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Wearable sensors, including accelerometers, are a widely accepted tool to assess gait in clinical and free-living environments. Methods to identify phases and subphases of the gait cycle are necessary for comprehensive assessment of pathological gait. The current study evaluated the accuracy of a finite state machine (FSM) algorithm to detect strides by identifying gait cycle subphases from ankle-worn accelerometry. Algorithm performance was challenged across a range of speeds (0.4-2.6 m/s), task conditions (e.g., single- and dual-task walking), and individual characteristics. Specifically, the study included a range of treadmill speeds in young adults and overground walking conditions in older adults with neurological disease. Manually counted and algorithm-derived stride detection from acceleration data were evaluated using error analysis and Bland-Altman plots for visualization. Overall, the algorithm successfully detected strides (>96 % accuracy) across gait speed ranges and tasks, for young and older adults. The accuracy of an FSM algorithm combined with ankle-worn accelerometers, provides an analytical approach with affordable and portable tools that permits comprehensive assessment of gait unbounded by setting and proves to perform well in in walking tasks characterized by variable walking. These algorithm capabilities and advancements are critical for identifying phase dependent gait impairments in clinical and free-living assessment., Competing Interests: Declaration of competing interest None declared, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chimeric antigen receptor (CAR) T cell therapy has become an important treatment for hematological cancers, and its success has spurred research into CAR T cell therapies for other diseases, including solid tumor cancers and autoimmune diseases. Notably, the development of CAR-based treatments for autoimmune diseases has shown great progress recently. Clinical trials for anti-CD19 and anti-BCMA CAR T cells in treating severe B cell-mediated autoimmune diseases, like systemic lupus erythematosus (SLE), have shown lasting remission thus far. CAR T cells targeting autoreactive T cells are beginning clinical trials for treating T cell mediated autoimmune diseases. Chimeric autoantigen receptor (CAAR) T cells specifically target and eliminate only autoreactive B cells, and they have shown promise in treating mucosal pemphigus vulgaris and MuSK myasthenia gravis. Regulatory CAR T cells have also been developed, which show potential in altering autoimmune affected areas by creating a protective barrier as well as helping decrease inflammation. These new treatments are only the beginning of potential CAR T cell applications in treating autoimmune disease. Novel CAR technologies have been developed that increase the safety, potency, specificity, and efficacy of CAR T cell therapy. Applying these novel modifications to autoimmune CARs has the potential to enhance the efficacy and applicability of CAR therapies to autoimmune disease. This review will detail several recently developed CAR technologies and discuss how their application to autoimmune disease will improve this emerging field. These include logic-gated CARs, soluble protein-secreting CARs, and modular CARs that enable CAR T cell therapies to be more specific, reach a wider span of target cells, be safer for patients, and give a more potent cytotoxic response. Applying these novel CAR technologies to the treatment of autoimmune diseases has the potential to revolutionize this growing application of CAR T cell therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cheever, Kang, O’Neill and Weber.)

Aim: To investigate the associations of the Dietary Approaches to Stop Hypertension (DASH) score with subcutaneous (SAT) and visceral (VAT) adipose tissue volume and hepatic lipid content (HLC) in people with diabetes and to examine whether changes in the DASH diet were associated with changes in these outcomes., Methods: In total, 335 participants with recent-onset type 1 diabetes (T1D) and type 2 diabetes (T2D) from the German Diabetes Study were included in the cross-sectional analysis, and 111 participants in the analysis of changes during the 5-year follow-up. Associations between the DASH score and VAT, SAT and HLC and their changes were investigated using multivariable linear regression models by diabetes type. The proportion mediated by changes in potential mediators was determined using mediation analysis., Results: A higher baseline DASH score was associated with lower HLC, especially in people with T2D (per 5 points: -1.5% [-2.7%; -0.3%]). Over 5 years, a 5-point increase in the DASH score was associated with decreased VAT in people with T2D (-514 [-800; -228] cm 3 ). Similar, but imprecise, associations were observed for VAT changes in people with T1D (-403 [-861; 55] cm 3 ) and for HLC in people with T2D (-1.3% [-2.8%; 0.3%]). Body mass index and waist circumference changes explained 8%-48% of the associations between DASH and VAT changes in both groups. In people with T2D, adipose tissue insulin resistance index (Adipo-IR) changes explained 47% of the association between DASH and HLC changes., Conclusions: A shift to a DASH-like diet was associated with favourable VAT and HLC changes, which were partly explained by changes in anthropometric measures and Adipo-IR., (© 2024 John Wiley & Sons Ltd.)

Background & Aims: Holo-Transcobalamin (holo-TC) is the biologically active form of vitamin B12, a vitamin essential in human metabolism. The association between vitamin B12 (total cobalamin) and mortality risk has been controversially reported, whereas the relation between holo-TC and survival is unknown. In a population-based sample (n = 862, female share 42.8%, median age 62.3 years), we related serum holo-TC to the risk of all-cause mortality., Methods: We measured serum holo-TC by electro-chemiluminescence. Multivariable-adjusted Cox proportional hazards regression models were used to quantify the association between serum holo-TC and all-cause mortality., Results: Over a median follow-up time of 10.9 years, n = 99 individuals died. We did not find significant associations between serum holo-TC and the risk of all-cause mortality (HR: 1.00 [95% CI 0.97-1.03] per 5-point increment in holo-TC), neither in the overall sample, nor in subgroups stratified by sex, diabetes, or hypertension., Conclusion: The biologically active form of vitamin B12, holo-TC, is not related to the risk of all-cause mortality in a moderate-sized sample from the general population., Competing Interests: Declaration of competing interest None of the authors declare a conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: Higher dietary intake or higher circulating levels of the trace element boron have been associated with beneficial effects on human health. However, the relationship between plasma boron levels and survival in the general population is not known. Therefore, we aimed to assess the association between plasma boron concentrations and all-cause mortality in a population-based cohort from northern Germany (n = 863 individuals; median age 62.3 years, 42.8% women)., Methods: Plasma boron concentrations (median 31.9 µg/L [22.9; 43.5]) were measured by inductively coupled plasma-mass spectrometry. Cox proportional hazards regression models adjusted for relevant confounders were used to associate plasma boron concentrations with all-cause mortality., Results: After a median follow-up time of 11 years, n = 99 individuals had died. In the overall sample, plasma boron concentrations were associated with all-cause mortality in the crude model (HR: 1.07 [95% CI 1.03-1.11] per 5-unit-increment). However, multivariable adjustment rendered the association non-significant (HR: 1.03 [95% CI 0.99-1.07]). Sex-stratified analyses revealed slightly higher mortality hazards with increasing plasma boron concentrations in women (HR: 1.11 [95% CI 1.03-1.18], p Interaction  = 0.034), but not in men (HR: 1.00 [95% CI 0.95-1.06])., Conclusion: We conclude that in a moderate-sized sample from the general population, higher plasma boron concentrations were associated with a higher risk of all-cause mortality in women, but not in men. Due to the low number of events in the female subsample (n = 27), this observation has to be interpreted with caution., (© 2024. The Author(s).)

Background and Aims: Differences of dietary pattern adherence across the novel diabetes endotypes are unknown. This study assessed adherence to pre-specified dietary patterns and their associations with cardiovascular risk factors, kidney function, and neuropathy among diabetes endotypes., Methods and Results: The cross-sectional analysis included 765 individuals with recent-onset (67 %) and prevalent diabetes (33 %) from the German Diabetes Study (GDS) allocated into severe autoimmune diabetes (SAID, 35 %), severe insulin-deficient diabetes (SIDD, 3 %), severe insulin-resistant diabetes (SIRD, 5 %), mild obesity-related diabetes (MOD, 28 %), and mild age-related diabetes (MARD, 29 %). Adherence to a Mediterranean diet score (MDS), Dietary Approaches to Stop Hypertension (DASH) score, overall plant-based diet (PDI), healthful (hPDI) and unhealthful plant-based diet index (uPDI) was derived from a food frequency questionnaire and associated with cardiovascular risk factors, kidney function, and neuropathy using multivariable linear regression analysis. Differences in dietary pattern adherence between endotypes were assessed using generalized mixed models. People with MARD showed the highest, those with SIDD and MOD the lowest adherence to the hPDI. Adherence to the MDS, DASH, overall PDI, and hPDI was inversely associated with high-sensitivity C-reactive protein (hsCRP) among people with MARD (β (95%CI): -9.18 % (-15.61; -2.26); -13.61 % (-24.17; -1.58); -19.15 % (-34.28; -0.53); -16.10 % (-28.81; -1.12), respectively). Adherence to the PDIs was associated with LDL cholesterol among people with SAID, SIRD, and MOD., Conclusions: Minor differences in dietary pattern adherence (in particular for hPDI) and associations with markers of diabetes-related complications (e.g. hsCRP) were observed between endotypes. So far, evidence is insufficient to derive endotype-specific dietary recommendations., Trial Registration: Clinicaltrials.gov: NCT01055093., Competing Interests: Declaration of competing interest MR is on scientific advisory boards of Boehringer-Ingelheim, Eli Lilly, NovoNordisk and Target RWE and received investigator-initiated support from Boehringer Ingelheim, Nutricia/Danone and Sanofi-Aventis to the German Diabetes Center (DDZ). SS reports research support from Alpro Foundation. None of these aforementioned relationships/activities are related to the content of your manuscript. KSW, AL, KS, HM, AZ, OPZ, AS, GB, JG, AEB, ST, RW, WL, and CH declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Thomas Skurk: Lecture fees: Novo NordiskDiana Rubin: Lecture fees: DGVS and Kaiserin-Friedrich-StiftungAnja Bosy-Westphal: noneArthur Grünerbel: Fees from KV Bayern, research funding by BMG, feesfrom Lilly,Stefan Kabisch: Fees and travel expenses by Sanofi, Berlin Chemie, Boehringer Ingelheim and Lilly; Travel expenses and research funding by J. Rettenmaier & Söhne, Holzmühle; further research funding by Beneo Südzucker and California Walnut CommissionPeter Kronsbein: noneKarsten Müssig: noneMarie-Christine Simon: noneAstrid Tombek: noneHelmut Nussbaumer: none

Purpose: Dietary pattern scores reflecting a high intake of beneficial food groups were associated with reduced mortality risk. Data on associations of such dietary pattern scores in population-based samples from northern Germany are lacking. Therefore, we examined the association of three dietary pattern scores with all-cause mortality in a moderate-sized prospective sample from northern Germany., Methods: The study sample comprised 836 participants (43.8% females, median age 62.4 years). Based on a validated, self-administered Food Frequency Questionnaire, the dietary scores Dietary Approaches to Stop Hypertension (DASH), Modified Mediterranean Diet Score (MMDS), and Healthy Nordic Food Index (HNFI) were calculated. Cox proportional hazard regression models, adjusted for age, sex, body mass index, waist to hip ratio, education, smoking status, total energy intake, and physical activity, were used to separately relate DASH, MMDS, and HNFI to all-cause mortality., Results: During a median follow-up period of 11 years, 93 individuals died. While DASH and MMDS scores were not associated with all-cause mortality, greater adherence to HNFI was associated with lower mortality hazards (HR: 0.47 [95% CI 0.25-0.89] when comparing the highest score quartile to the lowest; HR: 0.79 [95% CI 0.64-0.98] for HNFI modeled as a 1-Standard Deviation increment). Among different HNFI components, higher intake of oats and cereals displayed the most conclusive association with all-cause mortality (HR: 0.59 [95% CI 0.38-0.91] when comparing high and low intake)., Conclusion: In an elderly general population sample from northern Germany, we observed greater adherence to HNFI to be associated with lower all-cause mortality., (© 2023. The Author(s).)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

During the severe acute respiratory distress virus coronavirus type 2 (SARS-CoV-2) pandemic, many women were infected during their pregnancies. The SARS-CoV-2-induced coronavirus disease 19 (COVID-19) has an impact on maternal health and pregnancy outcomes; peripartum and perinatal morbidity and mortality are increased. Pregnancy is considered a risk factor for severe COVID-19 course. Additional risk factors during pregnancy are diabetes mellitus, gestational diabetes mellitus (GDM), and obesity. Systemic inflammation can lead to severe metabolic dysregulation with ketoacidosis. The endocrine pancreas is a target organ for SARS-CoV-2 and the fetal risk depends on inflammation of the placenta. Up to now there is no evidence that SARS-CoV-2 infection during pregnancy leads to permanent diabetes in mothers or their offspring via triggering autoimmunity or beta cell destruction. The frequently observed increased prevalence of GDM compared to the years before the pandemic is most likely due to changed lifestyle during lockdown. Furthermore, severe COVID-19 may be associated with the development of GDM due to worsening of glucose tolerance. Vaccination with a mRNA vaccine is safe and highly effective to prevent infection and to reduce hospitalization. Registries support offering evidence-based recommendations on vaccination for pregnant women. Even with the current omicron virus variant, there are increased risks for symptomatic and unvaccinated pregnant women., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: Thomas Skurk: Lecture fees: Novo Nordisk; Research funding: Savanna Ingredients GmbH and Tate & Lyle; Arthur Grünerbel: Fees from KV Bayern, research funding by BMG, fees from Lilly, Sandra Hummel: none; Stefan Kabisch: Fees and travel expenses by Sanofi, Berlin Chemie, Boehringer Ingelheim and Lilly; Travel expenses and research funding by J. Rettenmaier & Söhne, Holzmühle; further research funding by Beneo Südzucker and the California Walnut Commission; Winfried Keuthage: none; Karsten Müssig: none; Helmut Nussbaumer: none; Diana Rubin: Lecture fees: DGVS and Kaiserin-Friedrich Foundation.

Introduction: Pregnancy is a known independent risk factor for a severe course of COVID-19. The relationship of SARS-CoV-2 infection and gestational diabetes mellitus (GDM) on neonatal outcomes is unclear. Our aim was to determine if SARS-CoV-2 infection represents an independent risk factor for adverse perinatal outcomes in pregnancy with GDM., Research Design and Methods: We compared data from two German registries including pregnant women with GDM, established during the SARS-CoV-2 pandemic (COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS), a multicenter prospective observational study) and already existing before the pandemic (German registry of pregnant women with GDM; GestDiab). In total, 409 participants with GDM and SARS-CoV-2 infection and 4598 participants with GDM, registered 2018-2019, were eligible for analyses. The primary fetal and neonatal outcomes were defined as: (1) combined: admission to neonatal intensive care unit, stillbirth, and/or neonatal death, and (2) preterm birth before 37+0 weeks of gestation. Large and small for gestational age, maternal insulin therapy, birth weight > 4500 g and cesarean delivery were considered as secondary outcomes., Results: Women with SARS-CoV-2 infection were younger (32 vs 33 years) and had a higher median body mass index (28 vs 27 kg/m²). In CRONOS, more neonates developed the primary outcome (adjusted OR (aOR) 1.48, 95% CI 1.11 to 1.97) and were born preterm (aOR 1.50, 95% CI 1.07 to 2.10). Fasting glucose was higher in women in CRONOS versus GestDiab (5.4 vs 5.3 mmol/L) considering each 0.1 mmol/L increase was independently associated with a 5% higher risk of preterm birth among women in CRONOS only (aOR 1.05, 95% CI 1.01 to 1.09)., Conclusions: GDM with SARS-CoV-2 infection in pregnancy is associated with an increased risk of adverse fetal and neonatal outcomes as compared with GDM without SARS-CoV-2 infection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Diffuse large B-cell lymphoma (DLBCL) is a common, genomically heterogenous disease that presents a clinical challenge despite the success of frontline regimens and second-line chimeric antigen receptor T-cell (CAR-T) therapy. Recently, genomic alterations and tumor microenvironment features associated with poor CAR-T response have been identified, namely those to the TP53 tumor suppressor gene. This retrospective analysis aimed to integrate various data to identify genomic partnerships capable of providing further clarity and actionable treatment targets within this population. Publicly available data were analyzed for differential expression based on TP53 and 24-month event-free survival (EFS24) status, revealing enrichments of the BRD4 bromodomain oncogene (p < 0.0001, p = 0.001). High-BRD4 and TP53 alterations were significantly associated with lower CDKN1A (p21) and TNFRSF10B (TRAIL-R2), a key tumor suppressor and CAR-T modulator, respectively. Significant loss of CD8 T-cell presence within low-TNFRSF0B (p = 0.0042) and altered-TP53 (p = 0.0424) patients showcased relevant outcome-associated tumor microenvironment features. Furthermore, reduced expression of CDKN1A was associated with low TNFRSF10B (FDR < 0.0001) and increased BRD4 interactant genes (FDR < 0.0001). Promisingly, in vitro MDM2 inhibition with Idasnutlin and TP53 reactivation via Eprenetapopt was able to renew TNFRSF10B protein expression. Additionally, applying the BRD4-degrading PROTAC ARV-825 and the CDK4/6 inhibitor Abemaciclib as single-agents and in synergistic combination significantly reduced TP53-altered DLBCL cell line viability. Our analysis presents key associations within a genomic network of actionable targets capable of providing clarity within the evolving precision CAR-T treatment landscape., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Adherence to a Mediterranean-style dietary pattern is likely to have variable effects on body composition, but the impact of gut microbiome on this relationship is unknown., Objectives: To examine the potential mediating effect of the gut microbiome on the associations between Alternate Mediterranean Diet (aMed) scores, abdominal adiposity, and inflammation in population-level analysis., Design: In a community-based sample aged 25 to 83 y (n = 620; 41% female) from Northern Germany, we assessed the role of the gut microbiome, sequenced from 16S rRNA genes, on the associations between aMed scores, estimated using validated food-frequency questionnaires, magnetic resonance imaging-determined visceral (VAT) and subcutaneous (SAT) adipose tissue and C-reactive protein (CRP)., Results: Higher aMed scores were associated with lower SAT (-0.86 L (95% CI: -1.56, -0.17), P = 0.01), VAT (-0.65 L (95% CI: -1.03,-0.27), P = 0.01) and CRP concentrations (-0.35 mg/L; β: -20.1% (95% CI: 35.5, -1.09), P = 0.04) in the highest versus lowest tertile after multivariate adjustment. Of the taxa significantly associated with aMed scores, higher abundance of Porphyromonadaceae mediated 11.6%, 9.3%, and 8.7% of the associations with lower SAT, VAT, and CRP, respectively. Conversely, a lower abundance of Peptostreptococcaceae mediated 13.1% and 18.2% of the association with SAT and CRP levels. Of the individual components of the aMed score, moderate alcohol intake was associated with lower VAT (-0.2 (95% CI: -0.4, -0.1), P =0.01) with a higher abundance of Oxalobacteraceae and lower abundance of Burkholderiaceae explaining 8.3% and 9.6% of this association, respectively., Conclusion: These novel data suggest that abundance of specific taxa in the Porphyromonadaceae and Peptostreptococcaceae families may contribute to the association between aMed scores, lower abdominal adipose tissue, and inflammation., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Neuroinflammation is associated with several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Neuroinflammation provides protection in acute situations but results in significant damage to the nervous system if chronic. Overexpression of chemokines within the brain results in the recruitment and activation of glial and peripheral immune cells which can propagate a cascading inflammatory response, resulting in neurodegeneration and the onset of neurodegenerative disorders. Recent work has identified the role of atypical chemokine receptors (ACKRs) in neurodegenerative conditions. ACKRs are seven-transmembrane domain receptors that do not follow canonical G protein signaling, but regulate inflammatory responses by modulating chemokine abundance, location, and availability. This review summarizes what is known about the four ACKRs and three putative ACKRs within the brain, highlighting their known expression and discussing the current understanding of each ACKR in the context of neurodegeneration. The ability of ACKRs to alter levels of chemokines makes them an appealing therapeutic target for neurodegenerative conditions. However, further work is necessary to understand the expression of several ACKRs within the neuroimmune system and the effectiveness of targeted drug therapies in the prevention and treatment of neurodegenerative conditions.

The spinning disk technology has previously been utilized to isolate bacterial components from blood in hours instead of days. We hypothesized that this platform could be applied as an alternative approach to isolating plasma RNA from a whole blood sample. We consequently tested the efficacy of the spinning disk technology to extract plasma from whole blood upstream of RNA isolation and analysis. To do so, we collected plasma using either the spinning disk or the typical two-spin centrifuge method. We found that the spinning disk method results in significantly more hemolysis during collection than the conventional two-spin centrifuge method. However, when plasma RNA recovered from both collection methods was quantified using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), we found that the spinning disk method yielded a higher plasma RNA concentration than the two-spin centrifuge method. This suggests that the spinning disk may be an efficient alternative method to recover plasma RNA. Further work is needed to determine whether red blood cell RNA contamination is present in the plasma RNA extracted from spinning disk-processed plasma., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2023 by the authors.)

We aimed to relate circulating plasma zinc and copper to a broad spectrum of adiposity-related traits in a cross-sectional Northern German study (n = 841, 42% female, age: 61 ± 12 years). Zinc and copper were measured by inductively coupled plasma-mass spectrometry. Subcutaneous (SAT) and visceral (VAT) adipose tissue and liver fat were derived from 534 and 538 participants, respectively, via magnet resonance imaging. Associations were assessed using multivariable-adjusted linear regression analysis. An increase per one standard deviation (SD) in zinc was associated with direct linear increases in body mass index (BMI) (1.17%; 95% confidence interval (95%CI) 0.15-2.20%), waist circumference (0.85%; 95%CI 0.04-1.67%) and waist-to-hip ratio (0.64%; 95%CI 0.18-1.09%). A 1-SD increment in copper was directly associated with BMI (1.64%; 0.41-2.88%) and waist circumference (1.22%; 95%CI 0.25-2.20%) but not waist-to-hip ratio. Independent of fat intake, zinc displayed associations with VAT (5.73%; 95%CI 2.04-9.56%) and with liver fat (3.84%; 95%CI 1.49-6.25%), the latter association being also independent of BMI. Copper was directly associated with SAT (4.64%; 95%CI 0.31-9.15%) before accounting for BMI, but showed no association with VAT or liver fat. Observed associations suggest a possible relevance of zinc and copper to adiposity. Particularly zinc displayed associations with traits of abdominal adiposity and liver fat.

Background: Aneurysmal bone cysts (ABC) are benign cystic bone tumors of an osteolytic and locally aggressive nature. As an alternative to the primary treatment of choice, which consists of curettage with bone grafting, alternative treatment methods with promising results have been described. At our department, we have, in recent years, used percutaneous sclerotherapy with polidocanol. The objective of this study was to identify the healing rate and safety of sclerotherapy with polidocanol., Aim: To identify the efficacy and safety of sclerotherapy with polidocanol in primary and recurrent ABC., Methods: Twenty-two consecutive patients (median age 12.5 years; range 1-27) with 23 ABCs treated with sclerotherapy with polidocanol from 2016-2021 were included retrospectively. Eleven patients (48%) had undergone different forms of previous treatment with recurrence. Under general anesthesia and fluoroscopic guidance, repeated percutaneous injections of 4mg polidocanol/kg body weight were performed. Through review of the electronic medical records, the following were identified: healing and recurrence rate, number of treatments, gender, age, comorbidity, location of the tumor and side effects / complications, as well as any previous surgery for ABC. The median length of radiographic follow-up was 19.5 mo., Results: All ABCs except one (96%) showed healing or stable disease after a median of 4 (range 1-8) injections. Complete clinical and radiographic healing was observed in 16 cysts (70%), while partial radiographic healing with resolution of pain was seen in 6 cases (26%) and considered as stable disease. The cyst that failed to heal had previously undergone curettage twice with recurrence. One patient with a large pelvic ABC experienced, right after two injections, a sudden drop in blood pressure, which could quickly be reversed. One patient with a juxtaphyseal ABC in the femoral neck showed a minor limb length discrepancy because of deformity. Beyond that, no complications were observed., Conclusion: Percutaneous sclerotherapy with polidocanol appears to be a safe alternative for treatment of aneurysmal bone cysts. In our series of both primary and recurrent cysts, it showed the ability to achieve healing or stable disease in 22 of 23 cases (96%). Further studies are needed to decide if this provides a long-lasting effect., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: To investigate the associations of a lifestyle score with various cardiovascular risk markers, indicators for fatty liver disease as well as MRI-determined total, subcutaneous and visceral adipose tissue mass in adults with new-onset diabetes., Research Design and Methods: This cross-sectional analysis included 196 individuals with type 1 (median age: 35 years; median body mass index (BMI): 24 kg/m²) and 272 with type 2 diabetes (median age: 53 years; median BMI: 31 kg/m²) from the German Diabetes Study. A healthy lifestyle score was generated based on healthy diet, moderate alcohol consumption, recreational activity, non-smoking and non-obese BMI. These factors were summed to form a score ranging from 0 to 5. Multivariable linear and non-linear regression models were used., Results: In total, 8.1% of the individuals adhered to none or one, 17.7% to two, 29.7% to three, 26.7% to four, and 17.7% to all five favorable lifestyle factors. High compared with low adherence to the lifestyle score was associated with more favorable outcome measures, including triglycerides (β (95% CI) -49.1 mg/dL (-76.7; -21.4)), low-density lipoprotein (-16.7 mg/dL (-31.3; -2.0)), and high-density lipoprotein cholesterol (13.5 mg/dL (7.6; 19.4)), glycated hemoglobin (-0.5% (-0.8%; -0.1%)), high-sensitivity C reactive protein (-0.4 mg/dL (-0.6; -0.2)), as well as lower hepatic fat content (-8.3% (-11.9%; -4.7%)), and visceral adipose tissue mass (-1.8 dm³ (-2.9; -0.7)). The dose-response analyses showed that adherence to every additional healthy lifestyle factor was associated with more beneficial risk profiles., Conclusions: Adherence to each additional healthy lifestyle factor was beneficially associated with cardiovascular risk markers, indicators of fatty liver disease and adipose tissue mass. Strongest associations were observed for adherence to all healthy lifestyle factors in combination., Trial Registration Number: NCT01055093., Competing Interests: Competing interests: MR has been on scientific advisory boards of Allergan, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Gilead Sciences, Inventiva, Intercept Pharma, Novartis, Novo Nordisk, Servier Laboratories, Target NRW and Terra Firma; and received support for investigator-initiated studies from Boehringer Ingelheim, Nutricia/Danone and Sanofi-Aventis. CH received a research grant from Sanofi-Aventis outside the submitted work. SS received a research grant from ALPRO outside the submitted work. The other authors declare that they have no conflicts of interest to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: There has been tremendous growth in wearable technologies for health monitoring but limited efforts to optimize methods for sharing wearables-derived information with older adults and clinical cohorts. This study aimed to co-develop, design and evaluate a personalized approach for information-sharing regarding daily health-related behaviors captured with wearables., Methods: A participatory research approach was adopted with: (a) iterative stakeholder, and evidence-led development of feedback reporting; and (b) evaluation in a sample of older adults (n  =  15) and persons living with neurodegenerative disease (NDD) (n  =  25). Stakeholders included persons with lived experience, healthcare providers, health charity representatives and individuals involved in aging/NDD research. Feedback report information was custom-derived from two limb-mounted inertial measurement units and a mobile electrocardiography device worn by participants for 7-10 days. Mixed methods were used to evaluate reporting 2 weeks following delivery. Data were summarized using descriptive statistics for the group and stratified by cohort and cognitive status., Results: Participants (n  =  40) were 60% female (median 72 (60-87) years). A total of 82.5% found the report easy to read or understand, 80% reported the right amount of information was shared, 90% found the information helpful, 92% shared the information with a family member or friend and 57.5% made a behavior change. Differences emerged in sub-group comparisons. A range of participant profiles existed in terms of interest, uptake and utility., Conclusions: The reporting approach was generally well-received with perceived value that translated into enhanced self-awareness and self-management of daily health-related behaviors. Future work should examine potential for scale, and the capacity for wearables-derived feedback to influence longer-term behavior change., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Elevated concentrations of ferritin seem to be detrimental to human health while being quite common in the elderly. Data on dietary, anthropometric, and metabolic correlates of circulating ferritin levels in the elderly are scant., Objectives: We aimed to identify a dietary pattern, anthropometric, and metabolic traits associated with plasma ferritin status in an elderly cohort (n = 460, 57% male, age: 66 ± 12 y) from Northern Germany., Methods: Plasma ferritin levels were measured by immunoturbidimetry. Reduced rank regression (RRR) yielded a dietary pattern explaining 13% of the variation in circulating ferritin concentrations. Cross-sectional associations of anthropometric and metabolic traits with plasma ferritin concentrations were assessed using multivariable-adjusted linear regression analysis. Restricted cubic spline regression was used to identify nonlinear associations., Results: The RRR pattern was characterized by a high intake of potatoes, certain vegetables, beef, pork, processed meat, fats (frying and animal fat), and beer and a low intake of snacks, representing elements of the traditional German diet. BMI, waist circumference, and CRP were directly, HDL cholesterol inversely, and age nonlinearly associated with plasma ferritin concentrations (all P < 0.05). After additional adjustment for CRP, only the association of ferritin with age remained statistically significant., Conclusion: Higher plasma ferritin concentrations were associated with a traditional German dietary pattern. The associations of ferritin with unfavorable anthropometric traits and low HDL cholesterol were rendered statistically nonsignificant upon additional adjustment for chronic systemic inflammation (measured as elevated biomarker of the measurement of inflammation (CRP)), suggesting that these associations were largely driven by the proinflammatory role of ferritin (an acute-phase reactant)., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Graves' disease (GD) is a thyroid-specific autoimmune disease with a high prevalence worldwide. The disease is primarily mediated by B cells, which produce autoantibodies against the thyroid-stimulating hormone receptor (TSHR), chronically stimulating it and leading to high levels of thyroid hormones in the body. Interest in characterizing the immune response in GD has motivated many phenotyping studies. The immunophenotype of the cells involved and the interplay between them and their secreted factors are crucial to understanding disease progression and future treatment options. T cell populations are markedly distinct, including increased levels of Th17 and follicular helper T cells (Tfh), while Treg cells appear to be impaired. Some B cells subsets are autoreactive, and anti-TSHR antibodies are the key disease-causing outcome of this interplay. Though some consensus across phenotyping studies will be discussed here, there are also complexities that are yet to be resolved. A better understanding of the immunophenotype of Graves' disease can lead to improved treatment strategies and novel drug targets.

Background: Patients receiving total hip arthroplasty (THA) due to metastatic bone disease of the hip (MBD) are at an increased risk of post-operative joint dislocation compared to other populations. Different joint solutions have been developed with the purpose of reducing the dislocation risk compared to regular THAs. One of these solutions, the constrained liner (CL), has been used increasingly at our department in recent years. This design, however, is prone to polyethylene wear and higher revision rates. An alternative is the dual mobility cup (DM), which has been shown to reduce the risk of dislocation in other high-risk populations. Few studies have investigated DM for THA due to MBD, and no studies have directly compared these two treatments in this population. We therefore decided to conduct a trial to investigate whether DM is non-inferior to CL regarding the post-operative joint dislocation risk in patients receiving THA due to MBD., Materials and Methods: This study is a single-center, randomized, open-label, two-arm, non-inferiority trial. We will include 146 patients with MBD of the hip who are planned for THA at the Department of Orthopedic Surgery, Rigshospitalet. Patients with previous osteosynthesis or endoprosthetic surgery of the afflicted hip, or who are planned to receive partial pelvic reconstruction or total femoral replacement, will be excluded. Patients will be stratified by whether subtrochanteric bone resection will be performed and allocated to either CL or DM in a 1:1 ratio. The primary outcome is the 6 months post-operative joint dislocation rate. Secondary outcomes include overall survival, implant survival, the rate of other surgical- and post-operative complications, and quality of life and functional outcome scores., Discussion: This study is designed to investigate whether DM is non-inferior to CL regarding the risk of post-operative dislocation in patients receiving THA due to MBD. To our knowledge, this trial is the first of its kind. Knowledge gained from this trial will help guide surgeons in choosing a joint solution that minimizes the risk of dislocation and, ultimately, reduces the need for repeat surgeries in this patient population., Trial Registration: ClinicalTrials.gov Identifier: NCT05461313. Registered on July 15 2022. This trial is reported according to the items in the WHO Trial Registration Data Set (Version 1.3.1)., (© 2023. The Author(s).)

Background: Accurate measurement of daily physical activity (PA) is important as PA is linked to health outcomes in older adults and people living with complex health conditions. Wrist-worn accelerometers are widely used to estimate PA intensity, including walking, which composes much of daily PA. However, there is concern that wrist-derived PA data in these cohorts is unreliable due to slow gait speed, mobility aid use, disease-related symptoms that impact arm movement, and transient activities of daily living. Despite the potential for error in wrist-derived PA intensity estimates, their use has become ubiquitous in research and clinical application., Objective: The goals of this work were to (1) determine the accuracy of wrist-based estimates of PA intensity during known walking periods in older adults and people living with cerebrovascular disease (CVD) or neurodegenerative disease (NDD) and (2) explore factors that influence wrist-derived intensity estimates., Methods: A total of 35 older adults (n=23 with CVD or NDD) wore an accelerometer on the dominant wrist and ankle for 7 to 10 days of continuous monitoring. Stepping was detected using the ankle accelerometer. Analyses were restricted to gait bouts ≥60 seconds long with a cadence ≥80 steps per minute (LONG walks) to identify periods of purposeful, continuous walking likely to reflect moderate-intensity activity. Wrist accelerometer data were analyzed within LONG walks using 15-second epochs, and published intensity thresholds were applied to classify epochs as sedentary, light, or moderate-to-vigorous physical activity (MVPA). Participants were stratified into quartiles based on the percent of walking epochs classified as sedentary, and the data were examined for differences in behavioral or demographic traits between the top and bottom quartiles. A case series was performed to illustrate factors and behaviors that can affect wrist-derived intensity estimates during walking., Results: Participants averaged 107.7 (SD 55.8) LONG walks with a median cadence of 107.3 (SD 10.8) steps per minute. Across participants, wrist-derived intensity classification was 22.9% (SD 15.8) sedentary, 27.7% (SD 14.6) light, and 49.3% (SD 25.5) MVPA during LONG walks. All participants measured a statistically lower proportion of wrist-derived activity during LONG walks than expected (all P<.001), and 80% (n=28) of participants had at least 20 minutes of LONG walking time misclassified as sedentary based on wrist-derived intensity estimates. Participants in the highest quartile of wrist-derived sedentary classification during LONG walks were significantly older (t 16 =4.24, P<.001) and had more variable wrist movement (t 16 =2.13, P=.049) compared to those in the lowest quartile., Conclusions: The current best practice wrist accelerometer method is prone to misclassifying activity intensity during walking in older adults and people living with complex health conditions. A multidevice approach may be warranted to advance methods for accurately assessing PA in these groups., (©Kyle S Weber, F Elizabeth Godkin, Benjamin F Cornish, William E McIlroy, Karen Van Ooteghem. Originally published in JMIR Formative Research (https://formative.jmir.org), 15.03.2023.)

We present a chromosome-length genome assembly and annotation of the Black Petaltail dragonfly (Tanypteryx hageni). This habitat specialist diverged from its sister species over 70 million years ago, and separated from the most closely related Odonata with a reference genome 150 million years ago. Using PacBio HiFi reads and Hi-C data for scaffolding we produce one of the most high-quality Odonata genomes to date. A scaffold N50 of 206.6 Mb and a single copy BUSCO score of 96.2% indicate high contiguity and completeness., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

In recent years, the interplay between oral microbiota and systemic disease has gained attention as poor oral health is associated with several pathologies. The oral microbiota plays a role in the maintenance of overall health, and its dysbiosis influences chronic inflammation and the pathogenesis of gum diseases. Periodontitis has also been associated with other diseases and health complications such as cancer, neurogenerative and autoimmune disorders, chronic kidney disease, cardiovascular diseases, rheumatic arthritis, respiratory health, and adverse pregnancy outcomes. The host microbiota can influence immune cell development and immune responses, and recent evidence suggests that changes in oral microbiota composition may also contribute to sensitization and the development of allergic reactions, including asthma and peanut allergies. Conversely, there is also evidence that allergic reactions within the gut may contribute to alterations in oral microbiota composition. Here we review the current evidence of the role of the oral microbiota in inflammatory diseases and health complications, as well as its future relevance in improving health and ameliorating allergic disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Moreno, Boeree, Freitas and Weber.)

Competing Interests: Diana Rubin: Lecture fees: DGVS and Kaiserin-Friedrich-Stiftung; Anja Bosy-Westphal: none; Stefan Kabisch: Fees and travel expenses by Sanofi, Berlin Chemie, Boehringer Ingelheim and Lilly; Travel expenses and research funding by J. Rettenmaier & Söhne, Holzmühle; further research funding by Beneo Südzucker and California Walnut Commission; Peter Kronsbein: none; Marie-Christine Simon: none; Astrid Tombek: none; Katharina Weber: none; Thomas Skurk: Lecture fees: Novo Nordisk

Background and Aims: The dietary glycemic index (GI) and glycemic load (GL) are increasingly recognized as important for the prevention and management of diabetes mellitus. To extend the portfolio of assessment methods for large-scale epidemiological studies, we propose a GI-specific addition to an already established FFQ., Methods and Results: The German version of the EPIC-FFQ was extended by GI-specific questions for major carbohydrate sources varying notably in GI (breakfast cereals, bread, pasta, rice, potato etc.). We performed relative validation analyses comparing the GI-extended FFQ to three to four 3-day weighted dietary records (3-d WDR) in 100 middle-aged individuals with diabetes mellitus participating in the German Diabetes Study (GDS). Level of agreement between the two methods was assessed by correlation and cross-classification analyses as well as Bland-Altman-Plots, conducted separately for women and men. Spearman correlation analysis for female participants suggested good agreement between the GI-extended FFQ and 3-d WDRs for energy adjusted dietary GL (r = 0.52, p = 0.0004). For both women and men, agreement with the estimations of dietary GI, GL (for men) and carbohydrates from low and higher-GI food sources from the GI-extended FFQ was acceptable (r: 0.28-0.45). Classification of the dietary GI and GL in the opposite quartile was <10% comparing the GI-extended FFQ and 3-d WDR. Bland-Altman plots suggested a tendency for an overestimation of the dietary GI from the GI-extended FFQ in the lower GI-ranges, particularly for men., Conclusion: Compared to the 3-d WDR, the GI-extended FFQ showed a moderate to good relative validity for parameters of carbohydrate quality., Competing Interests: Declaration of competing interest AEB is a member of the International Carbohydrate Consortium and of the ILSI Europe Carbohydrate Task Force. All other authors have no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking., Objective: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19., Study Design: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints., Results: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m 2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight., Conclusion: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m 2 were a particularly vulnerable group in the case of COVID-19., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Thomas Skurk: has received lecture fees from Novo Nordisk. Diana Rubin: has received lecture fees from DGVS and Kaiserin-Friedrich-Stiftung. Anja Bosy-Westphal: none. Arthur Grünerbel: has received fees from Bavarian Medical Association, KV Bayern, Lilly, Novartis. Stefan Kabisch: has received fees and travel expenses from Sanofi, Berlin Chemie and Lilly; travel expenses and research support from J. Rettenmaier & Söhne, Holzmühle; further research support from Beneo Südzucker and California Walnut Commission. Peter Kronsbein: none. Karsten Müssig: none. Marie-Christine Simon: none. Astrid Tombek: none

Evaporative cooling is an energy efficient form of air conditioning in dry climates that functions by pulling hot, dry outdoor air across a wet evaporative pad. While evaporative coolers can help save energy, they also have the potential to influence human health. Studies have shown residential evaporative coolers may pull outdoor air pollutants into the home or contribute to elevated levels of indoor bioaerosols that may be harmful to health. There is also evidence that evaporative coolers can enable a diverse microbial environment that may confer early-life immunological protection against the development of allergies and asthma or exacerbate these same hypersensitivities. This review summarizes the current knowledge of bioaerosol and microbiological studies associated with evaporative coolers, focusing on harmful and potentially helpful outcomes from their use. We evaluate the effects of evaporative coolers on indoor bacterial endotoxins, fungal β-(1 → 3)-D-glucans, dust mite antigens, residential microbial communities, and Legionella pneumophila. To our knowledge, this is the first review to summarize and evaluate studies on the influence that evaporative coolers have on the bioaerosol and microbiological profile of homes. This brings to light a gap in the literature on evaporative coolers, which is the lack of data on health effects associated with their use., (© 2022 The Authors. Indoor Air published by John Wiley & Sons Ltd.)

(1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to "only-children", HRs for second- or later-born individuals were 0.70 (95% CI = 0.50-0.96) and 0.65 (95% CI = 0.45-0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults' T1D risk assessment for early detection.

For nearly three decades, chimeric antigen receptors (CARs) have captivated the interest of researchers seeking to find novel immunotherapies to treat cancer. CARs were first designed to work with T cells, and the first CAR T cell therapy was approved to treat B cell lymphoma in 2017. Recent advancements in CAR technology have led to the development of modified CARs, including multi-specific CARs and logic gated CARs. Other immune cell types, including natural killer (NK) cells and macrophages, have also been engineered to express CARs to treat cancer. Additionally, CAR technology has been adapted in novel approaches to treating autoimmune disease and other conditions and diseases. In this article, we review these recent advancements in alternative CAR therapies and design, as well as their mechanisms of action, challenges in application, and potential future directions.

Background: Accelerometery is commonly used to estimate physical activity, sleep, and sedentary behavior. In free-living conditions, periods of device removal (non-wear) can lead to misclassification of behavior with consequences for research outcomes and clinical decision making. Common methods for non-wear detection are limited by data transformations (e.g., activity counts) or algorithm parameters such as minimum durations or absolute temperature thresholds that risk over- or under-estimating non-wear time. This study aimed to advance non-wear detection methods by integrating a 'rate-of-change' criterion for temperature into a combined temperature-acceleration algorithm., Methods: Data were from 39 participants with neurodegenerative disease (36% female; age: 45-83 years) who wore a tri-axial accelerometer (GENEActiv) on their wrist 24-h per day for 7-days as part of a multi-sensor protocol. The reference dataset was derived from visual inspection conducted by two expert analysts. Linear regression was used to establish temperature rate-of-change as a criterion for non-wear detection. A classification and regression tree (CART) decision tree classifier determined optimal parameters separately for non-wear start and end detection. Classifiers were trained using data from 15 participants (38.5%). Outputs from the CART analysis were supplemented based on edge cases and published parameters., Results: The dataset included 186 non-wear periods (85.5% < 60 min). Temperature rate-of-change over the first five minutes of non-wear was - 0.40 ± 0.17 °C/minute and 0.36 ± 0.21 °C/minute for the first five minutes following device donning. Performance of the DETACH (DEvice Temperature and Accelerometer CHange) algorithm was improved compared to existing algorithms with recall of 0.942 (95% CI 0.883 to 1.0), precision of 0.942 (95% CI 0.844 to 1.0), F1-Score of 0.942 (95% CI 0.880 to 1.0) and accuracy of 0.996 (0.994-1.000)., Conclusion: The DETACH algorithm accurately detected non-wear intervals as short as five minutes; improving non-wear classification relative to current interval-based methods. Using temperature rate-of-change combined with acceleration results in a robust algorithm appropriate for use across different temperature ranges and settings. The ability to detect short non-wear periods is particularly relevant to free-living scenarios where brief but frequent removals occur, and for clinical application where misclassification of behavior may have important implications for healthcare decision-making., (© 2022. The Author(s).)

Periodontitis is a chronic inflammatory oral disease that affects approximately 42% of adults 30 years of age or older in the United States. In response to microbial dysbiosis within the periodontal pockets surrounding teeth, the host immune system generates an inflammatory environment in which soft tissue and alveolar bone destruction occur. The objective of this study was to identify diagnostic biomarkers and the mechanistic drivers of inflammation in periodontitis to identify drugs that may be repurposed to treat chronic inflammation. A meta-analysis comprised of two independent RNA-seq datasets was performed. RNA-seq analysis, signal pathway impact analysis, protein-protein interaction analysis, and drug target analysis were performed to identify the critical pathways and key players that initiate inflammation in periodontitis as well as to predict potential drug targets. Seventy-eight differentially expressed genes, 10 significantly impacted signaling pathways, and 10 hub proteins in periodontal gingival tissue were identified. The top 10 drugs that may be repurposed for treating periodontitis were then predicted from the gene expression and pathway data. The efficacy of these drugs in treating periodontitis has yet to be investigated. However, this analysis indicates that these drugs may serve as potential therapeutics to treat inflammation in gingival tissue affected by periodontitis.

Background: Remote health monitoring with wearable sensor technology may positively impact patient self-management and clinical care. In individuals with complex health conditions, multi-sensor wear may yield meaningful information about health-related behaviors. Despite available technology, feasibility of device-wearing in daily life has received little attention in persons with physical or cognitive limitations. This mixed methods study assessed the feasibility of continuous, multi-sensor wear in persons with cerebrovascular (CVD) or neurodegenerative disease (NDD)., Methods: Thirty-nine participants with CVD, Alzheimer's disease/amnestic mild cognitive impairment, frontotemporal dementia, Parkinson's disease, or amyotrophic lateral sclerosis (median age 68 (45-83) years, 36% female) wore five devices (bilateral ankles and wrists, chest) continuously for a 7-day period. Adherence to device wearing was quantified by examining volume and pattern of device removal (non-wear). A thematic analysis of semi-structured de-brief interviews with participants and study partners was used to examine user acceptance., Results: Adherence to multi-sensor wear, defined as a minimum of three devices worn concurrently, was high (median 98.2% of the study period). Non-wear rates were low across all sensor locations (median 17-22 min/day), with significant differences between some locations (p = 0.006). Multi-sensor non-wear was higher for daytime versus nighttime wear (p < 0.001) and there was a small but significant increase in non-wear over the collection period (p = 0.04). Feedback from de-brief interviews suggested that multi-sensor wear was generally well accepted by both participants and study partners., Conclusion: A continuous, multi-sensor remote health monitoring approach is feasible in a cohort of persons with CVD or NDD., (© 2021. Crown.)