Importance Mechanisms contributing to disability accumulation in multiple sclerosis (MS) are poorly understood. Blood neurofilament light chain (NfL) level, a marker of neuroaxonal injury, correlates robustly with disease activity in people with MS (MS); however, data on the association between NfL level and disability accumulation have been conflicting. Objective To determine whether and when NfL levels are elevated in the context of confirmed disability worsening (CDW). Design, Setting, and Participants This study included 2 observational cohorts: results from the Expression, Proteomics, Imaging, Clinical (EPIC) study at the University of California San Francisco (since 2004) were confirmed in the Swiss Multiple Sclerosis Cohort (SMSC), a multicenter study in 8 centers since 2012. Data were extracted from EPIC in April 2022 (sampling July 1, 2004, to December 20, 2016) and SMSC in December 2022 (sampling June 6, 2012, to September 2, 2021). The study included 2 observational cohorts in tertiary MS centers. All participants of both cohorts with available NfL results were included in the study, and no eligible participants were excluded or declined to participate. Exposure Association between NfL z scores and CDW. Main Outcome Measures CDW was defined as Expanded Disability Status Scale (EDSS) worsening that was confirmed after 6 or more months and classified into CDW associated with clinical relapses (CDW-R) or independent of clinical relapses (CDW-NR). Visits were classified in relation to the disability worsening events into CDW(-2) for 2 visits preceding event, CDW(-1) for directly preceding event, CDW(event) for first diagnosis of EDSS increase, and the confirmation visit. Mixed linear and Cox regression models were used to evaluate NfL dynamics and to assess the association of NfL with future CDW, respectively. Results A total of 3906 EPIC visits (609 participants; median [IQR] age, 42.0 [35.0-50.0] years; 424 female [69.6%]) and 8901 SMSC visits (1290 participants; median [IQR] age, 41.2 [32.5-49.9] years; 850 female [65.9%]) were included. In CDW-R (EPIC, 36 events; SMSC, 93 events), NfL z scores were 0.71 (95% CI, 0.35-1.07; P < .001) units higher at CDW-R(-1) in EPIC and 0.32 (95% CI, 0.14-0.49; P < .001) in SMSC compared with stable MS samples. NfL elevation could be detected preceding CDW-NR (EPIC, 191 events; SMSC, 342 events) at CDW-NR(-2) (EPIC: 0.23; 95% CI, 0.01-0.45; P = .04; SMSC: 0.28; 95% CI, 0.18-0.37; P < .001) and at CDW-NR(-1) (EPIC: 0.27; 95% CI, 0.11-0.44; P < .001; SMSC: 0.09; 95% CI, 0-0.18; P = .06). Those findings were replicated in the subgroup with relapsing-remitting MS. Time-to-event analysis confirmed the association between NfL levels and future CDW-R within approximately 1 year and CDW-NR (in approximately 1-2 years). Conclusions and Relevance This cohort study documents the occurrence of NfL elevation in advance of clinical worsening and may hint to a potential window of ongoing dynamic central nervous system pathology that precedes the diagnosis of CDW.

. The progress of additive manufacturing technology brings about many new questions and challenges. Additive manufacturing technology allows for designing machine elements with smaller mass, but at the same time with the same stiffness and stress loading capacity. By using additive manufacturing it is possible to produce gears in the form of shell shape with infill inside. This study is carried out as an attempt to answer the question which type of infill, and with how much density, is optimal for a spur gear tooth to ensure the best stiffness and stress loading capacity. An analysis is performed using numerical finite element method. Two new infill structures are proposed: triangular infill with five different densities and topology infill designed according to the already known results for 2D cantilever topology optimization, known as Michell structures. The von Mises stress, displacements and bending stiffness are analyzed for full body gear tooth and for shell body gear tooth with above mentioned types of infill structure.

SAŽETAK Perfuzija se odnosi na isporuku kiseonika i hranljive materije u tkiva putem protok krvi i jedan je od najosnovnijih fiziološki parametri. Poremećaji perfuzije takođe čine većinu vodeći uzroci medicinskog invaliditeta i mortalitet. Dok mjerenja od perfuzije imaju direktnu dijagnostičku vrijednost u vaskularni poremećaji, mjerenja perfuzije takođe služe kao biomarkeri za a širi spektar fizioloških i patofizioloških funkcije. Bliska sprega između cerebralnog krvotoka i metabolizma omogućava regionalnu funkciju mozga biti procijenjen mjerenjima od cerebralnu perfuziju i povećanu vaskularnost neoplazmi omogućava perfuziju tumora da se koristi kao mjera tumora stepena i za praćenje odgovora na tumor terapija. U oblasti MRI, najviše ljudi povezuju pojam perfuzije snimanje s dinamičkim kontrastom osjetljivosti snimanje pomoću kontrasta za opuštanje agent. ASL Perfuzija je tehnika MR perfuzije koja ne zahtjeva intravensku primjenu kontrastnog sredstva ( za razliku od DSc I DCE perfuzije). Umjesto toga, koristi sposobnost MRI-a da magnetski označi arterijsku krv. Parametar koji se najčešče izvodi je cerebralni protok krvi (CBF). ASL je vrlo pogodna tehnika za upotrebu u pedijatriji, u kojoj upotreba radioaktivnih tragova moze biti ograničena. Također je sigurna metoda za primjenu kod pacijenata sa oštečenom bubrežnom funkcijom.

This study aims to evaluate two distinct approaches for fiber radius estimation using diffusion‐relaxation MRI data acquired in biomimetic microfiber phantoms that mimic hollow axons. The methods considered are the spherical mean power‐law approach and a T2‐based pore size estimation technique.

There is an increasing demand for green plant walls in indoor environments because of their multifaced benefits, such as aesthetic appeal, indoor air quality improvement, or psychological well-being. Mosses are believed to be excellent for these walls due to their easy application and maintenance. However, so far there is no evidence for their indoor survival. In this study, we tested the moss species Hypnum cupressiforme, Bryachythecium rutabulum, Eurrhynchium angustirete, Thuidium tamariscinum, Streblotrichum convolutum, Syntrichia ruralis, and Ceratodon purpureus for indoor use in living moss walls. We evaluated their vitality through the monitoring of leaf coloration over a twelve month period, subjecting them to varying temperature ranges (14–20 °C), humidity levels (60–100%), and diverse irrigation methods (drip and spray irrigation, 300–1500 mL per day) within controlled climate chambers. Depending on the combination of these variables, mosses survived up to six months. Hypnum cupressiforme and Ceratodon purpureus performed best. However, as the time span of survival was limited, the use of living mosses for indoor purposes at the current stage cannot be recommended. An additional problem is that the requisition of living material such as in the culturing of moss under horticultural conditions is difficult and harvesting from natural environments is detrimental to most habitats.

Background The absence of the susceptibility vessel sign (SVS) in patients treated with mechanical thrombectomy (MT) is associated with poor radiological and clinical outcomes after 3 months. Underlying conditions, such as cancer, are assumed to influence SVS status and could potentially impact the long-term outcome. We aimed to assess SVS status as an independent predictor of long-term outcomes in MT-treated patients. Methods SVS status was retrospectively determined in consecutive MT-treated patients at a comprehensive stroke center between 2010 and 2018. Predictors of long-term mortality and poor functional outcome (modified Rankin Scale (mRS) ≥3) up to 8 years were identified using multivariable Cox and logistic regression, respectively. Results Of the 558 patients included, SVS was absent in 13% (n=71) and present in 87% (n=487) on baseline imaging. Patients without SVS were more likely to have active cancer (P=0.003) and diabetes mellitus (P<0.001) at the time of stroke. The median long-term follow-up time was 1058 days (IQR 533–1671 days). After adjustment for active cancer and diabetes mellitus, among others, the absence of SVS was associated with long-term mortality (adjusted HR (aHR) 2.11, 95% CI 1.35 to 3.29) and poor functional outcome in the long term (adjusted OR (aOR) 2.90, 95% CI 1.29 to 6.55). Conclusion MT-treated patients without SVS have higher long-term mortality rates and poorer long-term functional outcome. It appears that this association cannot be explained by comorbidities alone, and further studies are warranted.

Abstract Introduction The benefit of additional reperfusion attempts in patients with partial angiographic reperfusion (TICI2b) is unknown. The PROCEED model predicts subsequent favorable occurrence of complete reperfusion (i.e. delayed reperfusion [DR]) at 24 hours after initial incomplete angiographic reperfusion at the conclusion of thrombectomy. This study aims to externally validate the PROCEED model using pooled data from multiple international trials that systematically performed follow‐up perfusion imaging. Methods Individual patient data for external validation were obtained from the EXTEND‐IA, EXTEND‐IA TNK part 1 and 2 trials (clinicaltrials.gov, unique‐identifier: NCT01492725, NCT02388061 and NCT03340493). The model’s primary outcome of interest was the occurrence of DR, defined as the absence of any focal perfusion deficit on follow‐up CT or MRI perfusion imaging maps, despite initial incomplete angiographic reperfusion on the final thrombectomy angiography series. The updated model’s performance was evaluated with discrimination, calibration and clinical decision curves. Results We analyzed 267 patients for the external validation, with median age of 74 (IQR 64 – 80), 44.2% were female and 62% had DR. The externally validated model had good discrimination (C‐statistic 0.81, 95% CI 0.72 – 0.86) and was well calibrated (intercept 0.22, 95% CI 0.18‐0.33 and slope 0.96, 95% CI 0.81‐1.23). With threshold probability of R=12% (i.e. 88% chance of having DR), pursuing additional reperfusion attempts to pursue complete angiographic reperfusion in a patient with high‐likelihood of DR were seven times worse (Cost:Benefit Ratio 1:7, Figure 1) than no further endovascular maneuver. In terms of standardized net reduction, the PROCEED model could reduce one in five unnecessary interventions without missing an intervention for any patient who would eventually have DR. Across a wide range of threshold probabilities, the model outperformed the scenario of the typical decision‐making process in the angiography suite, based on the current treatment guidelines. Conclusion The externally validated model had good predictive accuracy and discrimination. Depending on the acceptable risk threshold, the model may compliment clinical judgment of the treating physicians and inform on natural progression of untreated incomplete reperfusion.

Abstract Introduction Clinical utility and diagnostic sensitivity of new‐generation flat‐panel computed tomography perfusion imaging (FPCTP) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCTP obtained directly after MT could provide additional potentially relevant information on tissue reperfusion status. Methods Qualitative, single‐center analysis of all consecutive acute stroke patients admitted between 06/2019 and 03/2021 who underwent MT and post‐interventional FPCTP (n=26). A core‐lab blinded to technical details and clinical data performed reperfusion grading on post‐interventional digital subtraction angiography (DSA) images and time‐sensitive FPCTP maps. All patients were classified according to agreement between DSA and FPCTP. Results In 10/26 patients FPCTP revealed new, potentially clinically relevant information. Core‐lab adjudicated dichotomized detection of hypoperfusion (present/absent) was concurring in 21/26 (81%) patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 (62%) patients, while in 5 (19%) patients with incomplete reperfusion, FPCTP showed additional hypoperfused areas missed on DSA. Of the remaining five patients subject to disagreement regarding the presence or absence of hypoperfusion, three showed complete reperfusion on DSA but hypoperfusion was noted on FPCTP, whereas two showed incomplete reperfusion on DSA without detectable hypoperfusion on FPCTP. FPCTP findings could have avoided Thrombolysis in Cerebral Infarction (TICI) overestimation in all false‐positive operator‐rated TICI3 cases. Conclusion In both core‐lab and real‐world operator assessment, FPCTP may provide additional clinically relevant information in a considerable percentage of patients undergoing MT. Hence, FPCTP may constitute a new standard for evaluating reperfusion efficacy and informed decision making in the angiography suite.

Urban logistics implementation causes environmental pollution; therefore, it is necessary to consider the impact on the environment when carrying out such logistics. Electric vehicles are alternative vehicles that reduce the impact on the environment. For this reason, this study investigated which electric vehicle has the best indicators for urban logistics. An innovative approach when selecting such vehicles is the application of a fuzzy–rough method based on expert decision making, whereby the decision-making process is adapted to the decision makers. In this case, two methods of multi-criteria decision making (MCDM) were used: SWARA (stepwise weight assessment ratio analysis) and MARCOS (measurement alternatives and ranking according to compromise solution). By applying the fuzzy–rough approach, uncertainty is included when making a decision, and it is possible to use linguistic values. The results obtained by the fuzzy–rough SWARA method showed that the range and price of electric vehicles have the greatest influence on the selection of an electric delivery vehicle. The results of applying the fuzzy–rough MARCOS method indicated that the Kangoo E-Tech Electric vehicle has the best characteristics according to experts’ estimates. These results were confirmed by validation and the application of sensitivity analysis. In urban logistics, the selection of an electric delivery vehicle helps to reduce the impact on the environment. By applying the fuzzy–rough approach, the decision-making problem is adjusted to the preferences of the decision makers who play a major role in purchasing a vehicle.

African swine fever virus (ASFV) is a complex DNA virus causing severe hemorrhagic disease in domestic pigs and wild boar. The disease has spread worldwide, with important socio-economic consequences. Early virus detection and control measures are crucial as there are no effective vaccines nor antivirals on the market. While the diagnosis of ASFV is fast and based primarily on qPCR, the detection of infectious ASFV is a labor-intensive process requiring susceptible macrophages and subsequent antibody-based staining or hemadsorption. The latter cannot detect ASFV isolates devoid of functional CD2v (EP402R) expression. Here, we report the development of a plasmid-based reporter assay (RA) for the sensitive detection and titration of infectious ASFV. To this end, we constructed a plasmid for secreted NanoLuc® luciferase (secNluc) expression driven by the ASFV DNA polymerase gene G1211R promoter. Infection of plasmid-transfected immortalized porcine kidney macrophages (IPKM) followed by measurement of secNluc from cell culture supernatants allowed reliable automated quantification of infectious ASFV. The RA-based titers matched the titers determined by conventional p72-staining or hemadsorption protocols. The novel assay is specific for ASFV as it does not detect classical swine fever virus nor porcine reproductive and respiratory syndrome virus. It is applicable to ASFV of different genotypes, virulence, and sources, including ASFV from sera and whole blood from infected pigs as well as non-hemadsorbing ASFV.

INTRODUCTION Diatom tests are rarely used during autopsy to confirm drowning as the cause of death (COD) because of limitations of the current literature involving these techniques. Instead, experts rely on physical examination by the pathologist. Due to interpretive concerns regarding Diatom tests, they are often insufficient in establishing a diagnosis, but offer the potential to be an extremely useful diagnostic tool with further understanding. The aim of study is to optimize "Diatom Tests" for use in forensic medicine in Bosnia and Herzegovina. METHODS A randomized prospective experimental study was conducted, using albino Wistar rat models (Rattus norvegicus), at the Veterinary Facility, University of Sarajevo. Thirty-two adult albino rats, were used and distributed into groups as follows: Group A (6 deceased rats with COD other than drowning, but due to mechanical asphyxia, which were then submerged for 1 h after death); Group B (6 deceased rats with COD other than drowning, but due to mechanical asphyxia, which were then submerged for 72 h after death); Group C (6 rats that were immediately autopsied after drowning, with COD determined as drowning); Group D (6 rats that underwent a 48-hour postmortem period after drowning); Group E (COD: drowning, post-mortem 72hrs after death, remained submerged in water until PM). Live algological material was collected for the research of the systematics of algae from the Bosna river, Sarajevo, and transported to the University of Sarajevo (Department of Biology, Faculty of Science). Periphyllon, epiphyllon and epipelon were used to collect phytobenthos. The material was fixed with 4% formalin solution. Laboratory processing of diatoms was performed using the methods described by Hustedt (16). In the process of obtaining pure diatom valves, part of the material is digested with potassium permanganate (KMnO4), sulfuric acid (H2SO4), and oxalic acid (C2H2O4). In the next step, the cleaned diatom valves were mounted in Canadian balsam. A light microscope under 1000x magnification (Best Scope 2020) was used to evaluate and analyze the species. The identification of diatoms was performed using the reference of Cantonati et al (17). The nomenclature of diatom species was performed according to Guiry & Guiry's worldwide electronic internet database. RESULTS No diatoms were found in Groups A and B. However, Navicula sp. and Sellaphora sp. cf., were discovered during bone analysis of Group C where rats were immediately autopsied after drowning. Hantzschia amphioxus taxon was present in Group D, which underwent a 48-hour postmortem period after drowning and before samples were taken. In Groups C and D, where drowning was the COD, Diatoma vulgaris i Pinnularia major, Achnanthidium minutissimum i Melosira varians were present in the tooth samples. CONCLUSION Optimization of the "Diatom Test" method could potentially lead to its future use as a routine method within experimental settings. This experimental study is a starting point that guides forenscic medicine pracitioners towards the optimization of tests and sampling in cases of unexplained etiology, where preserved soft tissue structures is not available. In these cases, teeth and bones serve as accessible materials for diagnosing COD, alongside standardized nonspecific findings in the absence of organs for micro- and macroanalysis.