tend to follow trends in updraft speed and volume. It has been suggested that lightning production is linked to the turbulent flow generated by updrafts as turbulent eddies organize charged hydrometeors into complex charge structures. These complex charge structures consist of local regions of increased charge magnitudes between which flash-initiating electric fields may be generated. How turbulent kinematics influences lightning production, however, remains unclear. In this study, lightning flashes produced in a multicell and two supercell storms simulated using The Collaborative Model for Multiscale Atmospheric Simulation (COMMAS) were examined to identify the kinematic flow structures within which they occurred. By relating the structures of updrafts to thermals, initiated lightning flashes were expected to be located where the rate of strain and rotational flow are equal, or between updraft and eddy flow features. Results showed that the average lightning flash is initiated in kinematic flow structures dominated by vortical flow patterns, similar to those of thermals, and the structures’ kinematics are characterized by horizontal vorticity and vertical shearing. These kinematic features were common across all cases and demonstrated that where flash-initiating electric fields are generated is along the periphery of updrafts where turbulent eddies are produced. Careful consideration of flow structures near initiated flashes is consistent with those of thermals rising through a storm.
Physiological and biochemical responses of strawberry crown and leaf tissues to freezing stress
Authors: Zareei Elnaz , Karami Farhad , Gholami Mansour , Ershadi Ahmad , Avestan Saber , Aryal Rishi , Gohari Gholamreza , Farooq Muhammad
Published: November 2021

Background

In northern Iran and other cold regions, winter freezing injury and resultant yield instability are major limitations to strawberry production. However, there is scarcity of information on the physiological and biochemical responses of strawberry cultivars to freezing stress. This study aimed to investigate the physiological and biochemical responses of strawberry cultivars (Tennessee Beauty, Blakemore, Kurdistan, Queen Elisa, Chandler, Krasnyy Bereg, and Yalova) to different freezing temperature treatments (− 5, − 10, − 15, − 20, and − 25 °C) under controlled conditions.

Results

All measured physiological and biochemical features were significantly affected by the interaction effect between low temperatures and cultivars. Tennessee Beauty showed the highest RWC at − 25 °C. The highest Fv/Fm was observed in Queen Elisa. Krasnyy Bereg had the least freezing injury (FI) in crown and leaf, while Yalova and Chandler showed the highest crown and leaf FI, respectively. At − 20 to − 25 °C, the highest carbohydrates contents of crown and leaf were noted in Blakemore and Krasnyy Bereg cultivars, respectively. The Yalova showed the highest protein content in both crown and leaf tissues at − 25 °C. The Tennessee Beauty and Blackmore cultivars showed the highest proline in crowns and leaves at − 15 °C, respectively. The highest ThioBarbituric Acid Reactive Substances (TBARS) contents in the crown and leaf were observed in Kurdistan and Queen Elisa, respectively. Queen Elisa and Krasnyy Bereg cultivars showed SOD and POD peaks in the crown at − 15 °C, respectively.

Conclusion

Freezing stress was characterized by decreased Fv/Fm and RWC, and increased FI, TBARS, total carbohydrates, total proteins, proline content, and antioxidant enzyme activity. The extent of changes in above mentioned traits was cultivar dependent. FI and TBARS were the best traits among destructive parameters for evaluating freezing tolerance. Moreover, maximum quantum yield of PSII (Fv/Fm index), as non-destructive parameters, showed a significant efficiency in rapid assessment for screening of freezing tolerant strawberry cultivars. The cultivars Krasnyy Bereg, Queen Elisa, and Kurdistan were the most tolerant cultivars to freezing stress. These cultivars can be used as parents in breeding programs to develop new freezing tolerant cultivars.
Application of BASNEF model in students training regarding cutaneous leishmaniasis prevention behaviors: a school-based quasi experimental study
Authors: Alizadeh Gholamreza , Shahnazi Hossein , Hassanzadeh Akbar
Published: November 2021

Background

Cutaneous leishmaniasis (CL) is endemic in 98 countries, and 350 million people are at risk of the disease worldwide. In endemic areas, conducting educational interventions is necessary to change preventive behaviors of CL. This study aimed to investigate the effect of an educational intervention based on the BASNEF model on CL preventive behavior in students.

Methods

The present quasi-experimental study examined 80 students living in endemic areas of leishmaniasis in Isfahan province, Iran based on the BASNEF model. The required data were collected twice before and two months after the educational intervention based on a questionnaire whose validity and reliability had been already proven in other studies. The intervention was performed in three educational sessions for the students in the intervention group and 1 educational session for teachers and parents. Data were analyzed by SPSS (VER26) using the chi-square test, independent t-test, analysis of covariance (ANCOVA), and Paired t-test.

Results

After intervention, the mean scores of Knowledge (P < 0.001), attitude (P = 0.02), subjective norms (P = 0.04), behavioral intention (P < 0.001), and behavior (P = 0.02) indicated significant differences between the intervention and control groups, but an increase in mean scores of enabling factors was not significant (P = 0. 93).

Conclusions

Providing students with the educational intervention based on the BASNEF model improve their ability to the extent that they transmit these educations to their family members, which would be effective in preventing and controlling CL in leishmaniasis-prone areas.

Trial registration

Name: Iranian Registry of Clinical Trials. Registration number: IRCT20201024049131N1. Registration date: 2020–11-20. Registration timing: prospective.
Impact of time of flight and point spread function on quantitative parameters of lung lesions in 18F-FDG PET/CT
Authors: Huang Kemin , Feng Yanlin , Liang Weitang , Li Lin
Published: November 2021

Background

Image reconstruction algorithm is one of the important factors affecting the quantitative parameters of PET/CT. The purpose of this study was to investigate the effects of time of flight (TOF) and point spread function (PSF) on quantitative parameters of lung lesions in 18F-FDG PET/CT.

Methods

This retrospective study evaluated 60 lung lesions in 39 patients who had undergone 18F-fluoro-deoxy-glucose (FDG) PET/CT. All lesions larger than 10 mm in diameter were included in the study. The PET data were reconstructed with a baseline ordered-subsets expectation–maximization (OSEM) algorithm, OSEM + PSF, OSEM + TOF and OSEM + TOF + PSF respectively. The differences of maximum standard uptake value (SUVmax), mean standard uptake value (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG)and signal to noise ratio (SNR)were compared among different reconstruction algorithms.

Results

Compared with OSEM reconstruction, using OSEM + TOF + PSF increased SUVmean and SUVmax by 23.73% and 22.71% respectively, and SNR increased by 70.18%, MTV decreased by 23.84% (p < 0.01). The percentage difference was significantly higher in smaller lesions (diameter 10–22 mm) than in larger lesions (diameter 23–44 mm), and significantly higher in low contrast lesions (SNR ≤ 15.31) than in high contrast lesions (SNR > 15.31). The difference of TLG among various reconstruction algorithms is relatively small, the highest value is − 6.48% of OSEM + TOF + PSF, and the lowest value is 0.81% of OSEM + TOF.

Conclusion

TOF and PSF significantly affected the quantitative parameters of lung lesions in 18F-FDG PET/CT. OSEM + TOF + PSF can significantly increased SUVmax, SUVmean and SNR, and significantly reduce MTV, especially in small lesions and low contrast lesions. TLG can be relatively stable in different reconstruction algorithms.
Relationship of shear wave elastography anisotropy with tumor stem cells and epithelial-mesenchymal transition in breast cancer
Authors: Leng Xiaoling , Japaer Rexida , Zhang Haijian , Yeerlan Mila , Ma Fucheng , Ding Jianbing
Published: November 2021

Background

This study is to examine the feasibility of shear wave elastography (SWE) anisotropy in assessing the prognosis of breast cancer.

Methods

We enrolled 119 breast cancer patients from January 2017 to October 2019. SWE was performed before operation. Emax (maximum elasticity value), Emean (average elasticity value), Esd (standard deviation of the lesion elasticity value), Eratio (elasticity value of adipose tissue), anisotropy coefficient and difference were recorded. After operation, we collected clinical pathological data, and performed immunohistochemistry and real-time PCR tests on CD44, CD24, E-cadherin, β-catenin, vimentin and N-cadherin. Finally, we analyzed the correlation among parameters of SWE, anisotropy and clinicopathology, and markers of CSCs (cancer stem cells) and EMT (epithelial-mesenchymal transition).

Results

Emax, Emean and Esd of the cross section were higher than those of the longitudinal section. Breast cancer with a higher elastic modulus was often accompanied by a hyperechoic halo, which was manifested as mixed echo and post-echo attenuation, and was accompanied by a higher BI-RADS (breast imaging reporting and data system) classification. When breast cancer had hyperechoic halo and weakened posterior echo, SWE of the lesion showed more obvious anisotropy. In addition, larger diameter of the longitudinal section indicated higher stiffness of the cross section. Correlation analysis showed that E-cadherin was negatively correlated with SWE in longitudinal section. CD44, N-cadherin, β-catenin were positively correlated with SWE in longitudinal and cross sections. Vimentin and CD24 had no correlation with SWE parameters.

Conclusion

SWE of breast cancer is anisotropic. The cross-sectional SWE is better than the longitudinal SWE, Emax is better than Emean, the anisotropy of SWE is better than SWE, and the anisotropy factor is better than the anisotropy difference.
X-ray repair cross-complementing protein 1 (XRCC1) loss promotes β-lapachone –induced apoptosis in pancreatic cancer cells
Authors: Zheng Yansong , Zhang Hengce , Guo Yueting , Chen Yuan , Chen Hanglong , Liu Yingchun
Published: November 2021

Background

β-lapachone (β-lap), the NQO1 bioactivatable drug, is thought to be a promising anticancer agent. However, the toxic side effects of β-lap limit the drug use, highlighting the need for a thorough understanding of β-lap’s mechanism of action. β-lap undergoes NQO1-dependent futile redox cycling, generating massive ROS and oxidative DNA lesions, leading to cell death. Thus, base excision repair (BER) pathway is an important resistance factor. XRCC1, a scaffolding component, plays a critical role in BER.

Methods

We knocked down XRCC1 expression by using pLVX-shXRCC1 in the MiaPaCa2 cells and BxPC3 cells and evaluated β-lap-induced DNA lesions by γH2AX foci formation and alkaline comet assay. The cell death induced by XRCC1 knockdown + β-lap treatment was analysed by relative survival, flow cytometry and Western blotting analysis.

Results

We found that knockdown of XRCC1 significantly increased β-lap-induced DNA double-strand breaks, comet tail lengths and cell death in PDA cells. Furthermore, we observed combining XRCC1 knockdown with β-lap treatment switched programmed necrosis with β-lap monotherapy to caspase-dependent apoptosis.

Conclusions

These results indicate that XRCC1 is involved in the repair of β-lap-induced DNA damage, and XRCC1 loss amplifies sensitivity to β-lap, suggesting targeting key components in BER pathways may have the potential to expand use and efficacy of β-lap for gene-based therapy.
NME6 is a phosphotransfer-inactive, monomeric NME/NDPK family member and functions in complexes at the interface of mitochondrial inner membrane and matrix
Authors: Proust Bastien , Radić Martina , Vidaček Nikolina Škrobot , Cottet Cécile , Attia Stéphane , Lamarche Frédéric , Ačkar Lucija , Mikulčić Vlatka Godinić , Tokarska-Schlattner Malgorzata , Ćetković Helena , Schlattner Uwe , Bosnar Maja Herak
Published: November 2021

Background

NME6 is a member of the nucleoside diphosphate kinase (NDPK/NME/Nm23) family which has key roles in nucleotide homeostasis, signal transduction, membrane remodeling and metastasis suppression. The well-studied NME1-NME4 proteins are hexameric and catalyze, via a phospho-histidine intermediate, the transfer of the terminal phosphate from (d)NTPs to (d)NDPs (NDP kinase) or proteins (protein histidine kinase). For the NME6, a gene/protein that emerged early in eukaryotic evolution, only scarce and partially inconsistent data are available. Here we aim to clarify and extend our knowledge on the human NME6.

Results

We show that NME6 is mostly expressed as a 186 amino acid protein, but that a second albeit much less abundant isoform exists. The recombinant NME6 remains monomeric, and does not assemble into homo-oligomers or hetero-oligomers with NME1-NME4. Consequently, NME6 is unable to catalyze phosphotransfer: it does not generate the phospho-histidine intermediate, and no NDPK activity can be detected. In cells, we could resolve and extend existing contradictory reports by localizing NME6 within mitochondria, largely associated with the mitochondrial inner membrane and matrix space. Overexpressing NME6 reduces ADP-stimulated mitochondrial respiration and complex III abundance, thus linking NME6 to dysfunctional oxidative phosphorylation. However, it did not alter mitochondrial membrane potential, mass, or network characteristics. Our screen for NME6 protein partners revealed its association with NME4 and OPA1, but a direct interaction was observed only with RCC1L, a protein involved in mitochondrial ribosome assembly and mitochondrial translation, and identified as essential for oxidative phosphorylation.

Conclusions

NME6, RCC1L and mitoribosomes localize together at the inner membrane/matrix space where NME6, in concert with RCC1L, may be involved in regulation of the mitochondrial translation of essential oxidative phosphorylation subunits. Our findings suggest new functions for NME6, independent of the classical phosphotransfer activity associated with NME proteins.
Novel Circulating Hypermethylated RASSF1A ddPCR for Liquid Biopsies in Patients With Pediatric Solid Tumors
Authors: van Zogchel Lieke M. J. , Lak Nathalie S. M. , Verhagen Onno J. H. M. , Tissoudali Ahmed , Gussmalla Nuru Mohammed , Gelineau Nina U. , Zappeij-Kannengieter Lily , Javadi Ahmad , Zijtregtop Eline A. M. , Merks Johannes H. M. , van den Heuvel-Eibrink Marry , Schouten-van Meeteren Antoinette Y. N. , Stutterheim Janine , van der Schoot C. Ellen , Tytgat Godelieve A. M.
Published: November 2021

PURPOSE

Liquid biopsies can be used to investigate tumor-derived DNA, circulating in the cell-free DNA (cfDNA) pool in blood. We aimed to develop a droplet digital polymerase chain reaction (ddPCR) assay detecting hypermethylation of tumor suppressor gene RASSF1A as a simple standard test to detect various pediatric tumor types in small volume blood samples and to evaluate this test for monitoring treatment response of patients with high-risk neuroblastoma.

METHODS

We developed a ddPCR assay to sensitively detect tumor-derived hypermethylated RASSF1A DNA in liquid biopsies. We tested this assay in plasma of 96 patients with neuroblastoma, renal tumors, rhabdomyosarcoma, or Hodgkin lymphoma at diagnosis and in cerebrospinal fluid of four patients with brain tumors. We evaluated the presence of hypermethylated RASSF1A in plasma samples during treatment and follow-up in 47 patients with neuroblastoma treated according to high-risk protocol and correlated results with blood mRNA–based and bone marrow mRNA–based minimal residual disease detection and clinical outcomes.

RESULTS

The total cfDNA level was significantly higher in patients with metastatic neuroblastoma and nephroblastoma compared with healthy adult and pediatric controls. Hypermethylated RASSF1A was present in 41 of 42 patients with metastatic neuroblastoma and in all patients with nephroblastoma, with the median percentage of 69% and 21% of total RASSF1A, respectively. Hypermethylated RASSF1A levels decreased during therapy and recurred at relapse.

CONCLUSION

Our findings demonstrate the value of ddPCR-based detection of hypermethylated RASSF1A as a circulating molecular tumor marker in neuroblastoma. Our preliminary investigation of RASSF1A hypermethylation detection in circulating cfDNA of other pediatric tumor entities demonstrates potential as a pan-tumor marker, but requires investigation in larger cohorts to evaluate its use and limitations.