bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of acupressure on pain intensity and physiological indices in patients undergoing extracorporeal shock wave lithotripsy: a randomized double-blind sham-controlled clinical trial
Authors: Safdari Ali , Khazaei Salman , Biglarkhani Mahdi , Mousavibahar Seyed Habibollah , Borzou Seyed Reza 
Published: January 2024

Abstract
Background
Despite the widespread use of extracorporeal shock wave lithotripsy (ESWL) as a treatment for kidney stones, it is essential to apply methods to control pain and improve patient comfort during this procedure. Therefore, this study aimed to investigate the effect of acupressure at the Qiu point on pain intensity and physiological indices in patients undergoing ESWL.

Methods
This randomized, sham-controlled clinical trial was conducted at the Shahid Beheshti Educational-medical Center in Hamadan City (western Iran) from May to August 2023. Seventy-four eligible patients were split into intervention (n = 37) and sham (n = 37) groups. Ten minutes before lithotripsy, the intervention group received acupressure at the Qiu point, while the sham group received touch at a neutral point. The primary outcomes were pain intensity measured by the Visual Analog Scale (VAS) and physiological indices such as blood pressure and heart rate at baseline, 1, 10, 20, 30, 40, and 50 min after the intervention. The secondary outcomes included lithotripsy success and satisfaction with acupressure application.

Results
The analysis of 70 patients showed no significant differences in the demographic and clinical information of the patients across the two groups before the study (P > 0.05). Generalized estimating equations revealed that the interaction effects of time and group in pain and heart rate were significant at 30 and 40 min (P < 0.05). The results of this analysis for systolic blood pressure revealed a significant interaction at 30 min (P = 0.035). However, no significant interaction effects were found for diastolic blood pressure changes (P > 0.05).

Conclusions
Acupressure at the Qiu point positively impacts pain in patients undergoing ESWL treatment and increases their satisfaction. However, these results for physiological indices require further studies. Thus, acupressure can be considered a simple, easy, and effective option for pain management in patients during this procedure.

Trial registration
[https://en.irct.ir/trial/69117], identifier [IRCT20190524043687N4].
The relationship between subjective compliance with isolation precautions and moral sensitivity in novice nurses: cross-sectional study
Authors: Tiryaki Şen Hanife , Polat Şehrinaz , Afşar Doğrusöz Leyla 
Published: January 2024

Abstract
Background
Increasing compliance with isolation precautions is important in reducing hospital-acquired infections and their consequences. It is not possible to achieve and maintain nurse compliance through supervision, control, pressure, or training. Therefore, nurses must personally demand compliance with isolation precautions. This study aimed to determine the relationship between compliance with isolation precautions and the moral sensitivity levels of nurses who have just started working.

Methods
This study employed a descriptive and cross-sectional research design. The study population consisted of 456 new nurses recruited during the pandemic. All of the new nurses who volunteered to participate in the study and completed the questionnaires completely were included in the study and 398 nurses constituted the sample of the study. Data were collected from 398 out of 456 novice nurses who agreed to participate in the study. The population coverage rate was 87.28%. Participants were selected using convenience sampling method. The data collection tools included an Introductory Information Form, The Isolation Compliance Precautions Scale (TIPCS), and the Moral Sensitivity Questionnaire (MSQ). Descriptive statistics, correlation analyses, and regression models were used to analyze data.

Findings
The mean score of the MSQ was high (mean ± SD = 90.49 ± 25.94; median (P25-P75) = 84 (range, 74–97), and the score for TIPCS was high (mean ± SD = 79.29 ± 7.68; median (P25-P75) = 82 (range, 76–85)). No correlation was found between MSQ and TIPCS (p > 0.05). According to the regression analysis, although the MSQ did not correlate with TIPCS, compliance with isolation measures was found to increase as the conflict subscale of moral sensitivity increased (β= -0.36, CI= -0.55 to -0.16; p < 0.001). Choosing the profession willingly had a positive correlation with compliance with isolation measures (β = 5.3, CI = 2.4 to 8.3; p < 0.001). In addition, starting the profession at an early age had a positive correlation with compliance with isolation measures (β= -0.49, CI= -0.8 to -0.17; p = 0.002).

Conclusion
The conflict sub-dimension of moral sensitivity is an important factor in nurses’ compliance with isolation measures, and conducting necessary training and other studies to improve nurses’ moral sensitivity may increase their compliance with isolation measures.
Identification of squalene epoxidase in triterpenes biosynthesis in Poria cocos by molecular docking and CRISPR-Cas9 gene editing
Authors: Liu Xiao-liu , Xie Jing , Xie Zhen-ni , Zhong Can , Liu Hao , Zhang Shui-han , Jin Jian 
Published: January 2024

Abstract
Background
Squalene epoxidase is one of the rate-limiting enzymes in the biosynthetic pathway of membrane sterols and triterpenoids. The enzyme catalyzes the formation of oxidized squalene, which is a common precursor of sterols and triterpenoids.

Result
In this study, the squalene epoxidase gene (PcSE) was evaluated in Poria cocos. Molecular docking between PcSE and squalene was performed and the active amino acids were identified. The sgRNA were designed based on the active site residues. The effect on triterpene synthesis in P. cocos was consistent with the results from ultra-high-performance liquid chromatography-quadruplex time-of-flight-double mass spectrometry (UHPLC-QTOF-MS/MS) analysis. The results showed that deletion of PcSE inhibited triterpene synthesis. In vivo verification of PcSE function was performed using a PEG-mediated protoplast transformation approach.

Conclusion
The findings from this study provide a foundation for further studies on heterologous biosynthesis of P. cocos secondary metabolites.
IFIT3 accelerates the progression of head and neck squamous cell carcinoma by targeting PD-L1 to activate PI3K/AKT signaling pathway
Authors: Liu Peng , Kong Xin , Yi Shijiang , Chen Ying , Luo Wenlong 
Published: January 2024

Abstract
Background
Emerging evidence has shown interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) may be predicted to be a candidate oncogene and involved in the onset and progression of cancer, but IFIT3’s potential role in cancer, particularly in head and neck squamous cell carcinoma (HNSC), is not well recognized. This study aims to reveal the role of IFIT3 in HNSC and the underlying molecular mechanism.

Methods
Bioinformatics analysis, immunohistochemical staining, RT-PCR, and Western blotting analysis were used to detect IFIT3 expression in HNSC. CCK-8 assays, colony formation assays, wound-healing assays, transwell assays, and sphere formation were used to explore proliferative, migratory, and invasive activities and cancer stemness of HNSC cells after IFIT3 knockdown and over-expressed. The alterations of EMT markers and PI3K/AKT pathway were detected by Western blotting. Animal studies were performed to analyze the effect of IFIT3 on tumor growth and metastasis of HNSC in vivo.

Results
In this study, we observed that IFIT3 was highly expressed in HNSC, and its higher expression contributed to poorer survival of patients with clinical stage IV or grade 3. Function assay indicated that IFIT3 promoted malignant behaviors in vitro, as well as tumor growth and lung metastasis in vivo. Meanwhile, PD-L1 knockdown or over-expressed reversed cancer cell stemness, migration, invasion, and PI3K/AKT signaling pathway which were regulated by IFIT3.

Conclusions
Our results reveal that IFIT3 promotes EMT and cancer stemness by targeting PD-L1 to activate PI3K/AKT signaling pathway in HNSC, and targeting IFIT3 may be a novel strategy for the treatment of patients with HNSC.
Inactivation and replantation of the knee joint: an infeasible surgical method
Authors: Tian Zhichao , Yang Yang , Zhang Peng , Wang Xin , Yao Weitao 
Published: January 2024

Abstract
Background
The inactivation and replantation of autologous tumor bones are important surgical methods for limb salvage in patients with malignancies. Currently, there are few reports on the inactivation and replantation of the knee joint. In this study, we aimed to evaluate the feasibility of our surgical approach.

Methods
This is a retrospective case series study. We retrospectively collected the clinical data of patients with sarcoma treated with knee joint inactivation and replantation and analyzed the efficacy of this surgical method. The bone healing and complications in these patients after inactivated autograft replantation were assessed.

Results
This study included 16 patients. Fifteen patients had osteosarcoma, and one had Ewing's sarcoma. The average length of the inactivated bone is 20.2 cm (range 13.5–25.3 cm). All the patients underwent internal plate fixation. The average follow-up duration was 30 months (range 8–60 months). Before the data deadline of this study, eight (50%) patients were still alive, and eight (50%) died of sarcoma metastasis. Eight (50%) patients achieved bone healing at the diaphysis site of the inactivated tumor bone, with an average bone healing time of 21.9 months (range, 12–36 months). Five (31%) patients died due to metastases and did not achieve bone healing. Two (12.5%) patients did not achieve bone healing because of infection, and one (6.3%) patient underwent amputation due to tumor recurrence. Ten (62.5%) patients experienced fractures around the joint ends of the inactivated replanted bone, and eight of these ten patients were combined with joint dislocation.

Conclusion
The incidence of joint deformities after the knee-joint inactivation and replantation is extremely high and is not recommended for use.
Synergistic use of anti-inflammatory ketorolac and gentamicin to target staphylococcal biofilms
Authors: Sekar Amita , Gil Dmitry , Tierney Peyton , McCanne Madeline , Daesety Vikram , Trendafilova Darina , Muratoglu Orhun K. , Oral Ebru 
Published: January 2024

Abstract
Background
While antibiotics remain our primary tools against microbial infection, increasing antibiotic resistance (inherent and acquired) is a major detriment to their efficacy. A practical approach to maintaining or reversing the efficacy of antibiotics is the use of other commonly used therapeutics, which show synergistic antibacterial action with antibiotics. Here, we investigated the extent of antibacterial synergy between the antibiotic gentamicin and the anti-inflammatory ketorolac regarding the dynamics of biofilm growth, the rate of acquired resistance, and the possible mechanism of synergy.

Methods
Control (ATCC 12600, ATCC 35984) and clinical strains (L1101, L1116) of Staphylococcus aureus and Staphylococcus epidermidis with varying antibiotic susceptibility profiles were used in this study to simulate implant-material associated low-risk and high-risk biofilms in vitro. The synergistic action of gentamicin sulfate (GS) and ketorolac tromethamine (KT), against planktonic staphylococcal strains were determined using the fractional inhibitory concentration measurement assay. Nascent (6 h) and established (24 h) biofilms were grown on 316L stainless steel plates and the synergistic biofilm eradication activity was determined and characterized using adherent bacteria count, minimum biofilm eradication concentration (MBEC) measurement for GS, visualization by live/dead imaging, scanning electron microscopy, gene expression of biofilm-associated genes, and bacterial membrane fluidity assessment.

Results
Gentamicin-ketorolac (GS-KT) combination demonstrated synergistic antibacterial action against planktonic Staphylococci. Control and clinical strains showed distinct biofilm growth dynamics and an increase in biofilm maturity was shown to confer further resistance to gentamicin for both ‘low-risk’ and ‘high-risk’ biofilms. The addition of ketorolac enhanced the antibiofilm activity of gentamicin against acquired resistance in staphylococcal biofilms. Mechanistic studies revealed that the synergistic action of gentamicin–ketorolac interferes with biofilm morphology and subverts bacterial stress response altering bacterial physiology, membrane dynamics, and biofilm properties.

Conclusion
The results of this study have a significant impact on the local administration of antibiotics and other therapeutic agents commonly used in the prevention and treatment of orthopaedic infections. Further, these results warrant the study of synergy for the concurrent or sequential administration of non-antibiotic drugs for antimicrobial effect.
Application of a new MDCKII-MDR1 cell model to measure the extent of drug distribution in vitro at equilibrium for prediction of in vivo unbound brain-to-plasma drug distribution
Authors: Langthaler Kristine , Jones Christopher R. , Saaby Lasse , Bundgaard Christoffer , Brodin Birger 
Published: January 2024

AbstractIntro: Reliable estimates of drug uptake from blood to brain parenchyma are crucial in CNS drug discovery and development. While in vivo Kp,uu,brain estimates are the gold standard for investigating brain drug disposition, animal usage is a limitation to high throughput application. This study investigates an in vitro model using P-gp expressing MDCKII-MDR1 cells for predicting in vivo brain drug penetration. Methods: In vitro equilibrium distribution studies were conducted in apical and basolateral solutions with high protein content to estimate Kp,brain and Kp,uu,brain values. The correlation between in vitro and in vivo Kp,brain values for a set of compounds was examined. Results: We observed a good correlation between in vitro and in vivo Kp,brain values (R2 = 0.69, Slope: 1.6), indicating that the in vitro model could predict in vivo drug brain penetration. The ‘unilateral (Uni-L)’ in vitro setup correctly classified 5 out of 5 unrestricted compounds and 3 out of 5 restricted compounds. Possible reasons for the observed disparities for some compounds have been discussed, such as difference in transport areas between in vitro and in vivo settings and effect of pH changes. Conclusion: The in vitro assay setup developed in this study holds promise for predicting in vivo drug brain penetration in CNS drug discovery. The correlation between in vitro and in vivo Kp,brain values, underscores that the model may have potential for early-stage screening. With minor refinements, this in vitro approach could reduce the reliance on in vivo experiments, accelerating the pace of CNS drug discovery and promoting a more ethical research approach.
CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension
Authors: Wardman Jonathan H. , Andreassen Søren Norge , Toft-Bertelsen Trine L. , Jensen Mette Nyholm , Wilhjelm Jens E. , Styrishave Bjarne , Hamann Steffen , Heegaard Steffen , Sinclair Alexandra J. , MacAulay Nanna 
Published: January 2024

Abstract
Background
Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by systemic metabolic dysregulation with a profile of increased androgen hormones. However, the contribution of obesity/hormonal perturbations to cerebrospinal fluid (CSF) dynamics remains unresolved.

Methods
We employed obese female Zucker rats and adjuvant testosterone to reveal IIH causal drivers. ICP and CSF dynamics were determined with in vivo experimentation and magnetic resonance imaging, testosterone levels assessed with mass spectrometry, and choroid plexus function revealed with transcriptomics.

Results
Obese rats had undisturbed CSF testosterone levels and no changes in ICP or CSF dynamics. Adjuvant testosterone treatment of obese rats elevated the CSF secretion rate, although with no effect on the ICP, due to elevated CSF drainage capacity of these rats.

Conclusions
Obesity in itself therefore does not suffice to recapitulate the IIH symptoms in rats, but modulation of CSF dynamics appears with adjuvant testosterone treatment, which mimics the androgen excess observed in female IIH patients. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH and could potentially serve as a future therapeutic target.
A qualitative assessment of Ukraine’s trauma system during the Russian conflict: experiences of volunteer healthcare providers
Authors: Lawry Lynn Lieberman , Korona-Bailey Jessica , Juman Luke , Janvrin Miranda , Donici Valentina , Kychyn Iurii , Maddox John , Koehlmoos Tracey Perez 
Published: January 2024

Abstract
Background
The Russian Federation’s invasion of Ukraine is characterized by indiscriminate attacks on civilian infrastructure, including hospitals and clinics that have devastated the Ukrainian health system putting trauma care at risk. International healthcare providers responded to the need for help with the increasing numbers of trauma patients. We aimed to describe their experiences during the conflict to explore the gaps in systems and care for trauma patients to refine the Global Trauma System Evaluation Tool (G-TSET) tool.

Methods
We conducted qualitative key informant interviews of healthcare providers and business and logistics experts who volunteered since February 2022. Respondents were recruited using purposive snow-ball sampling. Semi-structured, in-depth interviews were conducted virtually from January-March 2023 using a modified version of the G-TSET as an interview guide. Interviews were transcribed verbatim and deductive thematic content analysis was conducted using NVivo.

Findings
We interviewed a total of 26 returned volunteers. Ukraine’s trauma system is outdated for both administrative and trauma response practices. Communication between levels of the patient evacuation process was a recurrent concern which relied on handwritten notes. Patient care was impacted by limited equipment resources, such as ventilators, and improper infection control procedures. Prehospital care was described as highly variable in terms of quality, while others witnessed limited or no prehospital care. The inability to adequately move patients to higher levels of care affected the quality of care. Infection control was a key issue at the hospital level where handwashing was not common. Structured guidelines for trauma response were lacking and lead to a lack of standardization of care and for trauma. Although training was desired, patient loads from the conflict prohibited the ability to participate. Rehabilitation care was stated to be limited.

Conclusion
Standardizing the trauma care system to include guidelines, better training, improved prehospital care and transportation, and supply of equipment will address the most critical gaps in the trauma system. Rehabilitation services will be necessary as the conflict continues into its second year.
Protective effect of Luffa cylindrica fermentation liquid on cyclophosphamide-induced premature ovarian failure in female mice by attenuating oxidative stress, inflammation and apoptosis
Authors: Feng Yueying , Zhang Wei , Xu Xiaowei , Wang Wanzhen , Xu Yuanyuan , Wang Mengqi , Zhang Jinfeng , Xu Hengyi , Fu Fen 
Published: January 2024

AbstractPremature ovarian failure (POF) is a leading cause of women’s infertility without effective treatment. The purpose of this study was to investigate the protective effects of Luffa cylindrica fermentation liquid (LF) on cyclophosphamide (CTX) -induced POF in mice and to preliminarily investigate the underlying mechanisms. Thirty-two Balb/c mice were divided into four groups randomly. One group served as the control, while the other three received CTX injections to establish POF models. A 14-day gavage of either 5 or 10 μL/g LF was administered to two LF pretreatment groups. To analyze the effects of LF, the ovarian index, follicle number, the levels of serum sex hormones, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), inflammatory factors, and apoptosis of the ovarian cells were measured. The effects of LF pretreatment on the expression of TLR4/NF-κB and apoptosis pathways were also evaluated. We found that LF pretreatment increased the ovarian index and the number of primordial and antral follicles while decreasing those of atretic follicles. LF pretreatment also increased the serum levels of estradiol (E2) and anti-Müllerian hormone (AMH), while decreasing those of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Furthermore, LF pretreatment increased the levels of SOD and GSH in the ovaries, while decreasing those of MDA, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). LF administration reduced the amount of TUNEL+ ovarian cells and the levels of TLR4 and NF-κB P65 protein expression. In conclusion, LF has antioxidant, anti-inflammatory as well as anti-apoptotic effects against CTX-induced POF, and the inhibition of TLR4/NF-κB and apoptosis pathways may be involved in its mechanisms.
Graphical Abstract