bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-fly assemblies fill major phylogenomic gaps across the Drosophilidae Tree of Life
Authors: Kim Bernard Y. , Gellert Hannah R. , Church Samuel H. , Suvorov Anton , Anderson Sean S. , Barmina Olga , Beskid Sofia G. , Comeault Aaron A. , Nicole Crown K. , Diamond Sarah E. , Dorus Steve , Fujichika Takako , Hemker James A. , Hrcek Jan , Kankare Maaria , Katoh Toru , Magnacca Karl N. , Martin Ryan A. , Matsunaga Teruyuki , Medeiros Matthew J. , Miller Danny E. , Pitnick Scott , Simoni Sara , Steenwinkel Tessa E. , Schiffer Michele , Syed Zeeshan A. , Takahashi Aya , Wei Kevin H-C. , Yokoyama Tsuya , Eisen Michael B. , Kopp Artyom , Matute Daniel , Obbard Darren J. , O’Grady Patrick M. , Price Donald K. , Toda Masanori J. , Werner Thomas , Petrov Dmitri A.
Published: October 2023

Long-read sequencing is driving rapid progress in genome assembly across all major groups of life, including species of the family Drosophilidae, a longtime model system for genetics, genomics, and evolution. We previously developed a cost-effective hybrid Oxford Nanopore (ONT) long-read and Illumina short-read sequencing approach and used it to assemble 101 drosophilid genomes from laboratory cultures, greatly increasing the number of genome assemblies for this taxonomic group. The next major challenge is to address the laboratory culture bias in taxon sampling by sequencing genomes of species that cannot easily be reared in the lab. Here, we build upon our previous methods to perform amplification-free ONT sequencing of single wild flies obtained either directly from the field or from ethanol-preserved specimens in museum collections, greatly improving the representation of lesser studied drosophilid taxa in whole-genome data. Using Illumina Novaseq X Plus and ONT P2 sequencers with R10.4.1 chemistry, we set a new benchmark for inexpensive hybrid genome assembly at US $150 per genome while assembling genomes from as little as 35 ng of genomic DNA from a single fly. We present 183 new genome assemblies for 179 species as a resource for drosophilid systematics, phylogenetics, and comparative genomics. Of these genomes, 62 are from pooled lab strains and 121 from single adult flies. Despite the sample limitations of working with small insects, most single-fly diploid assemblies are comparable in contiguity (>1Mb contig N50), completeness (>98% complete dipteran BUSCOs), and accuracy (>QV40 genome-wide with ONT R10.4.1) to assemblies from inbred lines. We present a well-resolved multi-locus phylogeny for 360 drosophilid and 4 outgroup species encompassing all publicly available (as of August 2023) genomes for this group. Finally, we present a Progressive Cactus whole-genome, reference-free alignment built from a subset of 298 suitably high-quality drosophilid genomes. The new assemblies and alignment, along with updated laboratory protocols and computational pipelines, are released as an open resource and as a tool for studying evolution at the scale of an entire insect family.
Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction
Authors: Krogsaeter Einar K. , McKetney Justin , Marquez Angelica , Cakir Zeynep , Stevenson Erica , Jang Gwendolyn M. , Rao Antara , Zhou Anton , Huang Yadong , Krogan Nevan J. , Swaney Danielle L.
Published: October 2023

ApoE4 is the primary risk factor for Alzheimer’s Disease. While apoE is primarily expressed by astrocytes, AD pathology including endosomal abnormalities and mitochondrial dysfunction first occurs in neurons. Lysosomes are poised at the convergence point between these features. We find that apoE4-expressing cells exhibit lysosomal alkalinization, reduced lysosomal proteolysis, and impaired mitophagy. To identify driving factors for this lysosomal dysfunction, we performed quantitative lysosomal proteome profiling. This revealed that apoE4 expression results in lysosomal depletion of Lgals3bp and accumulation of Tmed5 in both Neuro-2a cells and postmitotic human neurons. Modulating the expression of both proteins affected lysosomal function, with Tmed5 knockdown rescuing lysosomal alkalinization in apoE4 cells, and Lgals3bp knockdown causing lysosomal alkalinization and reduced lysosomal density in apoE3 cells. Taken together, our work reveals that apoE4 exerts gain-of-toxicity by alkalinizing the lysosomal lumen, pinpointing lysosomal Tmed5 accumulation and Lgals3bp depletion as apoE4-associated drivers for this phenotype.
Loss of STIM2 in colorectal cancer drives growth and metastasis through metabolic reprogramming and PERK-ATF4 endoplasmic reticulum stress pathway
Authors: Pathak Trayambak , Benson J. Cory , Johnson Martin T. , Xin Ping , Abdelnaby Ahmed Emam , Walter Vonn , Koltun Walter A. , Yochum Gregory S. , Hempel Nadine , Trebak Mohamed
Published: October 2023

The endoplasmic reticulum (ER) stores large amounts of calcium (Ca2+), and the controlled release of ER Ca2+regulates a myriad of cellular functions. Although altered ER Ca2+homeostasis is known to induce ER stress, the mechanisms by which ER Ca2+imbalance activate ER stress pathways are poorly understood. Stromal-interacting molecules STIM1 and STIM2 are two structurally homologous ER-resident Ca2+sensors that synergistically regulate Ca2+influx into the cytosol through Orai Ca2+channels for subsequent signaling to transcription and ER Ca2+refilling. Here, we demonstrate that reduced STIM2, but not STIM1, in colorectal cancer (CRC) is associated with poor patient prognosis. Loss of STIM2 causes SERCA2-dependent increase in ER Ca2+, increased protein translation and transcriptional and metabolic rewiring supporting increased tumor size, invasion, and metastasis. Mechanistically, STIM2 loss activates cMyc and the PERK/ATF4 branch of ER stress in an Orai-independent manner. Therefore, STIM2 and PERK/ATF4 could be exploited for prognosis or in targeted therapies to inhibit CRC tumor growth and metastasis.

Highlights

STIM2 regulates ER Ca2+homeostasis independently of Orai and SOCE.

STIM2 downregulation in colorectal cancer cells causes enhanced ER Ca2+and is associated with poor patient prognosis.

STIM2 downregulation induces PERK/ATF4 dependent ER stress in colorectal cancer.

Increased ER stress drives colorectal cancer metabolic reprogramming, growth, and metastasis.
A novel iPSC model reveals selective vulnerability of neurons in Multiple Sulfatase Deficiency
Authors: Pham Vi , Finoti Livia Sertori , Cassidy Margaret M. , Maguire Jean Ann , Gagne Alyssa L. , Waxman Elisa A. , French Deborah L. , King Kaitlyn , Wongkittichotee Parith , Hong Xinying , Schlotawa Lars , Davidson Beverly L. , Ahrens-Nicklas Rebecca C.
Published: October 2023

Multiple sulfatase deficiency (MSD) is an ultra-rare, inherited lysosomal storage disease caused by mutations in the gene sulfatase modifying factor 1 (SUMF1). MSD is characterized by the functional deficiency of all sulfatase enzymes, leading to the storage of sulfated substrates including glycosaminoglycans (GAGs), sulfolipids, and steroid sulfates. Patients with MSD experience severe neurological impairment, hearing loss, organomegaly, corneal clouding, cardiac valve disease, dysostosis multiplex, contractures, and ichthyosis. Here, we generated a novel human model of MSD by reprogramming patient peripheral blood mononuclear cells to establish an MSD iPSC line (SUMF1p.A279V). We also generated an isogenic control iPSC line by correcting the pathogenic variant with CRISPR/Cas9 gene editing. We successfully differentiated these iPSC lines into neural progenitor cells (NPCs) and NGN2-induced neurons (NGN2-iN) to model the neuropathology of MSD. Mature neuronal cells exhibited decreasedSUMF1gene expression, increased lysosomal stress, impaired neurite outgrowth and maturation, reduced sulfatase activities, and GAG accumulation. Interestingly, MSD iPSCs and NPCs did not exhibit as severe of phenotypes, suggesting that as neurons differentiate and mature, they become more vulnerable to loss ofSUMF1. In summary, we demonstrate that this human iPSC-derived neuronal model recapitulates the cellular and biochemical features of MSD. These cell models can be used as tools to further elucidate the mechanisms of MSD pathology and for the development of therapeutics.
Chronic RNA G-quadruplex Accumulation in Aging and Alzheimer’s Disease
Authors: Kallweit Lena , Hamlett Eric D. , Saternos Hannah , Gilmore Anah , Granholm Ann-Charlotte , Horowitz Scott
Published: October 2023

INTRODUCTION

As the world population ages, new molecular targets in aging and Alzheimer’s Disease (AD) are needed to combat the expected influx of new AD cases. Until now, the role of RNA structure in aging and neurodegeneration has largely remained unexplored.

METHODS

In this study, we examined human hippocampalpostmortemtissue for the formation of RNA G-quadruplexes (rG4s) in aging and AD.

RESULTS

We found that rG4 immunostaining strongly increased in the hippocampus with both age and with AD severity. We further found that neurons with accumulation of phospho-tau immunostaining contained rG4s, that rG4 structure can drive tau aggregation, and that rG4 staining density depended on APOE genotype in the human tissue examined.

DISCUSSION

Combined with previous studies showing the dependence of rG4 structure on stress and the extreme power of rG4s at oligomerizing proteins, we propose a model of neurodegeneration in which chronic rG4 formation is linked to proteostasis collapse. These morphological findings suggest that further investigation of RNA structure in neurodegeneration is a critical avenue for future treatments and diagnoses.
Joint inference of discrete cell types and continuous type-specific variability in single-cell datasets with MMIDAS
Authors: Marghi Yeganeh , Gala Rohan , Baftizadeh Fahimeh , Sümbül Uygar
Published: October 2023

Reproducible definition and identification of cell types is essential to enable investigations into their biological function, and understanding their relevance in the context of development, disease and evolution. Current approaches model variability in data as continuous latent factors, followed by clustering as a separate step, or immediately apply clustering on the data. We show that such approaches can suffer from qualitative mistakes in identifying cell types robustly, particularly when the number of such cell types is in the hundreds or even thousands. Here, we propose an unsupervised method, MMIDAS, which combines a generalized mixture model with a multi-armed deep neural network, to jointly infer the discrete type and continuous type-specific variability. Using four recent datasets of brain cells spanning different technologies, species, and conditions, we demonstrate that MMIDAS can identify reproducible cell types and infer cell type-dependent continuous variability in both uni-modal and multi-modal datasets.
Molecular and Biochemical Analyses of Aging Hallmarks in the Central Nervous System of the Fast-Aging African Turquoise Killifish
Authors: Bergmans Steven , Vanhunsel Sophie , Zandecki Caroline , Seuntjens Eve , De Groef Lies , Moons Lieve
Published: October 2023

As modern society is graying, aging research and biogerontology models, in which the aging process can be studied, are becoming increasingly important. A proper aging model can be defined as one that displays many of the aging hallmarks. Here, we provide two different practical approaches—namely, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting—that can be used to investigate cellular senescence (RT-qPCR forp21andp27), altered intercellular communication/inflammaging (RT-qPCR foril-10,sirt-1,il-6,il-1b,il-8, andtnf), and oxidative stress (western blotting for 4-HNE) in the killifish central nervous system, and, more specifically, in the retina, optic tectum, and telencephalon. These molecular and biochemical analyses are a first step in confirming the aging characteristics but should preferably be combined with morphological analyses.
Investigating the recovery of community events in Scotland, post-COVID-19
Authors: Davies Nick , Robbins Lindsay , Baxter Daniel , Viol Maren , Graham Alannah , Halas Aleksandra
Published: October 2023

Purpose

Community events are significant for building community identity and cohesion. During 2020–2021, events largely halted due to coronavirus disease 2019 (COVID-19) and many communities lacked the capacity to recover their events quickly, in comparison to larger more well-resourced events. The study aims to understand and learn from the experiences of Scottish community event practitioners' during the disruption and recovery period for their events.

Design/methodology/approach

A targeted qualitative questionnaire elicited open-ended responses from people involved in the management and operation of community events in Scotland. Focus groups were also conducted with relevant practitioners to further elicit data.

Findings

Four key themes emerged as follows: (1) COVID-19 fractured stakeholder networks and impacted the ability of community events to operate. Practices adapted to incorporate virtual events. (2) Events were considered as important for place-building and wider collective community benefits. This was brought more into focus for practitioners as a result of the pandemic. (3) Local authorities were variable in the level and support they gave community events. (4) Some positive changes were enforced through COVID-19, such as collaboration between small event collectives that can build resilience for community events in the future.

Originality/value

The research provides an analysis of community events, which are often small-scale, diverse, local, unique to destinations and under-researched compared to large events. It particularly builds understanding of their resilience to sectoral disruption, through the lens of recovery from the COVID-19 pandemic, an extraordinary disruptive event. This paper provides practical strategies for community actors and local authorities to improve event delivery and leverage community events as place-builders.
Lean Six Sigma and quality performance in Italian public and private hospitals: a gender perspective
Authors: Ciasullo Maria Vincenza , Douglas Alexander , Romeo Emilia , Capolupo Nicola
Published: October 2023

Purpose

Lean Six Sigma in public and private healthcare organisations has received considerable attention over the last decade. Nevertheless, such process improvement methodologies are not generalizable, and their effective implementation relies on contextual variables. The purpose of this study is to explore the readiness of Italian hospitals for Lean Six Sigma and Quality Performance Improvement (LSS&QPI), with a focus on gender differences.

Design/methodology/approach

A survey comprising 441 healthcare professionals from public and private hospitals was conducted. Multivariate analysis of variance was used to determine the mean scores on the LSS&QPI dimensions based on hospital type, gender and their interaction.

Findings

The results showed that public healthcare professional are more aware of quality performance improvement initiatives than private healthcare professionals. Moreover, gender differences emerged according to the type of hospital, with higher awareness for men than women in public hospitals, whereas for private hospitals the opposite was true.

Research limitations/implications

This study contributes to the Lean Six Sigma literature by focusing on the holistic assessment of LSS&QPI implementation.

Practical implications

This study informs healthcare managers about the revolution within healthcare organisations, especially public ones. Healthcare managers should spend time understanding Lean Six Sigma as a strategic orientation to promote the “lean hospital”, improving processes and fostering patient-centredness.

Originality/value

This is a preliminary study focussing on analysing inter-relationship between perceived importance of soft readiness factors such as gender dynamics as a missing jigsaw in the current literature. In addition, the research advances a holistic assessment of LSS&QPI, which sets it apart from the studies on single initiatives that have been documented to date.
Towards a design science research (DSR) methodology for operational excellence (OPEX) initiatives
Authors: Antony Jiju , Sony Michael , Lameijer Bart , Bhat Shreeranga , Jayaraman Raja , Gutierrez Leopoldo
Published: October 2023

Purpose

Design science research (DSR) is a structured approach for solving complex ill-structured problems in organizations through the development of an artefact followed by its validation. This paper aims to evaluate existing DSR methodology and propose specific accents to promote DSR for environmental, social and governance (ESG)-oriented operational excellence (OPEX) initiatives within organizations.

Design/methodology/approach

This commentary paper is based on an abductive reasoning approach to evaluate and understand DSR and assess its effectiveness for developing solutions to typical ESG-oriented OPEX-based problems within organizations.

Findings

Existing literature on DSR is reviewed, after which it is evaluated on its ability to contribute to the implementation of sustainable solutions for ESG-oriented OPEX-based problems. Based on the review, specific DSR methodological accents are proposed for the development of ESG-oriented OPEX-based solutions in organizations.

Research limitations/implications

This conceptual paper contributes to the conceptual understanding of the applicability, limitations and contextual preconditions for applying DSR. This paper proposes an explicit and, in some ways, alternative view on DSR research for OPEX researchers to apply and further the body of knowledge on matters of sustainability (ESG) in operations management.

Practical implications

Currently, there is limited understanding and application of the DSR methodology for OPEX-based problem-solving initiatives, as appears in the scant literature on DSR applied for the implementation of OPEX based initiatives for ESG purposes. This paper aims to challenge and provide accents for DSR applied to OPEX-related problems by means of a DSR framework and thereby promotes intervention-based studies among researchers.

Originality/value

The proposed step-by-step methodology contains novel elements and is expected to be of help for OPEX-oriented academicians and practitioners in implementing DSR methodology for practical related problems which need research interventions from academics from Higher Education Institutions.
Negative density‐regulated contest performance promotes conflict resolution in a tree lizard
Authors: Hsu Jung‐Ya , Chou Chun‐Chia , Liao Chen‐Pan , Lin Jhan‐Wei , Cheng Ren‐Chung , Huang Wen‐San
Published: October 2023

Territoriality is a behavioural adaptation resulting from intraspecific competition and reflects the strategy of how individuals share limited resources in the environment. As a consequence, territorial contests and levels of aggressiveness are strongly influenced by population density.

The positive relationship between population density and the intensity of intraspecific competition may appear straightforward. However, empirical evidence regarding this association remains inconclusive. This ambiguity may be attributed to studies that have predominantly focussed on specific fight‐associated traits while overlooking potential interactions between multiple phenotypic characteristics and population dynamics.

To examine the effects of population density and other ecological factors on the variation in fight behaviour as well as fight‐associated morphology and performance. We conducted population surveys and behavioural experiments using the Swinhoe's tree lizard across eight populations.

Our findings revealed that males from higher density populations tended to engage in less intense fights and exhibited a weaker resident advantage in fights, which coincided with our findings on lower rates of injuries, weaker bite forces and smaller body sizes (and vice versa). Male‐specific variation in fight behaviour, morphology and performance along a density gradient suggests different evolutionary equilibria in territoriality influenced by local costs and benefits.

Our study supports the significant role of negative density dependence as a fundamental regulator of eco‐evolutionary dynamics. The observed phenotypic variation emphasizes the importance of ecological and social factors in shaping ontogenetic growth and life‐history strategies. Our findings provide a basis for future investigations into pace‐of‐life syndromes and shed light on how phenotypic adaptation may shape population structure.

Read the free Plain Language Summary for this article on the Journal blog.
Going the Extra Mile, Now or After a While: The Impact of Employee Proactivity in Retail Service Encounters on Customers’ Shopping Responses
Authors: Otterbring Tobias , Arsenovic Jasenko , Samuelsson Peter , Malodia Suresh , Dhir Amandeep
Published: October 2023

Employee proactivity has been discussed as a key predictor of firm success and organizational performance. However, previous proactivity research has rarely focused on customers, and the few available proactivity studies from retail settings are either cross‐sectional, solely based on subjective outcomes (e.g. customer satisfaction) or restricted to aggregated data of objective outcomes (e.g. profits per store). We investigate the causal effect of employee proactivity in retail service encounters on customers’ actual purchase behaviour and satisfaction ratings at the fine‐grained level of individual customers. By integrating theories on social perception with prior proactivity findings, we find that employee proactivity positively predicts customers’ shopping responses. This finding extends from correlational to experimental designs across sample types and paradigms, is replicated in actual retail settings, and is mediated by customers’ perceptions of employee warmth and competence. Furthermore, the effect generalizes across several focal outcomes, including behavioural variables (spending and purchase likelihood), and is moderated by the time to employee‐initiated contact in a way that goes against customers’ own beliefs. In sum, the present research quantifies the financial consequences of employee proactivity and indicates that in ordinary retail service encounters, high proactivity can compensate for delays, thus counteracting the aversive aspects of waiting.
Oil price movements and agricultural production from heterogeneous sub‐sectors: Analysing the Dutch disease in an African resource‐rich economy
Authors: Ike George N. , Usman Ojonugwa , Köksal Cihat
Published: October 2023

The economy of a developing country like Nigeria has evolved from a strong dependence on agricultural exports in the 1960s to an unhealthy reliance on crude oil exports. This has led to a large agricultural trade deficit that requires a better understanding of the dynamic relationship between oil price booms and agricultural production. To this end, the study not only isolates the effect of oil price movements on agricultural production from heterogeneous sub‐sectors in Nigeria but also tests for Dutch disease symptoms using annual data from 1970 to 2019. Employing the auto‐regressive distributed lag (ARDL) cointegration and dynamic simulations as well as dynamic Granger causality techniques, the study shows that in the long run, oil price booms affect the food sector and the livestock sector heterogeneously. An increase in the oil price undercuts the production performance of the food sector. Also, because of the strong linkage between domestic livestock production and the global livestock market, an increase in domestic production has a weak predictive content for oil price booms. The policy implications of these findings include the sterilization of oil revenues outside the country and collaboration with foreign investors to provide much‐needed investment in the agricultural sector through various incentive schemes.
Adherence to the Mediterranean diet is associated with a reduced DAS28 index among patients with rheumatoid arthritis: Case study from KRRD
Authors: Alawadhi Balqees , Alsaber Ahmad , Shatawan Israa , Al‐Herz Adeeba , Setiya Parul , Saleh Khulood , Al‐Awadhi Adel , Hasan Eman , Al‐Kandari Waleed , Mokaddem Khaled , Ghanem Aqeel , Attia Yousef , Hussain Mohammed , Alhadhood Naser , Ali Yaser , Tarakmeh Hoda , Aldabie Ghaydaa , AlKadi Amjad , Alhajeri Hebah , Aldei Ali
Published: October 2023

Background

Rheumatoid arthritis (RA) is a chronic, autoimmune disease that mostly affects the synovial joints. It has been hypothesized that dietary and other environmental and lifestyle factors contribute to the development of RA and its severity.

Objective

The present study aims to measure the effect of the Mediterranean diet (MedDiet) on the disease activity scores (DAS28) among patients with RA.

Methods

Adult patients who satisfied the American College of Rheumatology (ACR) classification criteria for RA from major hospitals in Kuwait were evaluated. A cross‐sectional study conducted on 754 RA patients visits aged (21–79) years. Patients were evaluated using the DAS28. Patients' levels of adherence to the MedDiet are assessed using a validated 14‐item Questionnaire (paper or web‐based). The data was analyzed using both multivariate and univariate statistics. Multivariate logistic regression was used to analyze the statistical relationship between MedDiet and RA disease activity.

Results

The finding suggests that a MedDiet can have a positive impact on DAS28 among patients with RA. In the DAS28 cohort (DAS28 < 3.2, DAS28 ≥ 3.2), several Mediterranean survey components showed statistically significant differences. Patients with a Mediterranean score ≤ 5 was more likely to have hazard effects for DAS28 than those with a Mediterranean score of ≥10 (HR = 0.17, CI [0.08–0.37], p < .001). The finding shows that, Mediterranean levels ≤5, on biologics treatment, CRP, and patient global assessment were significantly associated with overall survival. Additionally, the MedDiet was found to be a significant predictor of DAS28 in the random forest decision tree plot, along with tender, RF, and creatinine. MedDiet patients had a lower DAS28 score than others.

Conclusion

The findings suggest that optimal drug treatment and a restrictive diet can help to improve DAS28 score for patients with RA. More patients in the cohort DAS28 <3.2 used olive oil, servings of vegetables, fruits, and legumes. In contrast, more patients in the cohort DAS28 ≥ 3.2 consumed red meat, butter, sweetened or soft drinks, cakes, cookies, or biscuits, and tomato sauce.
Rituximab induction and reinduction in granulomatosis with polyangiitis and microscopic polyangiitis: A retrospective multicenter study in Taiwan
Authors: Hsieh Tsu‐Yi , Chen Ming‐Han , Wu Chen‐Ching , Hong Wei‐Jhe , Lu Cheng‐Hsun , Lu Chun‐Chi , Lu Ling‐Ying , Hsieh Song‐Chou , Tsai Chang‐Youh , Wu Chien‐Sheng ,   for the Taiwan Vasculitis Study Group
Published: October 2023

Objectives

This study aimed to investigate the clinical outcomes of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) under rituximab induction and reinduction therapy in Taiwan.

Methods

We performed a retrospective study in patients with GPA or MPA receiving rituximab therapy from August 2008 to July 2020 in seven medical centers in Taiwan. The clinical characteristics and outcomes of these patients were analyzed.

Results

In total, 53 patients (18 with GPA and 35 with MPA) were included. Kidney involvement (82.9% vs. 22.2%, p < .001) and initial creatinine (3.25 ± 2.37 vs. 1.07 ± 0.82, p < .001) were significantly higher in MPA. Within 24 weeks after the first course of rituximab, there were seven deaths (five due to infection and two due to active disease) in patients with MPA (7/35, 20%) compared to 0 in patients with GPA. Of 33 patients receiving rituximab for kidney involvement, 23 survived and were free from renal replacement therapy at 24 weeks. Their chronic kidney disease (CKD) stages improved in 2 but progressed in 7, while 24 had stable CKD stages. Death or end‐stage renal disease (ESRD) was associated with infection and higher initial creatinine. Reinduction therapy for relapse was required in 18 (39.1%) of 46 survivors, which was associated with anti‐proteinase 3 (PR3) positive (odds ratio 3.667, p = .049) and younger age with a cutoff of 49.4 (AUC = 0.679, p = .030, sensitivity = 66.67%, specificity = 75%).

Conclusion

Significant mortality occurred after rituximab induction, especially in patients with MPA. In survivors, age younger than 50 and anti‐PR3 positive were associated with the risk of relapse requiring reinduction.
Deletion of NADPH oxidase 2 in chondrocytes exacerbates ethanol‐mediated growth plate disruption in mice without major effects on bone architecture or gene expression
Authors: Pedersen K. , Watt J. , Maimone C. , Hang H. , Denys A. , Schroder K. , Suva L. J. , Chen J.‐R. , Ronis M. J. J.
Published: October 2023

Background

Excess reactive oxygen species generated by NADPH oxidase 2 (Nox2) in response to ethanol exposure mediate aspects of skeletal toxicity including increased osteoclast differentiation and activity. Because perturbation of chondrocyte differentiation in the growth plate by ethanol could be prevented by dietary antioxidants, we hypothesized that Nox2 in the growth plate was involved in ethanol‐associated reductions in longitudinal bone growth.

Methods

Nox2 conditional knockout mice were generated, where the essential catalytic subunit of Nox2, cytochrome B‐245 beta chain (Cybb), is deleted in chondrocytes using a Cre‐Lox model with Cre expressed from the collagen 2a1 promoter (Col2a1‐Cre). Wild‐type and Cre‐Lox mice were fed an ethanol Lieber‐DeCarli‐based diet or pair‐fed a control diet for 8 weeks.

Results

Ethanol treatment significantly reduced the number of proliferating chondrocytes in the growth plate, enhanced bone marrow adiposity, shortened femurs, reduced body length, reduced cortical bone volume, and decreased mRNA levels of a number of osteoblast and chondrocyte genes. Conditional knockout of Nox2 enzymatic activity in chondrocytes did not consistently prevent any ethanol effects. Rather, knockout mice had fewer proliferating chondrocytes than wild‐type mice in both the ethanol‐ and control‐fed animals. Additional analysis of tibia samples from Nox4 knockout mice showed that loss of Nox4 activity also reduced the number of proliferating chondrocytes and altered chondrocyte size in the growth plate.

Conclusions

Although Nox enzymatic activity regulates growth plate development, ethanol‐associated disruption of the growth plate morphology is independent of ethanol‐mediated increases in Nox2 activity.
Intrahousehold preference heterogeneity and demand for labor‐saving agricultural technology
Authors: Gulati Kajal , Ward Patrick S. , Lybbert Travis J. , Spielman David J.
Published: October 2023

Evaluations of agricultural technologies rarely consider the implications of how adoption may alter the labor allocation of different individuals within a household. We examine intrahousehold decision‐making dynamics that shape smallholder households' decision to use mechanical rice transplanting (MRT), a technology that disproportionately influences demand for women's labor. To study the adoption decision, we experimentally estimate the willingness to pay for MRT services both at the individual and household level. We find that women value MRT more than men, especially when they participate in transplanting on their own farms. This preference heterogeneity is evident in the unconditional differences between women's and men's valuation and differences conditional on their individual observable characteristics. Despite having stronger preferences for MRT, women have less influence on the household's technology adoption decision than men. This differential influence over the MRT adoption decision reflects the intrahousehold power structure: in households where women have less control over assets, they also have less influence over the MRT adoption decision. Our results highlight how technological changes interact with unobserved, gender‐based intrahousehold power relations to influence agricultural production decisions and, by extension, the gendered allocation of labor and welfare of women.
Test of the lateral angle method of sex estimation on Anglo‐Saxon and medieval archaeological populations with genetically estimated sex
Authors: Thompson Jess E. , Inskip Sarah A. , Scheib Christiana L. , Bates Jessica , Ge Xiangyu , Griffith Samuel J. , Wohns Anthony Wilder , Robb John E.
Published: October 2023

The lateral angle method of sex estimation is tested on an archaeological population with genetic sex estimates. Casts of the internal auditory canal were made using a quick drying impression material on 90 individuals (76 adults and 14 nonadults) from Anglo‐Saxon and Medieval Cambridgeshire. The anterior and posterior angles of the internal auditory canal were measured, and the relationship of the angle to genetic sex was tested. The posterior angle failed intra‐observer error tests, and only the anterior angle could be analysed. Using the previously published sectioning point for unburnt remains (45°), the method did not adequately distinguish between the sexes. Furthermore, the difference between male and female was insufficient to create population‐specific discriminant functions. The anterior angle does not meet the requirements for an osteological method of sex estimation, exhibiting no statistical correlation with genetic sex in this population.
UK Haemoglobin Disorders Peer Review: A Quality Standards‐based review programme for sickle cell disease and thalassaemia
Authors: Chakravorty S. , Drasar E. , Kaya B. , Kesse‐Adu R. , Velangi M. , Wright J. , Howard J.
Published: October 2023

We evaluated the impact of peer reviews in driving improvement in healthcare quality for people with haemoglobinopathy in the United Kingdom. We analysed compliance to four Quality Standards (QS)‐based peer reviews from 2010 to 2020 to evaluate its impact in driving healthcare quality. Seventeen paediatric and 29 adult haemoglobinopathy centres were reviewed in 2010/11 and 2012/13 respectively; 33 paediatric and 33 adult centres were reviewed in 2014/16, and 32 paediatric and 32 adult centres were reviewed in 2018/2020. Compliance with QS and participant feedback were analysed to assess the impact of peer review programmes to drive improvement in quality of care. We noted that haemoglobinopathy centres significantly improved their compliance to QS between the first two review programmes, but not in the final review programme. In comparison to other disease‐group reviews, the haemoglobinopathy departments were less able to address critical peer review recommendations in their own institutions. The peer review programme was unable to drive sustained improvement in healthcare quality, underscoring the need for sustained development and support for haemoglobinopathy services in the National Health Service. Further work is needed to understand why disparities exist among peer review‐driven improvement initiatives within different disease groups.
Transcriptome‐level discovery of survival‐associated biomarkers and therapy targets in non‐small‐cell lung cancer
Authors: Győrffy Balázs
Published: October 2023

Background and Purpose

Survival rate of patients with lung cancer has increased by over 60% in the recent two decades. With longer survival, the identification of genes associated with survival has emerged as an issue of utmost importance to uncover the most promising biomarkers and therapeutic targets.

Experimental Approach

An integrated database was set up by combining multiple independent datasets with clinical data and transcriptome‐level gene expression measurements. Univariate and multivariate survival analyses were performed to identify genes with higher expression levels linked to shorter survival. The strongest genes were filtered to include only those with known druggability.

Key Results

The entire database includes 2852 tumour specimens from 17 independent cohorts. Of these, 2227 have overall survival data and 1256 samples have progression‐free survival time. The most significant genes associated with survival were MIF, UBC and B2M in lung adenocarcinoma and ANXA2, CSNK2A2 and KRT18 in squamous cell carcinoma. We also aimed to reveal the best druggable targets in non‐smokers lung cancer. The three most promising hits in this cohort were MDK, THY1 and PADI2. The established lung cancer cohort was added to the Kaplan–Meier plotter (https://www.kmplot.com) enabling the validation of future gene expression‐based biomarkers in both the present and yet unexamined subgroups of patients.

Conclusions and Implications

In this study, we established a comprehensive database of transcriptome‐level data for lung cancer. The database can be utilized to identify and rank the most promising biomarkers and therapeutic targets for different subtypes of lung cancer.
Hybrid PABA‐glutamic acid conjugated 1,3,5‐triazine derivatives: Design, synthesis, and antimalarial activity screening targeting Plasmodium falciparum dihydro folate reductase enzyme
Authors: Choudhury Ayesha Aktar Khanam , Vinayagam Sathishkumar , Adhikari Nayana , Saha Ashmita , Ghosh Surajit Kumar , Bhat Hans Raj , Patgiri Saurav Jyoti
Published: October 2023

Despite the successful reduction in the malaria health burden in recent years, it continues to remain a significant global health problem mainly because of the emerging resistance to first‐line treatments. Also because of the disruption in malaria prevention services during the COVID‐19 pandemic, there was an increase in malaria cases in 2021 compared to 2020. Hence, the present study outlined the in silico study, synthesis, and antimalarial evaluation of 1,3,5‐triazine hybrids conjugated with PABA‐glutamic acid. Docking study revealed higher binding energy compared to the originally bound ligand WR99210, predominant hydrogen bond interaction, and involvement of key amino acid residues, like Arg122, Ser120, and Arg59. Fourteen compounds were synthesized using traditional and microwave synthesis. The in vitro antimalarial evaluation against chloroquine‐sensitive 3D7 and resistant Dd2 strain of Plasmodium falciparum showed a high to moderate activity range. Compounds C1 and B4 showed high efficacy against both strains and a further study revealed that compound C1 is non‐cytotoxic against the HEK293 cell line with no acute oral toxicity. In vivo, study was performed for the most potent antimalarial compound C1 to optimize the research work and found to be effectively suppressing parasitemia of Plasmodium berghei strain in the Swiss albino mice model.
Long‐term seizure and developmental outcomes of epilepsy surgery in children under 3 years old: A single‐center study of 113 patients
Authors: Yu Hao , Liu Qingzhu , Wang Ruofan , Liu Chang , Sun Yu , Wang Yao , Ji Taoyun , Wang Shuang , Liu Xiaoyan , Jiang Yuwu , Cai Lixin
Published: October 2023

Aims

To investigate the clinical characteristics, surgical strategy, developmental and seizure outcomes, and predictors of surgical outcome in children with drug‐resistant epilepsy (DRE) under 3 years old.

Methods

One hundred thirteen consecutive children younger than 3 years of age with DRE underwent curative surgical treatment after multidisciplinary preoperative evaluation using the strategy developed in the pediatric epilepsy center of Peking University First Hospital (PKFHPEC) between 2014 and 2018. These patients were selected for retrospective study. The relevant clinical data were collected and analyzed. The surgical prognoses were classified using the Engel classification, and the developmental assessment results were collected. Statistical analysis of the clinical data was performed to analyze the predictors of seizure outcomes and their correlation with developmental outcomes.

Results

All the patients were followed up for more than 3 years, and 98 (86.7%) patients had no seizure recurrence. One year after surgery, the seizure‐free rate was 86.7%, which was as high as that at the last follow‐up. Cortical dysplasia was the most frequent etiology of DRE in this cohort, accounting for 77.0%. According to the Engel classification, acute postoperative seizure (APOS; p < 0.001) was a predictor of seizure recurrence. No deaths occurred. No unpredicted long‐term severe complications occurred except for one ventricular peritoneal shunt. The patients' neurodevelopmental statuses were improved after successful surgery, while the scores of the pre‐ and postoperative developmental assessments were closely correlated.

Conclusions

For children who are younger than 3 years old and have DRE and structural abnormalities, early curative treatment can lead to long‐term good seizure outcomes and a low complication rate. The development of appropriate strategies for both presurgical evaluation and resection is crucial for the success of surgery.
A localization method of manipulator towards achieving more precision control
Authors: Gao Hongwei , Zhang Hongyang , Jiang Yueqiu , Sun Jian , Yu Jiahui
Published: October 2023

The monocular vision system is a crucial branch of machine vision research widely used in multiple industries as a research hotspot in the field of vision. Although the monocular vision system is of simple structure and cost‐effectiveness, its positioning accuracy is insufficient in some industries. This article researched the robot arm positioning method via monocular vision. First, we built a vision system model and designed the style of a cooperative target for target positioning. Second, a target feature screening method based on conditions is composed for the existence of interference. Furthermore, combining the principle of pose estimation on the PNP (Perspective‐n‐Point) problem with the results of the visual system calibration to realize the positioning of the target. Finally, complete the construction of the experimental platform and design accuracy evaluation experiments and positioning experiments. The experimental results show that the location measurement error range of the system in this article is below 4 mm, and the measurement error of the rotation angle is below 2. The system can adapt to the requirements of general industrial use.
Eliciting community‐preferred policy alternatives for achieving workable coexistence in a human‐dominated landscape: Insights from Chitwan National Park, Nepal
Authors: Ferdin Arockia E J , Lee Chun‐Hung , Dhungana Nabin , Chook Jia Wei , Baskaran Nagarajan , Pathak Abhinaya
Published: October 2023

Human‐wildlife conflict is a global issue that poses a major threat to biodiversity conservation and sustainable development. Wildlife adapted to human‐modified landscapes in developing countries can threaten the safety and livelihood of local communities. In such landscapes, where people and wildlife compete for resources, community involvement is promoted to achieve workable coexistence. We used a choice experiment methodology approach to identify community‐preferred policy alternatives in Chitwan National Park in south‐central Nepal. The results indicated that conflicts between the local community and wildlife are on the rise, crop damage being the highest form of damage and most perceived compensation and fencing as conflict‐mitigation tools. The choice experiment showed that residents have a positive preference for enhancing livelihood diversification skills, cultivating buffer crops, promoting alternative livelihoods, and strengthening rapid response teams. We identified concerned mitigators who are younger age group, encountered and concurred that HWC is increasing, and agreed that fencing and compensation are conflict‐mitigation tools. We designed scenario planning using community‐preferred policy alternatives to assist the park management. This is the first‐choice experiment study to design an evaluation framework under community resilience perspectives to achieve workable coexistence. Our study has potential implications for promoting coexistence in a human‐dominated landscape.
Longitudinal trajectory of medial gastrocnemius muscle growth in the first years of life
Authors: De Beukelaer Nathalie , Vandekerckhove Ines , Molenberghs Geert , Naulaers Gunnar , Thewissen Liesbeth , Costamagna Domiziana , Van Campenhout Anja , Desloovere Kaat , Ortibus Els
Published: October 2023

Aim

To define the longitudinal trajectory of gastrocnemius muscle growth in 6‐ to 36‐month‐old children with and without spastic cerebral palsy (SCP) and to compare trajectories by levels of gross motor function (Gross Motor Function Classification System, GMFCS) and presumed brain‐lesion timing.

Method

Twenty typically developing children and 24 children with SCP (GMFCS levels I–II/III–IV = 15/9), were included (28/16 females/males; mean age at first scan 15.4 months [standard deviation 4.93, range 6.24–23.8]). Three‐dimensional freehand ultrasound was used to repeatedly assess muscle volume, length, and cross‐sectional area (CSA), resulting in 138 assessments (mean interval 7.9 months). Brain lesion timing was evaluated with magnetic resonance imaging classification. Linear mixed‐effects models defined growth rates, adjusted for GMFCS levels and presumed brain‐lesion timing.

Results

At age 12 months, children with SCP showed smaller morphological muscle size than typically developing children (5.8 mL vs 9.8 mL, p < 0.001), while subsequently no differences in muscle growth were found between children with and without SCP (muscle volume: 0.65 mL/month vs 0.74 mL/month). However, muscle volume and CSA growth rates were lower in children classified in GMFCS levels III and IV than typically developing children and those classified in GMFCS levels I and II, with differences ranging from −56% to −70% (p < 0.001).

Interpretation

Muscle growth is already hampered during infancy in SCP. Muscle size growth further reduces with decreasing functional levels, independently from the brain lesion. Early monitoring of muscle growth combined with early intervention is needed.
Trademarks, Geographical Indications and Environmental Labelling to Promote Biodiversity: The Case of Agroforestry Coffee in India
Authors: Marie‐Vivien Delphine , Garcia Claude A. , Kushalappa C.G. , Vaast Philippe
Published: October 2023

The district of Kodagu, also called Coorg, in the Western Ghats of India produces 2% of the world's coffee, the expansion and intensification of which have reduced the forest cover by more than 30% in 20 years. Innovative actions are therefore urgently required to link economic development and biodiversity conservation, and stakeholders are exploring three strategies to add value to coffee from Coorg and prevent further biodiversity erosion: registration of trademarks; geographical indications; and environmental certification, via eco‐labels. This article analyses their respective strengths and weaknesses and discusses the synergies between them.
Drones: Designed for Product Delivery
Authors: Bamburry Dane
Published: October 2023

Talk about a disruptive technology: Drones are on the verge of blowing a big hole in the supply‐chain process. Big players are already skirmishing to get out in front.

Don't think of them as science fiction—Amazon, Google, UPS, and Domino's Pizza have big plans for drones.
We, Not I: The Rise and Impact of Korean Design
Authors: Kwon EunSook
Published: October 2023

Thoughts on design, national character, education, and the future from a native Korean who has been a student and a professor in the United States and in her home country.
Inclusion and Diversity: Are You Making Way or IN the Way?
Authors: Peck Tonya M. , Dunne Alex M.
Published: October 2023

Ask your colleagues, “How welcome do you feel in this meeting, right now?” You may be surprised by the answers you get.