bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential for reducing immobility times of a mobility monitor in-bed sensor system – a stepped-wedge cluster-randomised trial
Authors: Ziegler Sven , Schmoor Claudia , Schöler Lili M. , Schepputat Sam , Takem Eyere , Grotejohann Birgit , Steinbrenner Inga , Feuchtinger Johanna
Published: December 2023

Background

Pressure ulcer prophylaxis is a central topic in clinical care. Pressure-relieving repositioning is strongly recommended for all pressure-sensitive patients. The Mobility Monitor (MoMo) is a technical device that records a patient’s movements and transmits the data to a monitor. This study investigated the extent to which the MoMo sensor system, which records and visualises patients’ movements in bed, supports nurses in performing pressure-relieving repositioning in neurological and neurosurgical intensive care units (ICU).

Methods

This stepped-wedge cluster-randomised trial involved two clusters: one neurological and one neurosurgical ICU. The study was carried out in two steps over three periods between November 2018 and May 2019, with a two-month interval between each step. At the beginning of the study, we equipped 33 beds across the two ICUs with a MoMo system. Our primary endpoint was the immobility rate, which is defined as the patient’s inactive time in bed exceeding two hours without pressure-relieving movements divided by the time the MoMo was in the bed. The immobility rate ranges from 0 to below 1, with higher values indicating lower mobility. Secondary endpoints were the rate of new pressure ulcers and the rate of relevant pressure-relieving repositionings. Relevant repositionings are defined as the number of repositionings identified by the MoMo as a pressure-relieving repositioning divided by the total number of repositionings,

Results

808 patients were included in the study, of whom 403 were in the control group and 405 were in the intervention group.

The mean immobility rate was 0.171 during the control phase and 0.144 during the intervention phase. The estimated intervention effect was -0.0018 (95% confidence interval [-0.0471, 0.0436],p=0.94). The number of new pressure ulcers was 5/405 in the intervention phase and 15/403 in the control phase. We noted a small difference in the mean rate of relevant repositioningswith an estimated intervention effect of 0.046 (95% confidence interval [-0.018, 0.110],p=0.16).

Conclusion

Our results are insufficient to recommend the standardised use of mobility monitors in neurological or neurosurgical ICUs.

Clinical trial registration

The primary analysis was prespecified and the trial was registered in the German Clinical Trials Register (DRKS) under the reference number DRKS00015492 (31/10/2018).
A study on the impact of life meaning on occupational identity of nursing students in China:a cross-sectional study
Authors: Qiu Lingjing , Miao Qunfang , Zhao Yueyan , Zhu Li , Wang Yanling
Published: December 2023

Background

With the alterations of the Chinese epidemic prevention policy, China experienced a nationwide wave of the Coronavirus disease 2019 (COVID-19) pandemic from December 2022 to January 2023.The impact of the COVID-19 pandemic extends beyond individual perceptions of the meaning of life and attitudes toward life and death; it also affects the professional identity of nursing students.This study explored nursing students’ professional identity and life meaning of affected by the pandemic.

Methods

An online survey was conducted using the Chinese version of the Nursing Student Career Identity Scale and the Chinese version of the Meaning in Life Questionnaire to assess the current status of nursing students’ professional identity and sense of life meaning. Data were also collected on participant gender, education, clinical practice experience, and COVID-19 infection.

Results

The scores for nursing students’ sense of professional identity (61.58 ± 16.16) and sense of life meaning (45.29 ± 12.65) were both at an intermediate level. Compared to the scores before the COVID-19 pandemic, Chinese nursing students’ professional identity scores increased, while their sense of life meaning scores decreased. Moreover, we found a positive correlation between professional identity and sense of life meaning (p < 0.001); nursing students exhibited a stronger professional identity when they had a relatively higher sense of life meaning than those with a relatively lower sense of life meaning.

Conclusion

Enhancing nursing students’ sense of meaning in life is crucial for maintaining their professional identity. Attention should be given to life education for nursing students and the development of relevant educational curricula.
The impact of COVID-19-related restrictions on pregnancy and abortion rates in the Republic of Georgia
Authors: Khachidze Nia , Manjavidze Tinatin , Anda Erik Eik , Nedberg Ingvild Hersoug , Sandøy Ingvild Fossgard , Rylander Charlotta
Published: December 2023

Background

The Republic of Georgia implemented COVID-19-related restrictions starting on 31 March 2020, when it imposed a 1-month strict lockdown, after which the country continued with some form of restrictions for 1 year. These restrictions created barriers to healthcare access, affected healthcare services, caused severe economic degradation, and changed reproductive behavior. The aim of this study was to explore the impact of COVID-19-related restrictions on pregnancy and abortion rates in Georgia.

Methods

Information on pregnancy, abortion, and related variables was extracted from the Georgian Birth Registry from January 2018 through April 2022. The final study sample included 232,594 pregnancies and 86,729 abortions. We used interrupted time series analysis to study the impact of COVID-19-related restrictions.

Results

There were slightly decreasing trends in pregnancy and abortion rates in the pre-pandemic period (1 January 2018-31 March 2020). During the 1-month strict lockdown (1 April-30 April 2020), pregnancy and abortion rates decreased in all investigated age groups. There were no substantial differences in pregnancy or abortion rates in the pandemic period (for pregnancies: 1 April 2020-30 June 2021; for abortions: 1 April 2020-30 April 2022) compared to the pre-pandemic period. The precision of all estimates suggested that both small increases and decreases in pregnancy and abortion rates are reasonably compatible with our data.

Conclusions

Despite the 1-year-long COVID-19-related restrictions, our results did not indicate substantial long-term changes in pregnancy or abortion rates during the study period for any age group. This may indicate that the restrictions did not substantially influence access to contraception, abortion services, or reproductive behavior.
Stakeholder perspectives on short-stay joint replacement programs: results from a national cross-sectional study
Authors: Ackerman Ilana N , Berkovic Danielle , Soh Sze-Ee , Naylor Justine , Lewis Peter , de Steiger Richard , Buchbinder Rachelle , Ademi Zanfina , Vallance Patrick , Harris Ian A
Published: December 2023

Background

The capacity to meet anticipated growth in joint replacement demand requires safe, efficient models of care. While short-stay joint replacement programs are being used internationally, they have not been widely implemented in many countries. Importantly, the critical challenges that need to be addressed ahead of large-scale program implementation remain unclear. This study aimed to investigate stakeholder perspectives on short-stay joint replacement programs, including perceived barriers and enablers to implementation and sustainability, and understand current practices in Australia.

Methods

Four key stakeholder groups were invited to participate in this national study: (1) health professionals who provide joint replacement care; (2) hospital administrators involved in joint replacement provision; (3) patients with recent joint replacement; and (4) carers of people with recent joint replacement. Data on perceived feasibility (0 (not at all feasible) − 10 (highly feasible), appeal (0 (not at all appealing) − 10 (highly appealing), current practices, and barriers and enablers were collected using visual analogue scales, multiple response option and open-ended questions, via an online platform. Descriptive analysis and free-text content analysis was undertaken.

Results

Data were available from 1,445 participants including 360 health professionals, 20 hospital administrators, 1,034 patients, and 31 carers. Short-stay program implementation was considered moderately feasible by health professionals (median 6, interquartile range (IQR) 3–8) and hospital administrators (median 5, IQR 5–6). Short-stay programs were moderately appealing to patients (median 7, IQR 2–9) but of little appeal to carers (median 3, IQR 1–7). Prominent implementation barriers included perceived limited appropriateness of short-stay programs, inadequate home supports, and issues around reimbursement models or program funding. Not having daily physiotherapy access and concerns about pain and mobility at home were common barriers for patients. Concern about patients’ ability to manage daily activities was the most common barrier for carers. Access to post-discharge services, better funding models, improved staffing, and consistent protocols and national care standards were prominent enablers.

Conclusions

This national study has uniquely captured multiple stakeholder perspectives on short-stay joint replacement programs. The findings can guide future quality improvement and implementation initiatives and the development of resources to best support patients, carers, clinicians, and hospitals.
Tn3-like structures co-harboring of blaCTX-M-65, blaTEM-1 and blaOXA-10 in the plasmids of two Escherichia coli ST1508 strains originating from dairy cattle in China
Authors: Wang Weiwei , Wei Xiaojuan , Zhu Zhen , Wu Lingyu , Zhu Qiqi , Arbab Safia , Wang Chengye , Bai Yubin , Wang Qing , Zhang Jiyu
Published: December 2023

The purpose of this study was to determine the level of horizontal transmission of the blaCTX-M-65 gene and the role of its associated mobile genetic elements (MGEs) in the bovine-derived Escherichia coli. After PCR identification, two plasmids carrying blaCTX-M-65 were successfully transferred to the recipient E. coli J53 Azr through conjugation assays and subsequently selected for Whole-Genome sequencing (WGS) analysis. The resistance profiles of these two positive strains and their transconjugants were also determined through antimicrobial susceptibility tests. Whole genome data were acquired using both the PacBio sequencing platform and the Illumina data platform. The annotated results were then submitted to the Genbank database for accession number recording. For comparison, the genetic environment of plasmids carrying the resistance gene blaCTX-M-65 was mapped using the Easyfig software. WGS analysis revealed Tn3-like composite transposons bearing blaCTX-M-65, blaTEM-1, and blaOXA-10 in the IncHI2-type plasmids of these two E. coli ST1508 strains. A phylogenetic tree was generated from all 48 assembled E. coli isolates blaCTX-M-65, blaTEM-1, and blaOXA-10 from the NCBI Pathogen Detection database with our two isolates, showing the relationships and the contribution of SNPs to the diversity between genetic samples. This study suggests that the transmissibility of blaCTX-M-65 on Tn3-like composite transposons contributes to an increased risk of its transmission in E. coli derived from dairy cattle.
Bronchoalveolar cytokine profile differentiates Pulmonary Langerhans cell histiocytosis patients from other smoking-related interstitial lung diseases
Authors: Barril Silvia , Acebo Paloma , Millan-Billi Paloma , Luque Alfonso , Sibila Oriol , Tarín Carlos , Tazi Abdellatif , Castillo Diego , Hortelano Sonsoles
Published: December 2023

Background

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial lung disease (ILD) associated with smoking, whose definitive diagnosis requires the exclusion of other forms of ILD and a compatible surgical lung biopsy. Bronchoalveolar lavage (BAL) is commonly proposed for the diagnosis of ILD, including PLCH, but the diagnostic value of this technique is limited. Here, we have analyzed the levels of a panel of cytokines and chemokines in BAL from PLCH patients, in order to identify a distinct immune profile to discriminate PLCH from other smoking related-ILD (SR-ILD), and comparing the results with idiopathic pulmonary fibrosis (IPF) as another disease in which smoking is considered a risk factor.

Methods

BAL samples were collected from thirty-six patients with different ILD, including seven patients with PLCH, sixteen with SR-ILD and thirteen with IPF. Inflammatory profiles were analyzed using the Human Cytokine Membrane Antibody Array. Principal component analysis (PCA) was performed to reduce dimensionality and protein–protein interaction (PPI) network analysis using STRING 11.5 database were conducted. Finally, Random forest (RF) method was used to build a prediction model.

Results

We have found significant differences (p < 0.05) on thirty-two cytokines/chemokines when comparing BAL from PLCH patients with at least one of the other ILD. Four main groups of similarly regulated cytokines were established, identifying distinct sets of markers for each cluster. Exploratory analysis using PCA (principal component analysis) showed clustering and separation of patients, with the two first components capturing 69.69% of the total variance. Levels of TARC/CCL17, leptin, oncostatin M (OSM) and IP-10/CXCL10 were associated with lung function parameters, showing positive correlation with FVC. Finally, random forest (RF) algorithm demonstrates that PLCH patients can be differentiated from the other ILDs based solely on inflammatory profile (accuracy 96.25%).

Conclusions

Our results show that patients with PLCH exhibit a distinct BAL immune profile to SR-ILD and IPF. PCA analysis and RF model identify a specific immune profile useful for discriminating PLCH.
Longitudinal microbial and molecular dynamics in the cystic fibrosis lung after Elexacaftor–Tezacaftor–Ivacaftor therapy
Authors: Martin Christian , Guzior Douglas V. , Gonzalez Cely T. , Okros Maxwell , Mielke Jenna , Padillo Lienwil , Querido Gabriel , Gil Marissa , Thomas Ryan , McClelland Marc , Conrad Doug , Widder Stefanie , Quinn Robert A.
Published: December 2023

Background

Cystic fibrosis (CF) is a genetic disorder causing poor mucociliary clearance in the airways and subsequent respiratory infection. The recently approved triple therapy Elexacaftor–Tezacaftor–Ivacaftor (ETI) has significantly improved lung function and decreased airway infection in persons with CF (pwCF). This improvement has been shown to occur rapidly, within the first few weeks of treatment. The effects of longer term ETI therapy on lung infection dynamics, however, remain mostly unknown.

Results

Here, we applied 16S rRNA gene amplicon sequencing, untargeted metabolomics, and neutral models to high-resolution, longitudinally collected sputum samples from pwCF on ETI therapy (162 samples, 7 patients) and compared to similarly collected data set from pwCF not taking ETI (630 samples, 9 patients). Because ETI reduces sputum production, samples were collected in freezers provided in the subject’s homes at least 3 months after first taking ETI, with those on ETI collecting a sample approximately weekly. The lung function (%ppFEV1) of those in our longitudinal cohort significantly improved after ETI (6.91, SD = 7.74), indicating our study cohort was responsive to ETI. The daily variation of alpha- and beta-diversity of both the microbiome and metabolome was higher for those on ETI, reflecting a more dynamic microbial community and chemical environment during treatment. Four of the seven subjects on ETI were persistently infected with Pseudomonas or Burkholderia in their sputum throughout the sampling period while the total bacterial load significantly decreased with time (R = − 0.42, p = 0.01) in only one subject. The microbiome and metabolome dynamics on ETI were personalized, where some subjects had a progressive change with time on therapy, whereas others had no association with time on treatment. To further classify the augmented variance of the CF microbiome under therapy, we fit the microbiome data to a Hubbell neutral dynamics model in a patient-stratified manner and found that the subjects on ETI had better fit to a neutral model.

Conclusion

This study shows that the longitudinal microbiology and chemistry in airway secretions from subjects on ETI has become more dynamic and neutral and that after the initial improvement in lung function, many are still persistently infected with CF pathogens.
Evaluation of different scoring systems in the prediction of complications, morbidity, and mortality after laparoscopic radical gastrectomy
Authors: He Haoyu , Liu Yubiao , Liu Xin , Zhang Zhaoxiong , Wang Daohan , Fu Weihua
Published: December 2023

Background

This retrospective study aimed to assess the suitability of POSSUM and its modified versions, E-PASS and its modified score, SRS, and SORT scores for predicting postoperative complications and mortality in patients undergoing laparoscopic radical gastrectomy for gastric cancer.

Materials and methods

Data analysis was performed on 349 patients who underwent laparoscopic radical gastrectomy at Tianjin Medical University General Hospital between January 2016 and December 2021. The discriminative ability of the scoring systems was evaluated using the area under the receiver operating characteristic curve (AUC). The primary endpoint focused on the prediction of postoperative complications, while the secondary endpoint assessed the prediction of postoperative mortality.

Results

Among the scoring systems evaluated, the modified E-PASS (mE-PASS) score exhibited the highest AUC (0.846) and demonstrated the highest sensitivity (81%) and specificity (79%) for predicting postoperative complications. All other scores, except for POSSUM, showed moderate discriminative ability in predicting complications. In terms of predicting postoperative mortality, the E-PASS score had the highest AUC (0.978), while the mE-PASS score displayed the highest sensitivity (76%) and specificity (90%). Notably, both E-PASS and mE-PASS scores exhibited excellent discriminative ability.

Conclusions

The P-POSSUM, O-POSSUM, E-PASS, mE-PASS, SRS, and SORT scoring systems are useful tools for predicting postoperative outcomes in laparoscopic radical gastrectomy. Among them, the mE-PASS score demonstrated the best predictive power. However, the POSSUM system could only be applicable to predict postoperative mortality.
Can AMH levels predict the need to step up FSH dose for controlled ovarian stimulation following a long GnRH agonist protocol in PCOS women?
Authors: Huang Hui , Gao Haijie , Shi Yingying , Deng Bingbing , He Xuemei , Lin Jin , Li Ping
Published: December 2023

Background

To explore the role of anti-Mullerian hormone (AMH) in predicting the need to step up recombinant FSH (rFSH) dose following long GnRH agonist protocol in IVF/ICSI cycles of polycystic ovarian syndrome (PCOS) women.

Methods

This is a retrospective cohort study of 825 PCOS women undergoing long GnRH agonist protocol enrolled from Jan 2019 to Dec 2021. The daily rFSH dose at which the first response to rFSH were recorded. The dose at which the first response to rFSH was based on folliculometry during follow up in which two or more follicles reached ≥ 11 mm. A receiver operating characteristic (ROC) curve analysis was done to investigate the ability of AMH to predict the need to step up initial rFSH dose.

Results

PCOS women who needed to step up initial rFSH dose had a significantly higher AMH compared with those didn’t step up initial rFSH dose (11.37 ± 3.25ng/ml vs. 8.69 ± 3.16ng/ml, p < 0.001). In multivariate logistic regression analysis, increased AMH level was an independent factor for the need to step up initial rFSH dose in PCOS patients after adjusted for confounding factors. ROC curve analysis showed AMH could predict the need to step up initial rFSH dose (AUC = 0.738, 95%CI: 0.704–0.773), having 75.4% specificity and 63% sensitivity when the threshold AMH concentration was 9.30ng/ml. 58.8% PCOS women with AMH > 9.30 ng/ml required increased rFSH dose compared to 18.8% of women with AMH ≤ 9.30ng/ml (p < 0.001). Although the clinical pregnancy rate and live birth rate were not significantly different, there was a higher incidence of OHSS among women with AMH > 9.30 ng/ml vs. AMH ≤ 9.30ng/ml (20.8% vs. 15.3%, p = 0.043).

Conclusion

PCOS women with AMH > 9.30 ng/ml were resistant to rFSH stimulation and require increased dose for the cycle recruitment of ovarian follicles.
Blood circulating bacterial DNA in hospitalized old COVID-19 patients
Authors: Giacconi Robertina , D’Aquila Patrizia , Cardelli Maurizio , Piacenza Francesco , Pierpaoli Elisa , Sena Giada , Di Rosa Mirko , Bonfigli Anna Rita , Galeazzi Roberta , Cherubini Antonio , Fedecostante Massimiliano , Sarzani Riccardo , Di Pentima Chiara , Giordano Piero , Antonicelli Roberto , Lattanzio Fabrizia , Passarino Giuseppe , Provinciali Mauro , Bellizzi Dina
Published: December 2023

Background

Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients.

Results

BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65–99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes.

Conclusions

The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.
Jiedu Fuzheng decoction improves the proliferation, migration, invasion and EMT of non-small cell lung cancer via the Wnt/β-catenin pathway
Authors: Fang Fang , Jin Xiaowei , Meng Jinming , He Jiaqi , Wang Jiaxiao , Wang Changhong , Xie Sheng , Shi Wei
Published: December 2023

Objectives

This study aimed to investigate the effect of Jiedu Fuzheng decoction (JFD) in non-small cell lung cancer (NSCLC) and its potential therapeutic mechanism.

Results

We prepared JFD-medicated serum from rats and treated NSCLC cells (A549 and NCI-H1650) with 0.5, 1, and 2 mg/mL JFD-medicated serum. CCK-8 and colony formation assays were used to detect cell proliferation. Transwell assays showed that JFD attenuated cell migration and invasion. JFD and SKL2001 (Wnt/β-catenin activator) were simultaneously used to treat NSCLC cells to verify that JFD regulated the biological behavior of NSCLC via Wnt/β-catenin signaling. It was found that 2 mg/mL JFD had the most significant effect on the activity of NSCLC cells. JFD attenuated proliferation and metastasis but increased the proportion of apoptotic cells. At the same time, JFD downregulated N-cadherin, vimentin and β-catenin protein expression in cancer cells. SKL2001 could restore the improvement of JFD on proliferation, metastasis and apoptosis.

Conclusion

This study confirmed that JFD suppressed the occurrence and development of NSCLC by regulating Wnt/β-catenin signaling and provided a novel therapeutic scheme for NSCLC.
The versatile thoracodorsal artery perforator flap for extremity reconstruction: from simple to five types of advanced applications and clinical outcomes
Authors: Sui Xinlei , Qing Liming , Yu Fang , Wu Panfeng , Tang Juyu
Published: December 2023

Background

Application of the thoracodorsal artery perforator (TDAP) flap is known to be a popular and reliable method for extremity reconstruction. This manuscript presents our clinical outcomes in reconstructing soft tissue defects using simple and advanced TDAP flaps.

Methods

From 2013 to 2022, 53 patients with a mean age of 23 years (ranging from 2 to 72 years) underwent reconstructive surgery with different patterns of free TDAP flaps, including chimeric TDAP flaps, double skin paddle TDAP flaps, flow-through TDAP flaps, conjoined TDAP flaps, and microdissected debulking TDAP flaps.

Results

All TDAP flaps survived. The size of the TDAP skin paddle ranged between 5 × 3 and 25 × 10 cm2. Primary closure of the donor site was achieved in all patients in the simple application group, and one patient in the advanced application group underwent partial skin grafting. Partial flap loss occurred in one case in the simple TDAP flap group and four cases in the advanced application group. There was one case of flap bulkiness and two cases of scar hyperplasia in the simple TDAP flap group. The mean follow-up duration was 11 months (4–46 months).

Conclusions

The free TDAP flap, with five types of advanced applications, makes it versatile for reconstructing different kinds of soft tissue defects of the extremities that can be used to achieve individualized defect reconstruction, minimize donor site morbidities, and an aesthetic appearance.
Exploring the interaction between extracellular matrix components in a 3D organoid disease model to replicate the pathophysiology of breast cancer
Authors: Bhattacharya Anamitra , Alam Kamare , Roy Nakka Sharmila , Kaur Kulwinder , Kaity Santanu , Ravichandiran Velayutham , Roy Subhadeep
Published: December 2023

In vitro models are necessary to study the pathophysiology of the disease and the development of effective, tailored treatment methods owing to the complexity and heterogeneity of breast cancer and the large population affected by it. The cellular connections and tumor microenvironments observed in vivo are often not recapitulated in conventional two-dimensional (2D) cell cultures. Therefore, developing 3D in vitro models that mimic the complex architecture and physiological circumstances of breast tumors is crucial for advancing our understanding of the illness. A 3D scaffold-free in vitro disease model mimics breast cancer pathophysiology by allowing cells to self-assemble/pattern into 3D structures, in contrast with other 3D models that rely on artificial scaffolds. It is possible that this model, whether applied to breast tumors using patient-derived primary cells (fibroblasts, endothelial cells, and cancer cells), can accurately replicate the observed heterogeneity. The complicated interactions between different cell types are modelled by integrating critical components of the tumor microenvironment, such as the extracellular matrix, vascular endothelial cells, and tumor growth factors. Tissue interactions, immune cell infiltration, and the effects of the milieu on drug resistance can be studied using this scaffold-free 3D model. The scaffold-free 3D in vitro disease model for mimicking tumor pathophysiology in breast cancer is a useful tool for studying the molecular basis of the disease, identifying new therapeutic targets, and evaluating treatment modalities. It provides a more physiologically appropriate high-throughput platform for screening large compound library in a 96–384 well format. We critically discussed the rapid development of personalized treatment strategies and accelerated drug screening platforms to close the gap between traditional 2D cell culture and in vivo investigations.

Graphical Abstract
Combined treatment with basalt stone and placenta extract to improve the chronic pain and scar after breast cancer surgery: a case report
Authors: Inagaki Mioka , Otsuka Eriko , Hayashi Yuko , Ohsawa Masahiro , Hirano Eiichi
Published: December 2023

Background

The changes in body image caused by breast deformities and postoperative pain have a detrimental influence on the physical and mental health of patients with breast cancer. The postoperative quality of life (QOL) of these patients reduces significantly owing to the changes in the breast, an organ unique to women, that occur following breast cancer surgery.

Case presentation

This case report presents the case of a Asian woman in her early 40 s with postoperative hypertrophic scarring and contraction of the scar following mastectomy; the patient presented with decreased range of motion of the upper arm, hyperpigmentation from radiation burns, changes in breast shape, and chronic pain. The patient received a combination therapy comprising Basalt Stone Treatment and the application of horse placenta extract. As a result of a total of eight sessions conducted once every two weeks, the patient's pain and scar improved. No adverse events were observed after the therapy.

Conclusion

Combination therapy with Basalt Stone Treatment and horse placenta extract improved the chronic pain and scar after breast cancer surgery.
Glial cell changes in the corpus callosum in chronically-starved mice
Authors: Zimmermann Annelie , Böge Natalie , Schuster Katharina , Staffeld Anna , Lang Stephan , Gill Sadaf , Rupprecht Hanna , Frintrop Linda
Published: December 2023

Anorexia nervosa (AN) is characterized by emaciation, hyperactivity, and amenorrhea. Imaging studies in AN patients have revealed reductions in grey and white matter volume, which correlate with the severity of neuropsychological deficits. However, the cellular basis for the observed brain atrophy is poorly understood. Although distinct hypothalamic centers, including the arcuate nucleus (ARC) are critically involved in regulating feeding behavior, little is known about potential hypothalamic modifications in this disorder. Since glia e.g. astrocytes and microglia influence neuronal circuits, we investigated the glial changes underlying pathophysiology of starvation in the corpus callosum (CC) and hypothalamus. Female mice were given a limited amount of food once a day and had unlimited access to a running wheel until a 20% weight reduction was achieved (acute starvation). This weight reduction was maintained for two weeks to mimic chronic starvation. Immunohistochemistry was used to quantify the density of astrocytes, microglia, oligodendrocytes, and the staining intensity of neuropeptide Y (NPY), a potent orexigenic peptide. Chronic starvation induced a decreased density of OLIG2+ oligodendrocytes, GFAP+ astrocytes, and IBA1+ microglia in the CC. However, the densities of glial cells remained unchanged in the ARC following starvation. Additionally, the staining intensity of NPY increased after both acute and chronic starvation, indicating an increased orexigenic signaling. Chronic starvation induced glial cell changes in the CC in a mouse model of AN suggesting that glia pathophysiology may play a role in the disease.
The effectiveness of rational emotive behavior therapy (REBT) and mindfulness-based intervention (MBI) on psychological, physiological and executive functions as a proxy for sports performance
Authors: Tóth Renátó , Turner Martin James , Mannion Joe , Tóth László
Published: December 2023

Background

In the current study, we conducted a comparative analysis involving three distinct groups: one receiving group-based rational emotive behavior therapy (REBT), another undergoing a mindfulness-based intervention (MBI), and a third group serving as the control. The aim of the study was to explore the effectiveness of the two interventions on specific psychological (competitive anxiety, perfectionism, irrational beliefs), physiological (salivary cortisol levels), and neurocognitive (executive functions: working memory, inhibition, cognitive flexibility) functions in Hungarian junior ice hockey players.

Methods

The participants consisted of 10 females and 36 males (NREBT=12, NMINDFULNESS=14, NCONTROL=20). We used questionnaires to assess competitive anxiety, perfectionism, and irrational beliefs. The components of executive functions were measured using a computerized testing system, while cortisol levels were examined through salivary samples. Prior to and after the interventions, each participant underwent all measurements, after which we conducted repeated measures ANOVA on our data.

Results

We found REBT to be an effective intervention for the regulation of competitive anxiety, perfectionism, and irrational beliefs as well as for improving some components of executive functions (inhibition and cognitive flexibility). Mindfulness was found to improve athletes’ processing speed and set-shifting abilities, which are related to cognitive flexibility and metacognitive processes.

Conclusion

In conclusion, we explore implications of these findings regarding how each approach is posited to enhance sports performance, using neurocognitive functions as a proxy. These findings are useful for further research and practical implications.
Mimicking hypomethylation of FUS requires liquid–liquid phase separation to induce synaptic dysfunctions
Authors: Kim Seung Chan , Mitchell Scott J. , Qamar Seema , Whitcomb Daniel J. , Ruepp Marc-David , St George-Hyslop Peter , Cho Kwangwook
Published: December 2023

The hypomethylation of fused in sarcoma (FUS) in frontotemporal lobar degeneration promotes the formation of irreversible condensates of FUS. However, the mechanisms by which these hypomethylated FUS condensates cause neuronal dysfunction are unknown. Here we report that expression of FUS constructs mimicking hypomethylated FUS causes aberrant dendritic FUS condensates in CA1 neurons. These hypomethylated FUS condensates exhibit spontaneous, and activity induced movement within the dendrite. They impair excitatory synaptic transmission, postsynaptic density-95 expression, and dendritic spine plasticity. These neurophysiological defects are dependent upon both the dendritic localisation of the condensates, and their ability to undergo liquid–liquid phase separation. These results indicate that the irreversible liquid–liquid phase separation is a key component of hypomethylated FUS pathophysiology in sporadic FTLD, and this can cause synapse dysfunction in sporadic FTLD.
Targeting RACK1 to alleviate TDP-43 and FUS proteinopathy-mediated suppression of protein translation and neurodegeneration
Authors: Zhao Beibei , Cowan Catherine M. , Coutts Juliane A. , Christy Darren D. , Saraph Ananya , Hsueh Shawn C. C. , Plotkin Stephen S. , Mackenzie Ian R. , Kaplan Johanne M. , Cashman Neil R.
Published: December 2023

TAR DNA-binding protein 43 (TDP-43) and Fused in Sarcoma/Translocated in Sarcoma (FUS) are ribonucleoproteins associated with pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Under physiological conditions, TDP-43 and FUS are predominantly localized in the nucleus, where they participate in transcriptional regulation, RNA splicing and metabolism. In disease, however, they are typically mislocalized to the cytoplasm where they form aggregated inclusions. A number of shared cellular pathways have been identified that contribute to TDP-43 and FUS toxicity in neurodegeneration. In the present study, we report a novel pathogenic mechanism shared by these two proteins. We found that pathological FUS co-aggregates with a ribosomal protein, the Receptor for Activated C-Kinase 1 (RACK1), in the cytoplasm of spinal cord motor neurons of ALS, as previously reported for pathological TDP-43. In HEK293T cells transiently transfected with TDP-43 or FUS mutant lacking a functional nuclear localization signal (NLS; TDP-43ΔNLS and FUSΔNLS), cytoplasmic TDP-43 and FUS induced co-aggregation with endogenous RACK1. These co-aggregates sequestered the translational machinery through interaction with the polyribosome, accompanied by a significant reduction of global protein translation. RACK1 knockdown decreased cytoplasmic aggregation of TDP-43ΔNLS or FUSΔNLS and alleviated associated global translational suppression. Surprisingly, RACK1 knockdown also led to partial nuclear localization of TDP-43ΔNLS and FUSΔNLS in some transfected cells, despite the absence of NLS. In vivo, RACK1 knockdown alleviated retinal neuronal degeneration in transgenic Drosophila melanogaster expressing hTDP-43WT or hTDP-43Q331K and improved motor function of hTDP-43WT flies, with no observed adverse effects on neuronal health in control knockdown flies. In conclusion, our results revealed a novel shared mechanism of pathogenesis for misfolded aggregates of TDP-43 and FUS mediated by interference with protein translation in a RACK1-dependent manner. We provide proof-of-concept evidence for targeting RACK1 as a potential therapeutic approach for TDP-43 or FUS proteinopathy associated with ALS and FTLD.
Three-dimensional assessment of periodontal support of lower incisors for skeletal Class II malocclusion undergoing presurgical orthodontic treatment with different vertical skeletal patterns
Authors: Lyu Hangmiao , Ma Huimin , Wang Xiaoxia , Xu Li , Hou Jianxia , Zhao Yijiao , Li Weiran , Li Xiaotong
Published: December 2023

Background

The aim of the present study was to compare periodontal support changes during retraction of mandibular anterior teeth for skeletal Class II malocclusion with different facial divergence and to analyze relevant factors influencing bone remodeling by applying three-dimensional (3D) cone-beam computed tomography (CBCT) reconstruction technology.

Methods

Forty-eight patients with Class II malocclusion requiring surgical orthodontic treatment enrolled in the study were divided into the hyperdivergent group (n = 16), normodivergent group (n = 16) and hypodivergent group (n = 16) according to their vertical skeletal patterns. Cone-beam computed tomography (CBCT) scans were obtained before treatment (T1) and after presurgical orthodontic treatment (T2). The two-dimensional (2D) alveolar bone morphology, movement of mandibular central incisors and volume of the alveolar bone around incisors were measured on the labial and lingual sides by 3D CBCT reconstruction technology. Statistical analyses were performed with one-way ANOVA, paired t tests and multiple linear regression.

Results

During presurgical orthodontic treatment, the alveolar bone height on the labial side of the hyperdivergent group decreased significantly (P ≤ 0.05), but was maintained in the normodivergent and hypodivergent groups (P > 0.05). However, the alveolar bone volume, alveolar bone thickness at each level and alveolar bone height on the lingual side decreased significantly for all the groups. Apart from the initial morphometric measurements at T1, the morphology of lingual alveolar bone at T2 was significantly influenced by the direction and amount of tooth movement. Horizontal retraction and vertical protrusion of the root apex were negatively related to the alveolar bone on the lingual side after presurgical orthodontic treatment.

Conclusion

For Class II malocclusion patients undergoing presurgical orthodontic treatment, the changes in the periodontal support of the lower central incisors varied in different vertical skeletal patterns. There exists a great periodontal risk of alveolar bone resorption on the lingual side for various vertical types. To avoid alveolar bone deterioration, it is essential to investigate the bone remodeling of patients with different alveolar bone conditions and cautiously plan tooth movement prior to orthodontic treatment. Moreover, 3D measurements based on CBCT construction can provide complementary information to traditional 2D measurements.
Characterization of essential oil profiles, triterpenic acids, and biological assay in aerial parts of various Thymus persicus Jalas (Ronniger ex Rech.f.) populations
Authors: Bakhtiar Ziba , Mirjalili Mohammad Hossein , Selseleh Mohammad , Yavari Alireza , Ghorbanpour Mansour
Published: December 2023

Thymus persicus is a valuable natural source of anticancer triterpenic acids (TAs) such as betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA), which is growing wild in the northwest of Iran. In the present study, variability in morphological characteristics, phytochemical composition, and biological activity among T. persicus populations (TPPs) were investigated. The plants were phenotypically different with the highest variations in some morphological traits. In total, sixty-seven compounds representing 97.2‒99.9% of the essential oils were identified. Thymol (8.1‒43.9%), α-terpineol (1.8‒34.2%), and p-cymene (0.4‒13.4%) were the major components of the studied oils. The content of BA, OA, and UA was ranged as 530.55 ± 13.04‒856.89 ± 6.76, 419.35 ± 11.44‒584.43 ± 12.67, and 941.66 ± 11.49‒1070.82 ± 10.14 mg 100 g‒1 DW in the studied TPPs, respectively. The highest total phenol content (87.26 ± 4.35 mg GAE g–1 DW), total flavonoid content (72.34 ± 2.63 mg QE g–1 DW), and antioxidant property (IC50 = 64.28 ± 4.57 μg ml–1 and 61.68 ± 1.10 μmol Fe+2 g–1 DW) were recorded in TPP1 (Baderlu). The essential oil of the TPP3 (Angooran) showed the lowest minimal inhibitory concentration (MIC) against the bacteria (0.005‒0.080 mg ml–1) and fungi (0.077‒0.100 mg ml–1) among the studied TPPs. Multiple regression analysis showed an associated correlation among morphological, phytochemical characteristics, and biological activities. Canonical correspondence analysis also determined relationship between phytochemical traits and environmental factors. These findings contain valuable data for the conservation and sustainable exploitation of this valuable medicinal plant.

Graphical Abstract
Chromophoric cerium oxide nanoparticle-loaded sucking disk-type strip sensor for optical measurement of glucose in tear fluid
Authors: Park Sijin , Nam Dong Yeon , Jeon Hee-Jae , Han Jae Hoon , Jang Dawon , Hwang Juil , Park Yeong-Seo , Han Young-Geun , Choy Young Bin , Lee Dong Yun
Published: December 2023

Background

Noninvasive monitoring of tear glucose levels can be convenient for patients to manage their diabetes mellitus. However, there are issues with monitoring tear glucose levels, such as the invasiveness of some methods, the miniaturization, inaccuracy, or the high cost of wearable devices. To overcome the issues, we newly designed a sucking disk-type (SD) strip biosensor that can quickly suck tear fluid and contains cerium oxide nanoparticle (CNP) that causes a unique color change according to the glucose level of the tear without complicated electronic components.

Methods

The SD strip biosensor composed of three distinct parts (tip, channel, and reaction chamber) was designed to contain the sensing paper, onto which tear fluid can be collected and delivered. The sensing paper treated with CNP/APTS (aminopropyltriethoxysilane) /GOx (glucose oxidase) was characterized. Then we carried out the reliability of the SD strip biosensor in the diabetic rabbit animals. We quantitatively analyzed the color values of the SD strip biosensor through the colorimetric analysis algorithm.

Results

We contacted the inferior palpebral conjunctiva (IPC) of a diabetic rabbit eye using an SD strip biosensor to collect tears without eye irritation and successfully verified the performance and quantitative efficacy of the sensor. An image processing algorithm that can optimize measurement accuracy is developed for accurate color change measurement of SD strip biosensors. The validation tests show a good correlation between glucose concentrations measured in the tear and blood.

Conclusion

Our findings demonstrate that the CNP-embedded SD strip biosensor and the associated image processing can simply monitor tear glucose to manage diabetes mellitus.

Graphical Abstract
Absolute quantification of DNA damage response proteins
Authors: Matsuda Shun , Ikura Tsuyoshi , Matsuda Tomonari
Published: December 2023

Background

DNA damage response (DDR) and repair are vital for safeguarding genetic information and ensuring the survival and accurate transmission of genetic material. DNA damage, such as DNA double-strand breaks (DSBs), triggers a response where sensor proteins recognize DSBs. Information is transmitted to kinases, initiating a sequence resulting in the activation of the DNA damage response and recruitment of other DDR and repair proteins to the DSB site in a highly orderly sequence. Research has traditionally focused on individual protein functions and their order, with limited quantitative analysis, prompting this study’s attempt at absolute quantification of DNA damage response and repair proteins and capturing changes in protein chromatin affinity after DNA damage through biochemical fractionation methods.

Results

To assess the intracellular levels of proteins involved in DDR and repair, multiple proteins associated with different functions were quantified in EPC2-hTERT cells. H2AX had the highest intracellular abundance (1.93 × 106 molecules/cell). The components of the MRN complex were present at the comparable levels: 6.89 × 104 (MRE11), 2.17 × 104 (RAD50), and 2.35 × 104 (NBS1) molecules/cell. MDC1 was present at 1.27 × 104 molecules/cell. The intracellular levels of ATM and ATR kinases were relatively low: 555 and 4860 molecules/cell, respectively. The levels of cellular proteins involved in NHEJ (53BP1: 3.03 × 104; XRCC5: 2.62 × 104; XRCC6: 5.05 × 105 molecules/cell) were more than an order of magnitude higher than that involved in HR (RAD51: 2500 molecules/cell). Furthermore, we analyzed the dynamics of MDC1 and γH2AX proteins in response to DNA damage induced by the unstable agent neocarzinostatin (NCS). Using cell biochemical fractionation, cells were collected and analyzed at different time points after NCS exposure. Results showed that γH2AX in chromatin fraction peaked at 1 h post-exposure and gradually decreased, while MDC1 translocated from the isotonic to the hypertonic fraction, peaking at 1 hour as well. The study suggests increased MDC1 affinity for chromatin through binding to γH2AX induced by DNA damage. The γH2AX-bound MDC1 (in the hypertonic fraction) to γH2AX ratio at 1 h post-exposure was 1:56.4, with lower MDC1 levels which may attributed to competition with other proteins.

Conclusions

The approach provided quantitative insights into protein dynamics in DNA damage response.