bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeatability of Pulse Oximetry Measurements in Children During Triage in Two Ugandan Hospitals
Authors: Asdo Ahmad , Mawji Alishah , Agaba Collins , Komugisha Clare , Novakowski Stefanie K , Pillay Yashodani , Kaumu Stephen , Wiens Matthew O , Akech Samuel , Tagoola Abner , Kissoon Niranjan , Ansermino J Mark , Dunsmuir Dustin
Published: December 2022

Background

In low- and middle-income countries, health workers use pulse oximeters for intermittent spot measurements of SpO2. However, the accuracy and reliability when used for spot measurements has not been determined. We evaluated the repeatability of spot measurements, and the ideal observation time of measurement to guide recommendations during spot check measurements.

Methods

Two one-minute measurements were done for the 3,903 subjects enrolled in the study, collecting 1Hz SpO2and signal quality index (SQI) data. The repeatability between the two measurements was assessed using an intraclass correlation coefficient (ICC), calculated using a median of all seconds of non-zero SpO2values for each recording (any quality, Q1), and again with a quality filter only using seconds with SQI ≥ 90% (good quality, Q2). The ICC was also calculated for both these conditions using subsets of the minute, in increasing increments of 5 seconds, up to the whole minute. Lastly, the whole minute ICC was calculated with good quality (Q2), including only records where both measurements had a mean SQI > 70% (Q3).

Findings

The repeatability ICC with condition Q1 was 0.591 (95% confidence interval (CI) = 0.570, 0.611). Using only the first 5 seconds of each measurement reduced the repeatability to 0.200 (95% CI = 0.169, 0.230). Filtering with Q2, the whole minute ICC was 0.855 (95% CI = 0.847, 0.864). The ICC did not improve beyond the first 35 seconds. For Q3, the repeatability rose to 0.908 (95% CI = 0.901, 0.914).

Conclusions

Training guidelines must emphasize the importance of signal quality and duration of measurement, targeting a minimum of 35 seconds of adequate-quality, stable data. In addition, the design of new devices should incorporate user prompts and force quality checks to encourage more accurate pulse oximetry measurement.

Trial Registration

Clinical Trials.govIdentifier:NCT04304235, Registered 11 March 2020.
The Gender Gap in Leading Medical Journals - a Computational Audit
Authors: Brück Oscar
Published: December 2022

Background

Publication track record can impact careers of researchers. Therefore, monitoring gender representation in medical research is required to achieve equity in academia.

Methods

We gathered bibliometric data on original research articles published between 2010 and 2019 inThe New England Journal of Medicine, Nature Medicine, Journal of the American Medical Association, The BMJ, andThe Lancetusing the Web of Science indexing database. We associated publication and citation frequency with author gender, count, and institute affiliation, and research keywords.

Findings

We analyzed 10,558 articles and found that women published and were cited less than men. There were fewer women as senior (24.8%) than leading authors (34.5%, p<0.001). The proportion of female authors varied by country with 9.1% last authors from Austria, 0.9% from Japan, and 0.0% from South Korea. The gender gap decreased longitudinally and faster for last (−24.0 articles/year, p<0.001) than first authors (−14.5 articles/year, p=0.024). The trend varied by country and even increased in China and Israel. Author count was associated with higher citation count (R0.46, p<0.001) as well as with male first (n=11 vs. n=10, p<0.001) and last authors (n=11 vs. n=10, p<0.001). We also discovered that usage of research keywords varied by gender, and it partly accounted for the difference in citation counts by gender.

Interpretation

Gender representation has increased both at the leading and senior author levels although with country-specific variability. The study frame can be easily applied to any journal and time period to monitor changes in gender representation in science.
Investigating the association between fasting insulin, erythrocytosis and HbA1c through Mendelian randomization and observational analyses
Authors: Nguyen Anthony , Khafagy Rana , Hashemy Habiba , Kuo Kevin H.M. , Roshandel Delnaz , Paterson Andrew D. , Dash Satya
Published: December 2022

Background

Insulin resistance (IR)/hyperinsulinemia (HI), are early abnormalities in the etiology of prediabetes (preT2D) and type 2 diabetes (T2D). IR/HI also associate with increased erythrocytosis. Hemoglobin A1c (HbA1c) is commonly used to diagnose and monitor preT2D/T2D, but can be influenced by erythrocytosis independent of glycemi.

Methods

We undertook bidirectional Mendelian randomization (MR), in individuals of European ancestry, to investigate potential causal associations between increased fasting insulin adjusted for BMI (FI), erythrocytosis and its non-glycemic impact on HbA1c. We investigated the association between Triglyceride-glucose index (TGI), a surrogate measure of IR/HI, and glycation gap (difference between measured HbA1c and predicted HbA1c derived from linear regression of fasting glucose) in people with normoglycemia and preT2D.

Results

Inverse variance weighted MR (IVWMR) suggests increased FI increases haemoglobin (b=0.54+/-0.09, p=2.7 × 10-10), red cell count (RCC, b=0.54+/-0.12, p=5.38×10-6) and reticulocyte (RETIC, b=0.70+/-0.15, p=2.18×10-6). Multivariable MR indicates increased FI does not impact HbA1c (b=0.23+/-0.16, p=0.162) but reduces HbA1c after adjustment for T2D (b=0.31+/-0.13, p=0.016). Increased haemoglobin (b=0.03+/-0.01, p=0.02), RCC (b=0.02+/-0.01, p=0.04) and RETIC (b=0.03+/-0.01, p=0.002) might modestly increase FI. Increased TGI associates with decreased glycation gap, i.e. measured HbA1c was lower than expected based on fasting glucose, (b=-0.09±0.009, p<0.0001) in people with preT2D but not in normoglycemia (b=0.02±0.007, p<0.0001).

Conclusions

MR suggests increased FI increases erythrocytosis and might potentially decrease HbA1c by non-glycemic effects. Increased TGI, a surrogate measure of increased FI, associates with lower-than-expected HbA1 in people with preT2D. These findings merit confirmatory studies to evaluate its clinical significance.
MetaPathPredict: A machine learning-based tool for predicting metabolic modules in incomplete bacterial genomes
Authors: Geller-McGrath D. , Konwar Kishori M. , Edgcomb V.P. , Pachiadaki M. , Roddy J. W. , Wheeler T. J. , McDermott J. E.
Published: December 2022

The reconstruction of complete microbial metabolic pathways using ‘omics data from environmental samples remains challenging. Computational pipelines for pathway reconstruction that utilize machine learning methods to predict the presence or absence of KEGG modules in incomplete genomes are lacking. Here, we present MetaPathPredict, a software tool that incorporates machine learning models to predict the presence of complete KEGG modules within bacterial genomic datasets. Using gene annotation data and information from KEGG module databases, MetaPathPredict employs neural network and XGBoost stacked ensemble models to reconstruct and predict the presence of KEGG modules in a genome. MetaPathPredict can be used as a command line tool or as an R package, and both options are designed to be run locally or on a compute cluster. In our benchmarks, MetaPathPredict makes robust predictions of KEGG module presence within highly incomplete genomes.
A Synaptic Corollary Discharge Signal Suppresses Midbrain Visual Processing During Saccade-Like Locomotion
Authors: Ali Mir Ahsan , Lischka Katharina , Preuss Stephanie J. , Trivedi Chintan A. , Bollmann Johann H.
Published: December 2022

In motor control, the brain not only sends motor commands to the periphery, but it also generates concurrent internal signals known as corollary discharge that influence the processing of sensory information around the time of movement. Corollary discharge signals are important for the brain to identify sensory input arising from self-motion and to compensate for it, but the underlying mechanisms remain unclear. Using whole-cell patch clamp recordings from single neurons in the optic tectum of zebrafish, we discovered an inhibitory synaptic signal which was temporally locked to spontaneous and visually driven swim patterns. This motor-related synaptic signal transiently suppressed tectal output and was appropriately timed to counteract visually driven excitatory input arising from the fish’s own motion. High-resolution calcium imaging revealed brief, highly localized post-swim signals in the tectal neuropil, suggesting that corollary discharge enters the tectum in its most superficial layer. Our results demonstrate how spurious visual input is suppressed during self-motion by motor-related phasic inhibition in the tectum. This may help explain perceptual saccadic suppression observed in many species.
CherryML: Scalable Maximum Likelihood Estimation of Phylogenetic Models
Authors: Prillo Sebastian , Deng Yun , Boyeau Pierre , Li Xingyu , Chen Po-Yen , Song Yun S.
Published: December 2022

Phylogenetic models of molecular evolution are central to diverse problems in biology, but maximum likelihood estimation of model parameters is a computationally expensive task, in some cases prohibitively so. To address this challenge, we here introduce CherryML, a broadly applicable method that achieves several orders of magnitude speedup. We demonstrate its utility by applying it to estimate a general 400 × 400 rate matrix for amino acid co-evolution at protein contact sites.
High-resolution glucose tracing and in situ imaging reveals regulated lactate production in human pancreatic β cells
Authors: Cuozzo Federica , Viloria Katrina , Shilleh Ali H. , Nasteska Daniela , Frazer-Morris Charlotte , Jiao Zicong , Boufersaoui Adam , Marzullo Bryan , Smith Hannah R. , Bonner Caroline , Kerr-Conte Julie , Pattou Francois , Nano Rita , Piemonti Lorenzo , Johnson Paul R.V. , Spiers Rebecca , Roberts Jennie , Lavery Gareth G. , Clark Anne , Ceresa Carlo D.L. , Hodson Leanne , Davies Amy P. , Rutter Guy. A. , Oshima Masaya , Scharfmann Raphaël , Merrins Matthew J. , Akerman Ildem , Tennant Daniel A. , Ludwig Christian , Hodson David J.
Published: December 2022

Using13C6glucose labeling coupled to GC-MS and 2D1H-13C HSQC NMR spectroscopy, we have obtained a comparative high-resolution map of glucose fate underpinning β cell function. In both mouse and human islets, the contribution of glucose to the TCA cycle is similar. Pyruvate-fueling of the TCA cycle is primarily mediated by the activity of pyruvate dehydrogenase, with lower flux through pyruvate carboxylase. While conversion of pyruvate to lactate by lactate dehydrogenase (LDH) can be detected in islets of both species, lactate accumulation is six-fold higher in human islets. Human islets express LDH, with low-moderateLDHAexpression and β cell-specific LDHB expression. LDHB inhibition increases glucose-dependent lactate generation in mouse and human β cells, and decreases Ca2+-spiking frequency without affecting ATP/ADP levels. Thus, we show that LDHB limits glucose-stimulated lactate generation in β cells. Further studies are warranted to understand how lactate impacts β cell metabolism and/or function.

HIGHLIGHTS

Human and rodent islets generate lactate following glucose stimulation.

β cells specifically express LDHB, which acts to limit lactate generation.

LDHB inhibition influences Ca2+spiking frequency without affecting ATP/ADP ratio.

eTOC

Cuozzo et al show that glucose-stimulated rodent and human islets generate lactate. Transcriptomic and imaging analyses reveal that LDHB is specifically expressed in β cells and unexpectedly restrains lactate production. LDHB expression and thus regulated lactate generation might reflect a key mechanism underlying β cell metabolism, function and survival.
The vacuolar sugar transporterEarly Response to Dehydration 6-Like4regulates fructose signaling and plant growth
Authors: Khan Azkia , Cheng Jintao , Kitashova Anastasia , Fürtauer Lisa , Nägele Thomas , Picco Cristiana , Scholz-Starke Joachim , Keller Isabel , Neuhaus H. Ekkehard , Pommerrenig Benjamin
Published: December 2022

Regulation of intracellular sugar homeostasis is maintained by regulation of activities of sugar import and export proteins residing at the tonoplast. We show here that the EARLY RESPONSE TO DEHYDRATION6-LIKE4 protein, being the closest homolog to the proton/glucose symporter ERDL6, resides in the vacuolar membrane. Gene expression and subcellular fractionation studies indicated that ERDL4 was involved in fructose allocation across the tonoplast. Overexpression ofERDL4increased total sugar levels in leaves, due to a concomitantly induced stimulation ofTST2expression, coding for the major vacuolar sugar loader. This conclusion is supported by the finding thattst1-2knockout lines overexpressingERDL4lack increased cellular sugar levels. ERDL4 activity contributing to the coordination of cellular sugar homeostasis is also indicated by two further observations. Firstly,ERDL4andTSTgenes exhibit an opposite regulation during a diurnal rhythm, and secondly, theERDL4gene is markedly expressed during cold acclimation representing a situation in which TST activity needs to be upregulated. Moreover,ERDL4-overexpressing plants show larger size of rosettes and roots, a delayed flowering time and increased total seed yield. Consistently,erdl4knock-out plants show impaired cold acclimation and freezing tolerance along with reduced plant biomass. In summary, we show that modification of cytosolic fructose levels influences plant organ development and stress tolerance.

One sentence summary

The activity of the vacuolar sugar porter ERDL4 is important for balanced cytosolic monosaccharide homeostasis and influences plant growth and cold response in Arabidopsis

The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors is: Benjamin Pommerrenig (pommerre@bio.uni-kl.de).
Liam tackles complex multimodal single-cell data integration challenges
Authors: Rautenstrauch Pia , Ohler Uwe
Published: December 2022

Multi-omics characterization of single cells holds outstanding potential for profiling gene regulatory states of thousands of cells and their dynamics and relations. How to integrate multimodal data is an open problem, especially when aiming to combine data from multiple sources or conditions containing biological and technical variation. We introduce liam, a flexible model for the simultaneous horizontal and vertical integration of paired single-cell multimodal data. Liam learns a joint low-dimensional representation of two concurrently measured modalities, which proves beneficial when the information content or quality of the modalities differ. Its integration accounts for complex batch effects using a tuneable combination of conditional and adversarial training and can be optimized using replicate information while retaining selected biological variation. We demonstrate liam’s superior performance on multiple multimodal data sets, including Multiome and CITE-seq data. Detailed benchmarking experiments illustrate the complexities and challenges remaining for integration and the meaningful assessment of its success.
Mitochondrial folate metabolism inhibition drives differentiation through mTORC1 mediated purine sensing
Authors: Zarou Martha M. , Rattigan Kevin M. , Sarnello Daniele , Dawson Amy , Ianniciello Angela , Dunn Karen , Copland Mhairi , Sumpton David , Vazquez Alexei , Helgason G. Vignir
Published: December 2022

Supporting cell proliferation through nucleotide biosynthesis is an essential requirement for cancer cells. Hence, inhibition of folate-mediated one carbon (1C) metabolism, which is required for nucleotide synthesis, has been successfully exploited in anti-cancer therapy. Here, we reveal that mitochondrial folate metabolism is upregulated in patient-derived leukaemic stem cells (LSCs). We demonstrate that inhibition of mitochondrial 1C metabolism through impairment ofde novopurine synthesis has a cytostatic effect on chronic myeloid leukaemia (CML) cells. Consequently, changes in purine nucleotide levels lead to activation of AMPK signalling and suppression of mTORC1 activity. Notably, suppression of mitochondrial 1C metabolism increases expression of erythroid differentiation markers. Moreover, we find that increased differentiation occurs independently of AMPK signalling and can be reversed through reconstitution of purine levels and reactivation of mTORC1. Of clinical relevance, we identify that combination of 1C metabolism inhibition with imatinib, a frontline treatment for CML patients, decreases the number of therapy-resistant CML LSCs in a patient-derived xenograft model. Our results highlight a novel role for folate metabolism and purine sensing in stem cell fate decisions and leukaemogenesis.
Sex-biasedYap1oncogene function
Authors: Abdelfattah Nourhan , Natarajan Sivaraman , Maldonado Jose , Tran Han Nhat , McMinimy Rachael , Borland Hannah , Chen Shu-hsia , Camargo Fernando , Olson James , George Joshy , Yun Kyuson
Published: December 2022

The incidence of many human cancers differs according to sex, but little is known about the interplay between oncogenic events and sex as a variable in tumorigenesis. Here we report that the oncogeneYap1is sexually dimorphic in medulloblastoma progression and immune suppression. We show thatYap1promotes stemness and blocks differentiation in sonic hedgehog (SHH)-subtype medulloblastoma by at least two distinct but complementary molecular mechanisms to regulate the RNA expression and protein functions ofSox2, Atoh1, NeuroD1, and Zic1/2. Yap1also promotes an immune suppressive tumor microenvironment by directly regulatingCsf1, Igf1,andIgfbp3transcription and modulating IL6-JAK-STAT3, TNFR1, TGF-β, and CCL5 immune pathways. Notably,Yap1function is more critical in males and this is evolutionarily conserved: genes downstream of YAP1 identified in mouse models stratify male but not female medulloblastoma patient survival. In summary, we demonstrate a sex-based function for an oncogene, underscoring the critical need to incorporate sex as a variable in cancer mechanism and clinical response studies, particularly those involving YAP1.
TManual: Assistant for manually measuring length development in structures built by animals
Authors: Mizumoto Nobuaki
Published: December 2022

Structures built by animals are extended phenotypes, and animal behavior can be better understood by recording the temporal development of structure construction. For most subterranean and wood-boring animals, these structures consist of gallery systems, such as burrows made by mice, tunnel foraging by termites, and nest excavation in ants. Measurement of the length development of such structures is often performed manually. However, it is time-consuming and cognitively costly to track length development in nested branching structures, hindering the quantitative determination of temporal development.

Here, I introduce TManual, which aids the manual measurement of structure length development using a number of images. TManual provides a user interface to draw gallery structures and take over all other processes handling input datasets (e.g., zero-adjustment, scaling the units, measuring the length, assigning gallery identities, and extracting network structures). Thus, users can focus on the measuring process without interruptions.

As examples, I provide the results of the analysis of a dataset of tunnel construction by three termite species after successfully processing 1,125 images in ∼3 h. The output datasets clearly visualized the interspecific variation in tunneling speed and branching structures. Furthermore, I applied TManual to a complex gallery system by another termite species and extracted network structures.

Measuring the lengths of objects from images is an essential task in biological observation. TManual helps users handle many images in a realistic time scale, enabling a comparative analysis across a wide array of species. TManual does not require programming skills and outputs a tidy data frame in CSV format. Therefore, it is suitable for any user who wants to perform image analysis for length measurements.
Cdkn2aregulates beige fat maintenance through BECN1-mediated autophagy
Authors: Wu Ruifan , Park Jooman , Qian Yanyu , Shi Zuoxiao , Hu Ruoci , Yuan Yexian , Xiong Shaolei , Wang Zilai , Yan Gege , Ong Sang-Ging , Song Qing , Song Zhenyuan , Mohamed Abeer , Xu Pingwen , He Congcong , Arpke Robert W. , Kyba Michael , Shu Gang , Jiang Qingyan , Jiang Yuwei
Published: December 2022

A potential therapeutic target to curb the obesity and diabetes epidemic is thermogenic beige adipocytes. However, beige adipocytes quickly transition into white adipocytes upon removing stimuli. Here, we define the critical role ofCdkn2aas a molecular pedal for the beige-to-white transition. Beige adipocytes lackingCdkn2aexhibit prolonged lifespan, and mice are more resistant to diet-induced obesity, along with enhanced energy expenditure and improved glucose tolerance. Mechanistic studies demonstrate thatCdkn2apromotes the expression and activity of BECN1 by directly binding to its mRNA and its negative regulator BCL2L1, activating autophagy and accelerating the beige-to-white transition. Notably, reactivating autophagy by pharmacological or genetic methods abolishes beige adipocyte maintenance induced byCdkn2a-ablation. Furthermore, hyperactive BECN1 alone significantly accelerates the beige-to-white transition. Collectively, these findings show thatCdkn2a-mediated autophagy serves as a brake system for beige adipocyte maintenance and is a highly promising target for anti-obesity and anti-diabetes therapy.

Highlights

Cdkn2aablation promotes beige fat maintenance and ameliorates diet-induced obesity

Loss ofCdkn2aretains beige adipocytes by inhibiting BECN1-mediated autophagy

Cdkn2amodulates BECN1 by binding to its mRNA and its inhibitor BCL2L1, respectively

Hyperactive BECN1 is sufficient to accelerate the beige-to-white transition
CRISPR prime editing for unconstrained correction of oncogenicKRASvariants
Authors: Jang Gayoung , Kweon Jiyeon , Kim Yongsub
Published: December 2022

KRASis the most commonly mutated RAS family gene and is a primary cause of the occurrence of several types of cancer. However,KRASmutations have several unique and diverse molecular identities, making it difficult to find specific treatments. Here, we developed universal pegRNAs which can correct all types of G12 and G13 oncogenicKRASmutations with CRISPR-mediated prime editors (PEs). The universal pegRNAs were found to be capable of correcting 12 types ofKRASmutations, accounting for 94% of all knownKRASmutations. Using our PE system, we successfully corrected 12 types ofKRASmutations with up to 54.7 % correction efficiency in HEK293T/17 cells. We also applied the universal pegRNA to correct endogenousKRASmutations in pancreatic cancer cells and found that G12V and G12DKRASmutations were successfully corrected to wild-typeKRASsequences with up to 18.7% correction efficiency without unwanted mutations. We propose prime editing with the universal pegRNA as a ‘one–to–many’ potential therapeutic strategy forKRASoncogene variants.
Slow conformational changes in the rigid and highly stable chymotrypsin inhibitor 2
Authors: Gavrilov Yulian , Prestel Andreas , Lindorff-Larsen Kresten , Teilum Kaare
Published: December 2022

Slow conformational changes are often directly linked to protein function. It is however less clear how such processes may perturb the overall folding stability of a protein. We previously found that the stabilizing double mutant L49I/I57V in the small protein chymotrypsin inhibitor 2 from barley led to distributed increased nano second and faster dynamics. Here we asked what effect this mutant and the two individual mutants L49I and I57V have on the slow conformational dynamics of CI2. We used15N CPMG spin relaxation dispersion experiments to measure the kinetics, thermodynamics and structural changes associated with slow conformational change in CI2. These changes result in an excited state that is populated to 4.3% at 1 °C. As the temperature is increased the population of the excited state decreases. Structural changes in the transition to the excited state are associated with residues that interact with water molecules that have well defined positions and are found at these positions in all crystal structures of CI2. The mutations in CI2 have only little effect on the structure of the excited state whereas the stability of the excited state to some extent follows the stability of the main state. The minor state is thus most populated for the most stable CI2 variant and least populated for the least stable variant. We hypothesize that the interactions between the mutated residues and the well-ordered water molecules links subtle structural changes around the mutated residues to the region in the protein that experience slow conformational changes.
Blood transcriptome analysis suggests an indirect molecular association of early life adversities and adult social anxiety disorder by immune-related signal transduction
Authors: Edelmann Susanne , Wiegand Ariane , Hentrich Thomas , Pasche Sarah , Schulze-Hentrich Julia , Munk Matthias H. J. , Fallgatter Andreas J. , Kreifelts Benjamin , Nieratschker Vanessa
Published: December 2022

Social anxiety disorder (SAD) is a psychiatric disorder characterized by severe fear in social situations and avoidance of these. Multiple genetic as well as environmental factors contribute to the etiopathology of SAD. One of the main risk factors for SAD is stress, especially during early periods of life (early life adversity; ELA). ELA leads to structural and regulatory alterations contributing to disease vulnerability. This includes the dysregulation of the immune response. However, the molecular link between ELA and the risk for SAD in adulthood remain largely unclear. Evidence is emerging that long-lasting changes of gene expression patterns play an important role in the biological mechanisms linking ELA and SAD.

Therefore, we performed a transcriptome study of SAD and ELA using RNA sequencing. Analyzing differential gene expression, 13 significantly differentially expressed genes (DEGs) were identified with respect to SAD whilst no significant differences in expression were identified with respect to ELA. The most significantly expressed gene wasMAPK3being upregulated in the SAD group compared to control individuals. In contrary, weighted gene co-expression network analyses (WGCNA) identified only modules significantly associated with ELA, not with SAD. Furthermore, analyzing interaction networks of the genes from the ELA-associated modules and the SAD-related MAPK3) revealed complex interactions of those genes. Gene functional enrichment analyses indicate a role of signal transduction pathways as well as inflammatory responses supporting an involvement of the immune system in the association of ELA and SAD.

In conclusion, we did not identify a direct molecular link between ELA and adult SAD by transcriptional changes. However, our data indicate an indirect association of ELA and SAD mediated by the interaction of genes involved in immune-related signal transduction.
The role of aneuploidy and polyclonality in the adaptation of the Protozoan parasiteLeishmaniato high drug pressure
Authors: Negreira Gabriel H. , de Groote Robin , Van Giel Dorien , Monsieurs Pieter , Maes Ilse , de Muylder Geraldine , Van den Broeck Frederik , Dujardin Jean-Claude , Domagalska Malgorzata A.
Published: December 2022

Aneuploidy is generally considered harmful, but in some microorganisms, it can act as an adaptive mechanism against environmental stresses. Here, we usedLeishmania– a protozoan parasite with a remarkable genome plasticity – to study the early evolution of aneuploidy under high drug pressure (antimony or miltefosine) as stressor model. By combining single-cell genomics, lineage tracing with cellular barcodes and longitudinal genome characterization, we revealed that antimony-induced aneuploidy changes result from the polyclonal selection of pre-existing karyotypes, complemented by further and rapid de novo alterations in chromosome copy number along evolution. In the case of miltefosine, early parasite adaptation was associated with independent pre-existing point mutations in a miltefosine transporter gene and aneuploidy changes only emerged later, upon exposure to increased concentration of the drug. Thus, polyclonality and genome plasticity are hallmarks of parasite adaptation, but the scenario of aneuploidy dynamics is dependent on the nature and strength of the environmental stress as well as on the existence of other pre-adaptive mechanisms.
How AberrantN-Glycosylation Can Alter Protein Functionality and Ligand Binding: an Atomistic View
Authors: Castelli Matteo , Yan Pengrong , Rodina Anna , Digwal Chander S. , Panchal Palak , Chiosis Gabriela , Moroni Elisabetta , Colombo Giorgio
Published: December 2022

Protein assembly defects due to enrichment of aberrant conformational variants of proteins are emerging as a new frontier in therapeutics design. Understanding, atomistically, structural elements that remodel the energy landscape of proteins, with the consequence of rewiring the conformational dynamics of proteins and pathologically perturbing functionally-oriented ensembles, is key for development of inhibitors. This is particularly relevant for molecular chaperones, hub proteins for the assembly of large multiprotein complexes, where enrichment of aberrant conformers can have a large impact on the cellular proteome, and in turn, on phenotypes. Here, we integrate computational and experimental tools to unveil howN-glycosylation of specific residues in glucose-regulated protein 94 (GRP94) modulates internal dynamics and alters the conformational fitness of regions fundamental for interaction with the nucleotide and synthetic ligands, and impacts substructures dedicated to recognition of interacting proteins. We show howN-glycosylation plays an active role in modulating the energy landscape of the protein, with specific glycosylation patterns determining specific functionally-oriented dynamic signatures. Our results provide support for leveraging the structural-dynamics knowledge on distinct glycosylation variants to design molecules targeting GRP94 disease-associated conformational states and assemblies. Since glycosylation is the most abundant form of post-translational modification, our results and mechanistic models can readily be transferred to other targets and contexts for cancers and other diseases.
Spatial transcriptomics deconvolution at single-cell resolution by Redeconve
Authors: Zhou Zixiang , Zhong Yunshan , Zhang Zemin , Ren Xianwen
Published: December 2022

Computational deconvolution with single-cell RNA sequencing data as reference is pivotal to interpreting spatial transcriptomics data, but the current methods are limited to cell type resolution. Here we present Redeconve, an algorithm to deconvolute spatial transcriptomics data at single-cell resolution, enabling interpretation of spatial transcriptomics data with thousands of nuanced cell states. We benchmarked Redeconve with the state-of-the-art algorithms on diverse spatial transcriptomics datasets and platforms and demonstrated the superiority of Redeconve in terms of accuracy, resolution, robustness, and speed. Applications to a human pancreatic cancer dataset revealed cancer clone-specific T cell infiltration, and application to lymph node samples identified subtle cellular surroundings between IgA+ and IgG+ spots, providing novel insights into tumor immunology and the regulatory mechanisms underlying antibody class switch.
State-of-the-art image and video quality assessment with a metric based on an intrinsically nonlinear neural summation model
Authors: Luna Raúl , Zabaleta Itziar , Bertalmío Marcelo
Published: December 2022

The development of automatic methods for image and video quality assessment that correlate well with the perception of human observers is a very challenging open problem in vision science, with numerous practical applications in disciplines such as image processing and computer vision, as well as in the media industry. In the past two decades, the goal of image quality research has been to improve upon classical metrics by developing models that emulate some aspects of the visual system, and while the progress has been considerable, state-of-the-art quality assessment methods still share a number of shortcomings, like their performance dropping considerably when they are tested on a database that is quite different from the one used to train them, or their significant limitations in predicting observer scores for high framerate videos. In this work we propose a novel objective method for image and video quality assessment that is based on the recently introduced Intrinsically Non-linear Receptive Field (INRF) formulation, a neural summation model that has been shown to be better at predicting neural activity and visual perception phenomena than the classical linear receptive field. Here we start by optimizing, on a classic image quality database, the four parameters of a very simple INRF-based metric, and proceed to test this metric on three other databases, showing that its performance equals or surpasses that of the state-of-the-art methods, some of them having millions of parameters. Next, we extend to the temporal domain this INRF image quality metric, and test it on several popular video quality datasets; again, the results of our proposed INRF-based video quality metric are shown to be very competitive.
Multifactor uncertainty analysis of prefabricated building supply chain: qualitative comparative analysis
Authors: Wang Dan , Luo Jingyi , Wang Yongkun
Published: December 2022

Purpose

This paper constructs the uncertainty analysis model of prefabricated building supply chain risk. The model is designed to study the formation path of prefabricated building supply chain risk and is expected to be used by industry stakeholders for supply chain risk management.

Design/methodology/approach

Based on the uncertainty circle model, construct a configuration analysis framework for supply chain risks in prefabricated buildings. The fuzzy set qualitative comparative analysis (fsQCA) is used to study the configuration influence of five uncertain factors, including environment, plan-control, demand-supply, manufacturing and assembly-transportation, on the risk of the prefabricated building supply chain.

Findings

There are three paths to promote the high-risk generation of the prefabricated building supply chain: assembly-transportation-oriented, plan-control-oriented and manufacturing-oriented. There is a specific equivalent substitution relationship among the five causal conditions. Under specific conditions, different combinations of conditions have the same effect on promoting supply chain high-risk generation through equivalent substitution.

Originality/value

The multiple concurrent causal relationships of risk conditions in the assembly construction supply chain are studied under the grouping perspective, which helps to expand the research perspective of assembly construction supply chain risk and provides theoretical guidance for supply chain risk management of construction enterprises.
Leading change and innovation in Ghana’s banking sector: the mediating role of work autonomy
Authors: Kpinpuo Stephen Debar , Akolgo Isaac Gumah , Naimi Linda
Published: December 2022

Purpose

In recent times, employers are routinely advertising for position candidates with the capability to work with little or no supervision at all. This is probably because, as businesses strive to globalize operations, supervision has become both complex and expensive. While the general interest in employees with considerable levels of work autonomy may be a strategic one, particularly for banks, it is important to determine the impact of work autonomy on other critical success factors such as employee commitment to change management, innovativeness and quality supervisor-subordinate relationship. This study aims to examine the relationship between these variables by exploring the mediation effect of work autonomy on the relationship between employee innovativeness, quality of supervisor-subordination collaboration and employee commitment to change management in the banking sector of Ghana.

Design/methodology/approach

The study used quantitative empirical strategies involving the distribution of questionnaires to a randomly selected sample of 400 employees of selected banks in Ghana. Data, so collected, were analysed using the PLS-SEM Software.

Findings

Results of the study revealed significant relationships between the quality of supervisor-subordinate collaboration, innovativeness and commitment to change. The findings further established work autonomy as an explanatory variable between the three employee behaviours – innovativeness, quality of supervisor-subordinate connection and commitment to change.

Originality/value

The novelty of this study lies in the interplay of quality employee relations, innovative employee behaviour and commitment to change processes as refereed by work autonomy to promote effective change management activities in Ghanaian banks. The outcome of the study led to the development of a theoretical model for organizational change management.
A critical review of HR analytics: visualization and bibliometric analysis approach
Authors: Arora Meenal , Prakash Anshika , Dixit Saurav , Mittal Amit , Singh Swati
Published: December 2022

Purpose

This study aims to analyze the existing literature in human resource analytics and highlights the future research agenda and trends in the same context. It deals with evaluating regional distribution, identifying key authors, publications, journals and keyword occurrences while examining current literature.

Design/methodology/approach

A total of 127 articles exported from the Scopus database were systematically analyzed using bibliometric analysis through VOSviewer, including performance analysis and science mapping of the literature studied.

Findings

This research postulates the inconsistency between the number of publications and citations received by an author. There was an increase in collaborative research over the years. Human Resource Management Review was regarded as the most influential journal with maximum citation. Maximum publications came from Asian countries. The study revealed that the author with maximum citation were mostly the first authors of the most cited documents.

Practical implications

This research may be beneficial for both researchers and human resource (HR) practitioners because it identifies the research gaps and research needs in the HR analytics domain. Besides, this study recognizes the patterns in HR analytics literature that helps researchers better understand the subject area.

Originality/value

This research incorporates bibliometric analysis for analyzing HR analytics literature to establish a more exhaustive and systematic understanding of the research area. This research contributes to the existing body of literature and assists fellow researchers in future studies.
Working with patients with disruptions in symbolic capacity1
Authors: Winborn Mark
Published: December 2022

This article focuses on understanding and working with patients who have poorly developed symbolic capacity, or for whom symbolic capacity has been disrupted due to trauma, particularly as it pertains to the use of reverie and interpretation in the analytic process. Many patients who present for Jungian analysis will initially present with deficits in symbolic functioning. This situation results in necessary limitations or modifications in utilizing traditional Jungian techniques such as dream analysis, active imagination, sand tray and other expressive art techniques. The initial phase of analytic work with these patients requires a focus on developing their symbolic capacity before traditional Jungian techniques can be utilized effectively. During the paper Jung's concept of ‘the symbolic attitude’ will be examined as well as the conceptual models of Wilfred Bion and other post‐Bionians who outline theories and method for cultivating symbolic capacity and reflective functioning in patients for whom these capacities are impaired or poorly developed.
Density and climate effects on age‐specific survival and population growth: consequences for hibernating mammals
Authors: Combe F. J. , Juškaitis R. , Trout R. C. , Bird S. , Ellis J. S. , Norrey J. , Al‐Fulaij N. , White I. , Harris W. E.
Published: December 2022

The impact of factors such as density dependence, food availability and weather are known to be important for predicting population change in a wide range of species. However, a challenge in ecology is understanding the contributory and interactive role of these drivers on populations. This is necessary to design effective conservation and management strategies. Using data from long‐term studies of five hazel dormouse Muscardinus avellanarius populations in Europe, we tested the relationship between population density and weather and their impact on demographic rates. We used an integrated population modelling approach, estimating age‐specific overwinter survival, annual population growth and fecundity rates. We found strong negative effects of population density, precipitation and winter temperature on population growth rates. This suggests that warmer and wetter weather negatively affects dormouse survival for both adults and juveniles, but we found subtle differences in these effects between age classes. We also identified an interaction between weather measures and population density on age‐specific survival, possibly as a result of weather impacts during hibernation. Although we found low winter temperature was positively associated with population growth, we found evidence consistent with density dependence. We discuss our results in the context of woodland habitat conservation management.
Dementia lifestyle coach pilot program
Authors: Low Lee‐Fay , Barcenilla‐Wong Annica , Fitzpatrick Michael , Swaffer Kate , Brodaty Henry , Hancock Nicola , McLoughlin James , Naismith Sharon
Published: December 2022

Objectives

This study aimed to conduct a feasibility pilot of the Dementia Lifestyle Coach program; an individual coaching and counselling program for people recently diagnosed with dementia, to help them to adjust to the diagnosis and live well.

Methods

A randomised controlled pilot trial (n = 11) with wait‐list control group was undertaken over 12 months. Intervention group participants received immediate personalised counselling from a registered psychologist and monthly support (face‐to‐face or by telephone) from a trained peer mentor living with dementia. The wait‐listed control group commenced treatment 6 months after baseline.

Results

Recruitment and delivery of the Dementia Lifestyle Coach program was highly feasible. The program was acceptable, with nine of the 11 participants describing benefits including informational and emotional support, improving their outlook and mood, and family relationships. The planned program was adapted to participants' individual needs.

Conclusions

This small pilot showed that it is feasible to recruit for and deliver a counselling and peer mentoring program for people recently diagnosed with dementia. A larger hybrid implementation randomised control trial should be conducted to evaluate efficacy and effectiveness.
Short Research Article: Do demographic, socioeconomic and clinical characteristics influence the number of psychological intervention sessions attended by young people in need of mental health care?
Authors: Meddings John , Harries Anthony D. , Michelet Felix , Nall‐Evans Sharleen , Pender Fiona , Jaydeokar Sujeet
Published: December 2022

Background and method

A cohort study using secondary data assessed associations between baseline characteristics and psychological sessions attended in young persons discharged from a Children and Young People's Mental Health Service in 2019.

Results

There were 584 persons who attended a median of seven sessions. On multivariable regression analysis, males attended fewer sessions than females, young people from more affluent communities attended more sessions than those from poorer communities and those presenting with eating disorders and self‐harm in particular attended more sessions than those with anxiety.

Conclusions

Addressing why these associations occur may improve mental health care in young persons.
Long‐term results of kidney transplantation in patients with familial mediterranean fever
Authors: Bitik Berivan , Hatipoğlu Buğra , Sayın Burak , Kanbur Ayşenur Yalçıntaş , Bursa Nurbanu , Oygur Cağdaş Şahap , Özdemir Handan , Colak Turan , Haberal Mehmet , Yücel Ahmet Eftal
Published: December 2022

Introduction

Long‐term kidney transplantation (KT) results in patients with familial Mediterranean fever (FMF)‐related amyloidosis are not well studied. This study reviewed the long‐term survival outcomes of FMF patients who underwent KT.

Methods

We compared the outcomes of 31 patients who underwent (KT) for biopsy‐proven amyloidosis secondary to FMF with 31 control patients (five with diabetes mellitus and 26 with nondiabetic kidney disease) undergoing KT between 1994 and 2021 at Başkent University Hospital. All data were recorded retrospectively from patients’ files.

Results: The median age (quartile deviation

QD) at the time of KT in the FMF and control group were 31 (6.7) and 33 (11), respectively. The median follow‐up period (QD) after KT was 108 (57) months in the FMF and 132 (72) months in the control group. In the FMF group, graft and patient survivals were 71% and 84% at 5 years and 45% and 48% at 10 years, respectively. In the control group, graft and patient survivals were 79% and 100% at 5 years and 63% and 71% at 10 years, respectively. Patient survival in the FMF group at 5 years was significantly lower than in the control group (p = .045). There was no statistically significant difference between the FMF and control groups in terms of graft and patient survival, and serum creatinine levels at 10 years. All patients were given triple immunosuppressive treatment with cyclosporine, mycophenolate mofetil, and prednisolone. Three patients received anakinra and one received canakinumab in addition to colchicine treatment. One FMF patient also underwent heart transplantation due to AA amyloidosis. Of the FMF patients, 11 died during follow‐up.

Conclusion

We have found that the long‐term outcome of KT in patients with FMF amyloidosis is numerically worse but not statistically different from the control group. However, short‐ and long‐term complications still need to be resolved.