bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring membranous NECTIN‐4 expression patterns and enfortumab vedotin response in prostate cancer
Authors: Weiten Richard , Bernhardt Marit , Niemann Max , Kristiansen Glen , Grünwald Viktor , Ritter Manuel , Hölzel Michael , Eckstein Markus , Alajati Abdullah , Klümper Niklas , Krausewitz Philipp
Published: July 2024

Antibody‐drug conjugates (ADCs) represent a novel type of targeted cancer therapy combining the specificity of monoclonal antibodies with the cytotoxicity of conventional chemotherapy. Recently, ADCs have demonstrated practice‐changing efficacy across diverse solid cancers. The anti‐NECTIN‐4 ADC enfortumab vedotin (EV) has just been approved for patients with urothelial cancer and is currently under investigation for patients with castration‐resistant prostate cancer (CRPC e.g. Phase II ENCORE trial). Our objective was to evaluate the efficacy of EV in established prostate cancer (PCa) cell lines and to examine the membranous NECTIN‐4 expression in primary tumours (PRIM) and distant metastases (MET). NECTIN‐4 was heterogeneously expressed in the panel of PCa cell lines. EV led to growth inhibition in NECTIN‐4 expressing PCa cells (22Rv1 and LNCaP), whereas the NECTIN‐4‐negative PC‐3 cells were significantly less responsive to EV, emphasizing the dependence of EV response on its target expression. Immunohistochemical staining revealed moderate membranous NECTIN‐4 expression only in a small subgroup of CRPC patients with lung and peritoneal MET [n = 3/22 with H‐score ≥100, median H‐score 140 (IQR 130–150)], while 100% of PRIM (n = 48/48) and 86.4% of common MET sites (n = 19/22), including lymph node, bone and liver MET, were NECTIN‐4 negative. In summary, EV may be effective in NECTIN‐4‐positive PCa. However, our findings demonstrate that the tumoural NECTIN‐4 expression is predominantly low in metastatic PCa, which suggests that EV may only be effective in a biomarker‐stratified subgroup.
Perspectives of paediatric providers on antibiotic stewardship in a high‐prescribing rural region
Authors: Wattles Bethany A. , Brothers Kyle B. , Rich Carla A. , Ryan Lesa , Smith Michael J.
Published: July 2024

Purpose

Understanding drivers of antibiotic use is key to limiting the development of antimicrobial resistance. Outpatient antibiotic prescribing rates vary substantially across and within states. Kentucky is one of the highest prescribing states, and the southeastern region has rates that are drastically higher than the national average and urban areas of the state. We sought to examine provider perceptions of antibiotic use in this rural area to more effectively guide future interventions and policy.

Methods

This study utilized Medicaid prescription claims to identify providers who frequently prescribe antibiotics to children in southeastern Kentucky. Semistructured qualitative interviews were conducted to elicit provider perspectives on antibiotic overuse.

Findings

Individual, in‐person interviews were conducted with 25 providers from a variety of practices and training backgrounds (private, nonprofit, retail, physician, advanced practice registered nurses, etc.). The following themes emerged as issues that prescribers consider to contribute to antibiotic overuse: (1) caregiver pressure, especially from grandparents or families who desire a ‘quick fix’; (2) business concerns and competition and (3) cultural factors related to poverty and rural locations. Interviewed providers were supportive of public education and had mixed views on the effectiveness of delayed fill or provider feedback initiatives.

Conclusions

This study highlights unique challenges associated with antibiotic prescribing in rural areas. Findings will guide future interventions through adaptation of existing strategies to better serve this vulnerable population.
Role of social media in the presentation of disorders of gut–brain interaction: Review and recommendations
Authors: Salzberg Michael R , Kim Hannah , Basnayake Chamara , Holt Darcy , Kamm Michael A
Published: July 2024

As clinicians involved in the care of patients with disorders of gut–brain interaction (DGBIs), we—and many colleagues—have the impression that social media are adversely shaping the nature, presentation, and ability to manage these disorders, especially at the severe end of the DGBI clinical spectrum. We turned to the research literature to see if these clinical impressions were corroborated but found it virtually nonexistent. Social media have rapidly become a ubiquitous, pervasive part of the lives of most people on the planet. Although they bring many benefits, they are also replete with health misinformation, reinforcement of abnormal sick‐role behavior, and undermining of the legitimacy of psychological care. We first set out four reasons for concern about social media and DGBIs, particularly severe DGBIs. These reasons stem from phenomena described in medical fields outside DGBIs, but there is no reason to think DGBIs should be exempt from such phenomena. We then present the results of a literature search, which yielded only eight disparate recent empirical studies. We review these studies, which, although not uninformative, reveal a field in its infancy. We set out implications, most urgently multidisciplinary research directly addressing the role of social media and evaluation of interventions to mitigate its ill effects. Gastroenterological clinicians involved in DGBI care and research need to collaborate with experts in social media research, which is a very rapidly evolving, specialized field. Although knowledge is at an early stage, there are implications for specialist practice, education and training, and DGBI service delivery.
Quantitative proteomics unveils known and previously unrecognized alterations in neuropathic nerves
Authors: Defilippi Victoria , Petereit Juli , Handlos Valerie J. L. , Notterpek Lucia
Published: July 2024

Charcot–Marie–Tooth disease type 1E (CMT1E) is an inherited autosomal dominant peripheral neuropathy caused by mutations in the peripheral myelin protein 22 (PMP22) gene. The identical leucine‐to‐proline (L16P) amino acid substitution in PMP22 is carried by the Trembler J (TrJ) mouse and is found in CMT1E patients presenting with early‐onset disease. Peripheral nerves of patients diagnosed with CMT1E display a complex and varied histopathology, including Schwann cell hyperproliferation, abnormally thin myelin, axonal degeneration, and subaxonal morphological changes. Here, we have taken an unbiased data‐independent analysis (DIA) mass spectrometry (MS) approach to quantify proteins from nerves of 3‐week‐old, age and genetic strain‐matched wild‐type (Wt) and heterozygous TrJ mice. Nerve proteins were dissolved in lysis buffer and digested into peptide fragments, and protein groups were quantified by liquid chromatography‐mass spectrometry (LC–MS). A linear model determined statistically significant differences between the study groups, and proteins with an adjusted p‐value of less than 0.05 were deemed significant. This untargeted proteomics approach identified 3759 quality‐controlled protein groups, of which 884 demonstrated differential expression between the two genotypes. Gene ontology (GO) terms related to myelin and myelin maintenance confirm published data while revealing a previously undetected prominent decrease in peripheral myelin protein 2. The dataset corroborates the described pathophysiology of TrJ nerves, including elevated activity in the proteasome‐lysosomal pathways, alterations in protein trafficking, and an increase in three macrophage‐associated proteins. Previously unrecognized perturbations in RNA processing pathways and GO terms were also discovered. Proteomic abnormalities that overlap with other human neurological disorders besides CMT include Lafora Disease and Amyotrophic Lateral Sclerosis. Overall, this study confirms and extends current knowledge on the cellular pathophysiology in TrJ neuropathic nerves and provides novel insights for future examinations. Recognition of shared pathomechanisms across discrete neurological disorders offers opportunities for innovative disease‐modifying therapeutics that could be effective for distinct neuropathies.

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Impact of long contact areas for the management of varying levels of interdental papilla loss on the perception of smile esthetics between dentists and laypersons in asymmetric and symmetric situations
Authors: Ladia Ourania , Ntovas Panagiotis , Gogolas Nikolaos , Sarafianou Aspasia , Blatz Markus , Tarnow Dennis
Published: July 2024

Purpose

To determine the effect of restorations with long contact areas for the management of interdental papilla deficiencies, in smile attractiveness among laypersons and dentists.

Material and Methods

A full‐portrait image was used to create a set of digitally modified images, simulating the management of various levels of interdental papilla loss. In a total of 48 modified images, single as well as multiple loss of interdental papilla among the anterior teeth, treated with a single or multiple restorations were simulated for unilateral and bilateral situations. Through a digital monitor 160 laypeople and dentists were asked to assess the attractiveness of each displayed image utilizing a visual‐analog‐scale. Multiple Wilcoxon‐signed‐rank tests followed by Mann–Whitney U tests were performed considering a significance level of 0.05.

Results

The management of an open gingival embrasure due to interdental papilla loss, by simulating the restoration of both central incisors led to a significantly higher mean smile attractiveness compared to the restoration of a single central incisor. Among the investigated regions, the management of open gingival embrasure in the area of central incisors using a restorative approach was perceived as the least esthetic (p < 0.05).

Conclusions

Despite the restorative management of interdental papilla loss, with the establishment of longer contact areas for the reduction of open gingival embrasures, as the level of the interdental papilla loss is increased, facial esthetics are compromised. When a longer contact area is accomplished through a single restoration, asymmetry among the teeth can be induced, especially in the region of the central incisors.
Mindsets, contexts, and college enrollment: Taking the long view on growth mindset beliefs at the transition to high school
Authors: Hecht Cameron A. , Buontempo Jenny , Boylan Rebecca , Crosnoe Robert , Yeager David S.
Published: July 2024

Socioeconomic disparities in academic progress have persisted throughout the history of the United States, and growth mindset interventions—which shift beliefs about the malleability of intelligence—have shown promise in reducing these disparities. Both the study of such disparities and how to remedy them can benefit from taking the “long view” on adolescent development, following the tradition of John Schulenberg. To do so, this study focuses on the role of growth mindsets in short‐term academic progress during the transition to high school as a contributor to longer‐term educational attainment. Guided by the Mindset × Context perspective, we analyzed new follow‐up data to a one‐year nationally representative study of ninth graders (National Study of Learning Mindsets, n = 10,013; 50% female; 53% white; 63% from lower‐SES backgrounds). A conservative Bayesian analysis revealed that adolescents' growth mindset beliefs at the beginning of ninth grade predicted their enrollment in college 4 years later. These patterns were stronger for adolescents from lower‐SES backgrounds, and there was some evidence that the ninth‐grade math teacher's support for the growth mindset moderated student mindset effects. Thus, a time‐specific combination of student and teacher might alter long‐term trajectories by enabling adolescents to develop and use beliefs at a critical transition point that supports a cumulative pathway of course‐taking and achievement into college. Notably, growth mindset became less predictive of college enrollment after the onset of the COVID‐19 pandemic, which occurred in the second year of college and introduced structural barriers to college persistence.
Rural–urban differences in emergency medical services bypass routing of stroke in North Carolina
Authors: Patel Mehul D. , Chari Srihari V. , Cui Eric R. , Fernandez Antonio R. , Planey Arrianna Marie , Jauch Edward C. , Winslow James E.
Published: July 2024

Purpose

Acute stroke is a serious, time‐sensitive condition requiring immediate medical attention. Emergency medical services (EMS) routing and direct transport of acute stroke patients to stroke centers improves timely access to care. This study aimed to describe EMS stroke routing and transports by rurality in North Carolina (NC).

Methods

We conducted a retrospective study using existing data on EMS transports of suspected stroke patients in NC in 2019. The primary study outcome was EMS bypass of the nearest hospital for transport to a nonnearest hospital, determined by geographic information systems (GIS) analysis. Incident addresses were geocoded to census tracts and classified as urban, suburban, or rural by Rural–Urban Commuting Area codes. We compared the frequency of bypass and estimated additional transport times by urban, suburban, and rural incident locations.

Findings

Of 3666 patients, 1884 (51%) EMS transports bypassed the nearest hospital. Bypass occurred less often for rural EMS incidents (39%) compared to those in urban (57%) and suburban (63%) tracts. The estimated additional transport time for rural bypasses of nonendovascular‐capable stroke centers for endovascular‐capable stroke centers was a median of 25 min (interquartile range 13–33).

Conclusions

Using GIS analysis, we found nearly half of EMS transports of suspected stroke patients in NC bypassed the nearest hospital, including noncertified hospitals and stroke centers. Bypasses occurred less often in rural areas, though incurred significantly longer transport times, compared to urban areas. These findings are important for regional stroke system planning, especially for improving rural access to acute stroke care.
Range‐wide phylogeographic structure of the endangered Irrawaddy dolphin (Orcaella brevirostris) using expanded sampling from contemporary and historical specimens
Authors: McGowen Michael R. , Caballero Susana , Flores Mary Faith C. , Murphy Katherine R. , Archer Frederick I. , Ayyagari Sam , Beasley Isabel , Cohen C. Sarah , Dolar M. Louella L. , Junchompoo Chalatip , Kaewmong Patcharaporn , Klinsawat Worata , Kreb Danielle , Kuit Sui Hyang , Robertson Kelly , Sabin Richard , Sakornwimon Watchara , Smith Kerri J. , Teoh Zhi Yi , Budi Trifan , Ponnampalam Louisa S. , Hines Ellen
Published: July 2024

The Irrawaddy dolphin (Orcaella brevirostris) is an endangered cetacean that ranges throughout much of Southeast Asia and lives in coastal, estuarine, and riverine habitats including three river systems: Ayeyarwady, Mekong, and Mahakam. Many populations face risks from human interference, but overall rangewide diversity and connectivity is not well‐understood. Here we sequenced 77 complete mitogenomes from across the range of the Irrawaddy dolphin including all obligate riverine populations; eighteen of these were sequenced from historical museum specimens. Phylogenetic analysis showed haplotypes from each riverine population formed separate clades nested within the wider species implying each river system was separately invaded only once. All Irrawaddy dolphin mitogenomes were dated to a last common ancestor ~764 kya. Most lineages appeared after inundation cycles of the Sunda Shelf were initiated ~400 kya. Despite the lack of monophyly among many haplotypes from the same population, no population shared any haplotypes. Rangewide nucleotide diversity was average compared to other odontocetes, but riverine populations were especially low. Differentiation was significant among all populations analyzed with the most divergence occurring between isolated riverine populations. These analyses add more evidence for the necessity of conservation efforts directed towards riverine and other isolated populations of the Irrawaddy dolphin.
Estimating spatial mixing within the St. Lawrence Estuary beluga population by comparing local individual diversity and abundance
Authors: Bonnell Tyler R. , Michaud Robert , Dupuch Angélique , Lesage Véronique , Chion Clément
Published: July 2024

Interindividual variability in habitat preferences affect local abundance and residency times. Within a population range, this can lead to sectors having a continuous flow of unique individuals, with others being used by the same set of resident individuals. These patterns of habitat use by individuals, referred to here as individual spatial mixing, can have important implications for ecological and evolutionary processes. This study proposes a novel approach for estimating the degree of individual spatial mixing in an endangered beluga population, based on the comparison of local individual diversity obtained from photo‐identification data against abundance indices derived from systematic aerial surveys. Divergences between long‐term indices of abundance and diversity were observed across many sectors within the population's summer habitat. This was the case notably for the Saguenay Fjord, where on average only 1.8% of the total population count was detected during summer aerial surveys, but where 41% of all individuals identified in the photo‐identification data were found at least once. The comparative approach proposed in this study to estimate individual spatial mixing can help quantify site fidelity patterns in wildlife populations and estimate its vulnerability to local stressors such as anthropogenic noise.
Relationship between moral resilience and secondary traumatic stress among ICU nurses: A cross‐sectional study
Authors: Hu Mengyi , Zhang Hongli , Wu Chao , Li Lu , Liang Xinhui , Zhang Yu , Lang Hongjuan
Published: July 2024

Background

Since the outbreak of COVID‐19, researchers worldwide have focused more on the issue of secondary traumatic stress (STS) experienced by nurses. This stress has an adverse effect on the health of nurses and the quality of nursing care, potentially undermining the stability of the nursing team and hindering the ability to meet the growing demand for nursing services. The impact of the COVID‐19 pandemic, and the rise in global demand for ICU nursing, has placed a significant strain on ICU nurses, severely damaging their mental and physical health. Notably, ICU nurses also face high levels of moral distress, and moral resilience can effectively alleviate this distress and improve the quality of care.

Aim

This study aimed to examine the levels of moral resilience and STS among ICU nurses, to explore their relationship and identify the factors influencing STS.

Study Design

This cross‐sectional study involved 229 ICU nurses from two tertiary hospitals in Xi'an, China, who participated between November and December 2023. The data were collected through email using anonymous electronic questionnaires, encompassing a self‐designed demographic‐ and work–life‐related characteristic questionnaire; the Rushton Moral Resilience Scale; and the Secondary Traumatic Stress Scale. Descriptive statistics, t‐tests, analysis of variance and hierarchical regression analysis were performed to analyse the data.

Results

The findings of the study indicated that ICU nurses' moral resilience and STS scores were at an intermediate level. Hierarchical regression analysis indicated that STS was negatively correlated with the subscales of the Rushton Moral Resilience Scale, specifically moral adversity coping (β, −0.156; 95% CI, −1.241 to −0.039) and relational integrity (β, −0.245; 95% CI, −1.453 to −0.388), which are significant predictors of STS. Additionally, good sleep quality (β, −.396; 95% CI, −14.948 to −7.117) and seeking psychological counselling because of work difficulties (β, .107; 95% CI, 0.237–9.624) emerged as significant predictors of STS among ICU nurses, with the model's explanation of the variance in STS increasing to 45.5%, △R2 = .167, F = 16.482 (p < .001).

Conclusion

This study found that ICU nurses have moderate levels of moral resilience and STS, which are negatively correlated. This suggests that improving the moral resilience of ICU nurses may help reduce their STS levels.

Relevance to Clinical Practice

The study revealed that ICU nurses' moral resilience and secondary traumatic stress levels were at a moderate level, indicative of the need to take measures to enhance their moral resilience and reduce their secondary traumatic stress, as their presence not only affects the health of ICU nurses but also diminishes the quality of care and increases turnover rates.
Systems genetic analysis of lignin biosynthesis in Populus tremula
Authors: Luomaranta Mikko , Grones Carolin , Choudhary Shruti , Milhinhos Ana , Kalman Teitur Ahlgren , Nilsson Ove , Robinson Kathryn M. , Street Nathaniel R. , Tuominen Hannele
Published: July 2024

The genetic control underlying natural variation in lignin content and composition in trees is not fully understood. We performed a systems genetic analysis to uncover the genetic regulation of lignin biosynthesis in a natural ‘SwAsp’ population of aspen (Populus tremula) trees.

We analyzed gene expression by RNA sequencing (RNA‐seq) in differentiating xylem tissues, and lignin content and composition using Pyrolysis‐GC‐MS in mature wood of 268 trees from 99 genotypes.

Abundant variation was observed for lignin content and composition, and genome‐wide association study identified proteins in the pentose phosphate pathway and arabinogalactan protein glycosylation among the top‐ranked genes that are associated with these traits. Variation in gene expression and the associated genetic polymorphism was revealed through the identification of 312 705 local and 292 003 distant expression quantitative trait loci (eQTL). A co‐expression network analysis suggested modularization of lignin biosynthesis and novel functions for the lignin‐biosynthetic CINNAMYL ALCOHOL DEHYDROGENASE 2 and CAFFEOYL‐CoA O‐METHYLTRANSFERASE 3. PHENYLALANINE AMMONIA LYASE 3 was co‐expressed with HOMEOBOX PROTEIN 5 (HB5), and the role of HB5 in stimulating lignification was demonstrated in transgenic trees.

The systems genetic approach allowed linking natural variation in lignin biosynthesis to trees´ responses to external cues such as mechanical stimulus and nutrient availability.
Canopy temperatures strongly overestimate leaf thermal safety margins of tropical trees
Authors: Manzi Olivier Jean Leonce , Wittemann Maria , Dusenge Mirindi Eric , Habimana Jacques , Manishimwe Aloysie , Mujawamariya Myriam , Ntirugulirwa Bonaventure , Zibera Etienne , Tarvainen Lasse , Nsabimana Donat , Wallin Göran , Uddling Johan
Published: July 2024

Current estimates of temperature effects on plants mostly rely on air temperature, although it can significantly deviate from leaf temperature (Tleaf). To address this, some studies have used canopy temperature (Tcan). However, Tcan fails to capture the fine‐scale variation in Tleaf among leaves and species in diverse canopies.

We used infrared radiometers to study Tleaf and Tcan and how they deviate from air temperature (ΔTleaf and ΔTcan) in multispecies tropical tree plantations at three sites along an elevation and temperature gradient in Rwanda.

Our results showed high Tleaf (up to c. 50°C) and ΔTleaf (on average 8–10°C and up to c. 20°C) of sun‐exposed leaves during 10:00 h–15:00 h, being close to or exceeding photosynthetic heat tolerance thresholds. These values greatly exceeded simultaneously measured values of Tcan and ΔTcan, respectively, leading to strongly overestimated leaf thermal safety margins if basing those on Tcan data. Stomatal conductance and leaf size affected Tleaf and Tcan in line with their expected influences on leaf energy balance.

Our findings highlight the importance of leaf traits for leaf thermoregulation and show that monitoring Tcan is not enough to capture the peak temperatures and heat stress experienced by individual leaves of different species in tropical forest canopies.
Phylogeny and historical biogeography of the southern African lacewing genus Afroptera (Neuroptera: Nemopteridae: Nemopterinae)
Authors: Abdalla Ishtiag H. , Mansell Mervyn W. , Sole Catherine L. , Daniel Gimo M.
Published: July 2024

The lacewing genus Afroptera Abdalla & Mansell (Neuroptera: Nemopteridae: Nemopterinae) is endemic to southern Africa, predominantly found in the Fynbos and Succulent Karoo biomes. The taxonomy of the genus has been recently resolved. However, the monophyly and evolutionary history of the genus has never been addressed. This study employs an integrative phylogenetic approach, by incorporating three ribosomal genes (16S, 28S and 18S) and two protein‐coding genes (cytochrome oxidase subunit I and carbamoyl‐phosphate synthetase‐aspartate transcarbamoylase‐dihydroorotase), and morphological data to examine the monophyly and historical biogeography of Afroptera. We use Bayesian, parsimony and maximum likelihood phylogenetic methods to assess the monophyly and relatedness of Afroptera within the Nemopterinae. We also use ancestral range reconstruction and diversification analysis to infer the historical biogeography of the genus. Our analyses reveal the genus as a monophyletic lineage. The genus Afroptera originated during the Pliocene (5.24–3.13 Mya) in a desert environment, experiencing rapid speciation during the Pleistocene, primarily within the Fynbos and Succulent biomes; and secondarily dispersed into the Nama Karoo and Savannah (Kalahari) biomes. The current distribution patterns of Afroptera species likely stem from intensified aridification in the southwest during the Plio‐Pleistocene, consistent with the dry‐adapted nature of Afroptera's ancestors. Therefore, our findings suggest a climatically driven diversification model for the genus Afroptera.
Characterisation of the novel HLA‐DRB4*01:182 allele by sequencing‐based typing
Authors: Blandin Lucie , Cargou Marine , Wojciechowski Elodie , Lemal Richard , Rouzaire Paul
Published: July 2024

HLA‐DRB4*01:182 differs from HLA‐DRB4*01:03:01:01 by one nucleotide substitution in codon 172 in exon 3.
Identification of a novel HLA‐C allele, HLA‐C*02:246
Authors: Shi Xiu‐Min , Gao Su‐Jun
Published: July 2024

HLA‐C*02 246 has one nucleotide change from HLA‐C*02:02:02:01 at nucleotide 523 changing Arginine to Cysteine at residue 151.
Racial literacy and performative pedagogies in the German theater practicum
Authors: Koerner Morgan
Published: July 2024

This article explores the potential and pitfalls of performative pedagogies for teaching literature that thematizes issues of race and racism and argues that racial literacy requires a rethinking of drama‐pedagogical practice. An initial segment situates pedagogical discussions of race in North American German curricula within research on racial literacy and then considers the ethical limitations of the usual approaches from drama pedagogy (role‐play and identification exercises) when addressing literature about or from minoritized communities. The second half of the article outlines a case study of a performance‐oriented teaching unit in a German theater practicum course for German at the B2 level, which combined work on performing and staging poetry with a discussion of the Enlightenment's entanglement with white supremacy and scientific racism. Centering on Black German poet Philipp Khabo Köpsell's poem “The Brainage,” the unit raised the question of performative ethics, namely, how and whether the class, consisting of 11 white students and a white instructor, could ethically perform the poem in a live performance at the end of the semester. The article analyzes examples from student learning and the final live performance and makes the argument for performing the process of students’ encounter with literary form using theatrical means.
Unraveling the role of cytochrome P450 enzymes in oleanane triterpenoid biosynthesis in arjuna tree
Authors: Srivastava Gaurav , Vyas Poonam , Kumar Aashish , Singh Anamika , Bhargav Pravesh , Dinday Sandeep , Ghosh Sumit
Published: July 2024

Triterpenoids (C30‐isoprenoids) represent a major group of natural products with various physiological functions in plants. Triterpenoids and their derivatives have medicinal uses owing to diverse bioactivities. Arjuna (Terminalia arjuna) tree bark accumulates highly oxygenated β‐amyrin‐derived oleanane triterpenoids (e.g., arjunic acid, arjungenin, and arjunolic acid) with cardioprotective roles. However, biosynthetic routes and enzymes remain poorly understood. We mined the arjuna transcriptome and conducted cytochrome P450 monooxygenase (P450) assays using Saccharomyces cerevisiae and Nicotiana benthamiana to identify six P450s and two P450 reductases for oxidative modifications of oleanane triterpenoids. P450 assays using oleananes revealed a greater substrate promiscuity of C‐2α and C‐23 hydroxylases/oxidases than C‐28 oxidases. CYP716A233 and CYP716A432 catalyzed β‐amyrin/erythrodiol C‐28 oxidation to produce oleanolic acid. C‐2α hydroxylases (CYP716C88 and CYP716C89) converted oleanolic acid and hederagenin to maslinic acid and arjunolic acid. CYP716C89 also hydroxylated erythrodiol and oleanolic aldehyde. However, CYP714E107a and CYP714E107b catalyzed oleanolic acid/maslinic acid/arjunic acid, C‐23 hydroxylation to form hederagenin, arjunolic acid and arjungenin, and hederagenin C‐23 oxidation to produce gypsogenic acid, but at a lower rate than oleanolic acid C‐23 hydroxylation. Overall, P450 substrate selectivity suggested that C‐28 oxidation is the first P450‐catalyzed oxidative modification in the arjuna triterpenoid pathway. However, the pathway might branch thereafter through C‐2α/C‐23 hydroxylation of oleanolic acid. Taken together, these results provided new insights into substrate range of P450s and unraveled biosynthetic routes of triterpenoids in arjuna. Moreover, complete elucidation and reconstruction of arjunolic acid pathway in S. cerevisiae and N. benthamiana suggested the utility of arjuna P450s in heterologous production of cardioprotective compounds.
MatK impacts differential chloroplast translation by limiting spliced tRNA‐K(UUU) abundance
Authors: Muino Jose M. , Ruwe Hannes , Qu Yujiao , Maschmann Sascha , Chen Wei , Zoschke Reimo , Ohler Uwe , Kaufmann Kerstin , Schmitz‐Linneweber Christian
Published: July 2024

The protein levels of chloroplast photosynthetic genes and genes related to the chloroplast genetic apparatus vary to adapt to different conditions. However, the underlying mechanisms governing these variations remain unclear. The chloroplast intron Maturase K is encoded within the trnK intron and has been suggested to be required for splicing several group IIA introns, including the trnK intron. In this study, we used RNA immunoprecipitation followed by high‐throughput sequencing (RIP‐Seq) to identify MatK's preference for binding to group IIA intron domains I and VI within target transcripts. Importantly, these domains are crucial for splice site selection, and we discovered alternative 5′‐splice sites in three MatK target introns. The resulting alternative trnK lariat structure showed increased accumulation during heat acclimation. The cognate codon of tRNA‐K(UUU) is highly enriched in mRNAs encoding ribosomal proteins and a trnK‐matK over‐expressor exhibited elevated levels of the spliced tRNA‐K(UUU). Ribosome profiling analysis of the overexpressor revealed a significant up‐shift in the translation of ribosomal proteins compared to photosynthetic genes. Our findings suggest the existence of a novel regulatory mechanism linked to the abundance of tRNA‐K(UUU), enabling the differential expression of functional chloroplast gene groups.
A fully sequenced collection of homozygous EMS mutants for forward and reverse genetic screens in Arabidopsis thaliana
Authors: Carrère Sébastien , Routaboul Jean‐Marc , Savourat Pauline , Bellenot Caroline , López Hernán , Sahoo Amruta , Quiroz Monnens Thomas , Ricou Anthony , Camilleri Christine , Declerck Nathalie , Laufs Patrick , Mercier Raphaël , Noël Laurent D.
Published: July 2024

Genetic screens are powerful tools for biological research and are one of the reasons for the success of the thale cress Arabidopsis thaliana as a research model. Here, we describe the whole‐genome sequencing of 871 Arabidopsis lines from the Homozygous EMS Mutant (HEM) collection as a novel resource for forward and reverse genetics. With an average 576 high‐confidence mutations per HEM line, over three independent mutations altering protein sequences are found on average per gene in the collection. Pilot reverse genetics experiments on reproductive, developmental, immune and physiological traits confirmed the efficacy of the tool for identifying both null, knockdown and gain‐of‐function alleles. The possibility of conducting subtle repeated phenotyping and the immediate availability of the mutations will empower forward genetic approaches. The sequence resource is searchable with the ATHEM web interface (https://lipm‐browsers.toulouse.inra.fr/pub/ATHEM/), and the biological material is distributed by the Versailles Arabidopsis Stock Center.
Pidgin English proverbs as a source of structural nativization in Nigerian English
Authors: Callies Marcus , Oyebola Folajimi
Published: July 2024

In this paper, we explore the role of Nigerian Pidgin English (NPE) proverbs in language contact settings and their impact on the development of idiomatic phraseology in Nigerian English (NgE). In a set of 100 NPE proverbs, we identified lexical keywords that served as anchors for searches in the large‐scale Nairaland corpus to detect recurrent collocational patterns that in further proximity searches yielded frequent, lexico‐grammatically variable patterns that may be interpreted as innovations at the early stages of idiom formation. The findings suggest that cognitively motivated key lexical items of NPE proverbs may serve as a basis for the formation of variable but also lexico‐grammatically more condensed idiomatic expressions in NgE.
Elucidating the role of contributors enriching spiritual and religious inspirations for the Muslims to perform holy umrah pilgrimage in Saudi Arabia. A prospective study
Authors: BASHIR HAAMID
Published: July 2024

This prospective study delves into the multifaceted aspects that contribute to the spiritual and religious inspirations motivating Muslims to embark on the sacred journey of Umrah pilgrimage in Saudi Arabia. The research aims to elucidate the key factors and contributors, latest technology, that enhance the spiritual experience of Umrah, examining their influence on the decision-making process of potential pilgrims. The study is based on observational prospective study carried on 400 pilgrims who volunteered for this research during Jan 2017 to December 2023. The investigation explores the impact of various contributors, including religious teachings, social networks, cultural influences, and the role of pilgrimage organizers, on shaping individuals' motivations to undertake the Umrah pilgrimage. Additionally, the study seeks to understand how these contributors intersect and synergize to enrich the overall spiritual experience for the pilgrims. The prospective nature of the research allows for the identification of emerging trends and evolving dynamics in the context of Umrah pilgrimage. Findings from this study provide valuable insights for religious scholars, policymakers, and organizers involved in facilitating the Umrah pilgrimage experience. By gaining a deeper understanding of the contributing factors, the research findings contribute to the development of strategies that can further enhance the spiritual and religious dimensions of the Umrah pilgrimage, fostering a more meaningful and enriching journey for Muslims undertaking this sacred obligation.  Further improvement is needed in some sectors as per Saudi vision of 2030 to accommodate 30 millions of pilgrims especially slashing of E-Visa fee and accomodation charges of hotels.
APPLICATION OF MACHINE LEARNING TO PREDICTION OF TURBINE ROTOR VIBRATION IN STEAM POWER PLANT
Authors: Ajewole Titus O. , Ojuola Bosede    Mayowa , Olawuyi Abdulsemiu A. , Momoh Omonowo D. , Olukayode Olakunle
Published: July 2024

Abstract
Presented in this study is a predictive approach to the maintenance of turbine rotors in thermal power plants. Using a supervised machine learning technique, a model that could predict future vibrations was developed on the simulation platform MATLAB. Historical data on the vibration symptoms of the turbine-generator couple in a generating unit of a steam power plant was employed in the model to predict the future technical condition of the plant component after the model had already been trained with a portion of the turbine-generator section's operational data. Distribution of the test values of the data about the lines of regression was obtained by quantitative analysis; likewise, the model's ability to correctly predict items that were not used in the training process was also measured. Performance evaluation of the model shows mean square error and mean absolute error of 0.000013691 and 0.0025, respectively, at training, with 0.0011 and 0.0037, respectively, at prediction. Future maintenance needs of the turbine rotor can thus be determined by comparing predictions with the vibration safety threshold of the rotor. Operators of modern power plants can leverage the approach of this study to model and plan maintenance schemes that best suit individual unitofpowerplants, rather than premising maintenance of plant components on the rule-of-thumb.
Keywords:    turbine rotor, machine learning, power plant, predictive maintenance, electricity generation
SoleMate: The Design and Development of a Smart Insole System
Authors: Alali Obadah , Samir Basir Mohamed Ohoud , Sin Bie Kie  , Ong Ke Xin  , Yvonne Wong Liang Liang  , Ravathi Marathandi  , Shatiskumar Sugumaran  , Sathiamoorthi Sathiaseelan  , Siti Aisyah Mualif
Published: July 2024

The SoleMate smart insole system, introduced in this study, addresses the growing prevalence of foot disorders and their associated complications. Foot disorders affect a substantial portion of the population, leading to foot pain and gait abnormalities. This research presents a low-cost, innovative solution that combines force-sensitive resistors (FSR), vibration motors, and a gyroscope sensor integrated with an ESP32 microcontroller. This system offers continuous monitoring of foot alignment and plantar pressure, along with the ability to provide alerts for abnormal foot alignment. By utilizing the Internet of Things (IoT) technology through the Blynk app, users can remotely monitor and control the device, enhancing its usability and potential for early detection and intervention in foot-related issues. While the SoleMate system shows promise, there is room for improvement, including reducing the system's size, adding sensors to enhance data collection, and improving the user interface. With its potential to improve foot health and overall well-being, the SoleMate system holds promise for healthcare professionals and individuals seeking effective foot-related problem management and prevention.
Enzymatic Digestion of the Intervertebral Disc Alters Intradiscal Injection and Leakage Mechanics
Authors: Appel Zachary , Michalek Arthur J.
Published: July 2024

Intradiscal injection is required to deliver therapeutic agents to the intervertebral disc (IVD) nucleus pulposus (NP). However, injectate leakage following needle retraction may result in decreased treatment efficacy and adverse side effects. While enzymatic digestion is a common research approach for simulating degeneration in healthy animal IVDs, contributions to the leakage phenomenon are unknown. In this study, bovine caudal discs were treated with injection into the NP of either a tris buffer control, collagenase (to primarily target collagen), or trypsin (to primarily target proteoglycans) and then injected with fluorescent saline using a through-puncture defect protocol. Pressure–volume records during injection were used to determine volume and pressure at leakage. Discs were then frozen, transected, and photographed to visualize injectate dispersion. Collagenase treatment resulted in a large increase in injectate dispersion, along with a decrease in injection pressure relative to control. Trypsin treatment resulted in a moderate increase in dispersion, with no associated effect on pressure. This study concludes that care should be taken when employing enzymatic digestion to simulate IVD degeneration, as NP tissue disruption may affect both retention and dispersion of subsequent therapeutic injections.
On the Performance of Variable-Geometry Ducted E-Fans
Authors: Kavvalos Mavroudis D. , Schnell Rainer , Mennicken Maximilian , Trost Marco , Kyprianidis Konstantinos G.
Published: July 2024

Electrically driven ducted fans (e-fans), either underwing-mounted or located at the aft-fuselage, can potentially improve the system overall efficiency in hybrid-electric propulsion architectures by increasing their thrust share over the thrust generated by the main engines. However, the low design pressure ratio of such e-fans make them prone to operability issues at off-design conditions, i.e., takeoff, where nozzle pressure ratio is close or below the critical value. This paper investigates the operational limitations of such e-fans, proving the necessity of variable geometry. A component zooming approach is deployed by integrating a streamline curvature method within an aero-engine performance tool to investigate the e-fan installed performance and operability. The concepts of variable pitch fan (VPF) and variable area nozzle (VAN) are systematically explored to quantify any performance benefits, while the unavoidable added-weight challenges due to variable geometry are taken into account. Although e-fans with low design pressure ratio (PR) are more susceptible to operability issues compared to higher PR e-fans, the former show improved overall efficiency levels, mainly dominated by propulsive efficiency. It is found that variable geometry not only tackles operability but it can improve the off-design overall efficiency of e-fans even more. VPF mostly affects the component efficiency by reshaping the e-fan performance maps, while VAN has a greater impact on propulsive efficiency by moving the operating points.
Thermal Management and Entropy Minimization of Plain and Modified Shaped Plate Fin Heat Sinks Using Multi-Objective Genetic Algorithm
Authors: Kuru Muhammet Nasıf , Ünal Şaban , Efe Metin , Duman Necdet , Karasu İlyas , Erdinç Mehmet Tahir , Aydin Orhan
Published: July 2024

In this study, an optimization methodology is followed in order to explore better form of heat sinks which improve thermal performances. Optimum designs of plate fin heat sinks (PFHSs) and modified shaped plate fin heat sinks (MS-PFHSs) are numerically investigated. The objective functions are minimizations of base plate temperature, entropy generation and mass. For both PFHSs and MS-PFHSs, optimization variables include inlet velocity (Vin), fin height (Hfin), and number of fins (NL). Plate fin form is adjusted for MS-PFHSs by adding two optimization variables: the rib height (Hrib) and the number of patterns in the flow direction (Wp). For the multi-objective optimization problems, the maximum base plate temperature limit (Tbase<70 °C) is used. The multi-objective genetic algorithm (MOGA) is used to solve optimization problems, and three-dimensional parametric models for numerical optimization work are examined using the finite volume approach. The flow is steady, incompressible, and turbulent, and heat transfer in the heat sink is represented by conjugate heat transfer (CHT). It is shown that MS-PFHSs outperform in terms of the analyzed objective functions. For the optimum designs, Tbase values of MS-PFHS and PFHS are 60.23  °C and 65.25  °C, respectively, while the mass values are same. The results also indicate that Tbase obtained in the optimum design of MS-PFHS is 7.69% lower than that obtained in the optimum design of PFHS.
New lineages of RNA viruses from clinical isolates of
Rhizopus microsporus
revealed by fragmented and primer-ligated dsRNA sequencing (FLDS) analysis
Authors: Sa'diyah Wasiatus , Zhao Yan-Jie , Chiba Yuto , Kondo Hideki , Suzuki Nobuhiro , Ban Sayaka , Yaguchi Takashi , Urayama Syun-ichi , Hagiwara Daisuke
Published: July 2024

Rhizopus microsporus
is a species in the order Mucorales that is known to cause mucormycosis, but it is poorly understood as a host of viruses. Here, we examined 25 clinical strains of
R. microsporus
for viral infection with a conventional double-stranded RNA (dsRNA) assay using agarose gel electrophoresis (AGE) and the recently established fragmented and primer-ligated dsRNA sequencing (FLDS) protocol. By AGE, five virus-infected strains were detected. Then, full-length genomic sequences of 12 novel RNA viruses were revealed by FLDS, which were related to the families
Mitoviridae, Narnaviridae,
and
Endornaviridae,
ill-defined groups of single-stranded RNA (ssRNA) viruses with similarity to the established families
Virgaviridae
and
Phasmaviridae,
and the proposed family “Ambiguiviridae.” All the characterized viruses, except a potential phasmavirid with a negative-sense RNA genome, had positive-sense RNA genomes. One virus belonged to a previously established species within the family
Mitoviridae
, whereas the other 11 viruses represented new species or even new genera. These results show that the fungal pathogen
R. microsporus
harbors diverse RNA viruses and extend our understanding of the diversity of RNA viruses in the fungal order Mucorales, division Mucoromycota. Identifying RNA viruses from clinical isolates of
R. microsporus
may expand the repertoire of natural therapeutic agents for mucormycosis in the future.

IMPORTANCE

The diversity of mycoviruses in fungal hosts in the division Mucoromycota has been underestimated, mainly within the species
Rhizopus microsporus
. Only five positive-sense RNA genomes had previously been discovered in this species. Because current sequencing methods poorly complete the termini of genomes, we used fragmented and primer-ligated double-stranded RNA sequencing to acquire the full-length genomes. Eleven novel mycoviruses were detected in this study, including the first negative-sense RNA genome reported in
R. microsporus
. Our findings extend the understanding of the viral diversity in clinical strains of Mucoromycota, may provide insights into the pathogenesis and ecology of this fungus, and may offer therapeutic options.
Jet Quenching for Hadron-Tagged Jets in pA Collisions
Authors: Zakharov B. G.
Published: July 2024

We calculate the medium modification factor $${{I}_{{pA}}}$$ for 5.02 TeV $$p$$ + Pb collisions. We use the Monte Carlo Glauber model to determine the parameters of the quark–gluon plasma fireball in $$pA$$ jet events. Our calculations show that the jet quenching effect for $${{I}_{{pA}}}$$ turns out to be rather small. We have found that the theoretical $${{I}_{{pA}}}$$ as a function of the underlying event charged multiplicity density, within errors, agrees with data from ALICE [1] for 5.02 TeV $$p$$ + Pb collisions. However, the experimental errors are too large to draw a firm conclusion on the possible presence of jet quenching.
Transient haemoptysis after taking sildenafil
Authors: Karaduman Suheyla , Zarif Azmaeen , Talpeka Alesia , Haseeb Muhammed
Published: July 2024

We report a case of a man in his 70s who developed haemoptysis 3 days after commencing sildenafil. Before postulating a potential connection between sildenafil use and haemoptysis, it is important to rule out potential other causative factors and comorbidities. The patient suffers from multiple medical conditions and takes various medications. On examination, no abnormalities were discovered. There were no recent significant changes in his bloodwork. Cessation of sildenafil coincided with spontaneous symptom resolution. Chest CT was performed, and no abnormalities were reported. Pseudohaemoptysis or malignancy may be the main differential diagnoses of haemoptysis in elderly patients with multiple comorbidities. Concurrent anticoagulation of the patient may predispose to haemoptysis and is likely to be of greater clinical concern.