bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiographic outcomes of embolization in patients with intracranial aneurysms with coil- assisted Laser cut stent versus braided stents
Authors: Ortiz-Giraldo Andrés F , Vera Daniela D , Catalá Andrés J , Correa-Ruiz Paula , Flores-Sandoval Omar E , Rodriguez-Gelves Adriana , Lara Juan Jose , Serrano-Gómez Sergio , Reyes Adriana , Ferreira-Prada Carlos , Galvis-Méndez Melquizidel , Vargas-Pérez Oliverio , Mantilla-García Daniel E
Published: May 2023

Introduction

Intracranial aneurysms (IA) are a focal dilatation of the vessel wall, the rupture of these, causes subarachnoid hemorrhage. Until now, endovascular management is the ideal treatment, providing the interventionist a range of options among which the stent and coils embolization stands out because of its occlusion rate. This study presents the results of a retrospective cohort comparing the effectiveness, morbidity, and mortality of IA treatment with laser-cut stent-assisted coils versus braided stents.

Methodology

Retrospective cohort of patients diagnosed with unruptured intracranial aneurysms treated with coil-assisted laser-cut stents or braided stents between January 2014 and December 2021.

Results

In total, 138 patients with 147 intracranial aneurysms were analyzed, 91 of them were treated with laser-cut stent and 56 with braided stents. The main antecedent was arterial hypertension (48.55%). In the immediate angiographic control, a Raymond Roy scale (RRO) I was obtained in 86.81% of the patients with laser-cut stents and 87.50% of the patients with braided stents. In the angiographic follow-up at 12 months, an RRO I occlusion rate of 85.19% was reported in both groups. Perioperative complications occur in 16 patients treated with laser-cut stents and 12 patients treated with braided stents. Three patients presented bleeding complications during the 12-month follow-up, of which two correspond to patients treated with braided stents and one with a laser-cut stent.

Conclusion

Treatment of patients with intracranial aneurysms with laser-cut stents or braided stents and coils is just as safe and effective
Hyperparameter optimization of tapping center machines model using robust whale optimization algorithm
Authors: Yang Po-Yuan , Chang Ping-Yueh
Published: May 2023

To build a synchronization error prediction model for the machine tool efficiently, a robust whale optimization algorithm (RWOA) method proposed in this study is applied to the hyperparameter optimization of its model. The proposed RWOA method integrated a non-linear time-invariant inertia weighting (NTIW) method and a Taguchi-based adaptive parameter exploration (ATPE) to improve the performance of WOA and promote robustness. The NTIW method can improve the performance of other algorithms, so this study used the NTIW method in the WOA. In addition, the Taguchi method can get an excellent combination of variables with optimal values and stable performance, making the WOA robust. First, to verify the validity of the proposed RWOA method, 13 benchmark functions were used in this study. The results of the benchmark function tests include the mean, standard deviation, and p-value of the t-distribution test. The results show that 11 of the 13 functions differ significantly. In other non-significant difference functions, the means and standard deviations obtained by the proposed RWOA are considerably better than those obtained by WOA. Since the product cost of machine tools is higher, if a prediction model can be built effectively, it can reduce the cost. Therefore, in this study, the proposed RWOA was used to explore the best hyperparameter combination for the model. From the results, the model’s average MAPE (mean absolute percentage error) was 7.2604% for training data and 9.2603% for the testing data under 30 modeling runs. For the best one in 30 models, the MAPE was 6.8384% for the training data and 6.7372% for the testing data. This model was also introduced into the actual machine in this study, and the experimental results showed the MAPE 6.3447%. The proposed RWOA method effectively explores a suitable synchronization error model for the tool machine.
Knowledge and attitudes of mothers toward HPV vaccination: A cross-sectional study in Kazakhstan
Authors: Babi Aisha , Issa Torgyn , Issanov Alpamys , Akhanova Sholpan , Udalova Natalya , Koktova Svetlana , Balykov Askhat , Sattarkyzy Zhanna , Imankulova Balkenzhe , Kamzayeva Nazira , Almawi Wassim Y. , Aimagambetova Gulzhanat
Published: May 2023

Background:

Although recommended for all member states of World Health Organization, there is no national human papillomavirus vaccination program in Kazakhstan. Furthermore, there are no studies in Kazakhstan that evaluate the mothers’ perception of human papillomavirus vaccines.

Objectives:

This study aims to assess the knowledge and attitudes toward human papillomavirus vaccination among mothers in Kazakhstan and the factors associated with their attitudes.

Design:

A cross-sectional study was performed during the period of December 2021—February 2022. The STROBE guideline for cross-sectional studies was applied.

Methods:

Paper-based structured questionnaires were filled out by 191 mothers, 141 of whom had daughters. The attitude score was assessed as per the Likert-type scale. The Chi-square and Fisher’s exact tests, with a significance value of < 0.05 were used to analyze the relationships between the characteristics of mothers and their attitude scores.

Results:

The following factors were significantly associated with mothers’ attitudes toward human papillomavirus vaccination: a place of residence, family income, number of children, and refusal of vaccination for themselves (p < 0.005). Of all participants, only 45% of all mothers, 41% of mothers with a female, and 46% of mothers with male children had positive attitudes toward human papillomavirus vaccination. The child’s gender was not a significant determinant. Overall, the level of knowledge about human papillomavirus vaccination was found to be low. The median total score is 0 out of 12 for women who have negative and neutral attitudes toward human papillomavirus vaccines. Among women who have positive attitudes toward HPV vaccines, the median score is around 3 points.

Conclusion:

Before the implementation of the human papillomavirus vaccination program into the Kazakhstani national vaccination calendar, comprehensive and adequate information and education campaigns are required on the national level for parents and the population in general.
Usefulness of virtual autopsy in diagnosing pathologies in the paediatric population: A systematic review
Authors: Wickramasinghe Chathula Ushari , Edussuriya Deepthi , Perera Sriyani , Herath Nimashi
Published: May 2023

Objective:

Virtual autopsy is a non-invasive/minimally invasive method for conducting an autopsy, with the assistance of imaging techniques. We aim to review the benefits of virtual autopsy in detecting pathologies in the paediatric population.

Method:

The procedure adhered to Institute of Medicine and Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Seven databases including MEDLINE and SCOPUS were searched for articles published 2010–2020 worldwide in English. A narrative synthesis of the findings of included studies was carried out to discuss and summarize the results of the review.

Results:

From 686 studies on paediatric deaths, 23 met selection/quality criteria. Virtual autopsy was better than conventional autopsy in detecting skeletal lesions and bullet trajectory, thus a crucial tool in the investigation of traumatic and firearm deaths. Virtual autopsy was superior to conventional autopsy in identifying the point of bleeding in postoperative deaths and objectively quantifying air/fluid in body cavities. Virtual autopsy was a useful adjunct for detecting pulmonary thrombo-embolism, foreign body aspiration, drowning and metastatic malignancies. The use of non-contrast imaging in investigating natural paediatric deaths did not offer more information than conventional autopsy. Misinterpretation of normal post-mortem changes as pathological findings was another disadvantage of virtual autopsy leading to erroneous conclusions. But accuracy may be improved with contrast enhancement and post-mortem magnetic resonance imaging.

Conclusion:

Virtual autopsy is a crucial tool in the investigation of traumatic and firearm deaths in the paediatric population. Virtual autopsy will be useful as an adjunct to conventional autopsy in asphyxial deaths, stillbirths and decomposed bodies. Virtual autopsy has limited value in differentiating antemortem and post-mortem changes with the added risk of misinterpretations, therefore should be used with caution in natural deaths.
Work Stressors and the Buffering Functions of the Sense of Control in the United States and Japan: A Test of the Diminished Buffering Hypothesis
Authors: Narisada Atsushi
Published: May 2023

In the Stress Process Model, the sense of control is situated as a central psychosocial resource that buffers the effect of stressors on psychological distress. Although studies support this proposition, scholars have called for more research on whether buffering effects generalize across social contexts and groups. I address this call by examining cross-cultural differences in the sense of control’s buffering effects. Prior studies suggest that perceived control is a less important resource for well-being among individuals in collectivistic cultures compared with those in individualistic cultures. This has stimulated the diminished buffering hypothesis, which predicts weaker stress-buffering of perceived control among those in collectivistic cultures. This study tests this hypothesis using population-based data of Americans and Japanese, two groups that have been deemed quintessentially individualistic and collectivistic, respectively. Results show that across a set of five prominent work stressors, there are no differences in the stress-buffering functions of the sense of control between Americans and Japanese. These patterns pose questions about the view that sense of control is a less important resource for those in collectivistic cultures. As a stress-buffering resource, the sense of control appears to be just as important for Japanese as it is for Americans.
Debt, Credit Payment Holidays, and Their Relationship with Mental Health during the COVID-19 Pandemic in the United Kingdom
Authors: Sparkes Matthew , Wang Senhu , Wels Jacques
Published: May 2023

Although the relationship between debt and mental health is well documented, little is known about how changes in debt status and the specific policies implemented to assist borrowers during the COVID-19 pandemic have impacted the mental health of men and women. Particular attention is paid to the implementation of a non-neoliberal “credit payment holiday” scheme during the pandemic in the United Kingdom. Data come from three waves of the Understanding Society COVID-19 surveys. We use panel data models to assess the relationship between change in the presence of unsecured debt, credit payment holiday, and psychological distress (12-item General Health Questionnaire [GHQ-12] Likert score), controlling for confounders. The presence of debt is associated with significantly higher psychological distress, and the pattern is particularly pronounced for women than for men. Among the indebted population, the results show that credit payment holiday can significantly buffer the negative mental health effect of debt. While the buffering effect is larger for women, it is not significantly different across genders. The relationship between debt and mental health remains significant throughout the pandemic, but the credit payment holiday scheme has played a significant role in attenuating it and could be implemented as a policy tool outside the pandemic context.
Identifying Treatment Responders to Varenicline for Alcohol Use Disorder Using Two Machine-Learning Approaches
Authors: Grodin Erica N. , Montoya Amanda K. , Cruz Alondra , Donato Suzanna , Baskerville Wave-Ananda , Ray Lara A.
Published: May 2023

Varenicline has shown promise for treating alcohol use disorder (AUD); however, not everyone will respond to varenicline. Machine-learning methods are well suited to identify treatment responders. In the present study, we examined data from the National Institute on Alcohol Abuse and Alcoholism Clinical Intervention Group multisite clinical trial of varenicline using two machine-learning methods. Baseline characteristics taken from a randomized clinical trial of varenicline were examined as potential moderators of treatment response using qualitative interaction trees ( N = 199) and group least absolute shrinkage and selection operator interaction nets ( N = 200). Results align with prior research, highlighting smoking status, AUD severity, medication adherence, and drinking goal as predictors of treatment response. Novel findings included the interaction between age and cardiovascular health in predicting clinical response and stronger medication effects among individuals with lower craving. With increased integration of machine-learning methods, studies that effectively integrate methods and medication development have high potential to inform clinical practice.
Changing Livelihoods and New Opportunities: Experiences of Resettled Farmers in Two Farms in Shamva District, Mashonaland Central Province, Zimbabwe
Authors: Maimba Tanaka , Thebe Vusilizwe
Published: May 2023

This study set out to assess the impact of the land reform programme on two farms located in the Mashonaland Central Province of Zimbabwe, Tembo and Rutherdale, and to examine how the livelihoods of resettled farmers from this area evolved since relocation. Evidence through this study revealed that the land reform programme at the two farms largely benefited the beneficiaries of the scheme. The resettled farmers have grown in asset ownership due to access to land and have developed social networks to tackle their communities’ challenges. There is, however, a need for further government support and intervention with the intent to make the farmers more self-sufficient. The government could also come in as a facilitator to initiatives by the households themselves to solve their challenges.
Empathy and the Medical Student House Call: The Effect of Clinical Settings on Empathy in Third Year Medical Students
Authors: Collins Philip B. , Dinzeo Thomas , Sepede Jennifer C. , Bertagnolli John F. , White Christian
Published: May 2023

Objective

This study measured the effect the experience of house calls might have on third-year medical students.

Methods

Students were surveyed via an anonymous online survey at the start of their geriatrics clerkship, again at the end of their clerkship, and once more three months later. Empathy was measured using the Jefferson Scale of Empathy – Student version (JSE) and student attitudes towards the geriatrics population was measured using the UCLA Geriatrics Attitudes Scale (GAS). Data were analyzed using SPSS version 27.0.

Results

No changes in empathy were found when comparing students who completed house calls versus those who did not. However, students who trained in office settings were noted to have higher JSE scores at the three-month follow-up survey, students who worked in hospital settings had higher JSE scores at the completion of the clerkship, and student who worked in assisted living facilities had higher GAS scores at the completion of the clerkship.

Conclusions

Teaching students ways to improve empathy can be challenging. The setting in which a student trains may be an area of focus for improving empathy among trainees and should be researched further.
Prediction of residential and non-residential building usage in Germany based on a novel nationwide reference data set
Authors: Hartmann André , Behnisch Martin , Hecht Robert , Meinel Gotthard
Published: May 2023

Building usage is an important variable in modelling the energetic, material and social properties of a building stock. Gathering this data on large geographical scale, and in the necessary temporal and spatial resolution, that means, on building level, is a challenging task. Machine Learning algorithms like Random Forest have proven useful in predicting building-related features in the past but often resort to training sets of limited geographic scope, for example, cities. This study presents a workflow of predicting the semantic attribute of usage on the level of individual buildings. Based on screening data of the previous ENOB:dataNWG project, a novel building ground-truth data set distributed across Germany, a Random Forest algorithm is used to assess how the German building stock can be classified according to its residential or non-residential use. Different sampling strategies had been applied in order to find a robust evaluation metric for the classifier. Furthermore, the relevance of the feature set is highlighted and it is examined whether regional differences in classification quality exist. Results show that a classification of residential and non-residential building footprints has good prospects with an AUC of up to 0.9.
Assessment of the Bioclimatic Index for resilient urban spaces in Mediterranean cities
Authors: Chondrogianni Dimitra V , Stephanedes Yorgos J
Published: May 2023

To achieve urban resilience, assessment of the bioclimatic impact of various planning solutions should be given high priority in the decision-making process for the implementation of urban planning interventions. To aid in this process and improve the creation of resilient open spaces, the Bioclimatic Index has been developed as an evaluation tool and simple guide for local stakeholders. The assessment of the indicator is essential to determine the likelihood of its use in other Mediterranean cities as the methodological framework was based on the microclimate simulation results of the case study area of Patras Old Port, which is a seaside open space with a Mediterranean climate. In this framework, the Bioclimatic Index is used to rate the regenerated open spaces in Thessaloniki, Malaga, and Genoa, three Mediterranean seaside areas. The indicator values are compared to the microclimate simulation results created based on their planning solutions, aiming to test the accuracy, transferability and scalability of the indicator. The research result showed that the seaside space of Malaga, which has been evaluated as the optimal regeneration plan based on the Bioclimatic Index, creates the most favorable microclimate conditions through seasons, supporting the use of the indicator for evaluating the bioclimatic impact of regeneration plans in Mediterranean cities.
Quantifying care delivery team influences on the hospitalization outcomes of patients with multimorbidity: Implications for clinical informatics
Authors: Williams Tremaine B , Robins Taiquitha , Vincenzo Jennifer L , Lipschitz Riley , Baghal Ahmad , Sexton Kevin Wayne
Published: May 2023

The primary objective was to quantify the influences of care delivery teams on the outcomes of patients with multimorbidity. Electronic medical record data on 68,883 patient care encounters (i.e., 54,664 patients) were extracted from the Arkansas Clinical Data Repository. Social network analysis assessed the minimum care team size associated with improved care outcomes (i.e., hospitalizations, days between hospitalizations, and cost) of patients with multimorbidity. Binomial logistic regression further assessed the influence of the presence of seven specific clinical roles. When compared to patients without multimorbidity, patients with multimorbidity had a higher mean age (i.e., 47.49 v. 40.61), a higher mean dollar amount of cost per encounter (i.e., $3,068 v. $2,449), a higher number of hospitalizations (i.e., 25 v. 4), and a higher number of clinicians engaged in their care (i.e., 139,391 v. 7,514). Greater network density in care teams (i.e., any combination of two or more Physicians, Residents, Nurse Practitioners, Registered Nurses, or Care Managers) was associated with a 46–98% decreased odds of having a high number of hospitalizations. Greater network density (i.e., any combination of two or more Residents or Registered Nurses) was associated with 11–13% increased odds of having a high cost encounter. Greater network density was not significantly associated with having a high number of days between hospitalizations. Analyzing the social networks of care teams may fuel computational tools that better monitor and visualize real-time hospitalization risk and care cost that are germane to care delivery.
A follow-up evaluation of a coordinated police-social services response to recidivist family violence
Authors: Hamilton Gemma , Harris Lisa , McCook Sarah
Published: May 2023

Coordinated multi-agency approaches are a key strategy for responding to recidivist family violence. This paper presents a follow-up quantitative evaluation of Alexis: a coordinated police-social services approach to recidivist and high-risk family violence piloted in Victoria, Australia. State-wide police data was collected for 75 perpetrators 20 to 36 months since case closure following Alexis intervention. Results indicated that 38 perpetrators (51%) had no further recorded incidents of family violence. The remaining non-mutually exclusive categories indicated that 17 (22%) had perpetrated family violence against the original Alexis victim in another location (outside the pilot catchment zones); 28 (37%) had perpetrated family violence against a different victim; and 8 of the prior two groups (11%) had perpetrated violence against both Alexis and non-Alexis victims. Those classified as low recidivists before intervention were less likely to have a further recorded incident of family violence during the follow-up period compared to high recidivists. Implications for police and policy-makers are discussed with reference to intimate partner violence and parent abuse by adult children.
Pilot Observational Study of Patient Reported Outcome Measures for Long COVID Patients in Virtual Integrative Medical Group Visits
Authors: Barnhill Jessica L , Roth Isabel J , Miller Vanessa E , Baratta John M , Chilcoat Aisha , Kavalakatt Bethany M , Tiedt Malik K , Thompson Karla L , Gardiner Paula
Published: May 2023

Background

Long COVID is a common, debilitating post-infectious illness for which effective management is unknown. Integrative Medical Group Visits (IMGV) are effective interventions for chronic conditions and could benefit Long COVID patients. More information is needed regarding existing patient reported outcome measures (PROMs) to evaluate efficacy of IMGV for Long COVID.

Objective

This study assessed the feasibility of specific PROMS to evaluate IMGVs for Long COVID. Findings will inform future efficacy trials.

Methods

The Perceived Stress Scale (PSS-10), General Anxiety Disorder two-question tool (GAD-2), Fibromyalgia Symptom Severity scale (SSS), and Measure Yourself Medical Outcome Profile (MYMOP®) were collected pre- and post-group by teleconferencing platform or telephone and compared using paired t-tests. Patients were recruited from a Long COVID specialty clinic where they participated in 2-hour - 8 weekly IMGV sessions online.

Results

Twenty-seven participants enrolled and completed pre-group surveys. Fourteen participants were reachable by phone post-group and completed all pre and post PROMs (78.6% female, 71.4% non-Hispanic White, mean age 49). MYMOP® primary symptomatology was fatigue, shortness of breath and “brain fog”. Symptoms decreased in interference when compared to pre-group levels (mean difference −1.3 [95% CI-2.2, −.5]). PSS scores decreased (−3.4 [95% CI -5.8, −1.1]), and GAD-2 mean difference was −1.43 (95% CI –3.12, .26). There were no changes in SSS scores of fatigue (−.21 [95% CI -.68,0.25]), waking unrefreshed (.00 [95%CI -.32, −.32]), or trouble thinking (−.21 [95% CI -.78,0.35]).

Conclusion

All PROMs were feasible to administer via teleconferencing platform or telephone. The PSS, GAD-2 and MYMOP® are promising PROMs to track Long COVID symptomatology among IMGV participants. The SSS, while feasible to administer, did not change compared to baseline. Larger, controlled studies are needed to determine the efficacy of virtual IMGVs to address the needs of this large and growing population.
BET inhibition targets ABC-DLBCL constitutive B-cell receptor signaling through PAX5
Authors: Oien Derek B. , Sharma Samanta , Hattersley Maureen M. , DuPont Michelle , Criscione Steven W. , Prickett Laura , Goeppert Anne U. , Drew Lisa , Yao Yi , Zhang Jingwen , Chan Ho Man
Published: May 2023

B-cell receptor (BCR) signaling is essential for the diffuse large B-cell lymphoma (DLBCL) subtype that originates from activated B-cells (ABCs). ABC-DLBCL cells are sensitive to Bruton tyrosine kinase intervention. However, patients with relapsed or refractory ABC-DLBCL had overall response rates from 33% to 37% for Bruton tyrosine kinase inhibitors, suggesting the evaluation of combination-based treatment for improved efficacy. We investigated the efficacy and mechanism of the bromodomain and extraterminal motif (BET) inhibitor AZD5153 combined with the Bruton tyrosine kinase inhibitor acalabrutinib in ABC-DLBCL preclinical models. AZD5153 is a bivalent BET inhibitor that simultaneously engages the 2 bromodomains of BRD4. Adding AZD5153 to acalabrutinib demonstrated combination benefits in ABC-DLBCL cell line and patient-derived xenograft models. Differential expression analyses revealed PAX5 transcriptional activity as a novel downstream effector of this drug combination. PAX5 is a transcription factor for BCR signaling genes and may be critical for perpetually active BCR signaling in ABC-DLBCL. Our analyses further indicated significant alterations in BCR, RELB/alternative NF-κB, and toll-like receptor/interferon signaling. Validation of these results mapped a positive-feedback signaling loop regulated by PAX5. We demonstrated that AZD5153 decreased PAX5 expression, whereas acalabrutinib disruption of BCR signaling inhibited PAX5 activation. Furthermore, several interferon levels were decreased by AZD5153 and acalabrutinib in tumors. Adding interferon-beta1 (IFNβ1) to cells treated with acalabrutinib partially rescued PAX5 activation. Our results demonstrate that AZD5153 enhances the efficacy of acalabrutinib through PAX5 and BCR mechanisms that are critical for ABC-DLBCL.
Prevalence of frailty and its association with clinical outcomes in myeloproliferative neoplasms: a population-based study
Authors: Bankar Aniket , Chan Wing C. , Liu Ning , Cheung Matthew , Alibhai Shabbir , Gupta Vikas
Published: May 2023

Clinical implications of frailty in myeloproliferative neoplasms (MPN), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are unknown. In this population-based study, all incident cases of MPN from the Ontario cancer registry between 2004 and 2019 (N = 10 336; ET = 5108; PV = 3843; MF = 1385) and their matched controls (for age, sex, residence, and income) in a 1:4 ratio were included. Baseline frailty measured using the Johns Hopkins Adjusted Clinical Groups frailty indicator and McIsaac frailty index (mFI), categorized as fit, prefrail, or frail if mFI <0.10, 0.11 to 0.20, >0.20), was significantly higher in ET, PV, and MF compared with matched controls (standardized mean difference of 0.27, 0.27, and 0.28). Over 23%, 20%, and 34% of patients with ET, PV, and MF were frail or prefrail despite a younger age (<65 years) or minimal comorbidities. In Cox proportional regression, frailty was independently associated with worse overall survival (OS) after adjusting for age, sex, and comorbidities compared with mFI-fit patients. The hazard ratios (95% confidence interval) for OS for mFI-prefrail and mFI-frail patients were: 1.6 (1.3-1.9) and 3.6 (2.9-4.4) in ET, 1.3 (1.1-1.5) and 2.7 (2.1-3.4) in PV, and 1.2 (1.0-1.5) and 2.0 (1.5-2.7) in MF. Patients with MPN have a substantially higher prevalence of frailty compared with matched controls, which is associated with reduced OS, independent of age or comorbidities.
Cost-effectiveness of targeted treatment vs chemoimmunotherapy in treatment-naive unfit CLL without TP53 aberrations
Authors: Slot Matilde , Niemann Carsten Utoft , Ehlers Lars Holger , Rotbain Emelie Curovic
Published: May 2023

Several targeted treatments, such as venetoclax + obinutuzumab (VenO) and ibrutinib, have been developed to treat patients with treatment-naive chronic lymphocytic leukemia (CLL) and have been shown to improve progression-free survival compared with chlorambucil + obinutuzumab (ClbO). However, novel targeted agents are associated with a significant cost investment. The objective of this study was to investigate the cost-effectiveness of VenO compared with ClbO and ibrutinib in treatment-naive CLL without del17p/TP53 mutation in Denmark. We used a decision-analytic modeling approach to simulate hypothetical cohorts of patients with CLL from the initiation of first-line treatment to death, including the full treatment pathway and second-line therapy. VenO, ClbO, or ibrutinib was included as first-line therapy followed by either Ven + rituximab or ibrutinib. Model outcomes were expected quality-adjusted life years (QALYs), life years (LYs), and cost per patient, which were used to calculate incremental cost-effectiveness ratios (ICERs) with a willingness to pay from €23 600 to €35 600 per QALY. Compared with ClbO, VenO was associated with a QALY gain of 1.30 (1.42 LYs) over a lifetime. The incremental cost was €12 360, resulting in an ICER of €9491 per QALY gained, indicating that VenO is cost-effective. Compared with VenO, ibrutinib was associated with a QALY gain of 0.82 (1.74 LYs) but at a substantially increased incremental cost of €247 488 over a lifetime horizon. The ICER was €302 156 per QALY, indicating that ibrutinib in first-line treatment would not be considered cost-effective in Danish health care, compared with VenO. Future analyses in fit patients with CLL are needed to determine the cost-effectiveness of VenO.
Myogenic differentiation of human myoblasts and Mesenchymal stromal cells under GDF11 on Poly-ɛ-caprolactone-collagen I-Polyethylene-nanofibers
Authors: Cai Aijia , Schneider Paul , Zheng Zeng-Ming , Beier Justus P. , Himmler Marcus , Schubert Dirk W. , Weisbach Volker , Horch Raymund E. , Arkudas Andreas
Published: May 2023

Background

For the purpose of skeletal muscle engineering, primary myoblasts (Mb) and adipogenic mesenchymal stem cells (ADSC) can be co-cultured and myogenically differentiated. Electrospun composite nanofiber scaffolds represent suitable matrices for tissue engineering of skeletal muscle, combining both biocompatibility and stability Although growth differentiation factor 11 (GDF11) has been proposed as a rejuvenating circulating factor, restoring skeletal muscle function in aging mice, some studies have also described a harming effect of GDF11. Therefore, the aim of the study was to analyze the effect of GDF11 on co-cultures of Mb and ADSC on poly-ε-caprolactone (PCL)-collagen I-polyethylene oxide (PEO)-nanofibers.

Results

Human Mb were co-cultured with ADSC two-dimensionally (2D) as monolayers or three-dimensionally (3D) on aligned PCL-collagen I-PEO-nanofibers. Differentiation media were either serum-free with or without GDF11, or serum containing as in a conventional differentiation medium. Cell viability was higher after conventional myogenic differentiation compared to serum-free and serum-free + GDF11 differentiation as was creatine kinase activity. Immunofluorescence staining showed myosine heavy chain expression in all groups after 28 days of differentiation without any clear evidence of more or less pronounced expression in either group. Gene expression of myosine heavy chain (MYH2) increased after serum-free + GDF11 stimulation compared to serum-free stimulation alone.

Conclusions

This is the first study analyzing the effect of GDF11 on myogenic differentiation of Mb and ADSC co-cultures under serum-free conditions. The results of this study show that PCL-collagen I-PEO-nanofibers represent a suitable matrix for 3D myogenic differentiation of Mb and ADSC. In this context, GDF11 seems to promote myogenic differentiation of Mb and ADSC co-cultures compared to serum-free differentiation without any evidence of a harming effect.
The unrecognized role of fidelity in effectiveness-implementation hybrid trials: simulation study and guidance for implementation researchers
Authors: Trutschel Diana , Blatter Catherine , Simon Michael , Holle Daniela , Reuther Sven , Brunkert Thekla
Published: May 2023

Background

Effectiveness-implementation hybrid designs are a relatively new approach to evaluate efficacious interventions in real-world settings while concurrently gathering information on the implementation. Intervention fidelity can significantly influence the effectiveness of an intervention during implementation. However little guidance exists for applied researchers conducting effectiveness-implementation hybrid trials regarding the impact of fidelity on intervention effects and power.

Methods

We conducted a simulation study based on parameters from a clinical example study. For the simulation, we explored parallel and stepped-wedge cluster randomized trials (CRTs) and hypothetical patterns of fidelity increase during implementation: slow, linear, and fast. Based on fixed design parameters, i.e., the number of clusters (C = 6), time points (T = 7), and patients per cluster (n = 10) we used linear mixed models to estimate the intervention effect and calculated the power for different fidelity patterns. Further, we conducted a sensitivity analysis to compare outcomes based on different assumptions for the intracluster-correlation coefficient and the cluster size.

Results

Ensuring high fidelity from the beginning is central to achieve accurate intervention effect estimates in stepped-wedge and parallel CRTs. The importance of high fidelity in the earlier stages is more emphasized in stepped-wedge designs than in parallel CRTs. In contrast, if the increase of fidelity is too slow despite relatively high starting levels, the study will likely be underpowered and the intervention effect estimates will also be biased. This effect is more accentuated in parallel CRTs, here reaching 100% fidelity within the next measurement points is crucial.

Conclusions

This study discusses the importance of intervention fidelity for the study`s power and highlights different recommendations to deal with low fidelity in parallel and stepped-wedge CRTs from a design perspective. Applied researchers should consider the detrimental effect of low fidelity in their evaluation design. Overall, there are fewer options to adjust the trial design after the fact in parallel CRT as compared to stepped-wedge CRTs. Particular emphasis should be placed on the selection of contextually relevant implementation strategies.
Low plasma PD-L1 levels, early tumor onset and absence of peritoneal carcinomatosis improve prognosis of women with advanced high-grade serous ovarian cancer
Authors: Fanale Daniele , Brando Chiara , Corsini Lidia Rita , Cutaia Sofia , Di Donna Mariano Catello , Randazzo Ugo , Filorizzo Clarissa , Lisanti Chiara , Magrin Luigi , Gurrera Vittorio , Romano Raffaella , Dimino Alessandra , Bazan Russo Tancredi Didier , Olive Daniel , Vieni Salvatore , Pantuso Gianni , Giordano Antonio , Chiantera Vito , Russo Antonio , Bazan Viviana , Iovanna Juan Lucio
Published: May 2023

Background

The most common subtype of ovarian cancer (OC) showing immunogenic potential is represented by the high-grade serous ovarian cancer (HGSOC), which is characterized by the presence of tumor-infiltrating immune cells able to modulate immune response. Because several studies showed a close correlation between OC patient’s clinical outcome and expression of programmed cell death protein-1 or its ligand (PD-1/PD-L1), the aim of our study was to investigate if plasma levels of immunomodulatory proteins may predict prognosis of advanced HGSOC women.

Patients and methods

Through specific ELISA tests, we analyzed plasma concentrations of PD-L1, PD-1, butyrophilin sub-family 3A/CD277 receptor (BTN3A1), pan-BTN3As, butyrophilin sub-family 2 member A1 (BTN2A1), and B- and T-lymphocyte attenuator (BTLA) in one hundred patients affected by advanced HGSOC, before surgery and therapy. The Kaplan–Meier method was used to generate the survival curves, while univariate and multivariate analysis were performed using Cox proportional hazard regression models.

Results

For each analyzed circulating biomarker, advanced HGSOC women were discriminated based on long (≥ 30 months) versus short progression-free survival (PFS < 30 months). The concentration cut-offs, obtained by receiver operating characteristic (ROC) analysis, allowed to observe that poor clinical outcome and median PFS ranging between 6 and 16 months were associated with higher baseline levels of PD-L1 (> 0.42 ng/mL), PD-1 (> 2.48 ng/mL), BTN3A1 (> 4.75 ng/mL), pan-BTN3As (> 13.06 ng/mL), BTN2A1 (> 5.59 ng/mL) and BTLA (> 2.78 ng/mL). Furthermore, a lower median PFS was associated with peritoneal carcinomatosis, age at diagnosis > 60 years or Body Mass Index (BMI) > 25. A multivariate analysis also suggested that plasma concentrations of PD-L1 ≤ 0.42 ng/mL (HR: 2.23; 95% CI: 1.34 to 3.73; p = 0.002), age at diagnosis ≤ 60 years (HR: 1.70; 95% CI: 1.07 to 2.70; p = 0.024) and absence of peritoneal carcinomatosis (HR: 1.87; 95% CI: 1.23 to 2.85; p = 0.003) were significant prognostic marker for a longer PFS in advanced HGSOC patients.

Conclusions

The identification of high-risk HGSOC women could be improved through determination of the plasma PD-L1, PD-1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels.
A comprehensive analysis of different types of databases reveals that CDH1 mRNA and E-cadherin protein are not downregulated in most carcinoma tissues and carcinoma cell lines
Authors: Sicairos Brihget , Alam Shorna , Du Yuchun
Published: May 2023

Background

The CDH1 gene codes for the epithelial-cadherin (E-cad) protein, which is embedded in the plasma membrane of epithelial cells to form adherens junctions. E-cad is known to be essential for maintaining the integrity of epithelial tissues, and the loss of E-cad has been widely considered a hallmark of metastatic cancers enabling carcinoma cells to acquire the ability to migrate and invade nearby tissues. However, this conclusion has come under scrutiny.

Methods

To assess how CDH1 and E-cad expression changes during cancer progression, we analyzed multiple large transcriptomics, proteomics, and immunohistochemistry datasets on clinical cancer samples and cancer cell lines to determine the CDH1 mRNA and E-cad protein expression profiles in tumor and normal cells.

Results

In contrast to the textbook knowledge of the loss of E-cad during tumor progression and metastasis, the levels of CDH1 mRNA and E-cad protein are either upregulated or remain unchanged in most carcinoma cells compared to normal cells. In addition, the CDH1 mRNA upregulation occurs in the early stages of tumor development and the levels remain elevated as tumors progress to later stages across most carcinoma types. Furthermore, E-cad protein levels are not downregulated in most metastatic tumor cells compared to primary tumor cells. The CDH1 mRNA and E-cad protein levels are positively correlated, and the CDH1 mRNA levels are positively correlated to cancer patient’s survival. We have discussed potential mechanisms underlying the observed expression changes in CDH1 and E-cad during tumor progression.

Conclusions

CDH1 mRNA and E-cadherin protein are not downregulated in most tumor tissues and cell lines derived from commonly occurring carcinomas. The role of E-cad in tumor progression and metastasis may have previously been oversimplified. CDH1 mRNA levels may serve as a reliable biomarker for the diagnosis of some tumors (such as colon and endometrial carcinomas) due to the marked upregulation of CDH1 mRNA in the early stages of tumor development of these carcinomas.
Clinical activity of pembrolizumab with or without chemotherapy in advanced pulmonary large-cell and large-cell neuroendocrine carcinomas: a multicenter retrospective cohort study
Authors: Song Lianxi , Zhou Fei , Xu Tian , Zeng Liang , Xia Qing , Wang Zhan , Deng Li , Li Yizhi , Qin Haoyue , Yan Huan , Huang Zhe , Mi Jinye , Xu Qinqin , Yang Nong , Zhou Caicun , Zhang Yongchang
Published: May 2023

Background

Immune checkpoint inhibitors (ICI)-based combination strategies have improved the survival outcomes in advanced non-small cell lung cancers; however, data regarding their efficacy remains limited for uncommon histological types, including large-cell carcinoma (LCC) and large-cell neuroendocrine carcinoma (LCNEC).

Methods

We retrospectively analyzed a total of 60 patients with advanced LCC and LCNEC – 37 treatment-naïve and 23 pre-treated – who received pembrolizumab with or without chemotherapy. Treatment and survival outcomes were analyzed.

Results

Of the 37 treatment-naïve patients who received first-line pembrolizumab combined with chemotherapy, the 27 patients with LCC had an overall response rate (ORR) of 44.4% (12/27) and a disease control rate (DCR) of 88.9% (24/27); whereas 10 patients with LCNEC had an ORR of 70% (7/10) and DCR of 90% (9/10). The median progression-free survival (mPFS) was 7.0 months (95% confidence intervals [CI]: 2.2–11.8) and median overall survival (mOS) was 24.0 months (95%CI: 0.0–50.1) for first-line pembrolizumab plus chemotherapy of LCC (n = 27), whereas mPFS was 5.5 months (95%CI: 2.3–8.7) and mOS was 13.0 months (95%CI: 11.0–15.0) for first-line pembrolizumab plus chemotherapy of LCNEC (n = 10). Of the 23 pre-treated patients who received subsequent-line pembrolizumab with or without chemotherapy, mPFS was 2.0 months (95% CI: 0.6–3.4) and mOS was 4.5 months (95% CI: 0.0–9.0) for LCC and mPFS was 3.8 months (95% CI: 0.0–7.6) and mOS was not reached for LCNEC.

Conclusion

Our study provides real-world clinical evidence of the anti-tumor activity of pembrolizumab plus chemotherapy in advanced LCC and LCNEC, indicating that this regimen could serve as a treatment option, particularly as first-line therapy, for improving the survival outcomes of patients with these rare histological subtypes of lung cancer.

Trial registration

NCT05023837(ESPORTA, 27/08/2021).
Factors related to postoperative vitreous hemorrhage after small-gauge vitrectomy in proliferative diabetic retinopathy patients
Authors: Zhao Meng , Chandra Aman , Xu Jun , Li Jipeng
Published: May 2023

Background

The role of anticoagulation or antiplatelet on post-vitrectomy vitreous hemorrhage (POVH) in patients with proliferative diabetic retinopathy (PDR) is rarely investigated in the small-gauge vitrectomy era. We investigate the relationship between the long-term use of those medications and POVH in a group of PDR patients.

Methods

A retrospective cohort study was carried out in a group of PDR patients who underwent small-gauge vitrectomy in our center. The baseline data on diabetes, diabetic complications, long-term use of anticoagulants and antiplatelet agents, ocular findings, and vitrectomy details were collected. The occurrence of POVH was recorded during at least three-month follow-up. Factors related to POVH were analyzed using logistic analysis.

Results

During a median follow-up of 16 weeks, 5% (11/220) of patients had POVH, and 75 had received antiplatelet or anticoagulation agents before the operation. Factors related to persistent POVH were the use of antiplatelet or anticoagulation agents (5.98, 1.75–20.45, p = 0.004), the presence of myocardial revascularization (130.65, 3.53-4834.50, p = 0.008), the presence of coronary artery disease (CAD) treated with medicine (56.52, 1.99–1604.06, p = 0.018), and younger age (0.86, 0.77–0.96, p = 0.012). For those receiving preoperative antiplatelet or anticoagulation agents, the probability of developing POVH was higher in the patients whose previous therapy was adjusted compared to those with continued therapy (p = 0.02 by Log-rank test).

Conclusions

We identified long-term use of anticoagulation or antiplatelet medication, the presence of CAD, and younger age as three independent factors related to POVH. In PDR patients on long-term antiplatelet or anticoagulation medications, particular attention should be given to controlling intraoperative bleeding, and follow-up for POVH should be scheduled.
Nightshift work can induce oxidative DNA damage: a pilot study
Authors: Zou Yutong , Ma Xiaoli , Chen Qian , Xu Ermu , Yu Jialei , Tang Yueming , Wang Danchen , Yu Songlin , Qiu Ling
Published: May 2023

Background

Regular sleep is very important for human health; however, the short-term and long-term effects of nightshift with sleep deprivation and disturbance on human metabolism, such as oxidative stress, have not been effectively evaluated based on a realistic cohort. We conducted the first long-term follow-up cohort study to evaluate the effect of nightshift work on DNA damage.

Methods

We recruited 16 healthy volunteers (aged 33 ± 5 years) working night shifts at the Department of Laboratory Medicine at a local hospital. Their matched serum and urine samples were collected at four time points: before, during (twice), and after the nightshift period. The levels of 8-oxo-7,8-dihydroguanosine (8-oxoG) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), two important nucleic-acid damage markers, were accurately determined based on a robust self-established LC‒MS/MS method. The Mann–Whitney U or Kruskal–Wallis test was used for comparisons, and Pearson’s or Spearman’s correlation analysis was used to calculate the correlation coefficients.

Results

The levels of serum 8-oxodG, estimated glomerular filtration rate-corrected serum 8-oxodG, and the serum-to-urine 8-oxodG ratio significantly increased during the nightshift period. These levels were significantly higher than pre-nightshift work level even after 1 month of discontinuation, but no such significant change was found for 8-oxoG. Moreover, 8-oxoG and 8-oxodG levels were significantly positively associated with many routine biomarkers, such as total bilirubin and urea levels, and significantly negatively associated with serum lipids, such as total cholesterol levels.

Conclusion

The results of our cohort study suggested that working night shifts may increase oxidative DNA damage even after a month of discontinuing nightshift work. Further studies with large-scale cohorts, different nightshift modes, and longer follow-up times are needed to clarify the short- and long-term effects of night shifts on DNA damage and find effective solutions to combat the negative effects.