Miracle-dz/UniFAR-FTUs huggingface dataset:
Mesothelin-Specific CAR T Cells Target Ovarian Cancer

These findings demonstrate that MSLN-directed CAR T cells can provide antitumor immunity against ovarian cancer. New therapeutic options for patients with ovarian cancer are urgently needed. Therefore, we evaluated the efficacy of two second-generation mesothelin (MSLN)-directed CAR T cells in orthotopic mouse models of ovarian cancer. Treatment with CAR T cells expressing an MSLN CAR construct including the CD28 domain (M28z) significantly prolonged survival, but no persistent tumor control was observed. Despite lower response rates, MSLN-4–1BB (MBBz) CAR T cells induced long-term remission in some SKOV3–bearing mice. Tumor-infiltrating M28z and MBBz CAR T cells upregulated PD-1 and LAG3 in an antigen-dependent manner while MSLN+ tumor cells expressed the corresponding ligands (PD-L1 and HLA-DR), demonstrating that coinhibitory pathways impede CAR T-cell persistence in the ovarian tumor microenvironment. Furthermore, profiling plasma soluble factors identified a cluster of M28z- and MBBz-treated mice characterized by elevated T-cell secreted factors that had increased survival, higher CD8+ T-cell tumor infiltration, less exhausted CAR T-cell phenotypes, and increased HLA-DR expression by tumor cells. Altogether, our study demonstrates the therapeutic potential of MSLN-CAR T cells to treat ovarian cancer. Significance: These findings demonstrate that MSLN-directed CAR T cells can provide antitumor immunity against ovarian cancer.
A Raman spectroscopic study of the hydrogenation of aqueous pentacyanocobaltate(II)

Raman spectroscopy has been used to investigate the complexes formed during the hydrogenation of aqueous pentacyanocobaltate(II). The Raman spectra of hydridopentacyanocobaltate(III), the main species present in solution, and of its deuteriated analogue, are reported for the first time. The study also shows that in the presence of excess of CN– the hydrogenation may be accompanied by the formation of some hexacyanocobaltate(III). The reaction between pentacyanocobaltate(II) and borohydride was also studied.
TECSIS: Low-cost methodology to distinguish archaeological findings

The automatic or semi-automatic research of archaeological findings includes several methodologies and algorithms of computer vision. The reconstruction of a scene is one of the key steps to meeting that challenge. This paper addresses a methodology for the reconstruction of underwater scenes with mosaicing techniques. The reconstruction of various scenes will be a video mosaic of sea-bottom landscapes starting from single video frames. The methodology is based on the evaluation of optic flow between frames, and its motion estimation has been evaluated on features extracted from the common areas of pairs of consecutive frames. This approach takes the motion model from a geometric projection framework. The estimation of camera movement is a second key point in the mosaicing problem. The methodology used should be robust enough to produce a good performance because of the high level of noise and turbulence involved in sea-bottom video acquisition. For this purpose, geometrical transformations have been used to map each frame into a unique big common reference frame with dimensions similar to that of the union of frames.
Simultaneous measurement of water retention and electrical conductivity in soils: Testing the Mualem‐Friedman Tortuosity Model

A conceptual model that accounts for the influence of pore geometry is needed to obtain soil water conductivity from bulk soil electrical conductivity measurements in unsaturated soils. Mualem and Friedman [1991] proposed such a model, based on the hypothesis that the tortuosity factor affecting bulk soil electrical conductivity is identical to that defined for prediction of (odel output) of two soils were measured simultaneously over a wide range of soil water conductivity using a multistep outflow (MSO) experiment in combination with time domain reflectometry. The model with only one free parameter can describe the measured data. Predictions indicate a large dependence of the model outcome on the value of the fitting parameter. The fitted tortuosity parameters were used for inverse modeling of the water flow during the MSO experiments, obtaining unique estimates of the hydraulic conductivity.
Swertiamarin supplementation prevents obesity-related chronic inflammation and insulin resistance in mice fed a high-fat diet

ABSTRACT Obesity is characterized by low-grade chronic inflammation, which underlies insulin resistance and non-alcoholic fatty liver disease (NAFLD). Swertiamarin is a secoiridoid glycoside that has been reported to ameliorate diabetes and NAFLD in animal models. However, the effects of swertiamarin on obesity-related inflammation and insulin resistance have not been fully elucidated. Thus, this study investigated the effects of swertiamarin on inflammation and insulin resistance in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed a HFD or HFD containing swertiamarin for 8 weeks. Obesity-induced insulin resistance and inflammation were assessed in the epididymal white adipose tissue (eWAT) and livers of the mice. Swertiamarin attenuated HFD-induced weight gain, glucose intolerance, oxidative stress, and insulin resistance, and enhanced insulin signalling in mice. Compared to HFD-fed mice, the swertiamarin-treated mice exhibited increased lipolysis and reduced adipocyte hypertrophy and macrophage infiltration in eWAT. Moreover, swertiamarin alleviated HFD-mediated hepatic steatosis and inflammation by suppressing activation of the p38 MAPK and NF-κB pathways within the eWAT and liver of obese mice. In conclusion, supplementation with swertiamarin attenuated weight gain and hepatic steatosis, and alleviated obesity-associated inflammation and insulin resistance, in obese mice.
Chronotoxicity of Semen Strychni is associated with circadian metabolism and transport in mice.

OBJECTIVES We aimed to determine the circadian responses of mice to Semen Strychni and to investigate the role of pharmacokinetics in generating chronotoxicity. METHODS Total extract of Semen Strychni was administered by oral gavage to wild-type (WT) and Bmal1-/- (a circadian clock-deficient model) mice at different circadian time points for toxicity (including survival) and pharmacokinetic characterization. Nephrotoxicity and neurotoxicity were evaluated by measuring plasma creatinine and creatine kinase BB (CK-BB), respectively. Drug metabolism and transport assays were performed using liver/intestine microsomes and everted gut sacs, respectively. KEY FINDINGS Semen Strychni nephrotoxicity and neurotoxicity as well as animal survival displayed significant circadian rhythms (the highest level of toxicity was observed at ZT18 and the lowest level at ZT2 to ZT6). According to pharmacokinetic experiments, herb dosing at ZT18 generated higher plasma concentrations (and systemic exposure) of strychnine and brucine (two toxic constituents) compared with ZT6 dosing. This was accompanied by reduced formation of both dihydroxystrychnine and strychnine glucuronide (two strychnine metabolites) at ZT18. Bmal1 ablation sensitized mice to Semen Strychni-induced toxicity (with increased levels of plasma creatinine and CK-BB) and abolished the time dependency of toxicity. Metabolism of Semen Strychni (strychnine and brucine) in the liver and intestine microsomes of WT mice was more extensive at ZT6 than at ZT18. These time differences in hepatic and intestinal metabolism were lost in Bmal1-/- mice. Additionally, the intestinal efflux transport of Semen Strychni (strychnine and brucine) was more extensive at ZT6 than ZT18 in WT mice. However, the time-varying transport difference was abolished in Bmal1-/- mice. CONCLUSIONS Circadian responses of mice to Semen Strychni are associated with time-varying efflux transport and metabolism regulated by the circadian clock (Bmal1). Our findings may have implications for optimizing phytotherapy with Semen Strychni via timed delivery.
Willingness to Receive a COVID-19 Vaccination Among Incarcerated or Detained Persons in Correctional and Detention Facilities — Four States, September–December 2020

Incarcerated and detained persons are at increased risk for acquiring COVID-19. However, little is known about their willingness to receive a COVID-19 vaccination. During September-December 2020, residents in three prisons and 13 jails in four states were surveyed regarding their willingness to receive a COVID-19 vaccination and their reasons for COVID-19 vaccination hesitancy or refusal. Among 5,110 participants, 2,294 (44.9%) said they would receive a COVID-19 vaccination, 498 (9.8%) said they would hesitate to receive it, and 2,318 (45.4%) said they would refuse to receive it. Willingness to receive a COVID-19 vaccination was lowest among Black/African American (Black) (36.7%; 510 of 1,390) persons, participants aged 18-29 years (38.5%; 583 of 1,516), and those who lived in jails versus prisons (43.7%; 1,850 of 4,232). Common reasons reported for COVID-19 vaccine hesitancy were waiting for more information (54.8%) and efficacy or safety concerns (31.0%). The most common reason for COVID-19 vaccination refusal was distrust of health care, correctional, or government personnel or institutions (20.1%). Public health interventions to improve vaccine confidence and trust are needed to increase vaccination acceptance by incarcerated or detained persons.
An alternative splicing variant of PtRD26 delays leaf senescence by regulating multiple NAC transcription factors in Populus

Abstract During leaf senescence, the final stage of leaf development, nutrients are recycled from leaves to other organs, and therefore proper control of senescence is thus critical for plant fitness. Although substantial progress has been achieved in understanding leaf senescence in annual plants, the molecular factors that control leaf senescence in perennial woody plants are largely unknown. Using RNA sequencing, we obtained a high-resolution temporal profile of gene expression during autumn leaf senescence in poplar (Populus tomentosa). Identification of hub transcription factors (TFs) by co-expression network analysis of genes revealed that senescence-associated NAC family TFs (Sen-NAC TFs) regulate autumn leaf senescence. Age-dependent alternative splicing (AS) caused an intron retention (IR) event in the pre-mRNA encoding PtRD26, a NAC-TF. This produced a truncated protein PtRD26IR, which functions as a dominant-negative regulator of senescence by interacting with multiple hub Sen-NAC TFs, thereby repressing their DNA-binding activities. Functional analysis of senescence-associated splicing factors identified two U2 auxiliary factors that are involved in AS of PtRD26IR. Correspondingly, silencing of these factors decreased PtRD26IR transcript abundance and induced early senescence. We propose that an age-dependent increase of IR splice variants derived from Sen-NAC TFs is a regulatory program to fine tune the molecular mechanisms that regulate leaf senescence in trees.
Determination of Total Iron in Environmental Samples by Solid Phase Extraction with Dimethyl(E)‐2‐(2‐Methoxyphenoxy)‐2‐Butenedioate

A novel solid phase extraction technique for determination of total iron in environmental water samples was developed. The method is based on sorption of Fe(III) ions on octadecyl silica membrane disk modified with a new synthetic ligand dimethyl(E)-2-(2-methoxyphenoxy)-2-butenedioate (I). Iron(III) is quantitatively retained on the disk in the pH range of 3-7 at a flow rate of 1-7 mL min -1 . The Fe(III) eluted with 10 mL of 0.01 M EDTA and than was measured by flame atomic absorption spectrometry (FAAS) at 248.3 nm. The maximum capacity disk modified by 7 mg of ligand was found to be 197 ± 2 μg of iron(III). The breakthrough volume was greater than 2000 mL. The iron(III) was completely recovered (> 99%) from water with a preconcentration factor of more than 200. The limit of detection of the proposed method was 1.00 ng mL -1 . The various cationic and anionic interferences had no effect on the recovery of iron(III) from the binary mixtures. The proposed method was successfully applied to determination of total iron from three different water samples.
Signal-mediated localization of Candida albicans pheromone response pathway components

Summary A MAPK cascade consists of three kinases, (MEKK, MEK and MAPK), that are sequentially activated in response to a stimulus and serve to transmit signals. In C. albicans and in yeast, an MAPK cascade is linked to the pheromone pathway through a scaffold protein (Cst5 and Ste5, respectively). Cst5 is much shorter and lacks key domains compared to Ste5, so in C. albicans, other elements, in particular the MEKK Ste11, play key roles in controlling the associations and localizations of network components. Abstract Candida albicans opaque cells release pheromones to stimulate cells of opposite mating type to activate their pheromone response pathway. Although this fungal pathogen shares orthologous proteins involved in the process with Saccharomyces cerevisiae, the pathway in each organism has unique characteristics. We have used GFP-tagged fusion proteins to investigate the localization of the scaffold protein Cst5, as well as the MAP kinases Cek1 and Cek2, during pheromone response in C. albicans. In wild-type cells, pheromone treatment directed Cst5-GFP to surface puncta concentrated at the tips of mating projections. These puncta failed to form in cells defective in either the Gα or β subunits. However, they still formed in response to pheromone in cells missing Ste11, but with the puncta distributed around the cell periphery in the absence of mating projections. These puncta were absent from hst7Δ/Δ cells, but could be detected in the ste11Δ/Δ hst7Δ/Δ double mutant. Cek2-GFP showed a strong nuclear localization late in the response, consistent with a role in adaptation, while Cek1-GFP showed a weaker, but early increase in nuclear localization after pheromone treatment. Activation loop phosphorylation of both Cek1 and Cek2 required the presence of Ste11. In contrast to Cek2-GFP, which showed no localization signal in ste11Δ/Δ cells, Cek1-GFP showed enhanced nuclear localization that was pheromone independent in the ste11Δ/Δ mutant. The results are consistent with CaSte11 facilitating Hst7-mediated MAP kinase phosphorylation and also playing a potentially critical role in both MAP kinase and Cst5 scaffold localization.
“It's that longitudinal relationship that pays off”: A qualitative study of internal medicine residents’ perspectives on learning to prescribe buprenorphine

Background The opioid use disorder (OUD) epidemic is a national public health crisis. Access to effective treatment with buprenorphine is limited, in part because few physicians are trained to prescribe it. Little is known about how post-graduate trainees learn to prescribe buprenorphine or how to optimally train them to prescribe. We therefore aimed to explore the experiences and attitudes of residents learning to prescribe buprenorphine within two primary care-based opioid treatment models. Methods We performed semi-structured interviews with second- and third-year internal medicine residents at an urban academic residency program. Participating residents practiced in clinics providing buprenorphine care using either a nurse care manager model or a provider-centric model. Subjects were sampled purposively to ensure that a diversity of perspectives were included. Interviews were conducted until theoretical saturation was reached and were analyzed using principles of thematic analysis. The research team developed a consensus code list. Each transcript was then independently coded by two researchers. The team then summarized each code and generated a set of themes that captured the main ideas emerging from the data. Results We completed 14 interviews. Participants reported learning to prescribe buprenorphine through didactics, longitudinal outpatient prescribing, mentorship, and inpatient experiences. We characterized their attitudes toward patients with OUD, medication treatment of OUD, their own role in buprenorphine care, and future prescribing. Participants practicing in both clinical models viewed learning to prescribe buprenorphine as a normal part of their training and demonstrated positive attitudes toward buprenorphine prescribing. Conclusions Longitudinal outpatient experiences with buprenorphine prescribing can prepare residents to prescribe buprenorphine and stimulate interest in prescribing after residency. Both nurse care manager and provider-centric clinical models can provide meaningful experiences for medical residents. Educators should attend to the volume of patients and inductions managed by each trainee, patient-provider continuity, and supporting trainees in the clinical encounter.
Analysis of Ebastine in Pharmaceutical Preparations by High-Performance Thin-Layer Chromatography

A new simple, precise, rapid, and selective high-performance thin-layer chromatography (HPTLC) method has been developed for the analysis of finasteride in pharmaceutical formulations. The method uses loratadine as an internal standard. The stationary phase was silica gel 60F 254 prewashed with methanol; chloroform-ethyl acetate, 6 + 4 (v/v) was used as mobile phase. Detection and quantification were performed densitometrically at λ = 228 nm. The linear range of the analysis was 0.2-2.0 pg and the percentage recovery was 101.8%.
Mesenchymal stem cells and three‐dimensional‐osteoconductive scaffold regenerate calvarial bone in critical size defects in swine

Craniofacial bones protect vital organs, perform important physiological functions, and shape facial identity. Critical‐size defects (CSDs) in calvarial bones, which will not heal spontaneously, are caused by trauma, congenital defects, or tumor resections. They pose a great challenge for patients and physicians, and significantly compromise quality of life. Currently, calvarial CSDs are treated either by allogenic or autologous grafts, metal or other synthetic plates that are associated with considerable complications. While previous studies have explored tissue regeneration for calvarial defects, most have been done in small animal models with limited translational value. Here we define a swine calvarial CSD model and show a novel approach to regenerate high‐quality bone in these defects by combining mesenchymal stem cells (MSCs) with a three‐dimensional (3D)‐printed osteoconductive HA/TCP scaffold. Specifically, we have compared the performance of dental pulp neural crest MSCs (DPNCCs) to bone marrow aspirate (BMA) combined with a 3D‐printed HA/TCP scaffold to regenerate bone in a calvarial CSD (>7.0 cm2). Both DPNCCs and BMA loaded onto the 3D‐printed osteoconductive scaffold support the regeneration of calvarial bone with density, compression strength, and trabecular structures similar to native bone. Our study demonstrates a novel application of an original scaffold design combined with DPNCCs or BMA to support regeneration of high‐quality bone in a newly defined and clinically relevant swine calvarial CSD model. This discovery may have important impact on bone regeneration beyond the craniofacial region and will ultimately benefit patients who suffer from debilitating CSDs.
Development of a computed tomography perfusion protocol to support large animal resuscitation research

BACKGROUND Adequate cerebral perfusion is crucial for a positive neurological outcome in trauma; however, it is difficult to characterize in the acute setting with noninvasive methods. Intra-arterial computed tomography perfusion may offer a solution. The aim of this study was to develop an intra-arterial computed tomography perfusion protocol for resuscitation research. METHODS The study examined intra-arterial contrast administration for computed tomography perfusion (CTP) acquisition. It consisted of three phases: intra-arterial contrast dose finding, evaluation of reproducibility, and evaluation during hypotension. Blood pressure and laser Doppler flow data were collected. In phase 1, animals underwent CTPs using several intra-arterial contrast injection protocols. In phase 2, animals underwent two CTPs 7 hours apart using the 2.5 mL/s for 3-second protocol. In phase 3, animals underwent CTPs at several pressures following a computer-controlled bleed including euvolemia and at systolic pressures of 60, 40, and 20 mm Hg. Phase 1 CTPs were evaluated for contrast-to-noise ratio. In phase 2, CTPs were compared within each animal and with laser Doppler flow using linear regression. Phase 3 CTPs were graphed against systolic pressure and fitted with a nonlinear fit. RESULTS The protocol using 2.5mL/s for 3 seconds was optimal, demonstrating a contrast-to-noise ratio of 40.1 and a superior arterial input function curve compared with the 1 mL/s bolus. Cerebral blood flow demonstrated high concordance between baseline and end of study CTPs (R2 = 0.82, p < 0.001). Cerebral blood flow also compared moderately well against laser Doppler flow during 8 (R2 = 0.53, p = 0.03); however, laser Doppler flow did not perform well during hypovolemia, and the favorable concordance was not maintained (R2 = 0.45, p = 0.06). Cerebral blood flow was graphed against systolic blood pressure and fitted with a nonlinear fit (R2 = 0.95, p = 0.003). CONCLUSION Computed tomography perfusion using intra-arterial contrast injection may offer a novel alternative to traditional CTP protocols that could prove a useful additional tool in the setting of resuscitation research.
Concerted morphogenesis of genital ridges and nephric ducts in the mouse captured through whole embryo imaging.

During development of the mouse urogenital complex, the gonads undergo changes in three-dimensional structure, body position, and spatial relationship with the mesonephric ducts, kidneys, and adrenals. The complexity of genital ridge development obscures potential connections between morphogenesis and gonadal sex determination. To characterize the morphogenic processes implicated in regulating gonad shape and fate, we used whole embryo tissue clearing and light sheet microscopy to assemble a time course of gonad development in native form and context. Analysis revealed that gonad morphology is determined through anterior-to-posterior patterns as well as increased rates of growth, rotation, and separation in the central domain that may contribute to regionalization of the gonad. We report a close alignment of gonad and mesonephric duct movements and delayed duct development in a gonad dysgenesis mutant, which together support a mechanical dependency linking gonad and mesonephric duct morphogenesis.
Partial DnaK protein expression from Coxiella-like endosymbiont of Rhipicephalus annulatus tick

Q fever is one of the most important zoonotic diseases caused by the obligate intracellular bacteria, Coxiella burnetii. This bacterial infection has been frequently reported in both humans and animals, especially ruminants. Ticks are important ectoparasite and serve as reservoir hosts of Coxiella-like endosymbionts (CLEs). In this study, we have attempted to express chaperone-coding genes from CLEs of Rhipicephalus annulatus ticks collected fromcow path. The partial DnaK coding sequence has been amplified and expressed by Escherichia coli. Amino acid sequences have been analyzed by MS-MS spectrometry and the UniProt database. Despites nucleotide sequences indicating high nucleotide variation and diversity, many nucleotide substitutions are synonymous. In addition, amino acid substitutions compensate for the physicochemical properties of the original amino acids. Immune Epitope Database and Analysis Resource (IEDB-AR) was employed to indicate the antigenicity of the partial DnaK protein and predict the epitopes of B-and T-cells. Interestingly, some predicted HLA-A and B alleles of the MHC-I and HLA-DR alleles belonging to MHC-II were similar to T-cell responses to C. burnetii in Q fever patients. Therefore, the partial DnaK protein of CLE from R. annulatus could be considered a vaccine candidate and immunogenic marker with future prospects.