bluuebunny/crossref_metadata_2025 huggingface dataset:
The MINUTES bundle for the initial 30 min management of undifferentiated circulatory shock: an expert opinion
Authors: Hasanin Ahmed , Sanfilippo Filippo , Dünser Martin W , Ahmed Hassan M , Zieleskiewicz Laurent , Myatra Sheila Nainan , Mostafa Maha
Published: July 2024

Acute circulatory shock is a life-threatening emergency requiring an efficient and timely management plan, which varies according to shock etiology and pathophysiology. Specific guidelines have been developed for each type of shock; however, there is a need for a clear timeline to promptly implement initial life-saving interventions during the early phase of shock recognition and management. A simple, easily memorable bundle of interventions could facilitate standardized management with clear targets and specified timeline. The authors propose the “MINUTES” acronym which summarizes essential interventions which should be performed within the first 30 min following shock recognition. All the interventions in the MINUTES bundle are suitable for any patient with undifferentiated shock. In addition to the acronym, we suggest a timeline for each step, balancing the feasibility and urgency of each intervention. The MINUTES acronym includes seven sequential steps which should be performed in the first 30 min following shock recognition: Maintain “ABCs”, INfuse vasopressors and/or fluids (to support hemodynamic/perfusion) and INvestigate with simple blood tests, Ultrasound to detect the type of shock, Treat the underlying Etiology, and Stabilize organ perfusion.
Genomic diversity in Paenibacillus polymyxa: unveiling distinct species groups and functional variability
Authors: Wallner Adrian , Antonielli Livio , Mesguida Ouiza , Rey Patrice , Compant Stéphane
Published: July 2024

Background

Paenibacillus polymyxa is a bacterial species of high interest, as suggested by the increased number of publications on its functions in the past years. Accordingly, the number of described strains and sequenced genomes is also on the rise. While functional diversity of P. polymyxa has been suggested before, the available genomic data is now sufficient for robust comparative genomics analyses.

Results

Using 157 genomes, we found significant disparities among strains currently affiliated to P. polymyxa. Multiple taxonomic groups were identified with conserved predicted functions putatively impacting their respective ecology. As strains of this species have been reported to exhibit considerable potential in agriculture, medicine, and bioremediation, it is preferable to clarify their taxonomic organization to facilitate reliable and durable approval as active ingredients.

Conclusions

Strains currently affiliated to P. polymyxa can be separated into two major species groups with differential potential in nitrogen fixation, plant interaction, secondary metabolism, and antimicrobial resistance, as inferred from genomic data.
Potentially pathogenic culturable bacteria in hemodialysis waters
Authors: Ghafari Shokouh , Alavi Seyed Mohammad , Khaghani Soheila
Published: July 2024

Background

Hemodialysis patients are at risk of acquiring healthcare-related infections due to using non-sterile water to prepare hemodialysis fluid. Therefore, microbiological control and monitoring of used water are of crucial importance.

Materials and methods

In this work, we identified bacterial populations occupying a hemodialysis water distribution system for almost a 6-month period in Ahvaz city, southwest of Iran. A total of 18 samples from three points were collected. We found high colony counts of bacteria on R2A agar. 31 bacteria with different morphological and biochemical characteristics were identified by molecular-genetic methods based on 16 S rRNA gene sequencing. Endotoxin concentrations were measured, using Endosafe® Rapid LAL Single-Test Vials.

Results

A diverse bacterial community was identified, containing predominantly Gram-negative bacilli. The most frequently isolated genus was Sphingomonas. Five species including M. fortuitum, M. lentiflavum, M.szulgai, M. barrassiae, and M. gordonae was identified .Despite the presence of Gram-negative bacteria the endotoxin analysis of all samples revealed that their endotoxin values were below the detection limit.

Conclusion

The members of Sphingomonas genus along with Bosea and mycobacteria could be regarded as pioneers in surface colonization and biofilm creation. These bacteria with others like Pelomonas, Bradyrhizobium, staphylococcus, and Microbacterium may represent a potential health risk to patients under hemodialysis treatment.
Transcription factor TaNF-YB2 interacts with partners TaNF-YA7/YC7 and transcriptionally activates distinct stress-defensive genes to modulate drought tolerance in T. Aestivum
Authors: Zhao Ying-Jia , Ma Chun-Ying , Zheng Meng-Jing , Yao Yan-Rong , Lv Li-Hua , Zhang Li-Hua , Fu Xiao-Xin , Zhang Jing-Ting , Xiao Kai
Published: July 2024

Background

Drought stress limits significantly the crop productivity. However, plants have evolved various strategies to cope with the drought conditions by adopting complex molecular, biochemical, and physiological mechanisms. Members of the nuclear factor Y (NF-Y) transcription factor (TF) family constitute one of the largest TF classes and are involved in plant responses to abiotic stresses.

Results

TaNF-YB2, a NY-YB subfamily gene in T. aestivum, was characterized in this study focusing on its role in mediating plant adaptation to drought stress. Yeast two-hybrid (Y-2 H), biomolecular fluoresence complementation (BiFC), and Co-immunoprecipitation (Co-IP) assays indicated that TaNF-YB2 interacts with the NF-YA member TaNF-YA7 and NF-YC family member TaNF-YC7, which constitutes a heterotrimer TaNF-YB2/TaNF-YA7/TaNF-YC7. The TaNF-YB2 transcripts are induced in roots and aerial tissues upon drought signaling; GUS histochemical staining analysis demonstrated the roles of cis-regulatory elements ABRE and MYB situated in TaNF-YB2 promoter to contribute to target gene response to drought. Transgene analysis on TaNF-YB2 confirmed its functions in regulating drought adaptation via modulating stomata movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis. TaNF-YB2 possessed the abilities in transcriptionally activating TaP5CS2, the P5CS family gene involving proline biosynthesis and TaSOD1, TaCAT5, and TaPOD5, the genes encoding antioxidant enzymes. Positive correlations were found between yield and the TaNF-YB2 transcripts in a core panel constituting 45 wheat cultivars under drought condition, in which two types of major haplotypes including TaNF-YB2-Hap1 and -Hap2 were included, with the former conferring more TaNF-YB2 transcripts and stronger plant drought tolerance.

Conclusions

TaNF-YB2 is transcriptional response to drought stress. It is an essential regulator in mediating plant drought adaptation by modulating the physiological processes associated with stomatal movement, osmolyte biosynthesis, and reactive oxygen species (ROS) homeostasis, depending on its role in transcriptionally regulating stress response genes. Our research deepens the understanding of plant drought stress underlying NF-Y TF family and provides gene resource in efforts for molecular breeding the drought-tolerant cultivars in T. aestivum.
Effect of liver abnormalities on mortality in Fontan patients: a systematic review and meta-analysis
Authors: Liu Xiang , Han Linjiang , Zhou Ziqin , Tu Jiazichao , Ma Jianrui , Chen Jimei
Published: July 2024

Background

Fontan-associated liver disease (FALD) is one of the most common complications following Fontan procedure, but the impact of FALD on survival outcomes remains controversial. The aim of this systematic review and meta-analysis was to examine and quantify the influence of liver disease on the survival of Fontan patients.

Methods

The Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed, and relevant human studies published from inception up to 12 August 2022 were searched. Stata (version 17.0) was applied to perform the meta-analysis, using random effects (Mantel-Haenszel) models. The I2 statistic was used to assess the heterogeneity. Subgroup analysis and meta-regression were employed to explore the potential sources of heterogeneity and sensitivity analysis was performed to determine the potential influence of each study on the overall pooled results.

Results

A total of 312 records were initially identified and 8 studies involving 2,466 patients were selected for inclusion. Results revealed a significant association between the severity of liver disease following Fontan procedure and mortality, which was confirmed by sensitivity analysis and subgroup analysis assessing post-HT mortality. Meta-regression showed that diagnostic methods for liver disease may be a source of heterogeneity. After removal of the FALD patients identified by international classification of disease codes, heterogeneity was markedly reduced, and the positive association between all-cause mortality and the severity of liver disease became significant.

Conclusions

This meta-analysis showed the severity of liver disease following the Fontan procedure has a significant association with mortality. Lifelong follow-up is necessary and imaging examinations are recommended for routine surveillance of liver disease. Among patients with failing Fontan and advanced liver disease, combined heart-liver transplantation may provide additional survival benefits.
Educational interventions aimed at improving knowledge of delirium among nursing home staff—a realist review
Authors: Molitor Vincent , Busse Theresa Sophie , Giehl Chantal , Lauer Romy , Otte Ina Carola , Vollmar Horst Christian , Thürmann Petra , Holle Bernhard , Palm Rebecca
Published: July 2024

Background

Delirium is a neuropathological syndrome that is characterised by fluctuating impairments in attention, cognitive performance, and consciousness. Since delirium represents a medical emergency, it can be associated with adverse clinical and economic outcomes. Although nursing home residents face a high risk of developing delirium, health care professionals in this field appear to have limited knowledge of delirium despite the critical role they play in the prevention, diagnosis, and treatment of delirium in nursing homes.

Objective

The purpose of this realist review is to develop an initial programme theory with the goal of understanding how, why, and under what circumstances educational interventions can improve the delirium-specific knowledge of health care professionals in nursing homes.

Methods

This realist review was conducted in accordance with the RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines and includes the following steps: (1) search strategy and literature review; (2) study selection and assessment; (3) data extraction; (4) data synthesis; and (5) development of an initial programme theory. It also included stakeholder discussions with health care professionals recruited from nursing home care, which focused on their experiences with delirium.

Results

From a set of 1703 initially identified publications, ten publications were included in this realist review. Based on these publications, context-mechanism-outcome configurations were developed; these configurations pertained to (1) management support, (2) cognitive impairments among residents, (3) familiarity with residents, (4) participatory intervention development, (5) practical application, (6) case scenarios, (7) support from experts and (8) relevance of communication.

Conclusions

Educational interventions aimed at improving the delirium-specific knowledge of health care professionals should feature methodological diversity if they are to enhance health care professionals’ interest in delirium and highlight the fundamental contributions they make to the prevention, diagnosis, and treatment of delirium. Educational interventions should also take into account the multidimensional contextual factors that can have massive impacts on the relevant mode of action as well as the responses of health care professionals in nursing homes. The identification of delirium in residents is a fundamental responsibility for nursing home staff.

Trial registration

This review has been registered at Open Science Framework https://doi.org/10.17605/OSF.IO/6ZKM3
Indoor residual spraying of experimental huts in Cameroon highlights the potential of Fludora® Fusion to control wild pyrethroid-resistant malaria vectors
Authors: Thiomela Riccado F. , Tchouakui Magellan , Menze Benjamin D. , Nchoutpouen Elysee , Ngongang-Yipmo Emilie S. , Wood Oliver , Horstmann Sebastian , Mahob Raymond J. , Fomena Abraham , Wondji Charles S.
Published: July 2024

Elevated resistance to pyrethroids in major malaria vectors has led to the introduction of novel insecticides including neonicotinoids. There is a fear that efficacy of these new insecticides could be impacted by cross-resistance mechanisms from metabolic resistance to pyrethroids. In this study, after evaluating the resistance to deltamethrin, clothianidin and mixture of clothianidin + deltamethrin in the lab using CDC bottle assays, the efficacy of the new IRS formulation Fludora® Fusion was tested in comparison to clothianidin and deltamethrin applied alone using experimental hut trials against wild free-flying pyrethroid-resistant Anopheles funestus from Elende and field An. gambiae collected from Nkolondom reared in the lab and released in the huts. Additionally, cone tests on the treated walls were performed each month for a period of twelve months to evaluate the residual efficacy of the sprayed products. Furthermore, the L1014F-kdr target-site mutation and the L119F-GSTe2 mediated metabolic resistance to pyrethroids were genotyped on a subset of mosquitoes from the EHT to assess the potential cross-resistance. All Anopheles species tested were fully susceptible to clothianidin and clothianidin + deltamethrin mixture in CDC bottle assay while resistance was noted to deltamethrin. Accordingly, Fludora® Fusion (62.83% vs 42.42%) and clothianidin (64.42% vs 42.42%) induced significantly higher mortality rates in EHT than deltamethrin (42.42%) against free flying An. funestus from Elende in month 1 (M1) and no significant difference in mortality was observed between the first (M1) and sixth (M6) months of the evaluation (P > 0.05). However, lower mortality rates were recorded against An. gambiae s.s from Nkolondom (mortality rates 50%, 45.56% and 26.68%). In-situ cone test on the wall showed a high residual efficacy of Fludora® Fusion and clothianidin on the susceptible strain KISUMU (> 12 months) and moderately on the highly pyrethroid-resistant An. gambiae strain from Nkolondom (6 months). Interestingly, no association was observed between the L119F-GSTe2 mutation and the ability of mosquitoes to survive exposure to Fludora® Fusion, whereas a trend was observed with the L1014F-kdr mutation. This study highlights that Fludora® Fusion, through its clothianidin component, has good potential of controlling pyrethroid-resistant mosquitoes with prolonged residual efficacy. This could be therefore an appropriate tool for vector control in several malaria endemic regions.
Pembrolizumab plus either epacadostat or placebo for cisplatin-ineligible urothelial carcinoma: results from the ECHO-307/KEYNOTE-672 study
Authors: Necchi Andrea , Van der Heijden Michiel S. , Trukhin Dmytro , Peer Avivit , Gurney Howard , Alekseev Boris Y. , Parnis Francis X. , Leibowitz Raya , De Santis Maria , Grivas Petros , Clark Jason , Munteanu Mihaela , Kataria Ritesh , Jia Calvin , Balar Arjun V. , de Wit Ronald
Published: July 2024

Background

Indoleamine 2,3- dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been correlated with shorter disease-specific survival in patients with urothelial carcinoma (UC). IDO1 may counteract the antitumor effects of immune checkpoint inhibitors. Epacadostat is a potent and highly selective inhibitor of IDO1. In the phase I/II ECHO-202/KEYNOTE-037 study, epacadostat plus pembrolizumab resulted in a preliminary objective response rate (ORR) of 35% in a cohort of patients with advanced UC.

Methods

ECHO-307/KEYNOTE-672 was a double-blinded, randomized, phase III study. Eligible adults had confirmed locally advanced/unresectable or metastatic UC of the urinary tract and were ineligible to receive cisplatin-based chemotherapy. Participants were randomly assigned (1:1) to receive epacadostat (100 mg twice daily) plus pembrolizumab (200 mg every 3 weeks) or placebo plus pembrolizumab for up to 35 pembrolizumab infusions. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (version 1.1).

Results

A total of 93 patients were randomized (epacadostat plus pembrolizumab, n = 44; placebo plus pembrolizumab, n = 49). Enrollment was stopped early due to emerging data from the phase III ECHO-301/KEYNOTE-252 study. The median duration of follow-up was 64 days in both arms. Based on all available data at cutoff, ORR (unconfirmed) was 31.8% (95% CI, 22.46–55.24%) for epacadostat plus pembrolizumab and 24.5% (95% CI, 15.33–43.67%) for placebo plus pembrolizumab. Circulating kynurenine levels numerically increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and decreased in the epacadostat-plus-pembrolizumab arm. Epacadostat-plus-pembrolizumab combination treatment was well tolerated with a safety profile similar to the placebo arm. Treatment discontinuations due to treatment-related adverse events were more frequent with epacadostat (11.6% vs. 4.1%).

Conclusions

Treatment with epacadostat plus pembrolizumab resulted in a similar ORR and safety profile as placebo plus pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced/unresectable or metastatic UC. At a dose of 100 mg twice daily, epacadostat did not appear to completely normalize circulating kynurenine levels when administered with pembrolizumab. Larger studies with longer follow-up and possibly testing higher doses of epacadostat, potentially in different therapy settings, may be warranted.

Trial registration

ClinicalTrials.gov identifier: NCT03361865, retrospectively registered December 5, 2017.
Pembrolizumab plus epacadostat in patients with recurrent/metastatic head and neck squamous cell carcinoma (KEYNOTE-669/ECHO-304): a phase 3, randomized, open-label study
Authors: Cho Byoung Chul , Braña Irene , Cirauqui Beatriz , Aksoy Sercan , Couture Felix , Hong Ruey-Long , Miller Wilson H. , Chaves-Conde Manuel , Teixeira Margarida , Leopold Lance , Munteanu Mihaela , Ge Joy Yang , Swaby Ramona F. , Hughes Brett G. M.
Published: July 2024

Background

Advanced head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and new treatment options are needed. Combining immunotherapies with differing mechanisms of action may enhance clinical benefits compared with single-agent immunotherapy. Epacadostat, an indoleamine 2,3 dioxygenase 1 inhibitor, plus pembrolizumab, a PD-1 inhibitor, showed promising activity in advanced HNSCC in the phase 1/2 KEYNOTE-037/ECHO-202 trial.

Methods

KEYNOTE-669/ECHO-304 is a randomized, open-label, phase 3 study evaluating the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab with a platinum [carboplatin or cisplatin] and 5-fluorouracil) in recurrent/metastatic (R/M) HNSCC. Participants had no prior systemic therapy for R/M HNSCC and were randomly assigned (2:1:2) to pembrolizumab 200 mg intravenously every 3 weeks plus epacadostat 100 mg orally twice daily, pembrolizumab monotherapy, or EXTREME. The primary endpoint was objective response rate (ORR; investigator assessment). Secondary endpoints were safety and tolerability. Change in serum kynurenine was an exploratory endpoint. Study enrollment was discontinued early as a strategic decision on May 2, 2018, and response assessment was discontinued after first on-study imaging assessment at week 9. Data cut-off was January 17, 2019.

Results

Between December 1, 2017, and May 2, 2018, 89 patients were randomly allocated to pembrolizumab plus epacadostat (n = 35), pembrolizumab monotherapy (n = 19), or EXTREME (n = 35). ORR (95% CI) was 31% (17%–49%) for pembrolizumab plus epacadostat, 21% (6%–46%) for pembrolizumab monotherapy, and 34% (19%–52%) for EXTREME. Treatment-related adverse events (TRAEs) occurred in 82% (n = 28) of patients receiving pembrolizumab plus epacadostat, 63% (n = 12) receiving pembrolizumab monotherapy, and 100% (n = 34) receiving EXTREME. Grade 3–4 TRAEs occurred in 24% (n = 8) of patients receiving pembrolizumab plus epacadostat, 16% (n = 3) receiving pembrolizumab monotherapy, and 82% (n = 28) receiving EXTREME. No deaths occurred due to AEs. Pembrolizumab plus epacadostat treatment reduced kynurenine levels but not to that of healthy subjects.

Conclusions

Pembrolizumab plus epacadostat and pembrolizumab monotherapy provided a similar response rate to EXTREME and demonstrated a manageable safety profile in patients with R/M HNSCC.

Trial registration

NCT03358472. Date of trial registration: November 30, 2017.
Metabolic tumour area: a novel prognostic indicator based on 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma in the R-CHOP era
Authors: Cui Silu , Xin Wenchong , Wang Fei , Shao Xiaoliang , Shao Xiaonan , Niu Rong , Zhang Feifei , Shi Yunmei , Liu Bao , Gu Weiying , Wang Yuetao
Published: July 2024

Background

The metabolic tumour area (MTA) was found to be a promising predictor of prostate cancer. However, the role of MTA based on 18F-FDG PET/CT in diffuse large B-cell lymphoma (DLBCL) prognosis remains unclear. This study aimed to elucidate the prognostic significance of MTA and evaluate its incremental value to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) for DLBCL patients treated with first-line R-CHOP regimens.

Methods

A total of 280 consecutive patients with newly diagnosed DLBCL and baseline 18F-FDG PET/CT data were retrospectively evaluated. Lesions were delineated via a semiautomated segmentation method based on a 41% SUVmax threshold to estimate semiquantitative metabolic parameters such as total metabolic tumour volume (TMTV) and MTA. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values. Progression-free survival (PFS) and overall survival (OS) were the endpoints that were used to evaluate the prognosis. PFS and OS were estimated via Kaplan‒Meier curves and compared via the log-rank test.

Results

Univariate analysis revealed that patients with high MTA, high TMTV and NCCN-IPI ≥ 4 were associated with inferior PFS and OS (P < 0.0001 for all). Multivariate analysis indicated that MTA remained an independent predictor of PFS and OS [hazard ratio (HR), 2.506; 95% confidence interval (CI), 1.337–4.696; P = 0.004; and HR, 1.823; 95% CI, 1.005–3.310; P = 0.048], whereas TMTV was not. Further analysis using the NCCN-IPI model as a covariate revealed that MTA and NCCN-IPI were still independent predictors of PFS (HR, 2.617; 95% CI, 1.494–4.586; P = 0.001; and HR, 2.633; 95% CI, 1.650–4.203; P < 0.0001) and OS (HR, 2.021; 95% CI, 1.201–3.401; P = 0.008; and HR, 3.869; 95% CI, 1.959–7.640; P < 0.0001; respectively). Furthermore, MTA was used to separate patients with high NCCN-IPI risk scores into two groups with significantly different outcomes.

Conclusions

Pre-treatment MTA based on 18F-FDG PET/CT and NCCN-IPI were independent predictor of PFS and OS in DLBCL patients treated with R-CHOP. MTA has additional predictive value for the prognosis of patients with DLBCL, especially in high-risk patients with NCCN-IPI ≥ 4. In addition, the combination of MTA and NCCN-IPI may be helpful in further improving risk stratification and guiding individualised treatment options.

Trial registration

This research was retrospectively registered with the Ethics Committee of the Third Affiliated Hospital of Soochow University, and the registration number was approval No. 155 (approved date: 31 May 2022).
Validation of the extended e-health literacy scale: structural validity, construct validity and measurement invariance
Authors: Petrič Gregor , Atanasova Sara
Published: July 2024

Background

Given the rapid proliferation and use of online health resources, many of which may be of dubious quality, there is an increasing need to develop electronic health literacy (e-health literacy) skills among the population of internet users. E-health literacy encompasses the skills and abilities needed to access, understand, validate, evaluate, interpret, and apply online health-related information. Measuring e-health literacy has become crucial for developing targeted interventions, assessing their impact, and producing high-quality research findings that can inform health policy and clinical practice, which can lead to improved health outcomes and potentially reducing health inequalities. The scales need to be valid and reliable so that decisions are based on high-quality data. In this regard, the issue of the measurement invariance of scales across different demographic groups has been neglected. This is critical, as assessments should be valid across different sociodemographic groups to avoid bias when comparing them. The aim of this study was to validate the Extended e-health literacy scale (eHEALS-E) on general population and investigate its structural validity and internal consistency, construct validity in terms of convergent and discriminant validity, and examine its measurement invariance across gender, age, education and social status.

Methods

The data were collected as a part of a national health literacy survey conducted by the Slovenian National Institute of Public Health. For this survey the initial eHEALS-E scale was revised in order to address its limitations and applicability to general population. Based on a nationally representative sample, the final sample for the analysis comprised 1,944 individuals who at least occasionally used one of the various internet services to obtain health-related information. Multiple group confirmatory factor analysis was used to examine the measurement invariance of the scale.

Results

With some adjustments, the measurement model of the revised 6-dimensional eHEALS-E scale demonstrated a good fit to the data (χ2 = 2508, df = 282, RMSEA = 0.064, SRMR = 0.070, CFI = 0.90). The scale had good internal consistency (alpha = 0.89). Although evidence of the scale’s convergent and discriminant validity was partially provided, the analysis revealed robust measurement invariance across sociodemographic groups.

Conclusions

With a minor limitation, the scale ensures an unbiased e-health literacy assessment across different social groups, which is crucial for interventions that aim to reduce health-related social inequalities. This ensures that the interventions derived from the assessment of reality are equally valid and effective for everyone, regardless of their sociodemographic background.
Unlocking the potential of soil microbial communities for bioremediation of emerging organic contaminants: omics-based approaches
Authors: Alidoosti Fatemeh , Giyahchi Minoo , Moien Shabnam , Moghimi Hamid
Published: July 2024

The remediation of emerging contaminants presents a pressing environmental challenge, necessitating innovative approaches for effective mitigation. This review article delves into the untapped potential of soil microbial communities in the bioremediation of emerging contaminants. Bioremediation, while a promising method, often proves time-consuming and requires a deep comprehension of microbial intricacies for enhancement. Given the challenges presented by the inability to culture many of these microorganisms, conventional methods are inadequate for achieving this goal. While omics-based methods provide an innovative approach to understanding the fundamental aspects, processes, and connections among microorganisms that are essential for improving bioremediation strategies. By exploring the latest advancements in omics technologies, this review aims to shed light on how these approaches can unlock the hidden capabilities of soil microbial communities, paving the way for more efficient and sustainable remediation solutions.
Applications of nanotechnology in orthodontics: a comprehensive review of tooth movement, antibacterial properties, friction reduction, and corrosion resistance
Authors: He Longwen , Zhang Wenzhong , Liu Junfeng , Pan Yuemei , Li Simin , Xie Yueqiang
Published: July 2024

Nanotechnology has contributed important innovations to medicine and dentistry, and has also offered various applications to the field of orthodontics. Intraoral appliances must function in a complex environment that includes digestive enzymes, a diverse microbiome, mechanical stress, and fluctuations of pH and temperature. Nanotechnology can improve the performance of orthodontic brackets and archwires by reducing friction, inhibiting bacterial growth and biofilm formation, optimizing tooth remineralization, improving corrosion resistance and biocompatibility of metal substrates, and accelerating or decelerating orthodontic tooth movement through the application of novel nanocoatings, nanoelectromechanical systems, and nanorobots. This comprehensive review systematically explores the orthodontic applications of nanotechnology, particularly its impacts on tooth movement, antibacterial activity, friction reduction, and corrosion resistance. A search across PubMed, the Web of Science Core Collection, and Google Scholar yielded 261 papers, of which 28 met our inclusion criteria. These selected studies highlight the significant benefits of nanotechnology in orthodontic devices. Recent clinical trials demonstrate that advancements brought by nanotechnology may facilitate the future delivery of more effective and comfortable orthodontic care.
Gut microbiota affects the activation of STING pathway and thus participates in the progression of colorectal cancer
Authors: Liu Xinqiang , Cui Shasha , Zhang Lu , Wu Sainan , Feng Cunzhi , Liu Baozhi , Yang Huanlian
Published: July 2024

Background

More and more studies showed that gut microbiota was closely related to the development of colorectal cancer (CRC). However, the specific pathway of gut microbiota regulating CRC development is still unknown.

Methods

We collected fecal samples from 14 CRC patients and 20 normal volunteers for 16 S sequencing analysis. At the same time, 14 CRC patients’ tumors and their adjacent tissues were collected for the detection of STING pathway related protein level. Mice were injected with azoxymethane (AOM) to establish an animal model of CRC, and antibiotics were given at the same time to evaluate the influence of gut microbiota on STING pathway and whether it was involved in regulating the tumor development of CRC mice.

Results

The sequencing results showed that compared with the normal group, the gut microbiota gut microbiota of CRC patients changed significantly at different species classification levels. At the level of genus, Akkermansia, Ligilactobacillus and Subdoligranulum increased the most in CRC patients, while Bacteroides and Dialister decreased sharply. The expression of STING-related protein was significantly down-regulated in CRC tumor tissues. Antibiotic treatment of CRC mice can promote the development of tumor and inhibit the activation of STING pathway.

Conclusion

Gut microbiota participates in CRC progress by mediating STING pathway activation.
Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress
Authors: Lu Jinxin , Zhang Xiaoyu , Su Keyu , Luo Huandong , Liu Congcong , Yang Yuqing , He Bin , Wang Cenxin , Zhao Zhuoran , Liu Xianxian , Wang Xu , Meng Peixuan , Lv Dekang , Wang Chunli , Kelley Keith W. , Wang Ling , Cui Bai , Liu Quentin , Peng Fei
Published: July 2024

Background

Olanzapine (OLZ) reverses chronic stress-induced anxiety. Chronic stress promotes cancer development via abnormal neuro-endocrine activation. However, how intervention of brain-body interaction reverses chronic stress-induced tumorigenesis remains elusive.

Methods

KrasLSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model were used to study the effect of OLZ on cancer stemness and anxiety-like behaviors. Cancer stemness was evaluated by qPCR, western-blotting, immunohistology staining and flow-cytometry analysis of stemness markers, and cancer stem-like function was assessed by serial dilution tumorigenesis in mice and extreme limiting dilution analysis in primary tumor cells. Anxiety-like behaviors in mice were detected by elevated plus maze and open field test. Depression-like behaviors in mice were detected by tail suspension test. Anxiety and depression states in human were assessed by Hospital Anxiety and Depression Scale (HADS). Chemo-sensitivity of lung cancer was assessed by in vivo syngeneic tumor model and in vitro CCK-8 assay in lung cancer cell lines.

Results

In this study, we found that OLZ reversed chronic stress-enhanced lung tumorigenesis in both KrasLSL−G12D/WT lung cancer model and LLC1 syngeneic tumor model. OLZ relieved anxiety and depression-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing under chronic stress. NE activated ADRB2-cAMP-PKA-CREB pathway to promote CLOCK transcription, leading to cancer stem-like traits. As such, CLOCK-deficiency or OLZ reverses NE/chronic stress-induced gemcitabine (GEM) resistance in lung cancer. Of note, tumoral CLOCK expression is positively associated with stress status, serum NE level and poor prognosis in lung cancer patients.

Conclusion

We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.
Association of cerebrospinal fluid NPY with peripheral ApoA: a moderation effect of BMI
Authors: Zhao Danyang , Han Xiaoli , Mu Qingshuang , Wu Yan , Shan Ligang , Su Lidong , Wang Wenyan , Wang Pengxiang , Kang Yimin , Wang Fan
Published: July 2024

Background

Apoprotein A-I (ApoA-I) and Apoprotein B (ApoB) have emerged as novel cardiovascular risk biomarkers influenced by feeding behavior. Hypothalamic appetite peptides regulate feeding behavior and impact lipoprotein levels, which effects vary in different weight states. This study explores the intricate relationship between body mass index (BMI), hypothalamic appetite peptides, and apolipoproteins with emphasis on the moderating role of body weight in the association between neuropeptide Y (NPY), ghrelin, orexin A (OXA), oxytocin in cerebrospinal fluid (CSF) and peripheral ApoA-I and ApoB.

Methods

In this cross-sectional study, we included participants with a mean age of 31.77 ± 10.25 years, categorized into a normal weight (NW) (n = 73) and an overweight/obese (OW/OB) (n = 117) group based on BMI. NPY, ghrelin, OXA, and oxytocin levels in CSF were measured.

Results

In the NW group, peripheral ApoA-I levels were higher, while ApoB levels were lower than in the OW/OB group (all p < 0.05). CSF NPY exhibited a positive correlation with peripheral ApoA-I in the NW group (r = 0.39, p = 0.001). Notably, participants with higher CSF NPY levels had higher peripheral ApoA-I levels in the NW group and lower peripheral ApoA-I levels in the OW/OB group, showing the significant moderating effect of BMI on this association (R2 = 0.144, β=-0.54, p < 0.001). The correlation between ghrelin, OXA and oxytocin in CSF and peripheral ApoB in both groups exhibited opposing trends (Ghrelin: r = -0.03 and r = 0.04; OXA: r = 0.23 and r=-0.01; Oxytocin: r=-0.09 and r = 0.04).

Conclusion

This study provides hitherto undocumented evidence that BMI moderates the relationship between CSF NPY and peripheral ApoA-I levels. It also reveals the protective role of NPY in the NW population, contrasting with its risk factor role in the OW/OB population, which was associated with the at-risk for cardiovascular disease.
LC–ESI–MS/MS-based molecular networking, antioxidant, anti-glioma activity and molecular docking studies of Clematis graveolens
Authors: Ahmed Zubair , Ikram Muhammad , Khan Ishaq , Bashir Kashif , Shah Abdul Jabbar , Hussain Zahid , Khan Taous
Published: July 2024

Clematis graveolens Lindl., an indigenous climbing plant found in the Himalayan areas, is used by local communities for the treatment of neck tumors. The objective of this work is to examine the comprehensive metabolomic profile, antioxidant capability, in vitro and in silico anti-glioma effects on U-87 human glioma cell lines of the crude extract and fractions from C. graveolens. Liquid chromatography coupled with mass spectroscopy (LC–MS/MS) was used to establish detailed metabolite profiling of C. graveolens. The assessment of cell cytotoxicity was conducted using MTT cell viability assay on U-87 and BHK-21. Through molecular docking studies, the mode of inhibition and binding interaction between identified compounds and target proteins were also determined to evaluate the in vitro results. The use of LC–MS/MS-based global natural products social (GNPS) molecular networking analysis resulted in the identification of 27 compounds. The crude extract, ethyl acetate fraction, and chloroform fraction exhibited significant inhibitory activity against the U-87 cell lines, with IC50 values of 112.0, 138.1, and 142.7 µg/mL, respectively. The ethyl acetate fraction exhibited significant inhibitory concentration for 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity and the metal chelation activity with IC50 value of 39.50 µg/mL, 32.27 µg/mL, and 53.46 µg/mL, respectively. The crude extract showed maximum total phenolic, and total flavonoid concentration measuring 338.7 µg GAE/mg, and 177.04 µg QE/mg, respectively. The findings of this study indicate that C. graveolens consists of a diverse range of active phytoconstituents that possess antioxidant and anti-glioma properties.
Assessment of Financial Toxicity and Coping Strategies Associated With Cancer Treatment Among Caregivers of Patients With Cancer From a Lower-Middle–Income Country
Authors: Mathew Mebin , Rao Arathi P. , Pai Ananth , Sumit Kumar , Lewis Shirley
Published: July 2024

PURPOSE

The rising cost of cancer treatment causes out-of-pocket spending among patients or caregivers in lower-middle–income countries, resulting in acute misery and insolvency. This study aimed to assess the financial toxicity associated with cancer treatment and the coping strategies for cancer treatment adopted among the caregivers of patients with cancer in a tertiary cancer care center.

MATERIALS AND METHODS

This prospective cross-sectional study was conducted among the primary caregivers of patients with cancer undergoing curative treatment from March to June 2023. The estimated sample size was 403 caregivers. The financial toxicity was assessed using a modified Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy tool, and coping strategies were explored using a validated questionnaire of 20 questions. Univariate and multivariate analyses investigated the associations and factors influencing financial toxicity.

RESULTS

The caregivers recruited in the study were 403; 83.8% were younger than 50 years, and 66.5% were male. The common cancer types included were breast cancer (27.3%), GI cancer (17.9%), head and neck cancer (12.4%), and gynecological cancer (11.6%). The mean financial toxicity score was 22.32 (standard deviation, 9.55), with 64% experiencing moderate to severe financial toxicity. The most common coping strategies used were spending a portion or all of the savings, borrowing money from others, restructuring their spending habits, seeking financial assistance from the cancer center, and resorting to gold loans.

CONCLUSION

Screening patients and their primary caregivers using a modified COST tool can help identify families experiencing severe financial toxicity and provide necessary intervention.
Association Between State Medicaid Policies and Accrual of Black or Hispanic Patients to Cancer Clinical Trials
Authors: Schpero William L. , Takvorian Samuel U. , Blickstein Daniel , Shafquat Afrah , Liu Jingshu , Chatterjee Arnaub K. , Lamont Elizabeth B. , Chatterjee Paula
Published: July 2024

PURPOSE

It is unknown whether Medicaid expansion under the Affordable Care Act (ACA) or state-level policies mandating Medicaid coverage of the routine costs of clinical trial participation have ameliorated longstanding racial and ethnic disparities in cancer clinical trial enrollment.

METHODS

We conducted a retrospective, cross-sectional difference-in-differences analysis examining the effect of Medicaid expansion on rates of enrollment for Black or Hispanic nonelderly adults in nonobservational, US cancer clinical trials using data from Medidata's Rave platform for 2012-2019. We examined heterogeneity in this effect on the basis of whether states had pre-existing mandates requiring Medicaid coverage of the routine costs of clinical trial participation.

RESULTS

The study included 47,870 participants across 1,353 clinical trials and 344 clinical trial sites. In expansion states, the proportion of participants who were Black or Hispanic increased from 16.7% before expansion to 17.2% after Medicaid expansion (0.5 percentage point [PP] change [95% CI, –1.1 to 2.0]). In nonexpansion states, this proportion increased from 19.8% before 2014 (when the first states expanded eligibility under the ACA) to 20.4% after 2014 (0.6 PP change [95% CI, –2.3 to 3.5]). These trends yielded a nonsignificant difference-in-differences estimate of 0.9 PP (95% CI, –2.6 to 4.4). Medicaid expansion was associated with a 5.3 PP (95% CI, 1.9 to 8.7) increase in the enrollment of Black or Hispanic participants in states with mandates requiring Medicaid coverage of the routine costs of trial participation, but not in states without mandates (–0.3 PP [95% CI, –4.5 to 3.9]).

CONCLUSION

Medicaid expansion was not associated with a significant increase in the proportion of Black or Hispanic oncology trial participants overall, but was associated with an increase specifically in states that mandated Medicaid coverage of the routine costs of trial participation.
Neoadjuvant Chemotherapy in Colon Cancer: More Than Just an Optical Illusion
Authors: Peng Chengwei , Kircher Sheetal M.
Published: July 2024

The Oncology Grand Rounds series is designed to place original reports published in the
Journal
into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in
Journal of Clinical Oncology
, to patients seen in their own clinical practice
.
Adolescent Girls With Type 1 Diabetes Develop Changes in Bone Prior to Evidence of Clinical Neuropathy
Authors: Shen Ivana , Usala Rachel L , Mohseni Mahshid , Bouxsein Mary L , Mitchell Deborah M , Scheller Erica L
Published: July 2024

Context

Neuropathy and fracture are prevalent complications of type 1 diabetes (T1D). Although correlated in the clinical literature, it remains unknown whether neuropathy contributes to the initiation of bone loss at the earliest stages of disease.

Methods

We performed a single-center, cross-sectional study to quantify parameters of nerve and bone health in adolescent girls with T1D (n = 21) and associated controls (n = 12). Groups were well matched for age, height, strength, and physical activity.

Results

By high-resolution peripheral quantitative computed tomograpy, participants with T1D had lower trabecular bone volume fraction at the distal radius (−14.6%, P-adj = .095) and the tibia (−12.8%, P-adj = .017) and decreased trabecular thickness (−8.3% radius, P-adj = .007; −7.5% tibia, P-adj = .034) after adjustment for body size. In the tibia only, cortical bone mineral density was increased by 8.6% (P-adj = .024) and porosity was decreased by 52.9% with T1D (P-adj = .012). There were no significant differences in bone density by dual-energy x-ray absorptiometry. Participants with T1D also had lower circulating levels of osteocalcin (−30%, P = .057), and type I collagen cross-linked C-telopeptide (−36%, P = .035), suggesting low bone formation and turnover in T1D. Based on the Michigan Neuropathy Screening Instrument, 9.5% of those with T1D had clinical evidence of diabetic peripheral neuropathy. However, consideration of neuropathy status failed to explain the widespread T1D-associated changes in bone.

Conclusion

Our study defines early deficits in trabecular bone microarchitecture, decreased cortical porosity in the tibia, and suppression of biomarkers of bone turnover in adolescent girls with T1D, prior to the onset of symptomatic peripheral neuropathy. These findings inform our understanding of the rapid progression of skeletal disease in young girls with T1D and suggests that early detection and management strategies may help to prevent fracture and related comorbidities later in life.
Adverse Infant Health Outcomes Increased After the 2016 U.S. Presidential Election Among Non-White U.S.-born and Foreign-born Mothers
Authors: Langer Paola D. , Patler Caitlin , Hamilton Erin R.
Published: July 2024

Macro-level events such as elections can improve or harm population health across existing axes of stratification through policy changes and signals of inclusion or threat. This study investigates whether rates of, and disparities in, adverse birth outcomes between racialized and nativity groups changed after Donald Trump's November 2016 election, a period characterized by increases in xenophobic and racist messages, policies, and actions in the United States. Using data from 15,568,710 U.S. births between November 2012 and November 2018, we find that adverse birth outcomes increased after Trump's election among U.S.- and foreign-born mothers racialized as Black, Hispanic, and Asian and Pacific Islander (API), compared with the period encompassing the two Obama presidencies. Results for Whites suggest no change or a slight decrease in adverse outcomes following Trump's election, yet this finding was not robust to checks for seasonality. Black–White, Hispanic–White, and API–White disparities in adverse birth outcomes widened among both U.S.- and foreign-born mothers after Trump's election. Our findings suggest that Trump's election was a racist and xenophobic macro-level political event that undermined the health of infants born to non-White mothers in the United States.