bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIM2 kinase has a pivotal role in plasmablast generation and plasma cell survival, opening up novel treatment options in myeloma
Authors: Haas Marion , Caron Gersende , Chatonnet Fabrice , Manenti Stéphane , Alaterre Elina , Devin Julie , Delaloy Céline , Bertolin Giulia , Viel Roselyne , Pignarre Amandine , Llamas-Gutierrez Francisco , Marchalot Anne , Decaux Olivier , Tarte Karin , Delpy Laurent , Moreaux Jérôme , Fest Thierry 
Published: February 2022

Abstract
The differentiation of B cells into plasmablasts (PBs) and then plasma cells (PCs) is associated with extensive cell reprogramming and new cell functions. By using specific inhibition strategies (including a novel morpholino RNA antisense approach), we found that early, sustained upregulation of the proviral integrations of Moloney virus 2 (PIM2) kinase is a pivotal event during human B-cell in vitro differentiation and then continues in mature normal and malignant PCs in the bone marrow. In particular, PIM2 sustained the G1/S transition by acting on CDC25A and p27Kip1 and hindering caspase 3–driven apoptosis through BAD phosphorylation and cytoplasmic stabilization of p21Cip1. In PCs, interleukin-6 triggered PIM2 expression, resulting in antiapoptotic effects on which malignant PCs were particularly dependent. In multiple myeloma, pan-PIM and myeloid cell leukemia-1 (MCL1) inhibitors displayed synergistic activity. Our results highlight a cell-autonomous function that links kinase activity to the newly acquired secretion ability of the PBs and the adaptability observed in both normal and malignant PCs. These findings should finally prompt the reconsideration of PIM2 as a therapeutic target in multiple myeloma.
Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome
Authors: Grob Tim , Al Hinai Adil S. A. , Sanders  Mathijs A. , Kavelaars François G. , Rijken Melissa , Gradowska Patrycja L. , Biemond Bart J. , Breems Dimitri A. , Maertens Johan , van Marwijk Kooy Marinus , Pabst Thomas , de Weerdt Okke , Ossenkoppele Gert J. , van de Loosdrecht Arjan A. , Huls Gerwin A. , Cornelissen Jan J. , Beverloo H. Berna , Löwenberg Bob , Jongen-Lavrencic Mojca , Valk Peter J. M. 
Published: February 2022

Abstract
Substantial heterogeneity within mutant TP53 acute myeloid leukemia (AML) and myelodysplastic syndrome with excess of blast (MDS-EB) precludes the exact assessment of prognostic impact for individual patients. We performed in-depth clinical and molecular analysis of mutant TP53 AML and MDS-EB to dissect the molecular characteristics in detail and determine its impact on survival. We performed next-generation sequencing on 2200 AML/MDS-EB specimens and assessed the TP53 mutant allelic status (mono- or bi-allelic), the number of TP53 mutations, mutant TP53 clone size, concurrent mutations, cytogenetics, and mutant TP53 molecular minimal residual disease and studied the associations of these characteristics with overall survival. TP53 mutations were detected in 230 (10.5%) patients with AML/MDS-EB with a median variant allele frequency of 47%. Bi-allelic mutant TP53 status was observed in 174 (76%) patients. Multiple TP53 mutations were found in 49 (21%) patients. Concurrent mutations were detected in 113 (49%) patients. No significant difference in any of the aforementioned molecular characteristics of mutant TP53 was detected between AML and MDS-EB. Patients with mutant TP53 have a poor outcome (2-year overall survival, 12.8%); however, no survival difference between AML and MDS-EB was observed. Importantly, none of the molecular characteristics were significantly associated with survival in mutant TP53 AML/MDS-EB. In most patients, TP53 mutations remained detectable in complete remission by deep sequencing (73%). Detection of residual mutant TP53 was not associated with survival. Mutant TP53 AML and MDS-EB do not differ with respect to molecular characteristics and survival. Therefore, mutant TP53 AML/MDS-EB should be considered a distinct molecular disease entity.
IKK-mediated CYLD phosphorylation and cellular redox activity
Authors: Erol Adnan 
Published: February 2022

AbstractOxidative stress is important in the development of obesity-related nephropathy (ORN). A causal relationship between IKK and ORN via CYLD-mediated inhibition of NRF2 has been described. However, contradictory explanations about the functioning of the mechanisms that will be effective in the pathogenesis require clarification.
Slc25a5 regulates adipogenesis by modulating ERK signaling in OP9 cells
Authors: Zhu Shenglong , Wang Wei , Zhang Jingwei , Ji Siyu , Jing Zhe , Chen Yong Q. 
Published: February 2022

Abstract
Background
A comprehensive understanding of the molecular mechanisms of adipogenesis is a critically important strategy for identifying new targets for obesity intervention.

Methods
Transcriptomic and lipidomic approaches were used to explore the functional genes regulating adipogenic differentiation and their potential mechanism of action in OP9 cells and adipose-derived stem cells. Oil Red O staining was used to detect oil droplets in adipocytes.

Results
RNA sequencing (RNA-seq) showed that Slc25a5 expression was significantly upregulated in adipogenic differentiation. Depletion of Slc25a5 led to the suppressed expression of adipogenesis-related genes, reduced the accumulation of triglycerides, and inhibited PPARγ protein expression. Moreover, the knockdown of Slc25a5 resulted in significant reduction of oxidative phosphorylation (OXPHOS) protein expression (ATP5A1, CQCRC2, and MTCO1) and ATP production. The RNA-seq and real-time quantitative polymerase chain reaction (RT–qPCR) results suggested that adipogenic differentiation is possibly mediated by ERK1/2 phosphorylation, and this hypothesis was confirmed by intervention with PD98059 (an ERK 1/2 inhibitor).

Conclusions
This study indicates that Slc25a5 inhibits adipogenesis and might be a new therapeutic target for the treatment of obesity.
ERp57/PDIA3: new insight
Authors: Chichiarelli Silvia , Altieri Fabio , Paglia Giuliano , Rubini Elisabetta , Minacori Marco , Eufemi Margherita 
Published: February 2022

AbstractThe ERp57/PDIA3 protein is a pleiotropic member of the PDIs family and, although predominantly located in the endoplasmic reticulum (ER), has indeed been found in other cellular compartments, such as the nucleus or the cell membrane. ERp57/PDIA3 is an important research target considering it can be found in various subcellular locations. This protein is involved in many different physiological and pathological processes, and our review describes new data on its functions and summarizes some ligands identified as PDIA3-specific inhibitors.
Analysis of autosomal dominant genes impacted by copy number loss in 24,844 fetuses without structural abnormalities
Authors: Chen Lin , Wang Li , Yin Daishu , Tang Feng , Zeng Yang , Zhu Hongmei , Wang Jing 
Published: February 2022

Abstract
Background
The broad application of high-resolution chromosome detection technology in prenatal diagnosis has identified copy number loss (CNL) involving autosomal dominant (AD) genes in certain fetuses. Exon sequencing of fetuses exhibiting structural anomalies yields diagnostic information in up to 20% of cases. However, there is currently no relevant literature about the genetic origin and pregnancy outcome of CNL involving AD genes in fetuses without structural abnormalities.

Results
This was a prospective study involving pregnant women who underwent amniocentesis for fetal copy number variation sequencing (CNVseq). Detection of parent-of-origin was suggested in cases of samples with CNL involving AD genes and the pregnancy outcome was monitored. Amniotic fluid samples from 24,844 fetuses without structural abnormalities were successfully tested via CNVseq. The results showed that 134 fetuses (0.5%) had small CNL (< 10 Mb) containing AD genes, after excluding microdeletion and microduplication syndrome and polymorphisms. By monitoring the pregnancy outcomes of the 134 fetuses, we found that 104 (77.6%) were good, 13 (9.7%) were adverse, and 17 (12.7%) pregnant women voluntarily chose to terminate pregnancy. Of the 13 fetuses with adverse pregnancy outcomes, only 2 fetuses had phenotypes consistent with those of diseases caused by AD genes involved in CNL.

Conclusions
The overall prognosis for fetuses without family history or structural abnormalities but with small CNL containing AD genes detected during pregnancy is good. The genetic origin, overlap status of established haploinsufficient gene and/or region, size of the CNL, and genetic mode may affect the pathogenicity of the CNL.
Soil pH: a key edaphic factor regulating distribution and functions of bacterial community along vertical soil profiles in red soil of pomelo orchard
Authors: Muneer Muhammad Atif , Hou Wei , Li Jian , Huang Xiaoman , ur Rehman Kayani Masood , Cai Yuanyang , Yang Wenhao , Wu Liangquan , Ji Baoming , Zheng Chaoyuan 
Published: February 2022

Abstract
Background
Soil microbes exist throughout the soil profile and those inhabiting topsoil (0–20 cm) are believed to play a key role in nutrients cycling. However, the majority of the soil microbiology studies have exclusively focused on the distribution of soil microbial communities in the topsoil, and it remains poorly understood through the subsurface soil profile (i.e., 20–40 and 40–60 cm). Here, we examined how the bacterial community composition and functional diversity changes under intensive fertilization across vertical soil profiles [(0–20 cm (RS1), 20–40 cm (RS2), and 40–60 cm (RS3)] in the red soil of pomelo orchard, Pinghe County, Fujian, China.

Results
Bacterial community composition was determined by 16S rRNA gene sequencing and interlinked with edaphic factors, including soil pH, available phosphorous (AP), available nitrogen (AN), and available potassium (AK) to investigate the key edaphic factors that shape the soil bacterial community along with different soil profiles. The most dominant bacterial taxa were Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, Crenarchaeota, and Bacteriodetes. Bacterial richness and diversity was highest in RS1 and declined with increasing soil depth. The distinct distribution patterns of the bacterial community were found across the different soil profiles. Besides, soil pH exhibited a strong influence (pH ˃AP ˃AN) on the bacterial communities under all soil depths. The relative abundance of Proteobacteria, Actinobacteria, Crenarchaeota, and Firmicutes was negatively correlated with soil pH, while Acidobacteria, Chloroflexi, Bacteriodetes, Planctomycetes, and Gemmatimonadetes were positively correlated with soil pH. Co-occurrence network analysis revealed that network topological features were weakened with increasing soil depth, indicating a more stable bacterial community in the RS1. Bacterial functions were estimated using FAPROTAX and the relative abundance of functional bacterial community related to metabolic processes, including C-cycle, N-cycle, and energy production was significantly higher in RS1 compared to RS2 and RS3, and soil pH had a significant effect on these functional microbes.

Conclusions
This study provided the valuable findings regarding the structure and functions of bacterial communities in red soil of pomelo orchards, and highlighted the importance of soil depth and pH in shaping the soil bacterial population, their spatial distribution and ecological functioning. These results suggest the alleviation of soil acidification by adopting integrated management practices to preserve the soil microbial communities for better ecological functioning.
Sepsis due to kidney injury caused by a toothpick: a case report and literature review
Authors: Qi Qi , Chen Lingxin , Kou Guoxian 
Published: February 2022

Abstract
Background
Toothpicks are common foreign bodies which may injure surrounding organs leading to a series of atypical symptoms. We present a rare clinical case that septicemia caused by a toothpick penetrated into the right kidney.

Case presentation
We describe a 51-year-old patient who presented with right-sided backache and hematuresis for 2 days. Blood culture persistently grew Streptococcus gordonii. Ultrasound of the patient’s urinary tract revealed a strong striated echo in the middle of the right kidney. Complete abdominal computed tomography revealed a duodenal foreign body penetrating into the right kidney. The toothpick was removed under endoscopy and hemostasis was given. Antibiotic treatment was upgraded. The patient was recovered and discharged from his stay on the fifteenth day.

Conclusions
Early identification of the etiology of sepsis can effectively alleviate patient’s distress and reduce hospital stay. Clinicians should identify the source of sepsis through a medical history and examination.
Albumin levels predict mortality in sepsis patients with acute kidney injury undergoing continuous renal replacement therapy: a secondary analysis based on a retrospective cohort study
Authors: Sheng Song , Zhang Yan-Hong , Ma Hang-Kun , Huang Ye 
Published: February 2022

AbstractBackgroundAlbumin (ALB) levels are negatively associated with mortality in patients with sepsis. However, among sepsis patients with acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT), there has been no similar study on the correlation between ALB levels and mortality alone. This study tested the hypothesis that ALB levels are negatively associated with mortality among such patients.MethodsWe conducted a secondary analysis of 794 septic patients who were diagnosed with AKI and underwent CRRT in South Korea. For the Kaplan–Meier survival analysis, Cox proportional hazards models were used to study the hypotheses, with adjustments for the pertinent covariables. We also explore the possible nonlinear relationship and conducted sensitivity analyses including subgroup analyses and tests for interactions to investigate the association further. Additionally, ALB was used to construct model and we then compared the performance of ALB with that of APACHE II and SOFA in predicting mortality.ResultsThe ALB level was an independent prognostic factor for death at 28 and 90 days after CRRT initiation (HR = 0.75, 95% CI: 0.62–0.90,P = 0.0024 for death at 28 days andHR = 0.73, 95% CI: 0.63–0.86,P < 0.0001 for death at 90 days). A nonlinear association was not identified between ALB levels and the endpoints. Subgroup analyses and tests for interactions indicated that HCO3and CRP played an interactive role in the association. ROC analysis indicated ALB, SOFA and APACHE-II were separately inadequate for clinical applications.ConclusionA 1 g/dL increase in ALB levels was independently associated with a 25 and 27% decrease in the risk of death at 28 and 90 days, respectively. However, this conclusion needs to be taken with caution as this study has several limitations.
“This is hard to cope with”: the lived experience and coping strategies adopted amongst Australian women with pelvic girdle pain in pregnancy
Authors: Ceprnja Dragana , Chipchase Lucinda , Liamputtong Pranee , Gupta Amitabh 
Published: February 2022

Abstract
Background
Women with pregnancy-related pelvic girdle pain (PPGP) report diminished ability to perform physical activities and experience higher rates of mood disorders, such as anxiety and depression, than pregnant women without PPGP. Despite these physical and psychological impacts, little is known about the lived experiences of PPGP amongst Australian women and the ways in which they cope. Situated within biographical disruption and social support theories, this study sought to gain a conceptual understanding of the experience and impact of PPGP on daily life, and how women cope with this condition during pregnancy.

Methods
A qualitative research design, situated within a phenomenological framework, using individual, semi-structured interviews consisting of open-ended questions was used with a flexible and responsive approach. Purposive sampling of pregnant women attending a single hospital included 20 participants between 14 and 38 weeks gestation, classified with PPGP as per recommended guidelines, with a mean (SD) age of 31.37 (4.16) years. Thematic analysis was performed where interview data was transcribed, coded, grouped into meaningful categories and then constructed into broad themes.

Results
Three themes were identified: 1. a transformed biography; 2. coping strategies; and 3. what women want. The pain experienced created a dramatic change in women’s lives, making the pregnancy difficult to endure. Women utilised social support, such as family, to help them cope with pain, and a self-care approach to maintain a positive mindset and reduce stress. Although a few women received support from healthcare professionals, many reported a lack information on PPGP and limited societal recognition of the condition. Women wanted early education, personalised information and prompt referral to help them cope with PPGP.

Conclusions
Findings from this study highlighted the complexity of living with PPGP as women attempted to deal with the unexpected impact on daily life by seeking support from partners and families, while also struggling with societal expectations. Although women with PPGP used a number of coping strategies, they sought greater support from healthcare professionals to effectively manage PPGP. These findings have important implications for the provision of health care to women living with PPGP.

Trial registration
Australian New Zealand Clinical Trials Registry: ACTRN12618001423202.
Novel multifunctional robotically assisted bipolar instrument for simultaneous radiofrequency sealing and transection: preclinical and single-center experience
Authors: Ibanez Jimenez Cristina , Lath Adrit , Ringold Forrest 
Published: February 2022

Abstract
Background
A novel robotic-assisted bipolar radiofrequency (RF) multifunctional vessel seal-and-transection instrument (SynchroSeal, Intuitive Surgical, Inc., Sunnyvale, CA) has been developed. The objective of the current paper is to describe the design of SynchroSeal based on bench studies, assess the safety of SynchroSeal in ex vivo and in vivo porcine studies, and provide early clinical context.

Methods
SynchroSeal grasping, energy activation time, and jaw temperature were evaluated with those of the Harmonic Ace+7. Data were analyzed with descriptive statistics, with Mann–Whitney for comparisons and statistical significance p < 0.05. Ex vivo and in vivo animal safety assessments of tissue after SynchroSeal use were evaluated for burst pressure, thermal spread, and acute sealing. Last, a single-center analysis of the technical metrics of SynchroSeal and Vessel Sealer Extend (robotically assisted seal-and-transection instrument) in bariatric cases is provided.

Results
Bench studies of SynchroSeal and Harmonic Ace+7 evidenced SynchroSeal’s greater slip resistance force (8.4 ± 1.0 vs. 3.1 ± 0.4 N; p = 0.0002), lower grip pressure (3.0 ± 0.2 vs. 4.2 ± 0.5 kg/cm2; p = 0.0002), faster seal time (1.5 ± 0.4 vs. 11.6 ± 2.5 s; p < 0.0001), lower mean jaw temperature (109.7 ± 7.2 vs. 247.4 ± 8.6 °C; p = 0.0051), and faster cooling to 40 °C (53.6 ± 2.1 vs. 68.0 ± 3.5 s; p = 0.0051). SynchroSeal’s mean burst pressures after seal-and-transection and seal only modes were, respectively, 1169.1 ± 393.1 mmHg and 1159.2 ± 454.6 mmHg. Mean thermal spreads were, respectively, 1.2 ± 0.6 mm and 1.5 ± 0.55 mm. In the chronic animal study, 102 vessels were sealed; at 3 weeks post-procedure, there was no evidence of leakage or adverse events, such as non-target tissue thermal spread or tissue damage. In bariatrics cases, SynchroSeal was activated more frequently per case; however, its mean activation time was significantly shorter than Vessel Sealer Extend. No adverse events were reported for either device.

Conclusions
SynchroSeal’s multifunctional design provides enhanced sealing and transection capabilities with an acceptable safety profile.
Predicting the diagnosis of prostate cancer with a scoring system based on novel biomarkers
Authors: Jethwani Durvesh Lachman , Sivamoorthy Lameena Lalitha , Toh Charng Chee , Malek Rohan 
Published: February 2022

Abstract
Objective
To predict prostate cancer using novel biomarker ratios and create a predictive scoring system.

Materials and methods
Data of a total of 703 patients who consulted Urology Department of Selayang Hospital between January 2013 and December 2017 and underwent prostate biopsy were screened retrospectively. Prostate specific antigen (PSA) levels, prostate volumes (PV), neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), Prostate specific antigen density (PSAD) and histopathology were evaluated.

Results
Ages ranged from 43 to 89 years, divided into 2 groups as per biopsy results; positive for prostate cancer (n = 290, 41.3%) and negative for malignancy (n = 413; 58.7%). Intergroup comparative evaluations were performed. Independent variables with p < 0.001 in the univariate analysis were age, DRE, PV, NLR, PSAD. A scoring system was modelled using NLR < 0.9, PSAD > 0.4, Age > 70 and DRE. A score of 2 or more predicted prostate cancer with a Sensitivity of 83.8% and Specificity of 86.4%.

Conclusions
NLR is shown to be good predictor for prostate cancer its usage in this scoring system affords more disease specificity as compared to PSA alone.
Value of normative belief in intention to use workplace health promotion apps
Authors: Junker Maren , Böhm Markus , Franz Mareike , Fritsch Tobias , Krcmar Helmut 
Published: February 2022

Abstract
Background
Mobile applications (apps) have started to be used for workplace health promotion (WHP). However, the factors that lead to the usage of apps in the workplace from the end-user perspective remain unclear.

Methods
To investigate the research gap, the study evaluates a model for the adoption of WHP apps by combining the theory of planned behavior, the health belief model, and the technology acceptance model. A self-administered questionnaire with validated scales among 354 participants was used to evaluate the proposed model for WHP.

Results
Although the study indicated a limited overall model fit, interesting aspects were derived. In particular, the study demonstrated that normative belief (especially), perceived usefulness, and attitudinal belief play important roles in the intention to use WHP apps.

Conclusion
The study is among the first to validate the theoretical models of mHealth adoption for WHP. Moreover, it shows that not only normative belief but also adjustment to several target groups is a necessary factor to be considered in the development and implementation of an app for WHP.