The ATLAS detector at the Large Hadron Collider has been used to measure jet substructure modification and suppression in Pb+Pb collisions at a nucleon-nucleon center-of-mass energy $\sqrt{s_{_\mathrm{NN}}}=5.02~\mathrm{TeV}$ in comparison with $pp$ collisions at $\sqrt{s}=5.02~\mathrm{TeV}$. The Pb+Pb data, collected in 2018, have an integrated luminosity of $1.72~\mathrm{nb^{-1}}$, while the $pp$ data, collected in 2017, have an integrated luminosity of $260~\mathrm{pb}^{-1}$. Jets used in this analysis are clustered using the anti-$k_{t}$ algorithm with a radius parameter $R=0.4$. The jet constituents, defined by both tracking and calorimeter information, are used to determine the angular scale $r_\mathrm{g}$ of the first hard splitting inside the jet by reclustering them using the Cambridge-Aachen algorithm and employing the soft-drop grooming technique. The nuclear modification factor, $R_\mathrm{AA}$, used to characterize jet suppression in Pb+Pb collisions, is presented differentially in $r_\mathrm{g}$, jet transverse momentum, and in intervals of collision centrality. The $R_\mathrm{AA}$ value is observed to depend significantly on jet $r_\mathrm{g}$. Jets produced with the largest measured $r_\mathrm{g}$ are found to be twice as suppressed as those with the smallest $r_\mathrm{g}$ in central Pb+Pb collisions. The $R_\mathrm{AA}$ values do not exhibit a strong variation with jet $p_\mathrm{T}$ in any of the $r_\mathrm{g}$ intervals. The $r_\mathrm{g}$ and $p_\mathrm{T}$ dependence of jet $R_\mathrm{AA}$ is qualitatively consistent with a picture of jet quenching arising from coherence and provides the most direct evidence in support of this approach.

Adeno-associated virus (AAV) vectors are stored and shipped frozen which poses logistic and economic barriers for global access to these therapeutics. To address this issue, we developed a method to stabilize AAV serotype 9 (AAV9) in a film matrix that can be stored at ambient temperature and administered by systemic injection. AAV9 expressing the luciferase transgene was mixed with formulations, poured into molds and films dried under aseptic conditions. Films were packaged in individual particle-free bags with foil overlays and stored at various temperatures under controlled humidity. Recovery of AAV9 from films was determined by serial dilution of rehydrated film in media and infection of HeLa RC32 cells. Luciferase expression was compared to that of films rehydrated immediately after drying. Biodistribution of vector was determined by in vivo imaging and quantitative real-time PCR. Residual moisture in films was determined by Karl Fischer titration. AAV9 embedded within a film matrix and stored at 4 °C for 5 months retained 100% of initial titer. High and low viscosity formulations maintained 90 and 85% of initial titer after 6 months at 25 °C respectively. AAV was not detected after 4 months in a Standard Control Formulation under the same conditions. Biodistribution and transgene expression of AAV stored in film at 25 or 4 °C were as robust as vector stored at −80 °C in a Standard Control Formulation. These results suggest that storage of AAV in a film matrix facilitates easy transport of vector to remote sites without compromising in vivo performance. Adeno-associated viruses (AAVs) are small viruses that are used to deliver medicines and vaccines. Prior to administration, they are stored in freezers set to very low temperatures and must be discarded if they thaw during transportation to clinics. AAV was embedded in a film to protect the virus during transportation and storage. The virus remained stable for 6 months at room temperature and during shipment from Texas to North Carolina. The ability to store and transport AAV without the need for complex packaging and temperature control will increase global access to vaccines and other medicines that use AAVs for delivery. Doan et al. characterize and assess the stability of film matrix embedded Adeno-Associated Virus 9 (AAV9) vectors during storage and transport at ambient temperatures. High and low viscosity formulations of AAV9 stored at 25 °C maintain titer for 6 months.

Flaviviruses are a heterogeneous group of viruses that may induce broad antigenic cross-reactivity. We present a patient who was admitted to the infectious disease department with symptoms suggestive of aseptic meningitis. During the clinical workup, the patient reported a tick bite two weeks before the disease onset. High titers of IgM and IgG antibodies to tick-borne encephalitis virus (TBEV) were found in both serum and cerebrospinal fluid (CSF) samples, indicating acute TBEV infection. West Nile virus (WNV) and Usutu virus (USUV) IgM and/or IgG antibodies were also detected, and a virus neutralization test (VNT) was performed. A high titer of TBEV neutralizing (NT) antibodies (640) was detected, which confirmed acute TBE. However, NT antibodies to WNV and USUV were also detected (titer 80 for both viruses). After TBEV and WNV IgG avidity evaluation, previous flavivirus infection was highly suspected (avidity index 82% and 89%, respectively). Blood, CSF, and urine samples were negative for respective viruses’ RNA. The presented case highlights the challenges in flavivirus serodiagnosis. In the published literature, different degrees of cross-reactivity or cross-neutralization between TBEV and dengue, louping ill, Omsk hemorrhagic fever, Langat, and Powassan virus were also observed. Therefore, the serology results should be interpreted with caution, including the possibility of cross-reactivity. In areas where several flaviviruses co-circulate VNT is recommended for disease confirmation.

After a three-year quarantine from the deadliest global pandemic of the last century, ASTES is organizing to gather all health professionals in Tirana, The 6th Albanian Congress of Trauma and Emergency Surgery(ACTES 2022) on 11-12 November 2022, with the topic Trauma & Emergency Surgery and not only...with the aim of providing high quality, the best standards, and the best results, for our patients ...ACTES 2022 is the largest event that ASTES (Albanian Society for Trauma and Emergency Surgery) has organized so far with 230 presentations, and 67 foreign lecturers with enviable geography, making it the largest national and wider scientific event.The scientific program is as strong as ever, thanks to the inclusiveness, where all the participants with a mix of foreign and local lecturers, select the best of the moment in medical science, innovation, and observation.The scientific committee has selected all the presentations so that the participants of each medical discipline will have something to learn, discuss, debate, and agree with updated methods, techniques, and protocols.I hope you will join us on Friday morning, and continue the journey of our two-day event together.

Tuberculum sellae meningiomas represent 3% to 10% of all intracranial meningiomas and present with progressive visual deterioration secondary to optic apparatus compression. 1 Treatment options include open microsurgical or endoscopic endonasal approaches, with the size of the tumor, optic canal invasion, and the relationship to the surrounding neurovascular structures dictating the preferred approach. 2-10 Transcranial fronto-temporal skull base approaches offer excellent optic apparatus decompression, particularly when combined with anterior clinoidectomy and early sectioning of the falciform ligaments and release of the optic nerves. 2 - 4 , 11 - 14 We describe the case of a 57-year-old woman who presented to the senior author (KIA) with a large tuberculum sellae meningioma and signi fi cant optic apparatus compression causing a 2-month long worsening of vision that progressed to bilateral legal blindness for 2 weeks. The patient underwent a cranio-orbital pretemporal approach, 15 extradural anterior clinoidectomy, opening of falciform ligaments, release of optic nerve, and microsurgical resection of the tumor. To the best of our knowledge, this is the fi rst video case reporting on the reversal of bilateral preoperative blindness lasting 2 weeks preoperatively. The case presentation, surgical anatomy, operative nuances, and postoperative course with imaging are reviewed. The patient provided written informed consent for the publication of her image and PHI.

After a long period of no excessive ground shaking in Croatia and the region of ex-Yugoslavia, an earthquake that woke up the entire region was the one that shook Croatia on 22 March 2020. More than 25,000 buildings were severely damaged. A process of reconstruction and strengthening of existing damaged buildings is underway. This paper presents proposed strengthening measures to be conducted on a cultural-historical building located in the city of Zagreb, which is under protection and located in zone A. After a detailed visual inspection and on-site experimental investigations, modeling of the existing and strengthened structure was performed in 3Muri. It is an old unreinforced masonry building typical not only for this region but for relevant parts of Europe (north, central, and east). The aim was to strengthen the building to Level 3 while respecting the ICOMOS recommendations and Venice Charter. Some non-completely conservative concessions had to be made, to fully retrofit the building as requested. The structural strengthening consisted of a series of organic interventions relying on—in the weakest direction—a new steel frame, new steel-ring frames, and FRCM materials, besides fillings the cracks. Such intervention resulted in increasing the ultimate load in the X and Y directions, respectively, more than 650 and 175% with reference to the unstrengthened structure. Good consistency was obtained between the numerical modeling, visual inspection, and on-site testing.

Background: Painful and damaged nipples are frequently associated with breastfeeding cessation in the early postpartum period. The results of researchers’ studies utilizing different treatments have been inconclusive. Research Aim: To compare the intensity of nipple pain and the healing of damaged nipples during the first 10 days postpartum using either lanolin or human milk treatments. Methods: This single-blind randomized controlled trial included participants (N = 206) who were primiparous with painful and damaged nipples. Participants were recruited from the tertiary teaching hospital within the first 72 hr after delivery and randomized to the intervention group with lanolin (n = 103) and a human milk control group (n = 103). Data were collected in the maternity ward, 3 and 7 days after randomization. The primary outcome was nipple pain intensity and quality measured 3 and 7 days after randomization by the McGill Pain Questionnaire – short form. The nipple damage self-assessment questionnaire was used for the assessment of nipple healing. Breastfeeding self-efficacy, breastfeeding duration, and exclusivity were assessed as secondary outcomes. Results: Participants in both groups reported a statistically nonsignificant reduction in pain (quality and intensity of pain) as well as improved nipple healing 7 days after randomization. Participants in the lanolin group exclusively breastfed their infants 3 days after randomization—significantly more often than participants in the control group (p = .026). The study did not reveal any statistically significant differences for other secondary outcomes. Conclusion: Both lanolin and human milk are equally effective in treating painful and damaged nipples. Registered with Clinicaltrials.gov (NCT04153513)

Entre 2019 y 2021 el equipo de Global Digital Heritage (GDH), en colaboración con la Universidad de Sarajevo y el Museo Nacional de Bosnia y Herzegovina, ha llevado a cabo la digitalización 3D de un importante conjunto de stećci conservados tanto en el Museo Nacional de Bosnia y Herzegovina como en algunos cementerios medievales cercanos a la ciudad de Sarajevo y a la zona oriental de Bosnia. Los cementerios medievales de stećci constituyen un valioso patrimonio arqueológico de gran interés histórico pero poco conocido a nivel internacional pese a que algunos de ellos han sido declarados Patrimonio Mundial en 2016. A pesar de tratarse de un patrimonio en peligro apenas se han acometido trabajos de documentación 3D sistemáticos. Este artículo expone la metodología empleada y los resultados obtenidos por GDH, incluyendo las dificultades que ha sido necesario resolver y los retos que todavía han de abordarse para poder acometer la paulatina digitalización 3D del mayor número posible de cementerios medievales de stećci en Bosnia y Herzegovina. 

The respiratory rate is a vital sign indicating breathing illness. It is necessary to analyze the mechanical oscillations of the patient's body arising from chest movements. An inappropriate holder on which the sensor is mounted, or an inappropriate sensor position is some of the external factors which should be minimized during signal registration. This paper considers using a non-invasive device placed under the bed mattress and evaluates the respiratory rate. The aim of the work is the development of an accelerometer sensor holder for this system. The normal and deep breathing signals were analyzed, corresponding to the relaxed state and when taking deep breaths. The evaluation criterion for the holder's model is its influence on the patient's respiratory signal amplitude for each state. As a result, we offer a non-invasive system of respiratory rate detection, including the mechanical component providing the most accurate values of mentioned respiratory rate.

Circulating cell-free DNA (ccfDNA) sequencing for low-burden cancer monitoring is limited by sparsity of circulating tumor DNA (ctDNA), the abundance of genomic material within a plasma sample, and pre-analytical error rates due to library preparation, and sequencing errors. Sequencing costs have historically favored the development of deep targeted sequencing approaches for overcoming sparsity in ctDNA detection, but these techniques are limited by the abundance of ccfDNA in samples, which imposes a ceiling on the maximal depth of coverage in targeted panels. Whole genome sequencing (WGS) is an orthogonal approach to ctDNA detection that can overcome the low abundance of ccfDNA by supplanting sequencing depth with breadth, integrating signal across the entire tumor mutation landscape. However, the higher cost of WGS limits the practical depth of coverage and hinders broad adoption. Lower sequencing costs may thus allow for enhanced ctDNA cancer monitoring via WGS. We therefore applied emerging lower-cost WGS (Ultima Genomics, 1USD/Gb) to plasma samples at ∼120x coverage. Copy number and single nucleotide variation profiles were comparable between matched Ultima and Illumina datasets, and the deeper WGS coverage enabled ctDNA detection at the parts per million range. We further harnessed these lower sequencing costs to implement duplex error-corrected sequencing at the scale of the entire genome, demonstrating a ∼1,500x decrease in errors in the plasma of patient-derived xenograft mouse models, and error rates of ∼10−7 in patient plasma samples. We leveraged this highly de-noised plasma WGS to undertake cancer monitoring in the more challenging context of resectable melanoma without matched tumor sequencing. In this context, duplex-corrected WGS allowed us to harness known mutational signature patterns for disease monitoring without matched tumors, paving the way for de novo cancer monitoring.

Introduction: Dementia prevention trials have so far shown little benefit of multidomain interventions against cognitive decline. Recruitment strategies in these trials often centre around dementia risk or cardiovascular risk profile, but it is uncertain whether this leads to inclusion of individuals who may benefit most from the intervention. We determined the effects of eligibility criteria on the recruitment of potential trial participants in the general population. Methods: In a systematic search until January 1, 2022, we identified all published and ongoing large (≥500 participants), phase-3 multidomain trials for the prevention of cognitive decline or dementia. We applied trial eligibility criteria to 5,381 participants of the population-based Rotterdam Study (mean age: 72 years, 58% women), to compare participant characteristics, predicted risk of cardiovascular disease, and dementia risk, between trial eligible and ineligible persons. Results: We identified 10 trials, of which 5 had been published (DR’s EXTRA, FINGER, preDIVA, MAPT, and HATICE) and 5 are ongoing (US-POINTER, MIND-CHINA, MYB, AgeWell.de, and J-Mint). Among all Rotterdam Study participants, eligibility across published trials ranged from 48% for MAPT to 87% for preDIVA, in line with original trial reports. Variability in eligibility was wider for ongoing trials, from 1% for US-POINTER to over 94% for MYB trial. Over 70% of trial eligible individuals are recommended preventive intervention in routine care based on their cardiovascular risk, similar for lipid-lowering (71%) and blood pressure-lowering treatment (73%). Ten-year risks of dementia were similar for eligible compared to ineligible individuals (12 vs. 11%). Conclusion: Multidomain dementia prevention trials fail to preferentially include those at the highest risk of dementia and mostly include individuals who qualify for interventions already on the basis of cardiovascular prevention guidelines. These findings call for better targeted enrolment of individuals for whom trial results can improve clinical decision-making.

Background A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. Methods SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. Results Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time >28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. Conclusion Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. Trial registration number clinicaltrials.gov NCT03192332.

The European building stock presents pertinent issues needing suitable strategies to be solved. In detail, this regards seismic safety and energy efficiency of buildings to ensure more liveable and safe cities, which represents an important goal for modern societies. Energy performance includes both comfort and saving, the latter required for a more responsible resource consumption within the building sector, having a considerable contribution to the total demand. Current strategies do not seem to be able to simultaneously solve such aspects satisfactorily, both for higher economic requirements and poor technical feasibility implied by separated and disharmonious interventions. Thus, a holistic perspective should be adopted to pursue such an ambitious objective, which has recently gained increasing attention among researchers. Current requirements are firstly highlighted to show the need for an integrated approach to building retrofit. Secondly, a critical review of integrated strategies combining seismic and energy refurbishment proposed in the literature is reported. Then, special issues are discussed, including the feasibility of an integrated approach applied to heritage buildings. This study revealed that a fully efficient strategy for integrated retrofit has not still been proposed in the literature and there are several open issues to be solved. However, current solutions may be further developed to improve them and the several options currently available demonstrated the increasing attention and importance of the topic. Finally, concluding remarks on this research topic have been drawn to promote future studies.

Abstract Some recent findings suggest that metformin, an oral antidiabetic drug, may have antitumor properties. Studies have shown that metformin can alter cell metabolism, both tumor and immune cells, which can greatly influence disease outcome. In this review, we discuss the potential mechanisms in which metformin can directly induce apoptosis of tumor cells as well as mechanisms in which metformin can elicit or enhance antitumor immune response.