bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobile phone dependency and sleep quality in college students during COVID-19 outbreak: the mediating role of bedtime procrastination and fear of missing out
Authors: Huang Tao , Liu Yiting , Tan Teck Cheng , Wang Dong , Zheng Kefeng , Liu Wenxi
Published: June 2023

Objective

The purpose of this study was to investigate the associations between mobile phone dependency, bedtime procrastination, FoMO, and sleep quality among college students during the COVID-19 outbreak. Specifically, we examined whether bedtime procrastination and FoMO mediate the relationship between mobile phone dependency and sleep quality.

Methods

A total of 881 college students completed an online survey in May 2022 in Shanghai, China. Mobile Phone Involvement Questionnaire, Bedtime Procrastination Scale, Fear of Missing Out Scale and Pittsburgh Sleep Quality Index were used to assess mobile phone dependency, bedtime procrastination, fear of missing out, and sleep quality, respectively. Multiple linear regression and mediation analysis were conducted.

Results

The correlation analyses indicated mobile phone dependency was positively associated with fear of missing out, bedtime procrastination, and poor sleep quality among college students. The structural equation modeling analyses revealed that mobile phone dependency had significant indirect effects on sleep quality through bedtime procrastination (indirect effect: 0.030, 95%CI: 0.022–0.041) and fear of missing out (indirect effect: 0.013, 95%CI: 0.003–0.023).

Conclusion

The findings indicated that bedtime procrastination and fear of missing out are mediators mediating the relationship between mobile phone dependency with sleep quality. Bedtime procrastination and fear of missing out should be considered as potential intervention targets for reducing mobile phone dependency and improving sleep quality in college students.
Hearing loss and respiratory health symptoms among large-scale sawmill workers of the timber processing factories within the Gert Sibande District Municipality: a comparative cross-sectional study
Authors: Rathipe Moeletsi , Raphela Selepeng France
Published: June 2023

Background

Occupational exposure to wood dust may cause respiratory illnesses, while prolonged exposure to loud noise may cause noise-induced hearing loss.

Objective

The objective of the study was to assess the prevalence of hearing loss and respiratory symptoms among large-scale sawmill workers within the Gert Sibande Municipality in Mpumalanga Province, South Africa.

Methods

A comparative cross-sectional study consisting of 137 exposed and 20 unexposed randomly selected workers was undertaken from January to March 2021. The respondents completed a semi-structured questionnaire on hearing loss and respiratory health symptoms.

Data analyse

The data was analysed using Statistical Package for Social Sciences (SPSS) version 21 (Chicago II, USA). The statistical analysis of the difference between the two proportions was done using an independent student t-test. The level of significance was set at p < 0.05.

Results

There was a statistically significant difference between the exposed and unexposed workers on the prevalence of respiratory symptoms like phlegm (51.8 vs. 0.0%) and shortness of breath (chest pain) (48.2 vs. 50%). There was also a statistically significant difference between the exposed and unexposed workers on the signs and symptoms of hearing loss like tinnitus (ringing in the ears) (50 vs. 33.3%), ear infections (21.4 vs. 66.7%), ruptured ear drums (16.7 vs. 0.0%), and ear injuries (11.9 vs. 0.0%). The exposed workers reported always wearing personal protective equipment (PPE) (86.9%) compared to the unexposed workers (75%). The reason for not wearing PPE consistently by the exposed workers was due to not being available (48.5%), compared to the unexposed workers who reported other reasons (100%).

Conclusion

The prevalence of respiratory symptoms among the exposed workers was higher than that of the unexposed workers, except for chest pains (shortness of breath). The prevalence of symptoms of hearing loss among the exposed workers was higher than the unexposed workers, except for ear infections. The results suggest that measures should be implemented at the sawmill to help protect workers’ health.
Evaluating the performance of different Bayesian count models in modelling childhood vaccine uptake among children aged 12–23 months in Nigeria
Authors: Fagbamigbe A. F. , Lawal T. V. , Atoloye K. A.
Published: June 2023

Background

Choosing appropriate models for count health outcomes remains a challenge to public health researchers and the validity of the findings thereof. For count data, the mean–variance relationship and proportion of zeros is a major determinant of model choice. This study aims to compare and identify the best Bayesian count modelling technique for the number of childhood vaccine uptake in Nigeria.

Methods

We explored the performances of Poisson, negative binomial and their zero-inflated forms in the Bayesian framework using cross-sectional data pooled from the Nigeria Demographic and Health Survey conducted between 2003 and 2018. In multivariable analysis, these Bayesian models were used to identify factors associated with the number of vaccine uptake among children. Model selection was based on the -2 Log-Likelihood (-2 Log LL), Leave-One-Out Cross-Validation Information Criterion (LOOIC) and Watanabe-Akaike/Widely Applicable Information Criterion (WAIC).

Results

Exploratory analysis showed the presence of excess zeros and overdispersion with a mean of 4.36 and a variance of 12.86. Observably, there was a significant increase in vaccine uptake over time. Significant factors included the mother’s age, level of education, religion, occupation, desire for last-child, place of delivery, exposure to media, birth order of the child, wealth status, number of antenatal care visits, postnatal attendance, healthcare decision maker, community poverty, community illiteracy, community unemployment, rural proportion and number of health facilities per 100,000. The zero-inflated negative binomial model was best fit with -2Log LL of -27171.47, LOOIC of 54464.2, and WAIC of 54588.0.

Conclusion

The Bayesian zero-inflated negative binomial model was most appropriate to identify factors associated with the number of childhood vaccines received in Nigeria due to the presence of excess zeros and overdispersion. Improving vaccine uptake by addressing the associated risk factors should be promptly embraced.
Reparative dentin formation as a possible factor influencing the penetrability of dentin in human teeth with apical periodontitis: an ex vivo study
Authors: Ren Yueyue , Zhang Junsheng , Meng Tiantian , Li Wuli , Li Song
Published: June 2023

Background

There is still a lack of knowledge regarding the permeability and configuration of infected root dentin. The aim of this ex vivo study was to compare the dentin penetrability of healthy teeth and necrotic teeth with apical periodontitis by evaluating the penetration of sodium hypochlorite (NaOCl) and to analyze the histopathological features of root dentin.

Methods

Forty-eight molars were collected and divided into two groups. The clinical diagnosis for one group was pulp necrosis with apical periodontitis and the pulp and periapex were normal in the other group. Forty-eight straight roots were divided into two groups: infected and healthy. First, all root canals were stained with 2% methylene blue to visualize penetration after standard root canal instrumentation and irrigation. Transverse sections were obtained, and the dye penetration parameters were measured. The cross sections were processed to 20–30 μm and stained with hematoxylin and eosin for observation of the histopathological changes in the root dentin.

Results

The maximum penetration depth, median penetration depth and penetration percentage of NaOCl solutions, in infected root canals were significantly lower than those in healthy root canals. The histopathological analysis showed that the frequency of reparative dentin formation in infected root canals was significantly greater than that in healthy root canals.

Conclusions

The dentin penetrability of teeth with necrotic teeth and apical periodontitis was more superficial during root canal irrigation than that of healthy teeth. The histopathological changes in infected radicular dentin, namely the formation of reparative dentin, might be associated with the lower permeability of dentin tubules in human teeth with apical periodontitis.
Evaluation of endometrioma size effect on ovarian reserve, embryo quality and pregnancy outcome after in vitro fertilization cycle; a cross-sectional study
Authors: Zareii Afsson , Askary Elham , Ghahramani Ameneh , Chamanara Kefayat , Abadi Alimohammad Keshtvarz Hesam , Afzalzadeh Azadeh
Published: June 2023

Introduction

Investigation of endometrioma size and its laterality on the quality of the embryo in patients with endometrioma compared to healthy subjects.

Materials and methods

In this retrospective and cross-sectional study, 70 patients with unilateral and bilateral endometrioma were recruited and compared with 70 age-matched infertile patients as the control group in terms of AMH before ovum pick-up, embryo quality as well as pregnancy outcome. Additionally, in the case group, we divided both unilateral (n = 32) and bilateral endometrioma patients (n = 38) into three groups based on the size of endometrioma. (1–3 cm, 3–6 cm, 6–10 cm)

Results

There was no difference in terms of age, BMI, parity, and age of menarche between the case and control groups. Moreover, no significant difference was observed in the baseline level of AMH between the case 2.96 ± 2.72 ng/dl (0.21–11.3) and control 2.73 ± 2.39 (0.21–12.8) groups. (P = 0.59) There was also no significant difference concerning AMH level between unilateral 3.58 ± 3.20 ng/dl (0.21–12.8) and bilateral endometrioma 2.45 ± 2.14 (0.21 − 0.20) groups. In terms of the quality and number of embryos, there was no significant difference between the case and control groups. (P = 0.30) Although the AMH level decreased with the increase in endometrioma size, this difference was not statistically significant. (P = 0.07) There was no significant difference in terms of the embryo quality between the groups based on the size of endometrioma. (P = 0.77) In addition, no significant difference was observed between the case and control groups in the terms of birth weight and pregnancy complications, such as premature delivery, cesarean section rate, neonatal respiratory distress, jaundice, as well as hospitalization rate. Head circumference of the newborns was higher in the endometrioma group while their Apgar score was lower in the case compared to the control group.

Conclusion

The presence of endometrioma by itself does not affect the main result of IVF procedures, including the number and quality of embryos and pregnancy outcome. Thus, IVF and embryo preservation and even pregnancy before surgery seem to be reasonable for endometriotic patients.
Perception of overseas experiences among medical students in Japan: a national online survey
Authors: Iwata Junna , Todoroki Ryota , Hashimoto Takehiro , Hyakutake Misa , Gomi Harumi , Nishizono Akira
Published: June 2023

Background

Data on the perceptions of medical students on international experience in non-English-speaking high-income countries (HICs) are very limited. This study aimed to assess the perceptions of medical students in Japan toward overseas experience while in school and post-graduation, as well as to characterize the support they require to pursue their profession in international settings.

Methods

A cross-sectional national survey was administered online between September 16, 2020, and October 8, 2020. Participants were recruited from 69 medical schools using snowball sampling through acquaintances and social media platforms. The survey results were analyzed by two researchers.

Results

A total of 548 students from 59 medical schools responded to the survey. Among them, 381 respondents (69%) expressed interest in working abroad, while only 40% seriously considered it. The majority of students responded that they would like to pursue clinical training abroad for a short term or while they were medical students (54%) or during a residency/fellowship (53%). The most popular regions among the respondents for future international experiences were North America and Europe. Finally, the most reported reasons for hesitation to work abroad were language barriers (70%), followed by lack of clarity regarding career options after working abroad (67%), difficulties obtaining medical licensure abroad (62%), and the lack of role models (42%).

Conclusions

Although nearly 70% of participants reported a high interest in working overseas, various barriers to working abroad were identified. Our findings identified key problem areas that could be targeted when promoting international experiences for medical students in Japan.
Training primary healthcare workers on a task-strengthening strategy for integrating hypertension management into HIV care in Nigeria: implementation strategies, knowledge uptake, and lessons learned
Authors: Oladele David Ayoola , Odusola Aina Olufemi , Odubela Oluwatosin , Nwaozuru Ucheoma , Calvin Colvin , Musa Zaidat , Idigbe Ifeoma , Nwakwo Chioma , Odejobi Yemi , Aifah Angela , Kanneh Nafesa , Mishra Shivani , Onakomaiya Deborah , Iwelunmor Juliet , Ogedegbe Olugbenga , Ezechi Oliver
Published: June 2023

Background

With improved access to anti-retroviral drugs, persons living with HIV/AIDS (PLWHA) are living longer but with attendant increased risks of non-communicable diseases (NCDs). The increasing burden of NCDs, especially hypertension, could reverse gains attributed to HIV care. Nurses and Community Health Officers (CHO) in Nigeria are cardinal in delivering primary health care. A task-strengthening strategy could enable them to manage hypertension in HIV care settings. This study aimed to assess their knowledge and practice of hypertension management among Healthcare workers (HCWs) and to explore the challenges involved in conducting onsite training during pandemics.

Methods

Nurses and CHOs in the employment of the Lagos State Primary Health Care Board (LSPHCB), Lagos State, Nigeria, were recruited. They were trained through hybrid (virtual and onsite) modules before study implementation and a series of refresher trainings. A pre-and post-training test survey was administered, followed by qualitative interviews to assess skills and knowledge uptake, the potential barriers and facilitators of task-sharing in hypertension management in HIV clinics, and the lessons learned.

Results

Sixty HCWs participated in the two-day training at baseline. There was a significant improvement in the trainees' knowledge of hypertension management and control. The average score during the pre-test and post-test was 59% and 67.6%, respectively. While about 75% of the participants had a good knowledge of hypertension, its cause, symptoms, and management, 20% had moderate knowledge, and 5% had poor knowledge at baseline. There was also an increase in the mean score between the pre-test and post-test of the refresher training using paired t-tests (P < 0.05). Role-playing and multimedia video use improved the participants' uptake of the training. The primary barrier and facilitator of task sharing strategy in hypertension management reported were poor delineation of duties among HCWs and the existing task shifting at the Primary Healthcare Centres (PHC) level, respectively.

Conclusions

The task strengthening strategy is relevant in managing hypertension in HIV clinics in Nigeria. The capacity development training for the nurses and CHOs involved in the Integration of Hypertension Management into HIV Care in Nigeria: A Task Strengthening Strategy (TASSH-Nigeria) study yielded the requisite improvement in knowledge uptake, which is a reassurance of the delivery of the project outcomes at the PHCs.
Implementation of neurological group-based telerehabilitation within existing healthcare during the COVID-19 pandemic: a mixed methods evaluation
Authors: Ackerley Suzanne , Wilson Neil , Boland Paul , Read Jessica , Connell Louise
Published: June 2023

Background

There is a need to evaluate if and how telerehabilitation approaches might co-exist within healthcare in the long-term. Our aim was to implement and evaluate a multidisciplinary group-based telerehabilitation approach for people engaging in neurological rehabilitation.

Methods

NeuroRehabilitation OnLine (NROL) was adapted and implemented within an existing healthcare system as a programme of repeating six-week blocks. A robust evaluation was undertaken simultaneously using a convergent parallel design underpinned by implementation frameworks. This included service data, and patient and staff interviews. Implementation success was conceptualised using the outcomes of appropriateness, acceptability and sustainability.

Results

Eight NROL blocks delivered 265 sessions with 1347 patient contacts, and NROL continues as part of standard practice. The approach was appropriate for varied demographics and had positive patient opinions and outcomes for many. Staff perceived NROL provided a compatible means to increase therapy and help meet targets, despite needing to mitigate some challenges when fitting the approach within the existing system. NROL was considered acceptable due to good attendance (68%), low drop-out (12%), and a good safety record (one non-injury fall). It was accepted as a new way of working across rehabilitation disciplines as an ‘extra layer of therapy’. NROL had perceived advantages in terms of patient and staff resource (e.g. saving time, energy and travel). NROL provided staffing efficiencies (ratio 0.6) compared to one-to-one delivery. Technology difficulties and reluctance were surmountable with dedicated technology assistance. Leadership commitment was considered key to enable the efforts needed for implementation and sustained use.

Conclusion

Pragmatic implementation of group-based telerehabilitation was possible as an adjunct to neurological rehabilitation within an existing healthcare system. The compelling advantages reported of having NROL as part of rehabilitation supports the continued use of this telerehabilitation approach. This project provides an exemplar of how evaluation can be run concurrently with implementation, applying a data driven rather than anecdotal approach to implementation.
The construction and operational models of internet hospitals in China: a hospital-based survey study
Authors: Chen Xuejiao , Wu Xinxia , Zhang Qihang , Jing Ran , Cheng Weibin , Tian Junzhang , Jin Changxiao
Published: June 2023

Background

China has empowered and continues to empower internet hospitals, which saw an increase in their development due to the pandemic, to fight against COVID-19. The construction and operational models of internet hospitals can be categorized as self-constructed and self-managed models, self-constructed and enterprise-run models, hospital and enterprise joint-owned models, and hosted by a third-party platform. Despite the growing importance of internet hospitals, there have been few systematic summaries of their construction and operational models. The primary purpose of the study was to understand the construction and operational models of internet hospitals in China.

Methods

Data was collected from 39 internet hospitals and 356 medical staff between September 2020 and April 2021, via internet hospital and hospital staff surveys. T-tests were used to compare the continuous variables, while Chi-square tests were employed to compare the proportions of categorical variables. The self-perception of the internet hospitals’ services was assessed using a 5-point Likert scale on 16 aspects and a root cause analysis was conducted to identify the root causes and influencing factors of current deficiencies experienced by internet hospitals.

Results

Among the 39 internet hospitals, 22 (56.4%) were self-constructed and self-managed. Compared to other models of Internet hospitals, self-constructed and self-managed hospitals had lower percentages of professionals providing online services (P = 0.006), numbers of doctors outside of the entity (P = 0.006), numbers of online nurses (P = 0.004), and the ratio of online nurses to offline doctors (P < 0.001). Of the 16 aspects evaluated with regards to the medical staff’s self-perception of the internet hospital services, the highest scores were given for fee transparency, fee rationality, travel cost capital, patience and responsibility, and consultation behaviors. The root causes included five aspects: human, channels, prices, services, and time.

Conclusions

While the self-constructed and self-managed model was found to be the most prevalent form of internet hospital in China, the different models of internet hospitals can have an impact on both the quantity and quality of online healthcare services. This study contributes to the existing literature on internet hospitals' construction and operational models, offering additional policy implications for telemedicine management.
A non-coding variant in the Kozak sequence of RARS2 strongly decreases protein levels and causes pontocerebellar hypoplasia
Authors: Nicolle Romain , Altin Nami , Siquier-Pernet Karine , Salignac Sherlina , Blanc Pierre , Munnich Arnold , Bole-Feysot Christine , Malan Valérie , Caron Barthélémy , Nitschké Patrick , Desguerre Isabelle , Boddaert Nathalie , Rio Marlène , Rausell Antonio , Cantagrel Vincent
Published: June 2023

Bi-allelic variants in the mitochondrial arginyl-transfer RNA synthetase (RARS2) gene have been involved in early-onset encephalopathies classified as pontocerebellar hypoplasia (PCH) type 6 and in epileptic encephalopathy. A variant (NM_020320.3:c.-2A > G) in the promoter and 5’UTR of the RARS2 gene has been previously identified in a family with PCH. Only a mild impact of this variant on the mRNA level has been detected. As RARS2 is non-dosage-sensitive, this observation is not conclusive in regard of the pathogenicity of the variant.

We report and describe here a new patient with the same variant in the RARS2 gene, at the homozygous state. This patient presents with a clinical phenotype consistent with PCH6 although in the absence of lactic acidosis. In agreement with the previous study, we measured RARS2 mRNA levels in patient’s fibroblasts and detected a partially preserved gene expression compared to control. Importantly, this variant is located in the Kozak sequence that controls translation initiation. Therefore, we investigated the impact on protein translation using a bioinformatic approach and western blotting. We show here that this variant, additionally to its effect on the transcription, also disrupts the consensus Kozak sequence, and has a major impact on RARS2 protein translation. Through the identification of this additional case and the characterization of the molecular consequences, we clarified the involvement of this Kozak variant in PCH and on protein synthesis. This work also points to the current limitation in the pathogenicity prediction of variants located in the translation initiation region.
HOPX is a tumor-suppressive biomarker that corresponds to T cell infiltration in skin cutaneous melanoma
Authors: He Song , Ding Yu , Ji Zhonghao , Yuan Bao , Chen Jian , Ren Wenzhi
Published: June 2023

Background

Skin cutaneous melanoma (SKCM) is the most threatening type of skin cancer. Approximately 55,000 people lose their lives every year due to SKCM, illustrating that it seriously threatens human life and health. Homeodomain-only protein homeobox (HOPX) is the smallest member of the homeodomain family and is widely expressed in a variety of tissues. HOPX is involved in regulating the homeostasis of hematopoietic stem cells and is closely related to the development of tumors such as breast cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. However, its function in SKCM is unclear, and further studies are needed.

Methods

We used the R language to construct ROC (Receiver-Operating Characteristic) curves, KM (Kaplan‒Meier) curves and nomograms based on databases such as the TCGA and GEO to analyze the diagnostic and prognostic value of HOPX in SKCM patients. Enrichment analysis, immune scoring, GSVA (Gene Set Variation Analysis), and single-cell sequencing were used to verify the association between HOPX expression and immune infiltration. In vitro experiments were performed using A375 cells for phenotypic validation. Transcriptome sequencing was performed to further analyze HOPX gene-related genes and their signaling pathways.

Results

Compared to normal cells, SKCM cells had low HOPX expression (p < 0.001). Patients with high HOPX expression had a better prognosis (p < 0.01), and the marker had good diagnostic efficacy (AUC = 0.744). GO/KEGG (Gene Ontology/ Kyoto Encyclopedia of Genes and Genomes) analysis, GSVA and single-cell sequencing analysis showed that HOPX expression is associated with immune processes and high enrichment of T cells and could serve as an immune checkpoint in SKCM. Furthermore, cellular assays verified that HOPX inhibits the proliferation, migration and invasion of A375 cells and promotes apoptosis and S-phase arrest. Interestingly, tumor drug sensitivity analysis revealed that HOPX also plays an important role in reducing clinical drug resistance.

Conclusion

These findings suggest that HOPX is a blocker of SKCM progression that inhibits the proliferation of SKCM cells and promotes apoptosis. Furthermore, it may be a new diagnostic and prognostic indicator and a novel target for immunotherapy in SKCM patients.
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

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

Overcrowding 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

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

The 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

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

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

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

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

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

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

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.