Psychological Aspects of Motocross Racing Considering Expected, Perceived, and Actual Performance.

Motocross racing is a seldom-researched popular extreme sport. This field research aimed to investigate feeling states, perceived arousal, anxiety, and negative and positive affect in the anticipatory and recovery race periods and their relationship to expected and perceived performance. Twenty Motocross racers completed psychometric scales before and after a national championship race. Results revealed that objective performance was unrelated to psychological measures. Arousal, anxiety, and positive affect were lower after the race. Expected performance was unrelated to postrace measures. Still, perceived performance correlated significantly with the feeling state, anxiety, and positive affect after the race and the feeling state before the race. Furthermore, racers who performed as expected or better showed improved feeling states after the race compared with those who did worse than expected. The core affect of the latter group declined. This research on psychological states during Motocross races could motivate new initiatives for future studies.

Single thin-plate compression of multi-TW laser pulses to 3.9 fs.

Post-compression of 12-fs laser pulses with multi-TW peak power from an optical parametric chirped pulse amplification (OPCPA) system was performed by using a single thin fused silica plate in a vacuum. By optimizing the input pulses in both spatial and temporal domains, after compression with customized chirped mirrors, we achieved pulses as short as 3.87 fs, in combination with 12-mJ energy. The spatio-spectral quality of the post-compressed pulses was thoroughly analyzed. The generated 1.4-cycle pulses pave the way for next generation attosecond and particle acceleration experiments.

HUNCHEST-II contributes to a shift to earlier-stage lung cancer detection: final results of a nationwide screening program.

OBJECTIVES: The introduction of low-dose CT (LDCT) altered the landscape of lung cancer (LC) screening and contributed to the reduction of mortality rates worldwide. Here we report the final results of HUNCHEST-II, the largest population-based LDCT screening program in Hungary, including the screening and diagnostic outcomes, and the characteristics of the LC cases. METHODS: A total of 4215 high-risk individuals aged between 50 and 75 years with a smoking history of at least 25 pack-years were assigned to undergo LDCT screening. Screening outcomes were determined based on the volume, growth, and volume doubling time of pulmonary nodules or masses. The clinical stage distribution of screen-detected cancers was compared with two independent practice-based databases consisting of unscreened LC patients. RESULTS: The percentage of negative and indeterminate tests at baseline were 74.2% and 21.7%, respectively, whereas the prevalence of positive LDCT results was 4.1%. Overall, 76 LC patients were diagnosed throughout the screening rounds (1.8% of total participants), out of which 62 (1.5%) patients were already identified in the first screening round. The overall positive predictive value of a positive test was 58%. Most screen-detected malignancies were stage I LCs (60.7%), and only 16.4% of all cases could be classified as stage IV disease. The percentage of early-stage malignancies was significantly higher among HUNCHEST-II screen-detected individuals than among the LC patients in the National Koranyi Institute of Pulmonology's archive or the Hungarian Cancer Registry (p < 0.001). CONCLUSIONS: HUNCHEST-II demonstrates that LDCT screening for LC facilitates early diagnosis, thus arguing in favor of introducing systematic LC screening in Hungary. CLINICAL RELEVANCE STATEMENT: HUNCHEST-II is the so-far largest population-based low-dose CT screening program in Hungary. A positive test's overall positive predictive value was 58%, and most screen-detected malignancies were early-stage lesions. These results pave the way for expansive systematic screening in the region. KEY POINTS: • Conducted in 18 medical facilities, HUNCHEST-II is the so far largest population-based low-dose CT screening program in Hungary. • The vast majority of screen-detected malignancies were early-stage lung cancers, and the overall positive predictive value of a positive test was 58%. • HUNCHEST-II facilitates early diagnosis, thus arguing in favor of introducing systematic lung cancer screening in Hungary.

How Does a Novel In Situ Fixed-bearing Implant Design Perform in Revision Ankle Arthroplasty in the Short Term? A Survival, Clinical, and Radiologic Analysis.

BACKGROUND: Given the growing number of primary total ankle replacements (TAR), an increase in the number of patients undergoing subsequent revisions might be expected. Achieving a stable and balanced ankle while preserving the remaining bone stock as much as possible is crucial for success in revision TAR. Most reported techniques rely on bulky implants with extended fixation features. Since 2018, we have used a novel, three-component ankle prosthesis for revision that is converted in situ to a fixed-bearing, two-component ankle prosthesis once the components have found their position according to an individual's anatomy. The results of this novel concept (fixation, revision, pain, or function) have not, to our knowledge, been reported. QUESTIONS/PURPOSES: What are the short-term results with this new revision TAR design, in terms of (1) repeat revision surgery, (2) patient-reported outcomes on the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, (3) pain according to the VAS, and (4) radiographic signs of fixation? METHODS: Between February 2018 and February 2020, we performed 230 TAR surgeries (in 206 patients) for any indication in our clinic. The novel semiconstrained, uncemented Hintermann Series H2 © implant was used in 96% (220 of 230) of procedures (201 patients). Fifty-four percent (119 of 220) of these were converted from an existing TAR to H2, which was the focus of the present study. However, only 45% (54 of 119) of these conversions to H2 were eligible for analysis. These patients had a mean age of 63 ± 12 years, and 43% (23 of 54) were women. The median (range) follow-up time was 3.2 years (2.0 to 4.3). The H2 design allows in situ conversion to a fixed-bearing system, with minimal bone resection. It achieves translational and rotational stability while preserving function and supporting the periarticular soft tissues. We defined repeat revision as exchange of one or both metal components, ankle fusion, or amputation and assessed it using a cumulative incidence survivorship estimator. Factors potentially associated with revision were assessed using Cox regression analyses. Clinical and radiologic outcomes were assessed preoperatively and at the most recent follow-up interval. Clinical outcomes included pain on the VAS (average pain during normal daily activity during the past seven days) and AOFAS score. Radiologic outcomes were the tibial articular surface angle, tibiotalar surface angle, talar tilt angle in the coronal plane, and AP offset ratio in the sagittal plane, as well as radiolucent lines and radiographic signs of loosening, defined as change in position greater than 2° of the flat base of the tibia component in relation to the long axis of the tibia, subsidence of the talar component into the talus greater than 5 mm, or change in position greater than 5° relative to a line drawn from the top of the talonavicular joint to the tuberosity of the calcaneus, as seen on plain weightbearing radiographs. RESULTS: The cumulative incidence of repeat revision after 1 and 2 years was 5.6% (95% CI 0% to 11%) and 7.4% (95% CI 0% to 14%), respectively. With the numbers available, no clinical factors we analyzed were associated with the risk of repeat revision. The median values of all assessed clinical outcomes improved; however, not all patients improved by clinically important margins. The median (range) AOFAS ankle-hindfoot score increased (from 50 [16 to 94] to 78 [19 to 100], difference of medians 28; p < 0.01), and the median pain on the VAS decreased (from 5 [0 to 9] to 2 [0 to 9], difference of medians 3; p < 0.01) from before surgery to follow-up at a minimum of 2 years. Radiographically, lucency was seen in 12% (6 of 49 patients) and loosening was seen in 8% (4 of 49). One of these patients showed symptomatic loosening and was among the four patients overall who underwent revision. We could not assess risk factors for repeat revision because of the low number of events (four). CONCLUSION: The investigated new in situ fixed-bearing ankle design achieved overall better short-term results than those reported in previous research. Destabilization of the ankle joint complex, soft tissue insufficiency, and possible changes of the joint configuration need an optimal solution in revision arthroplasty. The studied implant might be the answer to this complex issue and help surgeons in the perioperative decision-making process. However, a relatively high percentage of patients did not achieve a clinically important difference. Observational studies are needed to understand long-term implant behavior and possibly to identify ankles benefiting the most from revision. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Temporal Speech Parameters Indicate Early Cognitive Decline in Elderly Patients With Type 2 Diabetes Mellitus.

INTRODUCTION: The earliest signs of cognitive decline include deficits in temporal (time-based) speech characteristics. Type 2 diabetes mellitus (T2DM) patients are more prone to mild cognitive impairment (MCI). The aim of this study was to compare the temporal speech characteristics of elderly (above 50 y) T2DM patients with age-matched nondiabetic subjects. MATERIALS AND METHODS: A total of 160 individuals were screened, 100 of whom were eligible (T2DM: n=51; nondiabetic: n=49). Participants were classified either as having healthy cognition (HC) or showing signs of MCI. Speech recordings were collected through a phone call. Based on automatic speech recognition, 15 temporal parameters were calculated. RESULTS: The HC with T2DM group showed significantly shorter utterance length, higher duration rate of silent pause and total pause, and higher average duration of silent pause and total pause compared with the HC without T2DM group. Regarding the MCI participants, parameters were similar between the T2DM and the nondiabetic subgroups. CONCLUSIONS: Temporal speech characteristics of T2DM patients showed early signs of altered cognitive functioning, whereas neuropsychological tests did not detect deterioration. This method is useful for identifying the T2DM patients most at risk for manifest MCI, and could serve as a remote cognitive screening tool.

Malignant pleural effusions for cancer genotyping: A matter of trans-pleural traffic of cell-free tumor DNA.

Body cavity fluids accumulating in progressive malignancies are potential subjects of regular clinical testing for cancer-related features. Besides the cellular component, the supernatant of the fluid proved to gain diagnostic impact as the cell-free DNA (cfDNA) fraction ideally reflects general molecular features of the related tumorous process, e.g. in lung carcinoma. Thus, malignant pleural effusions can be used for lung cancer genetic profiling and this might remain the only source for testing in critical cases. The cfDNA concentration of the pleural effusion depends on many factors in both benign and malignant conditions. Further to direct pleural metastatic spread, the redirection of tissue lymphatic circulation, tumor angiogenesis, inflammatory processes and other variables may contribute to or enhance the enrichment of the effusion tumor DNA from the earliest stages of carcinogenesis. Our review addresses the traffic of cfDNA in the pleural space and the diagnostic utility of effusion cfDNA from the perspective of the complex pleural pathophysiology.

Optimizing the Ultrasound Tongue Image Representation for Residual Network-Based Articulatory-to-Acoustic Mapping.

Within speech processing, articulatory-to-acoustic mapping (AAM) methods can apply ultrasound tongue imaging (UTI) as an input. (Micro)convex transducers are mostly used, which provide a wedge-shape visual image. However, this process is optimized for the visual inspection of the human eye, and the signal is often post-processed by the equipment. With newer ultrasound equipment, now it is possible to gain access to the raw scanline data (i.e., ultrasound echo return) without any internal post-processing. In this study, we compared the raw scanline representation with the wedge-shaped processed UTI as the input for the residual network applied for AAM, and we also investigated the optimal size of the input image. We found no significant differences between the performance attained using the raw data and the wedge-shaped image extrapolated from it. We found the optimal pixel size to be 64 × 43 in the case of the raw scanline input, and 64 × 64 when transformed to a wedge. Therefore, it is not necessary to use the full original 64 × 842 pixels raw scanline, but a smaller image is enough. This allows for the building of smaller networks, and will be beneficial for the development of session and speaker-independent methods for practical applications. AAM systems have the target application of a "silent speech interface", which could be helpful for the communication of the speaking-impaired, in military applications, or in extremely noisy conditions.

Telltale silence: temporal speech parameters discriminate between prodromal dementia and mild Alzheimer's disease.

This study presents a novel approach for the early detection of mild cognitive impairment (MCI) and mild Alzheimer's disease (mAD) in the elderly. Participants were 25 elderly controls (C), 25 clinically diagnosed MCI and 25 mAD patients, included after a clinical diagnosis validated by CT or MRI and cognitive tests. Our linguistic protocol involved three connected speech tasks that stimulate different memory systems, which were recorded, then analyzed linguistically by using the PRAAT software. The temporal speech-related parameters successfully differentiate MCI from mAD and C, such as speech rate, number and length of pauses, the rate of pause and signal. Parameters pauses/duration and silent pauses/duration linearly decreased among the groups, in other words, the percentage of pauses in the total duration of speech continuously grows as dementia progresses. Thus, the proposed approach may be an effective tool for screening MCI and mAD.

[1,5]-Hydride Shift-Cyclization versus C(sp2)-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4- and 1,5-Benzoxazepines.

Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp2)-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp3)-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp2)-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 µM IC50 value.

Tremorgenic and neurotoxic paspaline-derived indole-diterpenes: biosynthetic diversity, threats and applications.

Indole-diterpenes (IDTs) such as the aflatrems, janthitrems, lolitrems, paspalitrems, penitrems, shearinines, sulpinines, and terpendoles are biogenetically related but structurally varied tremorgenic and neurotoxic mycotoxins produced by fungi. All these metabolites derive from the biosynthetic intermediate paspaline, a frequently occurring IDT on its own right. In this comprehensive review, we highlight the similarities and differences of the IDT biosynthetic pathways that lead to the generation of the main paspaline-derived IDT subgroups. We survey the taxonomic distribution and the regulation of IDT production in various fungi and compare the organization of the known IDT biosynthetic gene clusters. A detailed assessment of the highly diverse biological activities of these mycotoxins leads us to emphasize the significant losses that paspaline-derived IDTs cause in agriculture, and compels us to warn about the various hazards they represent towards human and livestock health. Conversely, we also describe the potential utility of these versatile molecules as lead compounds for pharmaceutical drug discovery, and examine the prospects for their industrial scale manufacture in genetically manipulated IDT producers or domesticated host microorganisms in synthetic biological production systems.

Quantum-Limited Directional Amplifiers with Optomechanics.

Directional amplifiers are an important resource in quantum-information processing, as they protect sensitive quantum systems from excess noise. Here, we propose an implementation of phase-preserving and phase-sensitive directional amplifiers for microwave signals in an electromechanical setup comprising two microwave cavities and two mechanical resonators. We show that both can reach their respective quantum limits on added noise. In the reverse direction, they emit thermal noise stemming from the mechanical resonators; we discuss how this noise can be suppressed, a crucial aspect for technological applications. The isolation bandwidth in both is of the order of the mechanical linewidth divided by the amplitude gain. We derive the bandwidth and gain-bandwidth product for both and find that the phase-sensitive amplifier has an unlimited gain-bandwidth product. Our study represents an important step toward flexible, on-chip integrated nonreciprocal amplifiers of microwave signals.

Inactivation of the indole-diterpene biosynthetic gene cluster of Claviceps paspali by Agrobacterium-mediated gene replacement.

The hypocrealean fungus Claviceps paspali is a parasite of wild grasses. This fungus is widely utilized in the pharmaceutical industry for the manufacture of ergot alkaloids, but also produces tremorgenic and neurotoxic indole-diterpene (IDT) secondary metabolites such as paspalitrems A and B. IDTs cause significant losses in agriculture and represent health hazards that threaten food security. Conversely, IDTs may also be utilized as lead compounds for pharmaceutical drug discovery. Current protoplast-mediated transformation protocols of C. paspali are inadequate as they suffer from inefficiencies in protoplast regeneration, a low frequency of DNA integration, and a low mitotic stability of the nascent transformants. We adapted and optimized Agrobacterium tumefaciens-mediated transformation (ATMT) for C. paspali and validated this method with the straightforward creation of a mutant strain of this fungus featuring a targeted replacement of key genes in the putative IDT biosynthetic gene cluster. Complete abrogation of IDT production in isolates of the mutant strain proved the predicted involvement of the target genes in the biosynthesis of IDTs. The mutant isolates continued to produce ergot alkaloids undisturbed, indicating that equivalent mutants generated in industrial ergot producers may have a better safety profile as they are devoid of IDT-type mycotoxins. Meanwhile, ATMT optimized for Claviceps spp. may open the door for the facile genetic engineering of these industrially and ecologically important organisms.

HPLC-ECD and TDDFT-ECD study of hexahydropyrrolo[1,2-a]quinoline derivatives.

Synthesis of racemic hexahydropyrrolo[1,2-a]quinoline derivatives (1-8) was performed by utilizing the Knoevenagel-[1,5]-hydride shift-cyclization domino reaction. Separation of the enantiomers of the chiral products (1-8) was carried out by chiral high-performance liquid chromatography, and online high-performance liquid chromatography-electronic circular dichroism (ECD) spectra were recorded to elucidate the absolute configuration by comparing the experimental and time-dependent density functional theory-ECD spectra obtained at various theoretical levels. For 1 of the products, the time-dependent density functional theory-ECD calculations allowed determining both the relative and the absolute configuration by distinguishing the 4 stereoisomers. One of the compounds with spiro 1,3-cyclohexanedione moiety (7) possessed moderate acetylcholinesterase inhibitory activity, while 3 showed neuroprotective activity in oxygen-glucose deprivation-induced neurotoxicity in human neuroblastoma SH-SY5Y cells.

Postmortem immunohistochemical alterations following cerebral lesions: A possible pathohistological importance of the ß-dystroglycan immunoreactivity.

The frequency of cerebrovascular injuries raises the importance of their immunohistological investigation in postmortem materials. Most injuries involve the impairment of the blood-brain barrier. The barrier is maintained by the glio-vascular connections which break up following injuries. Some immunohistochemical alterations may refer to the impairment of the gliovascular connections. Laminin and the components of the dystroglycan complex show characteristic immunohistochemical alterations following various experimental injuries (stab wound, cryogenic lesion, arterial occlusions): immunoreactivity of ß-dystroglycan, α-dystrobrevin and aquaporin 4 disappeared while that of utrophin and laminin appeared along the vessels, whereas α-syntrophin visualized the reactive astrocytes but not the resting ones. The aims of the present study were to investigate whether these post-lesion alterations: (i) are reproducible with immersive fixation, which is used in postmortem histology; (ii) are resistant to a postmortem delay before fixation; and (iii) are to be attributed to a direct effect of the lesion, or are mediated by processes occurring only in the living brain. Three models were investigated: (i) following lesions, some brains were fixed by transcardial perfusion, others by immersion; (ii) following lesions, the animals were decapitated and stored at room temperature for 8 or 16 h before fixation; and (iii) the lesions were performed after decapitation. Cryogenic lesions were performed by applying a dry ice cooled copper rod to the brain surface of ketamine-xylazine anesthetized rats. The immunohistochemical reactions were performed on free-floating sections cut with vibratome. Both immunoperoxidase and immunofluorescence methods were used. The fixation method - perfusive or immersive - did not change the post-lesion phenomena investigated. The postmortem delay did not influence the ß-dystroglycan immunoreactivity, that is its lack delineated the area of the lesion. However, in the case of the other substances, various lengths of postmortem delay rendered the immunohistochemistry uninterpretable. The results suggest ß-dystroglycan immunostaining could be applied in the neuropathology to detect cerebrovascular impairments.

[Systemic mastocytosis with progressive disease course]. / Progresszív kórlefolyást mutató szisztémás mastocytosis.

Authors report on a case of a male patient of systemic mastocytosis that was associated with extensive cutaneous lesions. Chronic diarrhoea worsening his quality of life was well managed by the administration of antihistamines. The pleural fluid recurrence soon after drainage has been controlled by the administration of alpha interferon. 40 years after the onset of the first skin signs progression has been manifested in the development of "B" (bone marrow infiltration rate >30%, dysmyelopoiesis, serum tryptase >20 µg/L, hepato- and splenomegaly) and "C" symptoms (liver function test abnormalities, cytopenia, malabsorption, osteoporosis). The patient died at age of 87. The authors' aim was to attract attention on this rare disease and emphasize that symptomatic therapy with antihistamines and drugs available based on customised rights by the National Health Insurance Fund might provide good quality of life. Orv Hetil. 2018; 159(5): 192-196.

Challenging tumour immunological techniques that help to track cancer stem cells in malignant melanomas and other solid tumours.

AIM OF THE STUDY: The arsenal of questions and answers about the minor cancer initiating cancer stem cell (CSC) population put responsible for cancer invasiveness and metastases, has left with an unsolved puzzle. Specific aims of a complex project were partly focused on revealing new biomarkers of cancer. We designed and set up novel techniques to facilitate the detection of cancerous cells. MATERIALS AND METHODS: As a novel approach, we investigated B cells infiltrating breast carcinomas and melanomas (TIL-B) in terms of their tumour antigen binding potential. By developing the TIL-B phage display technology we provide here a new technology for the specific detection of highly tumour-associated antigens. Single chain Fv (scFv) antibody fragment phage ELISA, immunofluorescence (IF) FACS analysis, chamber slide technique with IF confocal laser microscopy and immunohistochemistry (IHC) in paraffin-embedded tissue sections were set up and standardized. RESULTS: We showed strong tumour-associated disialylated glycosphingolipid expression levels on various cancer cells using scFv antibody fragments, generated previously by uniquely invasive breast carcinoma TIL-B phage display library technology. CONCLUSIONS: We report herein a novel strategy to obtain antibody fragments of human origin that recognise tumour-associated ganglioside antigens. Our investigations have the power to detect privileged molecules in cancer progression, invasiveness, and metastases. The technical achievements of this study are being harnessed for early diagnostics and effective cancer therapeutics.

Morphometric characteristics and COI haplotype diversity of Arctodiaptomus spinosus (Copedoda) populations in soda pans in Hungary.

Arctodiaptomus spinosus (Daday, 1891) is a characteristic species of the soda pan zooplankton in the Great Hungarian Plain. The biogeographical distribution of the species is interesting, since its range expands from the Pannonian Biogeographic region to the other side of the Carpathians, occurring in saline lakes in Eastern Anatolia, Armenia, Iran and in temporary waters in Ukraine. Our investigations focused on the morphometric characteristics and the COI haplotype diversity of four Hungarian populations in the Kiskunság area. We detected substantial morphological differences between the Böddi-szék population and the rest of the sampling sites, however considerable differences were not observable in the COI haplotypes in the populations. The 20 animals investigated for COI haplotypes belonged to the same haplotype network. Tajima's D indicated departures from the neutral Wright - Fisher population model and suggested population expansion. The genetic composition of Arctodiaptomus spinosus populations in the Kiskunság area is rather uniform.

[Significance of the monitoring and screening for hereditary nonpolyposis colorectal carcinoma syndrome patients by presenting a case of a family tree]. / A hereditaer nonpolyposus colorectalis carcinoma szindrómás betegek szurésének és szoros utánkövetésének fontossága egy családfa bemutatása kapcsán.

INTRODUCTION: Hereditary nonpolyposis colorectal carcinoma (HNPCC) is an autosomal dominant disease, which shows familial clustering. AIM: We would like to emphasize the importance of monitoring the HNPCC syndrome patients by presenting a case of a proven MMR gene mutation carrier and her family tree encompassing 10 years. MATERIALS AND METHOD: To screen a suspected HNPCC Hungarian family member we are taking thorough family histories. If the diagnosis of HNPCC was further supported by immunohistology and the microsatellite status, sequencing of the MMR genes was carried out. RESULTS: A novel mutation in exon 6 of the hMSH2 gene leading to the deletion of two nucleotide pairs [c.969-970delTC] was detected in our patient. During the 10-year follow-up period of our patient new HNPCC-associated tumors have developed in several family members. Conslusion: Close surveillance of the patient and its family members at risk was effective, although it requires compliance from the subjects. Orv Hetil. 2017; 158(30): 1182-1187.

[Genetic information from tumor-infiltrating B lymphocytes as a driver tool ("GPS") for anti-tumor T cell CARs]. / A tumorban felhalmozódó B-limfociták genetikai információja, mint az immun T-sejt vezette tumorellenes "autó" (CAR, kiméra antigénreceptor) célba irányító "GPS"-e.

The rapidly growing field of gene therapy techniques to modify T cells with chimeric antigen receptors (CARs) for cancer care solutions, reached considerable achievements. However, there is an urgent need of reliable, well tolerable tumor-associated antigen specific antibodies. Tumor-infiltrating B (TIL-B) cell originated single chain Fv (scFv) gene regions could be selected with tumor specificity. DNA sequences of these antibody variable regions were subjects to get engineered into new CAR constructs. Our novel strategy harnesses tumor-infiltrating B cells' unique capacity to reveal highly tumor-associated disialylated glycosphingolipids (GD3 gangliosides). We used these human antibody fragments for generating GD3 ganglioside specific CAR gene constructs for potential usage in solid tumors.

Tetrahydroxanthene-1,3(2H)-dione derivatives from Uvaria valderramensis.

Two tetrahydroxanthene-1,3(2H)-dione metabolites, valderramenols A (1) and B (2), were isolated from the Philippine endemic Annonaceous species Uvaria valderramensis. Planar structures of the rac-xanthene-1,3-(2H)-diones 1 and 2 were established by MS and NMR measurements. Their enantiomers were separated by chiral HPLC, and the absolute configurations of the separated enantiomers were determined by comparison of the HPLC-ECD spectra with computed TDDFT-generated spectra. A TDDFT-ECD study of the known grandiuvarone (3) allowed the revision of its absolute configuration as S. Compound 1 showed antitubercular activity (MIC 10 µg/mL), while 3 and 4 had weaker activities (MIC 32 µg/mL). Oxepinone 3 exhibited cytotoxic activity against KB-562, a chronic myeloid leukemia cell line.