bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive and prognostic value of different cardiac troponin assays: a nationwide register-based cohort study
Authors: Hasselbalch Rasmus B , Schultz Martin , Schytz Philip A , Kristensen Jonas H , Strandkjær Nina , Pries-Heje Mia , Carlson Nicholas , Schou Morten , Bundgaard Henning , Torp-Pedersen Christian , Iversen Kasper K
Published: October 2022

Aims

Guidelines do not differentiate between the available assays of cardiac troponin (cTn). We compared the prognostic and predictive ability of cTn assays.

Methods and results

This was a nationwide cohort study of patients with acute coronary syndrome (ACS) and ≥ 2 cTn measurements of one of four assays: Roche high-sensitivity cTnT (hs-cTnT), Abbott high sensitivity cTnI (hs-cTnI), Siemens Vista cTnI, and Siemens cTnI Ultra. Data were collected from Danish registries from 2009–18. Peak cTn concentration normalized to the 99th percentile was used. Outcomes were myocardial infarction (MI) during admission, one-year all-cause-, cardiovascular-, and non-cardiovascular mortality. Receiver operating characteristics and logistic regression calculating odds ratios (OR) were used. A total of 90 705 patients were included, of which 20 550 (23%) had MI. Siemens Vista cTnI was the strongest predictor of MI, Area under the curve (auc) 0.93 (95% CI 0.93–0.93). In 1 year 9012 (9.9%) of patients had died. An inverted U-shape relationship was observed between concentration of cTn and all-cause mortality. Hs-cTnT OR 21.3 (95% CI 18.4–24.8) at 2–5 times the 99th percentile and 12.1 (95% CI 10.3–14.1) for concentrations >100 times the 99th percentile. The inverted U-shape relationship was only present for non-cardiovascular mortality. The strongest predictor of cardiovascular mortality was hs-cTnT, OR 11.3 (95% CI 6.4–21.8) at 1–2 times the 99th percentile and 88.8 (95% CI 53.2–163.0) for concentrations >100 times the 99th percentile.

Conclusion

Siemens Vista cTnI was the strongest predictor of MI and hs-cTnT was the strongest predictor of mortality. An inverted U-shape relationship was observed between cTn concentration and non-cardiovascular mortality.
Dynamic trophic shifts in bacterial and eukaryotic communities during the first 30 years of microbial succession following retreat of an Antarctic glacier
Authors: Vimercati Lara , Bueno de Mesquita Clifton P , Johnson Ben W , Mineart Dana , DeForce Emelia , Vimercati Molano Ylenia , Ducklow Hugh , Schmidt Steven K
Published: October 2022

We examined microbial succession along a glacier forefront in the Antarctic Peninsula representing ∼30 years of deglaciation to contrast bacterial and eukaryotic successional dynamics and abiotic drivers of community assembly using sequencing and soil properties. Microbial communities changed most rapidly early along the chronosequence, and co-occurrence network analysis showed the most complex topology at the earliest stage. Initial microbial communities were dominated by microorganisms derived from the glacial environment, whereas later stages hosted a mixed community of taxa associated with soils. Eukaryotes became increasingly dominated by Cercozoa, particularly Vampyrellidae, indicating a previously unappreciated role for cercozoan predators during early stages of primary succession. Chlorophytes and Charophytes (rather than cyanobacteria) were the dominant primary producers and there was a spatio-temporal sequence in which major groups became abundant succeeding from simple ice Chlorophytes to Ochrophytes and Bryophytes. Time since deglaciation and pH were the main abiotic drivers structuring both bacterial and eukaryotic communities. Determinism was the dominant assembly mechanism for Bacteria, while the balance between stochastic/deterministic processes in eukaryotes varied along the distance from the glacier front. This study provides new insights into the unexpected dynamic changes and interactions across multiple trophic groups during primary succession in a rapidly changing polar ecosystem.
Discovery of malathion resistance QTL in Drosophila melanogaster using a bulked phenotyping approach
Authors: Macdonald Stuart J , Long Anthony D
Published: October 2022

Drosophila melanogaster has proved an effective system with which to understand the evolutionary genetics and molecular mechanisms of insecticide resistance. Insecticide use has left signatures of selection in the fly genome, and both functional and quantitative genetic studies in the system have identified genes and variants associated with resistance. Here, we use D. melanogaster and leverage a bulk phenotyping and pooled sequencing “extreme quantitative trait loci” approach to genetically dissect variation in resistance to malathion, an organophosphate insecticide. We resolve 2 quantitative trait loci, one of which implicates allelic variation at the cytochrome P450 gene Cyp6g1, a strong candidate based on previous work. The second shows no overlap with hits from a previous genome-wide association study for malathion resistance, recapitulating other studies showing that different strategies for complex trait dissection in flies can yield apparently different architectures. Notably, we see no genetic signal at the Ace gene. Ace encodes the target of organophosphate insecticide inhibition, and genome-wide association studies have identified strong Ace-linked associations with resistance in flies. The absence of quantitative trait locus implicating Ace here is most likely because our mapping population does not segregate for several of the known functional polymorphisms impacting resistance at Ace, perhaps because our population is derived from flies collected prior to the widespread use of organophosphate insecticides. Our fundamental approach can be an efficient, powerful strategy to dissect genetic variation in resistance traits. Nonetheless, studies seeking to interrogate contemporary insecticide resistance variation may benefit from deriving mapping populations from more recently collected strains.
Assessing single-locus CRISPR/Cas9-based gene drive variants in the mosquito Aedes aegypti via single-generation crosses and modeling
Authors: Reid William , Williams Adeline E , Sanchez-Vargas Irma , Lin Jingyi , Juncu Rucsanda , Olson Ken E , Franz Alexander W E
Published: October 2022

The yellow fever mosquito Aedes aegypti is a major vector of arthropod-borne viruses, including dengue, chikungunya, and Zika viruses. A novel approach to mitigate arboviral infections is to generate mosquitoes refractory to infection by overexpressing antiviral effector molecules. Such an approach requires a mechanism to spread these antiviral effectors through a population, for example, by using CRISPR/Cas9-based gene drive systems. Critical to the design of a single-locus autonomous gene drive is that the selected genomic locus is amenable to both gene drive and appropriate expression of the antiviral effector. In our study, we used reverse engineering to target 2 intergenic genomic loci, which had previously shown to be highly permissive for antiviral effector gene expression, and we further investigated the use of 3 promoters (nanos, β2-tubulin, or zpg) for Cas9 expression. We then quantified the accrual of insertions or deletions (indels) after single-generation crossings, measured maternal effects, and assessed fitness costs associated with various transgenic lines to model the rate of gene drive fixation. Overall, MGDrivE modeling suggested that when an autonomous gene drive is placed into an intergenic locus, the gene drive system will eventually be blocked by the accrual of gene drive blocking resistance alleles and ultimately be lost in the population. Moreover, while genomic locus and promoter selection were critically important for the initial establishment of the autonomous gene drive, it was the fitness of the gene drive line that most strongly influenced the persistence of the gene drive in the simulated population. As such, we propose that when autonomous CRISPR/Cas9-based gene drive systems are anchored in an intergenic locus, they temporarily result in a strong population replacement effect, but as gene drive-blocking indels accrue, the gene drive becomes exhausted due to the fixation of CRISPR resistance alleles.
Identification of stable QTL controlling multiple yield components in a durum × cultivated emmer wheat population under field and greenhouse conditions
Authors: Peters Haugrud Amanda R , Zhang Qijun , Green Andrew J , Xu Steven S , Faris Justin D
Published: October 2022

Crop yield gains are needed to keep pace with a growing global population and decreasing resources to produce food. Cultivated emmer wheat is a progenitor of durum wheat and a useful source of genetic variation for trait improvement in durum. Here, we evaluated a recombinant inbred line population derived from a cross between the North Dakota durum wheat variety Divide and the cultivated emmer wheat accession PI 272527 consisting of 219 lines. The population was evaluated in 3 field environments and 2 greenhouse experiments to identify quantitative trait locus associated with 11 yield-related traits that were expressed in a consistent manner over multiple environments. We identified 27 quantitative trait locus expressed in at least 2 field environments, 17 of which were also expressed under greenhouse conditions. Seven quantitative trait locus regions on chromosomes 1B, 2A, 2B, 3A, 3B, 6A, and 7B had pleiotropic effects on multiple yield-related traits. The previously cloned genes Q and FT-B1, which are known to be associated with development and morphology, were found to consistently be associated with multiple traits across environments. PI 272527 contributed beneficial alleles for quantitative trait locus associated with multiple traits, especially for seed morphology quantitative trait locus on chromosomes 1B, 2B, and 6A. Three recombinant inbred lines with increased grain size and weight compared to Divide were identified and demonstrated the potential for improvement of durum wheat through deployment of beneficial alleles from the cultivated emmer parent. The findings from this study provide knowledge regarding stable and robust quantitative trait locus that breeders can use for improving yield in durum wheat.
Genetic determinants of polygenic prediction accuracy within a population
Authors: Lu Tianyuan , Forgetta Vincenzo , Richards John Brent , Greenwood Celia M T
Published: October 2022

Genomic risk prediction is on the emerging path toward personalized medicine. However, the accuracy of polygenic prediction varies strongly in different individuals. Based on up to 352,277 European ancestry participants in the UK Biobank, we constructed polygenic risk scores for 15 physiological and biochemical quantitative traits. We identified a total of 185 polygenic prediction variability quantitative trait loci for 11 traits by Levene’s test among 254,376 unrelated individuals. We validated the effects of prediction variability quantitative trait loci using an independent test set of 58,927 individuals. For instance, a score aggregating 51 prediction variability quantitative trait locus variants for triglycerides had the strongest Spearman correlation of 0.185 (P-value <1.0 × 10−300) with the squared prediction errors. We found a strong enrichment of complex genetic effects conferred by prediction variability quantitative trait loci compared to risk loci identified in genome-wide association studies, including 89 prediction variability quantitative trait loci exhibiting dominance effects. Incorporation of dominance effects into polygenic risk scores significantly improved polygenic prediction for triglycerides, low-density lipoprotein cholesterol, vitamin D, and platelet. In conclusion, we have discovered and profiled genetic determinants of polygenic prediction variability for 11 quantitative biomarkers. These findings may assist interpretation of genomic risk prediction in various contexts and encourage novel approaches for constructing polygenic risk scores with complex genetic effects.
High temporal resolution Nanopore sequencing dataset of SARS-CoV-2 and host cell RNAs
Authors: Tombácz Dóra , Dörmő Ákos , Gulyás Gábor , Csabai Zsolt , Prazsák István , Kakuk Balázs , Harangozó Ákos , Jankovics István , Dénes Béla , Boldogkői Zsolt
Published: October 2022

Background

Recent studies have disclosed the genome, transcriptome, and epigenetic compositions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the effect of viral infection on gene expression of the host cells. It has been demonstrated that, besides the major canonical transcripts, the viral genome also codes for noncanonical RNA molecules. While the structural characterizations have revealed a detailed transcriptomic architecture of the virus, the kinetic studies provided poor and often misleading results on the dynamics of both the viral and host transcripts due to the low temporal resolution of the infection event and the low virus/cell ratio (multiplicity of infection [MOI] = 0.1) applied for the infection. It has never been tested whether the alteration in the host gene expressions is caused by aging of the cells or by the viral infection.

Findings

In this study, we used Oxford Nanopore's direct cDNA and direct RNA sequencing methods for the generation of a high-coverage, high temporal resolution transcriptomic dataset of SARS-CoV-2 and of the primate host cells, using a high infection titer (MOI = 5). Sixteen sampling time points ranging from 1 to 96 hours with a varying time resolution and 3 biological replicates were used in the experiment. In addition, for each infected sample, corresponding noninfected samples were employed. The raw reads were mapped to the viral and to the host reference genomes, resulting in 49,661,499 mapped reads (54,62 Gbs). The genome of the viral isolate was also sequenced and phylogenetically classified.

Conclusions

This dataset can serve as a valuable resource for profiling the SARS-CoV-2 transcriptome dynamics, the virus–host interactions, and the RNA base modifications. Comparison of expression profiles of the host gene in the virally infected and in noninfected cells at different time points allows making a distinction between the effect of the aging of cells in culture and the viral infection. These data can provide useful information for potential novel gene annotations and can also be used for studying the currently available bioinformatics pipelines.
Feature extraction for margin lines using region growing with a dynamic weight function in a one-point bidirectional path search
Authors: Shin Hyoung-Sub , Li Zhi , Kim Jay J
Published: October 2022

A margin line, defined as the boundary curve of the contact area between a prepared tooth and a dental restoration, considerably influences the end shape of the dental restoration design. Most studies that have extracted margin lines from mesh models representing prepared teeth have faced convergence problems in the path search and therefore pose the inconvenience of specifying multiple input points as intermediate goal points. To overcome these problems, in this study, we propose a bidirectional path-search algorithm using a single input point. First, the algorithm classifies all nodes in a mesh model into a margin or fuzzy region to increase search efficiency. Then, the search starts from one point and proceeds on two paths in opposite directions, using the current node of the opposite path as the temporary goal of the currently searched path. During the search, a dynamic evaluation function that varies weights according to the region type is employed to improve the path convergence. Finally, to increase the practicality of the algorithm, the jagged initial margin line is converted into a smooth spline curve using an energy-minimization function specialized for margin lines. To evaluate the proposed algorithm, margin lines extracted from various types of prepared teeth are demonstrated and compared with those created using some relevant previous works and a commercial dental computer-aided design (CAD) system. The comparison verified that accurate margin lines could be calculated with only one input point using the proposed algorithm. Moreover, the proposed algorithm showed better performance for crown and inlay/only experimental models compared with a commercial dental CAD system under the same conditions.
An improved ant-tracking workflow based on divided-frequency data for fracture detection
Authors: Xie Qinghui , Zhao Chunduan , Rui Zhifeng , Guan Shoujun , Zheng Wenting , Fan Hongche
Published: October 2022

The conventional ant-tracking technique often results in weak transverse continuity or unobvious plane fracture patterns. It also has limited ability to identify small-scale natural fractures. To improve the image quality of fractures, a spectrum decomposition technique has been used in ant-tracking. Although it has achieved good results, it also brings a high workload and judgment difficulty. To solve these issues, we proposed an improved ant-tracking workflow based on frequency filtering to improve the accuracy of fracture detection, in which the tracking was performed on low-, medium- and high-frequency cubes. The workflow was applied in the H area of the Sichuan Basin with good results: (i) more continuous, sharper and more small-scale fractures were detected by the proposed workflow than the ones with the full-band seismic data. (ii) Compared to the ant-tracking methods based on a series of single-frequency data cubes, this not only requires less computation time, but is also easier to distinguish the differences between the three divided-frequency cubes. (iii) Comparing the ant-tracking effect, the results of medium- and high- frequency cubes are much better than the low- frequency. (iv) Compared with the traditional methods, the time of automatic fracture extraction is obviously shortened. This provided a solid data foundation for subsequent reservoir production prediction and well deployment.
The immigrant wage gap and assimilation in Korea
Authors: Kim Hyejin , Lee Chulhee
Published: October 2022

This study investigates the size of the initial wage disadvantage and the patterns of subsequent labor-market assimilation for immigrant workers in South Korea. We find that immigrants to Korea earn 17–29 percent less upon arrival than natives with similar characteristics, and the wage gap diminishes by 1.55 percent per year spent in the country. The patterns of assimilation differ by both gender and country of origin. Males and Asian immigrants generally follow the patterns of all foreign workers. However, females experience a smaller initial wage difference and no convergence, while immigrants from non-Asian countries and Japan initially earn higher wages than natives, but they then experience a relative decline in wages over time. The results of our out-migration analysis suggest that the negative assimilation of non-Asian and Japanese immigrants may be due to positively selected out-migration.
Widespread Gene Expression Divergence in Butterfly Sensory Tissues Plays a Fundamental Role During Reproductive Isolation and Speciation
Authors: Wu Ningning , Evans Elizabeth , van Schooten Bas , Meléndez-Rosa Jesyka , Ortiz Yadira , Planas Soto-Navarro Silvia M , Van Belleghem Steven M , Counterman Brian A , Papa Riccardo , Zhang Wei
Published: October 2022

Neotropical Heliconius butterflies are well known for their intricate behaviors and multiple instances of incipient speciation. Chemosensing plays a fundamental role in the life history of these groups of butterflies and in the establishment of reproductive isolation. However, chemical communication involves synergistic sensory and accessory functions, and it remains challenging to investigate the molecular mechanisms underlying behavioral differences. Here, we examine the gene expression profiles and genomic divergence of three sensory tissues (antennae, legs, and mouthparts) between sexes (females and males) and life stages (different adult stages) in two hybridizing butterflies, Heliconius melpomene and Heliconius cydno. By integrating comparative transcriptomic and population genomic approaches, we found evidence of widespread gene expression divergence, supporting a crucial role of sensory tissues in the establishment of species barriers. We also show that sensory diversification increases in a manner consistent with evolutionary divergence based on comparison with the more distantly related species Heliconius charithonia. The findings of our study strongly support the unique chemosensory function of antennae in all three species, the importance of the Z chromosome in interspecific divergence, and the nonnegligible role of nonchemosensory genes in the divergence of chemosensory tissues. Collectively, our results provide a genome-wide illustration of diversification in the chemosensory system under incomplete reproductive isolation, revealing strong molecular separation in the early stage of speciation. Here, we provide a unique perspective and relevant view of the genetic architecture (sensory and accessory functions) of chemosensing beyond the classic chemosensory gene families, leading to a better understanding of the magnitude and complexity of molecular changes in sensory tissues that contribute to the establishment of reproductive isolation and speciation.
MEPP: more transparent motif enrichment by profiling positional correlations
Authors: Delos Santos Nathaniel P , Duttke Sascha , Heinz Sven , Benner Christopher
Published: October 2022

Score-based motif enrichment analysis (MEA) is typically applied to regulatory DNA to infer transcription factors (TFs) that may modulate transcription and chromatin state in different conditions. Most MEA methods determine motif enrichment independent of motif position within a sequence, even when those sequences harbor anchor points that motifs and their bound TFs may functionally interact with in a distance-dependent fashion, such as other TF binding motifs, transcription start sites (TSS), sequencing assay cleavage sites, or other biologically meaningful features. We developed motif enrichment positional profiling (MEPP), a novel MEA method that outputs a positional enrichment profile of a given TF’s binding motif relative to key anchor points (e.g. transcription start sites, or other motifs) within the analyzed sequences while accounting for lower-order nucleotide bias. Using transcription initiation and TF binding as test cases, we demonstrate MEPP’s utility in determining the sequence positions where motif presence correlates with measures of biological activity, inferring positional dependencies of binding site function. We demonstrate how MEPP can be applied to interpretation and hypothesis generation from experiments that quantify transcription initiation, chromatin structure, or TF binding measurements. MEPP is available for download from https://github.com/npdeloss/mepp.
Five stories: international scientists in China
Authors: Zhao Weijie
Published: October 2022

A large number of Chinese scientists are working overseas, especially in the USA and Europe, where scientific communities are highly internationalized and diverse. In contrast, international scientists working in China are fewer, naturally generating some curiosity about them—why do they come to China, and how are their experiences in China? In this article, we introduce five such scientists and their stories.
Dexmedetomidine attenuates renal ischemia–reperfusion injury through activating PI3K/Akt‐eNOS signaling via α2 adrenoreceptors in renal microvascular endothelial cells
Authors: Shan Xisheng , Zhang Jiaxin , Wei Xiang , Tao Wenhui , Peng Ke , Liu Huayue , Wang Yiqing , Liu Hong , Meng Xiaowen , Ji Fuhai
Published: October 2022

Renal microvascular endothelial cells (RMECs), which are closely related to regulation of vascular reactivity and modulation of inflammation, play a crucial role in the process of renal ischemia and reperfusion (I/R) injury. Previous studies have reported the protective effects of dexmedetomidine (DEX) against renal I/R injury, but little is known about the role of DEX on RMECs. This study aimed to investigate whether DEX alleviated renal I/R injury via acting on the RMECs. Mice underwent bilateral renal artery clamping for 45 min followed by reperfusion for 48 h, and the cultured neonatal mice RMECs were subjected to hypoxia for 1 h followed by reoxygenation (H/R) for 24 h. The results suggest that DEX alleviated renal I/R injury in vivo and improved cell viability of RMECs during H/R injury in vitro. Gene sequencing revealed that the PI3K/Akt was the top enriched signaling pathway and the endothelial cells were widely involved in renal I/R injury. DEX activated phosphorylation of PI3K and Akt, increased eNOS expression, and attenuated inflammatory responses. In addition, the results confirmed the distribution of α2 adrenoreceptor (α2‐AR) in RMECs. Furthermore, the protective effects of DEX against renal I/R injury were abolished by α2‐AR antagonist (atipamezole), which was partly reversed by the PI3K agonist (740 Y‐P). These findings indicated that DEX protects against renal I/R injury by activating the PI3K/Akt‐eNOS pathway and inhibiting inflammation responses via α2‐AR in RMECs.
Evidence for a fragile X messenger ribonucleoprotein 1 (FMR1) mRNA gain‐of‐function toxicity mechanism contributing to the pathogenesis of fragile X‐associated premature ovarian insufficiency
Authors: Rosario Roseanne , Stewart Hazel L. , Choudhury Nila Roy , Michlewski Gracjan , Charlet‐Berguerand Nicholas , Anderson Richard A.
Published: October 2022

Fragile X‐associated premature ovarian insufficiency (FXPOI) is among a family of disorders caused by expansion of a CGG trinucleotide repeat sequence located in the 5′ untranslated region (UTR) of the fragile X messenger ribonucleoprotein 1 (FMR1) gene on the X chromosome. Women with FXPOI have a depleted ovarian follicle population, resulting in amenorrhea, hypoestrogenism, and loss of fertility before the age of 40. FXPOI is caused by expansions of the CGG sequence to lengths between 55 and 200 repeats, known as a FMRI premutation, however the mechanism by which the premutation drives disease pathogenesis remains unclear. Two main hypotheses exist, which describe an mRNA toxic gain‐of‐function mechanism or a protein‐based mechanism, where repeat‐associated non‐AUG (RAN) translation results in the production of an abnormal protein, called FMRpolyG. Here, we have developed an in vitro granulosa cell model of the FMR1 premutation by ectopically expressing CGG‐repeat RNA and FMRpolyG protein. We show that expanded CGG‐repeat RNA accumulated in intranuclear RNA structures, and these aggregates were able to cause significant granulosa cell death independent of FMRpolyG expression. Using an innovative RNA pulldown, mass spectrometry‐based approach we have identified proteins that are specifically sequestered by CGG RNA aggregates in granulosa cells in vitro, and thus may be deregulated as consequence of this interaction. Furthermore, we have demonstrated reduced expression of three proteins identified via our RNA pulldown (FUS, PA2G4 and TRA2β) in ovarian follicles in a FMR1 premutation mouse model. Collectively, these data provide evidence for the contribution of an mRNA gain‐of‐function mechanism to FXPOI disease biology.
Degeneration of biological heart valve grafts in a rat model of superoxide dismutase‐3 deficiency
Authors: Assmann Alexander , Schmidt Vera , Lepke Caroline , Sugimura Yukiharu , Assmann Anna Kathrin , Barth Mareike , Lichtenberg Artur , Akhyari Payam
Published: October 2022

While oxidative stress is known as key element in the pathogenesis of atherosclerosis and calcific aortic valve disease, its role in the degeneration of biological cardiovascular grafts has not been clarified yet. Therefore, the present study aimed to examine the impact of oxidative stress on the degeneration of biological cardiovascular allografts in a standardized chronic implantation model realized in rats exhibiting superoxide dismutase 3 deficiency (SOD3(−)). Rats with SOD3 loss‐of‐function mutation (n = 24) underwent infrarenal implantation of cryopreserved valved aortic conduits, while SOD3‐competent recipients served as controls (n = 28). After a follow‐up period of 4 or 12 weeks, comparative analyses addressed degenerative processes, hemodynamics, and evaluation of the oxidative stress model. SOD3(−)rats presented decreased circulating SOD activity (p = .0079). After 12 weeks, 58% of the implant valves in SOD3(−)rats showed regurgitation (vs. 31% in controls,p = .2377). Intima hyperplasia and chondro‐osteogenic transformation contributed to progressive graft calcification (p = .0024). At 12 weeks, hydroxyapatite deposition (p = .0198) and the gene expression of runt‐related transcription factor‐2 (Runx2) (p = .0093) were significantly enhanced in group SOD3(−). This study provides the first in vivo evidence that impaired systemic antioxidant activity contributes to biological cardiovascular graft degeneration.
RNA m6A reader IGF2BP3 promotes metastasis of triple‐negative breast cancer via SLIT2 repression
Authors: Jiang Tongtong , He Xinyi , Zhao Zhining , Zhang Xiao , Wang Ting , Jia Lintao
Published: October 2022

Triple‐negative breast cancer (TNBC) is a group of fatal malignancies characterized by high metastatic capacity, the underlying mechanisms of which remain largely elusive. We have found here that insulin‐like growth factor 2 mRNA binding protein 3 (IGF2BP3) is highly expressed in TNBC and correlates clinically with distant metastasis‐free survival of TNBC patients. IGF2BP3 promotes the migration and invasion capabilities of TNBC cells dependent upon cellular RNA N6‐methyladenosine (m6A) modification. Mechanistically, IGF2BP3 binds to and destabilizes m6A–methylated mRNA of the extracellular matrix glycoprotein, SLIT2, impairs its downstream signaling via the cognate receptor ROBO1, and consequently triggers the activation of canonical PI3K/AKT and MEK/ERK pathways. The IGF2BP3/SLIT2 axis is critically involved in the regulation of TNBC metastasis in vivo. These findings shed light into the regulatory network of distant metastasis of breast cancer and provide rationale for targeting the m6A machinery in the treatment of TNBC.
circBGN accelerates gastric cancer cell proliferation and invasion via activating IL6/STAT3 signaling pathway
Authors: Li Chenghui , Peng Xiang , Peng Zhiyong , Yan Bin
Published: October 2022

Circular RNAs participate in the pathogenesis of various tumors, including gastric cancer (GC). In this study, we investigated the role of circBGN in regulating proliferation and invasion of GC cells and elucidated the mechanism. The expression of circBGN was assessed by quantitative reverse‐transcription PCR and in situ hybridization. In addition, loss‐ and gain‐of‐function investigations in vitro and in vivo were performed to determine the biological functions of circBGN. Luciferase reporter assays and rescue experiments were applied to investigate the interaction between circBGN and miR‐149‐5p as well as the relationship between miR‐149‐5p and IL6. Our results showed that circBGN expression was significantly elevated in GC tissues and cells. Knockdown of circBGN dramatically suppressed GC cell proliferation and invasion in vitro. Xenograft experiments revealed that knockdown of circBGN delayed tumor growth in vivo. Furthermore, circBGN can directly bind to miR‐149‐5p, thereby preventing miR‐149‐5p from binding to its target mRNA [IL6 mRNA], thus activating IL6/STAT3 signaling pathway. Rescue assays indicated that circBGN regulates GC cell proliferation and invasion by upregulating miR‐149‐5p/IL6 axis output. Taken together, our investigation indicates that circBGN supports GC progression by activating IL6/STAT3 signaling pathway, thus pointing to a new possible therapeutic target in GC.
Toward Drainless Breast Reconstruction: A Pilot Study
Authors: Patel Harsh , Kulber David , Ray Edward
Published: October 2022

Background:

Implant-based breast reconstruction with immediate tissue expander placement is the predominant form of breast reconstruction in the United States. Closed-suction drains are frequently employed to minimize seroma accumulation, although they carry the risk of serving as a port of entry for bacteria, posing a concern in the presence of implanted materials such as breast implants or acellular dermal matrix. Introduction of a dual-port tissue expander designed to facilitate the collection and removal of seroma fluid provides a new way of performing breast reconstruction without external drains.

Methods:

We conducted a pilot study using the AlloX2 dual-port expander on five consecutive patients to demonstrate feasibility of this approach at Cedars-Sinai Medical Center by the two senior authors (E.R. and D.K.).

Results:

Patients averaged seven clinic visits before they were ready for expander exchange, totaling a mean of 137.5 days. Patients averaged 1.9 clinic visits before output was less than 40cm3 (1.6 for right breasts and 2.2 for left breasts), with two of the patients never reaching that output. There was one complication; a single patient had unilateral flap necrosis and implant exposure due to excessively large breasts and thin skin flaps, necessitating expander removal and latissimus flap reconstruction. The other four patients underwent successful implant reconstruction.

Conclusions:

This pilot study demonstrates the feasibility of breast reconstruction without external drains using a dual-port expander with built-in seroma reservoir. From these results, it is apparent that dual-port tissue expanders with built-in seroma reservoir offer a safe and effective way to perform breast reconstruction without drains in appropriately selected patients. A larger prospective cohort will be needed to definitively demonstrate lower infection and reconstructive failure rates.
Spare Part Reconstruction of Distal Pediatric Thumb Amputation
Authors: Tadisina Kashyap Komarraju , Teixeira Robert , Kells Amy
Published: October 2022

Thumb tip amputations can be reconstructive challenges, particularly in pediatric patients. Reconstruction using composite grafting and local flap options has been described for tip amputations in the adult population. The authors describe the use of a spare part reconstruction using autologous bone graft and a reverse cross finger flap to preserve length and function for a distal thumb tip amputation in a young man.
An Update and Report Failure of Surgical Syndactyly Repair in Harlequin Ichthyosis
Authors: Kahan Elias H. , Temple Brian , Carr Logan , Zellner Elizabeth
Published: October 2022

Harlequin ichthyosis (HI) is a rare congenital skin disorder caused by irregular epidermal differentiation. Syndactyly in HI is associated with thick hyperkeratotic skin flexion and angulation deformity of the hand and fingers resulting in limited function of the upper extremity. Traditional syndactyly release is limited as full-thickness skin grafts typically used in reconstruction are composed of diseased skin and require donor sites in a patient predisposed for adverse wound healing. This case report is a follow-up to a previous viewpoint written about digital escharotomies in a newborn with HI and outlines a second and fourth webspace syndactyly release with a dermal substitute. Despite early evidence of adequate release and improved hand function, recurrence of syndactyly was observed within 4 months of surgical release. Our experience described within this case report may suggest the limitations and possible alternatives of surgical release of syndactyly in the HI population.
Large Mammary Paget Disease without Underlying Breast Carcinoma
Authors: Chirappapha Prakasit , Adireklarpwong Lakkana , Sornmayura Pattana , Lertsithichai Panuwat , Rattadilok Chayanoot
Published: October 2022

Mammary Paget disease is an uncommon type of breast cancer. Redness, scaling, and thickness involving the nipple and areola are common clinical symptoms. Invasive breast cancer was found in nearly 90% of these patients. Only a few cases of mammary Paget disease with no underlying cancer have been described, with a better prognosis. Treatment options include wide excision or mastectomy. However, if the lesion is very extensive, breast reconstruction may be required. We reported a rare case of extensive Paget disease in a 65-year-old woman who had a 7-year history of a 14 × 19 cm progressively enlarging erythematous scaling lesion that covered her entire left breast. No evidence of related malignancy or metastatic lesion was seen. A left mastectomy with sentinel lymph node biopsy and immediate pedicled transverse rectus abdominis myocutaneous flap reconstruction was chosen. There is uncertainty about axillary node metastasis since multiple enlarged and palpable left axillary lymph nodes were seen. She had axillary lymph node dissection instead. A histological examination confirmed the diagnosis of Paget disease of the nipple in the absence of underlying breast cancer and there was no evidence of axillary lymph node metastasis. This article emphasizes the need to pay close attention to diagnosis, progression, and treatment of the disease.
Aberrant sensorimotor coupling and movement planning in complex regional pain syndrome
Authors: Floegel Mareike , Steinmetz Sebastian , Dimova Violeta , Kell Christian A. , Birklein Frank
Published: October 2022

Complex regional pain syndrome (CRPS) is characterized by inflammation and a failure of multimodal signal integration in the central nervous system (CNS). Central nervous system reorganization might account for sensory deficits, pain, and motor symptoms in CRPS, but it is not clear how motor control is affected by CNS mechanisms. The present study characterized the motor performance and related cortical activity of 16 CRPS patients and 16 control participants during the planning of visually guided unimanual grips, in patients with either the unaffected left or the affected right hand, and investigated resting-state sensorimotor coupling in MRI. Patients started isometric movements further in advance of the “go” cue and earlier than control participants. Even when accounting for this different timing, results showed side-independent overactivation in planning-related sensorimotor regions in CRPS during manual grips and increased functional coupling between those regions at rest. Fear of movement or individual pain scores contributed only marginally to the observed effects. The study suggests that changes in planning-related sensorimotor CNS regions may explain difficulties with force exertion and motor control in CRPS.

Perspective: Functional changes in motor planning-related brain regions might indicate that feedback-enhanced functional motor training may be effective for CRPS rehabilitation.
Subcutaneous Emphysema Risk Following Indwelling Pleural Catheter Insertion During Rigid Local Anesthetic Thoracoscopy
Authors: Ajmal Syed , Stockbridge Alison , Johnstone Sarah , Tufail Muhammad , Panchal Rakesh K.
Published: October 2022

Background:

Local anesthetic thoracoscopy (LAT) is important in the diagnosis of unilateral pleural effusions. Indwelling pleural catheters (IPC) can be inserted during LAT if a nonexpandable lung is suspected. Subcutaneous emphysema (SCE) is a known complication and is associated with increased morbidity and length of stay. It is unclear however if the incidence of SCE is affected if IPC is inserted through a separate incision to the LAT port. We aim to establish the incidence and grading of SCE when IPC is inserted during LAT and to determine if the site of IPC placement influences this.

Methods:

Retrospective analysis of LAT electronic records and radiology images over 8 years in a University Hospital. The incidence of SCE was assessed during admission and follow-up with the severity of SCE graded 0 to 4 (0 none; 1 at IPC site; 2 ipsilateral chest wall; 3 ipsilateral neck; 4 contralateral chest wall).

Results:

55 combined LAT and IPC procedures were performed. In 28 patients the IPC was inserted through the LAT port and in 27 the IPC was inserted in a separate intercostal space (ICS) to the LAT port. On day zero, the incidence of any SCE was lower if the IPC was inserted using a separate ICS to the LAT port compared with the same site as the LAT port(P=0.01). This was similarly reduced on discharge chest radiographs and subsequent follow-up.

Conclusion:

IPC insertion at LAT using a separate ICS to the LAT port is associated with a reduction in the incidence of SCE during admission and follow-up.
The current therapeutic approach for anaemia after kidney transplant
Authors: Nissaisorakarn Voravech , Nissaisorakarn Pitchaphon , Kantachuvesiri Surasak
Published: October 2022

Purpose of review

Anaemia after kidney transplantation is a common finding with no uniform management guideline. Most approaches are derived from the chronic kidney disease (CKD) population. Recent advances for the treatment of anaemia in patients with CKD/End stage renal disease include hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHi), a novel class of oral erythropoietin-stimulating agents (ESAs). We present relevant studies of HIF-PHi in the transplant population and its implications on the management of posttransplant anaemia.

Recent findings

Data on HIF-PHi use in the kidney transplant population are promising. Limited data demonstrate a significant increase in haemoglobin, with a comparable safety profile to epoetin. Reported adverse effects include overcorrection and low iron stores.

Current therapeutic approaches to anaemia in the kidney transplant population is mostly derived from the CKD population. More studies are needed on HIF-Phi, a novel class of ESAs that has thus far demonstrated promise in the kidney transplant population.
The COVID‐19 Pandemic and the Prevalence of Childhood Obesity in Turkiye
Authors: Salman Hakan , İssi Irlayici Fatma , Akçam Mustafa
Published: October 2022

Objectives:

To examine the prevalence of overweight and obesity in school‐age children in Isparta Province, Turkiye, during the coronavirus disease 2019 (COVID‐19) pandemic, and to compare the results with those of previous studies conducted in Isparta in 2005, 2009, and 2014.

Methods:

The study was carried out in schools in the city center of Isparta in March 2022, during which the weight and height of students were measured using a scale and stadiometer, and the body mass indices (BMI), BMI percentiles, and z scores were calculated.

Results:

Of the 8871 students assessed, 4547 (51.3%) were female and the mean age of the sample was 11.92 ± 3.42 (6–18.93) years. The prevalence of overweight was 12%, the prevalence of obesity was 14.5%, and the prevalence of overweight + obesity was 26.5%. A comparison of the figures since 2005 revealed the prevalence of overweight to be stable, while the prevalence of obesity and the prevalence of overweight + obesity were found to have witnessed a increase (χ2: 57.01, P < 0.001). The prevalence of obesity was 13% among girls under 11 years of age and 14.3% among girls over 11 years of age; and 18.2% and 12.8% among boys under and over 11 years of age, respectively (χ2: 23.26, P < 0.001). The prevalence of obesity was significantly higher in boys under 11 years of age.

Conclusions:

The prevalence of overweight + obesity was nearly stable in the 3 studies conducted over the 17‐year period, but we witnessed an increase in our most recent study conducted during the pandemic. The prevalence of obesity is significantly higher in boys under 11 years of age.
Autologous Recovery With Chromosomal Abnormalities After Unrelated Umbilical Cord Blood Transplantation With Myeloablative Conditioning in a Case of Pediatric Acute Lymphoblastic Leukemia
Authors: Uchihara Yoshinori , Kato Itaru , Hanaki Ryo , Saida Satoshi , Iwamoto Shotaro , Umeda Katsutsugu , Hiramatsu Hidefumi , Adachi Souichi , Takita Junko
Published: October 2022

Detailed case reports of autologous recovery of hematopoiesis after hematopoietic stem cell transplantation with myeloablative conditioning are scarce. We present a rare case of a 3-year-old male with relapsed KMT2A-rearranged acute lymphoblastic leukemia who experienced autologous recovery following secondary engraftment failure after cord blood transplantation with myeloablative conditioning. Similar to prior reports, we detected unusual chromosomal abnormalities, which differed at each bone marrow examination. He remains alive without relapse of acute lymphoblastic leukemia 8 months after cord blood transplantation. As the rate of recurrence or late occurrence of secondary malignant neoplasm remains unclear, careful follow-up is required, especially in pediatric patients.
Creating an Advanced Practice Registered Nurse Council Within a Regional Hospital Network
Authors: Brown Hayley , Galvez Adeline , Koepke Stephanie , Munsterman Ellen , Rabinovich Anna , Shepherd Stacey
Published: October 2022

This article describes the development of an advanced practice RN (APRN) council in a large hospital network. Despite obstacles, the council was able to demonstrate positive outcomes, which include standardization of the credentialing and onboarding process, productive networking, and an APRN-oriented education fair. The council has been able to guide workplace culture, establish and support vertical and horizontal interprofessional relationships, provide recommendations to relevant leadership boards, and develop standardized procedures.
Pathology of Crooke Cells in the Human Pituitaries: A Timely Review
Authors: Osamura Robert Y. , Inomoto Chie , Tahara Shigeyuki , Oyama Ken-ichi , Matsuno Akira , Teramoto Akira
Published: October 2022

Crooke cell change was first found in the regressed and suppressed corticotroph (adrenocorticotropic hormone–producing) cells, and now is known to occur in pituitary tumors. The tumor cells of this type can be recognized by morphology with immunohistochemistry, and are well known to predict aggressive behavior such as invasion and rare metastases. This is one of the representative neuroendocrine tumors in the pituitary which is now considered to have malignant potential as proposed in the pancreas and gastrointestinal tracts. It is important to emphasize the pituitary tumor pathology such as Crooke cell change for prognostication and appropriate therapies. This review article describes the evolution from the Crooke cells to Crooke cell tumors which is timely along with the Fifth WHO classification 2022 published online.