bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent stroke in a reproductive age women with patent foramen ovale
Authors: Ye Jing , Yang Yujia , Tang Li , He Li , Zhou Muke
Published: January 2024

Background

Patent foramen ovale (PFO) is a known cause of ischemic stroke in young adults and combined oral contraceptives (COCs) are widely used by women of reproductive age. If young women with PFO are taking COCs, they may be subjected to a synergistic increase in the occurrence of stroke, though reports of ischemic stroke in this population are rare. We report a woman of reproductive age who was taking COC suffered repetitive ischemic strokes before a patent foramen ovale (PFO) was detected and closed, which may raise concerns in this field.

Case presentation

A 31-year-old woman presented to the emergency department with sudden-onset right upper- and lower-limb weakness and dysarthria for 1 hour, whose only risk factor of stroke was oral contraceptive use. On admission, she was alert with left gaze deviation, dysarthria, and right-sided hemiplegia. Her symptoms improved after receiving the revascularization therapy. About 24 hours later, her left eye experienced sudden painless vision loss. Then the PFO with a substantial right-to-left shunt was detected and then she received a trans-catheter closure of the defect. Over 3 months of follow-up, there were no signs of stroke, but visual loss persisted.

Conclusion

This case of disabling stroke raises concerns regarding optimal management in primary and secondary prevention of stroke in young women on COCs with additional risk factors of stroke.
Creating allies: qualitative exploration of young women’s preferences for PrEP methods and parents’ role in PrEP uptake and user support in urban and rural Zambia
Authors: Wong Christina Misa , Munthali Tendai , Mangunje Featherstone G. , Katoka Mercy L. , Burke Holly M. , Musonda Bupe , Musonda Musonda , Todd Catherine S.
Published: January 2024

Background

Zambian adolescent girls and young women (AGYW) have high HIV incidence and face barriers to the use of pre-exposure prophylaxis (PrEP). Parental support improves PrEP use and adherence in some settings, but negative parental attitudes toward HIV prevention may inhibit engagement with AGYW. We explored perceptions of future PrEP methods among AGYW and parents and parent-youth engagement on HIV prevention and PrEP use.

Methods

We conducted a qualitative descriptive study among AGYW and parents of AGYW in five provinces in Zambia in September–October 2021. We conducted 10 focus group discussions (FGDs) and four in-depth interviews (IDIs) with AGYW participants (n = 87) and seven FGDs and four IDIs among parents of AGYW (n = 62). All FGDs and IDIs were audio-recorded, transcribed verbatim, and analyzed to identify qualitative themes.

Results

Most AGYW participants preferred the discreet nature and longer duration of injectable PrEP compared to the PrEP ring and oral PrEP. Many AGYWs reported inability to disclose PrEP use to their parents due to lack of parental support based on cultural taboos against premarital sex. Nevertheless, AGYW participants said they would like to talk to their parents about PrEP so their parents could support their use. Many parents also described difficulties discussing PrEP with their daughters because of cultural and religious beliefs about abstinence from sex before marriage. However, parents acknowledged that the threat of HIV is real and said they need PrEP knowledge and guidance on speaking with their children about HIV prevention and PrEP.

Conclusions

Although many parents are currently not playing a role in daughters’ decisions about PrEP use, both parents and AGYW are willing to engage with each other on HIV prevention issues. To foster parent-child engagement, HIV prevention programs should not only provide information about PrEP but also address social norms that impede discussion of HIV prevention and equip both parents and AGYW with skills and support for such conversations. Community sensitization is also needed as new PrEP products are introduced, to create an enabling environment for parent-child engagement by increasing awareness, countering misconceptions, and reducing stigma.
Involvement of TNFα, IL-1β, COX-2 and NO in the anti-inflammatory activity of Tamarix aphylla in Wistar albino rats: an in-vivo and in-vitro study
Authors: Fayez Nada , Khalil Waleed , Abdel-Sattar Essam , Abdel-Fattah Abdel-Fattah Mohamed
Published: January 2024

Background

With the emergence of many side effects from synthetic drugs, there is an urgent need to find a natural alternative to these products. Therefore, our primary aim was to evaluate the anti-inflammatory activity of Tamarix aphylla (TA) and investigate the potential mechanism underlying this action.

Methods

Initially, to ensure the safety of the extract and for dose selection, we performed an acute oral toxicity Assay through the oral administration of graded doses up to 4 g\kg in Wistar rats. then, we used the carrageenan-induced edema model to elucidate the anti-inflammatory activity. Using specific ELISA kits, we measured the levels of TNF-α, IL-1β, COX-2 and NO inside the inflamed paw tissue. Finally, for the in-vitro anti-inflammatory experiment, we used the erythrocyte membrane stability test.

Results

Based on the acute oral toxicity assay, T. aphylla was considered generally safe and three different doses of 100, 200, and 400 mg/kg were chosen for further experiments. Additionally, TA expressed a significant (P < 0.05) anti-inflammatory activity, showing the maximum inhibition percentage at the fifth hour of measurement at 53.47% and 70.06%, at doses of 200 and 400 mg/kg respectively, compared to 63.81% for the standard drug. Similarly, we found that TA effectively reduced the levels of TNF-α and IL-1β at all tested doses (100-200-400 mg/kg) to a greater extent than the standard drug. Moreover, at 400 mg/kg, TA was able to significantly lower the levels of COX-2 and NO inside the inflamed tissue to a level comparable (P < 0.05) with that measured inside the paw tissue of normal rats. Finally, Tamarix aphylla at 100, 200 and 400 mg/kg doses significantly (P < 0.05) inhibited the heat-induced hemolysis of RBCs membrane by 67.78, 74.82 and 82.08%, respectively, compared to 83.89% produced by Aspirin.

Conclusion

T. aphylla produced a significant (P < 0.05) anti-inflammatory activity compared to the standard drugs either through the reduction of pro-inflammatory mediators or the protection of the lysosomal membrane.
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

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

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

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

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

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

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

Intro: 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

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

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

Premature 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
Eco-epidemiology of Rickettsia amblyommatis and Rickettsia parkeri in naturally infected ticks (Acari: Ixodida) from South Carolina
Authors: Gual-Gonzalez Lídia , Self Stella C. W. , Zellars Kia , Meyer Madeleine , Dye-Braumuller Kyndall C. , Evans Chris L. , Cantillo-Barraza Omar , Torres Myriam W. , Nolan Melissa S.
Published: January 2024

Background

Spotted fever group Rickettsia (SFGR) is the largest group of Rickettsia species of clinical and veterinary importance emerging worldwide. Historically, SFGR cases were linked to Rickettsia rickettsii, the causal agent of Rocky Mountain spotted fever; however, recently discovered species Rickettsia parkeri and Rickettsia amblyommatis have been shown to cause a wide range of clinical symptoms. The role of R. amblyommatis in SFGR eco-epidemiology and the possible public health implications remain unknown.

Methods

This study evaluated statewide tick surveillance and land-use classification data to define the eco-epidemiological relationships between R. amblyommatis and R. parkeri among questing and feeding ticks collected across South Carolina between 2021 and 2022. Questing ticks from state parks and feeding ticks from animal shelters were evaluated for R. parkeri and R. amblyommatis using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) on pooled samples. A Bayesian multivariable logistic regression model for pool testing data was used to assess associations between R. parkeri or R. amblyommatis infection and land-use classification variables among questing ticks. The Spearman correlation was used to evaluate the relationship between the two tested pathogens.

Results

The infection prevalence for R. amblyommatis was 24.8% (23.4–26.3%) among questing ticks, and 39.5% (37.4–42.0%) among feeding ticks; conversely, for R. parkeri it was 19.0% (17.6–20.5%) among questing ticks and 22.4% (20.3–24.5%) among feeding ticks. A negative, refractory correlation was found between the species, with ticks significantly more likely to contain one or the other pathogen, but not both simultaneously. The Bayesian analysis revealed that R. amblyommatis infection was positively associated with deciduous, evergreen, and mixed forests, and negatively associated with hay and pasture fields, and emergent herbaceous wetlands. Rickettsia parkeri infection was positively associated with deciduous, mixed, and evergreen forests, herbaceous vegetation, cultivated cropland, woody wetlands, and emergent herbaceous wetlands, and negatively associated with hay and pasture fields.

Conclusions

This is the first study to evaluate the eco-epidemiological factors driving tick pathogenicity in South Carolina. The negative interactions between SFGR species suggest the possible inhibition between the two pathogens tested, which could have important public health implications. Moreover, land-use classification factors revealed environments associated with tick pathogenicity, highlighting the need for tick vector control in these areas.

Graphical Abstract
mRNA-based precision targeting of neoantigens and tumor-associated antigens in malignant brain tumors
Authors: Trivedi Vrunda , Yang Changlin , Klippel Kelena , Yegorov Oleg , von Roemeling Christina , Hoang-Minh Lan , Fenton Graeme , Ogando-Rivas Elizabeth , Castillo Paul , Moore Ginger , Long-James Kaytora , Dyson Kyle , Doonan Bently , Flores Catherine , Mitchell Duane A.
Published: January 2024

Background

Despite advancements in the successful use of immunotherapy in treating a variety of solid tumors, applications in treating brain tumors have lagged considerably. This is due, at least in part, to the lack of well-characterized antigens expressed within brain tumors that can mediate tumor rejection; the low mutational burden of these tumors that limits the abundance of targetable neoantigens; and the immunologically “cold” tumor microenvironment that hampers the generation of sustained and productive immunologic responses. The field of mRNA-based therapeutics has experienced a boon following the universal approval of COVID-19 mRNA vaccines. mRNA-based immunotherapeutics have also garnered widespread interest for their potential to revolutionize cancer treatment. In this study, we developed a novel and scalable approach for the production of personalized mRNA-based therapeutics that target multiple tumor rejection antigens in a single therapy for the treatment of refractory brain tumors.

Methods

Tumor-specific neoantigens and aberrantly overexpressed tumor-associated antigens were identified for glioblastoma and medulloblastoma tumors using our cancer immunogenomics pipeline called Open Reading Frame Antigen Network (O.R.A.N). Personalized tumor antigen-specific mRNA vaccine was developed for each individual tumor model using selective gene capture and enrichment strategy. The immunogenicity and efficacy of the personalized mRNA vaccines was evaluated in combination with anti-PD-1 immune checkpoint blockade therapy or adoptive cellular therapy with ex vivo expanded tumor antigen-specific lymphocytes in highly aggressive murine GBM models.

Results

Our results demonstrate the effectiveness of the antigen-specific mRNA vaccines in eliciting robust anti-tumor immune responses in GBM hosts. Our findings substantiate an increase in tumor-infiltrating lymphocytes characterized by enhanced effector function, both intratumorally and systemically, after antigen-specific mRNA-directed immunotherapy, resulting in a favorable shift in the tumor microenvironment from immunologically cold to hot. Capacity to generate personalized mRNA vaccines targeting human GBM antigens was also demonstrated.

Conclusions

We have established a personalized and customizable mRNA-therapeutic approach that effectively targets a plurality of tumor antigens and demonstrated potent anti-tumor response in preclinical brain tumor models. This platform mRNA technology uniquely addresses the challenge of tumor heterogeneity and low antigen burden, two key deficiencies in targeting the classically immunotherapy-resistant CNS malignancies, and possibly other cold tumor types.
Interactive training workshop to improve prostate mpMRI knowledge: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship
Authors: Barrett Tristan , Lee Kang-Lung , Illerstam Fredrik , Thomsen Henrik S. , Jhaveri Kartik S. , Løgager Vibeke
Published: January 2024

Purpose

Prostate MRI is established for the investigation of patients presenting with suspected early prostate cancer. Outcomes are dependent on both image quality and interpretation. This study assessed the impact of an educational intervention on participants’ theoretical knowledge of the technique.

Methods

Eighty-one clinicians from two centers with varying experience in prostate MRI participated. Baseline knowledge was assessed with 10 written and image-based multiple-choice questions (MCQs) prior to a course including didactic lectures and hands-on interactive workshops on prostate MRI interpretation. Post-course, participants completed a second 10-question MCQ test, matched by format, themes, and difficulty, to assess for any improvement in knowledge and performance. Results were assessed using the Wilcoxon rank sum test, and the Wilcoxon signed-rank test for paired data.

Results

Thirty-nine participants, including 25/49 (51.0%) and 14/32 (43.8%) at each center completed both assessments, with their results used for subsequent evaluation. Overall, there was a significant improvement from pre- (4.92 ± 2.41) to post-course scores (6.77 ± 1.46), p < 0.001 and at both Copenhagen (5.92 ± 2.25 to 7.36 ± 1.25) and Toronto (3.14 ± 1.51 to 5.71 ± 1.20); p = 0.005 and p = 0.002, respectively. Participants with no prostate MRI experience showed the greatest improvement (3.77 ± 1.97 to 6.18 ± 1.5, p < 0.001), followed by intermediate level (< 500 MRIs reported) experience (6.18 ± 1.99 to 7.46 ± 1.13, p = 0.058), then advanced (> 500 MRIs reported) experience (6.83 ± 2.48 to 7.67 ± 0.82, p = 0.339).

Conclusions

A dedicated prostate MRI teaching course combining didactic lectures and hands-on workshops significantly improved short-term theoretical knowledge of the technique for clinicians with differing levels of experience.

Critical relevance statement

A dedicated teaching course significantly improved theoretical knowledge of the technique particularly for clinicians with less reporting experience and a lower baseline knowledge. The multiple-choice questions format mapped improved performance and may be considered as part of future MRI certification initiatives.

Key points

• Prostate MRI knowledge is important for image interpretation and optimizing acquisition sequences.

• A dedicated teaching course significantly improved theoretical knowledge of the technique.

• Improved performance was more apparent in clinicians with less reporting experience and a lower baseline knowledge.

Graphical Abstract
A holistic approach to implementing artificial intelligence in radiology
Authors: Kim Bomi , Romeijn Stephan , van Buchem Mark , Mehrizi Mohammad Hosein Rezazade , Grootjans Willem
Published: January 2024

Objective

Despite the widespread recognition of the importance of artificial intelligence (AI) in healthcare, its implementation is often limited. This article aims to address this implementation gap by presenting insights from an in-depth case study of an organisation that approached AI implementation with a holistic approach.

Materials and methods

We conducted a longitudinal, qualitative case study of the implementation of AI in radiology at a large academic medical centre in the Netherlands for three years. Collected data consists of 43 days of work observations, 30 meeting observations, 18 interviews and 41 relevant documents. Abductive reasoning was used for systematic data analysis, which revealed three change initiative themes responding to specific AI implementation challenges.

Results

This study identifies challenges of implementing AI in radiology at different levels and proposes a holistic approach to tackle those challenges. At the technology level, there is the issue of multiple narrow AI applications with no standard use interface; at the workflow level, AI results allow limited interaction with radiologists; at the people and organisational level, there are divergent expectations and limited experience with AI. The case of Southern illustrates that organisations can reap more benefits from AI implementation by investing in long-term initiatives that holistically align both social and technological aspects of clinical practice.

Conclusion

This study highlights the importance of a holistic approach to AI implementation that addresses challenges spanning technology, workflow, and organisational levels. Aligning change initiatives between these different levels has proven to be important to facilitate wide-scale implementation of AI in clinical practice.

Critical relevance statement

Adoption of artificial intelligence is crucial for future-ready radiological care. This case study highlights the importance of a holistic approach that addresses technological, workflow, and organisational aspects, offering practical insights and solutions to facilitate successful AI adoption in clinical practice.

Key points

1. Practical and actionable insights into successful AI implementation in radiology are lacking.

2. Aligning technology, workflow, organisational aspects is crucial for a successful AI implementation

3. Holistic approach aids organisations to create sustainable value through AI implementation.

Graphical Abstract
Convolutional neural networks for the differentiation between benign and malignant renal tumors with a multicenter international computed tomography dataset
Authors: Klontzas Michail E. , Kalarakis Georgios , Koltsakis Emmanouil , Papathomas Thomas , Karantanas Apostolos H. , Tzortzakakis Antonios
Published: January 2024

Objectives

To use convolutional neural networks (CNNs) for the differentiation between benign and malignant renal tumors using contrast-enhanced CT images of a multi-institutional, multi-vendor, and multicenter CT dataset.

Methods

A total of 264 histologically confirmed renal tumors were included, from US and Swedish centers. Images were augmented and divided randomly 70%:30% for algorithm training and testing. Three CNNs (InceptionV3, Inception-ResNetV2, VGG-16) were pretrained with transfer learning and fine-tuned with our dataset to distinguish between malignant and benign tumors. The ensemble consensus decision of the three networks was also recorded. Performance of each network was assessed with receiver operating characteristics (ROC) curves and their area under the curve (AUC-ROC). Saliency maps were created to demonstrate the attention of the highest performing CNN.

Results

Inception-ResNetV2 achieved the highest AUC of 0.918 (95% CI 0.873–0.963), whereas VGG-16 achieved an AUC of 0.813 (95% CI 0.752–0.874). InceptionV3 and ensemble achieved the same performance with an AUC of 0.894 (95% CI 0.844–0.943). Saliency maps indicated that Inception-ResNetV2 decisions are based on the characteristics of the tumor while in most tumors considering the characteristics of the interface between the tumor and the surrounding renal parenchyma.

Conclusion

Deep learning based on a diverse multicenter international dataset can enable accurate differentiation between benign and malignant renal tumors.

Critical relevance statement

Convolutional neural networks trained on a diverse CT dataset can accurately differentiate between benign and malignant renal tumors.

Key points

• Differentiation between benign and malignant tumors based on CT is extremely challenging.

• Inception-ResNetV2 trained on a diverse dataset achieved excellent differentiation between tumor types.

• Deep learning can be used to distinguish between benign and malignant renal tumors.

Graphical Abstract
Novel insight into the lipid network of plasma extracellular vesicles reveal sex-based differences in the lipidomic profile of alcohol use disorder patients
Authors: Perpiñá-Clérigues Carla , Mellado Susana , Galiana-Roselló Cristina , Fernández-Regueras María , Marcos Miguel , García-García Francisco , Pascual María
Published: January 2024

Background

Alcohol use disorder (AUD) is one of the most common psychiatric disorders, with the consumption of alcohol considered a leading cause of preventable deaths worldwide. Lipids play a crucial functional role in cell membranes; however, we know little about the role of lipids in extracellular vesicles (EVs) as regulatory molecules and disease biomarkers.

Methods

We employed a sensitive lipidomic strategy to characterize lipid species from the plasma EVs of AUD patients to evaluate functional roles and enzymatic activity networks to improve the knowledge of lipid metabolism after alcohol consumption. We analyzed plasma EV lipids from AUD females and males and healthy individuals to highlight lipids with differential abundance and biologically interpreted lipidomics data using LINEX2, which evaluates enzymatic dysregulation using an enrichment algorithm.

Results

Our results show, for the first time, that AUD females exhibited more significant substrate-product changes in lysophosphatidylcholine/phosphatidylcholine lipids and phospholipase/acyltransferase activity, which are potentially linked to cancer progression and neuroinflammation. Conversely, AUD males suffer from dysregulated ceramide and sphingomyelin lipids involving sphingomyelinase, sphingomyelin phosphodiesterase, and sphingomyelin synthase activity, which relates to hepatotoxicity. Notably, the analysis of plasma EVs from AUD females and males demonstrates enrichment of lipid ontology terms associated with “negative intrinsic curvature” and “positive intrinsic curvature”, respectively.

Conclusions

Our methodological developments support an improved understanding of lipid metabolism and regulatory mechanisms, which contribute to the identification of novel lipid targets and the discovery of sex-specific clinical biomarkers in AUD.
Comparison of 18F-FDG PET and arterial spin labeling MRI in evaluating Alzheimer’s disease and amnestic mild cognitive impairment using integrated PET/MR
Authors: Bi Sheng , Yan Shaozhen , Chen Zhigeng , Cui Bixiao , Shan Yi , Yang Hongwei , Qi Zhigang , Zhao Zhilian , Han Ying , Lu Jie
Published: January 2024

Background

Developing biomarkers for early stage AD patients is crucial. Glucose metabolism measured by 18F-FDG PET is the most common biomarker for evaluating cellular energy metabolism to diagnose AD. Arterial spin labeling (ASL) MRI can potentially provide comparable diagnostic information to 18F-FDG PET in patients with neurodegenerative disorders. However, the conclusions about the diagnostic performance of AD are still controversial between 18F-FDG PET and ASL. This study aims to compare quantitative cerebral blood flow (CBF) and glucose metabolism measured by 18F-FDG PET diagnostic values in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) using integrated PET/MR.

Results

Analyses revealed overlapping between decreased regional rCBF and 18F-FDG PET SUVR in patients with AD compared with NC participants in the bilateral parietotemporal regions, frontal cortex, and cingulate cortex. Compared with NC participants, patients with aMCI exclusively demonstrated lower 18F-FDG PET SUVR in the bilateral temporal cortex, insula cortex, and inferior frontal cortex. Comparison of the rCBF in patients with aMCI and NC participants revealed no significant difference (P > 0.05). The ROC analysis of rCBF in the meta-ROI could diagnose patients with AD (AUC, 0.87) but not aMCI (AUC, 0.61). The specificity of diagnosing aMCI has been improved to 75.56% when combining rCBF and 18F-FDG PET SUVR.

Conclusion

ASL could detect similar aberrant patterns of abnormalities compared to 18F-FDG PET in patients with AD compared with NC participants but not in aMCI. The diagnostic efficiency of 18F-FDG-PET for AD and aMCI patients remained higher to ASL. Our findings support that applying 18F-FDG PET may be preferable for diagnosing AD and aMCI.
Predictive mobility and cost-aware flow placement in SDN-based IoT networks: a Q-learning approach
Authors: Huang Gan , Ullah Ihsan , Huang Hanyao , Kim Kyung Tae
Published: January 2024

Software-Defined Networking (SDN) has emerged as an innovative networking method that offers effective management and remarkable flexibility. However, current SDN-based solutions primarily focus on static networks or concentrate on backbone networks, where network dynamics have minimal impact. The existing methods for placing flow entries in Software-Defined Networking (SDN)-based Internet of Things (IoT) systems exhibit shortcomings in accurately predicting outcomes and efficiently reducing table misses and associated performance metrics. This research introduces a new approach, specifically the mobility-aware adaptive flow entry placement scheme for SDN-based Internet of Things (IoT) environments, to address the mobility aspect of networks. The proposed scheme utilizes the Q-learning algorithm to predict the next possible location of end devices, while the cost-sensitive AdaBoost algorithm is employed to select heavy and active flows. As a result, efficient flow rules for incoming flows can be dynamically implemented without controller intervention. Extensive computer simulations demonstrate that this approach significantly enhances match probability and prediction accuracy while concurrently reducing the number of table misses and resource expenditure compared to existing schemes.