Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing PD-L1 Expression Status Using Radiomic Features from Contrast-Enhanced Breast MRI in Breast Cancer Patients: Initial Results

Simple Summary To our knowledge, this is the first study assessing radiomics coupled with machine learning from MRI-derived features to predict PD-L1 expression status in biopsy-proven triple negative breast cancers and comparing the performance of this approach with the performance of qualitative assessment by two radiologists. This pilot study shows that radiomics analysis coupled with machine learning of DCE-MRI is a promising approach to derive prognostic and predictive information and to select patients who could benefit from anti-PD-1/PD-L1 treatment. This technique could also be used to monitor PD-L1 expression, as it can vary over time and between different regions of the tumor, thus avoiding repeated biopsies. Abstract The purpose of this retrospective study was to assess whether radiomics analysis coupled with machine learning (ML) based on standard-of-care dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict PD-L1 expression status in patients with triple negative breast cancer, and to compare the performance of this approach with radiologist review. Patients with biopsy-proven triple negative breast cancer who underwent pre-treatment breast MRI and whose PD-L1 status was available were included. Following 3D tumor segmentation and extraction of radiomic features, radiomic features with significant differences between PD-L1+ and PD-L1− patients were determined, and a final predictive model to predict PD-L1 status was developed using a coarse decision tree and five-fold cross-validation. Separately, all lesions were qualitatively assessed by two radiologists independently according to the BI-RADS lexicon. Of 62 women (mean age 47, range 31–81), 27 had PD-L1− tumors and 35 had PD-L1+ tumors. The final radiomics model to predict PD-L1 status utilized three MRI parameters, i.e., variance (FO), run length variance (RLM), and large zone low grey level emphasis (LZLGLE), for a sensitivity of 90.7%, specificity of 85.1%, and diagnostic accuracy of 88.2%. There were no significant associations between qualitative assessed DCE-MRI imaging features and PD-L1 status. Thus, radiomics analysis coupled with ML based on standard-of-care DCE-MRI is a promising approach to derive prognostic and predictive information and to select patients who could benefit from anti-PD-1/PD-L1 treatment.
The Association between Oral Health-Related Quality of Life, Loneliness, Perceived and Objective Social Isolation—Results of a Nationally Representative Survey

The aim was to examine the association between oral health-related quality of life and loneliness and perceived as well as objective social isolation. Data were used from a nationally representative survey with n = 3075 (late Summer 2021). The established Oral Health Impact Profile (OHIP-G5) was used to quantify oral health-related quality of life. Moreover, established tools were used to quantify the outcome measures (De Jong Gierveld loneliness scale, Bude/Lantermann scale and Lubben Social Network Scale). It was adjusted for several covariates in regression analysis. Linear regressions showed that low oral health-related quality of life is associated with higher loneliness (B = 0.03, p < 0.001), higher perceived social isolation (B = 0.06, p < 0.001) and higher objective social isolation (B = 0.07, p < 0.05). Further regressions were performed (e.g., stratified by denture usage). Our study stressed the importance of low oral health-related quality of life for loneliness and social isolation (both perceived and objective). This knowledge is important to address individuals at risk. Future studies should clarify the underlying mechanisms.
Knowledge, attitude and behavior towards vaccinations among nursing- and health care students in Hesse. An observational study

Objective: Work-related vaccinations are recommended for employees in nursing and health care professions due to their elevated risk of infection because of job-related exposure. These vaccinations prevent work-related infections, protect patients and help to maintain the medical infrastructure. Thorough training and imparting of knowledge about vaccinations and work-related infections are essential pillars of the vaccination decision and thus for achieving a protective immune status. The present study examines the knowledge, attitudes and behavior of nursing- and health care students in Hesse regarding work-related infections and vaccinations. Methods: In spring 2018, seven nursing schools in Hesse took part in an anonymous survey study. A total of 690 surveys from students of various health care professions were included in the study. The content of the survey was based on the recommendations of the Standing Committee on Vaccination (STIKO), a literature review and sample questions from the World Health Organization (WHO) regarding “vaccine hesitancy”. Vaccination cards were also evaluated based on the STIKO recommendations concerning standard vaccinations and occupational vaccinations for health care workers. Results: The risk of acquiring a work-related infection was estimated to be quite high over all years of training. Gaps in knowledge were particularly evident in the area of vaccinations. Only three quarter of those surveyed believed that the effectiveness of vaccinations has been proven, and nearly 30% believed that the doses of the drugs used in vaccines were dangerous. Over 80% of the students had never had an influenza vaccination documented in their vaccination card. Conclusions: The knowledge about vaccinations imparted in the course of the education should be expanded. A special course on the subject of vaccinations and the immune system with practical elements could contribute to a better understanding of how vaccinations work and misunderstandings could be eliminated in early stages of the training through the dialog between the students and the teacher in the classroom and the occupational physician as part of preventive occupational health check-ups.
Herd Routines and Veterinary Advice Related to Dry-Cow Therapy and Treatment with Internal Teat Sealants in Dairy Cows

Simple Summary At the end of lactation, antibiotics (DCT) or internal teat sealants (ITS) can be used to treat or prevent mastitis in dairy cows. Recommendations on how to perform such treatments are available, but little is known about how well these are followed by farmers and veterinarians. To increase this knowledge, questionnaires about farmer routines and veterinary advice were sent to 2472 farmers and 517 veterinarians in Sweden. Fourteen percent of the farmers and 25% of the veterinarians responded. Among the farmers, 81% used DCT to some cows, 3% used DCT to all cows, and 16% did not use DCT at all. Almost all veterinarians prescribed DCT, most only to some cows in a herd while 8% sometimes recommended DCT to all cows in a herd. Most of the farmers did not use ITS and half of the veterinarians never prescribed ITS. Milking system and milk production, and post-graduate training and number of mastitis cases per month were associated with several of the answers by the farmers and veterinarians, respectively. Overall, many farmers and veterinarians followed the recommendations, but it was also clear that more communication is needed as well as an up-date of the recommendations. Abstract Dry-cow therapy with antibiotics (DCT) and treatment with internal teat sealants (ITS) are often used to control mastitis in dairy cows. However, the knowledge on farmer and veterinary compliance with recommendations for DCT and ITS is scarce. Thus, the main aim was to collect information on farmer routines and veterinary advice for such treatments. Associations with herd and veterinary variables were also studied. Web-based questionnaires including questions on demographics and the use of DCT and ITS were sent to 2472 farmers and 517 veterinarians in Sweden. The answers were summarized descriptively, and associations with demographics were evaluated using univariable regression models. The response rate was 14% for farmers and 25% for veterinarians. Among the farmers, 81% used selective DCT (SDCT), 3% used blanket DCT (BDCT), and 16% did not use DCT. Almost all (93%) veterinarians prescribed DCT and among those most recommended SDCT while 8% recommended BDCT. Eighty-two percent of the farmers did not use ITS and 45% of the veterinarians never prescribed ITS. Milking system and milk production, and post-graduate training and number of mastitis cases per month were associated with the largest numbers of farmer and veterinary answers, respectively. In conclusion, many farmer routines and veterinary advice complied with the recommendations available at the time, but a clear need for more education was also identified. The results also indicated that an up-date of the national recommendations was warranted.
Use of Collagen Membrane in the Treatment of Periodontal Defects Distal to Mandibular Second Molars Following Surgical Removal of Impacted Mandibular Third Molars: A Comparative Clinical Study

Simple Summary Regeneration of the wounded/lost tissues post-surgery often requires a meticulous treatment plan. The present study assessed the use of a collagen membrane to aid in the regeneration of lost periodontal tissues following extraction of the tooth. The results show that the collagen membrane promoted wound stabilization, as indicated by improvement in all assessed clinical parameters. Thus, collagen membrane can be used regularly in clinical practice post-extraction to augment wound healing. Abstract The study aims to assess the efficacy of using collagen membrane in the treatment of distal periodontal defects of mandibular second molars following the removal of mesioangularly or horizontally impacted mandibular third molars surgically. Forty sites in twenty patients with bilaterally impacted mandibular third molars (mesioangular or horizontal) were considered for the study. In 20 test sites (Group A), after surgical removal of the mandibular third molar, a resorbable collagen membrane barrier was placed on the distal aspect of the mandibular second molar to cover the post-surgical bone defect. In the other control 20 sites (Group B), the same surgical procedure was repeated without placing any membrane barrier. The clinical parameters recorded were Oral Hygiene Index Simplified (OHI-S), Probing pocket depth (PPD), Clinical attachment level (CAL), and radiographic assessment of alveolar bone level (ABL). OHI-S score of most of the patients was observed to be satisfactory. Group A was observed to achieve a statistically significant reduction in PPD, CAL, and ABL gain compared to Group B. The improvements indicated that the use of collagen membrane facilitates early wound stabilization and promotes primary closure of the defect. This recovery is achieved through its unique property to assist fibrinogenesis over osteoconduction. Further longitudinal studies are needed to confirm the present findings.
Do Cognitive Abilities Influence Physical and Mental Fatigue in Patients with Chronic Pain after Walking According to a Clinical Guideline for Physical Exercise?

The objective of this study is to explore the mediator role of cognitive fusion and chronic pain acceptance on the effects that the walking pattern, following an established clinical guideline for physical exercise, can have on fatigue (physical and mental) in patients with chronic pain. The sample consisted of a total of 231 women with fibromyalgia with a mean age of 56.91 years (Standard Deviation SD = 9.58 years, range 30−78 years). The results show a significant indirect effect of the walking pattern on both physical and mental fatigue through cognitive fusion and chronic pain acceptance. Specifically, walking predicted less cognitive fusion, which predicted greater chronic pain acceptance, which, in turn, predicted less mental and physical fatigue (Beta-B- = −0.04, Standard Error SE = 0.02, 95% Confidence Interval 95% CI = [−0.09, −0.02]; B = −0.09, SE = 0.05, 95% CI = [−0.22, −0,15], respectively). It can be concluded that the walking pattern is linked to both physical and mental fatigue through cognitive defusion and chronic pain acceptance. These cognitive abilities would allow fibromyalgia patients to perceive an improvement in both physical and mental fatigue by carrying out the walking pattern. Emphasizing the training of cognitive defusion and pain acceptance would improve the adherence of these patients to walking.
Alteration of the corpus callosum in patients with Alzheimer’s disease: Deep learning-based assessment

Background Several studies have reported changes in the corpus callosum (CC) in Alzheimer’s disease. However, the involved region differed according to the study population and study group. Using deep learning technology, we ensured accurate analysis of the CC in Alzheimer’s disease. Methods We used the Open Access Series of Imaging Studies (OASIS) dataset to investigate changes in the CC. The individuals were divided into three groups using the Clinical Dementia Rating (CDR); 94 normal controls (NC) were not demented (NC group, CDR = 0), 56 individuals had very mild dementia (VMD group, CDR = 0.5), and 17 individuals were defined as having mild and moderate dementia (MD group, CDR = 1 or 2). Deep learning technology using a convolutional neural network organized in a U-net architecture was used to segment the CC in the midsagittal plane. Total CC length and regional magnetic resonance imaging (MRI) measurements of the CC were made. Results The total CC length was negatively associated with cognitive function. (beta = -0.139, p = 0.022) Among MRI measurements of the CC, the height of the anterior third (beta = 0.038, p <0.0001) and width of the body (beta = 0.077, p = 0.001) and the height (beta = 0.065, p = 0.001) and area of the splenium (beta = 0.059, p = 0.027) were associated with cognitive function. To distinguish MD from NC and VMD, the receiver operating characteristic analyses of these MRI measurements showed areas under the curves of 0.65–0.74. (total CC length = 0.705, height of the anterior third = 0.735, width of the body = 0.714, height of the splenium = 0.703, area of the splenium = 0.649). Conclusions Among MRI measurements, total CC length, the height of the anterior third and width of the body, and the height and area of the splenium were associated with cognitive decline. They had fair diagnostic validity in distinguishing MD from NC and VMD.
COVID-19 Specific Immune Markers Revealed by Single Cell Phenotypic Profiling

COVID-19 is a viral infection, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized by a complex inflammatory process and clinical immunophenotypes. Nowadays, several alterations of immune response within the respiratory tracts as well as at the level of the peripheral blood have been well documented. Nonetheless, their effects on COVID-19-related cell heterogeneity and disease progression are less defined. Here, we performed a single-cell RNA sequencing of about 400 transcripts relevant to immune cell function including surface markers, in mononuclear cells (PBMCs) from the peripheral blood of 50 subjects, infected with SARS-CoV-2 at the diagnosis and 27 healthy blood donors as control. We found that patients with COVID-19 exhibited an increase in COVID-specific surface markers in different subsets of immune cell composition. Interestingly, the expression of cell receptors, such as IFNGR1 and CXCR4, was reduced in response to the viral infection and associated with the inhibition of the related signaling pathways and immune functions. These results highlight novel immunoreceptors, selectively expressed in COVID-19 patients, which affect the immune functionality and are correlated with clinical outcomes.
Voluntary wheel running behaviour as a tool to assess the severity in a mouse pancreatic cancer model

Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore, performed an evidence-based severity assessment of experimental procedures used in a pancreatic cancer model including surgical tumour induction and subsequent chemotherapeutic treatment via repeated intraperitoneal injections. Cancer cell injection into the pancreas was performed during a laparotomy under general anaesthesia. After a four-day recovery phase, mice received either drug treatment (galloflavin and metformin) or the respective vehicle substances via daily intraperitoneal injections. In addition to clinical scoring, an automated home-cage monitoring system was used to assess voluntary wheel running (VWR) behaviour as an indicator of impaired well-being. After surgery, slightly elevated clinical scores and minimal body weight reductions, but significantly decreased VWR behaviour were observed. During therapy, body weight declined in response to chemotherapy, but not after vehicle substance injection, while VWR activity was decreased in both cases. VWR behaviour differed between treatment groups and revealed altered nightly activity patterns. In summary, by monitoring VWR a high impact of repeated injections on the well-being of mice was revealed and substance effects on well-being were distinguishable. However, no differences in tumour growth between treatment groups were observed. This might be due to the severity of the procedures uncovered in this study, as exaggerated stress responses are potentially confounding factors in preclinical studies. Finally, VWR was a more sensitive indicator of impairment than clinical scoring in this model.
Modelling wind speed dependence in system reliability assessment using copulas

Owing to geographic relationships of wind farms, wind speeds at different wind sites show certain dependence between them, which may create a considerable impact on the reliability of power systems containing wind energy. A new technique for establishing multivariate distribution of wind speeds using copulas is presented to model wind speed dependence in the study. The separation between marginal distributions of each single wind speed and dependence structure is a basic feature of the copula method, which leads to the effectiveness and simplicity in dealing with the dependence in a multivariate distribution. The case studies using two actual wind speed data indicate that the copula model can give a valid representation of multiple wind speed series. The impact of wind speed dependence between two wind regimes on system reliability is illustrated using a commonly recognised reliability test system. The results confirm that system reliability will decrease as the wind speed dependence increases.
Nucleofection of Adipose Mesenchymal Stem/Stromal Cells: Improved Transfection Efficiency for GMP Grade Applications

Nucleofection (NF) is a safe, non-viral transfection method, compatible with Good Manufacturing Practice guidelines. Such a technique is useful to improve therapeutic effectiveness of adipose tissue mesenchymal stem cells (ASC) in clinical settings, but improvement of NF efficiency is mandatory. Supernatant rich in growth factors (SRGF) is a clinical-grade medium additive for ASC expansion. We showed a dramatically increased NF efficiency and post-transfection viability in ASC expanded in presence of SRGF (vs. fetal bovine serum). SRGF expanded ASC were characterized by increased vesicle endocytosis but lower phagocytosis properties. SRGF increased n-6/n-3 ratio, reduced membrane lipid raft occurrence, and lowered intracellular actin content in ASC. A statistical correlation between NF efficiency and lipid raft availability on cell membranes was shown, even though a direct relationship could not be demonstrated: attempts to selectively modulate lipid rafts levels were, in fact, limited by technical constraints. In conclusion, we reported for the first time that tuning clinical-grade compatible cell culture conditions can significantly improve ASC transfection efficiency by a non-viral and safe approach. A deep mechanistic characterization is extremely complex, but we can hypothesize that integrated changes in membrane structure and intracellular actin content could contribute to explain SRGF impact on ASC NF efficiency.
Resective, Ablative and Radiosurgical Interventions for Drug Resistant Mesial Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis of Outcomes

Objectives: One-third of individuals with focal epilepsy do not achieve seizure freedom despite best medical therapy. Mesial temporal lobe epilepsy (MTLE) is the most common form of drug resistant focal epilepsy. Surgery may lead to long-term seizure remission if the epileptogenic zone can be defined and safely removed or disconnected. We compare published outcomes following open surgical techniques, radiosurgery (SRS), laser interstitial thermal therapy (LITT) and radiofrequency ablation (RF-TC). Methods: PRISMA systematic review was performed through structured searches of PubMed, Embase and Cochrane databases. Inclusion criteria encompassed studies of MTLE reporting seizure-free outcomes in ≥10 patients with ≥12 months follow-up. Due to variability in open surgical approaches, only comparative studies were included to minimize the risk of bias. Random effects meta-analysis was performed to calculate effects sizes and a pooled estimate of the probability of seizure freedom per person-year. A mixed effects linear regression model was performed to compare effect sizes between interventions. Results: From 1,801 screened articles, 41 articles were included in the quantitative analysis. Open surgery included anterior temporal lobe resection as well as transcortical and trans-sylvian selective amygdalohippocampectomy. The pooled seizure-free rate per person-year was 0.72 (95% CI 0.66–0.79) with trans-sylvian selective amygdalohippocampectomy, 0.59 (95% CI 0.53–0.65) with LITT, 0.70 (95% CI 0.64–0.77) with anterior temporal lobe resection, 0.60 (95% CI 0.49–0.73) with transcortical selective amygdalohippocampectomy, 0.38 (95% CI 0.14–1.00) with RF-TC and 0.50 (95% CI 0.34–0.73) with SRS. Follow up duration and study sizes were limited with LITT and RF-TC. A mixed-effects linear regression model suggests significant differences between interventions, with LITT, ATLR and SAH demonstrating the largest effects estimates and RF-TC the lowest. Conclusions: Overall, novel “minimally invasive” approaches are still comparatively less efficacious than open surgery. LITT shows promising seizure effectiveness, however follow-up durations are shorter for minimally invasive approaches so the durability of the outcomes cannot yet be assessed. Secondary outcome measures such as Neurological complications, neuropsychological outcome and interventional morbidity are poorly reported but are important considerations when deciding on first-line treatments.