bluuebunny/crossref_metadata_2025 huggingface dataset:
A pilot investigation of the association between HIV-1 Vpr amino acid sequence diversity and the tryptophan-kynurenine pathway as a potential mechanism for neurocognitive impairment
Authors: Asia Levanco Keegan , Van Vuren Esmé Jansen , Lindeque Zander , Williams Monray Edward
Published: February 2024

HIV infection compromises both the peripheral and central immune systems due to its pathogenic and neuropathogenic features. The mechanisms driving HIV-1 pathogenesis and neuropathogenesis involve a series of events, including metabolic dysregulation. Furthermore, HIV-subtype-specific variations, particularly alterations in the amino acid sequences of key viral proteins, are known to influence the severity of clinical outcomes in people living with HIV. However, the impact of amino acid sequence variations in specific viral proteins, such as Viral protein R (Vpr), on metabolites within the Tryptophan (Trp)-kynurenine (Kyn) pathway in people living with HIV remains unclear. Our research aimed to explore the relationship between variations in the Vpr amino acid sequence (specifically at positions 22, 41, 45, and 55, as these have been previously linked to neurocognitive function) and peripheral Trp-Kyn metabolites. Additionally, we sought to clarify the systems biology of Vpr sequence variation by examining the link between Trp-Kyn metabolism and peripheral inflammation, as a neuropathogenic mechanism. In this preliminary study, we analyzed a unique cohort of thirty-two (n = 32) South African cART naïve people living with HIV. We employed Sanger sequencing to ascertain blood-derived Vpr amino acid sequence variations and a targeted LC-MS/MS metabolomics platform to assess Trp-Kyn metabolites, such as Trp, Kyn, kynurenic acid (KA), and quinolinic acid (QUIN). Particle-enhanced turbidimetric assay and Enzyme-linked immunosorbent assays were used to measure immune markers, hsCRP, IL-6, suPAR, NGAL and sCD163. After applying Bonferroni corrections (p =.05/3) and adjusting for covariates (age and sex), only the Vpr G41 and A55 groups was nearing significance for higher levels of QUIN compared to the Vpr S41 and T55 groups, respectively (all p =.023). Multiple regression results revealed that Vpr amino acid variations at position 41 (adj R2 = 0.049, β = 0.505; p =.023), and 55 (adj R2 = 0.126, β = 0.444; p =.023) displayed significant associations with QUIN after adjusting for age and sex. Lastly, the higher QUIN levels observed in the Vpr G41 group were found to be correlated with suPAR (r =.588, p =.005). These results collectively underscore the importance of specific Vpr amino acid substitutions in influencing QUIN and inflammation (specifically suPAR levels), potentially contributing to our understanding of their roles in the pathogenesis and neuropathogenesis of HIV-1.
Incidence and influence factors of venous thromboembolism in traumatic rib fracture patient: a multicenter study
Authors: Zhang Dongsheng , Yang Yi , Yi Yunfeng , Wang Dongbin , Jiang Lei , Huang Hai , Jin Longyu , Meng Hui , Xia Fei , Guo Guangwei
Published: February 2024

Background

This study aimed to determine the incidence and influencing factors of venous thromboembolism (VTE) in patients with traumatic rib fractures.

Methods

The retrospective study analyzed medical records of patients with traumatic rib fractures from 33 hospitals.

Results

The overall incidence of VTE in hospitalized patients with traumatic rib fractures was 8.1%. Patients with isolated traumatic rib fractures had a significantly lower incidence of VTE (4.4%) compared to patients with rib fractures combined with other injuries (12.0%). Multivariate analysis identified the number of rib fractures as an independent risk factor for thrombosis. Surgical stabilization of isolated rib fractures involving three or more ribs was associated with a lower VTE incidence compared to conservative treatment.

Conclusions

Patients with rib fractures have a higher incidence of VTE, positively correlated with the number of rib fractures. However, the occurrence of thrombosis is relatively low in isolated rib fractures. Targeted thromboprophylaxis strategies should be implemented for these patients, and surgical stabilization of rib fractures may be beneficial in reducing the risk of VTE.
Biomechanical comparison of all-polyethylene total knee replacement and its metal-backed equivalent on periprosthetic tibia using the finite element method
Authors: Apostolopoulos Vasileios , Boháč Petr , Marcián Petr , Nachtnebl Luboš , Mahdal Michal , Pazourek Lukáš , Tomáš Tomáš
Published: February 2024

Background

Total knee arthroplasty (TKA) with all-polyethylene tibial (APT) components has shown comparable survivorship and clinical outcomes to that with metal-backed tibial (MBT). Although MBT is more frequently implanted, APT equivalents are considered a low-cost variant for elderly patients. A biomechanical analysis was assumed to be suitable to compare the response of the periprosthetic tibia after implantation of TKA NexGen APT and MBT equivalent.

Methods

A standardised load model was used representing the highest load achieved during level walking. The geometry and material models were created using computed tomography data. In the analysis, a material model was created that represents a patient with osteopenia.

Results

The equivalent strain distribution in the models of cancellous bone with an APT component showed values above 1000 με in the area below the medial tibial section, with MBT component were primarily localised in the stem tip area. For APT variants, the microstrain values in more than 80% of the volume were in the range from 300 to 1500 με, MBT only in less than 64% of the volume.

Conclusion

The effect of APT implantation on the periprosthetic tibia was shown as equal or even superior to that of MBT despite maximum strain values occurring in different locations. On the basis of the strain distribution, the state of the bone tissue was analysed to determine whether bone tissue remodelling or remodelling would occur. Following clinical validation, outcomes could eventually modify the implant selection criteria and lead to more frequent implantation of APT components.
Novel prognostic marker TGFBI affects the migration and invasion function of ovarian cancer cells and activates the integrin αvβ3-PI3K-Akt signaling pathway
Authors: Wang Hao , Xu Yin-hai , Guo Yi
Published: February 2024

Background

Individual patients with ovarian cancer show remarkably different prognosis. Present prognostic models for ovarian cancer mainly focus on clinico-pathological parameters, so quantifiable prognostic markers at molecular level are urgently needed. Platelets contribute to ovarian cancer progression, but have not been considered as biomarkers likely due to their instability. Here, we aimed to search for a stable prognostic marker from platelet-treated ovarian cancer cells, and explore its functions and mechanisms.

Methods

Microarrays analysis was done with platelet-treated SKOV-3 ovarian cancer cells. Relevant studies were searched in the Gene Expression Omnibus (GEO) database. The candidate genes were determined by differentially expressed genes (DEGs), Venn diagram drawing, protein-protein interaction (PPI) network, Cox proportional hazards model and Kaplan-Meier analysis. The expression of TGFBI in clinical samples was assessed by immunehistochemical staining (IHC), and the association of TGFBI levels with the clinic-pathological characteristics and prognosis in ovarian cancer patients was evaluated by univariate and multivariate analysis. The functions of TGFBI were predicted using data from TCGA, and validated by in vitro and in vivo experiments. The mechanism exploration was performed based on proteomic analysis, molecular docking and intervention study.

Results

TGFBI was significantly higher expressed in the platelet-treated ovarian cancer cells. An analysis of bioinformatics data revealed that increased expression of TGFBI led to significant decrease of overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) in ovarian cancer patients. Tissue microarray results showed that TGFBI was an independent factor for ovarian cancer, and TGFBI expression predict poor prognosis. Functionally, TGFBI affected the migration and invasion of ovarian cancer cells by regulation of epithelial mesenchymal transition (EMT) markers (CDH1 and CDH2) and extracellular matrix (ECM) degradation proteins (MMP-2). Mechanistically, TGFBI phosphorylated PI3K and Akt by combining integrin αvβ3.

Conclusions

We found out TGFBI as a novel prognostic indicator for ovarian cancer patients. TGFBI could promote metastasis in ovarian cancer by EMT induction and ECM remodeling, which might be associated with the activation of integrin αvβ3-PI3K-Akt signaling pathway.
SHARE-Topic: Bayesian interpretable modeling of single-cell multi-omic data
Authors: Kazwini Nour El , Sanguinetti Guido
Published: February 2024

Multi-omic single-cell technologies, which simultaneously measure the transcriptional and epigenomic state of the same cell, enable understanding epigenetic mechanisms of gene regulation. However, noisy and sparse data pose fundamental statistical challenges to extract biological knowledge from complex datasets. SHARE-Topic, a Bayesian generative model of multi-omic single cell data using topic models, aims to address these challenges. SHARE-Topic identifies common patterns of co-variation between different omic layers, providing interpretable explanations for the data complexity. Tested on data from different technological platforms, SHARE-Topic provides low dimensional representations recapitulating known biology and defines associations between genes and distal regulators in individual cells.
Trial protocol for the Building Resilience through Socio-Emotional Training (ReSET) programme: a cluster randomised controlled trial of a new transdiagnostic preventative intervention for adolescents
Authors: Viding Essi , Lloyd Alex , Law Roslyn , Martin Peter , Lucas Laura , Wu Tom Chin-Han , Steinbeis Nikolaus , Midgley Nick , Veenstra René , Smith Jaime , Ly Lili , Bird Geoffrey , Murphy Jennifer , Plans David , Munafo Marcus , Penton-Voak Ian , Deighton Jessica , Richards Kathleen , Richards Mya , Fearon Pasco
Published: February 2024

Background

Adolescence is a period of heightened vulnerability to developing mental health problems, and rates of mental health disorder in this age group have increased in the last decade. Preventing mental health problems developing before they become entrenched, particularly in adolescents who are at high risk, is an important research and clinical target. Here, we report the protocol for the trial of the ‘Building Resilience through Socioemotional Training’ (ReSET) intervention. ReSET is a new, preventative intervention that incorporates individual-based emotional training techniques and group-based social and communication skills training. We take a transdiagnostic approach, focusing on emotion processing and social mechanisms implicated in the onset and maintenance of various forms of psychopathology.

Methods

A cluster randomised allocation design is adopted with randomisation at the school year level. Five-hundred and forty adolescents (aged 12–14) will be randomised to either receive the intervention or not (passive control). The intervention is comprised of weekly sessions over an 8-week period, supplemented by two individual sessions. The primary outcomes, psychopathology symptoms and mental wellbeing, will be assessed pre- and post-intervention, and at a 1-year follow-up. Secondary outcomes are task-based assessments of emotion processing, social network data based on peer nominations, and subjective ratings of social relationships. These measures will be taken at baseline, post-intervention and 1-year follow-up. A subgroup of participants and stakeholders will be invited to take part in focus groups to assess the acceptability of the intervention.

Discussion

This project adopts a theory-based approach to the development of a new intervention designed to target the close connections between young people’s emotions and their interpersonal relationships. By embedding the intervention within a school setting and using a cluster-randomised design, we aim to develop and test a feasible, scalable intervention to prevent the onset of psychopathology in adolescence.

Trial registration

ISRCTN88585916. Trial registration date: 20/04/2023.
Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness
Authors: Coppens Grégoire , Vanhorebeek Ilse , Güiza Fabian , Derese Inge , Wouters Pieter J. , Téblick Arno , Dulfer Karolijn , Joosten Koen F. , Verbruggen Sascha C. , Van den Berghe Greet
Published: February 2024

Background

Critically ill children suffer from impaired physical/neurocognitive development 2 years later. Glucocorticoid treatment alters DNA methylation within the hypothalamus–pituitary–adrenal (HPA) axis which may impair normal brain development, cognition and behaviour. We tested the hypothesis that paediatric-intensive-care-unit (PICU) patients, sex- and age-dependently, show long-term abnormal DNA methylation within the HPA-axis layers, possibly aggravated by glucocorticoid treatment in the PICU, which may contribute to the long-term developmental impairments.

Results

In a pre-planned secondary analysis of the multicentre PEPaNIC-RCT and its 2-year follow-up, we identified differentially methylated positions and differentially methylated regions within HPA-axis genes in buccal mucosa DNA from 818 former PICU patients 2 years after PICU admission (n = 608 no glucocorticoid treatment; n = 210 glucocorticoid treatment) versus 392 healthy children and assessed interaction with sex and age, role of glucocorticoid treatment in the PICU and associations with long-term developmental impairments. Adjusting for technical variation and baseline risk factors and correcting for multiple testing (false discovery rate < 0.05), former PICU patients showed abnormal DNA methylation of 26 CpG sites (within CRHR1, POMC, MC2R, NR3C1, FKBP5, HSD11B1, SRD5A1, AKR1D1, DUSP1, TSC22D3 and TNF) and three DNA regions (within AVP, TSC22D3 and TNF) that were mostly hypomethylated. These abnormalities were sex-independent and only partially age-dependent. Abnormal methylation of three CpG sites within FKBP5 and one CpG site within SRD5A1 and AKR1D1 was partly attributable to glucocorticoid treatment during PICU stay. Finally, abnormal methylation within FKBP5 and AKR1D1 was most robustly associated with long-term impaired development.

Conclusions

Two years after critical illness in children, abnormal methylation within HPA-axis genes was present, predominantly within FKBP5 and AKR1D1, partly attributable to glucocorticoid treatment in the PICU, and explaining part of the long-term developmental impairments. These data call for caution regarding liberal glucocorticoid use in the PICU.
Ileo-ileal knot causing acute gangrenous small bowel obstruction: a case report
Authors: Molla Yohannis Derbew , Mequanint Melese Birara , Bisrat Solomon Hailesilassie , Workneh Gebrehiwot Aderaw , Alemu Hirut Tesfahun
Published: February 2024

Background

Ileo-ileal knotting is a very rare cause of small bowel obstruction, and only a few reports have been published. Small bowel obstruction (SBO) is one of the most common emergency surgical conditions that require urgent evaluation and treatment and is one of the leading causes of emergency surgical admission. There are many causes of SBO that are known in general surgical practice, and these causes are different in the developing and developed worlds.

Clinical presentation

In this article, we present a case of acute gangrenous SBO secondary to ileo-ileal knotting in a 37-year-old Ethiopian female patient after she presented with severe abdominal cramp, vomiting, and abdominal distension of 4 hours duration. The patient was operated on intraoperatively; she had gangrenous small bowel obstruction caused by ileo-ileal knotting. Later, the patient was discharged and improved after 12 days of hospital stay.

Conclusion

Ileo-ileal knotting should always be considered in the differential diagnosis of acute small-bowel obstruction. The diagnostic difficulty and the need for urgent treatment of this condition to yield optimal results are discussed.
Sustained control of recalcitrant chronic spontaneous urticaria after initiation of inflammatory airway diseases treatment: two case reports
Authors: Nguyen Doanh , Deitiker Philip
Published: February 2024

Background

Current classification of chronic urticaria is primarily based on clinical presentation of skin manifestations. Hence, therapeutic treatment is primarily aimed locally for immediate symptom relief. We reason that limiting therapeutic strategies to the skin pathology might be inadequate since cellular activation and inflammation might be triggered remotely.

Case presentation

In this series two patients had exhausted all current treatments for recalcitrant urticaria but remained symptomatic. The first case was 26-year-old Caucasian female and the second was 63-year-old African American female. Both cases had frequent breakthrough urticaria requiring frequent pulsating courses of prednisone to control urticaria despite treatment with omalizumab and antihistamines. When inflammatory airway disease was discovered and managed with inhaled corticosteroid, urticaria is controlled much faster without the need of high dose immunosuppression over several years of observation. Coincidentally, autoimmune thyroiditis and anti-immunogobulin-E immunoglobulin-G titers dropped significantly in one case with sustained inhaled corticosteroid therapy.

Conclusions

We suggest a novel approach of controlling remote epithelial site inflammation in these two cases that resulted in sustained-control of urticaria symptoms without the need for systemic corticosteroids or immunosuppressant. The changes of autoimmune antibodies might be the consequences of tolerance breaking from chronic lower airway inflammation as observed in other epithelial inflammatory condition like in celiac disease and rheumatoid arthritis.
New threats in the recovery of large carnivores inhabiting human-modified landscapes: the case of the Cantabrian brown bear (Ursus arctos)
Authors: Balseiro Ana , Herrero-García Gloria , García Marín Juan Francisco , Balsera Ramón , Monasterio Juana María , Cubero David , de Pedro Gabriel , Oleaga Álvaro , García-Rodríguez Alberto , Espinoza Israel , Rabanal Benjamín , Aduriz Gorka , Tuñón José , Gortázar Christian , Royo Luis José
Published: February 2024

Understanding mortality causes is important for the conservation of endangered species, especially in small and isolated populations inhabiting anthropized landscapes where both natural and human-caused mortality may hinder the conservation of these species. We investigated the mortality causes of 53 free-ranging brown bears (Ursus arctos) found dead between 1998 and 2023 in the Cantabrian Mountains (northwestern Spain), a highly human-modified region where bears are currently recovering after being critically threatened in the last century. We detected natural traumatic injuries in 52.63% and infectious diseases in 39.47% of the 38 bears for which the mortality causes were registered, with 21.05% of these cases presenting signs of both infectious diseases and traumas. More specifically, almost 30% of the bears died during or after intraspecific fights, including sexually selected infanticide (10.53%). In addition, primary infectious diseases such as infectious canine hepatitis, distemper, clostridiosis and colibacillosis caused the death of 15.79% of the bears. The number of direct human-caused deaths (i.e., shooting, poisoning, snare) decreased over the study period. This study also reveals three new mortality causes triggered by pathogens, two of which—Clostridium novyi and verotoxigenic Escherichia coli—not previously described in ursids, and the other one, canine distemper virus, never reported in brown bears as cause of death. New management strategies for the conservation of Cantabrian bears, which are urgently needed due to the rapid expansion of the population, should consider the mortality causes described in this study and must promote further research to elucidate how the high prevalence of infectious diseases may threaten the current recovery of the population.
Synergistic enhancement of the mouse Pramex1 and Pramel1 in repressing retinoic acid (RA) signaling during gametogenesis
Authors: Yang Mingyao , Diaz Francisco , Krause Ana Rita T. , Lei Yuguo , Liu Wan-Sheng
Published: February 2024

Background

PRAME constitutes one of the largest multi-copy gene families in Eutherians, encoding cancer-testis antigens (CTAs) with leucine-rich repeats (LRR) domains, highly expressed in cancer cells and gametogenic germ cells. This study aims to elucidate genetic interactions between two members, Pramex1 and Pramel1, in the mouse Prame family during gametogenesis using a gene knockout approach.

Result

Single-gene knockout (sKO) of either Pramex1 or Pramel1 resulted in approximately 7% of abnormal seminiferous tubules, characterized by a Sertoli-cell only (SCO) phenotype, impacting sperm count and fecundity significantly. Remarkably, sKO female mice displayed normal reproductive functions. In contrast, Pramex1/Pramel1 double knockout (dKO) mice exhibited reduced fecundity in both sexes. In dKO females, ovarian primary follicle count decreased by 50% compared to sKO and WT mice, correlating with a 50% fecundity decrease. This suggested compensatory roles during oogenesis in Pramex1 or Pramel1 sKO females. Conversely, dKO males showed an 18% frequency of SCO tubules, increased apoptotic germ cells, and decreased undifferentiated spermatogonia compared to sKO and WT testes. Western blot analysis with PRAMEX1- or PRAMEL1-specific antibodies on sKO testes revealed compensatory upregulation of each protein (30–50%) in response to the other gene’s deletion. Double KO males exhibited more severe defects in sperm count and litter size, surpassing Pramex1 and Pramel1 sKO accumulative effects, indicating a synergistic enhancement interaction during spermatogenesis. Additional experiments administering trans-retinoic acid (RA) and its inhibitor (WIN18,446) in sKO, dKO, and WT mice suggested that PRAMEX1 and PRAMEL1 synergistically repress the RA signaling pathway during spermatogenesis.

Conclusion

Data from sKO and dKO mice unveil a synergistic interaction via the RA signaling pathway between Pramex1 and Pramel1 genes during gametogenesis. This discovery sets the stage for investigating interactions among other members within the Prame family, advancing our understanding of multi-copy gene families involved in germ cell formation and function.
Association between frailty and clinical outcomes in patients undergoing craniotomy—systematic review and meta-analysis of observational studies
Authors: Licina Ana , Silvers Andrew , Thien Christopher
Published: February 2024

Background

Frailty in patients undergoing craniotomy may affect perioperative outcomes. There have been a number of studies published in this field; however, evidence is yet to be summarized in a quantitative review format. We conducted a systematic review and meta-analysis to examine the effects of frailty on perioperative outcomes in patients undergoing craniotomy surgery.

Methods

Our eligibility criteria included adult patients undergoing open cranial surgery. We searched MEDLINE via Ovid SP, EMBASE via Ovid SP, Cochrane Library, and grey literature. We included retrospective and prospective observational studies. Our primary outcome was a composite of complications as per the Clavien–Dindo classification system. We utilized a random-effects model of meta-analysis. We conducted three preplanned subgroup analyses: patients undergoing cranial surgery for tumor surgery only, patients undergoing non-tumor surgery, and patients older than 65 undergoing cranial surgery. We explored sources of heterogeneity through a sensitivity analysis and post hoc analysis.

Results

In this review of 63,159 patients, the pooled prevalence of frailty was 46%. The odds ratio of any Clavien–Dindo grade 1–4 complication developing in frail patients compared to non-frail patients was 2.01 [1.90–2.14], with no identifiable heterogeneity and a moderate level of evidence. As per GradePro evidence grading methods, there was low-quality evidence for patients being discharged to a location other than home, length of stay, and increased mortality in frail patients.

Conclusion

Increased frailty was associated with increased odds of any Clavien–Dindo 1-4 complication. Frailty measurements may be used as an integral component of risk-assessment strategies to improve the quality and value of neurosurgical care for patients undergoing craniotomy surgery.

Ethics and dissemination

Formal ethical approval is not needed, as primary data were not collected.

Systematic review registration

PROSPERO identification number: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=405240
Unified ensemble federated learning with cloud computing for online anomaly detection in energy-efficient wireless sensor networks
Authors: Gayathri S. , Surendran D.
Published: February 2024

Anomaly detection in Wireless Sensor Networks (WSNs) is critical for their reliable and secure operation. Optimizing resource efficiency is crucial for reducing energy consumption. Two new algorithms developed for anomaly detection in WSNs—Ensemble Federated Learning (EFL) with Cloud Integration and Online Anomaly Detection with Energy-Efficient Techniques (OAD-EE) with Cloud-based Model Aggregation. EFL with Cloud Integration uses ensemble methods and federated learning to enhance detection accuracy and data privacy. OAD-EE with Cloud-based Model Aggregation uses online learning and energy-efficient techniques to conserve energy on resource-constrained sensor nodes. By combining EFL and OAD-EE, a comprehensive and efficient framework for anomaly detection in WSNs can be created. Experimental results show that EFL with Cloud Integration achieves the highest detection accuracy, while OAD-EE with Cloud-based Model Aggregation has the lowest energy consumption and fastest detection time among all algorithms, making it suitable for real-time applications. The unified algorithm contributes to the system's overall efficiency, scalability, and real-time response. By integrating cloud computing, this algorithm opens new avenues for advanced WSN applications. These promising  approaches for anomaly detection in resource constrained and large-scale WSNs are beneficial for industrial applications.
The effect of oral supplementation of Paricalcitol on C-reactive protein levels in chronic kidney disease patients: GRADE-assessed systematic review and dose-response meta-analysis of data from randomized controlled trials
Authors: Arabi Seyyed Mostafa , Shahraki-Jazinaki Mostafa , Chambari Mahla , Bahrami Leila Sadat , Sabeti Sara , Gubari Mohammaed Ibrahim Mohaildeen , Roufogalis Basil D. , Sahebkar Amirhossein
Published: February 2024

Background

Previous studies investigating the effect of oral supplementation of paricalcitol on reactive protein levels in chronic kidney disease (CKD) patients reported inconsistent findings. In this systematic review and meta-analysis, we have analyzed and interpreted the results obtained from previous randomized clinical trials on the effect of paricalcitol on C-reactive protein in CKD patients in the literature.

Methods

MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched until January 2023 and related articles were obtained through a careful screening process allowing extraction of required data from selected articles. The effect size was calculated using a random effect model and weighted mean differences (WMD) and 95% confidence intervals (CI). Heterogeneity among studies was evaluated using Cochran’s Q test and I2.

Results

Amongst the 182 articles obtained from the initial search, 4 studies (6 arms) were finally included in the meta-analysis. Pooled analysis shows that C-reactive protein levels significantly decrease after oral supplementation with paricalcitol (WMD: -2.55 mg/L, 95% CI (-4.99 to -0.11; P = 0.04). The studies used in this meta-analysis showed significant heterogeneity (I2 = 66.3% and P = 0.01).

Conclusion

Oral paricalcitol supplementation in CKD patients can significantly reduce C-reactive protein levels, which may prevent CKD progression.
Pharmacovigilance study of BCR-ABL1 tyrosine kinase inhibitors: a safety analysis of the FDA adverse event reporting system
Authors: Zhao Dehua , Long Xiaoqing , Wang Jisheng
Published: February 2024

Background

With the increased use of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in cancer patients, adverse events (AEs) have garnered considerable interest. We conducted this pharmacovigilance study to evaluate the AEs of BCR-ABL1 TKIs in cancer patients using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods

To query AE reports from the FAERS database, we used OpenVigil 2.1. Descriptive analysis was then employed to describe the characteristics of TKIs-associated AE reports. We also utilized the disproportionality analysis to detect safety signals by calculating the proportional reporting ratio (PRR) and reporting odds ratios (ROR).

Results

From the FAERS database, a total of 85,989 AE reports were retrieved, with 3,080 significant AE signals identified. Specifically, imatinib, nilotinib, dasatinib, bosutinib, and ponatinib had significant AE signals of 1,058, 813, 232, 186, and 791, respectively. These significant signals were further categorized into 26 system organ classes (SOCs). The AE signals of imatinib and ponatinib were primarily associated with general disorders and administration site conditions. On the other hand, nilotinib, dasatinib, and bosutinib were mainly linked to investigations, respiratory, thoracic and mediastinal disorders, and gastrointestinal disorders, respectively. Notably, new signals of 245, 278, 47, 55, and 253 were observed in imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, respectively.

Conclusions

The results of this study demonstrated that AE signals differ among the five BCR-ABL1 TKIs. Furthermore, each BCR-ABL1 TKI displayed several new signals. These findings provide valuable information for clinicians aiming to reduce the risk of AEs during BCR-ABL1 TKI treatment.
Use of External Control Cohorts in Pediatric Brain Tumor Clinical Trials
Authors: Margol Ashley S. , Molinaro Annette M. , Onar-Thomas Arzu , Resnick Adam , Hanson Derek , Kieran Mark , Mishra-Kalyani Pallavi , Rivera Donna , Barone Amy , Arons David , Meehan Clair , Prados Michael
Published: February 2024

Why, when, and how to consider external control cohorts in pediatric brain tumor clinical trials.
Synchronization on higher-order networks
Authors: Liu Haoran , Zhou Jin , Li Bo , Huang Meng , Lu Jun-an , Shi Dinghua
Published: February 2024

Network science has already been fruitful and confirmed effective on the description of real-world or abstract systems. An increasing number of researches and instances have successfully verified, however, that interactions in systems may occur among three, four, or even more components. The introduction of higher-order perspective brings a revolution on network science, and refreshes researchers’ understanding of synchronization. Hence, an overview is presented here in regard of synchronization on higher-order networks. We start from an introduction of how the higher-order networks are represented using algebraic tools. Then a series of landmark researches on synchronization is reviewed under circumstances of whether or not the dynamics contains control. Finally, we summarize our conclusions and propose our outlooks on expectations of future works.
Quantitative Assessment of Hemodynamics Associated With Embolization Degree in Brain Arteriovenous Malformations
Authors: You Wei , Meng Xiangyu , Chen Ting , Ye Wanxing , Wang Yanwen , Lv Jian , Li Yuanjie , Sui Yutong , Zhang Yifan , Gong Wentao , Sun Yong , Jin Hengwei , Li Youxiang
Published: February 2024

BACKGROUND AND OBJECTIVES:

Grading systems, including the novel brain arteriovenous malformation endovascular grading scale (NBAVMES) and arteriovenous malformation embocure score (AVMES), predict embolization outcomes based on arteriovenous malformation (AVM) morphological features. The influence of hemodynamics on embolization outcomes remains unexplored. In this study, we investigated the relationship between hemodynamics and embolization outcomes.

METHODS:

We conducted a retrospective study of 99 consecutive patients who underwent transarterial embolization at our institution between 2012 and 2018. Hemodynamic features of AVMs were derived from pre-embolization digital subtraction angiography sequences using quantitative digital subtraction angiography. Multivariate logistic regression analysis was performed to determine the significant factors associated with embolization outcomes.

RESULTS:

Complete embolization (CE) was achieved in 17 (17.2%) patients, and near-complete embolization was achieved in 18 (18.2%) patients. A slower transnidal relative velocity (TRV, odds ratio [OR] = 0.71, P = .002) was significantly associated with CE. Moreover, higher stasis index of the drainage vein (OR = 16.53, P = .023), shorter transnidal time (OR = 0.15, P = .013), and slower TRV (OR = 0.9, P = .049) were significantly associated with complete or near-complete embolization (C/nCE). The area under the receiver operating characteristic curve for predicting CE was 0.87 for TRV, 0.72 for NBAVMES scores (ρ = 0.287, P = .004), and 0.76 for AVMES scores. The area under the receiver operating characteristic curve for predicting C/nCE was 0.77 for TRV, 0.61 for NBAVMES scores, and 0.75 for AVMES scores. Significant Spearman correlation was observed between TRV and NBAVMES scores and AVMES scores (ρ = 0.512, P < .001).

CONCLUSION:

Preoperative hemodynamic factors have the potential to predict the outcomes of AVM embolization. A higher stasis index of the drainage vein, slower TRV, and shorter transnidal time may indicate a moderate blood flow status or favorable AVM characteristics that can potentially facilitate embolization.
Tracking cell layer contribution during repair of the tympanic membrane
Authors: Dinwoodie Olivia M. , Tucker Abigail S. , Fons Juan M.
Published: February 2024

The tympanic membrane (i.e. eardrum) sits at the interface between the middle and external ear. The tympanic membrane is composed of three layers: an outer ectoderm-derived layer, a middle neural crest-derived fibroblast layer with contribution from the mesoderm-derived vasculature, and an inner endoderm-derived mucosal layer. These layers form a thin sandwich that is often perforated following trauma, pressure changes or middle ear inflammation. During healing, cells need to bridge the perforation in the absence of an initial scaffold. Here, we assessed the contribution, timing and interaction of the different layers during membrane repair by using markers and reporter mice. We showed that the ectodermal layer is retracted after perforation, before proliferating away from the wound edge, with keratin 5 basal cells migrating over the hole to bridge the gap. The mesenchymal and mucosal layers then used this scaffold to complete the repair, followed by advancement of the vasculature. Finally, differentiation of the epithelium led to formation of a scab. Our results reveal the dynamics and interconnections between the embryonic germ layers during repair and highlight how defects might occur.
Μελέτη ανοσολογικής απόκρισης, έκβασης και φαρμακο-οικονομικών χαρακτηριστικών σε ασθενείς με βακτηριαιμία, που οφείλεται σε ανθεκτικούς έναντι ευαίσθητους στα αντιβιοτικά μικροοργανιμούς
Authors: Σκιντζή Αικατερίνη
Published: February 2024

Η Αντιμικροβιακή αντοχή (AMR) είναι μια σημαντική παγκόσμια ανησυχία για την υγεία, που αποτελεί κρίσιμη πρόκληση για την αποτελεσματική διαχείριση των μολυσματικών ασθενειών. Αυτή η μελέτη είχε ως στόχο να συγκρίνει την ανοσολογική απόκριση, τα κλινικά αποτελέσματα και το σχετικό κόστος σε ασθενείς με βακτηριαιμία λόγω ανθεκτικών στα αντιβιοτικά έναντι ευπαθών βακτηριακών μικροοργανισμών. Μέθοδοι: Η παρούσα μελέτη ήταν μια μονοκεντρική, προοπτική μελέτη κοόρτης που διεξήχθη από τον Μάιο του 2017 έως τον Νοέμβριο του 2019. Ο πληθυσμός της μελέτης αποτελούνταν από ασθενείς που εισήχθησαν με επιβεβαιωμένη διάγνωση βακτηριαιμίας. Αποτελέσματα: Συνολικά συμπεριλήφθησαν 116 ασθενείς, με 53 από αυτούς (45,7%) να φέρουν μη πολυανθεκτικά (μη MDR) απομονωμένα βακτηριακά στελέχη και 63 (54,3%) με πολυανθεκτικά (MDR) στελέχη. Οι ασθενείς με βακτηριαιμία (MDR) είχαν πιο σοβαρές κλινικές εκδηλώσεις, όπως υποδεικνύεται από τις υψηλότερες βαθμολογίες SOFA και APACHE II. Τα αποτελέσματα αποκάλυψαν υψηλότερα ποσοστά θνητότητας από όλες τις αιτίες (39,7% έναντι 17%) και μέσο κόστος υγειονομικής περίθαλψης (4791 € έναντι 2843,5 €) στην ομάδα βακτηριαιμίας MDR. Επιπλέον, η βακτηριαιμία MDR συνδέθηκε με υψηλότερα επίπεδα TNF-α, υποδεικνύοντας διαφορική ανοσολογική απόκριση. Τέλος, η βακτηριαιμία MDR βρέθηκε ότι είναι ένας ανεξάρτητος προγνωστικός παράγοντας θνητότητας (OR = 3.216, 95% CI: 1.338–7.730, p = 0,009) και αυξημένου κόστους υγειονομικής περίθαλψης (μέγεθος επιπτώσεων περίπου 27,4%). Συμπέρασμα: Τα ευρήματα αυτά υπογραμμίζουν τη σημαντική επίδραση της AMR σε περιβάλλοντα υγειονομικής περίθαλψης, υπογραμμίζοντας την επείγουσα ανάγκη αντιμετώπισης των προκλήσεων που τίθενται από τους μικροοργανισμούς MDR.
Refugee Hiring and Organizational Performance
Authors: Santangelo Grazia D. , Rocha Vera , Sofka Wolfgang
Published: February 2024

Prior research on the performance effects of hiring immigrants has mainly considered people who choose to move to other countries. We shift attention to forced migrants (i.e., refugees) and study the relationship between their employment and firm performance. We focus on the specific labor market conditions that refugees face and theorize that performance improves among firms that hire refugees. We explain this relationship using two interconnected mechanisms that revolve around refugees’ limited outside options. First, as refugees have strong incentives to remain employed, they put extensive effort into their jobs, work long hours, and, thereby, reduce the employer’s labor costs related to worker turnover (effort mechanism). Second, as refugees are generally willing to accept low pay, hiring them reduces the employer’s labor costs related to salaries (remuneration mechanism). Moreover, we theorize that greater job insecurity at the hiring firm strengthens both mechanisms because it increases refugees’ perceived risk of being fired and their fear of being unemployed. We find support for our theoretical predictions in a matched sample of 27,782 firms in Denmark covering the period from 2001 to 2016.

History: This paper has been accepted for the Organization Science Special Issue on Migration and Organization.

Funding: V. Rocha received financial support from the Carlsberg Foundation [Grant CF21-0156].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2021.15980 .
A Closer Look at Fibrous Dysplasia Femur Fracture Five-year Follow-up: A Unique Case
Authors:   Department of Orthopaedics, Artemis Hospital and NC Medical College, Panipat, Haryana, India,, Sauhta Ravi , Makkar Dheeraj ,   Department of Orthopaedics, NC Medical College, Panipat, Haryana, India.
Published: February 2024

Introduction: Fibrous dysplasia (FD) is a benign skeletal disorder characterized by the replacement of normal bone tissue with disorganized fibrous tissue. Fractures are a significant complication of FD, particularly in the proximal femur, where deformities such as Shepherd’s crook deformity can increase the risk. Case Report: We present a case study of a 44-year-old male with unilateral monostotic FD, Shepherd’s crook deformity, and a pathological femoral shaft fracture. The initial surgical approach involved valgus osteotomy, dynamic condylar screw (DCS) fixation, and multiple osteotomies of the femoral shaft. However, the patient experienced a refracture and implant failure, necessitating a second surgical intervention with a double-angled DCS and additional fixation. Post-operative follow-up revealed successful bone union and deformity correction, although a limb length discrepancy was noted. Conclusion: This case highlights the challenges in managing FD-related fractures and the importance of addressing deformities and achieving optimal alignment. Individualized treatment approaches, careful implant selection, and post-operative rehabilitation are crucial for successful outcomes in FD-associated fractures. Keywords: Fibrous dysplasia, femur, dynamic condylar screw, shepherd crook.
Peri-prosthetic Joint Infection due to Candida albicans in a Young Immunocompetent Patient – A Rare Case Report
Authors:   Department of Orthopaedics and Joint Replacement, Apollo Sage Hospital, Bhopal, Madhya Pradesh, India,, Tiwari Vivek , Shendre Pooja ,   Department of Microbiology, AIIMS Nagpur, Nagpur, Maharashtra, India,, Nag Soumyabrata ,   Department of Microbiology, AIIMS Nagpur, Nagpur, Maharashtra, India,, Mishra Meena ,   Department of Microbiology, AIIMS Nagpur, Nagpur, Maharashtra, India,, Roy Mainak ,   Department of Orthopaedics, AIIMS Nagpur, Nagpur, Maharashtra, India., Dwidmuthe Samir ,   Department of Orthopaedics, AIIMS Nagpur, Nagpur, Maharashtra, India.
Published: February 2024

Introduction: The recent surge in joint replacement surgeries in India, particularly total knee and hip replacements, is notable. The majority of patients undergoing these procedures suffered from knee osteoarthritis or femoral head avascular necrosis. However, this increase in joint replacements has also led to a rise in periprosthetic joint infections (PJI), a severe and costly complication. PJI is responsible for 25% of total knee arthroplasty failures and 15% of total hip arthroplasty failures. Various risk factors, such as diabetes, fractures, and arthritis, are associated with PJI development. Bacterial infections, notably Staphylococcus species, are the primary cause of PJI, but rare fungal infections are often caused by Candida and Aspergillus. There is a lack of clinical trials and limited knowledge about the prevalence and treatment of fungal PJIs. Case Report: This report presents a unique case of delayed PJI caused by Candida albicans in an otherwise healthy patient. Conclusion: This case report emphasizes the need for further research and standardized treatment guidelines. Treatment typically involves a two-stage revision with extended antifungal therapy. The optimal duration of antifungal treatment remains uncertain. Keywords: Joint replacement surgeries, periprosthetic joint infections, fungal periprosthetic joint infections, Candida albicans, two-stage revision arthroplasty.
Outcome of Osteosynthesis of Late-Presenting Proximal Humerus Non-union: A Case Series
Authors:   Department of Orthopaedics, Paras HMRI Hospital, Patna, Bihar, India,, Mukhopadhaya John , Singh Niraj Narain ,   Department of Orthopaedics, ESIC Medical College and Hospital, Bihta, Patna, Bihar, India., Gupta Arvind Prasad ,   Department of Orthopaedics, Paras HMRI Hospital, Patna, Bihar, India,, Bhadani Janki Sharan ,   Department of Orthopaedics, Paras HMRI Hospital, Patna, Bihar, India,
Published: February 2024

Introduction: It can be challenging to treat proximal humeral non-union (PHN). The challenge gets compounded when they are presented either late or after previous surgery. The challenges are far greater due to small proximal fragments, scalloping of the head, medial bone defect, osteoporosis, soft tissue contractures, and problems related to the previous implants. Materials and Methods:In this retro-prospective study (2007–2020), we report on six cases of PHN which were presented to us more than 5 years after the original injury and managed using an intra-medullary autologous fibular strut graft (FSG) along with fixation with a proximal humeral locking plate and cancellous bone grafting. We quantified shoulder function based on constant score and disabilities of the arm, shoulder and hand (DASH) score. Results: The mean age of patients is found to be 54.3 years (range, 22–74 years) with females dominating our study. The mean pre-operative constant score is 26.33 which improved to 71.83 in the post-operative period. The mean DASH score is 77.98 preoperatively, which improved to 19.5 postoperatively. The paired sample t-test compared the difference in mean of the pre-operative and post-operative scores, which shows significant improvement in outcome. Conclusion: Even in very late PHN in poor-quality bone, the additional use of intramedullary strut grafts provides structural support to the fixation and further enhances the ability to withstand the load-start early motion and have a satisfactory functional outcome. Keywords: Non-union, proximal humerus non-union, proximal humerus fracture, proximal humerus internal locking system, locking plate, autogenous fibular strut graft.
A Qualitative Cost-Benefit Analysis of the Maritime Silk Road in Europe: Who Benefits from the Initiative and Who Does Not
Authors: Martínez-Galán Enrique , Leandro Francisco José B.S.
Published: February 2024

Abstract: China has traditionally been regarded as a continental power. However, the 21st Century Maritime Silk Road (MSR), launched in 2013, shapes China's intention to become a global maritime power. The initiative is the most significant contribution to increasing global maritime connectivity in recent decades. The volume and impact of Chinese investments in Europe's seaports are remarkable. This article proposes a fundamental framework to assess who benefits from the initiative. Since quantitative cost-benefit analyses (CBA) hardly apply to multifaceted and partially unquantifiable phenomena, we suggest assessing the MSR by means of a comprehensive qualitative CBA. We opted for a qualitative CBA due to ontological and epistemological reasons: on the one hand, the complex and multilayered nature of the problem is difficult to monetize, and, on the other hand, our argument is not final, as it attempts to assess a given policy before its implementation is sufficiently mature. In this vein, we apply the problem-solving methodology 'analytic hierarchy process'. While the media have disproportionately stressed the negative effects of the MSR, we conclude under this framework that (i) for China, MSR benefits largely outweigh associated costs; (ii) for participating countries, MSR benefits outweigh the associated costs only after cost-mitigating measures are incorporated; and (iii) for non-participating countries, MSR costs outweigh associated benefits.
Navigating the Indo-Pacific: Vietnam's Hedging Strategies Amid the Geopolitical Rivalry Between China and the United States
Authors: Wu Xiangning , Velasco Joseph Ching
Published: February 2024

Abstract: Vietnam has implemented hedging strategies in response to the geopolitical rivalry between China and the United States in the Indo-Pacific region. While the uncertainty from the dynamics of the Sino–US rivalry has been widely acknowledged, we examine how Vietnam's hedging strategy is also calibrated toward ongoing domestic political developments. We argue that while the international environment determines the overall structure of Vietnam's geopolitical hedging strategy, domestic factors, such as the success of Doi Moi, the interaction of party factions, and disagreements among public elites, influence the breadth of this strategy. Current global exigencies and internal domestic concerns require Hanoi to intelligently and delicately calibrate its interactions with great powers with little margin for error.
Full Havisham Effect
Authors: Mullen Mary
Published: February 2024

Abstract: Reflecting on Miss Havisham, one of the most famous ghosts in the marriage plot, this personal essay considers the importance of having space to grieve. While living as a lodger in my colleague’s home after ending my marriage, I dreamed of Miss Havisham’s Satis House: a space of my own where I could decay alongside the scraps, fragments, and stuff that makes a life. But when I moved into my apartment, I identified more with Catherine Dickens who mourned her mistreatment by Charles but moved on all the same. Ultimately, this essay celebrates the love that appears minor in the marriage plot but is major during separation.