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Summary: Background: Research in healthy young adults shows that characteristic patterns of brain activity define individual “brain-fingerprints” that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson’s disease (PD). Methods: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. Findings: The arrhythmic spectral components of cortical activity in patients with Parkinson’s disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson’s brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson’s symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson’s brain-fingerprint aligns with that of neurotransmitter systems affected by the disease’s pathophysiology. Interpretation: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson’s disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson’s disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. Funding: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer’s Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

Raynaud-Claes syndrome is rare condition characterized with intellectual disability and is caused by X-linked pathogenic variants in CLCN4 gene. Hemizygous missense variant NM_001830.4: c.1597G>A (p.V533M) was detected in a 6-year-old male followed up with intellectual disability, dysmorphism, and epileptic encephalopathy. The mother and one sister of the patient were also carrying the same variant. The clinical picture of the patient was significantly more severe, and the patient exhibited nonconvulsive status. Tonic status was observed with benzodiazepine treatment and the patient was successfully treated with a ketogenic diet. Many types of seizures can be seen in Raynaud-Claes syndrome, some of which can be life-threatening. CLCN4 variants can be investigated in patients who exhibit an increase in tonic seizures with benzodiazepine treatment. However, ketogenic dietary therapy as first-line treatment can be lifesaving in resistant epilepsy cases caused by the CLCN4 gene.

Abstract Our study investigated the emergence of spatial quasi-bound states (QBSs) in graphene monolayers induced by rectangular potential barriers. By solving the time-independent Dirac equation and using the transfer matrix formalism, we calculated the resonance energies and identify the QBSs based on probability density functions (PDF). We analyzed two types of structures: single and double barriers, and we find that the QBSs are located within the barrier region, at energies higher than the single barrier. Additionally, we observe QBSs in the double barrier and their position depends on the distance and width of the well between the two barriers. The width and height of the barrier significantly impact the QBSs while the well width influences the resonance energy levels of the QBSs in the double barrier. Interestingly, the QBSs can be manipulated in the graphene system, offering potential for optoelectronic devices. Finally, our results demonstrated that the spatial localization of these states is counter-intuitive and holds great promise for future research in optolectronic devices.

This study investigates AI bias in financial technology (FinTech)-based supply chain management in Pakistan. The study employs Structural Equation Modeling (SEM) to analyze data from diverse respondents. Hypotheses examine the relationships between AI integration, algorithm diversity, employee training, data quality, regulatory compliance, organizational culture, and AI bias. The findings reveal that higher AI integration leads to increased AI bias, Algorithm diversity reduces AI bias, while employee training decreases bias, Quality and diversity of data negatively correlate with AI bias, and regulatory compliance lowers bias. In addition, organizational culture mediates the relationship between AI integration and AI bias. This research contributes a holistic understanding of AI bias factors, guiding ethical AI adoption. Policymakers can use these insights to shape regulations, and industry practitioners can make informed decisions.

In 2021, we published the results of genomic analyses carried out on the famous bishop of Lund, Peder Winstrup, and the mummified remains of a 5–6-month-old fetus discovered in the same burial. We concluded that the two individuals were second-degree relatives and explored the genealogy of Peder Winstrup to further understand the possible relation between them. Through this analysis, we found that the boy was most probably Winstrup’s grandson and that the two were equally likely related either through Winstrup’s son, Peder, or his daughter, Anna Maria von Böhnen. To further resolve the specific kinship relation, we generated more genomic data from both Winstrup and the boy and implemented more recently published analytical tools in detailed Y chromosome- and X chromosome-based kinship analyses to distinguish between the competing hypotheses regarding maternal and paternal relatedness. We found that the individuals’ Y chromosome lineages belonged to different sub-lineages and that the X-chromosomal kinship coefficient calculated between the two individuals were elevated, suggesting a grandparent–grandchild relation through a female, i.e., Anna Maria von Böhnen. Finally, we also performed metagenomic analyses, which did not identify any pathogens that could be unambiguously associated with the fatalities.

يهدف البحث إلى بيان حجية إثبات التزييف العميق تقنياً وفقهياً في أنظمة الذكاء الاصطناعي، إذ لا يزال كثير من الناس يخشى ضرر هذا التطور في الذكاء الاصطناعي ومحاكاة بصمة الصوت والصورة ونحو ذلك. ويحتوي البحث على مفهوم الذكاء الاصطناعي، ثم التفصيل في طريقة كشف التزييف العميق تقنياً، ثم حجية التزييف العميق فقهياً ، ثم النتيجة وهي: أن القرائن المرجحة تعتبر أحد طرق الإثبات المعتبرة في القضاء في الإسلام، و أن وسائل الإثبات غير محصورة بعدد معين، وبناءً عليه: فإن تلك المقاطع المرئية أو المسموعة والتي تم الكشف عليها من خلال أدوات التزييف العميق ولم يثبت تزييفها أحد القرائن التي تختلف في قوتها وضعفها، وذلك مما يقدره القاضي وخبراء الاختصاص معه، ويترتب على ذلك بحسب القرائن: إثبات حجية الحقوق، أو إسقاطها.

ABSTRACTDendritic cells (DCs) play a key role in the induction of the adaptive immune response. They capture antigens in peripheral tissues and prime naïve T lymphocytes, triggering the adaptive immune response. In the course of inflammatory processes DCs face stressful conditions including hypoxia, low pH and high concentrations of reactive oxygen species (ROS), among others. How DCs survive under these adverse conditions remain poorly understood. Clusterin is a protein highly expressed by tumors and usually associated with bad prognosis. It promotes cancer cell survival by different mechanisms such as apoptosis inhibition and promotion of autophagy. Here, we show that, upon maturation, human monocyte-derived DCs (MoDCs) up-regulate clusterin expression. Clusterin protects MoDCs from ROS-mediated toxicity, enhancing DC survival and promoting their ability to induce T cell activation. In line with these results, we found that clusterin is expressed by a population of mature LAMP3+ DCs, called mregDCs, but not by immature DCs in human cancer. The expression of clusterin by intratumoral DCs was shown to be associated with a transcriptomic profile indicative of cellular response to stress. These results uncover an important role for clusterin in DC physiology.

BackgroundPatients with hepatic metastases from neuroendocrine tumors (NETs) benefit from an early diagnosis, which is crucial for the optimal therapy and management. Diagnostic procedures include morphological and functional imaging, identification of biomarkers, and biopsy. ObjectiveThe aim of six systematic reviews discussed in this study is to assess the predictive value of Ki67 index and other biomarkers, to compare the diagnostic accuracy of morphological and functional imaging, and to define the role of biopsy in the diagnosis and prediction of neuroendocrine tumor liver metastases. MethodsAn objective group of librarians will provide an electronic search strategy to examine the following databases: MEDLINE, EMBASE and The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects). There will be no restriction concerning language and publication date. The qualitative and quantitative synthesis of the systematic review will be conducted with randomized controlled trials (RCT), prospective and retrospective comparative cohort studies, and case-control studies. Case series will be collected in a separate database and only used for descriptive purposes. ResultsThis study is ongoing and presents a protocol of six systematic reviews to elucidate the role of histopathological and biochemical markers, biopsies of the primary tumor and the metastases as well as morphological and functional imaging modalities for the diagnosis and prediction of neuroendocrine liver metastases. ConclusionsThese systematic reviews will assess the value and accuracy of several diagnostic modalities in patients with NET liver metastases, and will provide a basis for the development of clinical practice guidelines. Trial RegistrationThe systematic reviews have been prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42012002644; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2644 (Archived by WebCite at http://www.webcitation.org/6LzCLd5sF), CRD42012002647; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2647 (Archived by WebCite at http://www.webcitation.org/6LzCRnZnO), CRD42012002648; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2648 (Archived by WebCite at http://www.webcitation.org/6LzCVeuVR), CRD42012002649; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2649 (Archived by WebCite at http://www.webcitation.org/6LzCZzZWU), CRD42012002650; http://www.metaxis.com/prospero/full_doc.asp?RecordID=2650 (Archived by WebCite at http://www.webcitation.org/6LzDPhGb8), CRD42012002651; http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42012002651#.UrMglPRDuVo (Archived by WebCite at http://www.webcitation.org/6LzClCNff).

IntroductionIt is unclear whether patients with diabetes are more susceptible to nerve toxicity of local anesthetics or whether nerve blocks can accelerate the progression of diabetic peripheral neuropathy. Bupivacaine is one of the most widely used local anesthetics for regional anesthesia despite many pre-clinical studies demonstrating neurotoxicity. Herein, we report the long-term functional consequences of sciatic nerve block with bupivacaine and liposomal bupivacaine (Exparel®) in an animal model of diabetes.MethodsMale Sprague Dawley rats were subject to standard chow/vehicle or high-fat diet/low-dose streptozotocin to induce a diabetic phenotype. Animals were then subdivided into groups that received repeated sciatic nerve blocks of saline, bupivacaine, or liposomal bupivacaine. Mechanical allodynia and thermal hyperalgesia were assessed prior to and 12 weeks following nerve blocks utilizing the von Frey and Hargreaves tests, respectively. Exploratory and locomotor activity were assessed with open field testing, and nerve conduction velocity testing was conducted prior to the termination of the study at 28 weeks.ResultsAnimals in the diabetic group developed sustained hyperglycemia >200 mg/dl and signs of peripheral neuropathy six weeks after treatment with streptozotocin, which persisted until the end of the study. Twelve weeks after a repeated sciatic nerve block with saline, bupivacaine, or liposomal bupivacaine, results indicate significant interaction effects of the disease group (control vs. diabetic) and local anesthetic treatment. Overall, diabetic status resulted in worse sensorimotor function compared to control animals. Treatment with perineural bupivacaine resulted in worse sensorimotor functions in both control and diabetic animals. Furthermore, bupivacaine treatment in diabetic animals with pre-existing neuropathy exacerbated sensorimotor function in some measures. In contrast, liposomal bupivacaine did not appear to cause any negative effects on functional outcomes for control or diabetic animals.ConclusionOur data indicate that bupivacaine, and not liposomal bupivacaine, causes long-term changes in tactile allodynia, thermal hyperalgesia, locomotor behaviors, and nerve conduction velocity in control as well as a high-fat diet/low-dose streptozotocin rodent model of diabetes. These results highlight the necessity to investigate safe peripheral nerve block strategies to preserve long-term functional independence in patients with or at risk for diabetic peripheral neuropathy.

The global economy relies heavily on oil production, but it is not without challenges. During the period of economic globalization, the revenue and costs associated with oil production have become disjointed, which has had a detrimental effect on the environment. As a result, environmental protection has been compromised, environmental regulations have been weakened, natural resources have been exploited, and climate change has been exacerbated. This study examines the impact of revenue minus the production cost of oil, energy use, and shadow economy on environmental degradation in APEC countries from 1991 to 2020, using the economic globalization index as a moderating variable. The result explains that revenue minus the oil production cost and the shadow economy are negatively associated with environmental degradation. Energy use and economic globalization are positively associated with environmental degradation in APEC countries. Revenue minus the production cost of oil and shadow economy improve the environment. Energy use and economic globalization degrade the environment in APEC countries. Policymakers are encouraged to advance technologies and upgrade infrastructure to reduce greenhouse gas emissions; also, promoting energy-efficient practices in other sectors, like transportation and manufacturing, could contribute to a healthier environment.

Introduction Growing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, LSD, MDMA and other substances. Data suggests that these compounds have the potential to treat mental health conditions that are especially prevalent in older adults such as depression, anxiety, existential distress and post-traumatic stress disorder. Objectives The goal of this study was to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population. Methods A systematic review was conducted following the 2020 PRISMA guidelines. Search criteria included all trials published in English using psychedelic substances to treat psychiatric conditions, including addiction as well as existential distress related to serious illness. Articles were identified from literature searches on PubMed, EBSCO and EMBASE. Results 4,376 manuscripts were identified, of which 505 qualified for further review, with 36 eventually meeting eligibility criteria. Of the 1,400 patients enrolled in the 36 studies, only 19 were identified as 65 or older, representing less than 1.4% of all trial participants. For 10 of these 19 older adults, detailed safety data was obtained. No serious adverse events (AEs) occurred in any older adults and only transient mild-to-moderate AEs related to anxiety, gastrointestinal upset, and hypertension were reported during the psychedelic dosing sessions. Conclusions While existing data in older adults is limited, it suggests that psychedelic-assisted psychotherapy is safe and well tolerated in older adults. Therefore, psychedelic-assisted psychotherapy should be more rigorously investigated for the treatment of psychiatric conditions in this population. Disclosure of Interest None Declared

Paleo-proxy data indicate that a “Green Sahara” thrived in northern Africa during the early- to mid-Holocene (MH; 11 000 to 5000 years before present), characterized by more vegetation cover and reduced dust emissions. Utilizing a state-of-the-art atmospheric chemical transport model, TM5-MP, we assessed the changes in biogenic volatile organic compound (BVOC) emissions, dust emissions and secondary organic aerosol (SOA) concentrations in northern Africa during this period relative to the pre-industrial (PI) period. Our simulations show that dust emissions reduced from 280.6 Tg a−1 in the PI to 26.8 Tg a−1 in the MH, agreeing with indications from eight marine sediment records in the Atlantic Ocean. The northward expansion in northern Africa resulted in an increase in annual emissions of isoprene and monoterpenes during the MH, around 4.3 and 3.5 times higher than that in the PI period, respectively, causing a 1.9-times increase in the SOA surface concentration. Concurrently, enhanced BVOC emissions consumed more hydroxyl radical (OH), resulting in less sulfate formation. This effect counteracted the enhanced SOA surface concentration, altogether leading to a 17 % increase in the cloud condensation nuclei at 0.2 % super saturation over northern Africa. Our simulations provide consistent emission datasets of BVOCs, dust and the SOA formation aligned with the northward shift of vegetation during the “Green Sahara” period, which could serve as a benchmark for MH aerosol input in future Earth system model simulation experiments.

ABSTRACTThis paper challenges the traditional perspective of a territorial core–periphery pattern as an organizing principle of space by introducing a relational perspective through an empirical approach. We study spatial processes of knowledge creation among advanced producer services in Germany between 2009 and 2019. We use a unique longitudinal dataset to analyse if German regions have become more integrated into the intra-firm location networks nationally and globally, and how this translates into the processes of centralization and peripheralization. The current conceptualization of core–periphery in Germany is too static and does not reflect the economic development of the regions. We find that there is no trend of urban areas becoming more integrated and peripheral areas less integrated into these networks. Instead, our research finds a discrepancy between the federal territorial classification and the functional orientation of German regions. Regions classified as peripheral have not generally decreased in connectivity to other regions. In contrast, some have increased their connectivity and have become more central in relational terms. Overall, we identified peripheralization and centralization as a relational process with dynamic, overlapping and trans-scalar networks.

To combat climate change successfully, enhancing existing processes is imperative alongside exploring new regenerative technologies. For this purpose, new components must be considered to improve the efficiency of thermodynamic processes. A promising candidate is the Ranque–Hilsch vortex tube due to its low investment cost and maintenance. Previous research has highlighted the thermodynamic advantages of employing a vortex tube in various applications, such as Brayton cycles or as a replacement for conventional expansion valves. However, to assess the potential of the vortex tube within a thermodynamic process, a computationally efficient but precise model of the vortex tube is required. Existing modeling approaches often fail to accurately predict experimental trends or require information such as geometry data that are not available for potential analyses. Thus, the present study proposes a novel thermodynamic-based black-box modeling approach: the vortex tube efficiency is introduced by incorporating operating and geometrical conditions into a single parameter. The vortex tube efficiency is systematically investigated for different operating conditions and various fluids and compared with available experimental results. The resulting modeling approach allows the qualitative and quantitative prediction of vortex tube behavior for air at various operating pressures and cold gas fractions. Further experimental investigations are required for a comprehensive quantitative description of vortex tubes with different geometries and working fluids.

Agricultural sustainability is dependent on the ability to predict crop yield, which is vital for farmers, consumers, and researchers. Most of the works used the amount of rainfall, average monthly temperature, relative humidity, etc. as inputs. In this paper, an attempt was made to predict the yield of the citrus crop (Washington Navel orange, Valencia orange, Murcott mandarin, Fremont mandarin, and Bearss Seedless lime) using weather factors and the accumulated heat units. These variables were used as input parameters in an artificial neural network (ANN) model. The necessary information was gathered during the growing seasons between 2010/2011 and 2021/2022 under Egyptian conditions. Weather factors were daily precipitation, yearly average air temperature, and yearly average of air relative humidity. A base air temperature of 13.0 °C was used to determine the accumulated heat units. The heat use efficiency (HUE) for cultivars was determined. The Bearss Seedless lime had the lowest HUE of 9.5 kg/ha °C day, while the Washington Navel orange had the highest HUE of 20.2 kg/ha °C day. The predictive performance of the ANN model with a structure of 9-20-1 with the backpropagation was evaluated using standard statistical measures. The actual and estimated yields from the ANN model were compared using a testing dataset, resulting in a value of RMSE, MAE, and MAPE of 2.80 t/ha, 2.58 t/ha, and 5.41%, respectively. The performance of the ANN model in the training phase was compared to multiple linear regression (MLR) models using values of R2; for MLR models for all cultivars, R2 ranged between 0.151 and 0.844, while the R2 value for the ANN was 0.87. Moreover, the ANN model gave the best performance criteria for evaluation of citrus yield prediction with a high R2, low root mean squared error, and low mean absolute error compared to the performance criteria of data mining algorithms such as K-nearest neighbor (KNN), KStar, and support vector regression. These encouraging outcomes show how the current ANN model can be used to estimate fruit yields, including citrus fruits and other types of fruit. The novelty of the proposed ANN model lies in the combination of weather parameters and accumulated heat units for accurate citrus yield prediction, specifically tailored for Egyptian regional citrus crops. Furthermore, especially in low- to middle-income countries such as Egypt, the findings of this study can greatly enhance the reliance on statistics when making decisions regarding agriculture and climate change. The citrus industry can benefit greatly from these discoveries, which can help with optimization, harvest planning, and postharvest logistics. We recommended furthering proving the robustness and generalization ability of the results in this study by adding more data points.

One of the key factors for sustainability in agricultural systems, particularly, for cultivation of date palms, is the identification of the performance parameters of the pollen grains of male date palms (Phoenix dactylifera L.). This study was carried out to predict the performance parameters of pollen grains using an artificial neural network (ANN) model. The morphological features of spathe length, spathe weight, number of pinnae per leaf, leaf length, leaf width, length of the pinna part, pinna length, pinna width, length of the spathe stem, and spathe width, as well as the concentrations of minerals such as Mg, N, K, P, and Ca in their leaves were used as inputs to the ANN model. For this purpose, we collected the required data from nine male date palms grown in Saudi Arabia. The ANN model utilized in this work included an input layer with 15 parameters, a hidden layer of 30 neurons, and an output layer with 8 neurons. The ANN model was trained with 27 patterns. Seven patterns were utilized for testing purposes. The coefficient of determination (R2) obtained between the observed and predicted performance parameters’ values using the testing dataset was 0.902 for the number of strands per spathe, 0.967 for strand length, 0.963 for the number of flowers per strand, 0.941 for the number of flowers per spathe, 0.985 for the weight of pollen grains per spathe, 0.810 for the pollen grains’ viability, 0.936 for the pollen grains’ length, and 0.992 for the pollen grains’ width. The length of the spathe stem had the most critical effect on how the ANN model predicted the values of the dependent variables, i.e., the number of strands per spathe, with a percentage of contribution of 17.66%; the weight of pollen grains per spathe, with 17.85%; the pollen grains’ length, with 19.78%, and the pollen grains’ width, with a percentage of contribution of 30.59%. Spathe weight had the most critical influence on strand length and pollen grains’ viability, with percentages of 26.29% and 14.92%, respectively. Leaf width had the most critical effect on the number of flowers per spathe, with a percentage of 12.55%. The elemental concentration of K in the male date palm leaves had the most critical effect on the number of flowers per strand, with a percentage of 13.98%. It was therefore concluded that using a modeling process with the ANN technique can help estimate the performance parameters of male date palms’ pollen grains for different purposes, such as providing a starting point for mathematical analyses associated with the physiological mechanisms of male date palm. Moreover, the outcomes of this research work can be supportive as a practical tool in this field of study.

Dual combination therapy with a phosphodiesterase-5 inhibitor (PDE5i) and endothelin receptor antagonist is recommended for most patients with intermediate-risk pulmonary arterial hypertension (PAH). The RESPITE and REPLACE studies suggest that switching from a PDE5i to a soluble guanylate cyclase (sGC) activator may provide clinical improvement in this situation. The optimal approach to escalation or transition of therapy in this or other scenarios is not well defined. We developed an expert consensus statement on the transition to sGC and other treatment escalations and transitions in PAH using a modified Delphi process. The Delphi process used a panel of 20 physicians with expertise in PAH. Panelists answered three questionnaires on the management of treatment escalations and transitions in PAH. The initial questionnaire included open-ended questions. Later questionnaires consolidated the responses into statements that panelists rated on a Likert scale from -5 (strongly disagree) to +5 (strongly agree) to determine consensus. The Delphi process produced several consensus recommendations. Escalation should be considered for patients who are at high risk or not achieving treatment goals, by adding an agent from a new class, switching from oral to parenteral prostacyclins, or increasing the dose. Switching to a new class or within a class should be considered if tolerability or other considerations unrelated to efficacy are affecting adherence. Switching from a PDE5i to an SGC activator may benefit patients with intermediate risk who are not improving on their present therapy. These consensus-based recommendations may be helpful to clinicians and beneficial for patients when evidence-based guidance is unavailable.

Background: The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may slow cognitive decline in older adults. A potential mechanism could be possible anti-inflammatory properties of the MIND-diet. Objective: To examine whether adherence to the MIND diet at baseline is associated with the odds of mild cognitive impairment (MCI) and changes in biomarkers of inflammation (High-sensitivity C-reactive Protein(hsCRP), interleukin-6(IL-6)) over three years in adults ≥70 years. Methods: Adherence to the MIND diet was assessed by food frequency questionnaire (FFQ) at baseline and after three years. Presence of MCI based on the Montreal Cognitive Assessment (MoCA) was defined as

Terrestrial wildlife species are important yet often overlooked taxa in the recovery of ecosystems following dam removal. Their presence can shape ecosystem recovery, signal restoration of ecosystem function, and influence food web dynamics and nutrient transfer. We used camera traps to examine seasonal use of two former reservoir beds and an upstream reference reach by the mammalian community following the removal of two large dams on the Elwha River, Washington, USA. For certain taxa, we compared current species use to data collected prior to dam removal. Camera traps revealed use by at least fifteen mammal species, including but not limited to American black bear (Ursus americanus), Columbian black-tailed deer (Odocoileus hemionus columbianus), Roosevelt elk (Cervus elaphus roosevelti), puma (Puma concolor), coyotes (Canis latrans), bobcats (Lynx rufus), and snowshoe hares (Lepus americanus). Coyotes were found mostly lower in the watershed outside the Olympic National Park boundary, while other species were distributed throughout the restoration area. We did not see major differences in species composition between the restoration areas and the upstream reference reach, though number of detections across study reaches differed for most species. Unlike previous findings, black bears were observed across all seasons in this study, suggesting a shift in seasonal use since dam removal. Full restoration of the terrestrial wildlife community could take decades to unfold, but early patterns demonstrate rapid establishment and use by wildlife on new riparian surfaces that are expected to continue to evolve with restoration of fish and vegetation communities.

Abstract Prey selection is a fundamental aspect of ecology that drives evolution and community structure, yet the impact of intraspecific variation on the selection for prey size remains largely unaccounted for in ecological theory. Here, we explored puma (Puma concolor) prey selection across six study sites in North and South America. Our results highlighted the strong influence of season and prey availability on puma prey selection, and the smaller influence of puma age. Pumas in all sites selected smaller prey in warmer seasons following the ungulate birth pulse. Our top models included interaction terms between sex and age, suggesting that males more than females select larger prey as they age, which may reflect experiential learning. When accounting for variable sampling across pumas in our six sites, male and female pumas killed prey of equivalent size, even though males are larger than females, challenging assumptions about this species. Nevertheless, pumas in different study sites selected prey of different sizes, emphasizing that the optimal prey size for pumas is likely context‐dependent and affected by prey availability. The mean prey weight across all sites averaged 1.18 times mean puma weight, which was less than predicted as the optimal prey size by energetics and ecological theory (optimal prey = 1.45 puma weight). Our results help refine our understanding of optimal prey for pumas and other solitary carnivores, as well as corroborate recent research emphasizing that carnivore prey selection is impacted not just by energetics but by the effects of diverse ecology.

Abstract The past ∼200 million years of Earth's geomagnetic field behavior have been recorded within oceanic basalts, many of which are only accessible via scientific ocean drilling. Obtaining the best possible paleomagnetic measurements from such valuable samples requires an a priori understanding of their magnetic mineralogies when choosing the most appropriate protocol for stepwise demagnetization experiments (either alternating field or thermal). Here, we present a quick, and non‐destructive method that utilizes the amplitude‐dependence of magnetic susceptibility to screen submarine basalts prior to choosing a demagnetization protocol, whenever conducting a pilot study or other detailed rock‐magnetic characterization is not possible. We demonstrate this method using samples acquired during International Ocean Discovery Program Expedition 391. Our approach is rooted in the observation that amplitude‐dependent magnetic susceptibility is observed in basalt samples whose dominant magnetic carrier is multidomain titanomagnetite (∼TM60–65, (Ti0.60–0.65Fe0.35–0.40)Fe2O4). Samples with low Ti contents within titanomagnetite or samples that have experienced a high degree of oxidative weathering do not display appreciable amplitude dependence. Due to their low Curie temperatures, basalts that possess amplitude‐dependence should ideally be demagnetized either using alternating fields or via finely‐spaced thermal demagnetization heating steps below 300°C. Our screening method can enhance the success rate of paleomagnetic studies of oceanic basalt samples.

Political polarization has proliferated online. Scholars have identified multiple types of polarizing speech, which elicit stronger public reactions on social media platforms. Little research has focused on how social media platforms might hasten growing partisanship among both elites and the public. The authors examine these dynamics using a sample of 134,442 tweets posted by 527 members of Congress in the period surrounding the 2022 midterm elections. Our findings confirm that all types of polarization increase engagement, but party affiliation plays an important role in the process. Polarizing rhetoric from Republicans generally elicits a stronger reaction relative to that from Democrats. The exception is an increase in retweets of issue-based polarization when posted by Democrats. The authors conclude that all politicians are incentivized to adopt a polarizing presence on social media to raise their profiles. The diffusion of polarization may be shaped by partisanship, with the different parties amplifying different types of content.

In this commentary, we provide a snapshot into the experiences and perspectives of college stu­dents and staff engaged in an on-campus urban farm run by a college. By delving into the chal­lenges faced by staff members and student work­ers, we seek to identify nuanced areas for improve­ment in the management, communication, and promotion of the on-campus farm’s work. This commentary emphasizes the imperative to bridge the gap between students and staff, address nega­tive perceptions, and amplify the educational and career value of on-campus farming experiences.

Summary: Background: SARS-CoV-2 infections still have a significant impact on the global population. The existing vaccinations have contributed to reducing the severe disease courses, decreasing hospitalisations, and lowering the mortality rate. However, due to the variability of COVID-19 symptoms, the emergence of new variants and the uneven global distribution of vaccines there is still a great need for new therapy options. One promising approach is provided by host-directed therapies. We assessed here the efficacy and safety of MP1032, a host-directed anti-viral/anti-inflammatory drug in hospitalised patients with moderate to severe COVID-19. Methods: In a randomised, double-blind, placebo-controlled, Phase IIa study, patients were randomised 2:1 to receive either 300 mg MP032 bid + Standard-of-Care (SoC) or placebo bid + SoC for 28 days. Eligible patients were ≥18 years old, tested positive for SARS-CoV-2, and had moderate to severe COVID-19 symptoms. The study spanned 20 sites in six countries (Bulgaria, France, Hungary, Italy, Romania, Spain), assessing disease progression according the NIAID scale as the primary outcome on day 14. Secondary objectives included disease progression (day 28), disease resolution (days 14 and 28), mortality rate, COVID-19 related parameters and safety. Exposure-response analyses were performed, linking MP1032 to COVID-19 biomarkers (eGFR, D-dimer). Findings: 132 patients were enrolled to receive MP1032 + SoC (n = 87) or placebo + SoC (n = 45). The patients were all white or Caucasian with a mean (median) age of 60.5 (63) years. Overall, only 10 patients were vaccinated, 5 in each group. No significant risk difference of disease progression could be detected between groups on both day 14 (9.8% MP1032 vs. 11.6% placebo) and day 28 with MH common risk differences of −0.276% (95% CI, −11.634 to 11.081; p = 0.962) and 1.722% (95% CI, −4.576 to 8.019; p = 0.592), respectively.The treatment with MP1032 + SoC was safe and well-tolerated. Overall, 182 TEAEs including 10 SAEs were reported in 53.5% (46/86) of patients of the verum group and in 57.8% (26/45) of patients of the placebo group; the SAEs occurred in 5.8% (5/86) and 6.7% (3/45) of verum and placebo patients, respectively. None of the SAEs was considered as related. Interpretation: Despite the study's limitation in size and the variation in concurrent SoCs, these findings warrant further investigation of MP1032 as a host-directed anti-viral drug candidate. Funding: The study was funded by the COVID-19 Horizon Europe work programme and MetrioPharm AG.

We present solutions to two of the most pressing issues in contemporary optical music recognition (OMR). We improve recognition accuracy on low-quality, real-world (i.e. containing ageing, lighting, or dirt artefacts among others) input data and provide confidence-rated model outputs to enable efficient human post-processing. Specifically, we present (i) a sophisticated input augmentation scheme that can reduce the gap between sanitised benchmarks and realistic tasks through a combination of synthetic data and noisy perturbations of real-world documents; (ii) an adversarial discriminative domain adaptation method that can be employed to improve the performance of OMR systems on low-quality data; (iii) a combination of model ensembles and prediction fusion, which generates trustworthy confidence ratings for each prediction. We evaluate our contributions on a newly created test set consisting of manually annotated pages of varying real-world quality, sourced from the International Music Score Library Project (IMSLP)/Petrucci Music Library. With the presented data augmentation scheme, we achieve a doubling in detection performance from 36.0% to 73.3% on noisy real-world data compared to state-of-the-art training. This result is then combined with robust confidence ratings paving the way for OMR to be deployed in the real world. Additionally, we show the merits of unsupervised adversarial domain adaptation for OMR raising the 36.0% baseline to 48.9%. All our code and data are freely available at: https://github.com/raember/s2anet/tree/TISMIR_publication.

BackgroundKlotho is a longevity and neuroprotective hormone encoded by the KLOTHO gene, and heterozygosity for the KL-VS variant confers a protective effect against neurodegenerative disease.ObjectiveTest whether klotho concentrations in serum or cerebrospinal fluid (CSF) vary as a function of KLOTHO KL-VS genotype, determine whether circulating klotho concentrations from serum and CSF differ from one another, and evaluate whether klotho levels are associated with Alzheimer's disease risk factors.MethodsCirculating klotho was measured in serum (n = 1,116) and CSF (n = 183) of cognitively intact participants (aged 62.4 ± 6.5 years; 69.5% female). KLOTHO KL-VS zygosity (non-carrier; heterozygote; homozygote) was also determined. Linear regression was used to test whether klotho hormone concentration varied as a function of KL-VS genotype, specimen source, and demographic and clinical characteristics.ResultsSerum and CSF klotho were higher in KL-VS carriers than non-carriers. Klotho concentration was higher in CSF than in serum. Females had higher serum and CSF klotho, while younger age was associated with higher klotho in CSF.ConclusionIn a cohort enriched for risk for Alzheimer's disease, heterozygotic and homozygotic carriers of the KL-VS allele, females, and younger individuals have higher circulating klotho. Fluid source, KL-VS genotype, age, and sex should be considered in analyses of circulating klotho on brain health.

IntroductionDementia as an inevitable aging consequence has been challenged and underscores the need for investigations of the factors that confer resilience. We examine whether the functionally advantageous KL-VS variant of the putative aging suppressor KLOTHO gene attenuates age-related cognitive decline and deleterious biomolecular changes.MethodsTrajectories of change in memory and executive function (N = 360; 2-12 visits) and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers-amyloid beta (Aβ)42, total tau (t-tau), phosphorylated tau (p-tau) (N = 112; 2-4 samplings)-were compared between KL-VS non-carriers and heterozygotes in middle-aged and older adults from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center studies.ResultsMemory and executive function declined (p's ≤ 0.001) and CSF t-tau, p-tau, t-tau/Aβ42, and p-tau/Aβ42 levels increased (all p's ≤ 0.004) with age. The rate of p-tau accumulation was attenuated for KL-VS heterozygotes (p = 0.03).DiscussionKL-VS heterozygosity may confer resilience to AD-associated biomolecular changes.

Introduction and objectivesWound healing after myocardial infarction (MI) is a dynamic and complex multiple phase process, and a coordinated cellular response is required for proper scar formation. The current paradigm suggests that pro-inflammatory monocytes infiltrate the MI zone during the initial pro-inflammatory phase and differentiate into inflammatory macrophages, and then switch their phenotypes to anti-inflammatory during the reparative phase. Visualization of the reparative phase post-MI is of great interest because it may reveal delayed resolution of inflammation, which in turn predicts adverse cardiac remodeling. Imaging of anti-inflammatory macrophages may also be used to assess therapy approaches aiming to modulate the inflammatory response in order to limit MI size. Reparative macrophages can be distinguished from inflammatory macrophages by the surface marker mannose receptor (MR, CD206). In this study we evaluated the feasibility of 68Ga-NOTA-anti-MMR Nb for imaging of MR on alternatively activated macrophages in murine MI models.MethodsWildtype and MR-knockout mice and Wistar rats were subjected to MI via permanent ligation of the left coronary artery. Non-operated or sham-operated animals were used as controls. MR expression kinetics on cardiac macrophages was measured in mice using flow cytometry. PET/CT scans were performed 1 h after intravenous injection of 68Ga-NOTA-anti-MMR Nb. Mice and rats were euthanized and hearts harvested for ex vivo PET/MRI, autoradiography, and staining. As a non-targeting negative control, 68Ga-NOTA-BCII10 was used.ResultsIn vivo-PET/CT scans showed focal radioactivity signals in the infarcted myocardium for 68Ga-NOTA-anti-MMR Nb which were confirmed by ex vivo-PET/MRI scans. In autoradiography images, augmented uptake of the tracer was observed in infarcts, as verified by the histochemistry analysis. Immunofluorescence staining demonstrated the presence and co-localization of CD206- and CD68-positive cells, in accordance to infarct zone. No in vivo or ex vivo signal was observed in the animals injected with control Nb or in the sham-operated animals. 68Ga-NOTA-anti-MMR Nb uptake in the infarcts of MR-knockout mice was negligibly low, confirming the specificity of 68Ga-NOTA-anti-MMR Nb to MR.ConclusionThis exploratory study highlights the potential of 68Ga-NOTA-anti-MMR Nb to image MR-positive macrophages that are known to play a pivotal role in wound healing that follows acute MI.