bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 3 SELENE study: ibrutinib plus BR/R-CHOP in previously treated patients with follicular or marginal zone lymphoma
Authors: Nastoupil Loretta J. , Hess Georg , Pavlovsky Miguel A. , Danielewicz Iwona , Freeman Jane , García-Sancho Alejandro Martin , Glazunova Valeria , Grigg Andrew , Hou Jing-Zhou , Janssens Ann , Kim Seok Jin , Masliak Zvenyslava , McKay Pam , Merli Francesco , Munakata Wataru , Nagai Hirokazu , Özcan Muhit , Preis Meir , Wang Tingyu , Rowe Melissa , Tamegnon Monelle , Qin Rui , Henninger Todd , Curtis Madeliene , Caces Donne Bennett , Thieblemont Catherine , Salles Gilles
Published: September 2023

The phase 3 SELENE study evaluated ibrutinib + chemoimmunotherapy (CIT; bendamustine and rituximab [BR]; or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) for patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Adult patients who had received ≥1 prior line of CIT were randomized 1:1 to oral ibrutinib (560 mg) or placebo daily, plus 6 cycles of BR/R-CHOP. The primary end point was investigator-assessed progression-free survival (PFS). Overall, 403 patients were randomized to ibrutinib + CIT (n = 202) or placebo + CIT (n = 201). Most patients received BR (90.3%) and had FL (86.1%). With a median follow-up of 84 months, median PFS was 40.5 months in the ibrutinib + CIT arm and 23.8 months in the placebo + CIT arm (hazard ratio [HR], 0.806; 95% confidence interval [CI], 0.626-1.037; P = .0922). Median overall survival was not reached in either arm (HR, 0.980; 95% CI, 0.686-1.400). Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 85.6% and 75.4% of patients in the ibrutinib + CIT and placebo + CIT arms, respectively. In each arm, 13 patients had TEAEs leading to death. The addition of ibrutinib to CIT did not significantly improve PFS compared with placebo + CIT. The safety profile was consistent with known profiles of ibrutinib and CIT. This trial was registered at www.clinicaltrials.gov as #NCT01974440.
Prognostic model using 18F-FDG PET radiomics predicts progression-free survival in relapsed/refractory Hodgkin lymphoma
Authors: Driessen Julia , Zwezerijnen Gerben J. C. , Schöder Heiko , Kersten Marie José , Moskowitz Alison J. , Moskowitz Craig H. , Eertink Jakoba J. , Heymans Martijn W. , Boellaard Ronald , Zijlstra Josée M.
Published: September 2023

Investigating prognostic factors in patients with relapsed or primary refractory classical Hodgkin lymphoma (R/R cHL) is essential to optimize risk-adapted treatment strategies. We built a prognostic model using baseline quantitative 18F-fluorodeoxyglucose positron emission tomography (PET) radiomics features and clinical characteristics to predict the progression-free survival (PFS) among patients with R/R cHL treated with salvage chemotherapy followed by autologous stem cell transplantation. Metabolic tumor volume and several novel radiomics dissemination features, representing interlesional differences in distance, volume, and standard uptake value, were extracted from the baseline PET. Machine learning using backward selection and logistic regression were applied to develop and train the model on a total of 113 patients from 2 clinical trials. The model was validated on an independent external cohort of 69 patients. In addition, we validated 4 different PET segmentation methods to calculate radiomics features. We identified a subset of patients at high risk for progression with significant inferior 3-year PFS outcomes of 38.1% vs 88.4% for patients in the low-risk group in the training cohort (P < .001) and 38.5% vs 75.0% in the validation cohort (P = .015), respectively. The overall survival was also significantly better in the low-risk group (P = .022 and P < .001). We provide a formula to calculate a risk score for individual patients based on the model. In conclusion, we developed a prognostic model for PFS combining radiomics and clinical features in a large cohort of patients with R/R cHL. This model calculates a PET-based risk profile and can be applied to develop risk-stratified treatment strategies for patients with R/R cHL. These trials were registered at www.clinicaltrials.gov as #NCT02280993, #NCT00255723, and #NCT01508312.
Potential selection for lipid kinase activity and spermatogenesis in Henan native pig breeds and growth shaping by introgression of European genes
Authors: Qiao Ruimin , Li Xinjian , Madsen Ole , Groenen Martien A. M. , Xu Pan , Wang Kejun , Han Xuelei , Li Gaiying , Li Xiuling , Li Kui
Published: September 2023

Background

China has one third of the worldwide indigenous pig breeds. The Henan province is one of the earliest pig domestication centers of China (about 8000 years ago). However, the precise genetic characteristics of the Henan local pig breeds are still obscure. To understand the origin and the effects of selection on these breeds, we performed various analyses on lineage composition, genetic structure, and detection of selection sweeps and introgression in three of these breeds (Queshan, Nanyang and Huainan) using genotyping data on 125 Queshan, 75 Nanyang, 16 Huainan pigs and 878 individuals from 43 Eurasian pig breeds.

Results

We found no clear evidence of ancestral domestic pig DNA lineage in the Henan local breeds, which have an extremely complicated genetic background. Not only do they share genes with some northern Chinese pig breeds, such as Erhualian, Hetaodaer, and Laiwu, but they also have a high admixture of genes from foreign pig breeds (33–40%). Two striking selection sweeps in small regions of chromosomes 2 and 14 common to the Queshan and Nanyang breeds were identified. The most significant enrichment was for lipid kinase activity (GO:0043550) with the genes FII, AMBRA1, and PIK3IP1. Another interesting 636.35-kb region on chromosome 14 contained a cluster of spermatogenesis genes (OSBP2, GAL3ST1, PLA2G3, LIMK2, and PATZ1), a bisexual sterility gene MORC2, and a fat deposition gene SELENOM. Reproduction and growth genes LRP4, FII, and ARHGAP1 were present in a 238.05-kb region on SSC2 under selection. We also identified five loci associated with body length (P = 0.004) on chromosomes 1 and 12 that were introgressed from foreign pig breeds into the Henan breeds. In addition, the Chinese indigenous pig breeds fell into four main types instead of the previously reported six, among which the Eastern type could be divided into two subgroups.

Conclusions

Admixture of North China, East China and foreign pigs contributed to high genetic diversity of Henan local pigs. Ontology terms associated with lipid kinase activity and spermatogenesis and growth shaping by introgression of European genes in Henan pigs were identified through selective sweep analyses.
An unsupervised deep learning framework for predicting human essential genes from population and functional genomic data
Authors: LaPolice Troy M. , Huang Yi-Fei
Published: September 2023

Background

The ability to accurately predict essential genes intolerant to loss-of-function (LOF) mutations can dramatically improve the identification of disease-associated genes. Recently, there have been numerous computational methods developed to predict human essential genes from population genomic data. While the existing methods are highly predictive of essential genes of long length, they have limited power in pinpointing short essential genes due to the sparsity of polymorphisms in the human genome.

Results

Motivated by the premise that population and functional genomic data may provide complementary evidence for gene essentiality, here we present an evolution-based deep learning model, DeepLOF, to predict essential genes in an unsupervised manner. Unlike previous population genetic methods, DeepLOF utilizes a novel deep learning framework to integrate both population and functional genomic data, allowing us to pinpoint short essential genes that can hardly be predicted from population genomic data alone. Compared with previous methods, DeepLOF shows unmatched performance in predicting ClinGen haploinsufficient genes, mouse essential genes, and essential genes in human cell lines. Notably, at a false positive rate of 5%, DeepLOF detects 50% more ClinGen haploinsufficient genes than previous methods. Furthermore, DeepLOF discovers 109 novel essential genes that are too short to be identified by previous methods.

Conclusion

The predictive power of DeepLOF shows that it is a compelling computational method to aid in the discovery of essential genes.
Identification, characterization and expression profiles of E2 and E3 gene superfamilies during the development of tetrasporophytes in Gracilariopsis lemaneiformis (Rhodophyta)
Authors: Wu Qiong , Yin Jingru , Jiang Min , Zhang Jingyu , Sui Zhenghong
Published: September 2023

E2 ubiquitin conjugating enzymes and E3 ubiquitin ligases play important roles in the growth and development of plants and animals. To date, the systematic analysis of E2 and E3 genes in Rhodophyta is limited. In this study, 14 E2 genes and 51 E3 genes were identified in Gracilariopsis lemaneiformis, an economically important red alga. E2 genes were classified into four classes according to the structure of the conserved domain, UBC. E3 genes were classified into 12 subfamilies according to individual conserved domains. A phylogenetic tree of seven algae species showed that functional differentiation of RING-type E3s was the highest, and the similarity between orthologous genes was high except in Chlamydomonas reinhardtii and Chara braunii. RNA-seq data analysis showed significant differential expression levels of E2 and E3 genes under the life stages of tetraspore formation and release, especially GlUBCN and GlAPC3. According to GO and KEGG analysis of two transcriptomes, GlUBCN and GlAPC3 were involved in ubiquitin-mediated proteolysis, and other subunits of the anaphase promoting complex or cyclosome (APC/C) and its activators GlCDC20 and GlCDH1 were also enriched into this process. The CDH1 and CDC20 in 981 were down-regulated during tetraspores formation and release, with the down-regulation of CDH1 being particularly significant; CDH1 and CDC20 in WLP-1, ZC, and WT were up-regulated during tetraspores formation and release, with CDC20 being more significantly up-regulated. Therefore, GlCDH1, rather than GlCDC20, in ‘981’ might play the leading role in the activation of the APC/C, and GlCDC20 might play the leading role rather than GlCDH1 in strains WLP-1, ZC and wild type. The low fertility of cultivar 981 might be highly correlated with the inactivity of activators CDH1 and CDC20. This study provided a basic and comprehensive understanding of characteristic of E2 and E3 genes in Gp. lemaneiformis and set a foundation for further understanding of E2 ubiquitin conjugating enzymes and E3 ubiquitin ligase in regulating tetrasporophytes development of Gp. lemaneiformis.
Large-scale analysis of sheep rumen metagenome profiles captured by reduced representation sequencing reveals individual profiles are influenced by the environment and genetics of the host
Authors: Hess Melanie K. , Hodgkinson Hannah E. , Hess Andrew S. , Zetouni Larissa , Budel Juliana C. C. , Henry Hannah , Donaldson Alistair , Bilton Timothy P. , van Stijn Tracey C. , Kirk Michelle R. , Dodds Ken G. , Brauning Rudiger , McCulloch Alan F. , Hickey Sharon M. , Johnson Patricia L. , Jonker Arjan , Morton Nickolas , Hendy Shaun , Oddy V. Hutton , Janssen Peter H. , McEwan John C. , Rowe Suzanne J.
Published: September 2023

Background

Producing animal protein while reducing the animal’s impact on the environment, e.g., through improved feed efficiency and lowered methane emissions, has gained interest in recent years. Genetic selection is one possible path to reduce the environmental impact of livestock production, but these traits are difficult and expensive to measure on many animals. The rumen microbiome may serve as a proxy for these traits due to its role in feed digestion. Restriction enzyme-reduced representation sequencing (RE-RRS) is a high-throughput and cost-effective approach to rumen metagenome profiling, but the systematic (e.g., sequencing) and biological factors influencing the resulting reference based (RB) and reference free (RF) profiles need to be explored before widespread industry adoption is possible.

Results

Metagenome profiles were generated by RE-RRS of 4,479 rumen samples collected from 1,708 sheep, and assigned to eight groups based on diet, age, time off feed, and country (New Zealand or Australia) at the time of sample collection. Systematic effects were found to have minimal influence on metagenome profiles. Diet was a major driver of differences between samples, followed by time off feed, then age of the sheep. The RF approach resulted in more reads being assigned per sample and afforded greater resolution when distinguishing between groups than the RB approach. Normalizing relative abundances within the sampling Cohort abolished structures related to age, diet, and time off feed, allowing a clear signal based on methane emissions to be elucidated. Genus-level abundances of rumen microbes showed low-to-moderate heritability and repeatability and were consistent between diets.

Conclusions

Variation in rumen metagenomic profiles was influenced by diet, age, time off feed and genetics. Not accounting for environmental factors may limit the ability to associate the profile with traits of interest. However, these differences can be accounted for by adjusting for Cohort effects, revealing robust biological signals. The abundances of some genera were consistently heritable and repeatable across different environments, suggesting that metagenomic profiles could be used to predict an individual’s future performance, or performance of its offspring, in a range of environments. These results highlight the potential of using rumen metagenomic profiles for selection purposes in a practical, agricultural setting.
Integrative analysis of genome and transcriptome reveal the genetic basis of high temperature tolerance in pleurotus giganteus (Berk. Karun & Hyde)
Authors: Yang Yang , Pian Yongru , Li Jingyi , Xu Lin , Lu Zhu , Dai Yueting , Li Qinfen
Published: September 2023

Background

Pleurotus giganteus is a commonly cultivated mushroom with notable high temperature resistance, making it significant for the growth of the edible fungi industry in the tropics. Despite its practical importance,, the genetic mechanisms underlying its ability to withstand high temperature tolerance remain elusive.

Results

In this study, we performed high-quality genome sequencing of a monokaryon isolated from a thermotolerant strain of P. giganteus. The genome size was found to be 40.11 Mb, comprising 17 contigs and 13,054 protein-coding genes. Notably, some genes related to abiotic stress were identified in genome, such as genes regulating heat shock protein, protein kinase activity and signal transduction. These findings provide valuable insights into the genetic basis of P. giganteus’ high temperature resistance. Furthermore, the phylogenetic tree showed that P. giganteus was more closely related to P. citrinopileatus than other Pleurotus species. The divergence time between Pleurotus and Lentinus was estimated as 153.9 Mya, and they have a divergence time with Panus at 168.3 Mya, which proved the taxonomic status of P. giganteus at the genome level. Additionally, a comparative transcriptome analysis was conducted between mycelia treated with 40 °C heat shock for 18 h (HS) and an untreated control group (CK). Among the 2,614 differentially expressed genes (DEGs), 1,303 genes were up-regulated and 1,311 were down-regulated in the HS group. The enrichment analysis showed that several genes related to abiotic stress, including heat shock protein, DnaJ protein homologue, ubiquitin protease, transcription factors, DNA mismatch repair proteins, and zinc finger proteins, were significantly up-regulated in the HS group. These genes may play important roles in the high temperature adaptation of P. giganteus. Six DEGs were selected according to fourfold expression changes and were validated by qRT-PCR, laying a good foundation for further gene function analysis.

Conclusion

Our study successfully reported a high-quality genome of P. giganteus and identified genes associated with high-temperature tolerance through an integrative analysis of the genome and transcriptome. This study lays a crucial foundation for understanding the high-temperature tolerance mechanism of P. giganteus, providing valuable insights for genetic modification of P. giganteus strains and the development of high-temperature strains for the edible fungus industry, particularly in tropical regions.
Evaluation of the relationship between serum interleukin-1β levels and expression of inflammasome-related genes in patients with COVID-19
Authors: Bagheri-Hosseinabadi Zahra , Shamsizadeh Ali , Bahrehmand Fatemeh , Abbasifard Mitra
Published: September 2023

Background

Inflammasomes are a group of molecules that are strongly involved in causing inflammation. This study aimed to evaluate the expression of NLR family pyrin domain containing 1 (NLRP1), NLRP3, and Apoptosis-associated speck-like protein containing a CARD (ASC) as well as their association with serum level of interleukin (IL)-1β in patients with coronavirus disease 2019 (COVID-19).

Methods

Thirty COVID-19 patients and 30 healthy subjects (HS) were recruited. Peripheral blood specimens were collected from subjects to assess NLRP1, NLRP3, and ASC gene expression by Real time-PCR technique. Serum levels of IL-1β were also measured via the enzyme-linked immunosorbent assay (ELISA).

Results

The findings showed no significant differences in serum IL-1β level between COVID-19 patients and the HS group. mRNA expression of ASC (P = 0.008) and NLRP1 (P = 0.03) gene had a significant increase in COVID-19 patients compared to HS, while there was no significant increase in the expression of NLRP3 between the studied group. There were significant correlations between patient’s data and expression levels of NLRP1, NLRP3, IL-1β, and ACS.

Conclusions

NLRP1 and ASC may have a more critical role in the generation of the active form of IL-1β in COVID-19 patients compared to NLRP3. However, serum levels of IL-1β in patients did not show a significant increase, which may be due to the patient’s condition and the application of virus escape mechanisms through impaired NLRP3 expression and its malfunction.
Detection of hemolytic Shiga toxin-producing Escherichia coli in fresh vegetables and efficiency of phytogenically synthesized silver nanoparticles by Syzygium aromaticum extract and gamma radiation against isolated pathogens
Authors: El-Bastawisy Hanan S. , El-Sayyad Gharieb S. , Abu Safe Feriala A.
Published: September 2023

Background

Shiga toxin-producing E. coli (STEC) is a major cause of foodborne diseases accompanied by several clinical illnesses in humans. This research aimed to isolate, identify, and combat STEC using novel alternative treatments, researchers have lately investigated using plant extract to produce nanoparticles in an environmentally acceptable way. At various gamma-ray doses, gamma irradiation is used to optimize the conditions for the biogenically synthesized silver nanoparticles (Ag NPs) using an aqueous extract of clove as a reducing and stabilizing agent.

Methods

On a specific medium, 120 vegetable samples were screened to isolate STEC and molecularly identified using real-time PCR. Moreover, the antibacterial and antibiofilm activities of biogenically synthesized Ag NPs against the isolated STEC were examined.

Results

Twenty-five out of 120 samples of eight types of fresh vegetables tested positive for E. coli, as confirmed by 16S rRNA, of which three were positive for the presence of Stx-coding genes, and six were partially hemolytic. Seven antibiotic disks were used to determine antibiotic susceptibility; the results indicated that isolate STX2EC had the highest antibiotic resistance. The results demonstrated that Ag NPs were highly effective against the STEC isolates, particularly the isolate with the highest drug resistance, with inhibition zones recorded as 19 mm for STX2EC, 11 mm for STX1EC1, and 10 mm for STX1EC2 at a concentration of 108 µg/mL. MICs of the isolates STX1EC1, and STX1EC2 were 13.5 µg/mL whereas it was detected as 6.75 µg/mL for STX2EC. The percentages of biofilm inhibition for STX1EC2, STX1EC1, and STX2EC, were 78.7%, 76.9%, and 71.19%, respectively.

Conclusion

These findings suggest that the biogenic Ag NPs can be utilized as a new promising antibacterial agent to combat biofouling on surfaces.
Isolation and characterization of glutathione S-transferase genes and their transcripts in Saccharina japonica (Laminariales, Phaeophyceae) during development and under abiotic stress
Authors: Lu Chang , Zhang Pengyan , Li Shuang , Cheng Mengzhen , Duan Delin
Published: September 2023

Background

Glutathione S-transferase (GST) is a crucial enzyme for metabolism, detoxification, and stress resistance in organisms. Many GSTs have been identified in seaweeds, but the isolation and functional analysis of GSTs in Saccharina japonica have not been completed.

Result

In this study, a total of 32 SjGST genes, localized on 10 scaffolds and 6 contigs, were identified and categorized into three groups. Most of these SjGSTs were presumed to be distributed in the cytoplasm. Tandem duplication had a significant influence on the expansion of the SjGST gene family. Functional analysis of cis-acting elements in the promoter regions demonstrated that SjGSTs enhance the stress resistance of the kelp. Quantitative real-time PCR tests confirmed that SjGSTs positively influence S. japonica sporophytes under stress from low salinity, drought, and high temperature. Recombinant yeast tests further affirmed the role of SjGSTs in stress resistance; SjGSTs improved the growth rate of recombinant yeast under 1.5 M NaCl or 8 mM H2O2. Analysis of biochemical parameters indicated that the optimum temperatures for SjGST20 and SjGST22 were 20 °C, and the optimum pH values were 7.0 and 8.0 for SjGST20 and SjGST22, respectively. The Km values for the substrate 1-chloro-2,4-dinitrobenzene (CDNB) were 2.706 mM and 0.674 mM and were 6.146 mM and 3.559 mM for the substrate glutathione (GSH) for SjGST20 and SjGST22, respectively.

Conclusion

SjGSTs are important stress resistant genes in S. japonica. This research results will enhance our understanding the function of GSTs in brown seaweeds, and explained its functional roles in stress resistance in marine environments.
Cytological observation and RNA-seq analysis reveal novel miRNAs high expression associated with the pollen fertility of neo-tetraploid rice
Authors: Li Xiang , Huang Xu , Wen Minsi , Yin Wei , Chen Yuanmou , Liu Yuanlong , Liu Xiangdong
Published: September 2023

Background

Neo-tetraploid rice lines exhibit high fertility and strong heterosis and harbor novel specific alleles, which are useful germplasm for polyploid rice breeding. However, the mechanism of the fertility associated with miRNAs remains unknown. In this study, a neo-tetraploid rice line, termed Huaduo21 (H21), was used. Cytological observation and RNA-sequencing were employed to identify the fertility-related miRNAs in neo-tetraploid rice.

Results

H21 showed high pollen fertility (88.08%), a lower percentage of the pollen mother cell (PMC) abnormalities, and lower abnormalities during double fertilization and embryogenesis compared with autotetraploid rice. A total of 166 non-additive miRNAs and 3108 non-additive genes were detected between H21 and its parents. GO and KEGG analysis of non-additive genes revealed significant enrichments in the DNA replication, Chromosome and associated proteins, and Replication and repair pathways. Comprehensive multi-omics analysis identified 32 pairs of miRNA/target that were associated with the fertility in H21. Of these, osa-miR408-3p and osa-miR528-5p displayed high expression patterns, targeted the phytocyanin genes, and were associated with high pollen fertility. Suppression of osa-miR528-5p in Huaduo1 resulted in a low seed set and a decrease in the number of grains. Moreover, transgenic analysis implied that osa-MIR397b-p3, osa-miR5492, and osa-MIR5495-p5 might participate in the fertility of H21.

Conclusion

Taken together, the regulation network of fertility-related miRNAs-targets pairs might contribute to the high seed setting in neo-tetraploid rice. These findings enhance our understanding of the regulatory mechanisms of pollen fertility associated with miRNAs in neo-tetraploid rice.
Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain
Authors: He Ren , Li Xiaohan , Zhang Silun , Liu Yuqiang , Xue Qingsheng , Luo Yan , Yu Buwei , Li Xiongjuan , Liu Zhiheng
Published: September 2023

Background

Dexamethasone (Dexa) has been recently found to exert an analgesic effect, whose action is closely related to IL-8. However, whether dexamethasone induces antinociception via glycolysis and mitochondria-related pathways is still unclear.

Methods

Right hind paw inflammatory pain in mice was induced by intraplantar injection of Freund’s Complete Adjuvant (FCA). Von Frey test was then used to measure the paw withdrawal threshold. The detection of glycolysis and mitochondrial pathway-related proteins and IL-8 were determined by Western blot and ELISA. The potential interaction between Dexa and fructose-1,6-bisphosphate (FBP, a PKM2 activator) was examined by simulation predictions using molecular docking.

Results

Intrathecal administration of Dexa (20 µg/20 µL) had an obvious analgesic effect in FCA-treated mice, which was counteracted by the glycolysis inhibitor 2-deoxyglucose (2-DG, 5 mg/20 µL) or the mitochondria-related pathway inhibitor oligomycin complex (Oligo, 5 µg/20 µL). In the glycolysis pathway, Dexa decreased GLUT3 and had no impact on HIF-1α expression during FCA-induced inflammation. Additionally, Dexa further increased the PKM2 level, accompanied by the formation of hydrogen bonds between Dexa and the PKM2 activator fructose-1,6-bisphosphate (FBP). In the mitochondrial pathway, Dexa downregulated the expression of Mfn2 protein but not the PGC-1α and SIRT-1 levels in the spinal cord. Moreover, both 2-DG and Oligo decreased Mfn2 expression. Finally, IL-8 level was reduced by the single or combined administration of Dexa, 2-DG, and Oligo.

Conclusion

Dexa attenuated IL-8 expression via glycolysis and mitochondrial pathway-related proteins, thus mediating the analgesic effect during inflammatory pain.
Supine transfer test-induced changes in cardiac index predict fluid responsiveness in patients without intra-abdominal hypertension
Authors: Zhao Zhiyong , Zhang Zhongwei , Liu Jing , Xia Zhili , Xing Qian , Zhang Yaodong , Zheng Yijun , Shen Lihua , Lin Qionghua , Gu Danyan , Wang Pengmei , Zhang Shan , Li Fangfang , Zhu Biao
Published: September 2023

Background

The reversible maneuver that mimics the fluid challenge is a widely used test for evaluating volume responsiveness. However, passive leg raising (PLR) does have certain limitations. The aim of the study is to determine whether the supine transfer test could predict fluid responsiveness in adult patients with acute circulatory failure who do not have intra-abdominal hypertension, by measuring changes in cardiac index (CI).

Methods

Single-center, prospective clinical study in a 25-bed surgery intensive care unit at the Fudan University Shanghai Cancer Center. Thirty-four patients who presented with acute circulatory failure and were scheduled for fluid therapy. Every patient underwent supine transfer test and fluid challenge with 500 mL saline for 15–30 min. There were four sequential steps in the protocol: (1) baseline-1: a semi-recumbent position with the head of the bed raised to 45°; (2) supine transfer test: patients were transferred from the 45° semi-recumbent position to the strict supine position; (3) baseline-2: return to baseline-1 position; and (4) fluid challenge: administration of 500 mL saline for 15–30 min. Hemodynamic parameters were recorded at each step with arterial pulse contour analysis (ProAQT/Pulsioflex). A fluid responder was defined as an increase in CI ≥ 15% after fluid challenge. The receiver operating characteristic curve and gray zone were defined for CI.

Results

Seventeen patients were fluid challenge. The r value of the linear correlations was 0.73 between the supine transfer test- and fluid challenge-induced relative CI changes. The relative changes in CI induced by supine transfer in predicting fluid responsiveness had an area under the receiver operating characteristic curve of 0.88 (95% confidence interval 0.72–0.97) and predicted a fluid responder with 76.5% (95% confidence interval 50.1–93.2) sensitivity and 88.2% (95% confidence interval 63.6–98.5) specificity, at a best threshold of 5.5%. Nineteen (55%) patients were in the gray zone (CI ranging from -3 and 8 L/min/m2).

Conclusion

The supine transfer test can potentially assist in detecting fluid responsiveness in patients with acute circulatory failure without intra-abdominal hypertension. Nevertheless, the small threshold and the 55% gray zone were noteworthy limitation.

Trial registration

Predicting fluid responsiveness with supine transition test (ChiCTR2200058264). Registered 2022–04-04 and last refreshed on 2023–03-26, https://www.chictr.org.cn/showproj.html?proj=166175.
Assoication between self-reported sleep duration, physcial activity and the risk of all cause and cardiovascular diseases mortality from the NHANES database
Authors: Wang Wenjie , Yang Jiaxin , Wang Kexin , Niu Jialong , Wang Jiang , Luo Zhi , Liu Hong , Chen Xiaoli , Ge Hailong
Published: September 2023

Objective

The purpose of this study was to investigate the combined effect of self-reported sleep durations and physical activity (PA) on all cause and cardiovascular diseases mortality.

Methods

Twenty-nine thousand fifty-eight participants (48.5% male, median age 49 years) from the National Health and Nutrition Examination Survey cycles 2007 to 2016 were included. We classified sleep duration into five categories (< 5.5 h/d,5.5–6.5 h/d,6.5–7.5 h/d,7.5–8.5 h/d, ≥ 8.5 h/d) and classified PA levels into three groups (high, medium and low). PA information and self-reported sleep duration were obtained by questionnaire. We derived 15 PA–sleep duration combinations. The primary endpoint was all-cause mortality, and the major secondary endpoint was cardiovascular diseases (CVD) mortality as of December 2022.

Results

Median follow-up was 91 months. Compared with standard sleep duration (6.5–7.5 h/d), both shorter (< 5.5 h/d) and longer (≥ 8.5 h/d) sleep durations increased risks of all-cause mortality and CVD mortality in low PA. The deleterious associations of sleep duration with all outcomes was amplified by lower PA. There was no significant reduction in CVD mortality risk associated with increased physical activity during short sleep duration (< 6.5 h/d). During standard sleep, low PA significantly increased CVD mortality risk. At medium physical activity, both short and long sleep increased cardiovascular mortality. It was also found that sleep duration (≥ 8.5 h/d) was associated with a increase in all-cause and cardiovascular mortality at both low and high PA levels.

Conclusions

This study suggested that low PA significantly increased the association of self-reported long and short sleep durations with all-cause and CVD mortality. All cause mortality appears to benefit from medium physical activity, while medium PA did not. Physical activity did not significantly reduce the risk of CVD mortality.
Nomogram predicts risk of perineural invasion based on serum biomarkers for pancreatic cancer
Authors: Zou Wenbo , Wu Dingguo , Wu Yunyang , Zhou Kuiping , Lian Yuanshu , Chang Gengyun , Feng Yuze , Liang Jifeng , Huang Gao
Published: September 2023

Background

Pancreatic cancer is a fatal tumor, and the status of perineural invasion (PNI) of pancreatic cancer was positively related to poor prognosis including overall survival and recurrence-free survival. This study aims to develop and validate a predictive model based on serum biomarkers to accurately predict the perineural invasion.

Materials and methods

The patients from No.924 Hospital of PLA Joint Logistic Support Force were included. The predictive model was developed in the training cohort using logistic regression analysis, and then tested in the validation cohort. The area under curve (AUC), calibration curves and decision curve analysis were used to validate the predictive accuracy and clinical benefits of nomogram.

Results

A nomogram was developed using preoperative total bilirubin, preoperative blood glucose, preoperative CA19-9. It achieved good AUC values of 0.753 and 0.737 in predicting PNI in training and validation cohorts, respectively. Calibration curves showed nomogram had good uniformity of the practical probability of PNI. Decision curve analyses revealed that the nomogram provided higher diagnostic accuracy and superior net benefit compared to single indicators.

Conclusion

The present study constructed and validate a novel nomogram predicted the PNI of resectable PHAC patients with high stability and accuracy. Besides, it could better screen high-risk probability of PNI in these patients, and optimize treatment decision-making.
A focus groups study of staff team experiences of providing interdisciplinary rehabilitation for people with dementia and their caregivers—a co-creative journey
Authors: Lindelöf Nina , Nilsson Ingeborg , Littbrand Håkan , Gustafson Yngve , Olofsson Birgitta , Fjellman-Wiklund Anncristine
Published: September 2023

Background

The World Health Organization claims that rehabilitation is important to meet the needs of persons with dementia. Rehabilitation programmes, however, are not routinely available. Person-centred, multidimensional, and interdisciplinary rehabilitation can increase the opportunities for older adults with dementia and their informal primary caregivers to continue to live an active life and participate in society. To our knowledge, staff team experiences of such rehabilitation programmes, involving older adults with dementia and their informal caregivers has not been previously explored.

Methods

The aim of this qualitative focus group study was to explore the experiences of a comprehensive staff team providing person-centred multidimensional, interdisciplinary rehabilitation to community-dwelling older adults with dementia, including education and support for informal primary caregivers. The 13 staff team members comprised 10 professions who, during a 16-week intervention period, provided individualised interventions while involving the rehabilitation participants. After the rehabilitation period the staff team members were divided in two focus groups who met on three occasions each (in total six focus groups) and discussed their experiences. The Grounded Theory method was used for data collection and analysis.

Results

The analysis resulted in four categories: Achieving involvement in rehabilitation is challenging, Considering various realities by acting as a link, Offering time and continuity create added value, and Creating a holistic view through knowledge exchange, and the core category: Refining a co-creative process towards making a difference. The core category resembles the collaboration that the staff had within their teams, which included participants with dementia and caregivers, and with the goal that the intervention should make a difference for the participants. This was conducted with flexibility in a collaborative and creative process.

Conclusions

The staff team perceived that by working in comprehensive teams they could provide individualised rehabilitation in creative collaboration with the participants through interaction, knowledge exchange, time and continuity, coordination and flexibility, and a holistic view. Challenges to overcome were the involvement of the person with dementia in goal setting and the mediating role of the staff team members. The staff pointed out that by refinement they could achieve well-functioning, competence-enhancing and timesaving teamwork.
Value of the short physical performance battery (SPPB) in predicting fall and fall-induced injury among old Chinese adults
Authors: Li Weiqiang , Rao Zhenzhen , Fu Yanhong , Schwebel David C. , Li Li , Ning Peishan , Huang Jiaqi , Hu Guoqing
Published: September 2023

Background

The short physical performance battery (SPPB) is an easy-to-use tool for fall risk prediction, but its predictive value for falls and fall-induced injuries among community dwellers has not been examined through a large-sample longitudinal study.

Methods

We analyzed five-round follow-up data (2, 3, 4, 5, 7 years) of the China Health and Retirement Longitudinal Study (CHARLS) (2011–2018). Data concerning falls and fall-induced injuries during multi-round follow-ups were collected through participant self-report. The Cochran-Armitage trend test examined trends in fall incidence rate across SPPB performance levels. Multivariable logistic regression and negative binomial regression models examined associations between SPPB performance and subsequent fall and fall-induced injury. The goodness-of-fit and area under the receiver operating curve (AUC) were used together to quantify the value of the SPPB in predicting fall and fall-induced injury among community-dwelling older adults.

Results

The CHARLS study included 9279, 6153, 4142, 4148, and 3583 eligible adults aged 60 years and older in the five included follow-up time periods. SPPB performance was associated with fall and fall-induced injury in two and three of the five follow-up time periods, respectively (P < 0.05). The goodness-of-fit for all predictive models was poor, with both Cox-Snell R2 and Nagelkerke R2 under 0.10 and AUCs of 0.53–0.57 when using only SPPB as a predictor and with both Cox-Snell R2 and Nagelkerke R2 lower than 0.12 and AUCs of 0.61–0.67 when using SPPB, demographic variables, and self-reported health conditions as predictors together. Sex and age-specific analyses displayed highly similar results.

Conclusions

Neither use of SPPB alone nor SPPB together with demographic variables and self-reported health conditions appears to offer good predictive performance for falls or fall-induced injuries among community-dwelling older Chinese adults.
BK viraemia as a cause of anaemia in after ABO-incompatible liver transplant: a case report
Authors: McMullen Lucy , Khoo Liane , Anderson Lyndal , Strasser Simone , Gracey David M
Published: September 2023

Background

While anaemia following liver transplant is common, anaemia in the context of BK viraemia is not a commonly recognised phenomenon.

Case presentation

We present the case of 59-year old gentleman with severe anaemia in the context of BK viraemia and nephropathy following ABO incompatible liver transplant. Severity of anaemia appeared to correlate with high titres of BK virus in the serum. Bone marrow biopsy revealed hypocellular marrow with normal cytogenetics. Anaemia improved with treatment with cidofovir, intravenous immunoglobulin, reduction in immunosuppression and erythropoietin stimulating agent.

Conclusion

To our knowledge, this is the first case of anaemia post liver transplant contributed to by BK viraemia.
Unsupervised registration of 3D knee implant components to biplanar X-ray images
Authors: Nguyen Dac Cong Tai , Benameur Said , Mignotte Max , Lavoie Frédéric
Published: September 2023

Background

Registration of three-dimensional (3D) knee implant components to radiographic images provides the 3D position of the implants which aids to analyze the component alignment after total knee arthroplasty.

Methods

We present an automatic 3D to two-dimensional (2D) registration using biplanar radiographic images based on a hybrid similarity measure integrating region and edge-based information. More precisely, this measure is herein defined as a weighted combination of an edge potential field-based similarity, which represents the relation between the external contours of the component projections and an edge potential field estimated on the two radiographic images, and an object specificity property, which is based on the distinction of the region-label inside and outside of the object.

Results

The accuracy of our 3D/2D registration algorithm was assessed on a sample of 64 components (32 femoral components and 32 tibial components). In our tests, we obtained an average of the root mean square error (RMSE) of 0.18 mm, which is significantly lower than that of both single similarity methods, supporting our hypothesis of better stability and accuracy with the proposed approach.

Conclusion

Our method, which provides six accurate registration parameters (three rotations and three translations) without requiring any fiducial markers, makes it possible to perform the important analyses on the rotational alignment of the femoral and tibial components on a large number of cases. In addition, this method can be extended to register other implants or bones.
Albumin redox state of maintenance haemodialysis patients is positively altered after treatment
Authors: Boss Kristina , Paar Margret , Waterstradt Katja , Schnurr Kerstin , Ickerott Philipp , Wieneke Ulrike , Spitthöver Ralf , Oettl Karl , Kribben Andreas
Published: September 2023

Background and Aim

Maintenance haemodialysis patients have increased morbidity and mortality which is mainly driven by an elevated inflammation level due to the uraemic milieu. A major part of this increased inflammation level is the degree of oxidative stress which can be assessed by albumin redox state (ARS). Aim of this study was to evaluate how the ARS is affected by a haemodialysis treatment and different dialyzer properties.

Methods

ARS was determined before and after haemodialysis treatment by fractionating it into reduced human mercaptalbumin (HMA), reversibly oxidized human non-mercaptalbumin 1 (HNA-1), and irreversibly oxidized human non-mercaptalbumin 2 (HNA-2) by high-performance liquid chromatography. In healthy individuals, albumin circulates in the following proportions: HMA 70–80%, HNA-1 20–30% and HNA-2 2–5%. High flux (FX 100 [Fresenius Medical Care], BG 1.8 [Toray], Xevonta Hi 18 [B. Braun], CTA-2000 [Kawasumi]) and low flux FX10 [Fresenius Medical Care] dialyzers were used.

Results

58 patients (59% male, median age 68 years, median time on haemodialysis 32 month) were included in the study. Before haemodialysis treatment, HMA (median 55.9%, IQR 50.1–61.2%) was substantially lower than in healthy individuals. Accordingly, oxidized albumin fractions were above the level of healthy individuals (median HNA-1 38.5%, IQR 33.3–43.2%; median HNA-2 5.8%, IQR 5.1–6.7%). Before haemodialysis treatment HMA was significantly higher in patients usually treated with high flux membranes (p < 0.01). After haemodialysis treatment there was a significant increase of HMA and a decrease of HNA-1 and HNA-2 (p < 0.01). These effects were more pronounced in patients treated with high flux dialyzers (p < 0.01). There were no differences of ARS alteration with regard to the dialyzer´s sterilization mode or the presence of diabetes.

Conclusion

The study confirms that the ARS is positively altered by haemodialysis and shows for the first time that this effect depends on dialyzer properties.
Efficacy of midwife-led role orientation of birth companions on maternal satisfaction and birth outcomes: a randomized control trial in Uganda
Authors: Wanyenze Eva Wodeya , Nalwadda Gorrette K. , Tumwesigye Nazarius Mbona , Byamugisha Josaphat K.
Published: September 2023

Background

The World Health Organization recommends birth companionship for all women in labor. There is insufficient evidence on birth companionship in low-income settings and it is not clear if role orientation impacts effectiveness. The aim of this study was to assess the efficacy of midwife-led role orientation of birth companions of on maternal satisfaction and birth outcomes in a sub-region in Uganda.

Methods

A stepped wedge cluster randomized trial conducted (control n = 240), intervention n = 235) from 4 clusters. Women who had a birth companion, in spontaneously established labor and, expecting a vaginal delivery were eligible. The intervention was “midwife-provided orientation of birth companions”. The admitting midwife provided an orientation session for the birth companion on supportive labor techniques. The primary outcome was the chance of having a spontaneous vaginal delivery. Assessors were not blinded. Independent t-test and Chi-Square tests were used to assess the differences by study period.

Results

Mean maternal satisfaction rate was significantly higher in the intervention period compared to the control period (P > 0.001). High maternal satisfaction levels were noted among the women who were; at the regional referral hospital, younger, first-time mothers, and unmarried (P < 0.001). Satisfaction with pain management was rated lowest across study periods. Satisfaction with humaneness was rated highest with a higher score in the intervention period (93%) than the control (79.5%). There were no statistically significant differences in the mode of delivery, need to augment labor, length of labor and Apgar scores.

Conclusion

Midwife-led role orientation of birth companions increased maternal satisfaction. Nevertheless, no significant effect was noted in the mode of delivery, length of labor, Apgar score, and need to augment labor. Findings could inform the integration of birth companions in the admission process of the woman in labor in similar settings.

Trial registration number

NCT04771325.
Expression signature and prognostic value of CREC gene family in human colorectal cancer
Authors: Ning Junya , Liu Min , Shen Jing , Wang Deping , Gao Lijuan , Li Huiyu , Cao Jimin
Published: September 2023

Colorectal cancer (CRC) is one of the malignant tumors with the highest morbidity and mortality and poor prognosis. The mammalian gene family of Cab45/reticulocalbin/ERC-45/calumenin (CREC) consists of RCN1, RCN2, RCN3, SDF4 and CALU. Although CREC family members have been associated with CRC, the expression pattern, prognostic value, and the role of CREC family in CRC remain unclear. In this study, the expression, survival and biological functions of CREC family in CRC were determined via bioinformatic datasets analysis and experimental verification on clinical CRC specimen. Bioinformatic analysis showed that the expression levels of most CREC family genes were higher in CRC tissues than in normal colorectal tissues. The qPCR and western blot results also revealed that the transcriptional and protein levels of CREC family were elevated in CRC tissues compared with adjacent tissues. Besides, CREC family was significantly correlated with advanced tumor stage and poor prognosis of CRC patients. The expression levels of CREC family had correlations with genomic mutation and methylation, and with the infiltration levels of CD4 + T cells, macrophages, neutrophils, and dendritic cells in the microenvironment of CRC. Functional networks enrichment analysis indicated that the genes of CREC family were essential factors for CRC metastasis. Collectively, these findings suggest that CREC family might be potential targets for the treatment of CRC and candidate prognostic markers for CRC patients.