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INTRODUCTION:In oncological drug development, animal studies continue to play a central role in which the volume of subcutaneous tumours is monitored to assess the efficacy of new drugs. The tumour volume is estimated by taking the volume to be that of a regular spheroid with the same dimensions. However, this method is subjective, insufficiently traceable, and is subject to error in the accuracy of volume estimates as tumours are frequently irregular. METHODS & RESULTS:This paper reviews the standard technique for tumour volume assessment, calliper measurements, by conducting a statistical review of a large dataset consisting of 2,500 tumour volume measurements from 1,600 mice by multiple operators across 6 mouse strains and 20 tumour models. Additionally, we explore the impact of six different tumour morphologies on volume estimation and the detection of treatment effects using a computational tumour growth model. Finally, we propose an alternative method to callipers for estimating volume-BioVolumeTM, a 3D scanning technique. BioVolume simultaneously captures both stereo RGB (Red, Green and Blue) images from different light sources and infrared thermal images of the tumour in under a second. It then detects the tumour region automatically and estimates the tumour volume in under a minute. Furthermore, images can be processed in parallel within the cloud and so the time required to process multiple images is similar to that required for a single image. We present data of a pre-production unit test consisting of 297 scans from over 120 mice collected by four different operators. CONCLUSION:This work demonstrates that it is possible to record tumour measurements in a rapid minimally invasive, morphology-independent way, and with less human-bias compared to callipers, whilst also improving data traceability. Furthermore, the images collected by BioVolume may be useful, for example, as a source of biomarkers for animal welfare and secondary drug toxicity / efficacy.

This article presents the role played by philosophy and biblical exegesis in controversy with Apollinarius of Laodicea. First of all it tries to present the gene­ral context of the dispute, then to develop Basil’s theological thinking and apply it to the problematic Christological field, where Apollinarius directed his challenge. Faced with the anthropological-soteriological problem relating to the defence of the integrity of Christ’s human nature, Basil draws on Stoic and Neoplatonic phi­losophical tradition. Then, this paper focuses attention on Basil’s interpretation of some biblical passages in the confutation of Apollinaris’ doctrine. Basil had star­ted the controversy by describing Apollinarius as supporter of fabulous theories, which are not based on the Scriptures, and of Judaizing ideas which concerned the eschatological renewal. Generally, the Cappadocian prefers to distance himself from Apollinaris and does not intervene in complete manner on the theological de­bate. The bishop – monk tries to unmask the errors of the opponents’ theories star­ting with the correct interpretation of the scriptural passages used by Apollinarius. In some points of his works, the Cappadocian insists that the Savior had a soul capable of feeling and suffering. According to the bishop of Caesarea some of anthropological and philosophical principles used by Apollinaris, along with the distorted reading of biblical texts, revealed the ambiguities and the inconsistencies of his arguments.

The project PROTECTFOREST deals with improvements in early bark beetle (e.g., Ips typographus and Pityogenes chalcographus) detection to allow for fast and effective response to initial infestation. The removal of trees in the early infestation stage can prohibit bark beetle population gradation and successive timber price decrease. A semiconductor gas sensor array was tested in the lab and attached to a drone under artificial and real-life field conditions. The sensor array was able to differentiate between α-pinene amounts and between different temperatures under lab conditions. In the field, the sensor responded to a strong artificial α-pinene source. The real-life field trial above a spruce forest showed preliminary results, as technical and environmental conditions compromised a proof of principle. Further research will evaluate the detection rate of infested trees for the new proposed sensor concept.

Artykuł otwiera przedstawienie mowy Przeciwko gniewliwym Bazylego Wielkiego w kontekście jego nauczania praktyczno-moralnego. Następnie zostają ukazane przyczyny i objawy gniewu. Poprzez przybliżenie kwestii niebezpiecznego uczucia Kapadocejczyk wyczula swoich słuchaczy na to, by unikać tego zgubnego grzechu, który czyni człowieka szalonym i powoduje jego zezwierzęcenie. Porównuje człowieka ogarniętego złością do niebezpiecznych i jadowitych zwierząt, osób dotkniętych chorobą psychiczną lub opętanych przez demona. Za pomocą sugestywnych metafor kaznodzieja ukazuje destrukcyjną siłę gniewu i jego zgubne konsekwencje. Uznaje jednak pozytywne jego skutki, gdyż to uczucie, odpowiednio ukierunkowane i odmienione, może służyć wielu dobrym aktom. Chrześcijanie mogą posłużyć się tym impulsem w walce ze złem. Środkami zaradczymi przeciwko gniewowi są: spokój, posłuszeństwo Słowu Bożemu, naśladowanie przykładu Chrystusa i postaci biblijnych.

Summary: The roles of the microbiome and innate immunity in the pathogenesis of multiple sclerosis (MS) remain unclear. We have previously documented abnormally low levels of a microbiome‐derived Toll‐like receptor (TLR)2‐stimulating bacterial lipid in the blood of MS patients and postulated that this is indicative of a deficiency in the innate immune regulating function of the microbiome in MS. We postulated further that the resulting enhanced TLR2 responsiveness plays a critical role in the pathogenesis of MS. As proof‐of‐concept, we reported that decreasing systemic TLR2 responsiveness by administering very low‐dose TLR2 ligands attenuated significantly the mouse model of MS, experimental autoimmune encephalomyelitis. Studies of Toll‐like receptor responses in patients with MS have been conflicting. Importantly, most of these investigations have focused on the response to TLR4 ligation and few have characterized TLR2 responses in MS. In the present study, our goal was to characterize TLR2 responses of MS patients using multiple approaches. Studying a total of 26 MS patients and 32 healthy controls, we now document for the first time that a large fraction of MS patients (50%) demonstrate enhanced responsiveness to TLR2 stimulation. Interestingly, the enhanced TLR2 responders include a significant fraction of those with progressive forms of MS, a subset of patients considered unresponsive to adaptive immune system‐targeting therapies. Our results suggest the presence of a pathologically relevant TLR2 related innate immune abnormality in patients with both relapsing–remitting and progressive MS. These findings may have significant implications for understanding the role of innate immunity in the pathogenesis of MS. [ABSTRACT FROM AUTHOR]

Spojrzenie na chrześcijańskie podejście do przyrody wymaga zanalizowania wzajemnych relacji pomiędzy koncepcjami antropocentryzmu i kosmocentryzmu. Obie te wizje rzeczywistości wydają się być kluczem do całościowego ujęcia relacji człowiek – natura. Chrześcijański antropocentryzm często jest obwiniany o to, że stał się przyczyną obecnego kryzysu ekologicznego. Wyznawcy Chrystusa są oskarżeni o niszczenie harmonii świata i jego zasobów. Jednak chrześcijański antropocentryzm nie był najwyższą i niezależną zasadą. Chrześcijaństwo musiało skonfrontować się z wizją natury i człowieka propagowaną przez filozofię grecką i rzymski realizm. Pisarzom Kościoła nasza cywilizacja zawdzięcza niezwykle cenne rozważania o dobroci i pięknie stworzenia. Według perspektywy patrystycznej człowiek zajmuje najważniejsze miejsce w świecie przyrody, lecz nie jest to pozycja despoty, który ma nieograniczone prawo do eksploatowania zasobów naturalnych. Istota ludzka, należąca do porządku stworzenia, ma specyficzną misję i obowiązki wobec widzialnego świata. Człowiek stanowi jakby pomost pomiędzy stworzeniami a Bogiem, jest jakby kapłanem liturgii kosmicznej. U Ojców Kościoła można było zauważyć odnośniki biblijne, przede wszystkim do Rdz i Rz 8,18-22. W przypadku perykopy pawłowej ma się do czynienia z podwójną tendencją interpretacyjną: antropologiczną i kosmologiczną. Ojcowie Wschodu, nawiązując do podziwu okazywanego siłom natury w cywilizacji greckiej, preferowali interpretację kosmologiczną. Z kolei na łacińskim Zachodzie na plan pierwszy wysuwała się kwestia podporządkowania ziemskiego istnienia wyższym zasadom, jakimi były teocentryzm i chrystocentryzm. W ten sposób cała rzeczywistość widzialna została przez chrześcijaństwo przemyślana i głęboko ubogacona.

The article describes the failure of the steel supporting structure of the pipeline caused by corrosion. The structure in question is a three-span steel bridge with truss girders. The structure was erected in the 1960s and is located above the railway track. Due to the specific shape of the hinges, which join the middle span with the rest of the structure one of them was damaged by corrosion, which caused it to break off. That led to situation where the middle span was retained by only three joints. To achieve proper safety of the structure it was additionally supported and strengthened. Due to the necessity of quick repair (there was a real threat of a collapse), some of the works performed had a provisional character. The article presents a description, detailed causes for failure and all the works, which were carried out in order to protect and repair the structure. The analysis of this case showed that, despite adequate protection of structural elements against corrosion, improper design resulting in retaining water led to serious failure.

The article focuses the story of the martyrdom of 60 Christian soldiers in Gaza who were executed for their refusal to convert to Islam during the Muslim inva­sion of Palestine. It is a final episode of varied Christian history of that region. Christian history of Gaza appears as complex and fascinating. In this region in the 4th century paganism was still strong but the monastic life developed in the vicinity of Gaza. Literary sources annotated the anti-Chalcedonian resistance of monastic circles in the wake of the council of Chalcedon. Christian history of the Gaza region ended dramatically with the Arab conquest in the 7th century. Just at that time a group of Christian soldiers refused the offer of the commander of the winners Muslims. The narrative of their martyrdom was preserved in a Latin translation of a Greek original. According to the text of the Passio, the Christian soldiers were executed in two groups: at Jerusalem and at Eleutheropolis. Bi­shop Sophronius of Jerusalem intervened in favor of these Martyrs and comforted them. He also gained the palm of martyrdom. The Passio in two different Latin recensions reveals a relatively neglected aspect in the history of the Holy Land during the period of heightened religious tension.

Evaluation of classifiers in diagnosis support systems is a non-trivial task. It can be done in a form of controlled and blinded clinical trial, which is often difficult and costly. We propose a new method for generating artificial medical cases from a knowledge base, utilizing the concept of so-called medical diamonds. Cases generated using this method have features analogous to that of double-blinded trial and, thus, can be used for measuring sensitivity and specificity of diagnostic classifiers. This is easy and low-cost method of evaluation and comparison of classifiers in diagnosis support systems. We demonstrate that this method is able to produce valuable results when used for evaluation of similarity-based classifiers as well as shallow and deep neural networks.

The article is an examination of Basil’s teaching about faith and its impor­tance in his large correspondence. The bishop of Caesarea describes faith as the acceptance of the Gospel, the conviction of the truth of the message, a confession of one’s belief in the Trinity. The Cappadocian emphasizes faith as an accep­tance and conviction of the truth which comes from the inspired Scriptures and the teaching of the Nicaea. The confession of faith formulated by the Council of Nicaea constituted the essence of the truth of the Christian faith. The bishop of Caesarea indicates the importance of the baptismal formula for the formula­tion of the true Christian doctrine. During the baptismal rite the baptizand makes their confession of faith and is thus admitted into the community of the faithful. Basil’s teaching of initiation into the Christian mistery is dominated by his use of the word mean the apostolic doctrines which constitute what the „Great Church” taught and believed. The Cappadocian points to the danger of false and heretical assemblies (parasynagogues) and of the false teachers of the faith. It is presented as a way of knowing God. There is also one important emphasis in Basil’s thought which especially characterizes his view of the human steps in the concrete realiza­tion of it: the knowledge of God and faith in Him is manifested in love to God and one’s neighbor.

The article presents the complex symbolism of salt that was strongly in­fluenced by the rites and beliefs of the pagan and the biblical world as well as early Christian literature. The salt is an element present in every aspect of human life (food, medicine and religious cults). It played an important role in sacrifices and offerings of Old Testament. For this reason, Jesus’ use of this metaphor was extremely familiar to His followers. On the biblical bases the various allegorical motifs of salt were present in Christian authors. Metaphors associated with the salt became precise and rich. Salt was a symbolic figure of wisdom, moral cleanness and incorruptibility. God’s salt enabled one to triumph over the spiritual enemy. The Fathers taught to point others to the way of life, to show how they might be preserved from death and destruction. They pointed out how the purpose of Christian life depended on their spiritual saltiness.

Ponerology is devoted to the study of evil in its different aspects. Indeed, also in the early Church it was created a kind of ponerological symbolism. This short study analyses some of these significant traditionally interpreted symbols. In the Christian symbolism holiness is full of fragrance, however the demons and sins emit a terrible odor. The symbolic value of darkness covers the negative aspects of human ignorance, evil, disbelief, danger and death. The fire represents not only illumination and light, but it has the punitive value. The serpent is first mentioned in connection with the history of the temptation and fall of the humanity. In the Christian tradition the serpent or the „dragon” represents Satan, the malicious ene­my. Babylon symbolizes all that is worldly and fell away from God. St. Augustine sees the world in which he lives as a mixture of the city of confusion and the city of heaven (Jerusalem). In the ponerological symbolism appears Amalek. The Fathers equated them with passion or evil. The faithful of Christ always fights against him. In Origen this approach is much more clearly defined in his explicitly spiritualizing reading. The ponerological symbolism of the ancient Christian lite­rature contained a moral or religious lessons or allegories.

The place of beginning of the Christian community was called „the Upper Church of the Apostles” in Mount Zion. It became the seat of the Mother Church under the leadership of fourteen bishops of Jewish stock from the beginning until the reign of Constantine. The authority of the bishops was symbolized by the throne of St. James. The complete transformation of Jerusalem into a „Roman city” operated by Emperor Aelius Hadrian meant the end of the Jewish hierar­chy in the Mother Church and the emergence of a new leadership of Gentile ori­gin. Until the time of bishop Maximus the Holy Sepulcher became the center of the Gentile Church. In the IV century we can say the growing rivalry between Caesarea and Jerusalem and appearing of many members of the hierarchy and the monastic communities participated very energetically in the problems of the local Church. In the time of Cyril of Alexandria can be seen the support given to him by the Palestinian bishops. The alliance Jerusalem – Alexandria would last until the beginning of the council of Chalcedon. At that time Juvenal of Jerusalem was striving for the recognition of patriarchal status for the see of the Holy City, decided to go over to the opposite side, formed by Constantinople, Rome and the Antiochenes, thus abandoning the „monophysite party”. Thanks to this dramatic change, the Church of the Holy Land was able to associate itself officially with the dogmatic decision of Chalcedon and the Metropolitan of Jerusalem was elevated to the status of Patriarch.

The paper presents the results of experimental studies of electrochemical machining process oriented on occurring in the treatment critical states caused by electrolyte flow hydrodynamic conditions in the gap between electrodes. Material forming in electrochemical machining is carried out by anodic dissolution. In general in ECM process, the essence of the treatment is that the workpiece is the anode and the tool is the cathode. The space between the anode and cathode is filled by electrolyte. The current flow between the electrodes causes anodic dissolution process, resulting in the removal of material from the anode. Choosing in the process of electrochemical machining, respectively: anode and cathode material, electrolyte and processing parameters, such conditions can be created that enable a high process efficiency and smoothness of the surface. Inappropriate selection of machining parameters can cause the emergence of critical states in the ECM, which are mainly related to the flow of the electrolyte in the gap between electrodes. This work is an attempt to assess the occurring critical states in ECM on the example of machining of curved surfaces with any sort of outline and curved rotating surfaces.

1Pt e scritta „ai pellegrini della diaspora”, ai quali e poi rivolta l’esortazione a comportarsi eon timore nel tempo del loro „pellegrinaggio” e ad astenersi dalie concupiscenze della carne. Alle nozioni scritturistiche va aggiunta osservazione che nella sua prima fase il cristianesimo era costituito da minoranze che vivevano tra loro in una situazione geografica di isolamento.

The Palestinian Church gave the remarkable contribution to patristic Christology. Origen and Eusebius gave the response to the developments of theology and dogma. This particular view of Christology was fostered the special conditions of the Holy Land, as one can see at first in the fourth century with Cyril of Jerusalem, then with Jerome in the fifth. The Holy Land was very favourable to a process of synthesis among different theological traditions and Jerome follows faithfully the footsteps of Origen.

Active co-delivery of tumor antigens (Ag) and α-galactosylceramide (α-GalCer), a potent agonist for invariant Natural Killer T ( i NKT) cells, to cross-priming CD8α + dendritic cells (DCs) was previously shown to promote strong anti-tumor responses in mice. Here, we designed a nanoparticle-based vaccine able to target human CD141 + (BDCA3 + ) DCs - the equivalent of murine CD8α + DCs - and deliver both tumor Ag (Melan A) and α-GalCer. This nanovaccine was inoculated into humanized mice that mimic the human immune system (HIS) and possess functional i NKT cells and CD8 + T cells, called HIS-CD8/NKT mice. We found that multiple immunizations of HIS-CD8/NKT mice with the nanovaccine resulted in the activation and/or expansion of human CD141 + DCs and i NKT cells and ultimately elicited a potent Melan-A-specific CD8 + T cell response, as determined by tetramer staining and ELISpot assay. Single-cell proteomics further detailed the highly polyfunctional CD8 + T cells induced by the nanovaccine and revealed their predictive potential for vaccine potency. This finding demonstrates for the first time the unique ability of human i NKT cells to license cross-priming DCs in vivo and adds a new dimension to the current strategy of cancer vaccine development., (Copyright © 2020 Huang, Zhou, Ghinnagow, Seki, Iketani, Soulard, Paczkowski, Tsuji, MacKay, Cruz, Trottein and Tsuji.)

Highly multiplexed single-cell functional proteomics has emerged as one of the next-generation toolkits for a deeper understanding of functional heterogeneity in cell. Different from the conventional population-based bulk and single-cell RNA-Seq assays, the microchip-based proteomics at the single-cell resolution enables a unique identification of highly polyfunctional cell subsets that co-secrete many proteins from live single cells and most importantly correlate with patient response to a therapy. The 32-plex IsoCode chip technology has defined a polyfunctional strength index (PSI) of pre-infusion anti-CD19 chimeric antigen receptor (CAR)-T products, that is significantly associated with patient response to the CAR-T cell therapy. To complement the clinical relevance of the PSI, a comprehensive visualization toolkit of 3D uniform manifold approximation and projection (UMAP) and t-distributed stochastic neighbor embedding (t-SNE) in a proteomic analysis pipeline is developed, providing more advanced analytical algorithms for more intuitive data visualizations. The UMAP and t-SNE of anti-CD19 CAR-T products reveal distinct cytokine profiles between nonresponders and responders and demonstrate a marked upregulation of antitumor-associated cytokine signatures in CAR-T cells from responding patients. Using this powerful while user-friendly analytical tool, the multi-dimensional single-cell data can be dissected from complex immune responses and uncover underlying mechanisms, which can promote correlative biomarker discovery, improved bioprocessing, and personalized treatment development., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: COVID-19 is caused by the severe acute respiratory syndrome virus SARS-CoV-2. It is widely recognized as a respiratory pathogen, but neurologic complications can be the presenting manifestation in a subset of infected patients., Case Presentation: We describe a 78-year old immunocompromised woman who presented with altered mental status after witnessed seizure-like activity at home. She was found to have SARS-CoV-2 infection and associated neuroinflammation. In this case, we undertake the first detailed analysis of cerebrospinal fluid (CSF) cytokines during COVID-19 infection and find a unique pattern of inflammation in CSF, but no evidence of viral neuroinvasion., Conclusion: Our findings suggest that neurologic symptoms such as encephalopathy and seizures may be the initial presentation of COVID-19. Central nervous system inflammation may associate with neurologic manifestations of disease.

Cancer immunotherapies, in particular adoptive T cell therapy and immune-checkpoint blockade therapy have demonstrated a remarkable success in the treatment of cancer. However, due to heterogeneous functionality and complex immune response of immune cells, it remains challenging to identify predictive biomarkers which have the potential to correlate with efficacy and adverse effects of immunotherapies and help selecting patients who might benefit from the therapy, developing more personalized therapeutics as well as reducing clinical trial cost. The single-cell IsoCode chip in conjunction with fluorescent ELISA-based assay enables a simultaneous detection up to 40+ proteins secreted from live single immune cells, providing a large portion of the assayable functions for each immune cell type, and thus precise assessment of multifunctional, or polyfunctional, heterogeneity of each immune cell type.This unique functional detection capability provides a powerful solution to unmet needs in immunotherapy patient profiling today. Recently, the single-cell metric termed polyfunctional strength index (PSI™) by IsoCode chip computed from preinfusion anti-CD19 chimeric antigen receptor (CAR)-T cell products has demonstrated a significant association with clinical response and cytokine release syndrome (CRS) of cancer patient to the therapy after cell product infusion. This chapter elucidates IsoPlexis single-cell highly multiplexed proteomic platform and provides technical details for characterizing cell products and various cell subsets from peripheral blood, bone marrow, or tumor tissues using this assay.

A 3D modeling system with all-inclusive functionality is too demanding for a casual 3D modeler to learn. There has been a shift towards more approachable systems, with easy-to-learn, intuitive interfaces. However, most modeling systems still employ mouse and keyboard interfaces, despite the ubiquity of tablet devices and the benefits of multi-touch interfaces. We introduce an alternative 3D modeling and fabrication paradigm using developable surfaces, inspired by traditional papercrafting, and we implement it as a complete system designed for a multi-touch tablet, allowing a user to fabricate 3D scenes. We demonstrate the modeling and fabrication process of assembling complex 3D scenes from a collection of simpler models, in turn shaped through operations applied to virtual paper. Our fabrication method facilitates the assembly of the scene with real paper by automatically converting scenes into a series of cutouts with appropriately added fiducial markers and supporting structures. Our system assists users in creating occluded supporting structures to help maintain the spatial and rigid properties of a scene without compromising its aesthetic qualities. We demonstrate several 3D scenes modeled and fabricated in our system, and evaluate the faithfulness of our fabrications relative to their virtual counterparts and 3D-printed fabrications.

After treatment with chimeric antigen receptor (CAR) T cells, interleukin-15 (IL-15) elevation and CAR T-cell expansion are associated with non-Hodgkin lymphoma (NHL) outcomes. However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. A single-cell analysis of the preinfusion CD19 CAR product from patients with NHL demonstrated that CAR products contain polyfunctional T-cell subsets capable of deploying multiple immune programs represented by cytokines and chemokines, including interferon-γ, IL-17A, IL-8, and macrophage inflammatory protein 1α. A prespecified T-cell polyfunctionality strength index (PSI) applied to preinfusion CAR product was significantly associated with clinical response, and PSI combined with CAR T-cell expansion or pretreatment serum IL-15 levels conferred additional significance. Within the total product cell population, associations with clinical outcomes were greater with polyfunctional CD4 + T cells compared with CD8 + cells. Grade ≥3 cytokine release syndrome was associated with polyfunctional T cells, and both grade ≥3 neurologic toxicity and antitumor efficacy were associated with polyfunctional IL-17A-producing T cells. The findings in this exploratory study show that a preinfusion CAR product T-cell subset with a definable polyfunctional profile has a major association with clinical outcomes of CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT00924326., (© 2018 by The American Society of Hematology.)

Background: It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies., Methods: We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods., Results: We demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-γ, MIP-1α, TNF-α), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors., Conclusions: Single-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high dimensional data requires new visualization methods to further define precise polyfunctional response differences in these products. The presented biomarker capture and analysis system provides a more sensitive and comprehensive functional assessment of CAR-T pre-infusion products and may provide insights into the safety and efficacy of CAR-T cell therapy.

On the basis of 20 years' experience, the authors present the immediate and long-term results of operative treatment of Zenker's diverticulum. Comparison of two methods of surgery - diverticulopexia (in 21 patients) and excision (in 16), both associated with upper esophageal sphincter myotomy - shows good immediate and longterm results (from 1 to 19 years), with disappearance of symptoms (dysphagia) in all patients. There was no perioperative mortality. Postoperative complications were most commonly of pulmonary origin and were observed in a third of patients in both groups. In two patients from the group treated with excision, a leak from the suture line occurred, which healed spontaneously. These two patients had transient dysphagia in the postoperative period. On the basis of this analysis, the authors conclude that diverticulopexia is a safer surgical procedure than excision, giving less complications and a very good long-term functional result., (© 1998 International Society for Diseases of the Esophagus/Harcourt Brace & Co. Ltd.)

Malaria is a severe infectious disease with relatively high mortality, thus having been a scourge of humanity. There are a few candidate malaria vaccines that have shown a protective efficacy in humans against malaria. One of the candidate human malaria vaccines, which is based on human malaria sporozoites and called PfSPZ Vaccine, has been shown to protect a significant proportion of vaccine recipients from getting malaria. PfSPZ Vaccine elicits a potent response of hepatic CD8+ T cells that are specific for malaria antigens in non-human primates. To further characterize hepatic CD8+ T cells induced by the sporozoite-based malaria vaccine in a mouse model, we have used a cutting-edge Single-cell Barcode (SCBC) assay, a recently emerged approach/method for investigating the nature of T-cells responses during infection or cancer. Using the SCBC technology, we have identified a population of hepatic CD8+ T cells that are polyfunctional at a single cell level only in a group of vaccinated mice upon malaria challenge. The cytokines/chemokines secreted by these polyfunctional CD8+ T-cell subsets include MIP-1α, RANTES, IFN-γ, and/or IL-17A, which have shown to be associated with protective T-cell responses against certain pathogens. Therefore, a successful induction of such polyfunctional hepatic CD8+ T cells may be a key to the development of effective human malaria vaccine. In addition, the SCBC technology could provide a new level of diagnostic that will allow for a more accurate determination of vaccine efficacy.

TiN and TiO(2) coatings, which are known from their low chemical reactivity, high hardness and wear and corrosion resistance, are used for protecting the NiTi surface. In the present work, nearly equiatomic NiTi (50.6 at.%) shape memory alloy was covered with the layers obtained by nitriding under glow discharge at 1073 K. Additionally, at the end of the process some amount of oxygen was added. Characterization of the nitrided/oxided layers structure was carried out using transmission and scanning electron microscopy. The investigations were focused on the structure of the multilayer nitrided/oxided NiTi surface. The surface is formed from nanocrystalline and columnar grains of the TiN phase. Between the top layer and beta-NiTi substrate the interface Ti(2)Ni layer was formed. Addition of oxygen at the end of the process created a thin layer of TiO(2) phase nanograins at the surface of the TiN phase. In the same areas, small amount of amorphous phase was identified. The combination of nitriding and oxidation formed layers that reveal relatively high corrosion resistance.

The structure of surface layer, obtained on the nearly equiatomic Ni-Ti alloy after nitriding under glow discharge conditions at temperatures 700 or 800 degrees C, was investigated. The structural characterization of the intruded layer was performed on cross-sectional thin foils by the use of the transmission and scanning electron microscopes. The obtained results show that the nitrided layers consist mainly of the nanocrystalline TiN phase and small amount of Ti(2)N. Between the nitrided layers and beta-NiTi matrix an intermediate Ti(2)Ni phase layer was observed.

The authors present their experience in the treatment of chronic lower limb ischaemia resulting from atherosclerosis by below knee amputation according to Ghormley's technique, with the immediate application of a semi-rigid plaster cast and early rehabilitation. From a group of 664 patients requiring major amputations, 61 patients (52 men) aged 64 +/- 11 fulfilled the criteria for unilateral below-knee amputation for critical limb ischaemia for atherosclerosis consequences. Peri-operative (30-days) mortality was of 3.28%. Stump healing was very good or good (no need for further surgery) in over 2/3 of patients, but in 20% the need for above-knee amputation developed. Postoperative knee contracture (defined as 15 degrees or more limitation to the movement range) was observed in 11.5% of patients.

Background. The purpose of this article is to present the problems encountered in treatment and rehabilitation, including prosthesis fitting, in the case of a 17-year-old female patient who underwent a bilateral leg amputation using Syme's method. Case history. The patient incurred crushing injuries of both feet and the knee joints, resulting from a severe multi-organ injury. As a result of post-traumatic changes and deformations of the feet, including algodystrophic changes, amputation proved to be the only procedure that would restore the patient locomotive capacity. Outcome. As a result of the treatment applied, the patient regained the ability to move about, while the primary limitation on her locomotive abilities turned out to be the status of her knee joints, which had been severely damaged in the accident.

Reduced blood cholesterol levels were reported in patients with a variety of malignant peripheral tumors. This fact is likely related to increased cholesterol demand by proliferating tumor cells. The question arises whether this 'tumor-associated hypocholesterolemia' occurs also in patients with brain tumors, and--if it does not--whether its absence can be related to the location of the tumors. We have compared fasting serum total cholesterol levels among three groups of patients: 52 patients with gliomas, 56 patients with symptomatic metastatic brain tumors, and 50 patients harboring malignant tumors of peripheral location but showing no clinical signs of brain metastases. Patients in the last group, despite being--on an average--more age-advanced, had lower total serum cholesterol levels than either the patients with gliomas, or the patients with brain metastases. No difference in the cholesterol levels was found between the two latter groups, and a majority of these patients had borderline or elevated cholesterol levels. This apparent absence of 'tumor-associated hypocholesterolemia' in brain tumor patients may be related to either brain tumors' ability to synthesize cholesterol de novo and their reduced dependence on peripheral cholesterol supply, the existence of brain tumor-blood barrier, effect of medications used to counteract brain edema and seizures, or a combination of these factors.

On the basis of 20 years' experience, the authors present the immediate and long-term results of operative treatment of Zenker's diverticulum. Comparison of two methods of surgery--diverticulopexia (in 21 patients) and excision (in 16), both associated with upper esophageal sphincter myotomy--shows good immediate and long-term results (from 1 to 19 years), with disappearance of symptoms (dysphagia) in all patients. There was no perioperative mortality. Postoperative complications were most commonly of pulmonary origin and were observed in a third of patients in both groups. In two patients from the group treated with excision, a leak from the suture line occurred, which healed spontaneously. These two patients had transient dysphagia in the postoperative period. On the basis of this analysis, the authors conclude that diverticulopexia is a safer surgical procedure than excision, giving less complications and a very good long-term functional result.

From 1976 to 1996, thirty nine patients were surgically treated for pharyngoesophageal diverticulum. The present study aimed to compare two methods of operative treatment of Zenker's diverticulum: excision (group I) and pexy, both of which were associated with upper esophageal sphincter myotomy. The main indication for surgery was dysphagia. The diagnosis of Zenker's diverticulum was based on clinical symptoms and the result of upper GI tract barium examination. In 75% of patients the diameter of diverticulum exceeded 2 cm. No patient died in the perioperative period. The main complications observed in the postoperative period were of pulmonary origin. In group I (excision) a leakage from the suture line occurred in 2 patients (12.5%). Time of follow-up ranged from 1 to 20 years (mean: 7 years). The comparison of both methods of treatment employed is in favour of diverticulopexy, being a safer and less complications-bearing method, although both of them give similar functional results.

The aim of the present study was to analyse the rate of postoperative complications in patients after esophageal resection for cancer, as well as the dependence of its frequency from surgical tactics employed during the operation. Postoperative complications occurring in 38 patients who underwent esophagectomy and intrathoracic esophagogastric anastomosis (treated from 1978 to 1987) were compared with the same data of 74 patients (1988-1996) in whom the operation consisted of the total intrathoracic esophagectomy, cardia, lesser curvature of the stomach and large regional lymph nodes dissection. In these latter cases the esophagogastric anastomosis was performed in the neck. The most frequent postoperative complications in both groups were of cardiopulmonary origin. The anastomotic leak occurred less frequently in patients with cervical esophagogastric anastomosis. However, when occurred, healing was more likely by local drainage and conservative treatment. Anastomotic leaks after intrathoracic esophagogatric anastomoses were usually fatal. In these cases the only chance of patient's survival was an aggressive surgical treatment consisting of disconnection of alimentary tract: esophageal fistula in the neck and feeding jejunostomy.

From 1990 to 1996 two hundred and sixteen patients with abdominal trauma were treated in our Department. In 170 cases there were blunt, and in 46-penetrating injuries (stab and gunshot wounds). Injuries of the other regions of the body coexisted in 117 patients (multiple trauma). In 42 cases (19.4%) abdominal trauma caused injury to the liver. In this group blunt mechanism of trauma also dominated (71%). The victims were usually young men (90% of the group, mean age - 35.3 years). The most common cause of injury were traffic accidents (47.6%), penetrating injury being the second commonest cause (12 patients i.e. 29%). Four patients were treated conservatively, the remaining 38 required surgical intervention. Most frequently liver suture and peritoneal drainage were performed (20), followed by liver tissue resections (16) and liver packing (12). Other surgical procedures to treat coexisting injuries were performed in 24 patients. In 22 patients postoperative complications occurred: liver abscess in 6 cases, hemorrhage in 4, wound infection in 4, biliary fistula in 2, intrahepatic aneurysm in 2 and other complications in 8 patients. The mean time of hospitalisation were of 20 days (range: 0-64 days). Mean volume of blood transfused equaled 6.9 U. There were 16 deaths (38%), in all cases in multiple trauma victims. All patients with penetrating liver trauma survived.

We present the technique and results of endoscopic neodymium-yttrium aluminum garnet laser treatment of benign tracheal stenoses. This therapy was used in 15 patients with tracheal stenoses. Benign tracheal granulomas were caused by prolonged tracheal intubation in eight patients, permanent maintenance of tracheostomy tube in five patients, and nonspecific inflammatory process of the trachea in two patients. The clinical picture was dominated by dyspnea and stridor. The achievement of normal tracheal patency required several laser therapy sessions, repeated at 5- to 7-day intervals. In 30% of patients additional laser vaporization was required as well. The immediate and short-term results were encouraging; in all cases the normal tracheal lumen was restored, resulting in alleviation of patients' symptoms.

The authors present 225 patients with various forms of portal system venous thrombosis (PSVT), of various origin and etiology. The largest group (120 patients) were the young people suffering from portal hypertension due to pre-hepatic venous obstruction of uncertain etiology, lasting since childhood. The next group consisted of 75 patients with liver cirrhosis coexisting with PSVT. In other cases PSVT was diagnosed as coincident with: Budd-Chiari Syndrome (8 cases), liver tumors (9 cases), chronic pancreatitis (3 cases) and polycythaemia (2 cases). In 3 cases PSCT developed postoperatively and in 5 cases after oral contraceptives. Diagnosis of coexisting PSVT deteriorates the prognosis in liver cirrhosis. The overall mortality was 16%. The course of the disease depends on extensiveness and dynamism of thrombosis, but consequently leads to the development of portal hypertension. The most effective diagnostic procedures are: CT and USG with Doppler flowmetry. Bleeding esophageal varices require either sclerotherapy or surgical treatment--decompressive shunts or "non-shunt" procedures. In the cases of recent thrombosis, without bleeding varices, thrombolytic therapy appears to be effective.

The authors present the technique and results of endoscopic Nd:YAG laser treatment of inflammatory tracheal stenoses. This kind of therapy was employed in 10 patients with tracheal stenosis, resulting from long-term nastotracheal intubation (6 cases), tracheostomy tube after radical laryngectomy (3 cases) and tracheal trauma. The laser fiber was introduced into trachea by the operative channel of a flexible bronchoscope and vaporization of obstructing tissues carried out using contact method in continuous mode of light emission (power 7-20 Watts). The achievement of normal tracheal patency usually required several laser therapy sessions (3-5), repeated in 3-5 days intervals. The short-term results are encouraging: in all cases the normal tracheal was lumen was restored, resulting in alleviation of patients' symptoms. In 3 cases a recurrent tracheal stenosis, requiring additional laser treatment was observed.