bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired Cardiac AMPK (5′‐Adenosine Monophosphate‐Activated Protein Kinase) and Ca
2+
‐Handling, and Action Potential Duration Heterogeneity in Ibrutinib‐Induced Ventricular Arrhythmia Vulnerability
Authors: Zhao Yanan , Du Beibei , Chakraborty Praloy , Denham Nathan , Massé Stéphane , Lai Patrick F.H. , Azam Mohammed Ali , Billia Filio , Thavendiranathan Paaladinesh , Abdel‐Qadir Husam , Lopaschuk Gary D. , Nanthakumar Kumaraswamy 
Published: June 2024

Background
We recently demonstrated that acute administration of ibrutinib, a Bruton's tyrosine kinase inhibitor used in chemotherapy for blood malignancies, increases ventricular arrhythmia (VA) vulnerability. A pathway of ibrutinib‐induced vulnerability to VA that can be modulated for cardioprotection remains unclear.

Methods and Results

The effects of ibrutinib on cardiac electrical activity and Ca
2+
dynamics were investigated in Langendorff‐perfused hearts using optical mapping. We also conducted Western blotting analysis to evaluate the impact of ibrutinib on various regulatory and Ca
2+
‐handling proteins in rat cardiac tissues. Treatment with ibrutinib (10 mg/kg per day) for 4 weeks was associated with an increased VA inducibility (72.2%±6.3% versus 38.9±7.0% in controls,
P
<0.002) and shorter action potential durations during pacing at various frequencies (
P
<0.05). Ibrutinib also decreased heart rate thresholds for beat–to–beat duration alternans of the cardiac action potential (
P
<0.05). Significant changes in myocardial Ca
2+
transients included lower amplitude alternans ratios (
P
<0.05), longer times‐to‐peak (
P
<0.05), and greater spontaneous intracellular Ca
2+
elevations (
P
<0.01). We also found lower abundance and phosphorylation of myocardial AMPK (5′‐adenosine monophosphate‐activated protein kinase), indicating reduced AMPK activity in hearts after ibrutinib treatment. An acute treatment with the AMPK activator 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside ameliorated abnormalities in action potential and Ca
2+
dynamics, and significantly reduced VA inducibility (37.1%±13.4% versus 72.2%±6.3% in the absence of 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside,
P
<0.05) in hearts from ibrutinib‐treated rats.

Conclusions
VA vulnerability inflicted by ibrutinib may be mediated in part by an impairment of myocardial AMPK activity. Pharmacological activation of AMPK may be a protective strategy against ibrutinib‐induced cardiotoxicity.
A simplified G-CSF–free procedure allows for in vivo HSC gene therapy of sickle cell disease in a mouse model
Authors: Li Chang , Anderson Anna K. , Ruminski Peter , Rettig Michael , Karpova Darja , Kiem Hans-Peter , DiPersio John F. , Lieber André 
Published: June 2024

Abstract
We have reported the direct repair of the sickle cell mutation in vivo in a disease model using vectorized prime editors after hematopoietic stem cell (HSC) mobilization with granulocyte colony-stimulating factor (G-CSF)/AMD3100. The use of G-CSF for HSC mobilization is a hurdle for the clinical translation of this approach. Here, we tested a G-CSF-free mobilization regimen using WU-106, an inhibitor of integrin α4β1, plus AMD3100 for in vivo HSC prime editing in sickle cell disease (SCD) mice. Mobilization with WU-106 + AMD3100 in SCD mice was rapid and efficient. In contrast to the G-CSF/AMD3100 approach, mobilization of activated granulocytes and elevation of the key proinflammatory cytokine interleukin-6 in the serum were minimal. The combination of WU-106 + AMD3100 mobilization and IV injection of the prime editing vector together with in vivo selection resulted in ∼23% correction of the SCD mutation in the bone marrow and peripheral blood cells of SCD mice. The treated mice demonstrated phenotypic correction, as reflected by normalized blood parameters and spleen size. Editing frequencies were significantly increased (29%) in secondary recipients, indicating the preferential mobilization/transduction of long-term repopulating HSCs. Using this approach, we found &lt;1% undesired insertions/deletions and no detectable off-target editing at the top-scored potential sites. Our study shows that in vivo transduction to treat SCD can now be done within 2 hours involving only simple IV injections with a good safety profile. The same-day mobilization regimen makes in vivo HSC gene therapy more attractive for resource-poor settings, where SCD does the most damage.
Compression properties of Japanese cedar (Cryptomeria japonica) treated with resin impregnation under loading perpendicular to the grain
Authors: Ogawa Keita , Kobayashi Kenji , Fukuta Satoshi 
Published: June 2024

AbstractThe compression properties of wood perpendicular to the grain is an important resistance mechanism in timber joints, especially wood-to-wood joints. Hence, improving the compression properties of wood is essential to developing timber joints with high resistance performance. In this study, we attempted to improve the compression properties using a resin impregnation technique. Three compression tests were conducted: loading at the full surface of the specimen, loading at the local part of the specimen with the unloaded part expanding in the tangential direction, and loading at the local part of the specimen with the unloaded part expanding in the longitudinal direction. Two types of resins were used: urethane and acryl. For compression loading on the full surface, the stiffness was increased by resin impregnation in the case of acryl impregnation. However, the yield load did not increase significantly. In the cases of compression loading in the local part and unloaded part expanding in the tangential direction, the stiffness increased when acryl was used, and the yield load increased when both resins were used. Significant increment in the properties were observed when the local compression load acted on the specimens with the unloaded parts expanding in the longitudinal direction. When urethane and a 10 mm incision depth were used, the stiffness and yield load increased 1.35 and 2.54 times, respectively. When using acryl and a 10 mm incision depth, the stiffness and yield load increased 1.64 and 2.93 times, respectively.
Characterization and application of the nanocompiste packaging films containing clay and TiO2 on preservation of tomato fruit under cold storage
Authors: Bodaghi Hojatollah 
Published: June 2024

Abstract
Background
Tomato (Lycopersicon esculentum), a valuable economic crop worldwide, often goes to waste due to improper packaging and handling. In the present study, three types of low-density polyethylene nanocomposite films containing 3% clay (Closite 20A), 3% TiO2 nanoparticles, and their combination were synthesized using melt blending method, and evaluated on the quality parameters of tomato fruit during 42 days of storage at 4 °C.

Results
Transmission electron microscopy confirmed the degree of dispersion and exfoliation of the nanoparticles. The TiO2/clay-nanocomposite films exhibited notable enhancements in Young's modulus and tensile strength compared to conventional films. The addition of clay and TiO2 nanoparticles resulted in reduced permeability to CO2, O2, and water vapor. Fruits packed with clay/TiO2 nanocomposite films showed decreased ethylene production, mitigated weight loss, and maintained pH, titratable acidity, total soluble solids, and firmness. Furthermore, clay/TiO2 nanocomposite films enhanced membrane stability, decreased membrane lipid peroxidation, and enhanced catalase and ascorbate peroxidase enzyme activity in fruits.

Conclusions
The relatively good exfoliation of clay nanoparticles and the proper dispersion of TiO2 nanoparticles, which were confirmed by TEM, led to an increase in mechanical and physical properties in the Clay/TiO2 nanocomposite. This film displayed more potential in maintaining the quality properties of tomato fruit during cold storage. Therefore, this film can be considered a practical solution for minimizing pathogen risks and contamination, and enhancing the overall quality of tomato fruit.
Sugammadex use in pediatric patients with stage IV-V chronic kidney disease in a quaternary referral hospital: a case series
Authors: Samba Sindhu N. , Daklallah Youssef , Brown Sydney E. S. , Colquhoun Douglas A. , Modi Zubin J. , Nause-Osthoff Rebecca 
Published: June 2024

Abstract
Background
Sugammadex is a pharmacologic agent that provides rapid reversal of neuromuscular blockade via encapsulation of the neuromuscular blocking agent (NMBA). The sugammadex-NMBA complex is primarily cleared through glomerular filtration from the kidney, raising the possibility that alterations in renal function could affect its elimination. In pediatric patients, the benefits of sugammadex have led to widespread utilization; however, there is limited information on its application in pediatric renal impairment. This study examined sugammadex use and postoperative outcomes in pediatric patients with severe chronic renal impairment at our quaternary pediatric referral hospital.

Methods
After IRB approval, we performed a retrospective analysis in pediatric patients with stage IV and V chronic kidney disease who received sugammadex from January 2017 to March 2022. Postoperative outcomes studied included new or increased respiratory requirement, unplanned intensive care unit (ICU) admission, postoperative pneumonia, anaphylaxis, and death within 48 h postoperatively, unplanned deferral of intraoperative extubation, and repeat administrations of NMBA reversal after leaving the operating room.

Results
The final cohort included 17 patients ranging from 8 months to 16 years old. One patient required new postoperative noninvasive ventilation on postoperative day 2, which was credited to hypervolemia. Another patient had bronchospasm intraoperatively resolving with medication, which could not definitively be associated sugammadex administration. There were no instances of deferred extubation, unplanned ICU or need for supplemental oxygen after tracheal extubation identified.

Conclusion
No adverse effects directly attributable to sugammadex in pediatric patients with severe renal impairment were detected. There may be a role for utilization of sugammadex for neuromuscular reversal in this population.
Validation of the Indian (Hindi) version of the life-space assessment scale among community-dwelling older adults: a multicentric cross-sectional study
Authors: Sahoo Durgesh Prasad , Sahoo Soumya Swaroop , Nirala Santosh Kumar , Rath Rama Shankar , Agarwal Neeraj , Panda Meely , Kakkar Rakesh , Pandey Sanjay , Singh C M , Joshi Hari Shanker , Nath Bhola 
Published: June 2024

Abstract
Background
The Life-Space Assessment (LSA) is an instrument that measures mobility in older adults as they reach different areas, defined as life-spaces extending from home to beyond towns or regions. The purpose of the study was to develop the Hindi version of the LSA (LSA- H) and to investigate the validity and reliability of the Hindi version as well as its cultural adaptation.

Methods
A cross-sectional study of two hundred forty-five older adults participated in the study from four different study practice areas. Following forward backwards translation, the LSA-H was developed, and the scores were correlated with those of the Activities-Specific Balance Confidence Scale Hindi (ABC- H), the Physical Health Subscale of the WHO-BREF Questionnaire and the Geriatric Depression Scale: Short Form Hindi (GDS-SFH) to test the criterion and concurrent validity.

Results
The mean score and standard deviation of the LSA-H questionnaire were 56.53 ± 35.99, those of the Physical Health Subscale of the WHO-BREF instrument were 18.54 ± 7.87, those of the GDS-SFH questionnaire were 6.95 ± 4.21 and those of the ABC- H questionnaire were 54.40 ± 28.96. The Pearson correlation coefficient (r) between the LSA-H score and ABC-H score was 0.707 (p value < 0.0001), that between the LSA-H score and the Physical Health Subscale of the WHO-BREF was 0.766 (p value < 0.0001), and that between the LSA-H score and GDS-SFG score was − 0.674 (p value < 0.0001).

Conclusion
This study demonstrated that the Hindi version of the LSA is a valid and reliable instrument for assessing living space among older adults in the Hindi language in an Indian population. Furthermore, the LSA-H was significantly correlated with other health assessment tools in terms of functional mobility, general health status and mental well-being.
Early initiation of combined therapy in severely immunocompromised patients with COVID-19: a retrospective cohort study
Authors: Rotundo Salvatore , Berardelli Lavinia , Gullì Sara , La Gamba Valentina , Lionello Rosaria , Russo Alessandro , Trecarichi Enrico Maria , Torti Carlo 
Published: June 2024

AbstractThis single-centre retrospective cohort study reports on the results of a descriptive (non-comparative) retrospective cohort study of early initiation of antivirals and combined monoclonal antibody therapy (mAbs) in 48 severely immunocompromised patients with COVID-19. The study assessed the outcomes and the duration of viral shedding. The patients started early combined therapy (ECT) a median of 2 days (interquartile range [IQR]: 1–3 days) after the diagnosis of SARS-CoV-2 infection. Except for 1 patient who died due COVID-19-related respiratory failure, patients had their first negative nasopharyngeal swab result after a median of 11 days (IQR: 6–17 days) after starting combined therapy. There were no reports of severe side effects. During a follow-up period of 512 days (interquartile range [IQR]: 413–575 days), 6 patients (12.5%) died and 16 (33.3%) were admitted to hospital. Moreover, 12 patients (25%) were diagnosed with SARS-CoV-2 reinfection a median of 245 days (IQR: 138–401 days) after starting combined treatment. No relapses were reported. Although there was no comparison group, these results compare favourably with the outcomes of severely immunocompromised patients with COVID-19 reported in the literature.
Development and validation of peritumoral vascular and intratumoral radiomics to predict pathologic complete responses to neoadjuvant chemotherapy in patients with triple-negative breast cancer
Authors: Xie Tianwen , Gong Jing , Zhao Qiufeng , Wu Chengyue , Wu Siyu , Peng Weijun , Gu Yajia 
Published: June 2024

Abstract
Background
To develop and validate a peritumoral vascular and intratumoral radiomics model to improve pretreatment predictions for pathologic complete responses (pCRs) to neoadjuvant chemoradiotherapy (NAC) in patients with triple-negative breast cancer (TNBC).

Methods
A total of 282 TNBC patients (93 in the primary cohort, 113 in the validation cohort, and 76 in The Cancer Imaging Archive [TCIA] cohort) were retrospectively included. The peritumoral vasculature on the maximum intensity projection (MIP) from pretreatment DCE-MRI was segmented by a Hessian matrix-based filter and then edited by a radiologist. Radiomics features were extracted from the tumor and peritumoral vasculature of the MIP images. The LASSO method was used for feature selection, and the k-nearest neighbor (k-NN) classifier was trained and validated to build a predictive model. The diagnostic performance was assessed using the ROC analysis.

Results
One hundred of the 282 patient (35.5%) with TNBC achieved pCRs after NAC. In predicting pCRs, the combined peritumoral vascular and intratumoral model (fusion model) yields a maximum AUC of 0.82 (95% confidence interval [CI]: 0.75, 0.88) in the primary cohort, a maximum AUC of 0.67 (95% CI: 0.57, 0.76) in the internal validation cohort, and a maximum AUC of 0.65 (95% CI: 0.52, 0.78) in TCIA cohort. The fusion model showed improved performance over the intratumoral model and the peritumoral vascular model, but not significantly (p > 0.05).

Conclusion
This study suggested that combined peritumoral vascular and intratumoral radiomics model could provide a non-invasive tool to enable prediction of pCR in TNBC patients treated with NAC.
Ultrasound contrast-enhanced radiomics model for preoperative prediction of the tumor grade of clear cell renal cell carcinoma: an exploratory study
Authors: Luo Yujie , Liu Xiaoling , Jia Yiping , Zhao Qin 
Published: June 2024

Abstract
Background
This study aims to explore machine learning(ML) methods for non-invasive assessment of WHO/ISUP nuclear grading in clear cell renal cell carcinoma(ccRCC) using contrast-enhanced ultrasound(CEUS) radiomics.

Methods
This retrospective study included 122 patients diagnosed as ccRCC after surgical resection. They were divided into a training set (n = 86) and a testing set(n = 36). CEUS radiographic features were extracted from CEUS images, and XGBoost ML models (US, CP, and MP model) with independent features at different phases were established. Multivariate regression analysis was performed on the characteristics of different radiomics phases to determine the indicators used for developing the prediction model of the combined CEUS model and establishing the XGBoost model. The training set was used to train the above four kinds of radiomics models, which were then tested in the testing set. Radiologists evaluated tumor characteristics, established a CEUS reading model, and compared the diagnostic efficacy of CEUS reading model with independent characteristics and combined CEUS model prediction models.

Results
The combined CEUS radiomics model demonstrated the best performance in the training set, with an area under the curve (AUC) of 0.84, accuracy of 0.779, sensitivity of 0.717, specificity of 0.879, positive predictive value (PPV) of 0.905, and negative predictive value (NPV) of0.659. In the testing set, the AUC was 0.811, with an accuracy of 0.784, sensitivity of 0.783, specificity of 0.786, PPV of 0.857, and NPV of 0.688.

Conclusions
The radiomics model based on CEUS exhibits high accuracy in non-invasive prediction of ccRCC. This model can be utilized for non-invasive detection of WHO/ISUP nuclear grading of ccRCC and can serve as an effective tool to assist clinical decision-making processes.
Blocking CCR5 activity by maraviroc augmentation in post-stroke depression: a proof-of-concept clinical trial
Authors: Tene Oren , Molad Jeremy , Rotschild Ofer , Alpernas Aviva , Hawwari Muhamad , Seyman Estelle , Giladi Nir , Hallevi Hen , Assayag Einor Ben 
Published: June 2024

Abstract
Background
Post-stroke depression (PSD) is a significant impediment to successful rehabilitation and recovery after a stroke. Current therapeutic options are limited, leaving an unmet demand for specific and effective therapeutic options. Our objective was to investigate the safety of Maraviroc, a CCR5 antagonist, as a possible mechanism-based add-on therapeutic option for PSD in an open-label proof-of-concept clinical trial.

Methods
We conducted a 10-week clinical trial in which ten patients with subcortical and cortical stroke, suffering from PSD. were administered a daily oral dose of 300 mg Maraviroc. Participants were then monitored for an additional eight weeks. The primary outcome measure was serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. The secondary outcome measure was a change in the Montgomery-Asberg Depression Rating Scale (MADRS).

Results
Maraviroc was well tolerated, with no reports of serious adverse events or discontinuations due to intolerance. The MADRS scores substantially reduced from baseline to week 10 (mean change: -16.4 ± 9.3; p < 0.001). By the conclusion of the treatment phase, a favorable response was observed in five patients, with four achieving remission. The time to response was relatively short, approximately three weeks. After the cessation of treatment, MADRS scores increased at week 18 by 6.1 ± 9.6 points (p = 0.014).

Conclusions
Our proof-of-concept study suggests that a daily dosage of 300 mg of Maraviroc may represent a well-tolerated and potentially effective pharmacological approach to treating PSD. Further comprehensive placebo-controlled studies are needed to assess the impact of Maraviroc augmentation on PSD.

Trial registration
ClinicalTrials.gov Identifier: NCT05932550, Retrospectively registered: 28/06/2023.
Use of contraception during first sexual intercourse among Norwegian adolescents: a national cross-sectional study
Authors: Nordhagen Live Solveig , Egge Hilde , Leonhardt Marja 
Published: June 2024

Abstract
Background
Most Norwegian adolescents experience their first sexual intercourse during late adolescence. Use of contraception is important to avoid unwanted pregnancy, while condoms can also protect against sexually transmitted diseases. There are few studies on the use of contraception at first sexual intercourse, most with varying results, and some studies have only examined the use of contraception among girls. In our study, we aimed to determine the use of contraception at first sexual intercourse, and to investigate associations between use of contraceptives at first sexual intercourse, sociodemographic factors, and alcohol and other substance use.

Methods
The study was based on data from the national electronic youth survey Ungdata, conducted in 2020–2022 among 113 049 upper secondary pupils (15–19 years) in Norway, which was around 65% of pupils attending upper secondary school during the study period. Descriptive analysis was used to estimate the prevalence of contraceptive use at first sexual intercourse, and multivariate logistic regression analyses to investigate the association between contraceptive use, sociodemographic factors, and alcohol intoxication and substance use.

Result
32% of Norwegian adolescents did not use contraception at first sexual intercourse. More girls (57.4%) than boys (42.6%) reported use of contraception. Factors associated with non-use of contraception during first sexual intercourse among boys were having parents with no college /university education (OR = 1.22: CI 1.13–1.32), perceived poor family finances (OR = 1.22: CI 1.06–1.40), alcohol intoxication, and use of cannabis or other narcotic substances during the past 12 months. The same factors were associated with non-use of contraception among girls. Additionally, being older than 16 years (OR = 1.13: CI 1.06–1.19) was also associated with non-use of contraception at first sexual intercourse.

Conclusion
Many adolescents did not use contraception at first sexual intercourse. Alcohol intoxication and use of cannabis or other narcotic substances were associated with a lower likelihood of using contraceptives. This highlights the importance of preventive efforts including earlier prevention education that focuses more on the consequences of not using contraception in order to prevent unwanted pregnancies and sexually transmitted infections.