bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug Utilization Evaluation Study of Ciprofloxacin Use and Adverse Events Occurrence: Role of Community Pharmacists
Authors: Dogheim Gaidaa M. , Werida Rehab H.
Published: December 2023

Background: Antimicrobial resistance is a global health crisis threatening optimal management of infectious diseases. Ciprofloxacin is a widely used fluoroquinolone in various disease conditions. Resistance against ciprofloxacin is increasing, leading to nonoptimal management of patients. Thus, the aim of this study was to assess ciprofloxacin use in the community setting in terms of appropriate prescribing, dosing, frequency, and duration of use. Methods: A cross-sectional, retrospective study was conducted by community pharmacists in 5 community pharmacies in Egypt from September 2021 to February 2022. Patients prescribed oral ciprofloxacin during the period of the study were included. Data on demographics, indications for ciprofloxacin, dosing regimen, adverse events, and drug interactions were collected. Results: A total of 151 patients’ record indicated for ciprofloxacin were included in the study, of whom 44.4% were men and 55.6% were women who were neither pregnant nor lactating. Based on international guidelines, 96.69% ciprofloxacin prescriptions were appropriate; 96.03% contained correct ciprofloxacin dosing whereas 3.97% were overdose. A total of 90. 73% had correct frequency of administration and 96.03% records had correct durations. Only 1.99% of patients were ≤18 years of age, which is an absolute contraindication. Interacting drugs with ciprofloxacin were 28.5% with acetaminophen, 31.1% with ibuprofen, 16.6% with antacids, 21.2% with chlorpheniramine, and 7.9% with prednisolone. Adverse events included 1.32% hypoglycemia, 0.66% hyperglycemia, 3.97% tendinitis, and 2.65% QTc (heart rate–corrected QT interval) prolongation. Conclusion and relevance: Ciprofloxacin use in community pharmacies is appropriate according to international guidelines. Ongoing drug utilization evaluation is necessary to ensure rational drug use, which in turn can decrease resistance rates.
Airway ciliated cells in adult lung homeostasis and COPD
Authors: Petit Laure M.G. , Belgacemi Randa , Ancel Julien , Saber Cherif Lynda , Polette Myriam , Perotin Jeanne-Marie , Spassky Nathalie , Pilette Charles , Al Alam Denise , Deslée Gaëtan , Dormoy Valérian
Published: December 2023

Cilia are organelles emanating from the cell surface, consisting of an axoneme of microtubules that extends from a basal body derived from the centrioles. They are either isolated and nonmotile (primary cilia), or grouped and motile (motile cilia). Cilia are at the centre of fundamental sensory processes and are involved in a wide range of human disorders. Pulmonary cilia include motile cilia lining the epithelial cells of the conductive airways to orchestrate mucociliary clearance, and primary cilia found on nondifferentiated epithelial and mesenchymal cells acting as sensors and cell cycle keepers. Whereas cilia are essential along the airways, their regulatory molecular mechanisms remain poorly understood, resulting in a lack of therapeutic strategies targeting their structure or functions. This review summarises the current knowledge on cilia in the context of lung homeostasis and COPD to provide a comprehensive overview of the (patho)biology of cilia in respiratory medicine with a particular emphasis on COPD.
Global birth prevalence of Robin sequence in live-born infants: a systematic review and meta-analysis
Authors: Wright Marie , Cortina-Borja Mario , Knowles Rachel , Urquhart Don S.
Published: December 2023

Robin sequence (RS), a congenital disorder of jaw maldevelopment and glossoptosis, poses a substantial healthcare burden and has long-term health implications if airway obstruction is suboptimally treated. This study describes the global birth prevalence of RS and investigates whether prevalence estimates differ by geographical location, ethnicity or study data source (registryversusnon-registry data). The protocol was prospectively registered with PROSPERO.

Databases were searched using keywords and subject terms for “Robin sequence”, “epidemiology”, “incidence” and “birth prevalence”. Meta-analysis was performed fitting random effects models with arcsine transformation.

From 34 eligible studies (n=2722 RS cases), pooled birth prevalence was 9.5 per 100 000 live births (95% CI 7.1–12.1) with statistical heterogeneity. One third of studies provided a case definition for RS and numerous definitions were used. A total of 22 countries were represented, predominantly from European populations (53% of studies). There was a trend towards higher birth prevalence in European populations and lower prevalence from registry-based studies. Only two studies reported ethnicity.

This study indicates that RS occurs globally. To investigate geographical differences in prevalence, additional studies from non-European populations and reporting of ethnicity are needed. Heterogeneity of estimates may be due to variable diagnostic criteria and ascertainment methods. Recently published consensus diagnostic criteria may reduce heterogeneity among future studies.
Effect of an Inclined Slots on the Power Consumption and Vortices Size in a Rushton Turbine Agitated Tank
Authors: Youcefi Sarra , Bouzit Mohamed , Youcefi Abdelkader , Mokhefi Abderrahim
Published: December 2023

Mechanical agitation in baffled vessels with turbines plays a vital role in achieving homogeneous fluid mixing and promoting various transfer operations. Therefore, designing vessels with optimal energy efficiency and flow dynamics is essential to enhance operational performance and eliminate flow perturbations. Hence, the present research focuses on a numerical investigation of the impact of inclined slots with different angles installed at the sidewall of a cylindrical vessel equipped with a Rushton turbine. This study explores power consumption and vortex size while considering various rotation directions of the impeller with different rotation speeds. The numerical simulations are conducted for Reynolds numbers ranging from 104 to 105, using the RANS k-ε turbulence model to govern the flow inside the stirred vessel, accounting for mass and momentum balances. The results have shown that the installation of slots reduces power consumption and vortex size compared to conventional vessel configurations. Moreover, increasing the slot angle from 0 to 32.5° further reduces energy consumption and vortex size, especially with negative rotation speeds. On the other hand, increasing the Reynolds numbers leads to a decrease in power consumption and an increase in vortex size. The present research therefore proposes a design for constructing Rushton-turbine stirred vessels offering optimal operation, characterized by reduced energy consumption and minimized vortex size.
Long-term trends in stream benthic macroinvertebrate communities are driven by chemicals
Authors: Nguyen Hong Hanh , Welti Ellen A. R. , Haubrock Phillip J. , Haase Peter
Published: December 2023

Background

Recent studies indicate a partial recovery of European stream macroinvertebrate diversity. However, the key determinants shaping the overall community trends are only partly explored, owing to insufficient long-term environmental data collected in parallel with community responses. We investigate long-term trends in stream macroinvertebrate communities (i.e., taxonomic and trait composition and metrics), and explore their relationships to diverse environmental drivers (i.e., land-use, runoff, water temperature, and in-stream chemicals). We use macroinvertebrate data collected annually in spring and summer between 2007 and 2021 at four sampling sites within the Rhine-Main-Observatory Long-Term Ecological Research site. These sampling sites encompass a gradient from less-disturbed to disturbed conditions.

Results

Over time, shifts in taxonomic and trait composition and metrics indicated an improvement in environmental conditions. Long-term trends of biological trait metrics mirrored those for taxonomic metrics; for example, increases over time in taxonomic richness were paralleled by increases in functional richness and functional dispersion. Meanwhile, trends of ecological trait metrics were particularly driven by changes in environmental drivers. Land-use, water temperature, and runoff explained around 20% of the overall variance in long-term trends of macroinvertebrate communities. Water temperature and land-use played relatively equal roles in shaping taxonomic and trait composition and metric responses in spring, while water temperature emerged as the most influential driver in summer. However, when incorporating long-term chemical data as a more direct measurement of changes in land-use, the overall variance explained in macroinvertebrate community trends increased to c.a. 50% in both seasons.

Conclusions

Examining more relevant driver variables beyond land-use and climate improves insights into why biodiversity exhibits long-term trends. We call for an increase in initiatives to link biodiversity monitoring with parallel sampling of relevant environmental drivers.
Detection for melanoma skin cancer through ACCF, BPPF, and CLF techniques with machine learning approach
Authors: Kavitha P. , Ayyappan G. , Jayagopal Prabhu , Mathivanan Sandeep Kumar , Mallik Saurav , Al-Rasheed Amal , Alqahtani Mohammed S. , Soufiene Ben Othman
Published: December 2023

Intense sun exposure is a major risk factor for the development of melanoma, an abnormal proliferation of skin cells. Yet, this more prevalent type of skin cancer can also develop in less-exposed areas, such as those that are shaded. Melanoma is the sixth most common type of skin cancer. In recent years, computer-based methods for imaging and analyzing biological systems have made considerable strides. This work investigates the use of advanced machine learning methods, specifically ensemble models with Auto Correlogram Methods, Binary Pyramid Pattern Filter, and Color Layout Filter, to enhance the detection accuracy of Melanoma skin cancer. These results suggest that the Color Layout Filter model of the Attribute Selection Classifier provides the best overall performance. Statistics for ROC, PRC, Kappa, F-Measure, and Matthews Correlation Coefficient were as follows: 90.96% accuracy, 0.91 precision, 0.91 recall, 0.95 ROC, 0.87 PRC, 0.87 Kappa, 0.91 F-Measure, and 0.82 Matthews Correlation Coefficient. In addition, its margins of error are the smallest. The research found that the Attribute Selection Classifier performed well when used in conjunction with the Color Layout Filter to improve image quality.
Strategies to manage tree pest and disease outbreaks: a balancing act
Authors: Dahlsjö Cecilia A. L.
Published: December 2023

Tree diseases are one of the major threats to forests worldwide. As the frequency and severity of disease outbreaks increase, effective prevention and mitigation strategies are urgently needed. Emerging methods are available to tackle this issue, however, trade-offs and potential ecological consequences should be considered for successful forest preservation.
Progressive shingles in a toddler due to reactivation of Varicella Zoster vaccine virus four days after infection with SARS-CoV-2; a case report
Authors: Miller Christine , Taylor-Salmon Emma , Emuren Leonard , Landry Marie , Gershon Anne , Miller George
Published: December 2023

Background

Herpes zoster (HZ) is the clinical syndrome associated with reactivation of latent varicella-zoster virus (VZV). Several factors have been implicated to promote VZV reactivation; these include immunosuppression, older age, mechanical trauma, physiologic stress, lymphopenia, and more recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS- CoV-2). Recent reports suggest an increase in the number of HZ cases in the general population during the global COVID-19 pandemic. However, it is unknown what proportion of HZ during the pandemic is due to reactivation of wild-type or vaccine-strain VZV.

Case

Here we report the first known case of HZ concomitant with SARS-CoV2 infection in a 20-month-old female who was treated with a single dose of dexamethasone, due to reactivation of the vaccine-type strain of VZV after presenting with a worsening vesicular rash.

Conclusion

In this case, we were able to show vaccine-strain VZV reactivation in the context of a mild acute symptomatic COVID-19 infection in a toddler. Being able to recognize HZ quickly and effectively in a pediatric patient can help stave off the significant morbidity and mortality associated with disease process.
Highlighting allelic variations at the interleukin-19 locus in term of preeclampsia predisposing factors and access to an accurate diagnostic/screening option
Authors: Parhoudeh Sara , Saadaty Aida , Khashei Varnamkhasti Khalil , Khashei Varnamkhasti Samire , Naeimi Leila , Naeimi Sirous
Published: December 2023

Background

Preeclampsia is the main cause of preterm parturition and maternal–fetal complications. T helper 1 and T helper 2 cytokines balance is a requirement in normal pregnancy and aberrant in this immunologic balance, play an important role in the pathology of preeclampsia. In previous studies single nucleotide polymorphisms have been associated with the alteration of serum cytokine levels.

Objective

This study was aimed to discover association between interleukin-13 (rs20541, and rs56035208) and interleukin-19 (rs1028181 (T/C) and rs2243191(T/C)) polymorphisms with susceptibility to preeclampsia.

Methods

In this case-control study 300 women with and without preeclampsia (n = 150/each) who referred to Zeynabieh Hospital- Shiraz, Iran, from February 2021 to April 2022 were enrolled. For genotyping the interleukin-13 and interleukin-19 polymorphisms, the Allele-specific polymerase chain reaction and direct sequencing method was carried out.

Results

Our statistical results revealed no significant differences in allele and genotype frequencies for interleukin-13 polymorphisms compared to controls. We found that the interleukin‐13 polymorphisms are significantly associated with vulnerability to edema at rs20541 position and maternal drinking at rs56035208 position. But it was interesting to note that the differences of both the allele and genotype frequencies of interleukin-19 polymorphisms and their contribution to the risk of preeclampsia susceptibility were significant.

Conclusions

No risk of preeclampsia was found in all comparisons for interleukin-13 polymorphisms. However, the interleukin-19 polymorphisms were found to confer the risk of preeclampsia in our population.
Prognostic factors for intermediate- or high-risk neuroblastomas in children in China
Authors: Zhang Yi , Zhang Wei-Ling , Huang Dong-Sheng , Wang Yi-Zhuo , Hu Hui-Min , Zhi Tian , Mei Yan-Yan
Published: December 2023

Background

Evidence regarding the characteristics and prognosis of neuroblastoma (NBL) in China is limited. We aimed to investigate the characteristics and prognosis of intermediate- or high-risk NBL in children in China.

Methods

We included 147 patients with intermediate- or high-risk NBL evaluated from January 2006 to March 2015. The patients were aged 1 month to 15.5 years, 66% of them were boys, and 117 (79.6%) were diagnosed with high-risk NBL.

Results

After a median follow-up of 32.5 months, 80 (45.6%) patients survived, with a median survival time of 48 months (95% confidence interval [CI]: 36.41–59.59). High-risk patients (hazard ratio [HR]: 12.467; 95% CI: 11.029–12.951), partial response (PR) (HR: 1.200; 95% CI: 1.475–2.509) or progression disease (PD) (HR: 1.924; 95% CI: 1.623–3.012) after induction chemotherapy, and intracranial metastasis (HR: 3.057; 95% CI: 0.941–4.892) were independent risk factors for survival (p < 0.05) and postrelapse survival (p < 0.05). NBL relapse, male sex, and PR or PD after induction chemotherapy were risk factors for event-free survival (p < 0.05).

Conclusions

In addition to previously established independent risk factors, such as age, risk group, and relapse, efficacy of induction chemotherapy and intracranial metastasis play significant roles in the prognosis of NBL.
Physical activity, sleep disorders, and type of work in the prevention of cognitive function decline in patients with hypertension
Authors: Zhang Mengdi , Jiao Huachen , Wang Cong , Qu Ying , Lv Shunxin , Zhao Dongsheng , Zhong Xia
Published: December 2023

Background

Hypertensive patients are likelier to have cognitive function decline (CFD). This study aimed to explore physical activity level, sleep disorders, and type of work that influenced intervention effects on cognitive function decline in hypertensive patients and to establish a decision tree model to analyze their predictive significance on the incidence of CFD in hypertensive patients.

Methods

This cross-sectional study recruited patients with essential hypertension from several hospitals in Shandong Province from May 2022 to December 2022. Subject exclusion criteria included individuals diagnosed with congestive heart failure, valvular heart disease, cardiac surgery, hepatic and renal dysfunction, and malignancy. Recruitment is through multiple channels such as hospital medical and surgical outpatient clinics, wards, and health examination centers. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Moreover, we obtained information on the patients' type of work through a questionnaire and their level of physical activity through the International Physical Activity Questionnaire (IPAQ).

Results

The logistic regression analysis results indicate that sleep disorder is a significant risk factor for CFD in hypertension patients(OR:1.85, 95%CI:[1.16,2.94]), mental workers(OR:0.12, 95%CI: [0.04,0.37]) and those who perform both manual and mental workers(OR: 0.5, 95%CI: [0.29,0.86]) exhibit protective effects against CFD. Compared to low-intensity, moderate physical activity(OR: 0.53, 95%CI: [0.32,0.87]) and high-intensity physical activity(OR: 0.26, 95%CI: [0.12,0.58]) protects against CFD in hypertension patients. The importance of predictors in the decision tree model was ranked as follows: physical activity level (54%), type of work (27%), and sleep disorders (19%). The area under the ROC curves the decision tree model predicted was 0.72 [95% CI: 0.68 to 0.76].

Conclusion

Moderate and high-intensity physical activity may reduce the risk of developing CFD in hypertensive patients. Sleep disorders is a risk factor for CFD in hypertensive patients. Hypertensive patients who engage in mental work and high-intensity physical activity effectively mitigate the onset of CFD in hypertensive patients.
The impact of perioperative enhanced recovery nursing model on postoperative delirium and rehabilitation quality in elderly patients with femoral neck fractures
Authors: Wang Cheng , Tan Bingyin , Qian Qing
Published: December 2023

Background

The aim of this study was to investigate the effects of introducing the Enhanced Recovery After Surgery (ERAS) nursing model on postoperative delirium occurrence and rehabilitation quality in elderly patients with femoral neck fractures.

Methods

A total of 160 elderly patients with femoral neck fractures, who met the inclusion criteria and were admitted between March 2021 to March 2023, were divided into two groups: the traditional care group and the ERAS nursing model group. In addition to traditional care measures, the ERAS nursing model group received interventions based on the principles of the ERAS nursing model. The occurrence of delirium and sleep quality were observed at 24, 48, and 72 h postoperatively, as well as during the overall hospital stay. The duration of hospitalization, time to first mobilization, and post-discharge follow-up on quality of life were compared between the two groups.

Results

The ERAS nursing model group exhibited a significant difference in the occurrence of delirium at 48 and 72 h postoperatively, as well as during the overall hospital stay (P < 0.05). However, there was no significant difference in the occurrence of delirium at 24 h postoperatively (P > 0.05). The sleep quality of the two groups showed a statistically significant difference (P < 0.05). The ERAS nursing model group had shorter time to first mobilization, reduced hospitalization duration, and higher Harris and SF-36 scores during post-discharge follow-up, compared to the traditional care group (P < 0.05).

Conclusions

The implementation of the ERAS nursing model in elderly patients with femoral neck fractures improved postoperative sleep quality, reduced delirium occurrence, shortened average hospitalization duration, and enhanced patients’ quality of life.
Effects of perceived spiritual management, work engagement, and organizational commitment on job satisfaction among clinical nurses: the mediating role of perceived spiritual management
Authors: Lee Eun-Hye , Yu Hea-Jin
Published: December 2023

Background

Spirituality in the workplace has a positive impact on organizations. It strengthens employees’ well-being and their quality of life. It also gives work a sense of purpose and meaning and creates a sense of interconnectedness.

Methods

This study is a descriptive cross-sectional survey which intends to determine how job satisfaction is impacted by spiritual management, work engagement, and organizational commitment from the perspective of clinical nurses. Responses to self-administered questionnaires were collected from 230 hospital nurses in South Korea from July to August, 2022.

Results

Job satisfaction was positively correlated with perceived spiritual management (r = .662), job commitment (r = .514), and organizational commitment (r = .587). Perceived spiritual management had the highest correlation with job satisfaction, followed by organizational commitment and job commitment. To determine the effect of these factors on clinical nurses’ job satisfaction, a hierarchical multiple regression analysis-in other words, a method that controls the entry order of a series of independent variables-was conducted. Model 4 ultimately explained 58.4% of job satisfaction (R2 = 0.584; F = 44.563; p < .001), with an additional 2.5 explained variance. Among the control variables in Model 4, only marital status (β = 0.173) was positively significant; perceived spiritual management (β = 0.388), work engagement (β = 0.208) and organizational commitment (β = 0.225) were all found to have significant positive effects on job satisfaction. The mediation analysis showed that perceived spiritual management had a partial mediating effect on the relationship between work engagement, organizational commitment, and job satisfaction.

Conclusion

The results of this study confirm that job satisfaction for nurses requires not only individual predispositions, but also active changes in management strategies, such as spirituality management at the hospital’s organizational level.
Ambient atmospheric PM worsens mouse lung injury induced by influenza A virus through lysosomal dysfunction
Authors: Li Shunwang , Ju Xiangwu , Liu Qiang , Yan Yiwu , Zhang Cong , Qin Yuhao , Deng Xingyu , Li Chang , Tian Mingyao , Zhang Yanli , Jin Ningyi , Jiang Chengyu
Published: December 2023

Background

Particulate matter (PM) air pollution poses a significant risk to respiratory health and is especially linked with various infectious respiratory diseases such as influenza. Our previous studies have shown that H5N1 virus infection could induce alveolar epithelial A549 cell death by enhancing lysosomal dysfunction. This study aims to investigate the mechanisms underlying the effects of PM on influenza virus infections, with a particular focus on lysosomal dysfunction.

Results

Here, we showed that PM nanoparticles such as silica and alumina could induce A549 cell death and lysosomal dysfunction, and degradation of lysosomal-associated membrane proteins (LAMPs), which are the most abundant lysosomal membrane proteins. The knockdown of LAMPs with siRNA facilitated cellular entry of both H1N1 and H5N1 influenza viruses. Furthermore, we demonstrated that silica and alumina synergistically increased alveolar epithelial cell death induced by H1N1 and H5N1 influenza viruses by enhancing lysosomal dysfunction via LAMP degradation and promoting viral entry. In vivo, lung injury in the H5N1 virus infection-induced model was exacerbated by pre-exposure to silica, resulting in an increase in the wet/dry ratio and histopathological score.

Conclusions

Our findings reveal the mechanism underlying the synergistic effect of nanoparticles in the early stage of the influenza virus life cycle and may explain the increased number of respiratory patients during periods of air pollution.
Identifying molecular tags selectively retained on the surface of brain endothelial cells to generate artificial targets for therapy delivery
Authors: Porro Giulia Maria , Lorandi Italo , Liu Xueying , Kataoka Kazunori , Battaglia Giuseppe , Gonzalez-Carter Daniel
Published: December 2023

Current strategies to identify ligands for brain delivery select candidates based on preferential binding to cell-membrane components (CMC) on brain endothelial cells (EC). However, such strategies generate ligands with inherent brain specificity limitations, as the CMC (e.g., the transferrin receptor TfR1) are also significantly expressed on peripheral EC. Therefore, novel strategies are required to identify molecules allowing increased specificity of therapy brain delivery. Here, we demonstrate that, while individual CMC are shared between brain EC and peripheral EC, their endocytic internalization rate is markedly different. Such differential endocytic rate may be harnessed to identify molecular tags for brain targeting based on their selective retention on the surface of brain EC, thereby generating ‘artificial’ targets specifically on the brain vasculature. By quantifying the retention of labelled proteins on the cell membrane, we measured the general endocytic rate of primary brain EC to be less than half that of primary peripheral (liver and lung) EC. In addition, through bio-panning of phage-displayed peptide libraries, we unbiasedly probed the endocytic rate of individual CMC of liver, lung and brain endothelial cells. We identified phage-displayed peptides which bind to CMC common to all three endothelia phenotypes, but which are preferentially endocytosed into peripheral EC, resulting in selective retention on the surface of brain EC. Furthermore, we demonstrate that the synthesized free-form peptides are capable of generating artificial cell-surface targets for the intracellular delivery of model proteins into brain EC with increasing specificity over time. The developed identification paradigm, therefore, demonstrates that the lower endocytic rate of individual CMC on brain EC can be harnessed to identify peptides capable of generating ‘artificial’ targets for the selective delivery of proteins into the brain vasculature. In addition, our approach identifies brain-targeting peptides which would have been overlooked by conventional identification strategies, thereby increasing the repertoire of candidates to achieve specific therapy brain delivery.
CircGPRC5A enhances colorectal cancer progress by stabilizing PPP1CA and inducing YAP dephosphorylation
Authors: Chen Zhenzhou , Li Yidan , He Kuan , Yang Jianguo , Deng Qican , Chen Yajun , Fu Zhongxue
Published: December 2023

Background

With the advancements in bioinformatic technology, an increasing number of circular RNAs (circRNAs) have been discovered and their crucial roles in the development and progression of various malignancies have been confirmed through multiple pathways. However, the specific mechanisms involving protein-binding circRNAs in colorectal cancer (CRC) remain largely unexplored.

Methods

Differential circRNA expression was assessed using a human circRNA microarray in five CRC tissue and paired normal samples. CircGPRC5A expression was then confirmed in the CRC tissues and paired normal samples using qRT-PCR. The biological function of circGPRC5A in CRC were studied in vitro and in vivo. Western blotting, fluorescence in situ hybridization, immunofluorescence, RNA pulldown, mass spectrometry, immunoprecipitation, quantitative phosphoproteomics, and RNA-binding protein immunoprecipitation assays were used to study circGPRC5A.

Results

Our analysis revealed that circGPRC5A expression was higher in CRC tissues compared to normal tissues and was associated with tumor size, tumor stage and lymph node status. CircGPRC5A promoted CRC cell proliferation, migration, and metastasis in vitro and in vivo. CircGPRC5A could stabilize PPP1CA protein by inhibiting the binding between UBA1 and PPP1CA, and increasing YAP dephosphorylation.

Conclusions

Our study revealed that circGPRC5A plays an essential function in CRC progression by stabilizing PPP1CA protein and enhancing YAP dephosphorylation. CircGPRC5A could act as a novel and potential target for CRC.
Effects of foot and ankle mobilisations combined with home stretches in people with diabetic peripheral neuropathy: a proof‐of‐concept RCT
Authors: Lepesis Vasileios , Paton Joanne , Rickard Alec , Latour Jos M. , Marsden Jonathan
Published: December 2023

Introduction

People with diabetic peripheral neuropathy (DPN) and limited joint mobility syndrome (LJMS) can experience increased forefoot peak plantar pressures (PPPs), a known risk factor for ulceration. The aim of this study was to investigate whether ankle and 1st metatarsophalangeal (MTP) joint mobilisations and home‐based stretches in people with DPN improve joint range of motion (ROM) and reduce forefoot PPPs.

Design and methods

Sixty‐one people with DPN (IWGDF risk 2), were randomly assigned to a 6‐week programme of ankle and 1st MTP joint mobilisations (n = 31) and home‐based stretches or standard care only (n = 30). At baseline (T0); 6‐week post intervention (T1) and at 3 months follow‐up (T2), a blinded assessor recorded dynamic ankle dorsiflexion range using 3D (Codamotion) motion analysis and the weight bearing lunge test, static 1st MTP joint dorsiflexion ROM, dynamic plantar pressure and balance.

Results

At T1 and T2 there was no difference between both groups in ankle dorsiflexion in stance phase, plantar pressure and balance. Compared to the control group, the intervention group showed a statistically significant increase in static ankle dorsiflexion range (Left 1.52 cm and 2.9cms, Right 1.62 cm and 2.7 cm) at 6 (T1) and 18 weeks (T2) respectively p < 0.01). Between group differences were also seen in left hallux dorsiflexion (2.75°, p < 0.05) at T1 and in right hallux dorsiflexion ROM (4.9°, p < 0.01) at T2 follow up. Further, functional reach showed a significant increase in the intervention group (T1 = 3.13 cm p < 0.05 and T2 = 3.9 cm p < 0.01). Intervention adherence was high (80%).

Conclusions

Combining ankle and 1st MTP joint mobilisations with home‐based stretches in a 6‐week programme in people with DPN is effective in increasing static measures of range. This intervention may be useful for improving ankle, hallux joint mobility and anteroposterior stability limits in people with diabetes and neuropathy but not for reducing PPP or foot ulcer risk.

Trial registration

https://classic.clinicaltrials.gov/ct2/show/NCT03195855.
Ambulance deployment without transport: a retrospective difference analysis for the description of emergency interventions without patient transport in Bavaria
Authors: Dax Florian , Trentzsch Heiko , Lazarovici Marc , Hegenberg Kathrin , Kneißl Katharina , Hoffmann Florian , Prückner Stephan
Published: December 2023

Background

Not all patients who call the ambulance service are subsequently transported to hospital. In 2018, a quarter of deployments of an emergency ambulance in Bavaria were not followed by patient transport. This study describes factors that influence patient transport rates.

Method

This is a retrospective cross-sectional study based on data from all Integrated Dispatch Centres of the Free State of Bavaria in 2018. Included were ambulance deployments without emergency physician involvement, which were subdivided into ambulance deployments without transport and ambulance deployments with transport. The proportion of transported patients were determined for the primary reasons for deployment and for the different community types. On-scene time was compared for calls with and without patient transport. Differences were tested for statistical significance using Chi2 tests and the odds ratio was calculated to determine differences between groups.

Results

Of 510,145 deployments, 147,621 (28.9%) could be classified as ambulance deployments without transport and 362,524 (71.1%) as ambulance deployments with transport.The lowest proportion of patients transported was found for activations where the fire brigade was involved (“fire alarm system” 0.6%, “fire with emergency medical services” 5.4%) and “personal emergency response system active alarm” (18.6%). The highest transport rates were observed for emergencies involving “childbirth/delivery” (96.9%) and “trauma” (83.2%). A lower proportion of patients is transported in large cities as compared to smaller cities or rural communities; in large cities, the odds ratio for emergencies without transport is 2.02 [95% confidence interval 1.98–2.06] referenced to rural communites. The median on-scene time for emergencies without transport was 20.8 min (n = 141,052) as compared to 16.5 min for emergencies with transport (n = 362,524). The shortest on-scene times for emergencies without transport were identified for activations related to “fire alarm system” (9.0 min) and “personal emergency response system active alarm” (10.6 min).

Conclusion

This study indicates that the proportion of patients transported depends on the reason for deployment and whether the emergency location is urban or rural. Particularly low transport rates are found if an ambulance was dispatched in connection with a fire department operation or a personal emergency medical alert button was activated. The on-scene-time of the rescue vehicle is increased for deployments without transport. The study could not provide a rationale for this and further research is needed.

Trial registration This paper is part of the study “Rettungswageneinsatz ohne Transport” [“Ambulance deployment without transport”] (RoT), which was registered in the German Register of Clinical Studies under the number DRKS00017758.
Genetic effect of metformin use on risk of cancers: evidence from Mendelian randomization analysis
Authors: Chen Yao , Bai Bingjun , Ye Shuchang , Gao Xing , Zheng Xinnan , Ying Kangkang , Pan Hongming , Xie Binbin
Published: December 2023

Background

Increasing number of studies reported the positive effect of metformin on the prevention and treatment of cancers. However, the genetic causal effect of metformin utilization on the risk of common cancers was not completely demonstrated.

Methods

Two-sample Mendelian Randomization (two-sample MR) analysis was conducted to uncover the genetically predicted causal association between metformin use and 26 kinds of cancers. Besides, two-step Mendelian Randomization (two-step MR) assessment was applied to clarify the mediators which mediated the causal effect of metformin on certain cancer. We utilized five robust analytical methods, in which the inverse variance weighting (IVW) method served as the major one. Sensitivity, pleiotropy, and heterogeneity were assessed. The genetic statistics of exposure, outcomes, and mediators were downloaded from publicly available datasets, including the Open Genome-Wide Association Study (GWAS), FinnGen consortium (FinnGen), and UK Biobank (UKB).

Results

Among 26 kinds of common cancers, HER-positive breast cancer was presented with a significant causal relationship with metformin use [Beta: − 4.0982; OR: 0.0166 (95% CI: 0.0008, 0.3376); P value: 0.0077], which indicated metformin could prevent people from HER-positive breast cancer. Other cancers only showed modest associations with metformin use. Potential mediators were included in two-step MR, among which total testosterone levels (mediating effect: 24.52%) displayed significant mediating roles. Leave-one-out, MR-Egger, and MR-PRESSO analyses produced consistent outcomes.

Conclusion

Metformin use exhibited a genetically protective effect on HER-positive breast cancer, which was partially mediated by total testosterone levels.
Epigenetics of the far northern Yakutian population
Authors: Kalyakulina Alena , Yusipov Igor , Kondakova Elena , Bacalini Maria Giulia , Giuliani Cristina , Sivtseva Tatiana , Semenov Sergey , Ksenofontov Artem , Nikolaeva Maria , Khusnutdinova Elza , Zakharova Raisa , Vedunova Maria , Franceschi Claudio , Ivanchenko Mikhail
Published: December 2023

Background

Yakuts are one of the indigenous populations of the subarctic and arctic territories of Siberia characterized by a continental subarctic climate with severe winters, with the regular January average temperature in the regional capital city of Yakutsk dipping below − 40 °C. The epigenetic mechanisms of adaptation to such ecologies and environments and, in particular, epigenetic age acceleration in the local population have not been studied before.

Results

This work reports the first epigenetic study of the Yakutian population using whole-blood DNA methylation data, supplemented with the comparison to the residents of Central Russia. Gene set enrichment analysis revealed, among others, geographic region-specific differentially methylated regions associated with adaptation to climatic conditions (water consumption, digestive system regulation), aging processes (actin filament activity, cell fate), and both of them (channel activity, regulation of steroid and corticosteroid hormone secretion). Further, it is demonstrated that the epigenetic age acceleration of the Yakutian representatives is significantly higher than that of Central Russia counterparts. For both geographic regions, we showed that epigenetically males age faster than females, whereas no significant sex differences were found between the regions.

Conclusions

We performed the first study of the epigenetic data of the Yakutia cohort, paying special attention to region-specific features, aging processes, age acceleration, and sex specificity.
Target detection based on generalized Bures–Wasserstein distance
Authors: Huang Zhizhong , Zheng Lin
Published: December 2023

Radar target detection with fewer echo pulses in non-Gaussian clutter background is a challenging problem. In this instance, the conventional detectors using coherent accumulation are not very satisfactory. In contrast, the matrix detector based on Riemannian manifolds has shown potential on this issue since the covariance matrix of radar echo data during one coherent processing interval(CPI) has a smooth manifold structure. The Affine Invariant (AI) Riemannian distance between the cell under test (CUT) and the reference cells has been used as a statistic to achieve improved detection performance. This paper uses the Bures–Wasserstein (BW) distance and Generalized Bures–Wasserstein (GBW) distance on Riemannian manifolds as test statistics of matrix detectors, and propose relevant target detection method. Maximizing the GBW distance is formulated as an optimization problem and is solved by the Riemannian trust-region (RTR) method to achieve enhanced discrimination for target detection. Our evaluation of simulated data and measured data show that the matrix detector based on GBW distance leads to a significant performance gain over existing methods.
Rural women and ecotourism: modeling entrepreneurial behavior in Iran
Authors: Aghdasi Sahar , Omidi Najafabadi Maryam , Farajollah Hosseini Seyed Jamal
Published: December 2023

Fars province, as one of the most susceptible ecotourism regions of Iran, has paid attention to the establishment of ecotourism residences with the priority of rural women through ecotourism entrepreneurial training in recent years. In this regard, the present study investigates the effective factors on entrepreneurial behavior with Fars rural women ecotourism approach in Iran. The participants of the study were 431 of rural women in Fars and 205 were decided by Cochran formula. It is inferred from the results that step-by-step procedure of changing norms towards the acceptance of rural women entrepreneurs as well as the acceptance of ecotourism culture through the establishment of local and regional institutions and organizations in a context of family support with strong bonds of commitment, solidarity, environmental and infrastructural foundations will lead to a strong desire to constitute ecotourism residence by rural women.
Characteristics and outcomes of patients hospitalized for infection with influenza, SARS-CoV-2 or respiratory syncytial virus in the season 2022/2023 in a large German primary care centre
Authors: Quarg C. , Jörres R. A. , Engelhardt S. , Alter P. , Budweiser S.
Published: December 2023

Background

In 2022/2023, Influenza A and Respiratory Syncytial Virus (RSV) reappeared in hospitalized patients, which was in parallel to ongoing SARS-CoV-2 infections. The aim of our study was to compare the characteristics and outcomes of these infections during the same time.

Methods

We included patients of all ages with a positive polymerase chain reaction (PCR) test for Influenza A/B, RSV, or SARS-CoV-2 virus hospitalized in the neurological, internal or paediatric units of the RoMed Hospital Rosenheim, Germany, between October 1st 2022 and February 28th 2023.

Results

A total of 906 patients were included (45.6% female; median age 68.0 years; 21.9% Influenza A, 48.2% SARS-CoV-2, 28.3% RSV). Influenza B (0.2%) and co-infections (1.5%) played a minor role. In patients aged ≥ 18 years (n = 637, 71%), Influenza A, SARS-CoV-2 and RSV groups differed in age (median 72, 79, 76 years, respectively; p < 0.001). Comorbidities, particularly asthma and COPD, were most prevalent for RSV. 103 patients were admitted to the intensive care unit (ICU) (16.3% Influenza A, 15.3% SARS-CoV-2, 19.2% RSV; p = 0.649), 56 died (6.8% Influenza A, 9% SARS-CoV-2, 11.1% RSV; p = 0.496). RSV showed the highest frequencies of low-flow oxygen supplementation for admission and stay. Differences in the length of stay were minor (median 7 days). Conversely, in patients aged < 18 years (n = 261, 28,8%), 19.5%, 17.6% and 60.2% were in the Influenza A, SARS-CoV-2 and RSV groups, respectively; 0.4% showed Influenza B and 2.3% co-infections. 17 patients were admitted to ICU (3.9% Influenza A, 9.6% RSV, 0% SARS-CoV-2); none died. RSV showed the highest frequencies of high- and low-flow oxygen supplementation, SARS-CoV-2 the lowest.

Conclusion

When comparing infections with Influenza, SARS-CoV-2 and RSV in the winter 2022/2023 in hospitalized adult patients, rates of ICU admission and mortality were similar. RSV showed the highest frequencies of obstructive airway diseases, and of oxygen supplementation. The latter was also true in children/adolescents, in whom RSV dominated. Thus, in the situation of declining importance of SARS-CoV-2, RSV showed a disease burden that was relatively higher than that from Influenza and SARS-CoV-2 across ages, and this might be relevant for the seasons coming.
Disulfidptosis-related signatures for prognostic and immunotherapy reactivity evaluation in hepatocellular carcinoma
Authors: Zhao Jiajing , Luo Zeminshan , Fu Ruizhi , Zhou Jinghong , Chen Shubiao , Wang Jianjie , Chen Dewang , Xie Xiaojun
Published: December 2023

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world and a nonnegligible health concern on a worldwide scale. Disulfidptosis is a novel mode of cell death, which is mainly caused by the collapse of the actin skeleton. Although many studies have demonstrated that various types of cell death are associated with cancer treatment, the relationship between disulfidptosis and HCC has not been elucidated.

Methods

Here, we mainly applied bioinformatics methods to construct a disulfidptosis related risk model in HCC patients. Specifically, transcriptome data and clinical information were downloaded from the Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) database. A total of 45 co-expressed genes were extracted between the disulfidptosis-related genes (DRGs) and the differential expression genes (DEGs) of liver hepatocellular carcinoma (LIHC) in the TCGA database. The LIHC cohort was divided into two subgroups with different prognosis by k-mean consensus clustering and functional enrichment analysis was performed. Subsequently, three hub genes (CDCA8, SPP2 and RDH16) were screened by Cox regression and LASSO regression analysis. In addition, a risk signature was constructed and the HCC cohort was divided into high risk score and low risk score subgroups to compare the prognosis, clinical features and immune landscape between the two subgroups. Finally, the prognostic model of independent risk factors was constructed and verified.

Conclusions

High DRGs-related risk score in HCC individuals predict poor prognosis and are associated with poor immunotherapy response, which indicates that risk score assessment model can be utilized to guide clinical treatment strategy.
Single-cell transcriptomic atlas of goat ovarian aging
Authors: Xu Dejun , Song Shuaifei , Wang Fuguo , Li Yawen , Li Ziyuan , Yao Hui , Zhao Yongju , Zhao Zhongquan
Published: December 2023

Background

The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process, and ovarian aging is shown by a decrease in the number and quality of oocytes. However, little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging, especially in goats. Therefore, the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution.

Results

For the first time, we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn, young and aging goats, and identified nine ovarian cell types with distinct gene-expression signatures. Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological processes, such as Wnt beta-catenin signalling was enriched in germ cells, whereas ovarian steroidogenesis was enriched in granulosa cells (GCs). Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system, oxidative phosphorylation, and apoptosis. Subsequently, we identified a series of dynamic genes, such as AMH, CRABP2, THBS1 and TIMP1, which determined the fate of GCs. Additionally, FOXO1, SOX4, and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging.

Conclusions

This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell type-specific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.