bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cumulative Sum Chart as Complement to Objective Assessment of Graduating Surgical Resident Competency: An Exploratory Study
Authors: Chen Xiaodong (Phoenix) , Harzman Alan , Go Michael , Arnold Mark , Ellison E Christopher 
Published: August 2023

Introduction:
Rater-based assessment and objective assessment play an important role in evaluating residents’ clinical competencies. We hypothesize that a cumulative sum (CUSUM) chart of operative time is a complement to the assessment of chief general surgery residents’ competencies with ACGME Milestones, aiding residency programs’ determination of graduating residents’ practice readiness.

Study Design:
We extracted ACGME milestone evaluations of performance of operations and procedures (POP) and three objective metrics (operative time, case type, and case complexity) from three procedures (cholecystectomy, colectomy, and inguinal hernia) performed by three cohorts of residents (N=15) during their PGY4-5. CUSUM charts were computed for each resident on each procedure type. A learning plateau was defined as at least four cases consistently locating around the centerline (target performance) at the end of a CUSUM chart with minimal deviations (range 0-1).

Results:
All residents reached the ACGME graduation targets for the overall POP by the end of chief year. A total of 2446 cases were included (cholecystectomy N=1234, colectomy N=507, and inguinal hernia N=705). Three CUSUM chart patterns emerged: skewed distribution, bimodal distribution, and peaks-and-valleys distribution. Analysis of CUSUM charts reveal surgery residents’ development process in the OR towards a learning plateau vary and only 46.7% residents reach a learning plateau in all three procedures upon graduation.

Conclusions:
CUSUM charts of operative time is a complement to the ACGME Milestones evaluations. The use of both may enable residency programs to holistically determine graduating residents’ practice readiness and provide recommendations for their upcoming career/practice transition.
Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients
Authors: Ben-Ami Roni , Loyfer Netanel , Cohen Eden , Fialkoff Gavriel , Sharkia Israa , Bogot Naama , Kochan Danit , Kalak George , Jarjoui Amir , Chen-Shuali Chen , Azulai Hava , Barhoum Hezi , Arish Nissim , Greenberger Moshe M , Vellema David , Kurd Ramzi , Chetrit Eli Ben , Bohm Davina , Wolak Talya , Quteineh Ahmad , Cann Gordon , Glaser Benjamin , Friedman Nir , Kaplan Tommy , Shemer Ruth , Rokach Ariel , Dor Yuval 
Published: August 2023

AbstractThe full spectrum of tissues affected by SARS-CoV-2 infection is crucial for deciphering the heterogenous clinical course of COVID-19. Here, we analyzed DNA methylation and histone modification patterns in circulating chromatin to assess cell type-specific turnover in severe and asymptomatic COVID-19 patients, in relation to clinical outcome. Patients with severe COVID-19 had a massive elevation of circulating cell-free DNA (cfDNA) levels, which originated in lung epithelial cells, cardiomyocytes, vascular endothelial cells and erythroblasts, suggesting increased cell death or turnover in these tissues. The immune response to infection was reflected by elevated B cell and monocyte/macrophage cfDNA levels, and by evidence of an interferon response in cells prior to cfDNA release. Strikingly, monocyte/macrophage cfDNA levels (but not monocyte counts), as well as lung epithelium cfDNA and vascular endothelial cfDNA, predicted clinical deterioration and duration of hospitalization. Asymptomatic patients had elevated levels of immune-derived cfDNA but did not show evidence of pulmonary or cardiac damage. Surprisingly, these patients showed elevated levels of vascular endothelial cell and erythroblast cfDNA, suggesting that sub-clinical vascular and erythrocyte turnover are universal features of COVID-19, independent of disease severity. Epigenetic liquid biopsies provide non-invasive means of monitoring COVID-19 patients, and reveal sub-clinical vascular damage and red blood cell turnover.
Induced pluripotent stem cell-derived human macrophages as an infection model forLeishmania donovani
Authors: Baert Lore , Rudy Serena , Pellisson Mélanie , Doll Thierry , Rocchetti Romina , Kaiser Marcel , Mäser Pascal , Müller Matthias 
Published: August 2023

AbstractThe parasiteLeishmania donovaniis one of the species causing visceral leishmaniasis in humans, a deadly infection claiming up to 40,000 lives each year. The current drugs for leishmaniasis treatment have severe drawbacks and there is an urgent need to find new anti-leishmanial compounds. However, the search for drug candidates is complicated by the intracellular lifestyle ofLeishmania. Here, we investigate the use of human induced pluripotent stem cell (iPS)-derived macrophages (iMACs) as host cells forL. donovani. iMACs obtained through embryoid body differentiation were infected withL. donovanipromastigotes, and high-content imaging techniques were used to optimise the iMACs seeding density and multiplicity of infection, allowing us to reach infection rates up to 70% five days after infection. IC50values obtained for miltefosine and amphotericin B using the infected iMACs or mouse peritoneal macrophages as host cells were comparable and in agreement with the literature, showing the potential of iMACs as an infection model for drug screening.Author SummaryYearly, up two million people in poverty-stricken areas contract leishmaniasis, a disease caused by parasites of the genusLeishmania. When an infected sandfly takes a blood meal,Leishmaniaparasites enter the host where they are taken up by macrophages. Inside the macrophage,Leishmaniaparasites establish a niche where they can proliferate. Although this infection often leads to disability or death, the drugs currently available are lacking due to toxic side effects, high expenses or difficulties in usage. Drug screening assays that are currently used for compound screening often rely on mouse peritoneal macrophages. We have generated human induced pluripotent stem cell derived macrophages and used these as new host cells forLeishmania donovaniin the testing of anti-leishmanial compounds. This model has many advantages. For one, it allows us to work with human cells, mimicking the natural infection more closely than possible with murine cells. Secondly, it allows to obtain bigger batches of uniform cells for screening campaigns. Finally, this approach aligns with the principle of 3R, replacing the use of animals for cultivation ofLeishmaniaand drug screening purposes.
Novel automaticity index reveals a cognitive ability-related decline in gait automaticity during dual-task walking
Authors: Liu Shuqi , Rosso Andrea L. , Baillargeon Emma M. , Weinstein Andrea M. , Rosano Caterina , Torres-Oviedo Gelsy 
Published: August 2023

AbstractGait automaticity refers to the ability to walk with minimal recruitment of attentional networks typically mediated through the prefrontal cortex (PFC). Reduced gait automaticity is common with aging, contributing to an increased risk of falls and reduced quality of life. A common assessment of gait automaticity involves examining PFC activation using near-infrared spectroscopy (fNIRS) during dual-task (DT) paradigms, such as walking while performing a cognitive task. However, neither PFC activity nor task performance in isolation measures automaticity accurately. For example, greater PFC activation could be interpreted as worse gait automaticity when accompanied by poorer DT performance, but when accompanied by better DT performance, it could be seen as successful compensation. Thus, there is a need to incorporate behavioral performance and PFC measurements for a more comprehensive evaluation of gait automaticity. To address this need, we propose a novel automaticity index as an analytical approach that combines changes in PFC activity with changes in DT performance to quantify gait automaticity. We validated the index in 173 participants (≥65 y/o) who completed DTs with two levels of difficulty while PFC activation was recorded with fNIRS. The two DTs consisted of reciting every other letter of the alphabet while walking over either an even or uneven surface. We found that as DT difficulty increases, more participants showed the anticipated decrease in automaticity as measured by the novel index compared to PFC activation. Furthermore, when comparing across individuals, lower cognitive function related to worse automaticity index, but not PFC activation or DT performance. In sum, the proposed index better quantified the differences in automaticity between tasks and individuals by providing a unified measure of gait automaticity that includes both brain activation and performance. This new approach opens exciting possibilities to assess participant-specific deficits and compare rehabilitation outcomes from gait automaticity interventions.
Phosphorylation of AHR by PLK1 promotes metastasis of LUAD via DIO2-TH signaling
Authors: Li Chaohao , Allison Derek B. , He Daheng , Mao Fengyi , Wang Xinyi , Rychahou Piotr , Imam Ibrahim A. , Kong Yifan , Zhang Qiongsi , Zhang Yanquan , Liu Jinghui , Wang Ruixin , Rao Xiongjian , Wu Sai , Shao Qing , Wang Chi , Li Zhiguo , Liu Xiaoqi 
Published: August 2023

AbstractMetastasis of Lung adenocarcinoma (LUAD) is a major cause of death in patients. Aryl hydrocarbon receptor (AHR) is an important transcription factor involved in the initiation and progression of lung cancer. Polo-like kinase 1 (PLK1), a serine/threonine kinase, is an oncogene that promotes the malignancy of multiple cancer types. Nonetheless, the interaction between these two factors and significance in lung cancer remains to be determined. Here, we demonstrate that PLK1 phosphorylates AHR at S489 in LUAD, which leads to epithelial-mesenchymal transition (EMT) and metastatic events. RNA-seq analyses show that type 2 deiodinase (DIO2) is responsible for EMT and enhanced metastatic potential. DIO2 converts tetraiodothyronine (T4) to triiodothyronine (T3), which then activates thyroid hormone signaling. In vitro and in vivo experiments demonstrate that treatment with T3 or T4 promotes the metastasis of LUAD, whereas depletion of DIO2 or deiodinase inhibitor disrupts this property. Taken together, our results identify the phosphorylation of AHR by PLK1 as a mechanism leading to the progression of LUAD and provide possible therapeutic interventions for this event.
Neural substrates of cold nociception inDrosophilalarva
Authors: Patel Atit A. , Cardona Albert , Cox Daniel N. 
Published: August 2023

AbstractMetazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus specific behaviors to either navigate away from injury- causing conditions or to perform protective behaviors that mitigate extensive injury. The ability of an animal to detect and respond to various sensory stimuli depends upon molecular diversity in the primary sensors and the underlying neural circuitry responsible for the relevant behavioral action selection. Recent studies inDrosophilalarvae have revealed that somatosensory class III multidendritic (CIII md) neurons function as multimodal sensors regulating distinct behavioral responses to innocuous mechanical and nociceptive thermal stimuli. Recent advances in circuit bases of behavior have identified and functionally validatedDrosophilalarval somatosensory circuitry involved in innocuous (mechanical) and noxious (heat and mechanical) cues. However, central processing of cold nociceptive cues remained unexplored. We implicate multisensory integrators (Basins), premotor (Down-and-Back) and projection (A09e and TePns) neurons as neural substrates required for cold-evoked behavioral and calcium responses. Neural silencing of cell types downstream of CIII md neurons led to significant reductions in cold-evoked behaviors and neural co-activation of CIII md neurons plus additional cell types facilitated larval contraction (CT) responses. Further, we demonstrate that optogenetic activation of CIII md neurons evokes calcium increases in these neurons. Finally, we characterize the premotor to motor neuron network underlying cold-evoked CT and delineate the muscular basis of CT response. Collectively, we demonstrate howDrosophilalarvae process cold stimuli through functionally diverse somatosensory circuitry responsible for generating stimulus-specific behaviors.
Single-cell RNA sequencing reveals characteristics of myeloid cells in pulmonary post-acute sequelae of SARS-CoV-2
Authors: Yoon Hyundong , Dean Logan S. , Jiyarom Boonyanudh , Khadka Vedbar , Deng Youping , Nerurukar Vivek R. , Chow Dominic C. , Shikuma Cecilia M. , Devendra Gehan , Koh Youngil , Park Juwon 
Published: August 2023

AbstractBackgroundAlthough our understanding of the immunopathology and subsequent risk and severity of COVID-19 disease is evolving, a detailed account of immune responses that contribute to the long-term consequences of pulmonary complication in COVID-19 infection remain unclear. Few studies have detailed the immune and cytokine profiles associated with post-acute sequalae of SARS-CoV-2 infection with persistent pulmonary symptoms (PPASC). However, the dysregulation of the immune system that drives pulmonary sequelae in COVID-19 survivors and PASC sufferers remains largely unknown.ResultsTo characterize the immunological features of pulmonary PASC (PPASC), we performed droplet-based single-cell RNA sequencing to study the transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from participants naïve to SARS-CoV-2 (Control) and infected with SARS-CoV-2 with chronic pulmonary symptoms (PPASC). We analyzed more than 34,139 PBMCs by integrating our dataset with previously reported control datasets (GSM4509024) cell distribution. In total, 11 distinct cell populations were identified based on the expression of canonical markers. The proportion of myeloid-lineage cells ([MLCs]; CD14+/CD16+monocytes and dendritic cells) was increased in PPASC compared to controls. MLCs from PPASC displayed up-regulation of genes associated with pulmonary symptoms/fibrosis, while glycolysis metabolism-related genes were downregulated. Similarly, pathway analysis showed that fibrosis- related (VEGF,WNT, andSMAD) and cell death pathways were up-regulated, but immune pathways were down-regulated in PPASC. In PPASC, we observed interactiveVEGFligand- receptor pairs among MLCs, and network modules in CD14+(cluster 4) and CD16+(Cluster 5) monocytes displayed a significant enrichment for biological pathways linked to adverse COVID- 19 outcomes, fibrosis, and angiogenesis. Further analysis revealed a distinct metabolic alteration in MLCs with a down-regulation of glycolysis/gluconeogenesis in PPASC compared to SARS- CoV-2 naïve samples.ConclusionThis study offers valuable insights into the immune response and cellular landscape in PPASC. The presence of elevated MLC levels and their corresponding gene signatures associated with fibrosis, immune response suppression, and altered metabolic states suggests their potential role as a driver of PPASC.
The relationship between diet, plasma glucose, and cancer prevalence across vertebrates
Authors: Kapsetaki Stefania E. , Basile Anthony J. , Compton Zachary T. , Rupp Shawn M. , Duke Elizabeth G. , Boddy Amy M. , Harrison Tara M. , Sweazea Karen L. , Maley Carlo C. 
Published: August 2023

AbstractCould diet and mean plasma glucose concentration (MPGluC) explain the variation in cancer prevalence across species? We collected diet, MPGluC, and neoplasia data for 160 vertebrate species from existing databases. We found that MPGluC negatively correlates with cancer and neoplasia prevalence, mostly of gastrointestinal organs. Trophic level positively correlates with cancer and neoplasia prevalence even after controlling for species MPGluC. Most species with high MPGluC (50/78 species = 64.1%) were birds. Most species in high trophic levels (42/53 species = 79.2%) were reptiles and mammals. Our results may be explained by the evolution of insulin resistance in birds which selected for loss or downregulation of genes related to insulin-mediated glucose import in cells. This led to higher MPGluC, intracellular caloric restriction, production of fewer reactive oxygen species and inflammatory cytokines, and longer telomeres contributing to longer longevity and lower neoplasia prevalence in extant birds relative to other vertebrates.
Borg extrachromosomal elements of methane-oxidizing archaea have conserved and expressed genetic repertoires
Authors: Schoelmerich Marie C. , Ly Lynn , West-Roberts Jacob , Shi Ling-Dong , Shen Cong , Malvankar Nikhil S. , Taib Najwa , Gribaldo Simonetta , Woodcroft Ben J. , Schadt Christopher W. , Al-Shayeb Basem , Dai Xiaoguang , Mozsary Christopher , Hickey Scott , He Christine , Beaulaurier John , Juul Sissel , Sachdeva Rohan , Banfield Jillian F. 
Published: August 2023

AbstractBorgs are huge extrachromosomal elements (ECE) of anaerobic methane-consuming “CandidatusMethanoperedens” archaea. Here, we used nanopore sequencing to validate published complete genomes curated from short reads and to reconstruct new genomes. 13 complete and four near-complete linear genomes share 40 genes that define a largely syntenous genome backbone. We use these conserved genes to identify new Borgs from peatland soil and to delineate Borg phylogeny, revealing two major clades. Remarkably, Borg genes encoding OmcZ nanowire-like electron-exporting cytochromes and cell surface proteins are more highly expressed than those of hostMethanoperedens, indicating that Borgs augment theMethanoperedensactivityin situ. We reconstructed the first complete 4.00 Mbp genome for aMethanoperedensthat is inferred to be a Borg host and predicted its methylation motifs, which differ from pervasive TC and CC methylation motifs of the Borgs. Thus, methylation may enableMethanoperedensto distinguish their genomes from those of Borgs. Very high Borg toMethanoperedensratios and structural predictions suggest that Borgs may be capable of encapsulation. The findings clearly define Borgs as a distinct class of ECE with shared genomic signatures, establish their diversification from a common ancestor with genetic inheritance, and raise the possibility of periodic existence outside of host cells.
Microclimate Shapes the Phylosymbiosis of Rodent Gut Microbiota in Jordan’s Great Rift Valley
Authors: Al-khlifeh Enas , Khadem Sanaz , Hausmann Bela , Berry David 
Published: August 2023

AbstractHost phylogeny and the environment play vital roles in shaping animal microbiomes. However, the effects of these variables on the diversity and richness of the gut microbiome in different bioclimatic zones remain underexplored. In this study, we investigated the effects of host phylogeny and bioclimatic zone on the diversity and composition of the gut microbiota of two heterospecific rodent species, the spiny mouseAcomys cahirinusand the house mouseMus musculus, in three bioclimatic zones of the African Great Rift Valley (GRV). We confirmed host phylogeny using theD-loopsequencing method and analyzed the influence of host phylogeny and bioclimatic zone parameters on the rodent gut microbiome using high-throughput amplicon sequencing of 16S rRNA gene fragments. Phylogenetic analysis supported the morphological identification of the rodents and revealed a marked genetic difference between the two heterospecific species. We found that bioclimatic zone had a significant effect on the gut microbiota composition while host phylogeny did not. Microbial alpha diversity of heterospecific hosts was highest in the Mediterranean forest bioclimatic zone, followed by the Irano–Turranian shrubland, and was lowest in the Sudanian savanna tropical zone. The beta diversity of the two rodent species showed significant differences across the Mediterranean, Irano–Turranian, and Sudanian regions. The phylaFirmicutesandBacteroideteswere highly abundant, andDeferribacterota, CyanobacteriaandProteobacteriawere also prominent. Amplicon sequence variants (ASVs) were identified that were unique to the Sudanian bioclimatic zone. The core microbiota families recovered in this study were consistent among heterospecific hosts. However, diversity decreased in conspecific host populations found at lower altitudes in Sudanian bioclimatic zone. The composition of the gut microbiota is linked to the adaptation of the host to its environment, and this study underscores the importance of incorporating climatic factors such as elevation and ambient temperature, in empirical microbiome research and is the first to describe the rodent gut microbiome from the GRV.
The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome
Authors: Krischuns T , Arragain B , Isel C , Paisant S , Budt M , Wolff T , Cusack S , Naffakh N 
Published: August 2023

SummaryThe current model is that the influenza virus polymerase (FluPol) binds either to host RNA polymerase II (RNAP II) or to the acidic nuclear phosphoprotein 32 (ANP32), which drives its conformation and activity towards transcription or replication of the viral genome, respectively. Here, we provide evidence that the FluPol-RNAP II binding interface has a so far overlooked function for replication of the viral genome. Using a combination of cell-based andin vitroapproaches, we show that the RNAP II C-terminal-domain, jointly with ANP32, enhances FluPol replication activity and we propose a model in which the host RNAP II is the anchor for transcription and replication of the viral genome. Our data open new perspectives on the spatial coupling of viral transcription and replication and the coordinated balance between these two activities.