bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strengthening local government policies to address health inequities: perspectives from Australian local government stakeholders
Authors: Schultz Sally , Zorbas Christina , Peeters Anna , Yoong Serene , Backholer Kathryn 
Published: June 2023

Abstract
Background
With their close connection to community and increasing preventive health remit, local governments are well positioned to implement policies and programs to address health inequities. Nevertheless, there is a lack of evidence of equity-focused policy action in this sector. We aimed to understand how local government representatives approach equity in the development and implementation of health and wellbeing policies and programs, and to identify potential enablers for strengthening an equity focus.

Methods
We conducted semi-structured interviews (June 2022-January 2023) with 29 health directorate representatives from 21 local governments in Victoria, Australia. Representatives were recruited from urban, regional and rural local government areas, with varying levels of socioeconomic position. Data was analysed inductively using Braun and Clarke’s reflexive thematic analysis, informed by social determinants of health theory and a public policy decision making framework.

Results
Local governments approach health equity in different ways including focusing on priority populations, disadvantaged geographic areas, or by targeting the upstream determinants of health, such as housing and employment. Enabling factors for more equity-oriented local government policy action included those internal to local governments: (i) having a clear conceptualisation of equity, (ii) fostering a strong equity-centric culture, and (iii) developing organisational-wide competency in health equity. External factors related to key stakeholder groups that support and/or influence local governments included: (iv) strong support from community, (v) state government leadership and legislation, and (vi) supportive local partners, networks and NGO’s.

Conclusions
Local governments have a responsibility to implement policies and programs that improve health and reduce health inequities. Local government’s capacity to leverage resources, structures, processes and relationships, internally and across sectors and community, will be key to strengthening equity-oriented local government health policies and programs.
Assessing the association between overcrowding and human physiological stress response in different urban contexts: a case study in Salzburg, Austria
Authors: Zhang Zhaoxi , Měchurová Kristýna , Resch Bernd , Amegbor Prince , Sabel Clive E. 
Published: June 2023

AbstractOvercrowding in densely populated urban areas is increasingly becoming an issue for mental health disorders. Yet, only few studies have examined the association between overcrowding in cities and physiological stress responses. Thus, this study employed wearable sensors (a wearable camera, an Empatica E4 wristband and a smartphone-based GPS) to assess the association between overcrowding and human physiological stress response in four types of urban contexts (green space, transit space, commercial space, and blue space). A case study with 26 participants was conducted in Salzburg, Austria. We used Mask R-CNN to detect elements related to overcrowding such as human crowds, sitting facilities, vehicles and bikes from first-person video data collected by wearable cameras, and calculated a change score (CS) to assess human physiological stress response based on galvanic skin response (GSR) and skin temperature from the physiological data collected by the wristband, then this study used statistical and spatial analysis to assess the association between the change score and the above elements. The results demonstrate the feasibility of using sensor-based measurement and quantitative analysis to investigate the relationship between human stress and overcrowding in relation to different urban elements. The findings of this study indicate the importance of considering human crowds, sitting facilities, vehicles and bikes to assess the impact of overcrowding on human stress at street level.
Glucocorticoid nanoformulations relieve chronic pelvic pain syndrome and may alleviate depression in mice
Authors: Yang Yang , Hu Ruimin , Zheng Jun , Wang Qianmei , Xu Senlin , Zhou Zhansong , Zhang Dinglin , Shen Wenhao 
Published: June 2023

Abstract
Background
Chronic pelvic pain syndrome (CPPS) is a typical symptom of chronic prostatitis (CP) in males that may cause abnormal urination, sexual dysfunction, or depression and significantly affect the quality of life of the patient. Currently, there is no effective treatment for CPPS due to its recurrence and intractability. For synergistic CPPS therapy, we developed pH/reactive oxygen species (ROS) dual-responsive dexamethasone (Dex) nanoformulations using a ROS-responsive moiety and phytochemical modified α-cyclodextrin (α-CD) as the carrier.

Results
Dex release from the nanoformulations can be controlled in acidic and/or ROS-rich microenvironments. The fabricated Dex nanoformulations can also be efficiently internalized by lipopolysaccharide (LPS)-stimulated macrophages, prostatic epithelial cells, and stromal cells. Moreover, the levels of proinflammatory factors (e.g., TNF-α, IL-1β, and IL-17 A) in these cells were significantly decreased by Dex nanoformulations treatment through the release of Dex, phytochemical and elimination of ROS. In vivo experiments demonstrated notable accumulation of the Dex nanoformulations in prostate tissue to alleviate the symptoms of CPPS through the downregulation of proinflammatory factors. Interestingly, depression in mice may be relieved due to alleviation of their pelvic pain.

Conclusion
We fabricated Dex nanoformulations for the effective management of CPPS and alleviation of depression in mice.
Utilizing nanozymes for combating COVID-19: advancements in diagnostics, treatments, and preventative measures
Authors: Wang Jia , Xie Qingpeng , Song Haoyue , Chen Xiaohang , Zhang Xiaoxuan , Zhao Xiangyu , Hao Yujia , Zhang Yuan , Li Huifei , Li Na , Fan Kelong , Wang Xing 
Published: June 2023

AbstractThe emergence of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses significant challenges to global public health. Despite the extensive efforts of researchers worldwide, there remains considerable opportunities for improvement in timely diagnosis, specific treatment, and effective vaccines for SARS-CoV-2. This is due, in part, to the large number of asymptomatic carriers, rapid virus mutations, inconsistent confinement policies, untimely diagnosis and limited clear treatment plans. The emerging of nanozymes offers a promising approach for combating SARS-CoV-2 due to their stable physicochemical properties and high surface areas, which enable easier and multiple nano-bio interactions in vivo. Nanozymes inspire the development of sensitive and economic nanosensors for rapid detection, facilitate the development of specific medicines with minimal side effects for targeted therapy, trigger defensive mechanisms in the form of vaccines, and eliminate SARS-CoV-2 in the environment for prevention. In this review, we briefly present the limitations of existing countermeasures against coronavirus disease 2019 (COVID-19). We then reviewed the applications of nanozyme-based platforms in the fields of diagnostics, therapeutics and the prevention in COVID-19. Finally, we propose opportunities and challenges for the further development of nanozyme-based platforms for COVID-19. We expect that our review will provide valuable insights into the new emerging and re-emerging infectious pandemic from the perspective of nanozymes.
Graphical Abstract
Prognostic analysis of patients with stage IIIC1p cervical cancer treated by surgery
Authors: Fan Xiang , Wang Yifei , Yang Ni , Zhu Pengfeng 
Published: June 2023

Abstract
Background
Cervical cancer (CC) is one of the most common gynaecologic malignancies. The prognosis of stage IIIC1p cervical cancer patients treated by surgery is heterogeneous. Therefore, the aim of this study was to analyse the factors influencing the prognosis in such patients.

Methods
From January 2012 to December 2017, 102 patients with cervical cancer who underwent surgical treatment in the Department of Gynaecology and Tumours, Changzhou Maternal and Child Health Hospital, and had pelvic lymph node metastasis confirmed by pathology were analysed retrospectively. All patients underwent radical hysterectomy with/without oophorectomy with pelvic lymphadenectomy with/without para-aortic lymphadenectomy. Clinical data was collected including age, surgical method, ovarian status, intraoperative blood loss, perioperative complications, tumour size, pathological type, depth of stromal invasion (DSI), whether the lymphatic vascular space was infiltrated, number of pelvic lymph node metastases, location of pelvic lymph node metastases, total number of lymph nodes resected, lymph node ratio (LNR), nature of vaginal margin, whether parametrium was involved, postoperative adjuvant therapy, preoperative neutrophil–lymphocyte ratio (NLR) and prognostic information of patients. Survival curves for overall survival (OS) and disease-free survival (DFS) were plotted using the Kaplan–Meier method, and the difference between the survival curves was tested using the log-rank test. Univariate and multivariate COX regression models were used to assess the factors associated with overall survival and disease-free survival in patients with stage IIIC1p cervical cancer. Nomogram plots were constructed to predict OS and DFS, and the predictive accuracy of the nomograms was measured by Harrell’s C-index and calibration curves.

Results
A total of 102 patients with stage IIIC1p cervical cancer were included in the study, and the median follow-up time was 63 months (range from 6 to 130 months). The 5-year OS was 64.7%, and the 5-year DFS was 62.7%. Multivariate analysis showed that no postoperative adjuvant therapy, LNR > 0.3 and NLR > 3.8 were independent risk factors for OS and DFS in patients with stage IIIC1p cervical cancer.

Conclusions
Patients with stage IIIC1p cervical cancer have a poor prognosis. Lower OS and DFS were associated with no postoperative adjuvant therapy, LNR > 0.3 and NLR > 3.8.
Anxiety increased among children and adolescents during pandemic-related school closures in Europe: a systematic review and meta-analysis
Authors: Ludwig-Walz Helena , Dannheim Indra , Pfadenhauer Lisa M. , Fegert Jörg M. , Bujard Martin 
Published: June 2023

Abstract
Background
Considering the heterogenous evidence, a systematic review of the change in anxiety in European children and adolescents associated with the COVID-19 pandemic is lacking. We therefore assessed the change compared with pre-pandemic baselines stratified by gender and age as well as evaluated the impact of country-specific restriction policies.

Methods
A registration on the ‘International Prospective Register of Systematic Reviews’ (PROSPERO) occurred and an a priori protocol was published. We searched six databases (PubMed, Embase, PsycINFO, Cochrane Central Register of Controlled Trials, Web of Science, WHO COVID-19) using a peer-reviewed search string with citation tracking and grey literature screening. Primary outcomes were: (1) general anxiety symptoms; and (2) clinically relevant anxiety rates. We used the Oxford COVID-19 Stringency Index as an indicator of pandemic-related restrictions. Screening of title/abstract and full text as well as assessing risk of bias (using the ‘Risk of Bias in Non-randomized Studies of Exposure’ [ROBINS-E]) and certainty of evidence (using the ‘Grading of Recommendations Assessment, Development and Evaluation’ [GRADE]) was done in duplicate. We pooled data using a random effects model. Reporting is in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) statement.

Results
Of 7,422 non-duplicate records, 18 studies with data from 752,532 pre-pandemic and 763,582 pandemic participants met full inclusion criteria. For general anxiety symptoms the total change effect estimate yielded a standardised mean difference (SMD) of 0.34 (95% confidence interval [CI], 0.17–0.51) and for clinically relevant anxiety rates we observed an odds ratio of 1.08 (95%-CI, 0.98–1.19). Increase in general anxiety symptoms was highest in the 11–15 years age group. Effect estimates were higher when pandemic-related restrictions were more stringent (Oxford Stringency Index > 60: SMD, 0.52 [95%-CI, 0.30–0.73]) and when school closures (School Closure Index ≥ 2: SMD, 0.44 [95%-CI, 0.23–0.65]) occurred.

Conclusion
General anxiety symptoms among children and adolescents in Europe increased in a pre/during comparison of the COVID-19 pandemic; particularly for males aged 11–15 years. In periods of stringent pandemic-related restrictions and/or school closures a considerable increase in general anxiety symptoms could be documented.
PROSPERO registration: CRD42022303714.
Targeted therapy using polymyxin B hemadsorption in patients with sepsis: a post-hoc analysis of the JSEPTIC-DIC study and the EUPHRATES trial
Authors: Osawa Itsuki , Goto Tadahiro , Kudo Daisuke , Hayakawa Mineji , Yamakawa Kazuma , Kushimoto Shigeki , Foster Debra M. , Kellum John A. , Doi Kent 
Published: June 2023

Abstract
Background
Polymyxin B hemadsorption (PMX-HA) reduces blood endotoxin levels, but characteristics of patients with sepsis likely to benefit from PMX-HA are not well known. We sought to identify patient subgroups likely to benefit from PMX-HA.

Methods
We retrospectively identified 1911 patients with sepsis from a retrospective observational study in Japan (the JSEPTIC-DIC study) and 286 patients with endotoxemic septic shock from a randomized controlled trial in North America that restricted patients to those with high endotoxin activity (the EUPHRATES trial). We applied the machine learning-based causal forest model to the JSEPTIC-DIC cohort to investigate heterogeneity in treatment effects of PMX-HA on 28-day survival after adjusting for potential confounders and ascertain the best criteria for PMX-HA use. The derived criteria for targeted therapy by PMX-HA were validated using the EUPHRATES trial cohort.

Results
The causal forest model revealed heterogeneity in treatment effects of PMX-HA. Since patients having higher treatment effects were more likely to have severe coagulopathy and hyperlactatemia, we identified the potential treatment targets of PMX-HA as patients with PT-INR > 1.4 or lactate > 3 mmol/L. In the EUPHRATES trial cohort, PMX-HA use on the targeted subpopulation (75% of all patients) was significantly associated with higher 28-day survival (PMX-HA vs. control, 68% vs. 52%; treatment effect of PMX-HA, + 16% [95% CI + 2.2% to + 30%], p = 0.02).

Conclusions
Abnormal coagulation and hyperlactatemia in septic patients with high endotoxin activity appear to be helpful to identify patients who may benefit most from PMX-HA. Our findings will inform enrollment criteria for future interventional trials targeting patients with coagulopathy and hyperlactatemia.
The occurrence and zoonotic potential of Cryptosporidium species in freshwater biota
Authors: Hayes Laura , Robinson Guy , Chalmers Rachel M. , Ormerod Steve J. , Paziewska-Harris Anna , Chadwick Elizabeth A. , Durance Isabelle , Cable Jo 
Published: June 2023

Abstract
Background
Protozoan pathogens from the genus Cryptosporidium cause the diarrhoeal disease cryptosporidiosis in humans and animals globally. Freshwater biota could act as potential reservoirs or zoonotic sources of Cryptosporidium infections for livestock and people, but Cryptosporidium occurrence in aquatic biota is largely unexplored. The aim of this study was to investigate the occurrence of Cryptosporidium in a range of freshwater organisms in upland rivers across England and Wales.

Methods
Fish were sampled by electrofishing, invertebrate larvae by kick sampling and the otter Lutra lutra and mink Mustela vison through faecal samples collected opportunistically as part of a nation-wide study. PCR targeting the small subunit ribosomal RNA gene was used to detect Cryptosporidium species.

Results
Cryptosporidium occurred in just 0.8% of all the samples and in none of 73 samples from nine invertebrate genera. Cryptosporidium was detected in two of 2/74 fish samples (2.7%), both salmonids, and in 2/92 otter faecal samples (2.17%), but there were no positive samples in mink (0/24) or the bullhead Cottus gobio (0/16).

Conclusions
Low detection rate of human-infective Cryptosporidium species in aquatic fauna indicates they may present a low risk of contamination of some upland freshwaters.

Graphical Abstract
Whole genome sequencing across clinical trials identifies rare coding variants in GPR68 associated with chemotherapy-induced peripheral neuropathy
Authors: Khan Zia , Jung Min , Crow Megan , Mohindra Rajat , Maiya Vidya , Kaminker Joshua S. , Hackos David H. , Chandler G. Scott , McCarthy Mark I. , Bhangale Tushar 
Published: June 2023

Abstract
Background
Dose-limiting toxicities significantly impact the benefit/risk profile of many drugs. Whole genome sequencing (WGS) in patients receiving drugs with dose-limiting toxicities can identify therapeutic hypotheses to prevent these toxicities. Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting neurological toxicity of chemotherapies with no effective approach for prevention.

Methods
We conducted a genetic study of time-to-first peripheral neuropathy event using 30× germline WGS data from whole blood samples from 4900 European-ancestry cancer patients in 14 randomized controlled trials. A substantial number of patients in these trials received taxane and platinum-based chemotherapies as part of their treatment regimen, either standard of care or in combination with the PD-L1 inhibitor atezolizumab. The trials spanned several cancers including renal cell carcinoma, triple negative breast cancer, non-small cell lung cancer, small cell lung cancer, bladder cancer, ovarian cancer, and melanoma.

Results
We identified a locus consisting of low-frequency variants in intron 13 of GRID2 associated with time-to-onset of first peripheral neuropathy (PN) indexed by rs17020773 (p = 2.03 × 10−8, all patients, p = 6.36 × 10−9, taxane treated). Gene-level burden analysis identified rare coding variants associated with increased PN risk in the C-terminus of GPR68 (p = 1.59 × 10−6, all patients, p = 3.47 × 10−8, taxane treated), a pH-sensitive G-protein coupled receptor (GPCR). The variants driving this signal were found to alter predicted arrestin binding motifs in the C-terminus of GPR68. Analysis of snRNA-seq from human dorsal root ganglia (DRG) indicated that expression of GPR68 was highest in mechano-thermo-sensitive nociceptors.

Conclusions
Our genetic study provides insight into the impact of low-frequency and rare coding genetic variation on PN risk and suggests that further study of GPR68 in sensory neurons may yield a therapeutic hypothesis for prevention of CIPN.
Epidemiological and transcriptome data identify potential key genes involved in iron overload for type 2 diabetes
Authors: Liu Xuekui , Hong Xiu , Jiang Shiqiang , Li Rui , Lv Qian , Wang Jie , Wang Xiuli , Yang Manqing , Geng Houfa , Li Yang 
Published: June 2023

Abstract
Background
Many previous studies have reported the association between iron overload (IO) and type 2 diabetes mellitus (T2DM). However, the underlying molecular mechanism is not clear.

Methods
Epidemiological data from the National Health and Nutrition Examination Survey 2017–2018 (NHANES) was used to systematically explore the association between IO and diabetes. Furthermore, transcriptome data from Gene Expression Omnibus (GEO) were analyzed using bioinformatics methods to explore the underlying functional mechanisms at the molecular level.

Results
Data from NHANES showed a “W” shape relationship between serum iron (frozen) and the risk of diabetes (P < 0.001) as well as a “∧” shape correlation between serum unsaturated iron binding capacity (UIBC) and the risk of diabetes (P = 0.007). Furthermore, the serum iron (frozen) was positively associated with fasting plasma glucose and HOMAB (P < 0.05), and UIBC was positively associated with fasting insulin (P < 0.05). Transcriptome data showed that two IO-related genes [Transferrin receptor (TFRC) and Solute carrier family-11 member-2 (SLC11A2)] were down-regulated in T2DM. The correlation analysis showed that expression levels of TFRC and SLC11A2 were significantly and positively correlated with genes involved in insulin secretion (P < 0.05). Protein–protein interaction network analysis showed that TFRC and SLC11A2 interacted with four key genes, including VAMP2, HIF1A, SLC2A1, and RAB11FIP2.

Conclusion
We found that IO status was associated with increased FPG and aggravated HOMAB, and two IO-related genes (TFRC and SLC11A2) might induce the occurrence of T2DM by influencing insulin secretion, which provides potential therapeutic targets for T2DM patients.
Atypical tibial fracture in breast cancer patient with bone metastasis receiving denosumab therapy: a case report and review of the literature
Authors: Yanagisawa Yohei , Suzuki Hidefumi , Gamada Hisanori , Yamazaki Masashi 
Published: June 2023

Abstract
Background
Denosumab therapy is often used to reduce skeletal-related events in metastatic bone disease. On the other hand, there have been some instances of atypical femoral fracture in patients with metastatic bone disease treated with denosumab. In this case report, we describe a patient with metastatic bone disease due to breast cancer who had been using denosumab for 4 years to prevent skeletal-related events and suffered an atypical tibial fracture.

Case presentation
We report here the case of an 82-year-old Japanese woman who had received yearly intravenous denosumab for 4 years and presented with a fracture fulfilling the criteria for an atypical fracture, except for being located at the tibial diaphysis. She was found to have stage 4 breast cancer with multiple bone metastases 4 years prior. She had difficulty walking due to her tibial pain and underwent surgical treatment. Four months after surgery, the tibial fracture site exhibited bone fusion.

Conclusion
In patients with long-term use of denosumab to prevent skeletal-related events in metastatic bone disease, it is important to be aware of shin and thigh pain and to examine for signs of atypical tibial fractures to pay attention to atypical femoral fractures.