Search

European journal of cancer 154, 227-234 (2021). doi:10.1016/j.ejca.2021.05.026, Published by Elsevier, Amsterdam [u.a.]

Relapse of acute leukemia is a frequent complication with uncertain outcome and poorly defined risk factors. From 1621 patients entered into two prospective clinical trials (AML02; n = 740 and AML04; n = 881), 74.2% reached complete remission (CR) 1 after induction(s) and 59 patients after additional induction ± hematopoietic cell transplantation (HCT). Of the non-refractory patients, 48.4% with a median age of 63 (range 17–85) years relapsed. Relapses occurred within 6 months after CR in 46.5%, between 7 and 18 months in 38.7%, and after 18 months in 14.8% of patients. Relapse treatment resulted in CR2 in 39% of patients depending upon age (54.5% of ≤ 60 and 28.6% of > 60 years), duration of CR1, and treatment of relapse. Overall survival (OS) was 10.9 (7.4–16.2) %, but OS after HCT ± intensive chemotherapy (ICT) was 39.3% (31.8–48.6) at 5 years and not different in younger and older patients. Donor lymphocyte infusion ± chemotherapy and ICT alone resulted only in OS of 15.4% and of 5%, respectively. Independent favorable factors for OS were long CR1 duration, and HCT, while non-monosomal disease was beneficial for OS in elderly patients. Leukemia-free survival [LFS; 24.9 (19.5–31.7) % at 10 years] was affected by similar risk factors. In a competing risk model, the relapse incidence at 5 years was 53.5 ± 3.5% and the non-relapse mortality rate 21.7 ± 2.9%. Lower relapse incidence was observed in patents with HCT, long CR1 duration, and female gender. Risk factors for non-relapse mortality were HCT in younger and type of AML in elderly patients. In conclusion, allogeneic HCT ± IC improved the results in relapsed AML in younger and elderly patients. Increasing CR2 rates and HCT frequency will be the challenge for the next years. Relapse of the disease remains the major problem. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-021-04565-1.

Most Asteraceae species are pollinated by insects, mainly bees and butterflies, although pollination by birds has been documented and pollination by bats has been suggested for some species. Here, we investigated the pollination of Gongylolepis martiana, a species supposedly pollinated by bats. We assessed floral traits and visitors in a population of G. martiana in the Brazilian Amazon, measuring pollen removal from anthers and deposition on stigmas by diurnal and nocturnal visitors. Florets opened at dusk and lasted for 4 days, with the male phase starting on the first night and the female phase on the third night. Accumulated nectar per capitulum was 69.6 μl per night and sugar concentration was 15%. Nectar-feeding bats and hummingbirds contacted the sexual parts, but pollen removal and deposition were greater throughout the night than during the day, when Meliponini bees considerably reduced pollen availability. Other nocturnal visitors of G. martiana were rare, including nocturnal bees and moths that foraged for pollen and nectar, respectively. Our results support that nectarivorous bats are the main pollinators of G. martiana, confirming Vogel's hypothesis of bat pollination in Asteraceae, particularly in the genus Gongylolepis. Since anthesis and each sexual floral phase started in the evening, nectarivorous bats and diurnal bees caused additive priority effects, preventing hummingbirds from being efficient pollinators. The high density of flowering individuals of G. martiana in patches from white-sand forests likely increases bat attraction, while the small amount of nectar per plant favours cross-pollination.

Background: The kind of attitude expressed by the nurses may have significant effect on the recovery process of the patient and on their decision to avail treatment. It is anticipated that by exploring the attitudes of the nurses towards AUD patients and understanding the factors which influences these attitudes, more effective interventions can be developed to provide help and support to this group of patient and also to the nurses in being effective and appropriate in responding to the needs of this group of patient.Purpose: The study was conducted to explore the prevailing attitudes of nurses towards AUD patients, and to further explore the factors influencing these attitudes.Methods: A total of fifteen nurses from Jigme Dorji Wangchuck National Referral Hosiptal were recruited based on convenience and purposive sampling techniques. Qualitative approach was employed by means of conducting face to face in-depth interviews using open ended questions. The qualitative data was analyzed using thematic analysis method.Results: The findings from the study suggest that possessing adequate knowledge on alcohol and addiction, being regularly engaged with AUD patients or having few years of experience working with AUD patients were some of the factors which resulted in more positive attitudes among the nurses. On the contrary, insufficient skills and knowledge related to alcohol addiction and exhibition of aggressive behaviour by the patients could cause negative feelings and ultimately lead to negative attitudes.Conclusion: Therefore, it is of paramount importance that a curriculum on alcohol addiction is introduced in diploma and degree nursing courses offered in Bhutan.

Das maligne Melanom ist diejenige Form von Hautkrebs, an der die meisten Menschen sterben. Im Fruhstadium ist das Melanom gut behandelbar, eine Fruherkennung ist also lebenswichtig. Kritiker bemangeln, dass seit der bundesweiten Einfuhrung des Hautkrebs-Screenings haufiger Melanome diagnostiziert werden, die Sterblichkeit am malignen Melanom jedoch nicht zuruckgegangen ist. Sie fuhren dies vor allem auf Uberdiagnosen zuruck. Ein Grund ist die zum Teil komplexe Unterscheidung zwischen benignen und malignen Lasionen. Hinzu kommt, dass es auch Ubergangsformen zwischen eindeutig gut- oder bosartigen Lasionen geben kann, und dass einige bosartige Lasionen so wenig aggressiv wachsen, dass sie nie lebensbedrohlich geworden waren. Bisher kann mangels entsprechender Biomarker nicht festgestellt werden, bei welchen Melanomen dies der Fall ist. Auch die Progressionswahrscheinlichkeit eines In-situ-Melanoms zu einem invasiven Tumor kann bisher nicht sicher beurteilt werden. Die Konsequenzen fur uberdiagnostizierte benigne Lasionen sind unnotige psychische und korperliche Belastungen fur die Betroffenen und anfallende Therapiekosten. Umgekehrt konnen Unterdiagnosen zu gravierenden Einschrankungen der Prognose der Betroffenen und zur Notwendigkeit belastender(er) Therapien fuhren. Prazisere Diagnosemoglichkeiten konnten die Anzahl der korrekten Diagnosen erhohen. Hier haben sich in Studien mit auf kunstlicher Intelligenz basierenden Assistenzsystemen bereits erste Erfolge gezeigt, die allerdings noch in die klinische und pathologische Routine ubertragen werden mussen.

Malignant melanoma is the skin tumor that causes most deaths in Germany. At an early stage, melanoma is well treatable, so early detection is essential. However, the skin cancer screening program in Germany has been criticized because although melanomas have been diagnosed more frequently since introduction of the program, the mortality from malignant melanoma has not decreased. This indicates that the observed increase in melanoma diagnoses be due to overdiagnosis, i.e. to the detection of lesions that would never have created serious health problems for the patients. One of the reasons is the challenging distinction between some benign and malignant lesions. In addition, there may be lesions that are biologically equivocal, and other lesions that are classified as malignant according to current criteria, but that grow so slowly that they would never have posed a threat to patient's life. So far, these "indolent" melanomas cannot be identified reliably due to a lack of biomarkers. Moreover, the likelihood that an in-situ melanoma will progress to an invasive tumor still cannot be determined with any certainty. When benign lesions are diagnosed as melanoma, the consequences are unnecessary psychological and physical stress for the affected patients and incurred therapy costs. Vice versa, underdiagnoses in the sense of overlooked melanomas can adversely affect patients' prognoses and may necessitate more intense therapies. Novel diagnostic options could reduce the number of over- and underdiagnoses and contribute to more objective diagnoses in borderline cases. One strategy that has yielded promising results in pilot studies is the use of artificial intelligence-based diagnostic tools. However, these applications still await translation into clinical and pathological routine.

The combination of Imatinib (IM) and hydroxyurea (HU) was explored for the treatment of chronic myelogenous leukemia (CML).AfterAdditive specific inhibition of CML cells by IM/HU was detectedIM/HU combination was more potent in selectively inhibiting CML cells

Background Khat (Catha edulis) is a stimulant leaf khat comes from a tree which grows in countries bordering the Red Sea which are along the east coast of Africa and in west Asia. The psycho- active component within these leaves is cathinone. In Ethiopia, Khat is chewed routinely by users for its euphoric effects and as a recreational drug, and chewing khat has an important role as well in both traditional and religious ceremonies. In this case report, we describe the case of a 33-year-old male patient presented with psychotic symptoms after prolonged and heavy khat chewing. Case presentation Findings on psychiatric evaluation encompassing detailed history and mental state examination suggest khat induced psychotic disorder severe in full remission; khat use disorder, severe, in early remission. Conclusions This case demonstrates that the use of excess khat above 2 bundles for prolonged duration can manifest with psychotic episodes. A small number of case studies had supported a causal relationship between heavy khat use and psychosis or psychotic symptoms. There have been suicidal attempts and homicidal acts in those who used excess and prolonged use of khat. In our case, the improvement attributed to stopping the khat rather than taking antipsychotics. Therefore, we recommend an urgent social intervention to change the community norms regarding Khat use through psycho-education in media, institution and in person about the relationship between khat use and mental illness. In addition, we suggest the role of religious institutions on the management of khat use not be overlooked. Finally, this study makes a powerful argument for researchers and policy makers to do clinical study to settle a causal effect relation of khat on mental health.

Background and aims Immunosuppressed patients are at risk of severe infections with vaccination preventable diseases. We evaluated vaccination rate and immunity of children and adolescents with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). Methods Immunization rate of 329 children with IBD (n = 300) and AIH (n = 29) was assessed in seven German centres using vaccination certificates, history of chicken pox and by determining anti-varicella zoster virus (VZV) and anti-measles IgG antibodies. Results Of the total cohort 86% received long-term immunosuppression. Four doses of a hexavalent vaccine were documented in 89%, at least one dose of measles, mumps, and rubella (MMR) vaccination was documented in 325 (99%), with 300 (92%) receiving two doses. Anti-measles IgG concentrations were insufficient in 11% of the immunized patients. VZV vaccination was officially recommended in Germany since 2004, and implemented in 88% born from 2005 onwards. In patients born earlier VZV catch up vaccination only reached 25% (n = 67). Of 118 patients with documented VZV vaccination 25 (21%) did not display sufficient anti-VZV IgG. Of 198 patients with a history of chicken pox, six had undetectable anti-VZV IgG. Of 29 patients having neither had chicken pox nor VZV vaccination, 20 were found to have sufficient anti-VZV IgG. Conclusions In our cohort vaccination coverage for hexavalent and MMR vaccinations was good, but insufficient for VZV vaccination in patients born before 2005. Neither the vaccination certificate nor the history of chicken pox is reliable to predict VZV immunity indicating a need for serologic investigations and if needed vaccination before initiating immunosuppressive therapy.

Objective This paper provides an overview of our Military Biomarkers Research Study (MBRS) designed to assess whether biomarkers can be used to retrospectively assess deployment exposures and health impacts related to deployment environmental exposures. Methods The MBRS consists of four phases. Phase I was a feasibility study of stored sera. Phase II looks at associations between exposures and biomarkers. Phase III examines relationships of biomarkers and health outcomes, and Phase IV investigates in vitro biomarker changes associated with exposures to chemicals of interest. This paper briefly summarizes work already published and introduces the new reports contained in this supplement. Results Novel biomarkers were identified. These were associated with deployment exposures. Conclusions Significant associations were noted between deployment exposures, microRNA biomarkers and metabolomic biomarkers, and deployment health outcomes.

OBJECTIVE A study was conducted to identify metabolic-related effects of benzo(ghi)perylene (BghiP) and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD), on primary human fibroblasts to verify biological associations previously found in occupational health research. METHODS Human lung fibroblasts were exposed to BghiP or HpCDD and extracts were analyzed with a metabolome-wide association study to test for pathways and metabolites altered relative to controls. Gene expression was measured by quantitative-real time polymerase chain reaction. RESULTS Metabolic perturbations in amino-acid, oxidative stress, and fatty-acid pathways were observed for BghiP and HpCDD. HpCDD but not BghiP exposure increased gene expression of the amino acid transporters SLC7A5 and SLC7A11. CONCLUSIONS Exposure to polycyclic aromatic hydrocarbons (PAH) or dioxins perturbs amino acid pathways at physiologically relevant concentrations with different mechanisms. These findings imply an effect on central homeostatic systems by environmental exposures which could have implications on disease susceptibility.

Objective The potential health risks of deployment to sites with open burn pits remain poorly understood, in part, because personal exposure monitoring was not performed. Here, we investigated whether postdeployment serum samples contain biomarkers associated with exposure to burn pits. Methods A total of 237 biomarkers were measured in 800 serum samples from deployed and never-deployed subjects. We used a regression model and a supervised vector machine to identify serum biomarkers with significant associations with exposures and deployment. Results We identified 101 serum biomarkers associated with polycyclic aromatic hydrocarbons, dioxins or furans, and 54 biomarkers associated with deployment. Twenty-six of these biomarkers were shared in common by the exposure and deployment groups. Conclusions We identify a potential signature of exposure to open burn pits, and provide a framework for using postexposure sera to identify exposures when contemporaneous monitoring was inadequate.

Objective To develop a computational approach to link clinical outcomes with environmental exposures and molecular variations measured in Department of Defense (DOD) serum-repository samples. Methods International Classification of Diseases, Ninth Division codes which corresponded to cardiopulmonary symptoms for service personnel were selected to test for associations with deployment-related inhalation hazards and metabolomics, micro-RNA, cytokine, plasma markers, and environmental exposure analyses for corresponding samples. xMWAS and Mummichog were used for integrative network and pathway analysis. Results Comparison between 41 personnel exhibiting new cardio-pulmonary diagnoses after deployment start-date to 25 personnel exhibiting no symptoms identified biomarkers associated with cardiopulmonary conditions. Integrative network and pathway analysis showed communities of clinical, molecular, and environmental markers associated with fatty acid, lipid, nucleotide, and amino acid metabolism pathways. Conclusions The current proof of principle study establishes a computational framework for integrative analysis of deployment-related exposures, molecular responses, and health outcomes.

Objective To use high-resolution metabolomics (HRM) to identify metabolic changes in military personnel associated with deployment to Balad, Iraq, or Bagram, Afghanistan. Methods Pre- and post-deployment samples were obtained from the Department of Defense Serum Repository (DoDSR). HRM and bioinformatics were used to identify metabolic differences associated with deployment. Results Differences at baseline (pre-deployment) between personnel deployed to Bagram compared with Balad or Controls included sex hormone and keratan sulfate metabolism. Deployment to Balad was associated with alterations to amino acid and lipid metabolism, consistent with inflammation and oxidative stress, and pathways linked to metabolic adaptation and repair. Difference associated with deployment to Bagram included lipid pathways linked to cell signaling and inflammation. Conclusions Metabolic variations in pre- and post-deployment are consistent with deployment-associated responses to air pollution and other environmental stressors.

Adaptation of osteology and myology lead to the formation of hydrofoil foreflippers in Cheloniidae (all recent sea turtles except \(\textit{Dermochelys coriacea}\)) which are used mainly for underwater flight. Recent research shows the biomechanical advantages of a complex system of agonistic and antagonistic tension chords that reduce bending stress in bones. Finite element structure analysis (FESA) of a cheloniid humerus is used to provide a better understanding of morphology and microanatomy and to link these with the main flipper function, underwater flight. Dissection of a \(\textit{Caretta caretta}\) gave insights into lines of action, that is, the course that a muscle takes between its origin and insertion, of foreflipper musculature. Lines of action were determined by spanning physical threads on a skeleton of \(\textit{Chelonia mydas}\). The right humerus of this skeleton was micro-CT scanned. Based on the scans, a finite element (FE) model was built and muscle force vectors were entered. Muscle forces were iteratively approximated until a uniform compressive stress distribution was attained. Two load cases, downstroke and upstroke, were computed. We found that muscle wrappings (m. coracobrachialis magnus and brevis, several extensors, humeral head of m. triceps) are crucial in addition to axial loading to obtain homogenous compressive loading in all bone cross-sections. Detailed knowledge on muscle disposition leads to compressive stress distribution in the FE model which corresponds with the bone microstructure. The FE analysis of the cheloniid humerus shows that bone may be loaded mainly by compression if the bending moments are minimized.

ObjectiveThe objective of this study is to investigate the effect of food insecurity on the mental health of patients with tuberculosis (TB) in Ethiopia.DesignA prospective cohort study.SettingHealth centres and hospitals located in Jimma zone, Southwest Ethiopia.ParticipantsPatients with TB who had recently been diagnosed with TB and started directly observed treatment in the selected 26 health institutions from October 2017 to October 2018. A total of 268 patients were followed for 6 months and data were collected at recruitment and two follow-up visits (at 2 and 6 months). Patients with multidrug-resistant TB were not included in the study.Main outcome measuresMental distress was measured by the Self-Reporting Questionnaire-20 while food insecurity was assessed by using the Household Food Insecurity Access Scale.ResultsA total of 268 patients were recruited and there was no lost to follow-up. The prevalence of food insecurity at baseline, first and second follow-up was 49.3%, 45.9% and 39.6%, respectively. Of these, 28.0% of them reported severe food insecurity at baseline which declined to 23.5% at the end of the sixth month. Likewise, the prevalence of mental distress at baseline was 61.2% but declined to 22.0% at the second follow-up. At baseline, 77.3% of patients with mental distress reported severe food insecurity but declined to 46.0% at second follow-up. In the final model, severe food insecurity (OR 4.7, 95% CI 2.4 to 9.4) and being a government employee (adjusted odds ratio (aOR) 0.3, 95% CI 0.1 to 0.9) were associated with mental distress.ConclusionIn this study, food insecurity was associated with mental distress over the course of follow-up. Likewise, there is a high prevalence of food insecurity and mental distress among patients with TB on treatment. Therefore, early assessment and interventions for food insecurity may improve the mental health of patients with TB on treatment.

Fossil fuels are still one of the world’s major sources of energy. Because of their reduced availability in the future, however, renewable resources like biodiesel provide an attractive substitute to meet the growing demand for energy supply. Significant problems associated with the use of biodiesel are low its oxidation stability and a higher NOx emission tendency. It was shown by Bar et al. (2017) [1] that 2,4,6-tris-isopropylbenzoic acid hydrazide and benzoic hydrazide can act as antioxidants in distilled biodiesel. Simultaneously, hydrazides showed the potential to lower NOx emissions [2]. In this context, 14 additional hydrazides and four phenolic antioxidants were tested for their antioxidant properties by using the Rancimat method (DIN EN 15751) and PetroOxy method (DIN EN 16091). All hydrazides were employed at a concentration of 7.26 mmol/kg, which corresponds to approximately 1000 ppm of benzoic hydrazide. It is shown that all hydrazides increase the oxidation stability. The Rancimat tests verified that m-anisic hydrazide was most effective and extended the induction period by 16.0 h, whereas isonicotinic hydrazide showed a maximum induction period extension of 24.47 min in the PetroOxy tests. Differences in measurement principles, temperatures and oxygen partial pressures of both methods might explain the varying result. However, the phenolic antioxidant 2,2′-methylenebis(6-tert-butyl-4-methyl-phenol) increased the induction period from 3.7 h for neat RME to a maximum of 21.2 h in the Rancimat test and from 16.18 min to a maximum of 71.91 min in the PetroOxy test.

Purpose Metallic resurfacing implants have been developed for the treatment of early, small, condylar and trochlear osteoarthritis (OA) lesions. They represent an option for patients who do not fulfill the criteria for unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA) or are too old for biological treatment. Although clinical evidence has been collected for different resurfacing types, the in vivo post-operative knee kinematics remain unknown. The present study aims to analyze the knee kinematics in subjects with patient-specific episealer implants. This study hypothesized that patient-specific resurfacing implants would lead to knee kinematics close to healthy knees, resulting in medial pivot and a high degree of femoral rollback during flexion. Methods Retrospective study design. Fluoroscopic analysis during unloaded flexion–extension and loaded lunge was conducted at > 12 months post-surgery in ten episealer knees, and compared to ten healthy knees. Pre- and post-operative clinical data of the episealer knees were collected using a visual analog scale (VAS), the EQ 5d Health, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaires. Results A consistent medial pivot was observed in both episealer and healthy knees. Non-significant differences were found in the unloaded (p = 0.15) and loaded (p = 0.51) activities. Although lateral rollback was observed in both groups, it was significantly higher for the episealer knees in both the unloaded (p = 0.02) and loaded (p = 0.01) activities. Coupled axial rotation was significantly higher in the unloaded (p = 0.001) but not in the loaded (p = 0.06) activity in the episealer knees. Improved scores were observed at 1-year post-surgery in the episealer subjects for the VAS (p = 0.001), KOOS (p = 0.001) and EQ Health (p = 0.004). Conclusion At 12 month follow-up, a clear physiological knee kinematics pattern of medial pivot, lateral femoral rollback and coupled axial external femoral rotation during flexion was observed in patients treated with an episealer resurfacing procedure. However, higher femoral rollback and axial external rotation in comparison to healthy knees was observed, suggesting possible post-operative muscle weakness and consequent insufficient stabilization at high flexion.

Background: Clinicians and pathologists traditionally use patient data in addition to clinical examination to support their diagnoses. Objectives: We investigated whether a combination of histologic whole slides image (WSI) analysis based on convolutional neural networks (CNNs) and commonly available patient data (age, sex and anatomical site of the lesion) in a binary melanoma/nevus classification task could increase the performance compared with CNNs alone. Methods: We used 431 WSIs from two different laboratories and analysed the performance of classifiers that used the image or patient data individually or three common fusion techniques. Furthermore, we tested a naive combination of patient data and an image classifier: for cases interpreted as ‘uncertain’ (CNN output score

ObjectivesIn Ethiopia, little is known about the association between substance use disorders and adherence to antituberculosis (anti-TB) medications. Therefore, the objective of this study was to assess the effect of substance use disorders on adherence to anti-TB medications in Southwest Ethiopia.DesignProspective cohort study.SettingsPatients were recruited from 22 health centres and four hospitals in Southwest Ethiopia.ParticipantsThis study was conducted among 268 patients with TB, aged 18–80 in Southwest Ethiopia between October 2017 and October 2018. At baseline, patients who were exposed substance use disorders (134 patients) and unexposed to substance use disorders (134 patients) were recruited. Patients were followed for 6 months, and data were collected on three occasions.Main outcome measureAdherence to anti-TB medications.ResultsPatients with substance use disorders had consistently higher prevalence of non-adherence than those without, 16.4% versus 3.0% at baseline, 41.7% versus 14.4% at 2-month follow-up and 45.7% versus 10.8% at 6-month follow-up assessments. Patients with khat use disorder were 3.8 times more likely to be non-adherent to anti-TB medications than patients without khat use disorder (Adjusted odds ratio (aOR)=3.8, 95% CI 1.8 to 8.0). Patients who had alcohol use disorder (AUD) were also 3.2 times likely to have poor adherence compared with their counterparts (aOR=3.2, 95% CI 1.6 to 6.6). In addition, being educated (aOR=4.4, 95% CI 1.7 to 11.3), and being merchant (aOR=6.1, 95% CI 1.2 to 30.8) were associated with non-adherence to anti-TB medications.ConclusionKhat and AUDs predict greater likelihood of non-adherence to anti-TB medication. This implies the need to integrate the management for substance use disorders into the existing TB treatment services.

Background: Multiple studies have compared the performance of artificial intelligence (AI)–based models for automated skin cancer classification to human experts, thus setting the cornerstone for a successful translation of AI-based tools into clinicopathological practice. Objective: The objective of the study was to systematically analyse the current state of research on reader studies involving melanoma and to assess their potential clinical relevance by evaluating three main aspects: test set characteristics (holdout/out-of-distribution data set, composition), test setting (experimental/clinical, inclusion of metadata) and representativeness of participating clinicians. Methods: PubMed, Medline and ScienceDirect were screened for peer-reviewed studies published between 2017 and 2021 and dealing with AI-based skin cancer classification involving melanoma. The search terms skin cancer classification, deep learning, convolutional neural network (CNN), melanoma (detection), digital biomarkers, histopathology and whole slide imaging were combined. Based on the search results, only studies that considered direct comparison of AI results with clinicians and had a diagnostic classification as their main objective were included. Results: A total of 19 reader studies fulfilled the inclusion criteria. Of these, 11 CNN-based approaches addressed the classification of dermoscopic images; 6 concentrated on the classification of clinical images, whereas 2 dermatopathological studies utilised digitised histopathological whole slide images. Conclusions: All 19 included studies demonstrated superior or at least equivalent performance of CNN-based classifiers compared with clinicians. However, almost all studies were conducted in highly artificial settings based exclusively on single images of the suspicious lesions. Moreover, test sets mainly consisted of holdout images and did not represent the full range of patient populations and melanoma subtypes encountered in clinical practice. info:eu-repo/semantics/publishedVersion

Tropical and subtropical plants provide to pollinators a range of nutritive and non-nutritive materials as alternative to pollen and nectar, including resins, which are gathered by females of several groups of social and solitary bees. Although resin-like material has previously been recorded in Maxillariinae, these investigations generally did not present data relating to pollinators. In fact, the collection of resins has never been recorded elsewhere in orchids. The aim of this paper was to provide a detailed study of the reproductive biology of an Amazonian Heterotaxis, H. superflua, based on records of flowering phenology, floral morphology, pollinator behavior and breeding system. Heterotaxis superflua offers resin-like material to pollinators and is pollinated by a single species of stingless bee. The resin is a heterogeneous material rich in mucilage, starch and sugars, while lipoidal substances occur as small droplets. Chemical analyses confirm the presence of sugar, which explain the presence of reducing sugars and mucilage detected in the histochemical investigations. Our data also showed the Heterotaxis is self-compatible and pollinator dependent. This study demonstrates for the first time the collection of resin-like material in orchids. The gathering of resin is frequently associated with the nest construction, since this material is considered to be a water-repellent and has anti-pathogen chemical properties. Despite offering of a floral reward, fruit set under natural conditions is lower than for experimental pollinations, suggesting limited pollen flow within the population.

Background The apparently physiological kinematics of the bicruciate-stabilized total knee arthroplasty (BCS TKA) systems have been attributed to the anterior and posterior post-cam mechanism. Although comparisons between TKA designs with either a retained or a sacrificed cruciate ligament have been conducted, we are not aware of any analyses of 2 implants with identical bearing geometry but different cruciate-ligament strategies under equal loading conditions. Knowledge about the kinematic effect of the different cruciate ligament strategies would potentially be valuable to facilitate preoperative planning and decision-making with regard to selecting the most appropriate implant for a patient. Methods This retrospective study included 20 patients: 10 treated with a BCS and 10 treated with a cruciate retaining (CR) TKA. Fluoroscopic analyses during high-flexion activities (unloaded flexion-extension and loaded lunge) were conducted at 24 months postsurgery. All patients completed the Knee Society Score, Forgotten Joint Score, and High-Flexion Knee Score questionnaires preoperatively and postoperatively. Results The BCS cohort showed greater femoral lateral rollback as well as a medial pivot in both activities. In contrast, the CR cohort showed a significant increase in anterior translation on the medial compartment as well as almost absent femoral lateral rollback. Higher clinical scores were observed in the BCS cohort. Conclusions At 24 months postsurgery, despite equal bearing geometry, retention of the posterior cruciate ligament in the CR cohort apparently was insufficient to reduce anterior shift. The BCS cohort showed expected knee joint kinematics; however, the kinematics in this cohort could eventually benefit from a smooth transition between the interchanging surfaces. Further investigation should be focused on the surgical technique and its interaction with the TKA design. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Die eosinophile Gastroenteropathie ist eine allergengetriggerte, immunvermittelte, lokal-entzundliche Erkrankung des oberen und unteren Gastrointestinaltrakts, die immer haufiger bereits im Kindes- und Jugendalter diagnostiziert wird. Erweist sich die Erkrankung als therapierefraktar gegenuber gangigen Behandlungsoptionen, kann dies zu einer erheblichen Einschrankung der Lebensqualitat fuhren. Im Rahmen eines „case report“ wird uber die erste erfolgreiche Behandlung mit Dupilumab bei einem 16-jahrigen Jugendlichen mit bisher therapierefraktarer eosinophiler Gastroenteropathie berichtet.

Journal of the American Academy of Dermatology : JAAD 86(3), 640-642 (2022). doi:10.1016/j.jaad.2021.02.009, Published by Elsevier, Amsterdam [u.a.]

Background and aims Children with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS). Methods This prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination. Tolerability and safety after immunization were assessed by questionnaire. The immune response was measured by the VZV-IgG concentration, relative avidity index (RAI), and specific lymphocyte proliferative response. Results A total of 29 VZV vaccinations were performed in 17 seronegative patients aged 3–16 years (IBD n = 15, AIH n = 2). Eight patients received high-intensity immunosuppression, another six low-intensity immunosuppression, and three patients interrupted IS before VZV vaccination. All 29 vaccinations were well tolerated; only minor side effects such as fever and abdominal pain, were reported in two patients. One patient experienced a flare of Crohn’s disease the day after vaccination. The VZV-IgG-concentration increased significantly (p = 0.018) after vaccination, and a specific lymphocyte response towards VZV in vitro was detected in all tested patients which correlated with the RAI (r = 0.489; p = 0.078). Conclusions VZV vaccination was well tolerated, safe and immunogenic in children receiving ongoing IS due to IBD and AIH. Ensuring immunoreactivity by clinical and laboratory parameters, rather than the type and dosage of IS, is a reasonable approach to decide on live-attenuated virus vaccinations in immunosuppressed children (German clinical trials DRKS00016357).

Accurate localization of complex human experiences such as emotions, dreaming, creativity, and consciousness to specific cerebral structures or neural networks has remained elusive despite technological advances. We report the use of acute deep brain stimulation (DBS) to evoke behavioral and emotional effects by applying electrical stimulation (ES) at various voltage strengths to the basolateral and central subnuclei of the amygdala in addition to the head of hippocampus (HC) for two subjects with medically refractory post-traumatic stress disorder (PTSD). Our results suggest that the amygdala could be a node in a neural network responsible for the generation of complex vivid mental imagery and integrated sensory experiences similar to John Hughlings Jackson's "dreamy state" and "double consciousness," which have been classically associated with temporal lobe epilepsy during uncinate seizures. That we were able to elicit similar vivid, dynamic, complex, bizarre, and original mental imagery with ES in non-epileptic subjects suggests that Jackson's seizure related "dreamy state" and "double consciousness" may arise from heightened innate brain mechanisms with the amygdala acting as a node in the neural network responsible for physiologic dreaming and creative functions. Furthermore, our subjects experienced different emotions with different stimulation strengths at various electrode contacts. Our results suggest that higher voltage stimulation of the amygdala and HC at 4-5 V leads to predominantly negative responses and 2-4 V stimulation showed inversely coupled positive and negative responses of the amygdala in either hemisphere which may imply hemispheric dominance of emotional valences without relation to handedness. Due to the unique and complex responses dependent on location and strength of stimulation, we advise that all patients receiving DBS of the amygdala undergo acute stimulation mapping in a monitored setting before selecting therapeutic parameters for chronic stimulation.

Precast concrete girders on bearing pads are subjected to instability depending on several variables such as span length, initial imperfections and bearing pads behavior. On this paper, numerical models are developed in order to assess the instability limit loads and the rotational stiffnesses of the pads in many combinations of span length, cross section of the girder and lateral sweep. The lift off phenomenon is considered in each analysis by a bearing pad model composed by springs with compression only behavior, with good results in comparison with the experimental values of the technical literature. The increase in spans and initial imperfections causes a decrease in the rollover limit load. The lift off effect is aggravated as the lateral eccentricities increase. In the analyzed combinations, the reduction of the rotational stiffness is about 37% for the critical situation, which span length about 40 m and lateral sweep of L/300, with loss of contact between 50% and 60%.

Background Deep brain stimulation (DBS) has been used for chronic pain for decades, but its use is limited due to a lack of reliable data about its efficacy for specific indications. Objective To report on 9 patients who underwent DBS for facial pain, with a focus on differences in outcomes between distinct etiologies. Methods We retrospectively reviewed 9 patients with facial pain who were treated with DBS of the ventral posteromedial nucleus of the thalamus and periventricular gray. We report on characteristics including facial pain etiology, complications, changes in pain scores using the visual analog scale (VAS), and willingness to undergo DBS again. Results Nine patients underwent DBS for either poststroke, post-traumatic, postherpetic, or atypical facial pain. Eight patients (89%) were permanently implanted. Seven patients had sufficient follow-up (mean 40.3 mo). Of these 7 patients, average VAS scores decreased from 9.4 to 6.1 after DBS. The average decrease in VAS was 55% for post-traumatic facial pain (2 patients), 45% for poststroke (2 patients), 15% for postherpetic neuralgia (2 patients), and 0% for atypical facial pain (1 patient). Three of the 8 implanted patients (38%) had complications which required removal of hardware. Only 2 of 7 (29%) patients met classical criteria for responders (50% decrease in pain scores). However, among 4 patients who were asked about willingness to undergo DBS again, all expressed that they would repeat the procedure. Conclusion There is a trend towards improvement in pain scores following DBS for facial pain, most prominently with post-traumatic pain.

PURPOSE: The sudden rise in the injury incidence during adolescence is also evident in soccer-related injuries to the groin. Submaximal passing applies high stress on the adductor muscles and pubic symphysis and is therefore likely to be connected to the occurrence of groin injuries. Therefore, the purpose of the study was to compare hip joint kinematics and adductor muscle forces of different adolescent age groups during submaximal soccer passing. METHODS: Sixty participants, in four groups, younger than 12, 15, 16. and 23 yr (U12, U15, U16, U23), were analyzed. A Footbonaut, equipped with a 3D motion capture system consisting of 16 cameras, was used to capture kinematic data of short passes. Inverse dynamic analysis was performed to calculate muscle forces of 10 passes of each subject. RESULTS: The U15 group showed reduced angular velocities. A rise in hip adductor muscle forces was evident from the youngest group up to the oldest groups. The largest increase (49%) was found between U12 and U15. Lower-limb mass was identified as the best predictor for the increasing adductor force. CONCLUSIONS: The reduced angular velocities of the U15 and the increase in muscle forces between all age groups were attributed to the increasing segment masses and length. This increases the moments of inertia of the leg segments thereby demanding higher forces to accelerate the segments. Most likely, the stress put upon the adductors apophyses increases during adolescence, as tendons are known to adapt slower than muscles, increasing the risk for overuse injuries. Coaches could use lower-limb mass as an indicator for fast increases in the force demand to identify players who would benefit from a reduced training volume.

Expression of the disialoganglioside GD2 has been identified as a marker antigen associated with a breast cancer stem-like cell (BCSC) phenotype. Here, we report on the evaluation of GD2 as a BCSC-specific target antigen for immunotherapy. GD2 expression was confirmed at variable degree in a set of breast cancer cell lines, predominantly in triple-negative breast cancer (TNBC). To target GD2, we have generated novel anti-GD2 chimeric antigen receptors (GD2-CAR), based on single-chain variable fragments (scFv) derived from the monoclonal antibody (mAb) ch14.18, also known as dinutuximab beta. Expressed on T cells, GD2-CARs mediated specific GD2-dependent T-cell activation and target cell lysis. In contrast to previously described GD2-CARs, no signs of exhaustion by tonic signaling were found. Importantly, application of GD2-CAR expressing T cells (GD2-CAR-T) in an orthotopic xenograft model of TNBC (MDA-MB-231) halted local tumor progression and completely prevented lung metastasis formation. In line with the BCSC model, GD2 expression was only found in a subpopulation (4-6%) of MDA-MB-231 cells before injection. Significant expansion of GD2-CAR-T in tumor-bearing mice as well as T-cell infiltrates in the primary tumor and the lungs were found, indicating site-specific activation of GD2-CAR-T. Our data strongly support previous findings of GD2 as a BCSC-associated antigen. GD2-targeted immunotherapies have been extensively studied in human. In conclusion, GD2-CAR-T should be considered a promising novel approach for GD2-positive breast cancer, especially to eliminate disseminated tumor cells and prevent metastasis formation.

The knee joint center of rotation is altered in the absence of the anterior cruciate ligament, which leads to substantially higher variance in kinematic patterns. To overcome this, total knee arthroplasty (TKA) designs with a high congruency in the lateral compartment have been proposed. The purpose of this study was to analyze the influence of a lateral pivot TKA-design on in-vivo knee joint kinematics. Tibiofemoral motion was retrospectively addressed in 10 patients during unloaded flexion-extension and loaded lunge using single plane fluoroscopy. During the unloaded flexion-extension movement, the lateral condyle remained almost stationary with little rollback at maximum flexion. The medial condyle exhibited anterior translation during the whole flexion cycle. During the loaded lunge movement, a higher degree of rollback compared to the unloaded activity was observed on the lateral condyle, whereas the medial condyle remained almost stationary. The results showed a clear lateral pivot during the unloaded activity, reflective of the implant's geometric characteristics, and a change to a medial pivot and a higher lateral rollback during the weight-bearing conditions, revealing the impact of load and muscle force. It remains unclear if the kinematics with a lateral TKA design could be considered as physiological, due to the limited knowledge available on native knee joint kinematics.

Due to low stiffness to lateral bending, long prestressed precast concrete beams are subject to lateral instability. For this reason, the safety analysis of these beams during the transitory stages of transport, lifting and assembly is fundamental. This work presents a nonlinear analytical model for the parametrical analysis of beams on bearing pads in their definitive location, without the effective connections being made. Such a solution determines a critical load of instability and considers the geometry of the cross-section, physical characteristics of the materials as well as geometric imperfections. A parametrical simulation is performed for the initial eccentricity, the initial rotation of the beam, concrete resistance, bearing pads dimensions, and the cross-section of the beam. The results show that the parameters of most considerable influence on beam stability are rotation stiffness of the bearing and the geometric characteristics of the cross-section of the beam, which can result in a reduction of about 50% of the critical rollover load. In addition, the cracking load may, in some cases, be close to the critical toppling load. resumo: Devido à baixa rigidez à flexão lateral, vigas pré-moldadas protendidas de concreto longas e esbeltas estão sujeitas aos riscos de instabilidade lateral. Nestes termos, é fundamental analisar a segurança dessas vigas durante as fases transitórias de transporte, içamento e montagem. Este trabalho apresenta um modelo analítico não linear para análise paramétrica de vigas já posicionadas em seu local definitivo sobre almofadas de apoio, quando as ligações ainda não foram efetivadas. A força crítica de instabilidade lateral foi calculada considerando a geometria da seção transversal, as características físicas dos materiais, bem como imperfeições geométricas. Uma simulação paramétrica foi feita para a influência da excentricidade lateral inicial da viga, a rotação inicial do apoio, a resistência à compressão do concreto, as dimensões do aparelho de apoio e a seção transversal da viga. Os resultados mostram que os parâmetros de maior influência na estabilidade da viga foi a rigidez a rotação do apoio e as características geométricas da seção transversal da viga, podendo resultar em redução da ordem de 50% da força crítica de tombamento. Além disso, a força de início da fissuração, em alguns casos, pode estar bem próxima a força crítica de tombamento.