bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating the properties of hot asphalt mixtures modified by Metakaolin
Authors: Oda Ahmed W. , El-Desouky Ahmed , Mahdy Hassan , Mousa Osama M.
Published: August 2022

The mineral filler has an important role in filling the voids between aggregates inside the asphalt matrix. This study investigates the effect of using Metakaolin (MK) as a modifier on the mechanical properties of hot mix asphalt. MK was added to the mixtures as a part of the filler used. As known, the hot mix asphalt (HMA) consists of coarse aggregate, fine aggregate, filler material, and asphalt binder with or without existing modifiers. The components of the HMA were subjected to validation tests to check the validity of the materials for producing HMA The asphalt binder used was bitumen 60/70. Tests performed on bitumen were penetration test, softening point test, flash and firing point test. The optimum asphalt content based on the designed control mix was 5.2%. the control mix has no content of MK. MK was added as a partial replacement of filler used (limestone powder). Mk was added to the HMA by replacing 20%, 40%, 60%, 80%, and 100% of the filler. A comparative study was performed to evaluate the effects of HMA modification by MK. Marshall quotient (MQ) increases by 10.37% for the mix modified by 40% MK. MK has significant effects on the indirect tensile strength (ITS).
Implementation of Secondary and Tertiary Treated Wastewater in Concrete Manufacturing
Authors: Micheal A , Abdel Salam H , Ghanem G M
Published: August 2022

Water scarcity is a problem that faces many regions. In a developing and arid country like Egypt, the need for freshwater is exponentially increasing. This research is an evaluation of the recycled wastewater to be used in concrete manufacturing. The treated wastewater is blended with potable water with percentages of 25%, 50%, and 100%. The mixture of the two types of water is used in concrete mixing and curing. Control specimens with pure potable water are cast for comparison. The setting time for Ordinary Portland Cement is tested using the different water mixes. The hardened concrete is tested in compression and flexural at age of 7 days and 28 days. The results show that the treated wastewater may delay both the initial and final setting. The phenomenon is more pronounced in secondary treated wastewater. For the compressive strength, both treatment regimens can be safely used. The flexural strength is reduced at late ages.
Land Subsidence Hazard Mapping in relation with Sinkholes in Saptosari District, Gunung Kidul, Indonesia
Authors: Fikrillah R R , Say S , Putra D P E
Published: August 2022

Saptosari is one of the areas in the karst terrain of Gunung Kidul Regency, Yogyakarta, Indonesia. In this area, sinkholes are very common, especially in weathered and covered by soil overburden. It is known a lot of land subsidence due to sinkholes are found and reported by the local community. Therefore, the purpose of this study was to map the land subsidence hazard zone due to the presence of sinkholes. To achieve this goal, field observations and evaluation of secondary data were carried out to collect slope data, lithology, lineament of geological structures, and the location of sinkholes and subsidence that already existed. Analytical Hierarchy Process (AHP) was carried out to determine the weight of the geomorphological parameter, lithological parameter, and the distance to geological structure in order to predict the occurrence of sinkholes. The weighted results of the AHP method are then used to create a land subsidence hazard map by using the GIS-overlay method. The study reveals three subsidence hazard zones in the research area, namely (1) high susceptible area with subsidence probability of 92%, (2) moderate susceptible area with subsidence probability of 4.7%, and (3) low susceptible area zones with 0% of subsidence probability.
Characteristics of Mengger Formation’s volcaniclastic in Cisaat River, Brebes, Central Java, Indonesia
Authors: Aini H N , Setiawan N I , Haq M N , Mahardika C A , Nugroho S , Setiawan R
Published: August 2022

The Cisaat River in Brebes Regency, Central Java, is one of the sites on Java Island where vertebrate fossils were found. Mengger Formation, composed of volcaniclastics material such as tuff and pumice fragments, contains these fossils. The presence of vertebrate fossils along with volcanic deposits has remained unclear of its deposition history. This research characterizes the volcaniclastic rocks in Mengger Formation based on geological field observation and petrography analysis. The study aims to identify and distinguish its primary and secondary volcaniclastic depositional processes. The measured stratigraphic sections reveal that the formation has 7 lithofacies from older to younger, namely grain-supported conglomerate, sandstone, siltstone, sandy mudstone, matrix-supported conglomerate, tuffaceous sandstone, and tuffaceous conglomerate. The primary volcaniclastic materials comprise pumice clast, plagioclase, pyroxene, hornblende, quartz, biotite, lithic fragments, and volcanic glass. In contrast, secondary volcaniclastic or epiclastic-sedimentary materials contain lithic fragments, quartz, plagioclase, pumice clast, and clay matrix. The origin of the resedimented volcaniclastic material was probably derived from a large volume of ignimbrite near the volcano. From the deposit and measurement section, it can be concluded that the type of the Mengger volcaniclastic.
Gold recovery from the residue of jewelry waste recycling: pre-treatment using shaking table separation and flotation
Authors: Jiga A P , Pasithbhattarabhorn J , Juntarasakul O , Pimolrat J , Soonthornwiphat N , Phengsaart T
Published: August 2022

Gold is one of the precious metals used all over the world. It is used in various ways, such as in electrical and electronic equipment, as well as in jewelry. Gold is constantly depleted, so recycling is a very important process for recovering valuable materials as secondary raw materials. In this study, the residue from a jewelry waste recycling process was used. Shaking table separation and flotation as the pre-treatment before the hydrometallurgical processes were investigated. For shaking table experiments, the effects of table angle and water flow rate were investigated and a batch-type mechanical flotation was used for the flotation experiment. The results showed that for the shaking table separation, gold recoveries were high, while the purity of gold was higher, with lower recovery.
Characteristics of Engineering Geology in Talegong Road, Talegong, Garut, West Java, Indonesia
Authors: Naufal M H , Setiawan H
Published: August 2022

Talegong road, Garut, West Java, is provincial road with a length of 7 kilometers that connects Garut and Bandung. The road segment KM 2.3 – KM 7 is located between the steep slope of high hills and has potential for landslide. To find out the landslide potential, determining the characteristics of geology and engineering geology at this road segment are needed. The methods used in this research are engineering geology mapping (geomorphology, lithology, structural geology and rock mass quality) and laboratory analyses of soil and rock properties index, shear strength test, petrographic analysis and uniaxial compressive strength test. The results of geological mapping show the aspect geomorphological in the area consists of high hills with rather steep to very steep slopes. Lithological, the area consists of aphanitic andesite and porphyritic andesite. The area is dominated by Northeast – Southeast stress regime. In term of rock mass quality, the study area consists of three class with value in Rock Mass Rating classification, which are good rock, fair rock, poor rock and no value rock (soil). The study area is divided into three units in the engineering geological map: (1) unit A has fair – good rock (II – III) with rather steep - very steep slope with low landslide potential, (2) unit B has fair rock (III) with steep – very steep slope with medium landslide potential, and (3) unit C has poor – no value rock or soil (IV – 0) with a very steep slope with high landslide potential.
Oxidation of ciprofloxacin by the synergistic effect of DBD plasma and persulfate: reactive species and influencing factors analysis
Authors: SONG Shilin , HUANG Yuyue , DU Yansheng , XIAO Sisi , HAN Song , HU Kun , ZHANG Huihui , WANG Huijuan , WU Chundu , A Qiong
Published: August 2022

A synergistic system of water falling film dielectric barrier discharge (DBD) plasma and persulfate (PS) was set up and used for oxidizing ciprofloxacin (CIP) in water. Results of reactive species formation in the DBD-only system as well as the DBD–PS system verified the PS activation in the DBD system. Influencing factors on CIP degradation and the degradation process were also been studied. The obtained results showed that the presence of PS could greatly improve the degradation and mineralization of CIP and that the degradation efficiency could reach 97.73% after only 40 min treatment with 4 mM PS addition. The increase of PS concentration, the lower CIP concentration, the acidic solution pH and the addition of metal ions (Fe2+ and Cu2+) enhanced the CIP degradation, while the existence of Cl− and HC

O

3

−

had a negative effect. The experiments related to scavenger addition confirmed the contribution of the main reactive species to the CIP oxidation. Three probable degradation pathways were proposed by analyzing the inorganic ions and organic byproducts formed during the CIP degradation. The toxicity evaluation results of the CIP and its intermediates confirmed the effectiveness of the DBD–PS synergistic system.
Adult Child Schooling and Older Parents’ Cognitive Outcomes in the Survey of Health, Aging and Retirement in Europe (SHARE): A Quasi-Experimental Study
Authors: Torres Jacqueline M , Yang Yulin , Rudolph Kara E , Meza Erika , Glymour M Maria , Courtin Emilie
Published: August 2022

A growing body of research suggests that adult child educational attainment benefits older parents’ cognitive outcomes via financial (e.g., direct monetary transfers) and nonfinancial (e.g., psychosocial) mechanisms. Quasi-experimental studies are needed to circumvent confounding bias. No such quasi-experimental studies have been completed in higher-income countries, where financial transfers from adult children to aging parents are rare. Using data on 8,159 adults aged ≥50 years in the Survey for Health, Aging and Retirement in Europe (2004/2005), we leveraged changes in compulsory schooling laws as quasi-experiments. Each year of increased schooling among respondents’ oldest children was associated with better verbal fluency (β = 0.07, 95% CI: 0.02, 0.12) scores; overall associations with verbal memory scores were null, with mixed and imprecise evidence of association in models stratified by parent gender. We also evaluated associations with psychosocial outcomes as potentially important mechanisms. Increased schooling among respondents’ oldest children was associated with higher quality-of-life scores and fewer depressive symptoms. Our findings present modest albeit inconsistent evidence that increases in schooling may have an “upward” influence on older parents’ cognitive performance even in settings where financial transfers from adult children to their parents are uncommon. Associations with parents’ psychosocial outcomes were more robust.
Interaction between patient and general practitioner according to the patient body weight: a cross-sectional survey
Authors: Gimenez Laëtitia , Kelly-Irving Michelle , Delpierre Cyrille , Rougé-Bugat Marie-Eve , Lepage Benoit , Lang Thierry
Published: August 2022

Objective

To analyse whether patient–general practitioner (GP) interaction, measured by their disagreement, varies among overweight or obese patients compared with normal-weight patients.

Methods

Twenty-seven GPs and 585 patients participated in the quantitative phase of the multidisciplinary INTERMEDE project and answered “mirrored” questionnaires collecting both GPs and patients’ perceptions on information and advice given at the end of the consultation. Multilevel logistic regressions were performed to explore associations between patient body mass index (BMI) and patient–GP disagreement on information and advice given during the consultation.

Results

Disagreement increased with the patients’ excess weight, and it was particularly pronounced for advice given by GPs on weight and lifestyle issues. Compared with patients with a “normal” BMI, overweight patients were more likely to disagree with their GP regarding advice given on weight loss (odds ratio [OR] = 10.7, 95% confidence interval [CI] = 4.1–27.3), advice given on doing more physical activity (OR = 1.9, 95% CI = 1.1–3.4), and nutritional advice (OR = 2.9, 95% CI = 1.5–5.6).

Conclusion

These disagreements could degrade the quality of patient–physician relationship. Our study provides an opportunity for GPs to reflect on how they communicate with overweight and obese patients, particularly with regard to lifestyle and weight-related advice and interventions taking into account the patient’s representations.
Genetic analysis of human RNA binding motif protein 48 (RBM48) reveals an essential role in U12-type intron splicing
Authors: Siebert Amy E , Corll Jacob , Paige Gronevelt J , Levine Laurel , Hobbs Linzi M , Kenney Catalina , Powell Christopher L E , Battistuzzi Fabia U , Davenport Ruth , Mark Settles A , Brad Barbazuk W , Westrick Randal J , Madlambayan Gerard J , Lal Shailesh
Published: August 2022

U12-type or minor introns are found in most multicellular eukaryotes and constitute ∼0.5% of all introns in species with a minor spliceosome. Although the biological significance for the evolutionary conservation of U12-type introns is debated, mutations disrupting U12 splicing cause developmental defects in both plants and animals. In human hematopoietic stem cells, U12 splicing defects disrupt proper differentiation of myeloid lineages and are associated with myelodysplastic syndrome, predisposing individuals to acute myeloid leukemia. Mutants in the maize ortholog of RNA binding motif protein 48 (RBM48) have aberrant U12-type intron splicing. Human RBM48 was recently purified biochemically as part of the minor spliceosome and shown to recognize the 5′ end of the U6atac snRNA. In this report, we use CRISPR/Cas9-mediated ablation of RBM48 in human K-562 cells to show the genetic function of RBM48. RNA-seq analysis comparing wild-type and mutant K-562 genotypes found that 48% of minor intron-containing genes have significant U12-type intron retention in RBM48 mutants. Comparing these results to maize rbm48 mutants defined a subset of minor intron-containing genes disrupted in both species. Mutations in the majority of these orthologous minor intron-containing genes have been reported to cause developmental defects in both plants and animals. Our results provide genetic evidence that the primary defect of human RBM48 mutants is aberrant U12-type intron splicing, while a comparison of human and maize RNA-seq data identifies candidate genes likely to mediate mutant phenotypes of U12-type splicing defects.
Molecular subclass of uterine fibroids predicts tumor shrinkage in response to ulipristal acetate
Authors: Kolterud Åsa , Välimäki Niko , Kuisma Heli , Patomo Joonatan , Ilves Sini T , Mäkinen Netta , Kaukomaa Jaana , Palin Kimmo , Kaasinen Eevi , Karhu Auli , Pasanen Annukka , Bützow Ralf , Heikinheimo Oskari , Kopp Kallner Helena , Aaltonen Lauri A
Published: August 2022

Precision medicine carries great potential for management of all tumor types. The aim of this retrospective study was to investigate if the two most common genetically distinct uterine fibroid subclasses, driven by aberrations in MED12 and HMGA2 genes, respectively, influence response to treatment with the progesterone receptor modulator ulipristal acetate. Changes in diameter and mutation status were derived for 101 uterine fibroids surgically removed after ulipristal acetate treatment. A significant difference in treatment response between the two major subclasses was detected. MED12 mutant fibroids had 4.4 times higher odds of shrinking in response to ulipristal acetate treatment as compared to HMGA2 driven fibroids (95% confidence interval 1.37–13.9; P = 0.013), and in a multivariate analysis molecular subclassification was an independent predictive factor. Compatible with this finding, gene expression and DNA methylation analyses revealed subclass specific differences in progesterone receptor signaling. The work provides a proof-of-principle that uterine fibroid treatment response is influenced by molecular subclass and that the genetic subclasses should be taken into account when evaluating current and future uterine fibroid therapies.
miR164g-MsNAC022 acts as a novel module mediating drought response by transcriptional regulation of reactive oxygen species scavenging systems in apple
Authors: Peng Xiang , Feng Chen , Wang Yan-Tao , Zhang Xiang , Wang Yan-Yan , Sun Yue-Ting , Xiao Yu-Qin , Zhai Ze-Feng , Zhou Xin , Du Bing-Yang , Wang Chao , Liu Yang , Li Tian-Hong
Published: August 2022

Under drought stress, reactive oxygen species (ROS) overaccumulate as a secondary stress that impairs plant performance and thus severely reduces crop yields. The mitigation of ROS levels under drought stress is therefore crucial for drought tolerance. MicroRNAs (miRNAs) are critical regulators of plant development and stress responses. However, the complex molecular regulatory mechanism by which they function during drought stress, especially in drought-triggered ROS scavenging, is not fully understood. Here, we report a newly identified drought-responsive miRNA, miR164g, in the wild apple species Malus sieversii and elucidate its role in apple drought tolerance. Our results showed that expression of miR164g is significantly inhibited under drought stress and it can specifically cleave transcripts of the transcription factor MsNAC022 in M. sieversii. The heterologous accumulation of miR164g in Arabidopsis thaliana results in enhanced sensitivity to drought stress, while overexpression of MsNAC022 in Arabidopsis and the cultivated apple line ‘GL-3’ (Malus domestica Borkh.) lead to enhanced tolerance to drought stress by raising the ROS scavenging enzymes activity and related genes expression levels, particularly PEROXIDASE (MsPOD). Furthermore, we showed that expression of MsPOD is activated by MsNAC022 in transient assays. Interestingly, Part1 (P1) region is the key region for the positive regulation of MsPOD promoter by MsNAC022, and the different POD expression patterns in M. sieversii and M. domestica is attributed to the specific fragments inserted in P1 region of M. sieversii. Our findings reveal the function of the miR164g-MsNAC022 module in mediating the drought response of M. sieversii and lay a foundation for breeding drought-tolerant apple cultivars.
Quantitative Fecal Microbiota Profiles Relate to Therapy Response During Induction With Tumor Necrosis Factor α Antagonist Infliximab in Pediatric Inflammatory Bowel Disease
Authors: Höyhtyä Miikka , Korpela Katri , Saqib Schahzad , Junkkari Sofia , Nissilä Eija , Nikkonen Anne , Dikareva Evgenia , Salonen Anne , de Vos Willem M , Kolho Kaija-Leena
Published: August 2022

Background

The role of intestinal microbiota in inflammatory bowel diseases is intensively researched. Pediatric studies on the relation between microbiota and treatment response are sparse. We aimed to determine whether absolute abundances of gut microbes characterize the response to infliximab induction in pediatric inflammatory bowel disease.

Methods

We recruited pediatric patients with inflammatory bowel disease introduced to infliximab at Children’s Hospital, University of Helsinki. Stool samples were collected at 0, 2, and 6 weeks for microbiota and calprotectin analyses. We defined treatment response as fecal calprotectin value <100 µg/g at week 6. Intestinal microbiota were analyzed by 16S ribosomal RNA gene amplicon sequencing using the Illumina MiSeq platform. We analyzed total bacterial counts using quantitative polymerase chain reaction and transformed the relative abundances into absolute abundances based on the total counts.

Results

At baseline, the intestinal microbiota in the treatment responsive group (n = 10) showed a higher absolute abundance of Bifidobacteriales and a lower absolute abundance of Actinomycetales than nonresponders (n = 19). The level of inflammation according to fecal calprotectin showed no statistically significant association with the absolute abundances of fecal microbiota. The results on relative abundances differed from the absolute abundances. At the genus level, the responders had an increased relative abundance of Anaerosporobacter but a reduced relative abundance of Parasutterella at baseline.

Conclusions

High absolute abundance of Bifidobacteriales in the gut microbiota of pediatric patients reflects anti-inflammatory characteristics associated with rapid response to therapy. This warrants further studies on whether modification of pretreatment microbiota might improve the outcomes.
Use of IBD Drugs in Patients With Hepatobiliary Comorbidities: Tips and Tricks
Authors: Massironi Sara , Pirola Lorena , Mulinacci Giacomo , Ciaccio Antonio , Viganò Chiara , Palermo Andrea , Zilli Alessandra , Invernizzi Pietro , Danese Silvio
Published: August 2022

Advanced therapies (biologic agents and small molecules) for inflammatory bowel diseases (IBD) have radically changed the management of these diseases during the last decade. Data about these drugs in patients with hepatic disorders derive mainly from real-life studies, as these conditions often represent an exclusion criterion from pivotal drug developmental trials. However, IBD patients sometimes have concomitant liver diseases. Nonalcoholic fatty liver disease is the most prevalent hepatic comorbidity, whereas viral hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, and hepatic vascular disorders are less frequent. This review aimed at describing the real-life data about the use of advanced therapies for IBD in patients with concomitant hepatobiliary disorders. Hepatitis B virus and hepatitis C virus infections do not represent an absolute contraindication for novel IBD therapeutic agents. Data from the literature suggest a safe hepatobiliary profile of biologic agents and small molecules in the case of nonalcoholic fatty liver disease, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis, and portal vein thrombosis. Consequently, although the liver disease does not affect a different therapeutic approach in patients with concomitant IBD and liver disease, a close risk/benefit analysis for each drug should be performed in these patients, especially in cirrhotic patients and in the postliver transplant setting.
Comparison of pharmacokinetics and stability of generics of cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs: an intravenous bioequivalence study in healthy volunteers
Authors: Bergmann Felix , Wulkersdorfer Beatrix , Oesterreicher Zoe , Bauer Martin , al Jalali Valentin , Nussbaumer-Pröll Alina , Wölfl-Duchek Michael , Jorda Anselm , Lackner Edith , Reiter Birgit , Stimpfl Thomas , Ballarini Nicolas , König Franz , Zeitlinger Markus
Published: August 2022

Objectives

The efficacy and quality of generic antibacterial drug formulations are often questioned by both healthcare specialists and patients. Therefore, the present study investigated the interchangeability of generic drugs with their originators by comparing bioequivalence parameters and stability data of generic cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs.

Methods

In this open-label, randomized, crossover bioequivalence study, three groups of 12 healthy volunteers each received a single intravenous infusion of either 2 g of cefepime or 4.5 g of piperacillin/tazobactam and two generic formulations, or 600 mg of linezolid and one generic formulation. Plasma sampling was performed, with a 5 day washout period between study days. Stability was tested by storing reconstituted generic and originator products according to their own storage specifications and those of the comparator products. All concentrations were measured by LC-MS.

Results

Similar ratios of generic/originator (90% CI) Cmax were observed for Cefepime-MIP/Maxipime [93.7 (88.4–99.4)], Cefepime Sandoz/Maxipime [95.9 (89.1–103.2)], Linezolid Kabi/Zyvoxid [104.5 (91.1–119.9)], Piperacillin Kabi/Tazobac [95.9 (90.4–101.7)], Piperacillin Aurobindo/Tazobac [99.7 (84.9–104.7)], Tazobactam Kabi/Tazobac [93.4 (87.4–99.8)] and Tazobactam Aurobindo/Tazobac [97.4 (89.7–105.8)]. Accordingly, similar ratios of AUC0–t were observed for Cefepime-MIP/Maxipime [91.1 (87.6–94.8)], Cefepime Sandoz/Maxipime [97.9 (92.5–103.5)], Linezolid Kabi/Zyvoxid [99.7 (93.3–106.6)], Piperacillin Kabi/Tazobac [92.2 (88.3–96.3)], Piperacillin Aurobindo/Tazobac [99.9 (97.0–102.8)], Tazobactam Kabi/Tazobac [91.4 (86.4–96.7)] and Tazobactam Aurobindo/Tazobac [98.8 (94.3–103.6)]. Stable and similar concentrations were measured for all contiguous substances, regardless of storage conditions.

Conclusions

Compared with their respective originator drugs, generic cefepime, linezolid and piperacillin/tazobactam met the predetermined bioequivalence criteria. All formulations were stable under the storage conditions of their respective comparators.
Comprehension, utility, and preferences of prostate cancer survivors for visual timelines of patient-reported outcomes co-designed for limited graph literacy: meters and emojis over comics
Authors: Snyder Lauren E , Phan Daniel F , Williams Kristen C , Piqueiras Eduardo , Connor Sarah E , George Sheba , Kwan Lorna , Villatoro Chavez Jefersson , Tandel Megha D , Frencher Stanley K , Litwin Mark S , Gore John L , Hartzler Andrea L
Published: August 2022

Objective

Visual timelines of patient-reported outcomes (PRO) can help prostate cancer survivors manage longitudinal data, compare with population averages, and consider future trajectories. PRO visualizations are most effective when designed with deliberate consideration of users. Yet, graph literacy is often overlooked as a design constraint, particularly when users with limited graph literacy are not engaged in their development. We conducted user testing to assess comprehension, utility, and preference of longitudinal PRO visualizations designed for prostate cancer survivors with limited literacy.

Materials and methods

Building upon our prior work co-designing longitudinal PRO visualizations with survivors, we engaged 18 prostate cancer survivors in a user study to assess 4 prototypes: Meter, Words, Comic, and Emoji. During remote sessions, we collected data on prototype comprehension (gist and verbatim), utility, and preference.

Results

Participants were aged 61–77 (M = 69), of whom half were African American. The majority of participants had less than a college degree (95%), had inadequate health literacy (78%), and low graph literacy (89%). Among the 4 prototypes, Meter had the best gist comprehension and was preferred. Emoji was also preferred, had the highest verbatim comprehension, and highest rated utility, including helpfulness, confidence, and satisfaction. Meter and Words both rated mid-range for utility, and Words scored lower than Emoji and Meter for comprehension. Comic had the poorest comprehension, lowest utility, and was least preferred.

Discussion

Findings identify design considerations for PRO visualizations, contributing to the knowledge base for visualization best practices. We describe our process to meaningfully engage patients from diverse and hard-to-reach groups for remote user testing, an important endeavor for health equity in biomedical informatics.

Conclusion

Graph literacy is an important design consideration for PRO visualizations. Biomedical informatics researchers should be intentional in understanding user needs by involving diverse and representative individuals during development.
Genus Lupinus (Fabaceae): a review of ethnobotanical, phytochemical and biological studies
Authors: Ishaq Ali Raza , El-Nashar Heba A S , Younis Tahira , Mangat Muhammad Asad , Shahzadi Mashal , Ul Haq Amina Shamsheer , El-Shazly Mohamed
Published: August 2022

Objectives

Lupinus is a large and diverse genus comprising approximately 200 species, belonging to the family Fabaceae. Lupinus plants have been used for heart stimulants, nerves, urinary tract infections, skin disorders, and psoriasis in folk medicine. This review aims to recap the traditional medicinal uses, nutritional value, phytochemical profile, and biological activities of Lupinus species.

Key findings

From the literature survey, Lupinus is considered as a factory of various phytochemicals like flavonoids, iso-flavonoids, alkaloids, triterpenoids. The presence of proteins, essential fatty acids, and amino acids, as well as alkaloids, minerals, and dietary fibers, indicated that the plants in this genus had a high nutritional value. The Lupinus extracts displayed promising antidiabetic, anticancer, antimicrobial, antidiabetic, antihypertensive, antioxidant, anti-inflammatory, and antimicrobial activities.

Conclusions

The current review provides updated information that could drive the researchers for further studies. The in vitro and in vivo experiments have demonstrated various pharmacological properties. Some pharmacokinetic and toxicological investigations are warranted to ensure its safety and validity for human use.
Chemically targeting the redox switch in AP1 transcription factor ΔFOSB
Authors: Kumar Ashwani , Aglyamova Galina , Yim Yun Young , Bailey Aaron O , Lynch Haley M , Powell Reid T , Nguyen Nghi D , Rosenthal Zachary , Zhao Wen-Ning , Li Yi , Chen Jianping , Fan Shanghua , Lee Hubert , Russell William K , Stephan Clifford , Robison Alfred J , Haggarty Stephen J , Nestler Eric J , Zhou Jia , Machius Mischa , Rudenko Gabby
Published: August 2022

The AP1 transcription factor ΔFOSB, a splice variant of FOSB, accumulates in the brain in response to chronic insults such as exposure to drugs of abuse, depression, Alzheimer's disease and tardive dyskinesias, and mediates subsequent long-term neuroadaptations. ΔFOSB forms heterodimers with other AP1 transcription factors, e.g. JUND, that bind DNA under control of a putative cysteine-based redox switch. Here, we reveal the structural basis of the redox switch by determining a key missing crystal structure in a trio, the ΔFOSB/JUND bZIP domains in the reduced, DNA-free form. Screening a cysteine-focused library containing 3200 thiol-reactive compounds, we identify specific compounds that target the redox switch, validate their activity biochemically and in cell-based assays, and show that they are well tolerated in different cell lines despite their general potential to bind to cysteines covalently. A crystal structure of the ΔFOSB/JUND bZIP domains in complex with a redox-switch-targeting compound reveals a deep compound-binding pocket near the DNA-binding site. We demonstrate that ΔFOSB, and potentially other, related AP1 transcription factors, can be targeted specifically and discriminately by exploiting unique structural features such as the redox switch and the binding partner to modulate biological function despite these proteins previously being thought to be undruggable.
A deafness-associated mitochondrial DNA mutation caused pleiotropic effects on DNA replication and tRNA metabolism
Authors: Meng Feilong , Jia Zidong , Zheng Jing , Ji Yanchun , Wang Jing , Xiao Yun , Fu Yong , Wang Meng , Ling Feng , Guan Min-Xin
Published: August 2022

In this report, we investigated the molecular mechanism underlying a deafness-associated m.5783C > T mutation that affects the canonical C50-G63 base-pairing of TΨC stem of tRNACys and immediately adjacent to 5′ end of light-strand origin of mitochondrial DNA (mtDNA) replication (OriL). Two dimensional agarose gel electrophoresis revealed marked decreases in the replication intermediates including ascending arm of Y-fork arcs spanning OriL in the mutant cybrids bearing m.5783C > T mutation. mtDNA replication alterations were further evidenced by decreased levels of PolγA, Twinkle and SSBP1, newly synthesized mtDNA and mtDNA contents in the mutant cybrids. The m.5783C > T mutation altered tRNACys structure and function, including decreased melting temperature, conformational changes, instability and deficient aminoacylation of mutated tRNACys. The m.5783C > T mutation impaired the 5′ end processing efficiency of tRNACys precursors and reduced the levels of tRNACys and downstream tRNATyr. The aberrant tRNA metabolism impaired mitochondrial translation, which was especially pronounced effects in the polypeptides harboring higher numbers of cysteine and tyrosine codons. These alterations led to deficient oxidative phosphorylation including instability and reduced activities of the respiratory chain enzyme complexes I, III, IV and intact supercomplexes overall. Our findings highlight the impact of mitochondrial dysfunction on deafness arising from defects in mitochondrial DNA replication and tRNA metabolism.
Exploration and analysis of R-loop mapping data with RLBase
Authors: Miller Henry E , Montemayor Daniel , Li Janet , Levy Simon A , Pawar Roshan , Hartono Stella , Sharma Kumar , Frost Bess , Chedin Frédéric , Bishop Alexander J R
Published: August 2022

R-loops are three-stranded nucleic acid structures formed from the hybridization of RNA and DNA. In 2012, Ginno et al. introduced the first R-loop mapping method. Since that time, dozens of R-loop mapping studies have been conducted, yielding hundreds of publicly available datasets. Current R-loop databases provide only limited access to these data. Moreover, no web tools for analyzing user-supplied R-loop datasets have yet been described. In our recent work, we reprocessed 810 R-loop mapping samples, building the largest R-loop data resource to date. We also defined R-loop consensus regions and developed a framework for R-loop data analysis. Now, we introduce RLBase, a user-friendly database that provides the capability to (i) explore hundreds of public R-loop mapping datasets, (ii) explore R-loop consensus regions, (iii) analyze user-supplied data and (iv) download standardized and reprocessed datasets. RLBase is directly accessible via the following URL: https://gccri.bishop-lab.uthscsa.edu/shiny/rlbase/.
In vivofunctional characterization of EGFR variants identifies novel drivers of glioblastoma
Authors: Yu Kwanha , Kong Kathleen , Lozzi Brittney , Luna-Figueroa Estefania , Cervantes Alexis , Curry Rachel , Mohila Carrie A , Rao Ganesh , Jalali Ali , Mills Gordon B , Scott Kenneth L , Deneen Benjamin
Published: August 2022

Background

Glioblastoma is the most common and aggressive primary brain tumor. Large-scale sequencing initiatives have cataloged its mutational landscape in hopes of elucidating mechanisms driving this deadly disease. However, a major bottleneck in harnessing this data for new therapies is deciphering “driver” and “passenger” events amongst the vast volume of information.

Methods

We utilized an autochthonous, in vivo screening approach to identify driver, EGFR variants. RNA-Seq identified unique molecular signatures of mouse gliomas across these variants, which only differ by a single amino acid change. In particular, we identified alterations to lipid metabolism, which we further validated through an unbiased lipidomics screen.

Results

Our screen identified A289I as the most potent EGFR variant, which has previously not been characterized. One of the mechanisms through which A289I promotes gliomagenesis is to alter cellular triacylglycerides through MTTP. Knockout of Mttp in mouse gliomas, reduces gliomagenesis in multiple models.

Conclusions

EGFR variants that differ by a single amino acid residue differentially promote gliomagenesis. Among the identified mechanism that drives glioma growth include lipid metabolism through MTTP. Understanding triacylglyceride accumulation may present a prospective therapeutic pathway for this deadly disease.
Population sorting and human capital accumulation
Authors: Azarnert Leonid V
Published: August 2022

This article analyses the effect of population sorting on economic growth. The analysis is performed in a two-region growth model with endogenous fertility, in which public knowledge spillovers from the more advanced core amplify the productivity of investment in children’s human capital in the periphery. I show how migration affects the inter-temporal evolution of human capital in each of the regions and the economy as a whole. I discuss how public policy interventions can help increase the per-capita human capital levels, if free uncontrolled migration leads to a reduction in human capital accumulation. I also analyse how migration and public policy interventions may affect population growth.
Identification as the Process to Determine the Content of Customary International Law
Authors: Lando Massimo
Published: August 2022

Scholars recently have been arguing that one can interpret rules of customary international law. This article argues that the case for the interpretability of custom is unpersuasive and that the content of customary rules is determined by the process to ascertain the existence of such rules, known as identification. The main thrust of this article is that state practice and opinio juris are central to determining the content of customary international law, but that the case for the interpretability of custom wrongly downplays that centrality. To develop its argument, this article discusses the overlap between content and existence of customary rules, the means to distinguish between putative customary rules (called ‘individuation’), the means to interpret customary rules and the possibility for customary rules to move between levels of abstraction without evidence of state practice or opinio juris (called ‘plasticity’). This article also criticises the legitimacy of interpreting customary international law.
A Guide to Plant Intracellular Temperature Imaging using Fluorescent Thermometers
Authors: Inada Noriko
Published: August 2022

All aspects of plant physiology are influenced by temperature. Changes in environmental temperature alter the temperatures of plant tissues and cells, which then affect various cellular activities, such as gene expression, protein stability and enzyme activities. In turn, changes in cellular activities, which are associated with either exothermic or endothermic reactions, can change the local temperature in cells and tissues. In the past 10 years, a number of fluorescent probes that detect temperature and enable intracellular temperature imaging have been reported. Intracellular temperature imaging has revealed that there is a temperature difference >1°C inside cells and that the treatment of cells with mitochondrial uncoupler or ionomycin can cause more than a 1°C intracellular temperature increase in mammalian cultured cells. Thermogenesis mechanisms in brown adipocytes have been revealed with the aid of intracellular temperature imaging. While there have been no reports on plant intracellular temperature imaging thus far, intracellular temperature imaging is expected to provide a new way to analyze the mechanisms underlying the various activities of plant cells. In this review, I will first summarize the recent progress in the development of fluorescent thermometers and their biological applications. I will then discuss the selection of fluorescent thermometers and experimental setup for the adaptation of intracellular temperature imaging to plant cells. Finally, possible applications of intracellular temperature imaging to investigate plant cell functions will be discussed.
Strigolactones act downstream of gibberellins to regulate fiber cell elongation and cell wall thickness in cotton (Gossypium hirsutum)
Authors: Tian Zailong , Zhang Yuzhou , Zhu Liping , Jiang Bin , Wang Huiqin , Gao Ruxi , Friml Jiří , Xiao Guanghui
Published: August 2022

Strigolactones (SLs) are a class of phytohormones that regulate plant shoot branching and adventitious root development. However, little is known regarding the role of SLs in controlling the behavior of the smallest unit of the organism, the single cell. Here, taking advantage of a classic single-cell model offered by the cotton (Gossypium hirsutum) fiber cell, we show that SLs, whose biosynthesis is fine-tuned by gibberellins (GAs), positively regulate cell elongation and cell wall thickness by promoting the biosynthesis of very long-chain fatty acids (VLCFAs) and cellulose, respectively. Furthermore, we identified two layers of transcription factors (TFs) involved in the hierarchical regulation of this GA–SL crosstalk. The top-layer TF GROWTH-REGULATING FACTOR 4 (GhGRF4) directly activates expression of the SL biosynthetic gene DWARF27 (D27) to increase SL accumulation in fiber cells and GAs induce GhGRF4 expression. SLs induce the expression of four second-layer TF genes (GhNAC100-2, GhBLH51, GhGT2, and GhB9SHZ1), which transmit SL signals downstream to two ketoacyl-CoA synthase genes (KCS) and three cellulose synthase (CesA) genes by directly activating their transcription. Finally, the KCS and CesA enzymes catalyze the biosynthesis of VLCFAs and cellulose, respectively, to regulate development of high-grade cotton fibers. In addition to providing a theoretical basis for cotton fiber improvement, our results shed light on SL signaling in plant development at the single-cell level.
Mesenchymal Stromal/Stem Cell Extracellular Vesicles and Perinatal Injury: One Formula for Many Diseases
Authors: Delavogia Eleni , Ntentakis Dimitrios P , Cortinas John A , Fernandez-Gonzalez Angeles , Alex Mitsialis S , Kourembanas Stella
Published: August 2022

Over the past decades, substantial advances in neonatal medical care have increased the survival of extremely premature infants. However, there continues to be significant morbidity associated with preterm birth with common complications including bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), neuronal injury such as intraventricular hemorrhage (IVH) or hypoxic ischemic encephalopathy (HIE), as well as retinopathy of prematurity (ROP). Common developmental immune and inflammatory pathways underlie the pathophysiology of such complications providing the opportunity for multisystem therapeutic approaches. To date, no single therapy has proven to be effective enough to prevent or treat the sequelae of prematurity. In the past decade mesenchymal stem/stromal cell (MSC)—based therapeutic approaches have shown promising results in numerous experimental models of neonatal diseases. It is now accepted that the therapeutic potential of MSCs is comprised of their secretome, and several studies have recognized the small extracellular vesicles (sEVs) as the paracrine vector. Herein, we review the current literature on the MSC-EVs as potential therapeutic agents in neonatal diseases and comment on the progress and challenges of their translation to the clinical setting.
Online Learning Challenges for Nursing Students in Appalachia
Authors: Morton Kelly , Phillips Brad
Published: August 2022

It is known that nursing students in an online learning environment may experience challenges related to their quality of life and well-being. However, it is unknown what additional challenges students face in a resource-limited environment like Appalachia. This descriptive study surveyed 154 undergraduate nursing students from a single institution in the Appalachian region at the beginning of the COVID-19 pandemic. Results reveal that students experienced unique resource-related barriers specific to underserved communities that impacted their online learning experiences. Findings offer unique implications for nurse educators facilitating online learning. Specific ideas for those teaching in resource-limited areas are presented.
Symmetry of Shoe Size and Calf Girth in Children With Treated Idiopathic Clubfoot: A Longitudinal Study
Authors: Baird Glen O. , Garcia Nancy L. , Mader Shelley , Mildes Rob , Harrison Barb , McMulkin Mark L.
Published: August 2022

Background:

Treatments for idiopathic clubfoot focus on obtaining a functional foot, typical gait pattern, and activity participation. Patients and families are also concerned about practical considerations regarding shoe wear and the appearance of the calf. The purpose of this study was to quantify whether children treated for idiopathic clubfoot have symmetry differences in shoe size and calf girth when presenting with unilateral versus bilateral involvement.

Methods:

Participants with a diagnosis of idiopathic clubfoot (treated with Ponseti or French functional methods) were prospectively recruited along with children who are typically developing. Shoe size and calf girth were measured at 5, 7, and 10 years of age.

Results:

Sixty-five participants, 45 with a diagnosis of idiopathic clubfoot (26 unilateral and 19 bilateral) and 20 who were typically developing, began the study at age 5. Children with clubfoot treated with the Ponseti versus French methods showed no differences in shoe size asymmetry, calf girth asymmetry, or absolute calf girth at age 5. Participants with unilateral clubfoot demonstrated an average of 1.5 size smaller shoes for the involved side at all 3 ages. Participants with bilateral clubfeet had a significantly smaller, <0.75 size difference between both feet. Participants with unilateral clubfoot demonstrated about a 2 cm smaller calf girth on the involved side compared with the uninvolved side at all 3 ages. Participants with bilateral clubfeet had a smaller, <0.5 cm calf difference between sides. Calf girths for involved limbs were significantly smaller than for uninvolved limbs.

Conclusions:

Children with unilateral clubfeet can expect to need a smaller shoe on their involved side. Children with bilateral clubfeet can expect a minimal shoe size discrepancy between limbs. All limbs with clubfoot involvement can expect to have a smaller calf girth than limbs that are typically developing.

Level of Evidence:

Level II. This is considered a prognostic study—investigating the effect of a treated clubfoot on shoe size and calf girth. This is a lesser-quality prospective study in which <80% of persons completed follow-up.