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Abstract Humans are significantly impacting ecosystems worldwide. Scientists of the IPBES Global Assessment are therefore calling for a transformative change that includes all aspects of society in order to address drivers of biodiversity loss. However, these calls are rather abstract, and thus it remains unclear how this goal can be achieved. With this conceptual contribution, we present an analytical framework for evaluating existing processes of societal change which are enhancing biodiversity, and we illustrate its application using three case studies in Germany. We argue that an empirical analysis provides insights into the causal mechanisms that initiate or promote change processes. In doing so, we can draw recommendations for future transformative change processes with regard to biodiversity conservation. In our analysis, we are dealing with questions concerning the following three areas: the drivers and context of societal change processes, the change processes themselves and finally their impacts. Subsequently, we generate recommendations on how to enhance and support the process of future societal transformation that aims at biodiversity conservation: (a) Retaining co‐benefits for biodiversity with goals that are primarily focussing on other objectives; (b) harmonising biodiversity use and conservation by turning conflicts into drivers of transformation; (c) prioritising biodiversity conservation by taking advantage of windows of opportunity. With our conceptual framework, we provide an analytical tool to learn from existing processes of societal change how to support future transformative change. This is an important step that contributes to the generation of relevant knowledge of promoting transformative change for nature and people. Read the free Plain Language Summary for this article on the Journal blog.

Background and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P

Abstract Lenvatinib is a multiple receptor tyrosine kinase inhibitor (TKI) approved for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). TKI are suspected of exacerbating muscle loss in patients with cancer. In this study, we analyze the role of muscle loss in patients with advanced HCC treated with lenvatinib. This is a retrospective analysis of a real-life cohort of 25 patients with advanced HCC who were treated with lenvatinib from 2018 to March 2021 in Germany. Patients were stratified for loss of skeletal muscle area during the first three months of lenvatinib therapy. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed for all patients, especially regarding loss of muscle before and during the first three months of therapy with lenvatinib. Three months after beginning of therapy with lenvatinib, a significant reduction of muscle mass was observed in 60% of patients (p = 0.035). Despite increase of loss of skeletal muscle, patients benefitted from lenvatinib in our cohort of patients in terms of OS and PFS and did not experience increased toxicity. Furthermore, muscle loss was not a negative predictor of survival in the univariate analysis (p = 0.675). Patients with advanced hepatocellular carcinoma experience muscle loss with lenvatinib therapy. However, despite progressive muscle loss, patients benefit from a therapy with lenvatinib in terms of OS and PFS without increased toxicity. However, assessment and prophylaxis of skeletal muscle status should be recommended during a therapy with lenvatinib.

Abstract Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants.

Abstract Regulated mobile health applications are called digital health applications (“DiGA”) in Germany. To qualify for reimbursement by statutory health insurance companies, DiGA have to prove positive care effects in scientific studies. Since the empirical exploration of DiGA cost-effectiveness remains largely uncharted, this study pioneers the methodology of cohort-based state-transition Markov models to evaluate DiGA for depression. As health states, we define mild, moderate, severe depression, remission and death. Comparing a future scenario where 50% of patients receive supplementary DiGA access with the current standard of care reveals a gain of 0.02 quality-adjusted life years (QALYs) per patient, which comes at additional direct costs of ~1536 EUR per patient over a five-year timeframe. Influencing factors determining DiGA cost-effectiveness are the DiGA cost structure and individual DiGA effectiveness. Under Germany’s existing cost structure, DiGA for depression are yet to demonstrate the ability to generate overall savings in healthcare expenditures.

Abstract Adult ADHD is associated with increased risk for suicide attempts, as indicated by investigations of population- and community-based cohorts. However, there is little data regarding suicide attempts in a clinical setting. To address this, we used a comprehensively phenotyped clinical adult ADHD (aADHD) cohort to assess to which extent comorbidity, psychosocial adversity, personality, and ADHD symptoms contribute to suicidal behavior in ADHD. Furthermore, we investigated a triallelic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR), which has previously been associated with suicidal behavior. Depression, substance use, eating, and posttraumatic stress disorders were independently associated with past suicide attempts, whereas anxiety, somatoform, and obsessive–compulsive spectrum disorders showed no association. Pulmonary diseases also showed an association with suicidal behavior. Psychosocial factors including occupational status, marital status/living situation, externalizing behavior and psychiatric family history were strongly associated with past suicide attempts. ADHD symptoms of inattention and hyperactivity/impulsivity were not associated with past suicide attempts after adjustment for psychiatric comorbidity and psychosocial adversity. However, the personality trait of neuroticism fully mediated the association between depression and suicidal behavior. 5-HTTLPR was not associated with suicidal behavior, but an interaction with ADHD symptoms and subtype was found. Our data suggest that psychiatric comorbidity and psychosocial adversity are key factors for suicidal behavior in aADHD, with neuroticism representing a critical mediator of the association between depression and suicidality. Further research, preferentially with longitudinal study designs is needed to better understand causal factors for suicidal behavior to enable effective preventive action.

Abstract Background Only a few cases of bilateral traumatic sternoclavicular dislocations have been reported in the literature. This injury is considered one of the rarest injuries of the human musculoskeletal system. Therefore, we present the first documented case of a cyclist with a third-degree open thoracic trauma (Gustilo–Anderson 3a) associated with a dislocated manubrium sterni fracture in the upper thoracic aperture, bilateral anterior dislocations of the sternoclavicular joints, rib fractures, and pleural ruptures. Case presentation The patient, a 27-year-old Caucasian male, incurred this injury while participating in a professional cycling race at Nürburgring, Germany and received immediate interdisciplinary surgical treatment and has encountered no complications. We conducted a 1-year follow-up and present the clinical findings of this follow up. Additionally, we conducted a comprehensive review of the existing literature on this injury. Conclusions Immediate interdisciplinary intervention, including surgical repair and meticulous postoperative care, facilitated successful patient recovery. This underscores the critical role of comprehensive trauma management in complex polytrauma cases. In conclusion, this case report highlights the rarity and complexity of a traumatic injury involving bilateral sternoclavicular dislocation, with this case being the first case reported with concomitant open thorax trauma. Our patient benefited greatly from immediate air-bound transportation to an interdisciplinary care provider, which houses both thoracic and trauma surgery departments.

Abstract The introduction of mammography screening programs has significantly reduced breast cancer mortality rates. Nevertheless, some lesions remain undetected, especially in dense breast tissue. Studies have shown that phase-contrast imaging can improve breast cancer diagnosis by increasing soft tissue contrast. Furthermore, grating-based phase-contrast imaging enables the simultaneous acquisition of absorption, phase-contrast, and scattering, so-called dark-field images. The latter allows the classification of microcalcifications. In addition, breast computed tomography (BCT) systems can identify and discriminate overlapping but clinically relevant structures. This study investigates the benefit of combining grating-based phase-contrast with BCT. We explore the potential of grating-based phase-contrast breast computed tomography (gbpc-BCT) with a breast phantom and a freshly dissected fibroadenoma. Improved image contrast could be achieved with radiation doses comparable to those used in clinical BCT.

Abstract Background Traditional medical research infrastructures relying on the Centers of Excellence (CoE) model (an infrastructure or shared facility providing high standards of research excellence and resources to advance scientific knowledge) are often limited by geographic reach regarding patient accessibility, presenting challenges for study recruitment and accrual. Thus, the development of novel, patient-centered (PC) strategies (e.g., the use of online technologies) to support recruitment and streamline study procedures are necessary. This research focused on an implementation evaluation of a design innovation with implementation outcomes as communicated by study staff and patients for CoE and PC approaches for a randomized controlled trial (RCT) for patients with vasculitis. Methods In-depth qualitative interviews were conducted with 32 individuals (17 study team members, 15 patients). Transcripts were coded using the Consolidated Framework for Implementation Research (CFIR). Results The following CFIR elements emerged: characteristics of the intervention, inner setting, characteristics of individuals, and process. From the staff perspective, the communication of the PC approach was a major challenge, but should have been used as an opportunity to identify one “point person” in charge of all communicative elements among the study team. Study staff from both arms were highly supportive of the PC approach and saw its promise, particularly regarding online consent procedures. Patients reported high self-efficacy in reference to the PC approach and utilization of online technologies. Local physicians were integral for making patients feel comfortable about participation in research studies. Conclusions The complexity of replicating the interpersonal nature of the CoE model in the virtual setting is substantial, meaning the PC approach should be viewed as a hybrid strategy that integrates online and face-to-face practices. Trial registrations 1) Name: The Assessment of Prednisone In Remission Trial – Centers of Excellence Approach (TAPIR). Trial registration number: ClinicalTrials.gov NCT01940094 . Date of registration: September 10, 2013. 2) Name: The Assessment of Prednisone In Remission Trial – Patient Centric Approach (TAPIR). Trial registration number: Clinical Trials.gov NCT01933724 . Date of registration: September 2, 2013.

Abstract Purpose The goal of this retrospective study was to perform a CT imaging assessment of thoracic pedicles to provide a representative understanding of pedicle morphology for pedicle-based fixation systems commonly used in orthopedics, trauma and neurosurgery. This study aimed to better understand the morphology of the spine and give spine surgeons a better understanding of thoracic spine anatomy. Methods In this study, we retrospectively measured the thoracic spine pedicles of a total of 16 males and 16 females, totaling in 768 individual pedicles. For the measurements, we used standardized planes in computed tomography imaging with a maximum slice thickness of 1 mm. Results In brief, we identified significant differences in various measurements of male and female pedicle morphology. The medial cortical wall of the pedicles was significantly thicker than the lateral wall, and, in both sexes, the thoracic vertebral body number four was the vertebra with the least amount of cortical bone in the pedicle. Conclusions Surgeons performing operations involving pedicle screw placement should be aware of the sex-specific differences in thoracic spine pedicle morphology noted in this research.

Abstract The COVID-19 pandemic posed a challenge for people living with HIV (PLWH), particularly immune non-responders (INR) with compromised CD4 T-cell reconstitution following antiretroviral therapy (CD4 count

Dit artikel geeft een samenvatting van mijn proefschrift1 met drie onderling samenhangende studies omtrent de ‘microgrondslagen van controlekwaliteit.’ Het proefschrift toont aan dat accountants vaak eenvoudige taken voorrang geven, wat de kwaliteit van hun werk kan verminderen, vooral onder tijdsdruk. Het identificeert ook dat leerprocessen op de werkplek verbeterd kunnen worden door actieve participatie en dat automatisering de professioneel-kritische instelling van accountants kan verminderen. Door middel van experimenten en een literatuurstudie biedt het inzichten in operationele interventies die accountantsorganisaties kunnen gebruiken om zulke effecten te verminderen, met als doel de controlekwaliteit te verbeteren en de rol van accountants als vertrouwenspersonen van het maatschappelijk verkeer te versterken.

The biomechanical efficacy of nail–plate constructs (NPCs) used in the treatment of traumatic distal femur fractures (DFFs) remains understudied compared to traditional approaches. This systematic review examines the biomechanical efficacy of NPCs compared to alternative approaches for the surgical fixation of DFFs to guide surgical decision-making and improve patient outcomes. This systematic review searched the PubMed, CINAHL, MEDLINE, Web of Science, and SPORT Discus databases from inception until 24 January 2024. Inclusion criteria were biomechanical studies that involved nail–plate combination constructs for DFFs. Six observational studies were included. Of the included studies, five studies utilized synthetic bone models in testing, and one study used both synthetic and cadaveric bone models. All studies found NPCs to have significantly higher axial and torsional stiffness and resistance to loading than distal lateral femoral locking plate (DLFLP) constructs. The 11 mm NPCs were significantly stiffer than the 9 mm NPCs under torsional and axial loading. Only one of two studies found NPCs to have greater axial stiffness than dual-plate (DP) constructs. NPCs and DP constructs had greater torsional and axial stiffness than the plate-only or DP with medial distal tibial plate constructs. NPCs had less displacement and torque than the plate- or nail-only constructs under axial and torsional loads. NPCs demonstrate superior axial and torsional stiffness and resistance to mechanical loads compared to DLFLP. The varying performance between 11 mm and 9 mm NPCs suggests that construct diameter plays a role in mechanical stability. NPCs and DP constructs performed better than plate-only constructs. Future research should explore the impact of varying nail diameters and plate configurations on stability, as well as the clinical efficacy of NPCs across different patient populations, particularly those with varying bone densities, to better understand their performance in real-world scenarios.

Abstract Microbubble-enhanced ultrasound provides a noninvasive physical method to locally overcome major obstacles to the accumulation of blood-borne therapeutics in the brain, posed by the blood-brain barrier (BBB). However, due to the highly nonlinear and coupled behavior of microbubble dynamics in brain vessels, the impact of microbubble resonant effects on BBB signaling and function remains undefined. Here, combined theoretical and prospective experimental investigations reveal that microbubble resonant effects in brain capillaries can control the enrichment of inflammatory pathways that are sensitive to wall shear stress and promote differential expression of a range of transcripts in the BBB, supporting the notion that microbubble dynamics exerted mechanical stress can be used to establish molecular, in addition to spatial, therapeutic windows to target brain diseases. Consistent with these findings, a robust increase in cytotoxic T-cell accumulation in brain tumors was observed, demonstrating the functional relevance and potential clinical significance of the observed immuno-mechano-biological responses.

Abstract Objectives Critically ill patients with severe pancreatitis exhibit substantial muscle wasting, which limits in-hospital and post-hospital outcomes. Survivors of critical illness undergo extensive recovery processes. Previous studies have explored pancreatic function, quality of life, and costs post-hospitalization for AP patients, but none have comprehensively quantified muscle loss and recovery post-discharge. By applying an AI-based automated segmentation tool, we aimed to quantify muscle mass recovery in ICU patients after discharge. Materials Muscle segmentation was performed on 22 patients, with a minimum of three measurements taken during hospitalization and one clinically indicated examination after hospital discharge. Changes in psoas muscle area (PMA) between admission, discharge and follow up were calculated. T-Test was performed to identify significant differences between patients able and not able to recover their muscle mass. Results Monitoring PMA shows muscle loss during and gain after hospitalization: The mean PMA at the first scan before or at ICU admission (TP1) was 17.08 cm², at the last scan before discharge (TP2), mean PMA was 9.61 cm². The percentage change in PMA between TP1 and TP2 ranged from − 85.42% to -2.89%, with a mean change of -40.18%. The maximum muscle decay observed during the stay was − 50.61%. After a mean follow-up period of 438.73 days most patients (81%) were able to increase their muscle mass. Compared to muscle status at TP1, only 27% of patients exhibited full recovery, with the majority still presenting a deficit of 31.96%. Conclusion Muscle recovery in ICU patients suffering from severe AP is highly variable, with only about one third of patients recovering to their initial physical status. Opportunistic screening of post-ICU patient recovery using clinically indicated imaging and AI-based segmentation tools enables precise quantification of patients’ muscle status and can be employed to identify individuals who fail to recover and would benefit from secondary rehabilitation. Understanding the dynamics of muscle atrophy may improve prognosis and support personalized patient care.

Abstract Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees (“fixed-rate model”, FRM) and up-front staffing and consumables (“up-front allocation model”, UFAM) lack transparency and fail to suitably accommodate variations in centre performance. We developed a performance-based reimbursement model (PBRM) with automated calculation of conducted activities and applied it to the cohorts of the National Pandemic Cohort Network (NAPKON) within the Network of University Medicine (NUM). The study protocol activities, which were derived from data management systems, underwent validation through standardized quality checks by multiple stakeholders. The PBRM output (first funding period) was compared among centres and cohorts, and the cost-efficiency of the models was evaluated. Cases per centre varied from one to 164. The mean case reimbursement differed among the cohorts (1173.21€ [95% CI 645.68–1700.73] to 3863.43€ [95% CI 1468.89–6257.96]) and centres and mostly fell short of the expected amount. Model comparisons revealed higher cost-efficiency of the PBRM compared to FRM and UFAM, especially for low recruitment outliers. In conclusion, we have developed a reimbursement model that is transparent, accurate, and flexible. In multi-centre collaborations where heterogeneity between centres is expected, a PBRM could be used as a model to address performance discrepancies. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04768998 ; https://clinicaltrials.gov/ct2/show/NCT04747366 ; https://clinicaltrials.gov/ct2/show/NCT04679584 .

BACKGROUND AND AIMS OF THE STUDY: Congenital syphilis is a rare complication of syphilis in pregnant women. Vertical transmission may occur at any time during pregnancy. The incidence of congenital syphilis has been increasing worldwide. Congenital syphilis has been a notifiable disease for many years in Switzerland but reporting does not include maternal features associated with syphilis in pregnancy or infantʼs subsequent development. We described syphilis cases among pregnant women screened over a 10-year period in Switzerland and subsequent cases of congenital syphilis, in order to identify maternal risk profiles and to optimise prevention. Second, we compared the characteristics of pregnant women screened early (1st trimester) vs late in pregnancy (2nd or 3rd trimester). Finally, we assessed the risk factors for premature birth among these women with syphilis. METHODS: A multicentre retrospective study conducted in Swiss hospitals from 2012 to 2021, including pregnant women who screened positive for syphilis (Treponema pallidum haemagglutination assay [TPHA] / T. pallidum particle agglutination assay [TPPA ] ≥1:80) and newborns exposed to T. pallidum in utero and/or congenitally infected and with a positive syphilis serology at birth. Data were collected from medical records. RESULTS: A total of 147 syphilis-positive pregnant women and 102 infants were included. A history of treated syphilis was known for 44% (65/147) of the mothers corresponding to a serological scar and the remaining 56% (82/147) were newly identified syphilis cases. Syphilis screening was done during the first trimester in 54%, second trimester in 29% and third trimester in 13% of cases. Two babies were diagnosed with congenital syphilis (1.96%). Several potential factors that could contribute to women’s risk of syphilis during pregnancy were identified such as a foreign origin (93% of mothers), lack of healthcare insurance (25%), no employment status (37%), drug use (5%), co-infection with other sexually transmitted infections (24%) and a late first antenatal consultation (42%). The number of pregnant women without insurance was higher in women diagnosed in the second or third trimester than in those diagnosed in the first trimester (odds ratio 0.41; 95% CI 0.19–0.89; p = 0.024). Syphilis diagnosed in the second or third trimester was associated with a late first antenatal consultation (odds ratio 77.82; 95% CI 9.81–617.21; p

Background Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). Methods We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. Results Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. Conclusion This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.

Background: Persons with acquired hemophilia A are often older and suffer from comorbidity or frailty. Little is known about the impact on clinically relevant outcomes of acquired hemophilia A. Objectives: To assess the relevance of age, physical performance status, comorbidity, and concomitant medication on the risk of bleeding and other outcomes. Methods: Post hoc analysis of data from the GTH-AHA-EMI study that used emicizumab for bleed protection and withheld immunosuppressive treatment during the early phase of management. Primary endpoint was the rate of clinically relevant new bleeding (CRNB) during the first 12 weeks of emicizumab prophylaxis. Results: Forty-seven patients were enrolled. Median age was 76 years; performance status (World Health Organization performance status [WHO-PS]) was 3 or worse in 41%; Charlson comorbidity index (CCI) was 5 or higher in 63%; antithrombotic drugs were reported in 34%. Rate of CRNB during 12 weeks of emicizumab prophylaxis was similar across subgroups of age, sex, WHO-PS, CCI, baseline factor VIII activity, and inhibitor titer. Patients with CRNB during the study had more severe anemia already at baseline. However, persistent severe anemia in week 4 was not related to risk of bleeding beyond this time. CRNB was associated with injury from falling in 7 of 14 patients. Adverse events grade 3 or higher were not related to baseline CCI or age but were more frequent in patients with poor WHO-PS. Conclusion: Emicizumab provided bleed protection regardless of age and comorbidity. Clinical baseline characteristics did not predict breakthrough bleeding under emicizumab. Poor WHO-PS at baseline was associated with severe adverse events during the study.

Abstract Background Orthopedic procedures often require removing bone or pathological tissue, with traditional methods involving instruments like curettes and rongeurs. However, these methods can be time-consuming and lead to increased blood loss. To mitigate these side effects, vacuum-assisted tools have been developed to aid in tissue removal. These devices enable surgeons to suction tissue without discarding it, potentially improving outcomes in conditions such as osteomyelitis or tumor removal while enabling collection of the material for downstream applications. Despite limited research, vacuum-assisted devices show promise beyond bone marrow harvesting. This study assesses infection and clearance rates, estimated blood loss, and total procedure time associated with the use of vacuum-assisted tissue removal, with a goal to understand if these devices can be used for tissue removal across a variety of pathologic conditions. Methods A retrospective cohort study was conducted on patients undergoing orthopedic procedures with the Avitus® Bone Harvester repurposed from its original design from December 1, 2021, to July 1, 2023. Procedures were categorized into oncology, and debridement for infection cases. Infection cases were further categorized into those secondary to trauma and those involving primary infections (osteomyelitis and periprosthetic joint infection). Clinical variables, including demographics, intraoperative details, complications, and follow-up, were reviewed. Statistical analysis included descriptive statistics computed with R Studio. Results The study included 44 patients, with debridement for infection cases being the most common (primary infection: 45.5%; infection secondary to trauma: 18.1%), followed by oncology cases (36.4%). In all oncology cases, a definitive diagnosis was established using the device, and no post-operative infections were reported. The infection clearance rate was 85.0% for primary infection cases and 50.0% for cases of infection following trauma. Across the entire cohort, the average blood loss was 314.52 mL (sd: 486.74), and the average total procedure time was 160.93 min (sd: 91.07). The overall reoperation rate was 47.7%, with an unplanned reoperation rate of 11.4%. Conclusion The vacuum-assisted bone harvester was effectively utilized in a wide range of debridement and curettage procedures across diverse orthopedic surgeries. In oncology cases, the device enabled effective tissue removal with comparable recurrence rates, demonstrating its potential to minimize contamination while preserving tissue for accurate diagnoses. Additionally, a high rate of osteomyelitis eradication was observed in debridement for primary infection cases (85%). Despite the relatively high reoperation rate of 47.7%, it is crucial to interpret this figure within the context of the varied reasons for reoperation. Many of these reoperations were planned as part of a staged approach to treatment or were unrelated to the device's performance. It is crucial to acknowledge that isolating the device's contribution to these results can be difficult. The utilization of the device should be guided by considerations of cost-effectiveness and patient-specific risk factors.

Abstract Sex differences and age-related changes in the human heart at the tissue, cell, and molecular level have been well-documented and many may be relevant for cardiovascular disease. However, how molecular programs within individual cell types vary across individuals by age and sex remains poorly characterized. To better understand this variation, we performed single-nucleus combinatorial indexing (sci) ATAC- and RNA-Seq in human heart samples from nine donors. We identify hundreds of differentially expressed genes by age and sex and find epigenetic signatures of variation in ATAC-Seq data in this discovery cohort. We then scale up our single-cell RNA-Seq analysis by combining our data with five recently published single nucleus RNA-Seq datasets of healthy adult hearts. We find variation such as metabolic alterations by sex and immune changes by age in differential expression tests, as well as alterations in abundance of cardiomyocytes by sex and neurons with age. In addition, we compare our adult-derived ATAC-Seq profiles to analogous fetal cell types to identify putative developmental-stage-specific regulatory factors. Finally, we train predictive models of cell-type-specific RNA expression levels utilizing ATAC-Seq profiles to link distal regulatory sequences to promoters, quantifying the predictive value of a simple TF-to-expression regulatory grammar and identifying cell-type-specific TFs. Our analysis represents the largest single-cell analysis of cardiac variation by age and sex to date and provides a resource for further study of healthy cardiac variation and transcriptional regulation at single-cell resolution.

Abstract Background Primary sclerosing cholangitis (PSC) is a chronic liver disease leading to inflammation with scaring and strictures of bile ducts, which can lead to liver cirrhosis. A subtype of PSC characterized by high serum IgG4 (sIgG4) levels has been reported to be associated with poor outcomes, but the exact role and the longitudinal development of sIgG4 levels in PSC progression remains to be clarified. The aim of this study was to investigate if subsequent analysis of sIgG4 levels allows the identification of the PSC phenotype with high sIgG4. Methods sIgG4 values were repeatedly analysed in a well-characterized European PSC cohort of 110 individuals. Biochemical parameters, clinical endpoints, death and liver transplantation were compared between PSC subgroups. Results 12.7% (n = 14) of PSC patients showed increased sIgG4 levels (PSC-IgG4). The values normalized in 57.1% (n = 8; PSC-IgG4norm) during follow-up measurements, whereas the values remained permanently elevated in 42.9% (n = 6; PSC-IgG4const). Serum values of AP and γGT were significantly higher in PSC-IgG4const compared to PSC-IgG4norm at final blood sampling. Furthermore, mean age at PSC diagnosis was markedly lower in PSC-IgG4const compared to PSC-IgG4norm. Conclusions This is the first study analyzing longitudinal development of sIgG4 in PSC. Our data indicate that only sequential determination of sIgG4 levels allow to accurately distinguish between the PSC phenotype with high sIgG4 and PSC with low sIgG4. Graphical abstract

Abstract The basolateral amygdala (BLA) contains discrete neuronal circuits that integrate positive or negative emotional information and drive the appropriate innate and learned behaviors. Whether these circuits consist of genetically-identifiable and anatomically segregated neuron types, is poorly understood. Also, our understanding of the response patterns and behavioral spectra of genetically-identifiable BLA neurons is limited. Here, we classified 11 glutamatergic cell clusters in mouse BLA and found that several of them were anatomically segregated in lateral versus basal amygdala, and anterior versus posterior regions of the BLA. Two of these BLA subpopulations innately responded to valence-specific, whereas one responded to mixed - aversive and social - cues. Positive-valence BLA neurons promoted normal feeding, while mixed selectivity neurons promoted fear learning and social interactions. These findings enhance our understanding of cell type diversity and spatial organization of the BLA and the role of distinct BLA populations in representing valence-specific and mixed stimuli.

Abstract Key message Populations of the European white elm (Ulmus laevis Pall.) in Switzerland can be considered natural. They show no evidence of genetic differentiation from other European populations. In the past, the U. laevis populations were probably more widespread and continuous in Switzerland with a larger gene flow. Context In Switzerland, at the margin of its distribution range, U. laevis is rare and considered endangered. Whether the species is native to Switzerland has been disputed, and it is often surmised to be solely cultivated, without any natural population in the country. Aims The structure of genetic diversity among Swiss populations of U. laevis and comparison to European populations are expected to shed light on the origin of local populations and support their management. Methods We analyzed 19 populations (194 individuals) in Switzerland and 15 populations (158 individuals) from other European countries, using a set of five microsatellite loci. Results (1) 90% of the genetic variation in European and Swiss populations occurs within populations. (2) We did not detect isolation by distance at the regional or continental scale. (3) Clustering analysis did not reveal any spatial pattern in the level of admixture of individuals within Swiss or other European populations. Conclusion Moderate levels of genetic diversity and evidence for recent gene flow between populations indicate that habitat deterioration, loss, and fragmentation are the main threats to the persistence of U. laevis populations in Switzerland.

Abstract Herbivorous insects alter biogeochemical cycling within forests, but the magnitude of these impacts, their global variation, and drivers of this variation remain poorly understood. To address this knowledge gap and help improve biogeochemical models, we established a global network of 74 plots within 40 mature, undisturbed broadleaved forests. We analyzed freshly senesced and green leaves for carbon, nitrogen, phosphorus and silica concentrations, foliar production and herbivory, and stand-level nutrient fluxes. We show more nutrient release by insect herbivores at non-outbreak levels in tropical forests than temperate and boreal forests, that these fluxes increase strongly with mean annual temperature, and that they exceed atmospheric deposition inputs in some localities. Thus, background levels of insect herbivory are sufficiently large to both alter ecosystem element cycling and influence terrestrial carbon cycling. Further, climate can affect interactions between natural populations of plants and herbivores with important consequences for global biogeochemical cycles across broadleaved forests.

Abstract Pancreatic cancer (PC) is a clinically challenging tumor to combat due to its advanced stage at diagnosis as well as its resistance to currently available therapies. The absence of early symptoms and known detectable biomarkers renders this disease incredibly difficult to detect/manage. Recent advances in the understanding of PC biology have highlighted the importance of cancer-immune cell interactions, not only in the tumor micro-environment but also in distant systemic sites, like the bone marrow, spleen and circulating immune cells, the so-called macro-environment. The response of the macro-environment is emerging as a determining factor in tumor development by contributing to the formation of an increasingly immunogenic micro-environment promoting tumor homeostasis and progression. We will summarize the key events associated with the feedback loop between the tumor immune micro-environment (TIME) and the tumor immune macroenvironment (TIMaE) in pancreatic precancerous lesions along with how it regulates disease development and progression. In addition, liquid biopsy biomarkers capable of diagnosing PC at an early stage of onset will also be discussed. A clearer understanding of the early crosstalk between micro-environment and macro-environment could contribute to identifying new molecular therapeutic targets and biomarkers, consequently improving early PC diagnosis and treatment.

Abstract Background Giant cell arteritis (GCA) is the most common systemic vasculitis in adults. Presenting features include new-onset headaches, constitutional symptoms, jaw claudication, polymyalgia rheumatica, and visual symptoms. Arterial inflammation with subsequent stenosis and occlusion may cause tissue ischemia, leading to blindness, strokes, and myocardial infarction. Oral antiplatelet therapy has been hypothesized to reduce GCA-related ischemic events. However, previous studies have demonstrated conflicting results regarding the efficacy of antiplatelet agents in GCA. The objective of this systematic review is to assess the safety and efficacy of antiplatelet therapy for the prevention of these events in adults with giant cell arteritis. Methods In this systematic review, we will include randomized controlled trials (RTCs), quasi-randomized trials, non-randomized intervention studies, cohort studies, and case–control studies on patients with new-onset or relapsing GCA. The intervention of interest will be pre-existing use or initiation of an oral antiplatelet medication (aspirin, clopidogrel, prasugrel, or ticagrelor) at GCA onset or relapse. The comparator of interest will be the absence of antiplatelet therapy. Endpoints will be evaluated after 6 and 12 months of follow-up. The primary outcome will be GCA-related ischemic events, including permanent blindness, stroke, myocardial infarction, and ischemic event-related deaths. Adverse events such as major bleeding and death caused by a bleeding event will be assessed. Discussion GCA-related ischemic events are catastrophic, sudden, often irreversible, and lead to significant morbidity. Antiplatelet agents are affordable, accessible, and could be effective for the prevention of these events. Nevertheless, the potential benefits of platelet aggregation inhibition must be weighed against their associated risk of bleeding. Assessing the efficacy and safety of antiplatelet therapy in GCA is therefore clinically important. Systematic review registration Our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42023441574.

Abstract Total internal reflection fluorescence (TIRF) microscopy offers powerful means to uncover the functional organization of proteins in the plasma membrane with very high spatial and temporal resolution. Traditional TIRF illumination, however, shows a Gaussian intensity profile, which is typically deteriorated by overlaying interference fringes hampering precise quantification of intensities—an important requisite for quantitative analyses in single-molecule localization microscopy (SMLM). Here, we combine flat-field illumination by using a standard πShaper with multi-angular TIR illumination by incorporating a spatial light modulator compatible with fast super-resolution structured illumination microscopy (SIM). This distinct combination enables quantitative multi-color SMLM with a highly homogenous illumination. By using a dual camera setup with optimized image splitting optics, we achieve a versatile combination of SMLM and SIM with up to three channels. We deploy this setup for establishing robust detection of receptor stoichiometries based on single-molecule intensity analysis and single-molecule Förster resonance energy transfer (smFRET). Homogeneous illumination furthermore enables long-term tracking and localization microscopy (TALM) of cell surface receptors identifying spatial heterogeneity of mobility and accessibility in the plasma membrane. By combination of TALM and SIM, spatially and molecularly heterogenous diffusion properties can be correlated with nanoscale cytoskeletal organization and dynamics.

Wetlands are present within intricate ecological settings, exhibiting dynamic changes over time and across different areas with regard to their functional and structural diversity. Several approaches have been introduced for ecosystem analysis and management since 1990s, where Driver – Pressure – State – Impact – Response (DPSIR) framework is one of the widely used approaches for assessing and managing environmental problems. In this study, we proposed a DPSIR framework as a model in the Sebkhates of Aures wetland complex (SAWC, Northeast of Algeria), in order to create a regional wetland observatory to deliver ecosystem services within current state of changes resulted from socioeconomic drivers. DPSIR facilitates the identification of essential indicators to detect threats to the Sebkahtes of Aures wetlands complex (SAWC), influencing policymakers to enhance the protection and management of these wetlands. In line with the established DPSIR framework. This same approach and methodology could be applied to the other 15 wetlands complexes known in Algeria, culminating in the creation of a national wetland observatory. Furthermore, DPSIR can be employed as an analytical tool for policy making in the context of sustainable management of wetland ecosystems and can serve as a model in the establishment and development of various observatory programs in Algeria.

Abstract Background While potential risk factors for multiple sclerosis (MS) have been extensively researched, it remains unclear how persons with MS theorize about their MS. Such theories may affect mental health and treatment adherence. Using natural language processing techniques, we investigated large-scale text data about theories that persons with MS have about the causes of their disease. We examined the topics into which their theories could be grouped and the prevalence of each theory topic. Methods A total of 486 participants of the Swiss MS Registry longitudinal citizen science project provided text data on their theories about the etiology of MS. We used the transformer-based BERTopic Python library for topic modeling to identify underlying topics. We then conducted an in-depth characterization of the topics and assessed their prevalence. Results The topic modeling analysis identifies 19 distinct topics that participants theorize as causal for their MS. The topics most frequently cited are Mental Distress (31.5%), Stress (Exhaustion, Work) (29.8%), Heredity/Familial Aggregation (27.4%), and Diet, Obesity (16.0%). The 19 theory topics can be grouped into four high-level categories: physical health (mentioned by 56.2% of all participants), mental health (mentioned by 53.7%), risk factors established in the scientific literature (genetics, Epstein-Barr virus, smoking, vitamin D deficiency/low sunlight exposure; mentioned by 47.7%), and fate/coincidence (mentioned by 3.1%). Our study highlights the importance of mental health issues for theories participants have about the causes of their MS. Conclusions Our findings emphasize the importance of communication between healthcare professionals and persons with MS about the pathogenesis of MS, the scientific evidence base and mental health.

Abstract The current prostate cancer (PCa) screen test, prostate-specific antigen (PSA), has a high sensitivity for PCa but low specificity for high-risk, clinically significant PCa (csPCa), resulting in overdiagnosis and overtreatment of non-csPCa. Early identification of csPCa while avoiding unnecessary biopsies in men with non-csPCa is challenging. We built an optimized machine learning platform (ClarityDX) and showed its utility in generating models predicting csPCa. Integrating the ClarityDX platform with blood-based biomarkers for clinically significant PCa and clinical biomarker data from a 3448-patient cohort, we developed a test to stratify patients’ risk of csPCa; called ClarityDX Prostate. When predicting high risk cancer in the validation cohort, ClarityDX Prostate showed 95% sensitivity, 35% specificity, 54% positive predictive value, and 91% negative predictive value, at a ≥ 25% threshold. Using ClarityDX Prostate at this threshold could avoid up to 35% of unnecessary prostate biopsies. ClarityDX Prostate showed higher accuracy for predicting the risk of csPCa than PSA alone and the tested model-based risk calculators. Using this test as a reflex test in men with elevated PSA levels may help patients and their healthcare providers decide if a prostate biopsy is necessary.

Abstract Dysregulated epigenetic states are a hallmark of cancer and often arise from genetic alterations in epigenetic regulators. This includes missense mutations in histones, which, together with associated DNA, form nucleosome core particles. However, the oncogenic mechanisms of most histone mutations are unknown. Here, we demonstrate that cancer-associated histone mutations at arginines in the histone H3 N-terminal tail disrupt repressive chromatin domains, alter gene regulation, and dysregulate differentiation. We find that histone H3R2C and R26C mutants reduce transcriptionally repressive H3K27me3. While H3K27me3 depletion in cells expressing these mutants is exclusively observed on the minor fraction of histone tails harboring the mutations, the same mutants recurrently disrupt broad H3K27me3 domains in the chromatin context, including near developmentally regulated promoters. H3K27me3 loss leads to de-repression of differentiation pathways, with concordant effects between H3R2 and H3R26 mutants despite different proximity to the PRC2 substrate, H3K27. Functionally, H3R26C-expressing mesenchymal progenitor cells and murine embryonic stem cell-derived teratomas demonstrate impaired differentiation. Collectively, these data show that cancer-associated H3 N-terminal arginine mutations reduce PRC2 activity and disrupt chromatin-dependent developmental functions, a cancer-relevant phenotype.

Abstract Background Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is an ultra-rare, autosomal-dominant small vessel disease caused by loss-of-function variants in the gene TREX1. Recently, elevated serum levels of von Willebrand Factor Antigen (vWF-Ag) pointed to an underlying endotheliopathy, and microvascular ischemia was suggested to contribute to the neurodegeneration in RVCL-S. Aim of this study was to further elucidate the endotheliopathy in RVCL-S. Methods vWF-Ag and ADAMTS-13 activity were repeatedly measured in two patients with genetically confirmed RVCL-S. Renal biopsy of both RVCL-S patients and autoptic brain, renal, hepatic, and pulmonary specimen of one patient with RVCL-S were examined immunohistochemically in comparison to matched controls. In addition, cerebral methylome analysis was performed in the autoptic brain specimen calculating differentially methylated positions compared to controls. Results While vWF-Ag and activity was strongly elevated, ADAMTS-13 activity was low in RVCL-S and further decreased over the course of the disease. Autoptic brain specimen showed signs of thromboinflammation in cerebral small vessels, and vWF-Ag staining was strongly positive in cerebral and renal small vessels in RVCL-S, while only a light to moderate vWF-Ag staining was found in controls. Cerebral methylome analysis yielded 115 differentially methylated CpGs (p

Objectives: The optimal treatment strategy for symptomatic young infants with tetralogy of Fallot (TOF) is unclear. We sought to compare the outcomes of staged repair (SR) (shunt palliation followed by second-stage complete repair) versus primary repair (PR) at 2 institutions that have exclusively adopted each strategy. Methods: We performed propensity score-matched comparison of 143 infants under 4 months of age who underwent shunt palliation at one institution between 1993 and 2021 with 122 infants who underwent PR between 2004 and 2018 at another institution. The primary outcome was mortality. Secondary outcomes were postoperative complications, durations of perioperative support and hospital stays, and reinterventions. Median follow-up was 8.3 years (interquartile range, 8.1-13.4 years). Results: After the initial procedure, hospital mortality (shunt, 2.8% vs PR, 2.5%; P = .86) and 10-year survival (shunt, 95%; 95% confidence interval [CI], 90%-98% vs PR, 90%; 95% CI, 81%-95%; P = .65) were similar. The SR group had a greater risk of early reinterventions but similar rates of late reinterventions. Propensity score matching yielded 57 well-balanced pairs. In the matched cohort, the SR group had similar freedom from reintervention (55%; 95% CI, 39%-68% vs 59%; 95% CI, 43%-71%; P = .85) and greater survival (98%; 95% CI, 88%-99.8% vs 85%; 95% CI, 69%-93%; P = .02) at 10 years, as the result of more noncardiac-related mortalities in the PR group. Conclusions: In symptomatic young infants with TOF operated at 2 institutions with exclusive treatment protocols, the SR strategy was associated with similar cardiac-related mortality and reinterventions as the PR strategy at medium-term follow-up.

Potentially toxic elements (PTE), such as antimony (Sb), are dangerous putative contaminants for ground and surface waters around abandoned mines and ore deposits in Slovakia. Nearby mines antimony is commonly coprecipitated in ochre sediments precipitated from Fe-rich drainage waters and, therefore, these sites function as natural scavengers of this metalloid. Bacteria are well known to contribute to the process of redox state maintenance, biosorption and bioaccumulation of antimony and, consequently, to antimony precipitation or release from iron oxides complexes. Here we isolated 48 bacterial strains from circumneutral hydrous ferric oxides (HFO) rich iron ochres accumulated in the waters running from tailing pounds nearby Budúcnosť mine, Pezinok, Slovakia and polluted with high, but fluctuating, concentrations of antimony (130 μg/l Sb in water and 2317 mg/kg Sb in iron ochre in average). The isolated strains were V1-V9 16S rRNA sequenced and the resulting taxonomic affiliations of isolated strains were compared with taxonomy assignments obtained by V4 16S rRNA next generation sequencing approach, including two independent NGS analysis pipelines and different taxonomy classifiers ((IDTAXA (RDP, GTDB, SILVA, CONTAX), MEGAN (NCBI), RDP a SILVAngs). A Sb resistant subgroup of isolated strains (Pseudomonas A60B, Pseudomonas A59, Pseudomonas A28, Aeromonas A21, Aeromonas A13, Aeromonas A60A, Acinetobacter A14, Buttiauxella A58, Shewanella A20A a Yersinia A68), well growing at high Sb concentration (300 mg/l Sb), was tested for an ability of the strains to retain Sb from cultivation media. Based on ICP-MS measurements of the dried biomasses we concluded that all the strains can retain antimony from growth media to some extent, with strains Shewanella A20A, Buttiauxella A58, Yersinia A68 and Aeromonas A60A being the most effective.

Remote longitudinal studies are on the rise and promise to increase reach and reduce participation barriers in chronic disease research. However, maintaining long-term retention in these studies remains challenging. Early identification of participants with different patterns of long-term retention offers the opportunity for tailored survey adaptations. Using data from the online arm of the Swiss Multiple Sclerosis Registry (SMSR), we assessed sociodemographic, health-related, and daily-life related baseline variables against measures of long-term retention in the follow-up surveys through multivariable logistic regressions and unsupervised clustering analyses. We further explored follow-up survey completion measures against survey requirements to inform future survey designs. Our analysis included data from 1,757 participants who completed a median of 4 (IQR 2-8) follow-up surveys after baseline with a maximum of 13 possible surveys. Survey start year, age, citizenship, MS type, symptom burden and independent driving were significant predictors of long-term retention at baseline. Three clusters of participants emerged, with no differences in long-term retention outcomes revealed across the clusters. Exploratory assessments of follow-up surveys suggest possible trends in increased survey complexity with lower rates of survey completion. Our findings offer insights into characteristics associated with long-term retention in remote longitudinal studies, yet they also highlight the possible influence of various unexplored factors on retention outcomes. Future studies should incorporate additional objective measures that reflect participants' individual contexts to understand their ability to remain engaged long-term and inform survey adaptations accordingly.

ABSTRACT For over a century, the filamentous Ascomycete fungus Aspergillus niger has played a pivotal role in the industrial production of citric acid. A critical fermentation parameter that sustains high-yield citric acid accumulation is the suboptimal concentration of manganese(II) ions in the culture broth at the early stages of the process. However, the requirement for this deficiency has not been investigated on a functional genomics level. In this study, we compared the transcriptome of the citric acid hyper-producer A. niger NRRL2270 strain grown under citric acid-producing conditions in 6-L scale bioreactors at Mn2+ ion-deficient (5 ppb) and Mn2+ ion-sufficient (100 ppb) conditions at three early time points of cultivation. Of the 11,846 genes in the genome, 963 genes (8.1% of the total) were identified as significantly differentially expressed under these conditions. Disproportionately high number of differentially regulated genes encode predicted extracellular and membrane proteins. The most abundant gene group that was upregulated in Mn2+ ion deficiency condition encodes enzymes acting on polysaccharides. In contrast, six clusters of genes encoding secondary metabolites showed downregulation under manganese deficiency. Mn2+ deficiency also triggers upregulation of the cexA gene, which encodes the citrate exporter. We provide functional evidence that the upregulation of cexA is caused by the intracellular accumulation of citrate or acetyl-CoA and is a major factor in triggering citrate overflow.IMPORTANCECitric acid is produced on industrial scale by batch fermentation of the filamentous fungus Aspergillus niger. High-yield citric acid production requires a low (

This article interrogates the Western “confrontational” model of argumentation, discourse/counter-discourse, and a possible alternative to the Toulminian model, through the prism of Chinese argumentation. It is based on a selection of translated extracts from classical Chinese texts. The passages studied range from Confucius (6th century CE) to the 1st century CE. AEC. The conditions for working with translations are specified in a text using analogy. An argument based on a play on homonymous words (and considered invalid by the translator) falls into the vast domain of arguments based purely on linguistic maneuvers. Numerous cases illustrate the fundamental role of contradiction and ad hominem refutation as possible sources of an argumentative situation. The Western tradition has produced many systems of “rules for an honorable controversy”; we have come across a set of rules on a similar but different issue: the precautions to be selected when choosing a discussion partner. §4 is devoted to what seems to be a general characteristic of the period under consideration (Graham 1989), which produces sophisticated argumentation, without referring it to a theory of argumentation, but to the notion of ritual. In conclusion: the Western style of analysis is robust and can account for facts that are constant in other cultures. Perhaps the differences lie elsewhere?

Objective After infection with SARS-CoV-2, a substantial proportion of patients develop long-lasting sequelae. These sequelae include fatigue (potentially as severe as that seen in ME/CFS cases), cognitive dysfunction, and psychiatric symptoms. Because the pathophysiology of these sequelae remains unclear, existing therapeutic concepts address the symptoms through pacing strategies, cognitive training, and psychological therapy. Methods Here, we present a protocol for a digital multimodal structured intervention addressing common symptoms through three intervention modules: BRAIN, BODY, and SOUL. This intervention includes an assessment conducted via a mobile “post-COVID-19 bus” near the patient's home, as well as the use of wearable devices and mobile applications to support pacing strategies and collection of data, including ecological momentary assessment. Results We will focus on physical component subscore of the SF36 as Quality of Life parameter as the primary outcome parameter for WATCH to take into account the holistic approach that is necessary for care of post-COVID patients Conclusion In the current project, we present a protocol for a holistic and multimodal structured therapeutic concept which is easily accessible, and scalable for post-COVID patients.

Political expression is a focal point for understanding how digital media have transformed political engagement. Privacy concerns tend to impede online political expression, but this relationship is still poorly understood. Based on the theory of reasoned action, this study focuses on the role of social influence and institutional privacy concerns in political expression on Facebook. We draw on research on the privacy calculus to examine how observing the behavior of Facebook friends moderates the relationship between privacy concerns and online political expression. We use survey data gathered in 2023 from Canada, France, Germany, the United Kingdom, and the United States ( n = 5,936). Across all five countries, we find that observing Facebook friends posting political content bolsters political expression on Facebook, as per our preregistered analysis. In all countries except Germany, privacy concerns impede political expression on Facebook. Also, the importance of institutional privacy concerns for political expression depends on the observed posting behavior of Facebook friends. This moderated effect is only observed in three of the five examined countries, however. Our findings offer new insights into the factors that encourage and discourse political expression, particularly on Facebook which is a platform that has been widely criticized for failing to protect its users’ privacy.

Dieser Artikel beschreibt Herausforderungen, Ziele und Möglichkeiten strategischer Kommunikation zum Forschungsdatenmanagement. Er zeigt, wie das Chemie-Konsortium zur Umsetzung einer Nationalen ForschungsDatenInfrastruktur NFDI4Chem arbeitet, um mit begrenzten Ressourcen möglichst effektiv den Einsatz von Forschungsdatenmanagement und den Output FAIRer Daten in der Chemie zu erhöhen. Beschrieben wird die Erstellung und Umsetzung einer Kommunikationsstrategie von der Analyse über die Planung und Implementierung bis hin zur Evaluierung.

ABSTRACT The number of Vibrio-related infections in humans, e.g., by Vibrio vulnificus, has increased along the coasts of the Baltic Sea. Due to climate change, vibriosis risk is expected to increase. It is, therefore, pertinent to design a strategy for mitigation of the vibriosis threat in the Baltic Sea area, but a prerequisite is to identify the environmental conditions promoting the occurrence of pathogenic Vibrio spp., like V. vulnificus. To address this, we sampled three coastal Baltic sites in Finland, Germany, and Denmark with salinities between 6 and 21 from May to October 2022. The absolute and relative abundances of Vibrio spp. and V. vulnificus in water were compared to environmental conditions, including the presence of the eelgrass Zostera marina, which has been suggested to reduce pathogenic Vibrio species abundance. In the water column, V. vulnificus only occurred at the German station between July and August at salinity 8.1–11.2. Temperature and phosphate (PO43–) were identified as the most influencing factors for Vibrio spp. and V. vulnificus. The accumulation of Vibrio spp. in the sediment and the co-occurrence with sediment bacteria in the water column indicate that sediment resuspension contributed to V. vulnificus abundance. Interestingly, V. vulnificus co-occurred with specific cyanobacteria taxa, as well as specific bacteria associated with cyanobacteria. Although we found no reduction in Vibrio spp. or V. vulnificus associated with eelgrass beds, our study underscores the importance of extended heatwaves and sediment resuspension, which may elevate the availability of PO43–, for Vibrio species levels at intermediate salinities in the Baltic Sea.IMPORTANCEElevated sea surface temperatures are increasing the prevalence of pathogenic Vibrio at higher latitudes. The recent increase in Vibrio-related wound infections and deaths along the Baltic coasts is, therefore, of serious health concern. We used culture-independent data generated from three Baltic coastal sites in Denmark, Germany, and Finland from May to October (2022), with a special focus on Vibrio vulnificus, and combined it with environmental data. Our temporal model shows that temperature, combined with sediment resuspension, drives the prevalence of V. vulnificus at intermediate salinities in the coastal Baltic Sea.

Background: To determine any differences in clinical outcomes between patients in the supine vs the lateral position during anterior-based muscle sparing (ABMS) total hip arthroplasty (THA). Methods: A retrospective review was performed of 368 patients undergoing THA via the ABMS approach (201 lateral vs 167 supine position) at our institution (2015-2019) with a minimum follow-up of 12 months. Inclusion criteria were all patients undergoing primary THA. Exclusion criteria were any revision surgeries and patients who did not undergo the ABMS THA. Outcomes assessed were postoperative complication rates, ambulation distance, length of stay, and Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness, and physical function scores at 3 time periods (preoperative, 3 months postoperative, and 1 year postoperative). Results: The supine group had significantly greater postoperative day 0 ambulation distance (150 vs 60 meters; P < .001), while no difference was observed on postoperative day 1 (210 meters in supine vs 200 in lateral; P = .921). Median length of stay was significantly shorter in the supine group (1; interquartile range 0-1) with respect to the lateral group (1; interquartile range 0-2; P < .001). The in-hospital complication rates (2.4% in supine vs 1.5% in lateral; P = .780), return to operating room rates (2.4% in supine vs 1.5% in lateral; P = .780), and readmission rates (5.4% in supine vs 5.0% in lateral; P = .631) were not significantly different between the groups. No significant differences were observed across any Western Ontario and McMaster Universities Osteoarthritis Index scores. Conclusions: Both supine and lateral patient positioning provide acceptable early surgical outcomes, suggesting that satisfactory results can be obtained via both positions in THAs.

Most malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and PfHRP3, but deletions of pfhrp2 and phfrp3 genes make parasites undetectable by RDTs. We analyzed 19,313 public whole-genome-sequenced P. falciparum field samples to understand these deletions better. Pfhrp2 deletion only occurred by chromosomal breakage with subsequent telomere healing. Pfhrp3 deletions involved loss from pfhrp3 to the telomere and showed three patterns: no other associated rearrangement with evidence of telomere healing at breakpoint (Asia; Pattern 13-TARE1); associated with duplication of a chromosome 5 segment containing multidrug-resistant-1 gene (Asia; Pattern 13-5++); and most commonly, associated with duplication of a chromosome 11 segment (Americas/Africa; Pattern 13-11++). We confirmed a 13–11 hybrid chromosome with long-read sequencing, consistent with a translocation product arising from recombination between large interchromosomal ribosome-containing segmental duplications. Within most 13-11++ parasites, the duplicated chromosome 11 segments were identical. Across parasites, multiple distinct haplotype groupings were consistent with emergence due to clonal expansion of progeny from intrastrain meiotic recombination. Together, these observations suggest negative selection normally removes 13-11++pfhrp3 deletions, and specific conditions are needed for their emergence and spread including low transmission, findings that can help refine surveillance strategies.

O entendimento da modernidade como um evento global e simbiótico é o que justifica este ensaio. Global, pois, como desdobramento cultural da Revolução Industrial, alcançou os rincões mais ou menos conectados com a ordem mundial; simbiótico porque, apesar do discurso hegemônico eurocêntrico, declaramos a constante retroalimentação dos processos de experimentação artística que equiparam as experiências de todos os continentes. Discorreremos comparativamente sobre a obra de Oscar Niemeyer (1907-2012), Jean-François Zevaco (1916-2003) e Vann Molyvann (1926-2017), em ensaio organizado em duas seções. A primeira busca os aspectos dirigidos pela leitura do território, entendido como a conjunção de fatores físicos e humanos do lugar em que se desenvolve a arquitetura; aponta estratégias de aceitação da contribuição vernacular e de sua interpretação à luz do instrumental moderno. A segunda avança sobre os termos construtivos do pensamento dos arquitetos, localizando o contextualismo estrutural como ação plástica deliberada.

Abstract Li‐Hectorite (Li‐Hec) clays have inherent 2D diffusion slits offering high lithium (Li+) ion conductivity. Such Li‐Hec clays spontaneously delaminate into flexible nanosheets, allowing them to be coated on high‐temperature stable polybenzimidazole (PBI) nanofibers laid randomly onto each other in the form of non‐woven membranes. Here such Li‐Hec coated PBI nonwovens are shown to be excellent Li‐ion battery separators. An effective strategy based on electrospinning PBI followed by a filtration‐through coating of delaminated Li‐Hec nanosheets of appropriate diameter is applied to prepare the separators without the use of any binder. The composite separator shows excellent properties, such as superior wettability (solvent uptake 413%), thermostability (>500 °C), superior flame resistance, and interfacial compatibility. Additionally, the presented separator shows excellent ion conductivity, Li‐ion transference number, cycling stability, and a rate performance that outperforms the common commercial separators. In summary, this work allows for a better balance between safety, high performance, and separator functionality.

Across Europe, the public sector is expanding its efforts to introduce data-driven decision-support and intelligent systems in the administration of welfare. The growing body of research that highlights the impact and harms these systems have on citizens’ lives, raises questions about the guiding ideas, values, and norms that are at the heart of current transformations in welfare. Research in critical data studies contends a silent marketisation of social protection and governance. It implies an intricate entanglement between the procedures and output of service provision on the one hand and the normative outcomes in terms of the well-being and flourishing of society as a whole on the other hand. Thinking with the capabilities approach and buen vivir as well as with the concept of data justice, our paper asks how to conceptualise this relation. It discusses how (in)justice may become a sociomaterial component in automated welfare and emphasises that welfare outcomes and welfare practices, including their procedural aspects, are rather co-produced than just interdependent. We conclude that whether future infrastructures of welfare will create public value or not, depends on the institutional arrangements, policies, and norms built to distribute the emerging benefits and risks equally in society.

Individuals utilizing Life Cycle Assessment within the emerging field of circular carbon might phrase and understand matters differently, causing ambiguity, due to different educational backgrounds and lacking definitions of central terms. Our research addresses the question, whether misleading or ambiguous terms exist, which impair transparency and scientific accuracy in carbon (dioxide) accounting in LCA. A structured literature research was performed to screen LCA standards, ISO standards, and the European legal database EUR-Lex. Nine terms with potential ambiguity in meaning or usage in LCA were identified: Avoided burden, avoided carbon, avoided CO2, carbon capture, carbon credit, circular carbon, circular CO2, negative emission, and net zero emission. A workflow was introduced to either obtain a consensus-based definition from standard literature or from peer-reviewed publications. For all terms, except avoided carbon, a recommended definition was found and showcased within case studies on the topic of mechanical recycling of plastics to produce a taxonomy suggestion for precise descriptions of different carbon dioxide (equivalent) accounting methods in LCA.

BackgroundDespite the increased accessibility and availability of technology in recent years, equality and access to health-related technology remain limited to some demographics. In particular, patients who are older or from rural communities represent a large segment of people who are currently underusing mobile health (mHealth) solutions. System usability continues to hinder mHealth adoption among users with nontraditional digital literacy. ObjectiveThis study aims to investigate if state-of-the-art mobile app interfaces from open-source libraries provide sufficient usability for rural patients with cancer, with minimal design changes and forgoing the co-design process. MethodsWe developed Assuage (Network Reconnaissance Lab) as a research platform for any mHealth study. We conducted a pilot study using Assuage to assess the usability of 4 mobile user interfaces (UIs) based on open-source libraries from Apple’s ResearchKit and CareKit. These UIs varied in complexity for reporting distress symptoms. Patients with cancer were recruited at the Markey Cancer Center, and all research procedures were conducted in person. Participants completed the distress assessment using a randomly selected UI in Assuage with little to no assistance. Data were collected on participant age, location, mobile app use, and familiarity with mHealth apps. Participants rated usability with the System Usability Scale (SUS), and usability issues were documented and compared. A one-way ANOVA was used to compare the effect of the UIs on the SUS scores. ResultsWe recruited 30 current or postsurgery patients with cancer for this pilot study. Most participants were aged >50 years (24/30, 80%), from rural areas (25/30, 83%), had up to a high school education (19/30, 63%), and were unfamiliar with mHealth apps (21/30, 70%). General mobile app use was split, with 43% (14/30) of the patients not regularly using mobile apps. The mean SUS score across the UIs was 75.8 (SD 22.2), with UI 3 and UI 4 achieving an SUS score ≥80, meeting the industry standard for good usability of 80. Critical usability issues were related to data input and navigation with touch devices, such as scale-format questions, vertical scrolling, and traversing multiple screens. ConclusionsThe findings from this study show that most patients with cancer (20/30, 67%) who participated in this study rated the different interfaces of Assuage as above-average usability (SUS score >68). This suggests that Apple’s ResearchKit and CareKit libraries can provide usable UIs for older and rural users with minimal interface alterations. When resources are limited, the design stage can be simplified by omitting the co-design process while preserving suitable usability for users with nontraditional technical proficiency. Usability comparable to industry standards can be achieved by considering heuristics for interface and electronic survey design, specifically how to segment and navigate surveys, present important interface elements, and signal gestural interactions.

Background Poor air quality can both trigger and aggravate lung and heart conditions, as well as affecting child development. It can even lead to neurological and mental health problems. However, the precise mechanisms by which air pollution affect human health are not well understood. Aims To promote interdisciplinary dialogue and better research based on a critical summary of evidence on air quality and health, with an emphasis on mental health, and to do so with a special focus on bioaerosols as a common but neglected air constituent. Method A rapid narrative review and interdisciplinary expert consultation, as is recommended for a complex and rapidly changing field of research. Results The research methods used to assess exposures and outcomes vary across different fields of study, resulting in a disconnect in bioaerosol and health research. We make recommendations to enhance the evidence base by standardising measures of exposure to both particulate matter in general and bioaerosols specifically. We present methods for assessing mental health and ideal designs. There is less research on bioaerosols, and we provide specific ways of measuring exposure to these. We suggest research designs for investigating causal mechanisms as important intermediate steps before undertaking larger-scale and definitive studies. Conclusions We propose methods for exposure and outcome measurement, as well as optimal research designs to inform the development of standards for undertaking and reporting research and for future policy.