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Enormous scientific and technological development has brought the requirement of appropriate implementation of technologies into the educational process. The use of educational technologies is determined by several factors. One of them are teachers, for whom the effective integration of educational technologies is still a challenging task. Teachers' attitude toward technology makes a crucial point in this issue. An important element that determines teachers' interest for using educational technologies is their perception of the effectiveness in the educational process and also their skills in using technology. This study presents the results of a research, which's aim was to identify whether there are any statistically significant differences between science teachers' self-efficacy and self-assessment, based on the TPACK frame, and their attitudes toward using technologies in educational processes. Science teachers rated their own TPACK moderately positive. They had the highest mean scores on the component items focusing on pedagogical knowledge and content knowledge. Lower mean scores were recorded in the components associated with technological knowledge, where teachers perceiving their technological content knowledge to be the worst one. [ABSTRACT FROM AUTHOR]

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly referred to as nonalcoholic fatty liver disease, impacts 30% of the global population. This educational pilot focused on the role primary care providers may play in the delivery of guidelines-based metabolic dysfunction-associated steatohepatitis (MASH) care. Objective: Accelerate the application of guidelines-based MASH care pathways to clinical workflows. Methods: A panel of six hepatologists was convened in 2021 to develop the care pathway and the subsequent pilot occurred between 2022 – 2023. The pilot was conducted across three U.S. health systems: Boston Medical Center (Boston), Methodist Health System (Dallas), and Weill Cornell Medicine (New York). Clinicians were educated on the care pathway and completed baseline/follow-up assessments. 19 primary care clinicians participated in the educational pilot baseline assessment, nine primary care clinicians completed the two-month assessment, and 15 primary care clinicians completed the four-month assessment. The primary endpoint was to assess clinician-reported adherence to and satisfaction with the care pathway. The pilot was deemed exempt by the Western Consensus Group Institutional Review Board. Results: At baseline, 38.10% (n = 8) of respondents felt they had received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and 42.86% (n = 9) had not referred any patients suspected of metabolic dysfunction-associated liver disease to hepatology within a month. At four months post-intervention, 79% (n = 15) of respondents agreed or strongly agreed they received sufficient training on when to refer a patient suspected of metabolic dysfunction-associated liver disease to hepatology, and there was a 25.7% increase in self-reported adherence to the institution's referral guidelines. Barriers to care pathway adherence included burden of manually calculating fibrosis-4 scores and difficulty ordering non-invasive diagnostics. Conclusions: With therapeutics anticipated to enter the market this year, health systems leadership must consider opportunities to streamline the identification, referral, and management of patients with metabolic dysfunction-associated steatohepatitis. Electronic integration of metabolic dysfunction-associated steatohepatitis care pathways may address implementation challenges. [ABSTRACT FROM AUTHOR]

Summary: Background: The quantitative HepQuant SHUNT test of liver function and physiology generates a disease severity index (DSI) that correlates with risk for clinical complications, such as large oesophageal varices (LEVs). A derivative test, HepQuant DuO, generates an equivalent DSI and simplifies testing by requiring only oral administration of the test solution and two blood samples at 20 and 60 min. Aims: Since the DSIs measured from DuO and SHUNT are equivalent, we compared the diagnostic performance for large oesophageal varices (LEVs) between the DSIs measured from DuO and SHUNT tests. Methods: This study combined the data from two prospectively conducted US studies: HALT‐C and SHUNT‐V. A total of 455 subjects underwent both the SHUNT test and esophagogastroduodenoscopy (EGD). Results: DSI scores correlated with the probability of LEVs (p < 0.001) and demonstrated a stepwise increase from healthy lean controls without liver disease to subjects with chronic liver disease and no, small or large varices. Furthermore, a cutoff of DSI ≤ 18.3 from DuO had a sensitivity of 0.98 (missing only one case) and, if applied to the endoscopy (EGD) decision, would have prevented 188 EGDs (41.3%). The AUROC for DSI from DuO did not differ from that of the reference SHUNT test method (0.82 versus 0.81, p = 0.3500). Conclusions: DSI from HepQuant DuO links liver function and physiology to the risk of LEVs across a wide spectrum of patient characteristics, disease aetiologies and liver disease severity. DuO is minimally invasive, easy to administer, quantitative and may aid the decision to avoid or perform EGD for LEVs. [ABSTRACT FROM AUTHOR]

We give exact and asymptotic counting results for the number of galled networks and reticulation-visible networks with few reticulation vertices. Our results are obtained with the component graph method, which was introduced by L. Zhang and his coauthors, and generating function techniques. For galled networks, we in addition use analytic combinatorics. Moreover, in an appendix, we consider maximally reticulated reticulation-visible networks and derive their number, too. [ABSTRACT FROM AUTHOR]

Background: Shorter hip stems have shown promising mid-term results but lack long-term data. High rates of distal cortical hypertrophy (CH) have been described, suggesting a more diaphyseal load transmission. This study aimed to determine patient-specific and surgery-related factors influencing CH and their impact on 10-year outcomes. Methods: It included 100 consecutive total hip arthroplasties (THAs) using the Fitmore stem (Zimmer, Warsaw, Indiana), with clinical and radiographic follow-ups at 1, 2, 5, and at least 10 years post-surgery. Results: No revisions were performed due to aseptic loosening after a mean of 11.6 years (range: 10–13.5 years). CH was observed in 26% of hips, primarily in Gruen zones 3 and 5. There was no significant difference in the Harris Hip Score between patients with and without CH. Larger stem sizes and greater axial subsidence significantly correlated with CH occurrence (OD 1.80, (1.13–1.92), p = 0.004; OD 1.47, (1.04–2.08), p = 0.028). The Fitmore stem demonstrated excellent survival rates and favorable outcomes over 10 years. Conclusions: Despite a lower CH rate compared to other studies, significant correlations with stem size and subsidence were identified. This study underscores the importance of patient selection and achieving high primary stability to maintain the metaphyseal anchoring concept. [ABSTRACT FROM AUTHOR]

The paper presents the framework and discusses the outcomes of the "Mass Movements in Germany" project—a collaboration of five State Geological Surveys (SGSs) and the Federal Institute for Geosciences and Natural Resources (BGR) to conduct a feasibility study for a nationwide landslide susceptibility map in Germany using harmonized datasets. Therefore, distinct methods representing heuristic, physically-based, and data-driven approaches were employed. In 14 consecutive modeling cases, we investigated parameter selection and preparation, model building, evaluation, and transferability issues. The results show that nationally harmonized datasets, deemed high-quality, exhibited data generalization at regional scales, affecting the reliability of the landslide susceptibility patterns. While using regional datasets on larger scales mitigated some generalization effects, heterogeneities in inventory datasets among distinct federal states pose challenges in creating a nationwide applicable model. Heterogeneous data require locally adjusted model designs affecting the model's transferability and comparability of data-driven models across large regions. Heuristic methods operate without observational data but require in-depth knowledge of the regional-geological conditions by involving expert groups rather than single experts. The physically-based model shows promising results with parametrization based on the pedotransfer functions and soil database supplementing the national soil map. However, this approach is limited to shallow translational landslides. Thus, considering all mass movement types, a single comprehensive approach for creating a nationwide landslide susceptibility map for Germany is currently not feasible. Close collaboration and further harmonization of datasets and methods involving all SGSs are needed. [ABSTRACT FROM AUTHOR]

Introduction: Spatial hearing is most accurate using both ears, but accuracy decreases in persons with asymmetrical hearing between ears. In participants with deafness in one ear but normal hearing in the other ear (single-sided deafness [SSD]), this difference can be compensated by a unilateral cochlear implant (CI). It has been shown that a CI can restore sound localization performance, but it is still unclear to what extent auditory spatial discrimination can be improved. Methods: The present study investigated auditory spatial discrimination using minimum audible angles (MAAs) in 18 CI-SSD participants. Results were compared to 120 age-matched normal-hearing (NH) listeners. Low-frequency (LF) and high-frequency (HF) noise bursts were presented from 4°, 30°, and 60° azimuth on the CI side and on the NH side. MAA thresholds were tested for correlation with localization performance in the same participants. Results: There were eight good performers and ten poor performers. There were more poor performers for LF signals than for HF signals. Performance on the CI side was comparable to performance on the NH side. Most difficulties occurred at 4° and at 30°. Eight of the good performers in the localization task were also good performers in the MAA task. Only the localization ability at 4° on the CI side was positively correlated with the MAA at that location. Conclusion: Our data suggest that a CI can restore localization ability but not necessarily auditory spatial discrimination at the same time. The ability to discriminate between adjacent locations may be trainable during rehabilitation to enhance important auditory skills. [ABSTRACT FROM AUTHOR]

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Simple Summary: Patients with Hodgkin lymphoma show excellent survival rates, emphasizing the importance of the long-term side effects of the treatment itself. This analysis aims at a cardiopulmonary risk evaluation in the context of radiation treatment for early-stage Hodgkin lymphoma using normal tissue complication probability calculations. Overall, a low cardiopulmonary risk was estimated, not exceeding 2%. Concerning radiation dose, 30 Gy is associated with consistently higher risks as compared to 20 Gy. Further individualization of treatment will be attempted in the future. Purpose: Hodgkin lymphoma is a hematologic malignancy with excellent outcomes even in advanced stages. Consequently, the importance of treatment-associated toxicity increases. However, the exact estimation of individualized rates is difficult due to different disease extents, treatment strategies and techniques. The following analysis aims at a pre-treatment estimation of relevant mediastinal toxicities. Methods: Normal tissue complication probability calculations were used to evaluate the toxicity rates for the heart, lungs and female breast of patients undergoing radiotherapy for early-stage Hodgkin lymphoma. Overall, 45 Patients of the HD16 and HD17 trials by the German Hodgkin study group were included and risks were calculated using the Lyman–Kutcher–Burman model. Results: The median values for pericarditis, pneumonitis and fibrosis of the left or right breast were 0.0%, 0.0%, 0.7% and 0.6% in the HD16 cohort, and 0.0%, 0.1%, 1.1% and 1.0% in the HD17 cohort, respectively. Correspondingly, none of the included patients displayed any of the evaluated toxicities during clinical follow-up. The use of higher doses (30 Gy) in the HD17 cohort led to an increase in toxicity compared to the HD16 cohort (20 Gy). No significant influence of the planning target volume size or the radiation technique could be found in this study. Conclusion: Both the clinically observed and calculated toxicity rates corroborate the overall low-risk profile of radiotherapy for Hodgkin lymphoma. Further treatment individualization will be attempted in the future. [ABSTRACT FROM AUTHOR]

This introduction to this special issue of Comparative American Studies outlines the significance of animals - in particular animal representations - to the US imagination. As the two national animals, the bald eagle and the American bison encapsulate some of the paradoxes characteristic of American animals: charged with symbolic force but nearly driven to extinction - only to become part of American success stories of conservation and restoration. [ABSTRACT FROM AUTHOR]

Institutionalized supporter participation is a traditional part of German professional football clubs. Due to commercialization, some challenging issues have arisen in recent years regarding supporter participation. To develop new approaches for improving participation, the study uses a social sustainability perspective, illustrating that social sustainability elements help to develop and structure the potential for improvement of participation in German professional football. By identifying and discussing links between social sustainability and institutionalized supporter participation, we contribute to the conceptualization of sustainable participation. Our research supports the creation of an inclusive and sustainable fan community where fans can actively participate in decisions and actions that affect their current and future fandom environment. Based on the social sustainability principles of health, influence, competence, impartiality, and meaning-making, we compile the following characteristics of sustainable participation: social well-being oriented participation, direct influence, regular voting rights, representative participation, appealable resolutions, information-based participation, barrier-free participation, democratic voting, established constitutions, and encouraged participation. This conceptualization provides approaches and foundations for future investigations regarding participation research in football and practical implications for member associations, association members, league organizers, and other stakeholders to establish and improve institutionalized participation. [ABSTRACT FROM AUTHOR]

Background: Although articular wear has been thoroughly investigated, the effects of abnormal limb alignment on cartilage degeneration over time remain poorly understood. An exact assessment of the correlation between lower limb alignment abnormalities and MRI-observed articular degradation may be helpful for understanding the progression of osteoarthritis and planning future treatment. Question/purpose: In patients with moderate to advanced osteoarthritis, (1) is there a correlation between overall alignment of the knee and the location of cartilage degradation over time, as measured by cartilage metrics on MRI? (2) Is there a correlation between tibial alignment and the location of cartilage degradation over time, as measured by cartilage metrics on MRI? (3) Is there a correlation between femoral alignment and the location of cartilage degradation over time, as measured by cartilage metrics on MRI? Methods: Between April 2020 and September 2022, we retrospectively evaluated 3106 patients aged 45 to 79 years who were at risk of experiencing knee osteoarthritis. Of those, we considered as potentially eligible 600 symptomatic index knees with radiographic evidence of osteoarthritis—Kellgren-Lawrence Grades 2 or 3—at the baseline visit. Of those, 22% (134 of 600) were excluded because of a lack of proper alignment measurements, leaving 466 knees with measurements of radiologic alignment angles and quantitative MRI cartilage measurements of 16 subregions of the femorotibial compartment at baseline and 12 and 24 months, and 64 knees at the 48-month visit for investigation in the current study. Data regarding cartilage measurements of the patellofemoral compartment were not available for analysis. The knees were categorized into one of the possible 25 different phenotypes of the lower extremity established by previous research, based on the neutral, valgus, or varus distal mechanical angle of the femur and proximal tibial mechanical angle on full-limb radiographs. We applied ANOVA to estimate the effect size of the overall, femoral, and tibial alignments on the location of cartilage degradation over time, as measured by cartilage metrics on MRI. Results: We found that the overall combinations of a valgus femur with valgus tibia or a valgus femur with varus tibia were associated with the highest loss of cartilage in the internal medial tibial subregion and anterior lateral tibial subregion (η2p = 0.39 and 0.17, respectively). For the tibia, we found that the combination of a valgus femur with valgus tibia was associated with an increase in the area of subchondral bone denuded of cartilage in the central lateral tibial subregion (η2p = 0.2). For the femur, we found that the combination of a valgus femur with valgus tibia was associated with loss of cartilage thickness in the central weightbearing lateral femorotibial compartment (η2p = 0.15). Conclusion: We found that certain alignment patterns are associated with rapid deterioration of cartilage and exposure of subchondral bone, even over short time periods. In particular, the valgus femur with valgus tibia and valgus femur with varus tibia phenotypes deserve special attention, because they exhibited a strong, atypical correlation with the internal medial tibial subregion and anterior lateral tibial subregion, respectively. This is important because valgus and varus malalignment cause isolated lateral and medial compartment disease, respectively. Therefore, these findings suggest that a more individualized approach for limb axis deformities is valuable, and hint at a more meticulous radiologic and clinical investigation, perhaps using different imaging modalities, especially when assessing the exact cartilage state and planning an intervention. Future studies, ideally biomechanical, might help in assessing the long-term effects of the various phenotypes on cartilage degradation and their relevance in reconstructive surgery. Level of Evidence: Level II, prognostic study. [ABSTRACT FROM AUTHOR]

Cholestenoic acid (CA) has been reported as an important biomarker of many severe diseases, but its physiological and pathological roles remain unclear. This study aimed to investigate the potential role of CA in hepatic lipid homeostasis. Enzyme kinetic studies revealed that CA specifically activates DNA methyltransferases 1 (DNMT1) at low concentration with EC50 = 1.99 10-6 M and inhibits the activity at higher concentration with IC50 = 9.13 106 M, and specifically inhibits DNMT3a, and DNMT3b activities with IC50= 8.41 10-6 M and IC50= 4.89 10-6 M, respectively. In a human hepatocyte in vitro model of high glucose (HG)- induced lipid accumulation, CA significantly increased demethylation of 5mCpG in the promoter regions of over 7,000 genes, particularly those involved in master signaling pathways such as calcium-AMPK and 0.0027 at 6 h. RNA sequencing analysis showed that the downregulated genes are affected by CA encoding key enzymes, such as PCSK9, MVK, and HMGCR, which are involved in cholesterol metabolism and steroid biosynthesis pathways. In addition, untargeted lipidomic analysis showed that CA significantly reduced neutral lipid levels by 60% in the cells cultured in high-glucose media. Administration of CA in mouse metabolic dysfunction-associated steatotic liver disease (MASLD) models significantly decreases lipid accumulation, suppresses the gene expression involved in lipid biosynthesis in liver tissues, and alleviates liver function. This study shows that CA as an endogenous epigenetic regulator decreases lipid accumulation via epigenetic regulation. The results indicate that CA can be considered a potential therapeutic target for the treatment of metabolic disorders. NEW & NOTEWORTHY To our knowledge, this study is the first to identify the mitochondrial monohydroxy bile acid cholestenoic acid (CA) as an endogenous epigenetic regulator that regulates lipid metabolism through epigenome modification in human hepatocytes. The methods used in this study are all big data analysis, and the results of each part show the global regulation of CA on human hepatocytes rather than narrow point effects. [ABSTRACT FROM AUTHOR]

Teachers can develop science literacy among pupils through Inquiry-Based Science Education. IBSE helps to evolve the inquiry skills necessary for understanding the world of science and nature. To be able to improve the level of inquiry skills systematically, we need to know the current level among pupils. For this reason, we designed a multiple-choice test that measures the level of inquiry skills among 13 to 15 years old pupils. The design of the test consisted of six steps: selection of inquiry skills, construction and administration of open-ended test, creation of a database of distractors, construction of multiple-choice test, pilot testing and application of optimised test in pedagogical research. The designed test can be considered a valid and reliable research instrument and the individual test items show a relatively high discriminating power, optimal level of difficulty and a high number of functional distractors. By analysing the most common incorrect answers, we were able to identify various difficulties pupils have, regarding the application of inquiry skills in solving items. These results will help us to design appropriate strategies for improving pupils' inquiry skills in science education. [ABSTRACT FROM AUTHOR]

We prove limit laws for the number of occurrences of a pattern on the fringe of a ranked tree-child network which is picked uniformly at random. Our results extend the limit law for cherries proved by Bienvenu et al. (Random Struct. Algoritm. 60 (2022), no. 4, 653–689). For patterns of height 1 and 2, we show that they either occur frequently (mean is asymptotically linear and limit law is normal) or sporadically (mean is asymptotically constant and limit law is Poisson) or not all (mean tends to 0 and limit law is degenerate). We expect that these are the only possible limit laws for any fringe pattern. [ABSTRACT FROM AUTHOR]

Objectives: The prognostic relevance of metabolic tumor volume (MTV) having recently been demonstrated in patients with early‐stage favorable and advanced‐stage Hodgkin lymphoma. The current study aimed to assess the potential prognostic value of 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) in early‐stage unfavorable Hodgkin lymphoma patients treated within the German Hodgkin Study Group HD17 trial. Methods: 18F‐FDG PET/CT images were available for MTV analysis in 154 cases. We used three different threshold methods (SUV2.5, SUV4.0, and SUV41%) to calculate MTV. Receiver‐operating‐characteristic analysis was performed to describe the value of these parameters in predicting an adequate therapy response. Therapy response was evaluated as PET negativity after 2 cycles of eBEACOPP followed by 2 cycles of ABVD. Results: All three threshold methods analyzed for MTV showed a positive correlation with the PET response after chemotherapy. Areas under the curve (AUC) were 0.70 (95% CI 0.53–0.87) and 0.65 (0.50–0.80) using the fixed thresholds of SUV4.0 and SUV2.5, respectively, for MTV‐ calculation. The calculation of MTV using a relative threshold of SUV41% showed an AUC of 0.63 (0.47–0.79). Conclusions: MTV does have predictive value after chemotherapy in early‐stage unfavorable Hodgkin lymphoma, particularly when the fixed threshold of SUV4.0 is used for MTV calculation. Trial registration: ClinicalTrials.gov NCT01356680. [ABSTRACT FROM AUTHOR]

Purpose: Only a few publications considered the influence of the spinopelvic parameters on below-hip anatomy. There is a lack of evidence about the relationship between the anatomic spinopelvic parameters and the posterior tibial slope (PTS). Therefore, the aim of this study was to analyze the association between fixed anatomic spinopelvic parameters and PTS. Methods: Adult patients presenting with lumbar, thoracic, or cervical complaints together with knee pain at a single hospital between 2017 to 2022 with available standing full-spine lateral radiograph and lateral knee radiograph were retrospectively reviewed. The measured parameters included the pelvic incidence (PI), the sacral kyphosis (SK), the pelvisacral angle, the sacral anatomic orientation (SAO), the sacral table angle, the sacropelvic angle and the PTS. Pearson's correlations and linear regression analyses were conducted. Results: A total of 80 patients (44 women), median age 63 years were analyzed. A strong positive correlation was identified between PI and PTS (r = 0.70, p < 0.001). A strong negative correlation was observed between PI and SAO (r = − 0.74, p < 0.001). A strong positive correlation was observed between PI and SK (r = 0.81, p < 0.001). A univariable linear regression analysis showed that PTS can be deduced from PI according to the following formula: PTS = 0.174 × PI − 1.138. Conclusion: This study is the first to support a positive correlation between the PI and the PTS. We demonstrate that knee anatomy is individually correlated to pelvic shape and therefore influences spinal posture. [ABSTRACT FROM AUTHOR]

Introduction: After pelvic osteotomy for the treatment of symptomatic hip dysplasia, the longevity of the hip joint can be compromised by acetabular overcorrection. This iatrogenic pincer-type deformity is considered to be one of the major risk factors for persistent pain and progressing osteoarthritis. There is evidence that acetabula in the borderline range, defined by a lateral center edge angle (LCEA) between 18° and 25°, are more delicate to be orientated physiologically. The aim of this study was to assess the quality of acetabular orientation by triple pelvic osteotomy (TPO), established by Tönnis and Kalchschmidt, especially with respect to acetabular overcorrection. Materials and methods: A retrospective examination on 368 consecutive hips treated with TPOs was conducted. On the preoperative pelvic radiograph and the radiographic control 5 days after surgery, LCEA, acetabular index (AI), and anterior (AWI) and posterior wall index (PWI) were measured. According to the above-mentioned definition, the hips were divided into a borderline (n = 196) and a dysplastic (n = 172) group. Acetabular overcorrection was defined as when LCEA exceeded 35°, AI was below 0° and AWI exceeded 0.60, postoperatively. The postoperative occurrence of a relevant femoroacetabular impingement was correlated to these thresholds. Statistics comprised a priori power analysis, correlation analyses and receiver operating characteristics (ROC). Results: In the borderline group, in 64 hips (32.7%), LCEA and AI indicated lateral overcorrection. In the dysplastic group, in 14 hips (8.1%), solely AI indicated overcorrection. In none of the hips, relevant anterior overcorrection was detected since AWI never exceeded 0.60. Chi-square test demonstrated a significant correlation between the occurrence of a postoperative femoroacetabular impingement and LCEA exceeding 35°, as well as AI below 0° (p < 0.001, resp.). Bravais–Pearson's analysis showed a significant correlation between the pre- and postoperative values of all parameters in the borderline and the dysplasia group (p < 0.001). Thus, ROC analysis could be performed and provided preoperative cutoff values for LCEA (23°) and AI (12.5°), hinting at postoperative overcorrection. Conclusion: The comparison of radiographic parameters after TPO showed a considerably greater percentage of laterally overcorrected acetabula in the borderline hips than in the dysplastic hips. According to the wall indices, anterior overcorrection was not observed. ROC analysis anticipated unfavorable lateral overcorrection when preoperative LCEA was above 23° and AI below 12.5°. These findings should sensitize the surgeon to the delicate acetabular correction in borderline dysplastic hips. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a joint disease featuring cartilage breakdown and chronic pain. Although age and joint trauma are prominently associated with OA occurrence, the trigger and signaling pathways propagating their pathogenic aspects are ill defined. Following long-term catabolic activity and traumatic cartilage breakdown, debris accumulates and can trigger Toll-like receptors (TLRs). Here we show that TLR2 stimulation suppressed the expression of matrix proteins and induced an inflammatory phenotype in human chondrocytes. Further, TLR2 stimulation impaired chondrocyte mitochondrial function, resulting in severely reduced adenosine triphosphate (ATP) production. RNA-sequencing analysis revealed that TLR2 stimulation upregulated nitric oxide synthase 2 (NOS2) expression and downregulated mitochondria function-associated genes. NOS inhibition partially restored the expression of these genes, and rescued mitochondrial function and ATP production. Correspondingly, Nos2−/− mice were protected from age-related OA development. Taken together, the TLR2–NOS axis promotes human chondrocyte dysfunction and murine OA development, and targeted interventions may provide therapeutic and preventive approaches in OA. [ABSTRACT FROM AUTHOR]

Simple Summary: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. Since pathological characteristics and clinical presentation of NLPHL differ from classical HL and often resemble indolent B-cell non-Hodgkin lymphoma (B-NHL), nodular lymphocyte-predominant B-cell lymphoma has been proposed as an alternative name. In recent years, NLPHL has increasingly been treated with B-NHL-directed approaches, although more data are available on HL-directed treatment strategies. Overall, the outcomes of NLPHL patients are excellent, and the excess mortality in comparison with the general population is low. Future research in NLPHL will thus aim to determine strategies to reduce treatment intensity whenever possible. The definition of the optimal use of HL-directed and B-NHL-directed approaches in this disease is also pending. Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare B cell-derived lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. In recent decades, patients with newly diagnosed NLPHL have usually been treated very similarly to classical HL (cHL). The 10-year overall survival rates with HL-directed approaches are in excess of 90%. However, pathological and clinical characteristics of NLPHL resemble indolent B-cell non-Hodgkin lymphoma (B-NHL) in some aspects. Thus, nodular lymphocyte-predominant B-cell lymphoma has been proposed as an alternative name, and the use of B-NHL-directed treatment strategies has become more common in NLPHL despite limited data. Given the often indolent clinical course of NLPHL, even in the case of relapse, the majority of patients with disease recurrence do not require high-dose chemotherapy and autologous stem cell transplantation but are treated sufficiently with low-intensity approaches such as single-agent anti-CD20 antibody treatment. The establishment of novel prognostic scores for NLPHL patients may optimize risk group and treatment allocation in newly diagnosed and relapsed disease. [ABSTRACT FROM AUTHOR]

Introduction: In hip preservation surgery, the term "borderline hip dysplasia" was used when the lateral center edge angle (LCEA), historically described by Wiberg, measured 18–25°. In recent years, several radiographic parameters have been described to assess the antero posterior coverage of the femoral head, for example, the anterior and posterior wall index (AWI and PWI). This allowed an increasingly comprehensive understanding of acetabular morphology and a questioning of the borderline definition. Material and methods: A retrospective review of 397 consecutive hips was performed, all treated with triple pelvic osteotomy (TPO) due to symptomatic hip dysplasia. On all preoperative pelvic radiographs with a LCEA of 18–25°, acetabular index (AI), AWI and PWI were measured. With these values, the hips were categorized into laterally, antero-laterally and postero-laterally dysplastic and stratified by gender. Intra- and interobserver correlation of the parameters was analyzed by intraclass correlation coefficient (ICC). Results: According to LCEA, 192 hips were identified as "borderline dysplastic". Based on AWI and PWI, the categorization resulted in 116 laterally dysplastic (60.4%), 33 antero-laterally (17.2%) and 43 postero-laterally dysplastic hips (22.4%). Gender stratification revealed that male acetabula seemed to be slightly more postero-laterally deficient than female (mean PWI 0.80 vs 0.89; p = 0.017). ICC confirmed highly accurate and reproducible readings of all parameters. Conclusion: The rather high proportion of symptomatic hips labelled borderline dysplastic suggested, that there might be substantial acetabular deficiency not recognizable by LCEA. Comprehensive deformity analysis using LCEA, AI, AWI and PWI showed, that 40% of these hips were deficient either antero-laterally or postero-laterally. Male acetabula were more deficient postero-laterally than female. [ABSTRACT FROM AUTHOR]

Introduction: The German Hodgkin Study Group (GHSG) HD17 trial established the omission of radiotherapy (RT) for patients with early-stage unfavorable Hodgkin lymphoma being PET-negative after 2 cycles of BEACOPP escalated plus 2 cycles of ABVD. This patient group reveals heterogeneity in characteristics and disease extent which prompted us to perform a decisive dosimetric analysis according to GHSG risk factors. This may help to tailor RT individually balancing risks and benefits. Methods: For quality assurance, RT-plans were requested from the treating facilities (n= 141) and analyzed centrally. Dose-volume histograms were scanned either paper-based or digitally to obtain doses to mediastinal organs. These were registered and compared according to GHSG risk factors. Results: Overall, RT plans of 176 patients were requested, 139 of which had dosimetric information on target volumes within the mediastinum. Most of these patients were stage II (92.8%), had no B-symptoms (79.1%) and were aged < 50 years (89.9%). Risk factors were present in 8.6% (extranodal involvement), 31.7% (bulky disease), 46.0% (elevated erythrocyte sedimentation rate) and 64.0% (three involved areas), respectively. The presence of bulky disease significantly affected the mean RT doses to the heart (p=0.005) and to the left lung (median: 11.3 Gy vs. 9.9 Gy; p=0.042) as well as V5 of the right and left lung, respectively (median right lung: 67.4% vs. 51.0%; p=0.011; median left lung: 65.9% vs. 54.2%; p=0.008). Significant differences in similar organs at risk parameters could be found between the sub-cohorts with the presence or absence of extranodal involvement, respectively. In contrast, an elevated erythrocyte sedimentation rate did not deteriorate dosimetry significantly. No association of any risk factor with radiation doses to the female breast was found. Conclusion: Pre-chemotherapy risk factors may help to predict potential RT exposure to normal organs and to critically review treatment indication. Individualized risk-benefit evaluations for patients with HL in early-stage unfavorable disease are mandatory. [ABSTRACT FROM AUTHOR]

Google Scholar Crossref Search ADS PubMed WorldCat 7 Quante M, Hesse M, Dohnert M et al.; LIFE Child Study Investigators. Google Scholar Crossref Search ADS PubMed WorldCat 9 Enzenbach C, Wicklein B, Wirkner K, Loeffler M. Evaluating selection bias in a population-based cohort study with low baseline participation: the LIFE-Adult-Study. Google Scholar Crossref Search ADS PubMed WorldCat 2 Holle R, Happich M, Lowel H, Wichmann HE; MONICA/KORA Study Group. Key Features The LIFE-Adult-Study is a population-based cohort study investigating the prevalence and incidence of common diseases and subclinical disease phenotypes, the complex interactions between genetic and lifestyle factors regarding the co-occurrence and development of subclinical phenotypes and diseases, and the role of biomarkers to predict disease initiation and progression. [Extracted from the article]

Pemphigus vulgaris is a life-threatening blistering skin disease caused by autoantibodies destabilizing desmosomal adhesion. Current therapies focus on suppression of autoantibody formation and thus treatments directly stabilizing keratinocyte adhesion would fulfill an unmet medical need. We here demonstrate that apremilast, a phosphodiesterase 4 inhibitor used in psoriasis, prevents skin blistering in pemphigus vulgaris. Apremilast abrogates pemphigus autoantibody-induced loss of keratinocyte cohesion in ex-vivo human epidermis, cultured keratinocytes in vitro and in vivo in mice. In parallel, apremilast inhibits keratin retraction as well as desmosome splitting, induces phosphorylation of plakoglobin at serine 665 and desmoplakin assembly into desmosomal plaques. We established a plakoglobin phospho-deficient mouse model that reveals fragile epidermis with altered organization of keratin filaments and desmosomal cadherins. In keratinocytes derived from these mice, intercellular adhesion is impaired and not rescued by apremilast. These data identify an unreported mechanism of desmosome regulation and propose that apremilast stabilizes keratinocyte adhesion and is protective in pemphigus. Pemphigus vulgaris is a life-threatening blistering skin disease caused by autoantibodies which destabilize cell adhesion of keratinocytes. The phosphodiesterase 4 inhibitor apremilast prevents skin blistering by stabilizing the keratin filament anchorage of desmosomes. [ABSTRACT FROM AUTHOR]

Jared Muralt's ongoing comics series The Fall (2018–) depicts a post-apocalyptic world ravaged by a flu pandemic, in which the responses to and consequences of the fictional disease outbreak premediated the reality of the COVID-19 spread. While embedding the narrative in mainstream post-apocalyptic tropes and plot developments, Muralt adopts European western comic conventions and draws on specific representations of place, landscape, and social conflict to shape his take on a pandemic state of exception in different configurations in urban and rural contexts. Focusing on the first six issues of The Fall, this article demonstrates how the deathscape created by Muralt resonates with necropolitical measures implemented during the COVID-19 pandemic, leading to the formation of fictional makeshift communities in the Alps in which rule is based on threats of violence and the marginalization of the sick and refugees. [ABSTRACT FROM AUTHOR]

Desmoglein 3 (Dsg3) is a desmosomal cadherin mediating cell adhesion within desmosomes and is the antigen of the autoimmune blistering skin disease pemphigus vulgaris. Therefore, understanding of the complex desmosome turnover process is of high biomedical relevance. Recently, super resolution microscopy was used to characterize desmosome composition and turnover. However, studies were limited because adhesion measurements on living cells were not possible in parallel. Before desmosomal cadherins are incorporated into nascent desmosomes, they are not bound to intermediate filaments but were suggested to be associated with the actin cytoskeleton. However, direct proof that adhesion of a pool of desmosomal cadherins is dependent on actin is missing. Here, we applied single-molecule force spectroscopy measurements with the novel single molecule hybrid-technique STED/SMFS-AFM to investigate the cytoskeletal anchorage of Dsg3 on living keratinocytes for the first time. By application of pharmacological agents we discriminated two different Dsg3 pools, only one of which is anchored to actin filaments. We applied the actin polymerization inhibitor Latrunculin B to modify the actin cytoskeleton and the PKCα activator PMA to modulate intermediate filament anchorage. On the cellular surface Dsg3 adhesion was actin-dependent. In contrast, at cell–cell contacts, Dsg3 adhesion was independent from actin but rather is regulated by PKC which is well established to control desmosome turn-over via intermediate filament anchorage. Taken together, using the novel STED/SMFS-AFM technique, we demonstrated the existence of two Dsg3 pools with different cytoskeletal anchorage mechanisms. [ABSTRACT FROM AUTHOR]

The Sackin and Colless indices are two widely-used metrics for measuring the balance of trees and for testing evolutionary models in phylogenetics. This short paper contributes two results about the Sackin and Colless indices of trees. One result is the asymptotic analysis of the expected Sackin and Colless indices of tree shapes (which are full binary rooted unlabelled trees) under the uniform model where tree shapes are sampled with equal probability. Another is a short direct proof of the closed formula for the expected Sackin index of phylogenetic trees (which are full binary rooted trees with leaves being labelled with taxa) under the uniform model. [ABSTRACT FROM AUTHOR]

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