bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNFAIP2 confers cisplatin resistance in head and neck squamous cell carcinoma via KEAP1/NRF2 signaling
Authors: Xu Teng , Yang Yuemei , Chen Zhihong , Wang Jinsong , Wang Xiaolei , Zheng Yang , Wang Chao , Wang Yachen , Zhu Zaiou , Ding Xu , Zhou Junbo , Li Gang , Zhang Hongchuang , Zhang Wei , Wu Yunong , Song Xiaomeng 
Published: August 2023

Abstract
Background
Drug resistance limits the treatment effect of cisplatin-based chemotherapy in head and neck squamous cell carcinoma (HNSCC), and the underlying mechanism is not fully understood. The aim of this study was to explore the cause of cisplatin resistance in HNSCC.

Methods
We performed survival and gene set variation analyses based on HNSCC cohorts and identified the critical role of tumor necrosis factor alpha-induced protein 2 (TNFAIP2) in cisplatin-based chemotherapy resistance. Half-maximal inhibitory concentration (IC50) examination, colony formation assays and flow cytometry assays were conducted to examine the role of TNFAIP2 in vitro, while xenograft models in nude mice and 4-nitroquinoline N-oxide (4NQO)-induced HNSCC models in C57BL/6 mice were adopted to verify the effect of TNFAIP2 in vivo. Gene set enrichment analysis (GSEA) and coimmunoprecipitation coupled with mass spectrometry (Co-IP/MS) were performed to determine the mechanism by which TNFAIP2 promotes cisplatin resistance.

Results
High expression of TNFAIP2 is associated with a poor prognosis, cisplatin resistance, and low reactive oxygen species (ROS) levels in HNSCC. Specifically, it protects cancer cells from cisplatin-induced apoptosis by inhibiting ROS-mediated c-JUN N-terminal kinase (JNK) phosphorylation. Mechanistically, the DLG motif contained in TNFAIP2 competes with nuclear factor-erythroid 2-related factor 2 (NRF2) by directly binding to the Kelch domain of Kelch-like ECH-associated protein 1 (KEAP1), which prevents NRF2 from undergoing ubiquitin proteasome-mediated degradation. This results in the accumulation of NRF2 and confers cisplatin resistance. Positive correlations between TNFAIP2 protein levels and NRF2 as well as its downstream target genes were validated in HNSCC specimens. Moreover, the small interfering RNA (siRNA) targeting TNFAIP2 significantly enhanced the cisplatin treatment effect in a 4NQO-induced HNSCC mouse model.

Conclusions
Our results reveal the antioxidant and cisplatin resistance-regulating roles of the TNFAIP2/KEAP1/NRF2/JNK axis in HNSCC, suggesting that TNFAIP2 might be a potential target in improving the cisplatin treatment effect, particularly for patients with cisplatin resistance.
The effects of sodium butyrate supplementation on the expression levels of PGC-1α, PPARα, and UCP-1 genes, serum level of GLP-1, metabolic parameters, and anthropometric indices in obese individuals on weight loss diet: a study protocol for a triple-blind, randomized, placebo-controlled clinical trial
Authors: Amiri Parichehr , Hosseini Seyed Ahmad , Roshanravan Neda , Saghafi-Asl Maryam , Tootoonchian Mitra 
Published: August 2023

Abstract
Background
Obesity is a multifaceted disease characterized by an abnormal accumulation of adipose tissue. Growing evidence has proposed microbiota-derived metabolites as a potential factor in the pathophysiology of obesity and related metabolic conditions over the last decade. As one of the essential metabolites, butyrate affects several host cellular mechanisms related to appetite sensations and weight control. However, the effects of butyrate on obesity in humans have yet to be studied. Thus, the present study was aimed to evaluate the effects of sodium butyrate (SB) supplementation on the expression levels of peroxisome proliferator activated-receptor (PPAR) gamma coactivator-1α (PGC-1α), PPARα and uncoupling protein 1 (UCP1) genes, serum level of glucagon-like peptide (GLP1), and metabolic parameters, as well as anthropometric indices in obese individuals on a weight loss diet.

Methods
This triple-blind randomized controlled trial (RCT) will include 50 eligible obese subjects aged between 18 and 60 years. Participants will be randomly assigned into two groups: 8 weeks of SB (600 mg/day) + hypo-caloric diet or placebo (600 mg/day) + hypo-caloric diet. At weeks 0 and 8, distinct objectives will be pursued: (1) PGC-1α, PPARα, and UCP1 genes expression will be evaluated by real-time polymerase chain reaction; (2) biochemical parameters will be assayed using enzymatic methods; and (3) insulin and GLP1 serum level will be assessed by enzyme-linked immunosorbent assay kit.

Discussion
New evidence from this trial may help fill the knowledge gap in this realm and facilitate multi-center clinical trials with a substantially larger sample size.

Trial registration
Iranian Registry of Clinical Trials: IRCT20190303042905N2. Registered on 31 January 2021.
Antibiotic treatment failure of uncomplicated urinary tract infections in primary care
Authors: Koh Sky Wei Chee , Ng Tracy Si Min , Loh Victor Weng Keong , Goh Jun Cong , Low Si Hui , Tan Wei Zhi , Wong Hung Chew , Durai Pradeep , Sun Louisa Jin , Young Doris , Tambyah Paul Anantharajah 
Published: August 2023

Abstract
Background
Higher resistance rates of > 20% have been noted in Enterobacteriaceae urinary isolates towards ciprofloxacin and co-trimoxazole (C + C) in Singapore, compared with amoxicillin-clavulanate and nitrofurantoin (AC + N). This study examined if treatment failure varied between different antibiotics, given different resistant rates, for uncomplicated urinary tract infections (UTIs) managed in primary care. We also aimed to identify gaps for improvement in diagnosis, investigations, and management.

Methods
A retrospective cohort study was conducted from 2019 to 2021 on female patients aged 18–50 with uncomplicated UTIs at 6 primary care clinics in Singapore. ORENUC classification was used to exclude complicated UTIs. Patients with uncomplicated UTIs empirically treated with amoxicillin-clavulanate, nitrofurantoin, ciprofloxacin or co-trimoxazole were followed-up for 28 days. Treatment failure was defined as re-attendance for symptoms and antibiotic re-prescription, or hospitalisation for UTI complications. After 2:1 propensity score matching in each group, modified Poisson regression and Cox proportional hazard regression accounting for matched data were used to determine risk and time to treatment failure.

Results
3194 of 4253 (75.1%) UTIs seen were uncomplicated, of which only 26% were diagnosed clinically. Urine cultures were conducted for 1094 (34.3%) uncomplicated UTIs, of which only 410 (37.5%) had bacterial growth. The most common organism found to cause uncomplicated UTIs was Escherichia coli (64.6%), with 92.6% and 99.4% of isolates sensitive to amoxicillin-clavulanate and nitrofurantoin respectively. Treatment failure occurred in 146 patients (4.57%). Among 1894 patients treated with AC + N matched to 947 patients treated with C + C, patients treated with C + C were 50% more likely to fail treatment (RR 1.49, 95% CI 1.10–2.01), with significantly higher risk of experiencing shorter time to failure (HR 1.61, 95% CI 1.12–2.33), compared to patients treated with AC + N.

Conclusion
Treatment failure rate was lower for antibiotics with lower reported resistance rates (AC + N). We recommend treating uncomplicated UTIs in Singapore with amoxicillin-clavulanate or nitrofurantoin, based on current local antibiograms. Diagnosis, investigations and management of UTIs remained sub-optimal. Future studies should be based on updating antibiograms, highlighting its importance in guideline development.
Multi-isotope (δ2H, δ13C, δ15N) feather profiles and morphometrics inform patterns of migratory connectivity in three species of North American swallows
Authors: Hobson Keith A. , Kardynal Kevin J. 
Published: August 2023

AbstractAerial insectivorous birds have suffered steep population declines in North America over the last 60 years. A lack of information on migratory connectivity between breeding and non-breeding grounds for these species limits our ability to interpret factors affecting their population-specific trends. We determined likely Latin American non-breeding regions of Bank (Riparia riparia), Barn (Hirundo rustica) and Cliff (Petrochelidon pyrrhonota) swallow from populations across their breeding ranges. We used predicted feather hydrogen (δ2Hf) and carbon (δ13Cf) isoscapes for winter-grown feathers to indicate areas of highest probability of moult origin and incorporated these results into a cluster analysis to determine likely broad non-breeding regions. We also assessed variation in wing length among populations to determine the potential for this metric to differentiate population moult origins. We then investigated patterns of multi-isotopic (δ2Hf,δ13Cf,δ15Nf) and wing-length niche occupancy by quantifying niche size and overlap among populations under the assumption that broad niches were consistent with low within-species migratory connectivity and narrow and non-overlapping niches with higher connectivity. Multivariate assignment identified different non-breeding regions and potential clusters of moult origin generally corresponding to Central America and northern South America, eastern and south-central South America, and the western and southern part of that continent, with variation within and among populations and species. Separate niche space indicated different wintering habitat or areas used by species or populations whereas niche overlap indicated only potential spatial similarity. Wing length varied significantly among populations by species, being longer in the west and north for Bank and Cliff Swallow and longer in eastern Canadian Barn Swallow populations. Barn Swallow occupied consistently larger isotopic and wing length niche space than the other species. Comparisons among populations across species showed variable isotopic and wing-length niche overlap generally being greater within breeding regions and lower between western and eastern breeding populations supporting a general North American continental divide for all species with generally low migratory connectivity for all species. We present a novel approach to assessing connectivity using inexpensive and broad isotopic approaches that provides the basis for hypothesis testing using more spatially explicit expensive techniques.
In silico prediction of siRNA to silence the SARS-CoV-2 omicron variant targeting BA.4, BA.5, BQ.1, BQ1.1. and XBB: an alternative to traditional therapeutics
Authors: Islam Rahatul , Shahriar Asif , Fatema Nour , Uddin Muhammad Ramiz , Acharjee Mrityunjoy , Shepon Md Mukhlesur Rahman , Sarkar Avishek , Aurin Khosnur Jahan 
Published: August 2023

Abstract
Background
After the first infection in December 2019, the mutating strains of SARS-CoV2 have already affected a lot of healthy people around the world. But situations have not been as devastating as before the first pandemic of the omicron strains of SARS-CoV2. As of January 2023, five more Omicron offshoots, BA.4, BA.5, B.Q.1, B.Q.1.1 and XBB are now proliferating worldwide. Perhaps there are more variants already dormant that require only minor changes to resurrect. So, this study was conducted with a view to halting the infection afterwards. The spike protein found on the virus outer membrane is essential for viral attachment to host cells, thus making it an attractive target for vaccine, drug, or any other therapeutic development. Small interfering RNAs (siRNAs) are now being used as a potential treatment for various genetic conditions or as antiviral or antibacterial therapeutics. Thus, in this study, we looked at spike protein to see if any potential siRNAs could be discovered from it.

Results
In this study, by approaching several computational assays (e.g., GC content, free energy of binding, free energy of folding, RNA–RNA binding, heat capacity, concentration plot, validation, and finally molecular docking analysis), we concluded that two siRNAs could be effective to silence the spike protein of the omicron variant. So, these siRNAs could be a potential target for therapeutic development against the SARS-CoV2 virus by silencing the spike protein of this virus.

Conclusion
We believe our research lays the groundwork for the development of effective therapies at the genome level and might be used to develop chemically produced siRNA molecules as an antiviral drug against SARS-CoV2 virus infection.

Graphical abstract
Removal of obstructive organized tracheo-bronchial clots under respiratory support using veno-venous extracorporeal membrane oxygenation in a patient with blunt thoracic trauma: a case report
Authors: Tanikawa Atsushi , Fujita Motoo , Kudo Yasushi , Katsuta Ken , Kurokawa Yoshiaki , Sato Takeaki , Kushimoto Shigeki 
Published: August 2023

Abstract
Background
It has been reported that veno-venous extracorporeal membrane oxygenation is useful for treating patients with acute respiratory failure following severe thoracic trauma. However, the removal of an obstructive organized tracheo-bronchial clot under respiratory support using extracorporeal membrane oxygenation in a patient with trauma has never been reported.

Case presentation
A teenage female was injured in a fall and experienced right open hemopneumothorax and bilateral lung contusions. Since she was in refractory shock due to bleeding into the right thoracic cavity, we performed right thoracotomy and resection of the lacerated right middle lobe. After hemorrhage control, her respiratory status could not be maintained under mechanical respiratory support. Therefore, we initiated veno-venous extracorporeal membrane oxygenation. Although her respiratory failure gradually improved, the removal of obstructing tracheo-bronchial organized blood clots using bronchoscopy was required daily. Because of the size and firm adherence of organized clots to the airway membrane, we performed a tracheostomy to remove organized clots directly through the incision under extracorporeal membrane oxygenation without any adverse events on day 9. The next day, she was successfully removed from extracorporeal membrane oxygenation.

Conclusions
Extracorporeal membrane oxygenation could provide respiratory support not only for acute respiratory failure but also for removal of obstructing tracheo-bronchial organized clots in patients with severe lung injury following trauma.
Cost-effectiveness analysis of physical activity interventions for people with schizophrenia or bipolar disorder: systematic review
Authors: Jin Huajie , Kolawole Oluwafunso , Wang Zhengwei 
Published: August 2023

BackgroundClinical guidelines recommend providing physical activity interventions (PAIs) to people with schizophrenia or bipolar disorder for weight management. However, the cost-effectiveness of PAIs is unknown.AimsTo evaluate the availability and methodological quality of economic evaluations of PAIs for people with schizophrenia or bipolar disorder.MethodFour databases (MEDLINE, Embase, PsycInfo and Scopus) were searched on 5 July 2022. Based on the retrieved studies, forward and backward citation searches were conducted. Two reviewers independently selected studies for inclusion. Study quality was assessed using the Drummond checklist. Review results were presented using narrative synthesis.ResultsFourteen articles reporting nine studies were included. All included studies assessed PAIs within a multicomponent lifestyle intervention. Mixed findings were reported on the cost-effectiveness of multicomponent lifestyle intervention: three studies reported it as cost-effective; four studies reported it as not cost-effective; and two studies did not conclude whether it was cost-effective or not. Very limited evidence suggests that certain patient subgroups might be more likely to benefit from multicomponent lifestyle interventions with a PAI component: men; individuals with comorbid type 2 diabetes; and individuals who have been psychiatric hospital in-patients for ≥1 year. The quality of included studies ranged from moderate to high.ConclusionsThe current economic evidence suggests that not all modalities of multicomponent lifestyle intervention including a PAI component are cost-effective for people with schizophrenia or bipolar disorder; and not all people with schizophrenia or bipolar disorder would benefit equally from the intervention. Future research is urgently needed to identify the cost-effective modality of PAI for different patient subgroups.
Enhancement and Implementation of a Health Information Technology Module to Improve the Discrete Capture of Cancer Staging in a Diverse Regional Health System
Authors: Walesa Macy B. , Denny Ashley , Patel Alpa , Mulcahy Mary , Kircher Sheetal , George Christopher , Tsarwhas Dean , Ross Ashley , Platanias Leonidas C. , Poylin Vitaly , Yang Anthony D. , Barnard Cynthia , Bilimoria Karl Y. , Merkow Ryan P. 
Published: August 2023

PURPOSE Cancer staging is the foundation for all cancer management decisions. For real-time use, stage must be embedded in the electronic health record as a discrete data element. The objectives of this quality improvement (QI) initiative were to (1) identify barriers to utilization of an existing discrete cancer staging module, (2) identify health information technology (HIT) solutions to support discrete capture of cancer staging data, and (3) increase capture across the oncology enterprise in our diverse health system. METHODS Six sigma QI methodologies were used to define barriers and solutions to improve discrete cancer staging. Design thinking principles informed solution development to test prototypes. Two multidisciplinary teams of disease-specific clinicians within GI and genitourinary conducted phased testing pilots to determine health system solutions. Solutions were expanded to all oncology specialties across our health system. RESULTS Baseline average discrete staging capture across our health system was 31%. Poor workflow efficiency, limited accountability, and technical design gaps were key barriers to timely, complete staging. Implementation of more than 25 design enhancements to a HIT solution and passive user alerts led to a postimplementation capture rate of 58% across 55 outpatient clinics involving more than 400 clinicians. CONCLUSION We identified key barriers to discrete data capture and designed solutions through iterative use of QI methodologies and disease-specific pilots. After implementation, discrete capture of cancer staging nearly doubled across our diverse health system. This approach is scalable and transferable to other initiatives to develop and implement clinically relevant HIT solutions across a diverse health system.
A new species of Perinereis Kinberg, 1865 (Annelida: Nereididae) from the Western Mediterranean Sea revealed by morphological and molecular approaches
Authors: REZZAG MAHCENE HIBA , VILLALOBOS-GUERRERO TULIO  F , KURT GÜLEY , DENIS FRANCOISE , DAAS TAREK 
Published: August 2023

This study uses morphological and molecular evidence to describe a new intertidal species of Perinereis Kinberg, 1865 (Annelida: Nereididae) from northeast Algeria. Perinereis louizomarum n. sp. belongs to Subgroup 1A, which is distinguished by a single bar shaped paragnath on area VI of the proboscis and a dorsal ligule that is either slightly or not expanded in the posterior parapodia. The new species differs from P. cultrifera and similar congeners by having a bare area V and slightly enlarged posterior dorsal ligules. Furthermore, using newly generated and mined sequences from online databases, and mined sequences of Perinereis species from online, the analysis of cytochrome c oxidase subunit 1 (COI) mitochondrial gene sequences supported its status as new species. An identification key of the Perinereis species belonging to Subgroup 1A is also provided.
Redefinition of Rural Spaces: A Methodological Tool
Authors: Kanaraki Evanthia , Konstantopoulou Anastasia , Ntogou Elina , Klabatsea Rena , Konstantinidou Elena 
Published: August 2023

The desolation of rural areas and historic settlements is a particularly intense phenomenon in recent decades. Gradually, the tradition and history of these places are being worn away leading to the alteration of their identity. The economy is monopolized by the service and tourism sectors and quite often, this converts them into a seasonal touristic product.
The "redefinition" of the rural space is a necessary condition in order to formulate a sustainable strategic plan which will respond to contemporary needs and at the same time, respect the uniqueness of the place and preserve its cultural identity.
This paper attempts to highlight a methodological tool for the planning of the rural areas, in terms of protecting and promoting them, on the occasion of the research carried out in the context of a diploma project for the broader region of Fodele village, in northern Heraklion (Crete).
A key element for the research is the utilization of endogenous resources and their correlation with extraneous trends. Using this tool, conceptual networks of different resource types are created. By projecting these networks onto the space, and taking into consideration geospatial criteria (proximity, topography, type of resource), spatial units of particular identity are being formed. Resources- networks of social type and stakeholders co-act to implement a strategic plan for the revitalization and promotion of the spatial units (anthropogenic and physical environment).
The procedure relates to a system of successive space readings and interpretative mapping at multiple scales. The conclusions derived from each stage lead to the next. Ultimately, this interdisciplinary process forms the essential background and design principles, for the articulation of a comprehensive strategic plan, aiming at the revitalization of the rural space and its sustainable development/enhancement (cultural, heritage, economic, environmental, etc.) in contemporary terms.
Mutational profile of primary clear cell renal cell carcinoma predicts recurrence and potential candidacy for adjuvant immune checkpoint inhibition
Authors: Vlachostergios Panagiotis J. , Papathanassiou Maria , Anagnostou Maria , Thodou Eleni , Tamposis Ioannis , Mitrakas Lampros , Zachos Ioannis , Ioannou Maria , Koukoulis George K. , Samara Maria , Tzortzis Vassilios 
Published: August 2023

Background: The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment. Methods: Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451). Results: VHL was the most frequently mutated gene (51%), followed by PBRM1 (27%), BAP1 (13%), SETD2 (13%), KDM5C (5%), ATM (5%), MTOR (5%), and PTEN (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without VHL was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or VHL-only mutations as opposed to three relapses in patients with non-VHL somatic mutations (p=0.06). Presence of somatic mutations in PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, or PTEN genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01). Conclusions: Preliminary findings from this ongoing study support the prognostic value of non-VHL mutations including PBRM1, BAP1, SETD2, KDM5C, ATM, MTOR, and PTEN in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.