bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical impact of the accelerate PhenoTest® BC system on patients with gram-negative bacteremia and high risk of antimicrobial resistance: a prospective before-after implementation study
Authors: Brosh-Nissimov Tal , Tzur Anka , Grupel Daniel , Cahan Amos , Ma’aravi Nir , Heled-Akiva Maya , Jawamis Hasan , Leskes Hanna , Barenboim Erez , Sorek Nadav
Published: July 2023

Background

The Accelerate PhenoTest® BC system (AXDX) is a novel assay for rapid bacterial identification and antimicrobial susceptibility (AST). We report an evaluation of its impact on treatment of patients with Gram-negative bacteremia (GNB) with a high risk of antimicrobial resistance (AMR).

Methods

A prospective single-center evaluation before and after implementation of AXDX in addition to standard-of-care (SOC) microbiology and antimicrobial stewardship program (ASP). Patients with GNB reported during laboratory working hours and prespecified risk factors for AMR were included. The primary outcome was an ASP-oriented beneficial antimicrobial change, defined as either an escalation of an inappropriate empiric treatment or de-escalation of a broad-spectrum treatment of a susceptible organism. Main secondary outcomes were time to an appropriate treatment, antimicrobial treatment duration, length of stay (LOS) and mortality.

Results

Included were 46 and 57 patients in the pre- and post-intervention periods, respectively. The median time to an AST-oriented beneficial change was 29.2 h vs. 49.6 h, respectively (p < 0.0001). There were no significant differences in the time to appropriate treatment, LOS or mortality. Antimicrobial treatment duration was longer during the intervention period (10 vs. 8 days, p = 0.007). AXDX failed to correctly identify pathogens in all 6 cases of polymicrobial bacteremia. In two cases patient care was potentially compromised due to inappropriate de-escalation.

Conclusions

AXDX implementation resulted in a 20.4-hour shorter time to an ASP-oriented beneficial antimicrobial change. This should be weighed against the higher costs, the lack of other proven clinical benefits and the potential harm from mis-identification of polymicrobial bacteremias.
Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies
Authors: Muhammad Shan , Fan Tao , Hai Yang , Gao Yibo , He Jie
Published: July 2023

Interleukin-2 (IL-2) and its receptor (IL-2R) are essential in orchestrating immune responses. Their function and expression in the tumor microenvironment make them attractive targets for immunotherapy, leading to the development of IL-2/IL-2R-targeted therapeutic strategies. However, the dynamic interplay between IL-2/IL-2R and various immune cells and their dual roles in promoting immune activation and tolerance presents a complex landscape for clinical exploitation. This review discusses the pivotal roles of IL-2 and IL-2R in tumorigenesis, shedding light on their potential as diagnostic and prognostic markers and their therapeutic manipulation in cancer. It underlines the necessity to balance the anti-tumor activity with regulatory T-cell expansion and evaluates strategies such as dose optimization and selective targeting for enhanced therapeutic effectiveness. The article explores recent advancements in the field, including developing genetically engineered IL-2 variants, combining IL-2/IL-2R-targeted therapies with other cancer treatments, and the potential benefits of a multidimensional approach integrating molecular profiling, immunological analyses, and clinical data. The review concludes that a deeper understanding of IL-2/IL-2R interactions within the tumor microenvironment is crucial for realizing the full potential of IL-2-based therapies, heralding the promise of improved outcomes for cancer patients.
Systemic inflammatory proteins in offspring following maternal probiotic supplementation for atopic dermatitis prevention
Authors: Zakiudin Dinastry Pramadita , Rø Anne Dorthea Bjerkenes , Videm Vibeke , Øien Torbjørn , Simpson Melanie Rae
Published: July 2023

Background

Maternal probiotic supplementation has a promising effect on atopic dermatitis (AD) prevention in infancy. In the randomised controlled study, Probiotics in the Prevention of Allergy among Children in Trondheim (ProPACT), maternal probiotics reduced the cumulative incidence of AD in their offspring by 40% at 2 years of age. However, our understanding on how probiotics prevented AD is still limited, and the role of inflammatory proteins in infants following maternal probiotic supplementation is unclear. We hypothesised that maternal probiotics lowered pro-inflammatory proteins and increased anti-inflammatory proteins in their 2-year-old children as a mechanism of AD prevention. We aimed to explore this hypothesis and the association between these proteins and the presence of AD, severity of AD, and the degree of preventive effect of probiotics.

Methods

Plasma samples were collected from 2-year-old children (n = 202) during the ProPACT study, a randomised placebo-controlled trial of maternal probiotic supplementation. These samples were analysed for 92 inflammatory proteins using a multiplex proximity extension assay. Associations between inflammatory proteins and the presence and severity of AD, and the degree of preventive effect, was estimated individually using regression analysis and then collectively using unsupervised cluster analysis.

Results

Several proteins were observed to differ between the groups. The probiotic group had lower CCL11 and IL-17C, while children with AD had higher IL-17C, MCP-4, uPA, and CD6. Cytokine CCL20 and IL-18 had moderate correlation (r = 0.35 and r = 0.46) with the severity of AD. The cluster analysis revealed that children in the cluster of samples with the highest value of immune checkpoint receptors and inflammatory suppressor enzymes showed the greatest AD preventive effect from probiotics.

Conclusions

The proteins associated with both maternal probiotic supplementation and the presence and severity of AD warrant attention because of their potential biological relevance. Cluster analysis may provide a new insight when considering which subgroups benefit from probiotic supplementation. Larger studies are needed to confirm the results.

Trial registration number: The study was retrospectively registered at ClinicalTrials.gov (NCT00159523) on 12nd September 2005.
Non-disclosure of drug injection practices as a barrier to HCV testing: results from the PrebupIV community-based research study
Authors: Anwar Ilhame , Donadille Cécile , Protopopescu Camelia , Michels David , Herin Joris , Pladys Adélaïde , Bader Danièle , Carrieri Patrizia , Roux Perrine
Published: July 2023

Background

Hepatitis C virus (HCV) infection prevalence is particularly high in people who inject drugs (PWID), a population that faces many barriers to HCV testing and care. A better understanding of the determinants of access to HCV testing is needed to improve their engagement in the HCV care cascade. We used data from a cross-sectional survey of people who inject drugs, mainly opioids, to identify factors associated with recent HCV testing.

Methods

Self-reported data on HCV antibody testing were analyzed for 550 of the 557 PWID enrolled in PrebupIV, a French cross-sectional community-based survey which assessed PWID acceptability of injectable buprenorphine as a treatment. Factors associated with recent (i.e., in the previous six months) HCV antibody testing were identified performing multivariable logistic regression.

Results

Among the study sample, 79% were men and 31% reported recent HCV antibody testing. Multivariable analysis found that PWID who did not disclose their injection practices to anyone (aOR [95% CI] 0.31 [0.12,0.82], p = 0.018), older PWID (aOR [95% CI] 0.97 [0.95,1.00], p = 0.030) and employed respondents (aOR [95% CI] 0.58 [0.37,0.92], p = 0.019) were all less likely to report recent HCV testing. No association was found between opioid agonist therapy and HCV testing.

Conclusions

Our findings suggest that non-disclosure of injection practices, employment and age were all barriers to HCV antibody testing. Preventing stigma around injection practices, developing the HCV testing offer in primary care and addiction care services, and training healthcare providers in HCV care management could improve HCV testing and therefore, the HCV care cascade in PWID.
Population norms for the EQ-5D-3L and EQ-5D-5L in Romania
Authors: Olariu Elena , Caplescu Raluca , Vale Luke , Niculescu-Aron Ileana Gabriela , Oluboyede Yemi , Paveliu Marian Sorin
Published: July 2023

Background

The majority of patient reported outcome measures (PROMs) don’t have population norms in Romania. This is the case with the EQ-5D as well. Therefore, we aimed to estimate population norms for the Romanian versions of the EQ-5D-5L, EQ-5D-3L, their indexes, and the EQ-VAS.

Methods

A cross-sectional survey was conducted in all regions of Romania from November 2018 to November 2019. A three-stage probability sampling procedure stratified by region and settlement size was used to select a representative sample. Interviews were computer-assisted and conducted in respondents’ homes by trained interviewers. Health status was assessed with the EQ-5D-5L, the EQ-5D-3L and the EQ VAS. Descriptive statistics were used to estimate population norms by age groups and sex for the EQ-5D-5L, the EQ-5D-3L, their indexes and the EQ VAS. Population norms were weighted using survey weights. Indexes for the EQ-5D questionnaires were estimated using the recently developed Romanian value sets.

Results

Data from 1,649 interviews was analysed in the present study. Survey weights were used so that sex and place of residence ratios for the weighted sample matched the Romanian general population distribution. Participants’ mean age was 47.4 years (SE = 1.157) and 50.3% of them reported being in good health. The dimension for which people reported the highest number of problems for both questionnaires was the pain/discomfort dimension. Men aged 35 plus reported fewer problems with pain/discomfort than women for both the EQ-5D-5L and EQ-5D-3L. Health decreased with age as shown by the decrease from age group 18–24 to age group 75 plus in the indexes of both questionnaires: from 0.977 (SE = 0.005) to 0.765 (SE = 0.017) for EQ-5D-5L and from 0.981 (SE = 0.005) to 0.784 (SE = 0.019) for EQ-5D-3L. There was 29.9 points drop in the EQ VAS score between the youngest and oldest group.

Conclusions

Population norms for the Romanian versions of the EQ-5D-5L, EQ-5D-3L, their indexes, and the EQ VAS are now available. These can now be used as reference values by healthcare professionals, researchers and decision-makers leading to a further development of health-related quality of life research in Romania.
Cross-cultural adaptation and validation of a self-reporting tool to assess health-related quality of life for Egyptians with extremity bone sarcomas in childhood or adolescence
Authors: Farid Nesma , Chun Sungsoo , Hassanain Omneya , Salama Mohamed , Esam Elham , Adel Fatima , Rashad Ismail , El Ghoneimy Ahmed Mohamed
Published: July 2023

Background

Validated self-reporting tools are required to evaluate the functional outcome and health-related quality of life (HRQOL) for those who had extremity bone sarcomas in their childhood or adolescence. Our study pursued cross-cultural adaptation and validation of the pediatric Toronto Extremity Salvage Score (pTESS) and Toronto Extremity Salvage Score (TESS) to assess the functional outcome for Egyptian children and adult survivors following surgeries of extremity bone sarcomas. In the modified versions of pTESS and TESS, mental domains were added to allow the evaluation of HRQOL using a specific instrument for childhood bone cancer.

Methods

The internal consistency and test–retest reliability of the studied forms were assessed with Cronbach’s alpha and Intra-class coefficients (ICC), respectively. For convergent validity, correlations between scores of the generic Pediatric Quality of Life Inventory (PedsQL 4.0) and pTESS /TESS scores were reported. Factor Analysis was feasible for pTESS-leg; due to the insufficient samples, only the average inter-item correlation coefficients were reported for the remaining versions.

Results

Out of 233 participants, 134 responded to pTESS-leg, 53 to TESS-leg, 36 to pTESS-arm, and only 10 to TESS-arm. All versions showed excellent internal consistency (Cronbach’s alpha >0.9), good test–retest reliability (ICC >0.8), moderate to strong correlations with PedsQL, and acceptable average inter-item correlation coefficients (≥0.3). Three factors were extracted for the pTESS-leg, in which all mental items were loaded on one separate factor with factor loadings exceeding 0.4. Active chemotherapy, less than one year from primary surgery, or tibial tumors were associated with significantly inferior pTESS/TESS scores in the lower extremity group.

Conclusion

The Egyptian pTESS and TESS are valid and reliable self-reporting tools for assessing the functional outcome following surgeries for extremity bone sarcomas. The modified pTESS and TESS versions, which include additional mental domains, enabled the assessment of the overall health status of our population. Future studies should include a larger sample size and evaluate the ability of pTESS/TESS to track progress over time.
Lymphedema self-care: economic cost savings and opportunities to improve adherence
Authors: Karaca-Mandic Pinar , Solid Craig A. , Armer Jane M. , Skoracki Roman , Campione Elizabeth , Rockson Stanley G.
Published: July 2023

Background

Breast cancer-related lymphedema (BCRL) imposes a significant economic burden on patients, providers, and society. There is no curative therapy for BCRL, but management through self-care can reduce symptoms and lower the risk of adverse events.

Main body

The economic burden of BCRL stems from related adverse events, reductions in productivity and employment, and the burden placed on non-medical caregivers. Self-care regimens often include manual lymphatic drainage, compression garments, and meticulous skin care, and may incorporate pneumatic compression devices. These regimens can be effective in managing BCRL, but patients cite inconvenience and interference with daily activities as potential barriers to self-care adherence. As a result, adherence is generally poor and often worsens with time. Because self-care is on-going, poor adherence reduces the effectiveness of regimens and leads to costly treatment of BCRL complications.

Conclusion

Novel self-care solutions that are more convenient and that interfere less with daily activities could increase self-care adherence and ultimately reduce complication-related costs of BCRL.
Randomized, double-blinded, placebo-controlled pilot study: efficacy of faecal microbiota transplantation on chronic fatigue syndrome
Authors: Salonen Tapani , Jokinen Elina , Satokari Reetta , Lahtinen Perttu
Published: July 2023

Background

Chronic fatigue syndrome (CFS) is a disabling illness of unknown aetiology. Disruption of gut microbiota may play a role in several neurological disorders. In this study, the effect of faecal microbiota transplantation (FMT) on fatigue severity and health-related quality of life (HRQOL) in patients with CFS was evaluated.

Methods

Randomized, placebo-controlled pilot trial. Patients and researchers were blinded to treatment assignment. 11 patients with CFS (10 female and 1 male, mean age 42.2 years and mean duration of CFS 6.3 years) were randomly assigned to receive either FMT from a universal donor (n = 5) or autologous FMT (n = 6) via colonoscopy. Patients’ HRQOL was assessed by using visual analog scale (VAS) and self-reporting questionnaires Modified Fatigue Impact Scale (MFIS), 15D and EQ-5D-3L. Patients’ HRQOL was evaluated at baseline, and 1 and 6 months after the FMT.

Results

The baseline VAS scores in the FMT and placebo groups were 62.4 and 76.0 (p = 0.29). 1-month scores were 60.0 and 73.7 and 6-months scores 72.8 and 69.5, respectively. Total MFIS scores in the FMT and placebo groups were 59.6 and 61.0 at the baseline (p = 0.80), 53.5 and 62.0 at 1 month and 58.6 and 56.2 at 6 months. Compared to the baseline scores, differences at 1 and 6 months were statistically insignificant both in VAS and in MFIS. The 15D and EQ-5D-3L profiles did not change after the FMT or placebo. FMT-related adverse events were not reported.

Conclusion

FMT was safe but did not relieve symptoms or improve the HRQOL of patients with CFS. Small number of study subjects limits the generalizability of these results.

Trial Registration ClinicalTrials.gov Identifier NCT04158427, https://register.clinicaltrials.gov, date of registration 08/08/2019.
Targeted ablation of signal transducer and activator of transduction 1 alleviates inflammation by microglia/macrophages and promotes long-term recovery after ischemic stroke
Authors: Han Wenxuan , Pu Hongjian , Li Sicheng , Liu Yaan , Zhao Yongfang , Xu Mingyue , Chen Caixia , Wu Yun , Yang Tuo , Ye Qing , Wang Hong , Stetler R. Anne , Chen Jun , Shi Yejie
Published: July 2023

Background

Brain microglia and macrophages (Mi/MΦ) can shift to a harmful or advantageous phenotype following an ischemic stroke. Identification of key molecules that regulate the transformation of resting Mi/MΦ could aid in the development of innovative therapies for ischemic stroke. The transcription factor signal transducer and activator of transduction 1 (STAT1) has been found to contribute to acute neuronal death (in the first 24 h) following ischemic stroke, but its effects on Mi/MΦ and influence on long-term stroke outcomes have yet to be determined.

Methods

We generated mice with tamoxifen-induced, Mi/MΦ-specific knockout (mKO) of STAT1 driven by Cx3cr1CreER. Expression of STAT1 was examined in the brain by flow cytometry and RNA sequencing after ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The impact of STAT1 mKO on neuronal cell death, Mi/MΦ phenotype, and brain inflammation profiles were examined 3–5 days after MCAO. Neurological deficits and the integrity of gray and white matter were assessed for 5 weeks after MCAO by various neurobehavioral tests and immunohistochemistry.

Results

STAT1 was activated in Mi/MΦ at the subacute stage (3 days) after MCAO. Selective deletion of STAT1 in Mi/MΦ did not alter neuronal cell death or infarct size at 24 h after MCAO, but attenuated Mi/MΦ release of high mobility group box 1 and increased arginase 1-producing Mi/MΦ 3d after MCAO, suggesting boosted inflammation-resolving responses of Mi/MΦ. As a result, STAT1 mKO mice had mitigated brain inflammation at the subacute stage after MCAO and less white matter injury in the long term. Importantly, STAT1 mKO was sufficient to improve functional recovery for at least 5 weeks after MCAO in both male and female mice.

Conclusions

Mi/MΦ-targeted STAT1 KO does not provide immediate neuroprotection but augments inflammation-resolving actions of Mi/MΦ, thereby facilitating long-term functional recovery after stroke. STAT1 is, therefore, a promising therapeutic target to harness beneficial Mi/MΦ responses and improve long-term outcomes after ischemic stroke.
Intelligent identification on cotton verticillium wilt based on spectral and image feature fusion
Authors: Lu Zhihao , Huang Shihao , Zhang Xiaojun , shi Yuxuan , Yang Wanneng , Zhu Longfu , Huang Chenglong
Published: July 2023

Background

Verticillium wilt is the major disease of cotton, which would cause serious yield reduction and economic losses, and the identification of cotton verticillium wilt is of great significance to cotton research. However, the traditional method is still manual, which is subjective, inefficient, and labor-intensive, and therefore, this study has proposed a novel method for cotton verticillium wilt identification based on spectral and image feature fusion. The cotton hyper-spectral images have been collected, while the regions of interest (ROI) have been extracted as samples including 499 healthy leaves and 498 diseased leaves, and the average spectral information and RGB image of each sample were obtained. In spectral feature processing, the preprocessing methods including Savitzky-Golay smoothing (SG), multiplicative scatter correction (MSC), de-trending (DT) and mean normalization (MN) algorithms have been adopted, while the feature band extraction methods have adopted principal component analysis (PCA) and successive projections algorithm (SPA). In RGB image feature processing, the EfficientNet was applied to build classification model and 16 image features have been extracted from the last convolutional layer. And then, the obtained spectral and image features were fused, while the classification model was established by support vector machine (SVM) and back propagation neural network (BPNN). Additionally, the spectral full bands and feature bands were used as comparison for SVM and BPNN classification respectively.

Result

The results showed that the average accuracy of EfficientNet for cotton verticillium wilt identification was 93.00%. By spectral full bands, SG-MSC-BPNN model obtained the better performance with classification accuracy of 93.78%. By feature bands, SG-MN-SPA-BPNN model obtained the better performance with classification accuracy of 93.78%. By spectral and image fused features, SG-MN-SPA-FF-BPNN model obtained the best performance with classification accuracy of 98.99%.

Conclusions

The study demonstrated that it was feasible and effective to use fused spectral and image features based on hyper-spectral imaging to improve identification accuracy of cotton verticillium wilt. The study provided theoretical basis and methods for non-destructive and accurate identification of cotton verticillium wilt.
Mono-valent salt corrections for RNA secondary structures in the ViennaRNA package
Authors: Yao Hua-Ting , Lorenz Ronny , Hofacker Ivo L. , Stadler Peter F.
Published: July 2023

Background

RNA features a highly negatively charged phosphate backbone that attracts a cloud of counter-ions that reduce the electrostatic repulsion in a concentration dependent manner. Ion concentrations thus have a large influence on folding and stability of RNA structures. Despite their well-documented effects, salt effects are not handled consistently by currently available secondary structure prediction algorithms. Combining Debye-Hückel potentials for line charges and Manning’s counter-ion condensation theory, Einert et al. (Biophys J 100: 2745-2753, 2011) modeled the energetic contributions of monovalent cations on loops and helices.

Results

The model of Einert et al. is adapted to match the structure of the dynamic programming recursion of RNA secondary structure prediction algorithms. An empirical term describing the salt dependence of the duplex initiation energy is added to improve co-folding predictions for two or more RNA strands. The slightly modified model is implemented in the package in such way that only the energy parameters but not the algorithmic structure is affected. A comparison with data from the literature show that predicted free energies and melting temperatures are in reasonable agreement with experiments.

Conclusion

The new feature in the package makes it possible to study effects of salt concentrations on RNA folding in a systematic manner. Strictly speaking, the model pertains only to mono-valent cations, and thus covers the most important parameter, i.e., the NaCl concentration. It remains a question for future research to what extent unspecific effects of bi- and tri-valent cations can be approximated in a similar manner.

Availability

Corrections for the concentration of monovalent cations are available in the package starting from version 2.6.0.
Comparison of the results of open PLIF versus UBE PLIF in lumbar spinal stenosis: postoperative adjacent segment instability is lesser in UBE
Authors: Li Xiaobin , Liu Jie , Liu Zhiwei
Published: July 2023

Objective

To compare the difference in efficacy between open PLIF and UBE for lumbar spinal stenosis and the effect on postoperative adjacent segment instability.

Method

The clinical data of 37 patients with PLIF and 32 patients with UBE for lumbar spinal stenosis were retrospectively analyzed to compare the differences in perioperative conditions and short- and medium-term outcomes.

Results

All 69 patients completed the surgery successfully. The operating time, number of intraoperative fluoroscopies and hospital days were higher in the UBE group than in the open PLIF group. Intraoperative bleeding and postoperative drainage were lower than in the open PLIF group (P < 0.05). The visual analogue scale (VAS) of low back pain was lower in the UBE group than in the open PLIF group at 1 month and 3 months postoperatively (P < 0.05), and there were no statistically significant VAS scores for low back pain in the two groups at 1 day and 6 months postoperatively (P > 0.05). Leg pain VAS scores were lower in the UBE group than in the open PLIF group at 1 month, 3 months and 6 months postoperatively (P < 0.05), and leg pain VAS scores were not statistically significant in both groups at 1 day postoperatively (P > 0.05). The ODI index was lower in the UBE group than in the open PLIF group at 1 day and 1 month postoperatively (P < 0.05) and was not statistically significant in the two groups at 3 months and 6 months postoperatively (P > 0.05). There was no statistically significant difference between the two groups in postoperative interbody height, sagittal diameter of the spinal canal, efficacy of modified MacNab and interbody fusion (P > 0.05). The open PLIF group was more prone to postoperative adjacent vertebral instability than the UBE group, and the difference was statistically significant (P < 0.05).

Conclusion

With appropriate indications, the open PLIF group and the UBE group had similar short- and medium-term clinical outcomes for the treatment of lumbar spinal stenosis, but patients in the UBE group had better symptomatic improvement than the open PLIF group at 3 months postoperatively, and the effect on postoperative adjacent vertebral instability was smaller in the endoscopic group than in the open PLIF group.
Optimizing detection of Alzheimer’s disease in mild cognitive impairment: a 4-year biomarker study of mild behavioral impairment in ADNI and MEMENTO
Authors: Ismail Zahinoor , Leon Rebeca , Creese Byron , Ballard Clive , Robert Philippe , Smith Eric E.
Published: July 2023

Background

Disease-modifying drug use necessitates better Alzheimer disease (AD) detection. Mild cognitive impairment (MCI) leverages cognitive decline to identify the risk group; similarly, mild behavioral impairment (MBI) leverages behavioral change. Adding MBI to MCI improves dementia prognostication over conventional approaches of incorporating neuropsychiatric symptoms (NPS). Here, to determine if adding MBI would better identify AD, we interrogated associations between MBI in MCI, and cerebrospinal fluid biomarkers [β-amyloid (Aβ), phosphorylated-tau (p-tau), and total-tau (tau)-ATN], cross-sectionally and longitudinally.

Methods

Data were from two independent referral-based cohorts, ADNI (mean[SD] follow-up 3.14[1.07] years) and MEMENTO (4.25[1.40] years), collected 2003–2021. Exposure was based on three-group stratification: 1) NPS meeting MBI criteria; 2) conventionally measured NPS (NPSnotMBI); and 3) noNPS. Cohorts were analyzed separately for: 1) cross-sectional associations between NPS status and ATN biomarkers (linear regressions); 2) 4-year longitudinal repeated-measures associations of MBI and NPSnotMBI with ATN biomarkers (hierarchical linear mixed-effects models-LMEs); and 3) rates of incident dementia (Cox proportional hazards regressions).

Results

Of 510 MCI participants, 352 were from ADNI (43.5% females; mean [SD] age, 71.68 [7.40] years), and 158 from MEMENTO (46.2% females; 68.98 [8.18] years). In ADNI, MBI was associated with lower Aβ42 (standardized β [95%CI], -5.52% [-10.48-(-0.29)%]; p = 0.039), and Aβ42/40 (p = 0.01); higher p-tau (9.67% [3.96–15.70%]; p = 0.001), t-tau (7.71% [2.70–12.97%]; p = 0.002), p-tau/Aβ42 (p < 0.001), and t-tau/Aβ42 (p = 0.001). NPSnotMBI was associated only with lower Aβ42/40 (p = 0.045). LMEs revealed a similar 4-year AD-specific biomarker profile for MBI, with NPSnotMBI associated only with higher t-tau. MBI had a greater rate of incident dementia (HR [95%CI], 3.50 [1.99–6.17; p < 0.001). NPSnotMBI did not differ from noNPS (HR 0.96 [0.49–1.89]; p = 0.916). In MEMENTO, MBI demonstrated a similar magnitude and direction of effect for all biomarkers, but with a greater reduction in Aβ40. HR for incident dementia was 3.93 (p = 0.004) in MBI, and 1.83 (p = 0.266) in NPSnotMBI. Of MBI progressors to dementia, 81% developed AD dementia.

Conclusions

These findings support a biological basis for NPS that meet MBI criteria, the continued inclusion of MBI in NIA-AA ATN clinical staging, and the utility of MBI criteria to improve identification of patients for enrollment in disease-modifying drug trials or for clinical care.
The new world of RNA diagnostics and therapeutics
Authors: Blandino Giovanni , Dinami Roberto , Marcia Marco , Anastasiadou Eleni , Ryan Brid M. , Palcau Alina Catalina , Fattore Luigi , Regazzo Giulia , Sestito Rosanna , Loria Rossella , Díaz Méndez Ana Belén , Cappelletto Maria Chiara , Pulito Claudio , Monteonofrio Laura , Calin George A. , Sozzi Gabriella , Cheong Jit Kong , Aharonov Ranit , Ciliberto Gennaro
Published: July 2023

The 5th Workshop IRE on Translational Oncology was held in Rome (Italy) on 27–28 March at the IRCCS Regina Elena National Cancer Institute. This meeting entitled “The New World of RNA diagnostics and therapeutics” highlightes the significant progress in the RNA field made over the last years. Research moved from pure discovery towards the development of diagnostic biomarkers or RNA-base targeted therapies seeking validation in several clinical trials. Non-coding RNAs in particular have been the focus of this workshop due to their unique properties that make them attractive tools for the diagnosis and therapy of cancer.

This report collected the presentations of many scientists from different institutions that discussed recent oncology research providing an excellent overview and representative examples for each possible application of RNA as biomarker, for therapy or to increase the number of patients that can benefit from precision oncology treatment.

In particular, the meeting specifically emphasized two key features of RNA applications: RNA diagnostic (Blandino, Palcau, Sestito, Díaz Méndez, Cappelletto, Pulito, Monteonofrio, Calin, Sozzi, Cheong) and RNA therapeutics (Dinami, Marcia, Anastasiadou, Ryan, Fattore, Regazzo, Loria, Aharonov).
Sertaconazole-repurposed nanoplatform enhances lung cancer therapy via CD44-targeted drug delivery
Authors: Liu Ruolan , Li Qiong , Qin Siyuan , Qiao Ling , Yang Mei , Liu Shanshan , Nice Edouard C. , Zhang Wei , Huang Canhua , Zheng Shaojiang , Gao Wei
Published: July 2023

Background

Lung cancer is one of the most frequent causes of cancer-related deaths worldwide. Drug repurposing and nano-drug delivery systems are attracting considerable attention for improving anti-cancer therapy. Sertaconazole (STZ), an antifungal agent, has been reported to exhibit cytotoxicity against both normal and tumor cells, and its medical use is limited by its poor solubility. In order to overcome such shortcomings, we prepared a drug-repurposed nanoplatform to enhance the anti-tumor efficiency.

Methods

Nanoplatform was prepared by thin film dispersion. Drug release studies and uptake studies were measured in vitro. Subsequently, we verified the tumor inhibition mechanisms of HTS NPs through apoptosis assay, immunoblotting and reactive oxygen species (ROS) detection analyses. Antitumor activity was evaluated on an established xenograft lung cancer model in vivo.

Results

Our nanoplatform improved the solubility of sertaconazole and increased its accumulation in tumor cells. Mechanistically, HTS NPs was dependent on ROS-mediated apoptosis and pro-apoptotic autophagy to achieve their excellent anti-tumor effects. Furthermore, HTS NPs also showed strong inhibitory ability in nude mouse xenograft models without significant side effects.

Conclusions

Our results suggest that sertaconazole-repurposed nanoplatform provides an effective strategy for lung cancer treatment.
Protocol for a systematic literature review of smartphone apps to support the self-management of rheumatic and musculoskeletal diseases: development strategies, theoretical underpinnings and barriers to engagement
Authors: Barnett Rosemarie , Clarke Christopher , Sengupta Raj , Rouse Peter C.
Published: July 2023

Background

Rheumatic and musculoskeletal diseases (RMDs) cause significant burden to the individual and society, requiring lifelong management and specialist healthcare resource use. Costing over 200 billion euros per year in Europe, RMDs are the most expensive of all diseases for European healthcare systems. The incidence and burden of RMDs are projected to rise with the ageing global population and increase in sedentary, obesogenic lifestyles. In parallel, there is a global crisis in the rheumatology workforce, whereby capacity to deliver specialist care is being exceeded by demand. Pervasive, scalable mobile health technologies, such as apps, are being developed to support the self-management of RMDs and reduce pressure on healthcare services. However, it is unknown whether these apps are informed by theory or their use supported by an appropriate evidence base. The purpose of this review is therefore to provide a comprehensive overview of the development strategies, interventional components and theoretical underpinnings of existing smartphone apps, designed to support the self-management of RMDs.

Methods

Searches will be conducted within PubMed, Scopus, Web of Science, Embase, MEDLINE and PsycINFO. Reference lists and citing articles of the included studies will be searched. Identified publications will be screened for eligibility by two independent reviewers. Any discrepancies between reviewers will be resolved by consensus, with input from a third reviewer if required. Data will be extracted on study designs, methods, populations, setting, utilised theoretical frameworks, intervention components, behaviour change techniques, methods to evaluate effectiveness and barriers/facilitators to intervention engagement. Exploratory outcomes include reported effectiveness, acceptability and usability. A systematic, narrative synthesis of evidence will be presented. If appropriate (depending on quality and pool of evidence identified), qualitative meta-summary techniques will be used to combine and summarise qualitative findings regarding barriers/facilitators to intervention engagement.

Discussion

The results of this systematic literature review will provide insights for healthcare professionals, researchers, app designers and policy makers, to inform future development and implementation of smartphone apps to support self-management of RMDs. Evidence gaps for future research will be identified. Findings will be disseminated through a final manuscript/publication of results and via a conference abstract, patient organisations and social media.

Systematic review registration

PROSPERO CRD42022359704.
3-D thermal structure and dehydration near the Chile Triple Junction and its relation to slab window, tectonic tremors, and volcanoes
Authors: Iwamoto Kaya , Suenaga Nobuaki , Yoshioka Shoichi , Ortega-Culaciati Francisco , Miller Matthew , Ruiz Javier
Published: July 2023

The southern Chile subduction zone is a complex tectonic environment, where the Chile Ridge, the Nazca (NZ) and Antarctic (AN) plates subduct underneath the South American (SA) plate. The intersection between the NZ, AN and SA plates is referred to as the Chile Triple Junction (CTJ). In this region, a gap, often referred to as a slab window, has been formed between the NZ and AN slabs due to the divergence in their plate motion velocities, with volcanoes existing mainly above the subducted NZ and AN plates. In this study, we constructed a three-dimensional thermomechanical model associated with simultaneous subduction of the NZ and AN plates near the CTJ. The results show that the current temperature distributions on the upper surface of the slabs are higher closer to the Chile Ridge, and the AN plate has a distribution of elevated temperatures relative to the NZ plate at the same depth due to the northward migration of the CTJ and the slower convergence rate of the AN plate. Moreover, we calculated the water content and dehydration gradient from the temperature distribution near the upper surface of the slab and discussed their relationship to the distribution of volcanoes. In the northern part of the model domain, high dehydration gradients were obtained below the volcanic chain. Therefore, we suggest that the water released from the slab and the mantle wedge decreased the melting point of the mantle wedge just above the slab and produced melts, which may have contributed to form the overlying volcanoes.
Open‐wedge high tibial osteotomy with a slight valgus correction from neutral limb alignment achieves clinical improvements comparable with those for knees with varus deformity
Authors: Itou Junya , Kuwashima Umito , Itoh Masafumi , Okazaki Ken
Published: July 2023

Purpose

The effect of open‐wedge high tibial osteotomy (OWHTO) on the preoperative neutral alignment of the knee is unknown. The purpose of this study was to clarify the clinical outcome of OWHTO with neutral alignment, defined as within 4 degrees of varus.

Methods

This retrospective study included 72 knees with varus that underwent medial OWHTO. The knees were divided according to the preoperative hip‐knee‐ankle angle into a neutral alignment group (≤ 4° of varus alignment) and a varus alignment group (> 4° of varus alignment). The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Forgotten Joint Score‐12 (FJS‐12) were evaluated preoperatively and during at least 2 years of follow‐up postoperatively.

Results

There were no significant differences between the preoperative FJS‐12 (17.9 versus 23.7; p = 0.16) and postoperative FJS‐12 (57.3 versus 60.6; p = 0.52) or KOOS subscale scores (p > 0.05) in the neutral alignment group or the varus alignment group. Each group had a mean change in the KOOS subscale scores that exceeded the minimum clinically important difference.

Conclusion

The short‐term clinical results of OWHTO for neutral alignment were as favourable as those for varus malalignment.

Level of evidence

IV.
Oral semaglutide in kidney transplant recipients with metabolic syndrome: three Japanese cases
Authors: Miyazaki Ryoichi , Miyagi Kyoko
Published: July 2023

Background

Renal transplant recipients with chronic kidney disease often develop post-transplant diabetes mellitus or metabolic syndrome (MetS), which are poor prognostic factors after renal grafts. Although recent studies have reported the protective effects of glucagon-like peptide-1 receptor agonist (GLP-1RA) on the heart and kidneys, few have assessed its effects in renal transplant patients. Moreover, to our knowledge there have been no studies on the effects of oral GLP-1RA (semaglutide) in renal transplantation recipients in Japan.

Case presentation

Case 1 was a 52-year-old male renal transplant recipient with MetS. Semaglutide was administered orally for 12 months, starting at 3 mg/day and titrating up to 14 mg/day. Over time, his HbA1c level decreased from 5.9 to 5.5% and weight from 100.6 to 96.3 kg. No adverse events were observed. Case 2 was a 62-year-old male renal transplant recipient with MetS. Oral semaglutide was started at 3 mg/day. However, the patient had severe nausea, and the dose was reduced to 1.5 mg/day and then gradually increased to 14 mg/day for 12 months. Over time, triglyceride decreased from 308 to 277 mg/dL and weight decreased from 75.4 to 63.2 kg. Case 3 was a 59-year-old male renal transplant recipient with MetS and fatty liver. Oral semaglutide was started at 3 mg/day and titrated up to 12 mg/day for 12 months. Over time, triglyceride decreased from 205 to 119 mg/dL and weight decreased from 79.1 to 76.4 kg. No adverse events were observed.

Conclusions

In all three patients, oral semaglutide significantly reduced body weight and improved metabolic parameters. Additional studies are needed to further evaluate the efficacy of oral semaglutide and the incidence of associated adverse events in a large number of renal transplant recipients.

Trial registration: UMIN, UMIN000050853. Registered 14 April 2023—Retrospectively registered, https://center6.umin.ac.jp/cgi-bin/ctr/ctr_reg_rec.cgi
Hematemesis or hemoptysis? Pulmonary hydatidosis presenting with hemoptysis, case report
Authors: Saad Moustafa Ali , Gamal Galila , Elsabagh Yumn A. , El Gendy Hala Ibrahem
Published: July 2023

Background

Pulmonary hydatidosis is a zoonotic infection caused by the tapeworm of the genus Echinococcus.

Case presentation

In this case report we present a case of a 38-year-old woman presenting with hemoptysis as a manifestation of pulmonary hydatidosis. Hemoptysis was falsely interpreted at first as hematemesis leading to multiple non-indicated gastroscopies. The patient was diagnosed by pathological examination of the lobectomy sample.

Conclusions

Proper history, in differentiating hemoptysis from hematemesis, guides proper management. Also, pulmonary hydatidosis should be considered in the differential diagnosis of cavitary lung lesions, especially in endemic areas.
Giant cardiac hemangioma in the right atrium: an asymptomatic surgical case
Authors: Kondo Yuki , Yasutsune Toru , Kado Yuichiro , Jinzai Yuki , Takigawa Tomoya , Kishigami Takehiro , Inaba Yuna , Nishimura Yosuke
Published: July 2023

Background

Cardiac hemangiomas are rare, accounting for only 5% of benign cardiac tumors. In the past, there have been few reports of giant cardiac hemangiomas that were > 100 mm in size but were asymptomatic.

Case presentation

A 44-year-old woman presented with a large asymptomatic intracardiac mass that was accidentally detected on echocardiography. The tumor was surgically resected. During surgery, a sharply margined tumor was located in the right atrium; the tumor was histopathologically diagnosed as a cavernous hemangioma. The patient was discharged uneventfully on the 18th postoperative day. No signs of recurrence were observed at 1 year postoperatively.

Conclusions

We report on a surgical case of an asymptomatic giant cardiac hemangioma 115 mm × 92 mm in size, as measured by echocardiography. It is difficult to diagnose cardiac tumors before surgery based on symptoms and imaging. Surgical resection is the most reliable treatment because of its accurate diagnosis and favorable prognosis.
Enhanced Surgical Decision-Making Tools in Breast Cancer: Predicting 2-Year Postoperative Physical, Sexual, and Psychosocial Well-Being following Mastectomy and Breast Reconstruction (INSPiRED 004)
Authors: Xu Cai , Pfob André , Mehrara Babak J. , Yin Peimeng , Nelson Jonas A. , Pusic Andrea L. , Sidey-Gibbons Chris
Published: July 2023

Background

We sought to predict clinically meaningful changes in physical, sexual, and psychosocial well-being for women undergoing cancer-related mastectomy and breast reconstruction 2 years after surgery using machine learning (ML) algorithms trained on clinical and patient-reported outcomes data.

Patients and Methods

We used data from women undergoing mastectomy and reconstruction at 11 study sites in North America to develop three distinct ML models. We used data of ten sites to predict clinically meaningful improvement or worsening by comparing pre-surgical scores with 2 year follow-up data measured by validated Breast-Q domains. We employed ten-fold cross-validation to train and test the algorithms, and then externally validated them using the 11th site’s data. We considered area-under-the-receiver-operating-characteristics-curve (AUC) as the primary metric to evaluate performance.

Results

Overall, between 1454 and 1538 patients completed 2 year follow-up with data for physical, sexual, and psychosocial well-being. In the hold-out validation set, our ML algorithms were able to predict clinically significant changes in physical well-being (chest and upper body) (worsened: AUC range 0.69–0.70; improved: AUC range 0.81–0.82), sexual well-being (worsened: AUC range 0.76–0.77; improved: AUC range 0.74–0.76), and psychosocial well-being (worsened: AUC range 0.64–0.66; improved: AUC range 0.66–0.66). Baseline patient-reported outcome (PRO) variables showed the largest influence on model predictions.

Conclusions

Machine learning can predict long-term individual PROs of patients undergoing postmastectomy breast reconstruction with acceptable accuracy. This may better help patients and clinicians make informed decisions regarding expected long-term effect of treatment, facilitate patient-centered care, and ultimately improve postoperative health-related quality of life.
PREVENTIVE ZINC SUPPLEMENTATION EFFECT ON REDOX STATUS IN RAT MODEL OF MAFLD
Authors: Nikonorova Eugenia R. , Nikonorov Alexandr A. , Popova Elizaveta V. , Agletdinov Eduard F. , Sinitskii Anton I. , Tinkov Alexey A.
Published: July 2023

Background. Oxidative stress plays an important role in the pathogenesis of metabolic-associated fatty liver disease (MAFLD). Antioxidant trace elements as cofactors of antioxidant enzymes and metalloproteins are involved in this process. Zinc being an important antioxidant may have a positive effect on the treatment of liver pathology. The study aimed to assess the effect of preventive zinc supplementation on MAFLD in rats.

Materials and Methods. A total of 26 three-month-old female Wistar rats were used in the present study. The activity of the antioxidant enzymes superoxide dismutase and catalase, some redox status markers, such as ceruloplasmin, oxidized tryptophan, dithyrosines, total thiols, carbonyls, TBARS, and uric acid were evaluated. Oxidative stress biomarkers were studied spectrophotometrically.

Results. MAFLD was accompanied by hyperuricemia and a decrease in serum dityrosines. The addition of Zn to the diet prevented the development of steatosis, decreased the level of oxidized tryptophan in the liver, and paradoxically caused hyperuricemia in the MAFLD model used. Zn supplementation had a positive effect on the prevention of MAFLD, had a little effect on redox status of animals but caused paradoxical hyperuricemia. Future studies are needed to establish the mechanisms of the Zn effect at the cellular level.