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Highlights A deep learning-based machine vision system was developed for pine seedling counting. Automated seedling counting achieved less error than the manual sampling-based practice. Regression-based counting from optical flow inputs achieved the best performance. Machine counting produces seedling density maps for management practice improvement. Abstract. The southern U.S. produces over 1 billion pine seedlings for market sales per year, with prices varying from 50 to 435 dollars per thousand seedlings. An accurate inventory of seedlings provides nursery management with insights into how many seedlings can be sold and/or if there is any loss due to washout, mechanical damage, or pest/diseases that can still be mitigated. In this study, we developed a system to count pine seedlings at production sites and map the seedling density in the field. A system with three cameras was developed to collect video from different drills in the seedling bed. The videos were preprocessed to restrict the region of interest to the center portion of the image in each camera and separated each drill into individual videos. Two different modalities, i.e., video and optical flow, were evaluated as inputs to a convolutional neural network followed by a long short-term recurrent network to model the sequence of frames and regress to the seedling count for each plot. The mean absolute percentage error (MAPE) of our best performing model was 7.5%, which is an improvement over the baseline manual sampling-based approach with a MAPE of 11%. The results showed that the proposed approach was able to count seedlings in a crowded scene under complex field conditions with higher accuracy than the standard manual practice. Therefore, the proposed system and results demonstrated the potential to replace manual counting and even provide further information such as a seedling density map over the field for precision forest nursery management and seedling harvesting. Keywords: CNN, LSTM, Nursery Inventory, Optical Flow, Pine Seedling, Regression.

Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1-196), the 3-year progression-free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3-year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper-CVAD or auto-SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.

The opioid epidemic has forced orthopaedic surgeons to reevaluate prescribing patterns and led hospitals to develop postoperative opioid-sparing protocols for patients undergoing total hip arthroplasty (THA). The purpose of this study was to investigate patient-reported pain and narcotic requirements in patients undergoing THA for fracture (F-THA) or nonfracture diagnoses (THA-E). A retrospective analysis was performed on patients who underwent primary THA at a single academic institution between January 2013 and December 2020. Patients with postoperative opioid prescription and Visual Analog Scale (VAS) pain score data were included. Patients who underwent primary THA with a diagnosis of femoral neck fracture (THA-F) were matched 1:1 with patients without primary fracture diagnoses (THA-E) using nearest-neighbor propensity-score matching. Operative time, length of stay (LOS), discharge disposition, 90-day readmission rates, 90-day opioid prescription amounts (quantified by morphine milligram equivalents [MME]), and daily postoperative VAS pain scores (averaged over 24-hour periods) were compared. A total of 8,714 patients met inclusion criteria (THA-E: 8,362; THA-F: 352). The THA-F group was older and had a higher proportion of females and a lower mean body mass index than the THA-E group. There were 331 THA-F patients successfully matched to 331 THA-E patients. Operative time (113.6 ± 41.3 vs. 914.9 ± 32.6 minutes, p

The authors of the article analyze the specifics of the formation of the linguistic picture of bilinguals, in whose minds two cultural codes are combined. The authors suggest that the linguistic picture of the world of bilinguals differs from the picture of a native speaker. When forming a bilingual linguistic personality, two cultures merge in his mind; many historical, social facts, influenced by individual and personal views, judgments, assessments, get a brighter color, are described differently, which makes it possible to understand the worldview of another person. Natural bilinguals, unlike artificial ones, have a combination of two pictures of the world, two cultural codes. However, both pictures in the mind of a bilingual, who is not divorced from one of the language environments, combine, change and eventually form another one with its own specific features. Bilingual writers, in whose minds two different languages are combined, using, for example, the Russian language when creating their work, nevertheless find themselves in the system of images of their native language, native culture. As a result, expressions, stylistic techniques and other means of artistic expression that are atypical for native speakers appear. This is how a new cultural code appears, which requires special linguistic means. A bilingual writer evaluates any phenomenon from the point of view of the native cultural The article provides examples: some characteristic features of the work of the Swedish bilingual writer of Greek origin Theodor Kallifatides, Russian-American writer V.V. Russian Russian and Kyrgyz literature by Chingiz Aitmatov, Russian French writer Andrei Makin. A bilingual author, in whose mind two different worlds are connected, nevertheless is closer to the system of images of his native language, native culture.

Since the introduction of the Grammont-style reverse total shoulder arthroplasty, the humeral stem design has been modified with improved clinical outcomes. Two distinct humeral designs have been used extensively: the inlay design, in which the humeral tray is seated within the metaphysis, and the onlay design, in which the humeral tray sits on the metaphysis at the level of the humeral neck cut. The purpose of this systematic review was to determine whether there are differences in clinical outcomes and complication rates between these designs.The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used to perform this systematic review. A search of MEDLINE, PubMed, and Embase was performed to identify all studies comparing the clinical results of both humeral designs. Primary outcomes included patient-reported outcome measures, shoulder range of motion, and incidence of complications.From the 156 identified publications, 12 studies were included in the final review. A total of 1447 patients were included, with a minimum follow-up period of 12 months. At final follow-up, both implants demonstrated significant improvements in comparison to preoperative baseline. On comparison of the inlay vs. onlay groups, the American Shoulder and Elbow Surgeons score was higher in the inlay group (mean difference, 2.53 [95% confidence interval, 0.27-4.78]; P = .03). Postoperative motion, even if statistically greater in the onlay group (differences of 5° in forward flexion [P .001], 3° in abduction [P = .003], and 4° in external rotation [P .001]), was not clinically different. On comparison of complications, the inlay group showed more instances of scapular notching (93 of 322 patients vs. 70 of 415 patients; odds ratio, 0.35; P .001) but fewer scapular spine fractures (26 of 727 patients vs. 21 of 559 patients, P = .09).Inlay and onlay humeral tray designs in reverse total shoulder arthroplasty demonstrate similar clinical improvements postoperatively. Onlay implants have a low rate of scapular notching but a higher rate of scapular spine fracture. Understanding the strengths and weaknesses of the 2 humeral tray designs is important to provide surgeons with options to tailor surgical plans for high-risk patients.

The mortality of the population from external causes ranks third after circulatory diseases and oncological pathology. The purpose of the review is to study the prevalence of firearms in the regions of the world and its impact on the frequency of homicides and suicides (intentional external causes of death) in various socio-demographic groups of the population. The issue of allowing firearms is solved in different ways – from a ban on its storage, carrying and use among the population to free sale and wide circulation in a particular country. In general, there is a growing trend in the number of people owning firearms, including the Russian Federation and its subjects. Availability of firearms at home, as well as free access to their use (among police officers, military personnel, etc.) increases the risk of suicide in these population groups several times with lethal outcomes in 85–91% of cases. Although the murder rate has been declining in recent years in the world and Russia, the share of violent crimes involving firearms is increasing. The number of mass murders committed by young people (schoolchildren, students, military personnel, recently conscripted into the army), whose victims are primarily their peers, is growing. Both murders and suicides are many (3-9) times more likely to be committed by males of mature (able-bodied) age. People having previous criminal records for illegal acquisition, transfer, sale, possession of firearms and other misdeeds often turn out to be murderers, and persons with mental pathology – self-murderers. At this, murders with subsequent suicide are most often committed with the use of firearms. Legislative restrictions on trafficking in firearms contribute primarily to reducing mass murders, as well as to reducing its use as instruments of murder and suicide.

The review presents current data on the structure and functional role of cell adhesion molecules belonging to the selectin family (selectins P, L and E), and their involvement in the pathogenesis of cardiovascular diseases. On the one hand, intercellular adhesion molecules of the vascular wall endothelium, platelets and leukocytes are an important link in the processes of vasculogenesis, development and regeneration of the vascular system. On the other hand, these molecules participate in the earliest stages of endothelial dysfunction with the subsequent development of pathology. For this reason, figuring out the mechanisms of activity of this group of molecules is very important for understanding the molecular basis of the cardiovascular diseases pathogenesis. The adhesion of molecules, both between cells and between cells and a component of the extracellular matrix, is the most important stage of physiological and biochemical processes. According to present knowledge, five classes of intercellular adhesion molecules are known: integrins, cadherins, immunoglobulins (including nectins), selectins and addressins. All of them are bonded to a cytoplasmic membrane and provide the interaction of cells with each other. Some of them are transmembrane and associated with the cytoskeleton of the cell. On the cell surface, intercellular adhesion molecules can be located in clusters, forming multipoint binding sites and thereby determining the degree of avidity. One of the most significant functions of selectins is participation in the initial stage of the leukocyte adhesion cascade, which results in their binding to the endothelium, rolling and further extravasation into tissues. The first stage of this process is mediated by specific non-covalent interactions between selectins and their glycan ligands, with the glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains one of the main strategies aimed at developing new methods of treating immune, inflammatory and oncological diseases.

The purpose is to investigate the incidence of wound complications for total knee arthroplasty (TKA) following tibial plateau open reduction and internal fixation (ORIF).A prospective arthroplasty registry was queried for patients with CPT codes for primary TKA, tibial plateau ORIF, removal of hardware (ROH), and diagnosis of post-traumatic arthritis. Patients were included if they had undergone tibial plateau ORIF and subsequent TKA. Chart review was performed to obtain demographic, clinical and post-operative information.Twenty-one patients were identified, with average age of 56.23 ± 13.2 years at time of tibial plateau ORIF and 62.91 ± 10.8 years at time of TKA. Seven (33.3%) patients had a tibial plateau fracture-related infection (FRI). Eight (38.1%) patients underwent ROH prior to TKA. Seven (33.3%) patients' TKA incision incorporated the prior plateau incisions. Eight (36.4%) patients developed wound complications following TKA and 5 (23.8%) developed an acute periprosthetic joint infection (PJI) following TKA and had the plateau incision incorporated into the TKA incision. FRI history did not increase the rate of wound complications but did increase the rate of ROH prior to TKA.Previous FRI involving tibial plateau repair surgery doesn't correlate with PJI after conversion TKA for post traumatic OA. Surgeon-controlled factors such as staged ROH and incision placement can help reduce the rate of wound complications following TKA performed after tibial plateau ORIF.Prognostic Level IV.The online version contains supplementary material available at 10.1007/s43465-022-00709-1.

Objective: The aim of this study was to assess the topography of the femoral and popliteal vessels focusing mainly on the venous variants, in patients with chronic venous disease (CVD). Materials and Methods: Duplex ultrasonography (DUS) was performed on 200 patients with varicose veins (VVs) and 253 patients with postthrombotic syndrome (PTS). In addition, an anatomical dissection was performed on 30 amputated lower extremities, without signs of CVD. Results: Duplication of the femoral vein (FV) was found in 14% of patients with VVs. Multiple FV trunks were identified in 42% of patients with PTS. One patient had a developmental anomaly with a hypoplastic FV and dilated deep FV. Two trunks of the popliteal vein (PV) below the knee level were detected in 83.3% of cases during anatomical dissection, in 87.5% of cases in patients with VVs, and in 90.1% of cases in PTS subjects during DUS. In 98.2% of cases, popliteal artery (PA) had a typical bifurcation. One patient was presented with a duplication of PA above the level of the knee. In 1.8% of cases, the PA was divided into an anterior tibial and peroneal artery. Conclusion: This study found variant anatomy in the FV and PV, which is frequent, with major changes occurring in patients with PTS. Variant anatomy of the PA was also found and is considered uncommon, occurring in less than 2% of cases.

Background: Transverse tubules (t-tubules) form gradually in the developing heart, critically enabling maturation of cardiomyocyte Ca 2+ homeostasis. The membrane bending and scaffolding protein BIN1 (bridging integrator 1) has been implicated in this process. However, it is unclear which of the various reported BIN1 isoforms are involved, and whether BIN1 function is regulated by its putative binding partners MTM1 (myotubularin), a phosphoinositide 3′-phosphatase, and DNM2 (dynamin-2), a GTPase believed to mediate membrane fission. Methods: We investigated the roles of BIN1, MTM1, and DNM2 in t-tubule formation in developing mouse cardiomyocytes, and in gene-modified HL-1 and human-induced pluripotent stem cell-derived cardiomyocytes. T-tubules and proteins of interest were imaged by confocal and Airyscan microscopy, and expression patterns were examined by RT-qPCR and Western blotting. Ca 2+ release was recorded using Fluo-4. Results: We observed that in the postnatal mouse heart, BIN1 localizes along Z-lines from early developmental stages, consistent with roles in initial budding and scaffolding of t-tubules. T-tubule proliferation and organization were linked to a progressive and parallel increase in 4 detected BIN1 isoforms. All isoforms were observed to induce tubulation in cardiomyocytes but produced t-tubules with differing geometries. BIN1-induced tubulations contained the L-type Ca 2+ channel, were colocalized with caveolin-3 and the ryanodine receptor, and effectively triggered Ca 2+ release. BIN1 upregulation during development was paralleled by increasing expression of MTM1. Despite no direct binding between MTM1 and murine cardiac BIN1 isoforms, which lack exon 11, high MTM1 levels were necessary for BIN1-induced tubulation, indicating a central role of phosphoinositide homeostasis. In contrast, the developing heart exhibited declining levels of DNM2. Indeed, we observed that high levels of DNM2 are inhibitory for t-tubule formation, although this protein colocalizes with BIN1 along Z-lines, and binds all 4 isoforms. Conclusions: These findings indicate that BIN1, MTM1, and DNM2 have balanced and collaborative roles in controlling t-tubule growth in cardiomyocytes.

The recently described peatlands of northern Peruvian Amazonia are relatively intact compared with peatlands elsewhere in the tropics. They make an important contribution to regional biodiversity and, by sequestering carbon, to climate change mitigation. Research to date has focused on their physical and biological aspects, but peatlands are not simply natural phenomena: they are used, valued and understood socially and culturally in profoundly different ways by different groups of people.This research project used an interdisciplinary participatory approach, working with peatland communities and stakeholders in Peru, to bring together the different perspectives needed to produce a comprehensive understanding which the natural sciences cannot achieve alone. The three central aims of the project were to 1) characterise the ecology and sociocultural values of the ecosystem types identified by local communities; 2) identify the strategies and challenges around community management of natural resources; and 3) identify opportunities for peatland conservation and maintenance of livelihoods. We worked with five peatland forest communities, three mestizo and two indigenous, in the Pastaza-Marañón Basin, which is the largest peat-forming area in lowland Peru. To address our aims we used a range of methods, both ecological (plot-based vegetation survey, measuring peat properties) and sociological (participatory mapping, interviews, focus groups).A key outcome of this work is a better understanding of the multifaceted importance of peatlands to local communities. The resources and spaces provided by peatland ecosystems were important culturally and socioeconomically to all five communities, but with pronounced differences relating to the communities’ different sociocultural and economic experiences and contexts. Another striking finding was that the nature of communities’ relationships with external actors, and their exposure to different opportunities and challenges, varied very markedly from one community to the next. For example, our study communities have experienced different interventions, some more successful and enduring than others, by government agencies and NGOs focusing mainly on biodiversity conservation; the success or otherwise of these past projects is likely to shape the willingness of communities to engage with future conservation efforts. Some communities have been more heavily influenced than others by the expansion of regional markets and value chains for timber and non-timber forest products into remote peatland areas over recent decades; other communities have been profoundly affected by activities of multinational extractive industries, including the oil industry and plantation agriculture.We conclude that future peatland conservation efforts and sustainable development projects in Peruvian Amazonia will need to recognize the significant variations from one community to the next in terms of the ways in which they use and value the peatlands, and in terms of their wider socio-economic and cultural contexts. Long-term protection of the peatlands will only be possible by engaging with communities individually, taking into account the concerns, needs, desires, threats, and opportunities particular to each one.

Genus Kamopanorpa Martynov, 1928 Type species. Kamopanorpa lata Martynov, 1928., Published as part of SUKATSHEVA, IRINA D. & SINITSHENKOVA, NINA D., 2023, A new caddisfly species Kamopanorpa aristovi sp. nov. of the family Microptysmatidae (Insecta, Trichoptera) from the Middle Permian of Udmurtya, Russia, pp. 120-123 in Palaeoentomology 6 (2) on page 120, DOI: 10.11646/palaeoentomology.6.2.3, http://zenodo.org/record/7942954

SUKATSHEVA, IRINA D., SINITSHENKOVA, NINA D. (2023): A new caddisfly species Kamopanorpa aristovi sp. nov. of the family Microptysmatidae (Insecta, Trichoptera) from the Middle Permian of Udmurtya, Russia. Palaeoentomology 6 (2): 120-123, DOI: 10.11646/palaeoentomology.6.2.3, URL: http://dx.doi.org/10.11646/palaeoentomology.6.2.3

Kamopanorpa aristovi Sukatsheva & Sinitshenkova sp. nov. (Fig. 1) Holotype. PIN, no 3695/141, part and counterpart of the caddisfly fore wing of good preservation. Etymology. The new species is named in memory of the late palaeoentomologist Daniil S. Aristov. Diagnosis. The fore wing of K. aristovi sp. nov. is of medium size, RS and M branching almost at the same level, the fork on R is absent, RS seven-branched. Locality and horizon. The Kostovaty site, Middle Urals, Udmurtya, right bank of the Kama River, 1.3 km upstream of the Kostovaty village and 6.4 km downstream of the Galevo pier. The deposits of Ilyinskaya Member in Lower Urzhum Formation of Urzhum Horizon are dated to the Middle Permian. Description. Fore wing rather narrow, length almost three times width, with greatest width at level of SC entering anterior wing margin. Anterior margin straight, apex broadly rounded. SC long, straight, ending in middle of third quarter of wing length. Costal area at wing base twice as wide as at wing apex, crossed by four crossveins. Subcostal area wide in its middle part, R straight, long, with very slight scooplike bend at apex. RS 1 simple, with straight crossvein r-rs 1+2. RS base at beginning of second quarter of wing length, RS seven-branched. RS 1+2 stem 2.6× as long as RS 3+4 stem. F 1 three-branched, F 2 four-branched. Additional fork on RS 2 of medium size, shorter than that on RS 4 and significantly longer than that on RS 3. F 1 fork 0,6× as long as F 2 fork. Cells DC and MC open. M with five branches, forks slightly distal to RS fork almost at the middle of wing. M 2, M 3 and M 4 simple. M 1 bifurcation short, almost equal in length to its trunk. CuA fork of same size as M 1 fork. Long arcuate cross vein m 3+4 -cua 1+2 present. Y-shaped vein not visible. CuP simple, short, entering wing trailing margin separately from A 1. A 2 long, 0.76× as long as A 1 and 2.6× so as A 3. Anal field narrow. Wing membrane with no coloration. Wing length 8.0 mm, width 3.5 mm. Remarks. According to the type of branching of RS and M (almost at the same level), the size of the forewing, the absence of a fork on R the described new species is closest to K. grossa Novokshonov, 1993 from the same locality of Kostovaty, differing from it in the much longer stems of R 1+4 and M 1 +3 and an open DC. The new species differs from all other species of the genus Kamopanorpa, including K. grossa, by its seven-branched RS (Martynov, 1933; Sukatsheva, 1976: Novokshonov, 1992, 1993; Sukatsheva & Aristov, 2017)., Published as part of SUKATSHEVA, IRINA D. & SINITSHENKOVA, NINA D., 2023, A new caddisfly species Kamopanorpa aristovi sp. nov. of the family Microptysmatidae (Insecta, Trichoptera) from the Middle Permian of Udmurtya, Russia, pp. 120-123 in Palaeoentomology 6 (2) on pages 120-121, DOI: 10.11646/palaeoentomology.6.2.3, http://zenodo.org/record/7942954, {"references":["Novokshonov, V. G. (1993) Caddis flies (Insecta, Trichoptera, Microptysmatidae). Paleontological Journal, 27 (1 A), 90 - 101.","Martynov, A. V. (1933) Permian fossil insects from the Arkhangelsk district. Pt. 1. The order Mecoptera. Trudy Paleontologicheskogo Instituta Akademiya Nauk SSSR, 2, 23 - 62.","Sukatsheva, I. D. (1976) Caddisflies of the suborder Permotrichoptera. Paleontological Journal, 10 (2), 198 - 209.","Novokshonov, V. G. (1992) Caddisflies of the genus Kamopanorpa (Trichoptera, Microptysmatidae) from the Kungurian of Chekarda (Perm District). Paleontological Journal, 26 (3), 136 - 141.","Sukatsheva, I. D. & Aristov, D. S. (2017) New insects (Insecta: Trichoptera, Eoblattida) from the Lower Permian of Russia. Paleontological Journal, 51 (4), 374 - 381. https: // doi. org / 10.1134 / S 0031030117040116"]}

Glycerol has found its applications as a heat-transfer fluid in heat exchangers, and as a compo-nent of functional solutions in biosensor analysis. Flowing non-aqueous fluids are known to be able to induce electromagnetic fields due to triboelectric effect. These triboelectrically generated electromagnetic fields can affect biological macromolecules. Horseradish peroxidase (HRP) is widely employed as a convenient model object for studying how external electric, magnetic, and electromagnetic fields affect enzymes. Herein, we have studied whether the flow of glycerol in a ground-shielded cylindrical coil affects the HRP enzyme incubated at a 2 cm distance near the coil’s side. Atomic force microscopy (AFM) has been employed in order to study the effect of glycerol flow on HRP at the nanoscale. Increased aggregation of HRP on mica has been observed after the incubation of the enzyme near the coil. Moreover, the enzymatic activity of HRP has also been affected. The results reported can find their application in biotechnology, food technology and life sciences application, considering the development of triboelectric generators, en-zyme-based biosensors and bioreactors with surface-immobilized enzymes. Our data can also be of interest for scientists studying triboelectric phenomena.

Severe aplastic anemia (SAA) is a marrow failure disorder with high morbidity and mortality. It is treated with bone marrow transplantation (BMT) for those with fully matched donors or immunosuppressive therapy (IST) for those who lack such a donor, which is often the case for underrepresented minorities. We conducted a prospective phase II trial of reduced-intensity conditioning HLA-haplo BMT and post-transplantation cyclophosphamide (PTCy)-based graft-versus-host (GVHD) prophylaxis as initial therapy for patients with SAA. The median age was 25 (range 3-63) years and the median follow-up was 40.9 months (95% CI: 29.4, 55.7 mos). Over 35% of enrollment was from underrepresented racial/ethnic groups. The cumulative incidence of grade II-IV aGVHD at day 100 is 7% (95% CI: NA, 17%) and chronic GVHD at 2 years is 4% (95% CI: NA, 11%). The overall survival for 27 patients is 92% (95% CI: 83,100%) at one, two, and three years. The first 7 patients received lower dose total body irradiation (200 versus 400 cGY), but these patients were more likely to have graft failure, 3 of 7, compared to 0 out of 20 patients in the higher dose group (p=0.01, Fisher exact). HLA-haploidentical BMT with PTCy using 400cGY total body irradiation resulted in 100% overall survival with minimal GVHD in 20 consecutive patients. Not only does this approach avoid the ramifications of IST and its low failure-free survival, but also the use of haploidentical donors expands access to BMT across all populations. Clinical trial: NCT02833805

The prospective use of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) for cardiac regenerative medicine strongly depends on the electro-mechanical properties of these cells, especially regarding the Ca2+-dependent excitation–contraction (EC) coupling mechanism. Currently, the immature structural and functional features of hiPSC-CM limit the progression towards clinical applications. Here, we show that a specific microarchitecture is essential for functional maturation of hiPSC-CM. Structural remodelling towards a cuboid cell shape and induction of BIN1, a facilitator of membrane invaginations, lead to transverse (t)-tubule-like structures. This transformation brings two Ca2+ channels critical for EC coupling in close proximity, the L-type Ca2+ channel at the sarcolemma and the ryanodine receptor at the sarcoplasmic reticulum. Consequently, the Ca2+-dependent functional interaction of these channels becomes more efficient, leading to improved spatio-temporal synchronisation of Ca2+ transients and higher EC coupling gain. Thus, functional maturation of hiPSC-cardiomyocytes by optimised cell microarchitecture needs to be considered for future cardiac regenerative approaches.

The aim of study was to investigate epidemiology aspects of magnetic resonance imaging (MRI) during COVID-19 pandemic. The study comprised depersonalized residents of Tomsk and Tomsk Region (n = 1714). Invitations to take online survey were sent to 50,000 residents by target SMS with response rate of 1.2% (n = 727, Cohort 1). Cohort 2 comprised retrospective patients (n = 987) who underwent contrast-enhanced cardiac MRI (CMR) in 2019-2022. Referrals, clinical characteristics, diagnosis, gender, age, past COVID-19, MRI study protocols, and MRI data were analyzed. 29% of respondents in cohort 1 received MRI examination within past two years; 26% of respondents considered MRI the most informative imaging modality for detecting COVID-19 pneumonia; 12% of respondents reported MRI unavailable. Proportion of CMR among MRI studies increased during COVID-19 pandemic, and maximum incidence of cardiac diseases detected by MRI was in 2021. Incidence of myocardial fibrosis increased from ~67% in 2019 to ~84% in 2022. The rate of outpatient MRI studies significantly increased in 2020, but returned to pre-pandemic level in 2021. COVID-19 pandemic increased the need for MRI and CMR. Patients with history of COVID-19 had persistent and newly occurring symptoms of myocardial damage suggesting chronic cardiac involvement requiring continuous follow-up.

New therapies are needed for patients with relapsed/refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) who do not benefit from or are ineligible for stem cell transplant and chimeric antigen receptor therapy. The CD30-targeted, antibody-drug conjugate brentuximab vedotin (BV) and the immunomodulator lenalidomide (Len) have demonstrated promising activity as single agents in this population. We report the results of a phase 1/dose expansion trial evaluating the combination of BV/Len in rel/ref DLBCL. Thirty-seven patients received BV every 21 days, with Len administered continuously for a maximum of 16 cycles. The maximum tolerated dose of the combination was 1.2 mg/kg BV with 20 mg/d Len. BV/Len was well tolerated with a toxicity profile consistent with their use as single agents. Most patients required granulocyte colony-stimulating factor support because of neutropenia. The overall response rate was 57% (95% CI, 39.6-72.5), complete response rate, 35% (95% CI, 20.7-52.6); median duration of response, 13.1 months; median progression-free survival, 10.2 months (95% CI, 5.5-13.7); and median overall survival, 14.3 months (95% CI, 10.2-35.6). Response rates were highest in patients with CD30+ DLBCL (73%), but they did not differ according to cell of origin (P = .96). NK cell expansion and phenotypic changes in CD8+ T-cell subsets in nonresponders were identified by mass cytometry. BV/Len represents a potential treatment option for patients with rel/ref DLBCL. This combination is being further explored in a phase 3 study (registered on https://clinicaltrials.org as NCT04404283). This trial was registered on https://clinicaltrials.gov as NCT02086604.

Background. In all cases of critical lower limb ischemia revascularization should be performed. However, the overlay of diabetic angiopathy significantly worsens the prognosis of the surgery, and the conservative therapy also frequently turns out to be ineffective even in the nearest future. Therapeutic stimulation of angiogenesis in this group of patients is an additional application point for the possible improvement of treatment results. Aim. Evaluating treatment results of patients with critical ischemia and underlying diabetes after 5 years from the beginning of supervising, as well as assessing the benefits of additional angiogenesis as a part of treatment. Material and methods. The study included data from 140 patients with critical ischemia and diabetes mellitus, divided into 4 groups, who received surgical [groups IA (n=45) and IB (n=30)] or therapeutic [groups IIA (n=40) and IIB (n=25)] treatment. Additional angiogenic therapy was also carried out in two groups (groups IB and IIB). Treatment outcomes were assessed over a 5-year period. Efficacy criteria were evaluated in the form of limb preservation and patient survival. The results were studied using descriptive statistics methods. Qualitative data were analyzed by constructing 22 contingency tables and using the xi-square method. Results. The best indices of limb preservation and the lowest mortality of patients were obtained in the group after revascularization with additional angiogenic therapy. Gene therapy induction significantly improved the course of disease in limb preservation for periods from 6 months to 2 years (30% amputations by 2 years of follow-up, p=0.045). Angiogenic induction of angiogenesis also made it possible to improve the treatment results in the groups of conservative therapy but reliably better indicators of limb preservation were obtained in two groups with surgical interventions. Conclusion. The optimal management tactic for patients with critical lower limb ischemia and underlying diabetes mellitus is direct revascularizing intervention on the lower limb arteries with additional angiogenic therapy in the postoperative period. Additional gene therapy induction of angiogenesis makes it possible to reduce the number of amputations both as part of combined surgical or therapeutic treatment , but it cannot be an alternative to surgery.

Richter transformation (RT) refers to the development of an aggressive lymphoma in patients with pre-existing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). It carries a poor prognosis secondary to poor response to therapy or rapid disease relapse. Currently there are no randomized trials to guide treatment. Therapeutic decisions are often influenced by the presence or absence of a clonal relationship between the underlying CLL/SLL and the new lymphoma given the poor prognosis of patients with clonally related RT. Chromosomal microarray analysis (CMA) can help to establish clonality while also detecting genomic complexity and clinically relevant genetic variants such as loss of CDKN2A and/or TP53. As a result, CMA has potential prognostic and therapeutic implications. For this study, CMA results from patients with Richter transformation were evaluated in paired CLL/SLL and transformed lymphoma samples. CMA revealed that 86% of patients had common aberrations in the two samples indicating evidence of common clonality. CMA was also useful in detecting aberrations associated with a poor prognosis in 71% of patients with RT. This study highlights the potential clinical utility of CMA to investigate the clonal relationship between CLL/SLL and RT, provide prognostic information, and possibly guide therapeutic decision making for patients with Richter transformation.

Aim: To analyze the dynamics of oncogynecological morbidity level in Sumy region and to identify barriers for prevention and early diagnosis of oncogynecological diseases in women. Materials and Methods: study structure included: desk study (collection and analysis of statistical data), medical and sociological research on definition of barriers for prevention and early detection of oncogynecological diseases on the basis of primary medical level, which was conducted by questioning among women of Sumy region with an anonymous questionnaire with subsequent statistical processing of data using the license package of programs “PSQ” (processing of sociological questionnaires), a computer program of primary sociological information analysis. Results: in the process of analyzing the dynamics of morbidity, mortality, annual mortality and neglect of diseases of oncopathology, a decreasing in the rate of morbidity was found with simultaneous increasing of annual mortality and neglect, which highlights a decrease in carrying out preventive examinations in women. This, in turn, worsens the possibility of diagnosis of gynecological oncopathology at the early stages and their prevention. Conclusions: this requires development of a set of measures that would provide maximum coverage of regular gynecological preventive examinations in women. This mechanism can be effectively implemented through involvement the territorial communities in the process.

Multimodal prehabilitation programs to improve physical fitness before surgery often include nutritional interventions. This study evaluates the efficacy of and adherence to a nutritional intervention among colorectal and esophageal cancer patients undergoing the multimodal Fit4Surgery prehabilitation program. The intervention aims to achieve an intake of ≥1.5 g of protein/kg body weight (BW) per day through dietary advice and daily nutritional supplementation (30 g whey protein). This study shows 56.3% of patients met this goal after prehabilitation. Mean daily protein intake significantly increased from 1.20 ± 0.39 g/kg BW at baseline to 1.61 ± 0.41 g/kg BW after prehabilitation (p < 0.001), with the main increase during the evening snack. BW, BMI, 5-CST, and protein intake at baseline were associated with adherence to the nutritional intervention. These outcomes suggest that dietary counseling and protein supplementation can significantly improve protein intake in different patient groups undergoing a multimodal prehabilitation program.

Introduction: As with many other surgical interventions, the implantation of a pacemaker may be associated with adverse outcomes in the immediate or distant period. The search for probable risk factors of adverse outcomes may promote the development of effective and safe management methods of patients with pacemaker postoperatively. One of the important directions in this field is the investigation of the effect of pacemaker implantation on the hemostasis system of these patients. Aim: To evaluate the effect of the implantation of dual-chamber pacemaker on the hemostasis system of patients with different kinds of bradyarrhythmias and to determine probable risk factors for unfavorable outcomes in this groupof patients. Materials and methods: The study was performed with the financial support of the Russian Foundation for Basic Research within the Scientific Project No. 19-315-90109. The prospective study (ClinicalTrials.gov ID, NCT04499612) enrolled 61 patients (men, 45.9%) with a mean age of 71.5 8.8 years. The groupwho received surgical treatment included 23 patients with atrioventricular (AV) block and 25 patients with sick sinus syndrome (SSS), and the groupwith conservative treatment included 13 patients with AV blocks and SSS, but without indications for pacemaker implantation. Anticoagulant therapy was given to one patient with AV block, 12 patients with SSS, and five patients with conservative therapy. All the remaining patients received antiplatelet therapy. The surgical groupunderwent ultrasound examination of the veins of the upper and lower extremities and sampling of peripheral venous blood before and 7 days after pacemaker implantation to determine the level of fibrinogen (FI) and activity of blood coagulation factors VIII (FVIII) and IX (FIX), antithrombin III (AT III), and protein C. In the conservative group, a similar examination was conducted only on inclusion in the study. Results: In patients with AV block, a significant increase in blood fibrinogen was noted at 7 days after surgery (р=0.042). In the intergroupcomparison, the activity of AT III after the implantation was higher in the surgical groupthan in the conservative group(р=0.018 and р=0.006, respectively). After surgery, the activity of FVIII and FIX was lower in patients with SSS on anticoagulant therapy than in patients with antiplatelet therapy (р=0.048 and р=0.015, respectively). Based on the receiver operating characteristics analysis, the risk factors for lethal outcomes were reduced activity of AT III in patients with AV block and increased activity of FIX in patients with SSS. Conclusions: The balance of the hemostasis system in patients with AV blocks on antiplatelet therapy was shifted toward hypercoagulation within at least 7 days after pacemaker implantation. The use of anticoagulants in patients with SSS caused a shift toward hypocoagulation. The reduced activity of AT III in patients with AV block and increased activity of FIX in patients with SSS are prognostic factors for lethal outcomes.

PURPOSE Diagnosis of AIDS lymphoma in low-resource settings, like South Africa, is often delayed, leaving patients with limited treatment options. In tuberculosis (TB) endemic regions, overlapping signs and symptoms often lead to diagnostic delays. Assessment of plasma cell-free DNA (cfDNA) by next-generation sequencing (NGS) may expedite the diagnosis of lymphoma but requires high-quality cfDNA. METHODS People living with HIV with newly diagnosed aggressive B-cell lymphoma and those with newly diagnosed TB seeking care at Chris Hani Baragwanath Academic Hospital and its surrounding clinics, in Soweto, South Africa, were enrolled in this study. Each participant provided a whole blood specimen collected in cell-stabilizing tubes. Quantity and quality of plasma cfDNA were assessed. NGS of the immunoglobulin heavy chain was performed. RESULTS Nine HIV+ patients with untreated lymphoma and eight HIV+ patients with TB, but without lymphoma, were enrolled. All cfDNA quantity and quality metrics were similar between the two groups, except that cfDNA accounted for a larger fraction of recovered plasma DNA in patients with lymphoma. The concentration of cfDNA in plasma also trended higher in patients with lymphoma. NGS of immunoglobulin heavy chain showed robust amplification of DNA, with large amplicons (> 250 bp) being more readily detected in patients with lymphoma. Clonal sequences were detected in five of nine patients with lymphoma, and none of the patients with TB. CONCLUSION This proof-of-principle study demonstrates that whole blood collected for cfDNA in a low-resource setting is suitable for sophisticated sequencing analyses, including clonal immunoglobulin NGS. The detection of clonal sequences in more than half of patients with lymphoma shows promise as a diagnostic marker that may be explored in future studies.

The paper is devoted to developing a methodology for analysing the stability of Instrumentation and Control Systems (ICS) of Nuclear Power Plants (NPPs) to the impact of computer attacks aimed at producing an accident event (targeted computer attacks). The paper demonstrates the need to consider the impact of threats to information security when analysing the safety of the process control system of the NPP power unit. Various methods of safety analysis of ICS of NPPs are considered. Their fundamental shortcomings are highlighted: the lack of consideration of the factors of anthropogenic threats to information security, dependence of failures, the complexity of presentation of modelling results with a large number of subsystems. Based on the analysis of existing practices, the requirements for the developed methodology are formed. As a result, a methodology is developed for analysing the stability of ICS of NPPs to the impact of targeted computer attacks based on the use of risk assessment matrix models: failure impact matrices and criticality matrix hierarchies. The procedure for analysing and modelling computer attacks using influence matrices and a hierarchy of criticality matrices is described. The application of the method is demonstrated by the example of the ICS segment of NPP: a scenario of a targeted computer attack is modelled using the criticality matrix hierarchy. The expediency of using failure impact matrices and a criticality matrix hierarchy for modelling targeted computer attacks on the ICS of NPPs is substantiated. The scientific novelty of the study consists in the proposal of a methodology for analysing the stability of ICS of NPPs, which takes into account the dependence of failures and allows modelling scenarios of computer attacks. Since the risk assessment matrix models are an indistinct extension of the applied Failure Mode and Effects Critical Analysis, the developed methodology can be integrated into existing practices of safety analysis of the ICS of NPPs.

The article examines the attitude of contemporary African writers to the traditional zoomorphic and anthropomorphic masks. In the 1960s–70s, for the supporters of the theory of negritude, the sacred mask embodied the spirit of ancestors and an inextricable connection with tradition. In a transitional era (the 1990s – the early 21st century), the process of desacralisation of the mask has been observed and such works appear in which the idea of the death of tradition is carried out. The article consistently examines the history of the emergence and strengthening of interest in the image of the African mask as the most striking symbol of African traditions on the part of cultural, art and scientific workers and the reflection of this symbol in the works of representatives of Francophone literature in West and Central Africa in different periods of time. The article concludes about the transformation of the views of the studied writers on the future of African traditions from an enthusiastic and romantic (as, for example, in the lyrics of Léopold Sédar Senghor or Samuel-Martin Eno Belinga) attitude to the images of the African past and tradition – masks, ancestor cult – to despair and bitterness from the awareness of the desacralisation of traditional objects and images and the profanation of tradition under the pressure of the realities of the present day (drama by Koffi Kwahulé). The attitude of African writers to the image of the mask, which is directly related to the themes of preserving traditions and the search of their identity by African literary heroes, is gradually changing, demonstrating the pessimistic view of Francophone African writers on the future of African traditions.

Summary Background In the primary analysis of the pivotal JULIET trial of tisagenlecleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, the best overall response rate was 52% and the complete response rate was 40% in 93 evaluable adult patients with relapsed or refractory aggressive B-cell lymphomas. We aimed to do a long-term follow-up analysis of the clinical outcomes and correlative analyses of activity and safety in the full adult cohort. Methods In this multicentre, open-label, single-arm, phase 2 trial (JULIET) done at 27 treatment sites in ten countries (Australia, Austria, Canada, France, Germany, Italy, Japan, the Netherlands, Norway, and the USA), adult patients (≥18 years) with histologically confirmed relapsed or refractory large B-cell lymphomas who were ineligible for, did not consent to, or had disease progression after autologous haematopoietic stem-cell transplantation, with an Eastern Cooperative Oncology Group performance status of 0–1 at screening, were enrolled. Patients received a single intravenous infusion of tisagenlecleucel (target dose 5 × 108 viable transduced CAR T cells). The primary endpoint was overall response rate (ie, the proportion of patients with a best overall disease response of a complete response or partial response using the Lugano classification, as assessed by an independent review committee) at any time post-infusion and was analysed in all patients who received tisagenlecleucel (the full analysis set). Safety was analysed in all patients who received tisagenlecleucel. JULIET is registered with ClinialTrials.gov , NCT02445248 , and is ongoing. Findings Between July 29, 2015, and Nov 2, 2017, 167 patients were enrolled. As of Feb 20, 2020, 115 patients had received tisagenlecleucel infusion and were included in the full analysis set. At a median follow-up of 40·3 months (IQR 37·8–43·8), the overall response rate was 53·0% (95% CI 43·5–62·4; 61 of 115 patients), with 45 (39%) patients having a complete response as their best overall response. The most common grade 3–4 adverse events were anaemia (45 [39%]), decreased neutrophil count (39 [34%]), decreased white blood cell count (37 [32%]), decreased platelet count (32 [28%]), cytokine release syndrome (26 [23%]), neutropenia (23 [20%]), febrile neutropenia (19 [17%]), hypophosphataemia (15 [13%]), and thrombocytopenia (14 [12%]). The most common treatment-related serious adverse events were cytokine release syndrome (31 [27%]), febrile neutropenia (seven [6%]), pyrexia (six [5%]), pancytopenia (three [3%]), and pneumonia (three [3%]). No treatment-related deaths were reported. Interpretation Tisagenlecleucel shows durable activity and manageable safety profiles in adult patients with relapsed or refractory aggressive B-cell lymphomas. For patients with large B-cell lymphomas that are refractory to chemoimmunotherapy or relapsing after second-line therapies, tisagenlecleucel compares favourably with respect to risk–benefit relative to conventional therapeutic approaches (eg, salvage chemotherapy). Funding Novartis Pharmaceuticals.

The influence of an external constant strong electric field, formed using a pyramidal structure under a high electric potential, on an enzyme located near its apex, is studied. Horseradish peroxidase (HRP) is used as a model. In our experiments, a 27 kV direct current (DC) voltage was applied to two electrodes with a conducting pyramidal structure attached to one of them. The enzyme particles were visualized by atomic force microscopy (AFM) after the adsorption of the enzyme from its 0.1 µM solution onto mica AFM substrates. It is demonstrated that after the 40 min exposure to the electric field, the enzyme forms extended structures on mica, while in control experiments compact HRP particles are observed. After the exposure to the electric field, the majority of mica-adsorbed HRP particles had a height of 1.2 nm (as opposed to 1.0 nm in the case of control experiments), and the contribution of higher (>2.0 nm) particles was also considerable. This indicates the formation of high-order HRP aggregates under the influence of an applied electric field. At that, the enzymatic activity of HRP against its substrate 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) remains unaffected. These results are important for studying macroscopic effects of strong electromagnetic fields on enzymes, as well as for the development of cellular structure models.

This study aimed to assess the efficacy and safety of Actovegin for the treatment of patients with Fontaine stage IIB peripheral arterial disease (PAD).The study included 366 patients with Fontaine stage IIB PAD from 19 centers (Russia, Georgia, Kazakhstan). Placebo or Actovegin (1200 mg daily [QD]) were administered intravenously for two weeks, followed by a 10-week course of oral administration (placebo or Actovegin 1200 mg QD). The primary efficacy outcome was percentage change in the initial claudication distance (ICD) by week 12. Secondary outcomes included percent and absolute changes in ICD, absolute claudication distance (ACD) and changes in Quality of Life (QoL) assessed by the SF-36 Mental Health Score.The increase in ICD after 12 weeks of Actovegin treatment was 29.19% (LS mean [Actovegin vs. placebo]; 95% CI: 9.35-49.02; P=0.0041). The percentage increase in ICD at 24 weeks was 35.51% (LS mean; 95% CI: 10.96-60.05; P=0.0047), which correspond to an increase in absolute ICD of 41.22 m (LS mean; 95% CI: 16.77-65.66; P=0.0010). The percentage increase in ACD after 24 weeks was 36.47% compared with the baseline (LS mean; 95% CI: 10.07-62.88; P=0.0069), which corresponded to an absolute increase in ACD of 50.92 m (LS mean; 95% CI: 18.35-83.49; P=0.0023). A statistically significant improvement in QoL with Actovegin compared with placebo was demonstrated within 24 weeks (LS mean 2.28; 95% CI: 0.88-3.68; P=0.0015). Actovegin demonstrated an acceptable safety and tolerability profile with minor differences from placebo.The results of this 12-week course of Actovegin demonstrated its superiority over placebo in the increase in ICD and ACD at weeks 2, 12 and 24 from the start of treatment. Actovegin has an acceptable safety and tolerability profile.

Las competencias emprendedoras están relacionadas con capacidades, destrezas, habilidades y aptitudes que posee un emprendedor, o puede adquirir, a través de procesos formativos y de capacitación. Así, el objetivo de la investigación es identificar las competencias emprendedoras en los estudiantes de la carrera de Administración de Empresas de la Universidad Técnica de Oruro, Bolivia, adquiridas en los procesos de formación profesional. El tipo de investigación es descriptivo-correlacional, con diseño de campo, transeccional. Se realizó una encuesta a 290 estudiantes de pregrado, seleccionados de forma intencional. Los principales resultados establecen que el coeficiente de correlación (R) alcanza un valor de 0.153, lo que indica la existencia de una asociación entre las variables; sin embargo, el coeficiente de determinación (R2) tiene un valor de 0.024, lo que permite sostener que la relación de las variables es muy baja, siendo nada significativa la misma. Se concluye que los tipos de competencias que deben desarrollar los estudiantes para generar una cultura emprendedora son las actitudinales, como la motivación, creatividad, liderazgo, toma de decisiones y pensamiento crítico; además, de las conceptuales, como el conocimiento operativo de un negocio, comprensión de la gestión del talento humano, conocimiento de finanzas y el de marketing.

The association of tibial shaft fractures (TSFs) with posterior malleolar fractures is well described. The purpose of this study was to identify specific radiographic parameters that are predictive of any pattern of associated distal intra-articular fractures in TSFs.All TSFs presenting over a 6-year period were identified. A radiographic review of plain radiographs and CT scans included: identification of any associated ankle fracture, classification using the OTA System, measurements of the TSF obliquity angle (FOA), relative distance from distal extent of the TSF to plafond (DFP%), and presence and level of any associated fibular fractures. Patients with and without associated ankle fractures were statistically compared. Multivariate logistic regression determined independent predictors of associated ankle fractures.405 TSFs in 397 patients were identified, with 145 TSFs with associated distal intra-articular fractures. There were 94 (23.2%) posterior malleolar fractures, 19 (13.1%) medial malleolar fractures, 42 (29.0%) lateral malleolar fractures involving the syndesmosis and 14 (9.7%) Chaput fragments. Multivariate regression demonstrated AO/OTA classification type 42-A1, 42-B1 or 42-C1 (OR 2.3 [95% CI 1.3-4.0]; p = 0.003), FOA greater than 45° (OR 2.7 [95% CI 1.5-4.8]; p = 0.001) and DFP% less than 33% (OR 4.1 [95% CI 2.0-9.0]; p = 0.005) were independent correlates of associated ankle fractures regardless of mechanism of injury.Different patterns of intra-articular fractures beyond posterior malleolar fractures can occur in TSFs. Fracture angles greater than 45° and extent into the distal 33% of the tibial shaft are independent predictors of distal intra-articular fractures in TSFs regardless of mechanism of injury.Diagnostic Level III.

Approximately 25% of all patients who sustain perilunate dislocations present in a delayed fashion.While management of acute injuries is relatively well-described, treatment of chronic injuries can be complex and there is a paucity of scientific evidence to guide management.Treatment options include open reduction internal fixation, proximal row carpectomy, scaphoid or lunate excision with or without arthrodesis, and total wrist arthrodesis, although indications vary based on chronicity of injury and patient factors.The purpose of this article was to determine the quality of evidence supporting surgical options for the treatment of these injuries.