Miracle-dz/UniFAR-FTUs huggingface dataset:
Preclinical Evidence of Nanomedicine Formulation to Target Mycobacterium tuberculosis at Its Bone Marrow Niche

One-third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis (Mtb). Recently, we found that dormant Mtb hides in bone marrow mesenchymal stem cells (BM-MSCs) post-chemotherapy in mice model and in clinical subjects. It is known that residual Mtb post-chemotherapy may be responsible for increased relapse rates. However, strategies for Mtb clearance post-chemotherapy are lacking. In this study, we engineered and formulated novel bone-homing PEGylated liposome nanoparticles (BTL-NPs) which actively targeted the bone microenvironment leading to Mtb clearance. Targeting of BM-resident Mtb was carried out through bone-homing liposomes tagged with alendronate (Ald). BTL characterization using TEM and DLS showed that the size of bone-homing isoniazid (INH) and rifampicin (RIF) BTLs were 100 ± 16.3 nm and 84 ± 18.4 nm, respectively, with the encapsulation efficiency of 69.5% ± 4.2% and 70.6% ± 4.7%. Further characterization of BTLs, displayed by sustained in vitro release patterns, increased in vivo tissue uptake and enhanced internalization of BTLs in RAW cells and CD271+BM-MSCs. The efficacy of isoniazid (INH)- and rifampicin (RIF)-loaded BTLs were shown using a mice model where the relapse rate of the tuberculosis was decreased significantly in targeted versus non-targeted groups. Our findings suggest that BTLs may play an important role in developing a clinical strategy for the clearance of dormant Mtb post-chemotherapy in BM cells.
Social Support and Antibody Responses to Vaccination: A Meta-Analysis.

BACKGROUND Social support and social integration have been linked to lower rates of morbidity and mortality. However, the biological mechanisms responsible for such links need greater attention. Vaccine paradigms provide an integrative window into immune system involvement in the protective influence of social support/integration. PURPOSE The main aim of this article was to conduct a meta-analytic review of the association between social support/social integration and antibody responses to vaccines. Exploratory analyses also examined effect sizes and confidence intervals as a function of several factors to inform future research. METHOD A literature search was conducted using the ancestry approach and with PsycInfo, Medline, and the Psychology and Behavioral Science Collection by crossing the exact keywords of social support or social integration with vaccine or antibodies. The review identified nine studies with a total of 672 participants. RESULTS The omnibus meta-analysis showed that social support/social integration was related to higher antibody levels following vaccination, but the average effect size was small and the lower bound of the confidence interval included zero (Zr = 0.06 [-.04, .15]). These results did not appear to differ much as a function of the operationalization of social relationships, participant age, or follow-up period, although effect sizes appeared larger for studies using a primary antigen. CONCLUSIONS These data provide some evidence that social support may be linked to antibody responses to vaccines. However, effect sizes are mostly small and zero overall effect cannot be ruled out. Future studies would benefit from larger sample sizes and greater consideration of methodological issues associated with secondary immune responses to antigen.
High level expression of recombinant chicken interferon-α using baculovirus

Bioactive recombinant chicken interferon-alpha (ChIFN-alpha) was expressed in a baculovirus system. For easy purification, it was expressed as ChIFN-alpha bearing histidine hexamer (His-tag) at C-terminal, designated ChIFN-alphaHis. The expressed proteins were detected by SDS-PAGE analysis with Coomassie brilliant blue staining as around 23 and 19 kDa bands thought to be immature and matured ChIFN-alphaHis respectively. The purified ChIFN-alphaHis with a nickel chelated column showed anti-viral activity in vitro.
Phase-Specific Predictors of Countermovement Jump Performance That Distinguish Good From Poor Jumpers

Abstract Krzyszkowski, J, Chowning, LD, and Harry, JR. Phase-specific predictors of countermovement jump performance that distinguish good from poor jumpers. J Strength Cond Res 36(5): 1257–1263, 2022—The modified-reactive strength index (RSImod) is commonly examined during the countermovement vertical jump (CMJ) to assess neuromuscular characteristics (i.e., explosiveness, fatigue, adaptation, etc.) of an athlete. However, both phase-specific variables explaining RSImod and corresponding differences between good and poor jumpers are not well understood in trained populations. This study sought to (a) identify predictors of RSImod during the CMJ based on phase-specific temporal and rate of force development (RFD) variables, and (b) identify differences in those predictors between performers with high and low RSImod performances from a sample of collegiate male basketball players (n = 22; 20 ± 2 years; 1.99 ± 0.06 month; 93.8 ± 7.5 kg). Subjects performed 3 maximal effort CMJ trials while ground reaction force data was recorded using 2 force platforms. Phase-specific temporal and RFD variables were calculated and entered into separate stepwise regression models using backward elimination to identify predictors RSImod. Individuals were then categorized into high (n = 11; RSImod = 0.68 ± 0.10) and low (n = 11; RSImod = 0.48 ± 0.04) RSImod groups according to the overall median RSImod (RSImod = 0.55). Independent t-tests (α = 0.05) were conducted and supplemented by Cohen's d effect sizes (d ≥ 1.2, large) to compare groups relative to significant predictors identified by the linear regression models and related variables. The temporal regression model (R2 = 0.530) retained unloading time and concentric time, whereas the RFD regression model (R2 = 0.429) retained unloading RFD and braking RFD. The high RSImod group exhibited significantly greater RSImod scores (d = 2.51, p < 0.001) and jump heights (d = 1.58, p < 0.001), shorter times to takeoff (d = 1.27, p = 0.007) and concentric times (d = 1.51, p = 0.002), and a greater braking RFD (d = 1.41, p = 0.005) than the low RSImod group. Individuals targeting enhanced CMJ performance may consider exploring strategies or interventions to develop quicker unloading and concentric phases and increasing eccentric RFD abilities.
Immunochemical methods for mycotoxin analysis: from radioimmunoassay to biosensors

Immunochemical methods have been used in diagnosis of diseases both for humans and animals for many years. However, wide application of these methods for analytical purpose was not initiated until the nineteen fifties when Yalow developed a radioimmunoassy for insulin1). In addition to the specific antibody, the modern immunochemical methods use a sensitive marker for the analyte and a good method to separate the bound and free analyte in the specific antigen (Ag) and antibody (Ab) interaction. The assay systems became a new highly sensitive, specific and simplified versatile tool for the analysis of many biologically active substances, including low molecular contaminants such as mycotoxin. In the last four decades, new approaches to make sensitive markers have been made. For example, by conjugating the enzymes to the Ag or Ab to amplify the signal, more sensitive and versatile enzyme-immunoassay systems have been developed. With the availability of sensitive instruments, more fluorescence-tagged markers are now being used. Simplified and effective methods for the separation of free and bound species are now available. In addition to using animals for Ab production, monoclonal Ab technology was introduced. Such developments have led to a wide application of immunoassays for the analysis of contaminants in foods and agricultural products. Recent development of novel separation techniques and sensitive detection systems have led to the development of several immunochemical based biosensors. Thus, a new dimension of immunoassay system is now emerged. Whereas many types of immunoassays are now available for mycotoxins, most approaches are based on the competition of binding between unlabeled toxin in the sample and labeled toxin in the assay system for the specific binding sites of Ab molecules. Because of limited space, this review will focus only on important developments and applications of immunoassays for mycotoxins. For details, the readers should consult the original papers and recent reviews both on the overall analytical methods2-9) and immunoassays for mycotoxins10-18).
Neuroendocrine Cancer of the Breast: A Rare Entity

Neuroendocrine breast cancer (NEBC) is a rare histotype of breast carcinoma that presents, in most cases, positive hormone receptors and negative HER2. Indeed, the analysis of gene expression profiles revealed that NEBC belongs mainly to the luminal subtype. Cases of HER2-positive and triple-negative NEBC are rare. The cardinal treatment of early NEBC is surgery, similar to the treatment of invasive non-special histological type carcinoma. The use of radiotherapy follows the criteria applied in infiltrating breast cancer of non-special histotype. In the post-operative phase, therefore after the surgical treatment of mammary quadrantectomy, or mastectomy associated with homolateral sentinel lymph node removal ± axillary dissection, based on the histopathological characteristics of the tumor, the use of chemotherapy (anthracycline + taxane) and/or hormone therapy, whether or not associated with anti-HER2 therapy (trastuzumab) is the rule. Literature data report the use of cisplatin and etoposide, as in small cell lung cancers. Most of the information currently available derive from single case reports or a series of clinical cases; it follows the difficulty of formulating definite recommendations on the correct management of this histological type of breast cancer. This review describes available knowledge on this rare entity to improve the diagnostic and therapeutic strategies and offer insights to stimulate exploration of the many aspects still unknown.
Evolutionary history, biogeography and eco‐climatological differentiation of the genus Anthemis L. (Compositae, Anthemideae) in the circum‐Mediterranean area

Aim To reconstruct the temporal, geographical and eco‐climatological differentiation of the genus Anthemis (Compositae, Anthemideae) in the circum‐Mediterranean region, in order to evaluate the relative importance of geographical vs. climatological differentiation processes in influencing the actual distribution patterns in this plant group.
Evaluation of the MBT STAR-Carba Assay for the Detection of Carbapenemase Production in Enterobacteriaceae and Hafniaceae with a Large Collection of Routine Isolates from Plate Cultures and Patient-Derived Positive Blood Cultures.

The spread of carbapenemase-producing Enterobacterales is a major public health concern worldwide, and methods for their prompt and reliable detection are highly demanded for therapeutic and hygiene control purposes. In this study, we evaluate the MBT STAR®-Carba assay (Bruker Daltonik) to detect the carbapenemase production in clinical and surveillance isolates from plate cultures and directly from patient-derived positive blood cultures bottles. Overall, n = 1,307 samples were analyzed (n = 900 plate cultures, and n = 407 positive blood cultures, using the bacterial pellet obtained with the Sepsityper® Kit; Bruker Daltonik), including n = 793 carbapenemase producers (n = 579 klebsiella pneumoniae carbapenemase, n = 161 metallo-beta-lactamases, n = 45 OXA-48, and eight isolates harboring two different enzymes), n = 239 carbapenem-resistant noncarbapenemase producers, and n = 275 carbapenem-susceptible strains. The STAR-Carba assay detected 657/661 (99.4%) carbapenemase producers from plate cultures, and 132/132 (100%) from positive blood cultures. Specificity resulted in 100% for carbapenem-susceptible strains, and 91.6% for carbapenem-resistant strains resulted negative for carbapenamase production with the routine methods used in this study. In this study, the MBT STAR-Carba assay proved to be a highly reliable method for the detection of carbapenemase-producing Enterobacterales, regardless of the enzyme family, and from both plate cultures and positive blood culture bottles.
Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing

Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1–9 from L. shawii and 10–20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D (1H and 13C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds 1–3, 7, and 12, which depicted IC50 values in the range of 35–60 μM, while 8, 6, and 9 also demonstrated IC50 values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC50 = 14.4 µM), 12 (IC50 = 23.3), and 2 (IC50 = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 μM) activity followed by 14 (241 μM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs.
The β-arrestin-biased β-adrenergic receptor blocker carvedilol enhances skeletal muscle contractility

Significance We recently demonstrated that the effects of the β2AR agonist clenbuterol to enhance skeletal muscle strength and hypertrophy are mediated via β-arrestin1-dependent signaling. The present study reports the unique ability of carvedilol, previously identified as a β-arrestin-biased agonist at the β2AR, to enhance skeletal muscle contractility. This observation was unique among βAR antagonists tested as metoprolol and nadolol failed to stimulate skeletal muscle contractility. Our findings provide insight into the mechanism of carvedilol’s effect on skeletal muscle contractility and demonstrate the unconventional potential utility of a commonly used pharmacologic agent for a previously unappreciated clinical use. We hypothesize that the observed β-arrestin-dependent signaling pathway could be targeted in various clinical conditions associated with decreased functional exercise capacity. A decrease in skeletal muscle strength and functional exercise capacity due to aging, frailty, and muscle wasting poses major unmet clinical needs. These conditions are associated with numerous adverse clinical outcomes including falls, fractures, and increased hospitalization. Clenbuterol, a β2-adrenergic receptor (β2AR) agonist enhances skeletal muscle strength and hypertrophy; however, its clinical utility is limited by side effects such as cardiac arrhythmias mediated by G protein signaling. We recently reported that clenbuterol-induced increases in contractility and skeletal muscle hypertrophy were lost in β-arrestin 1 knockout mice, implying that arrestins, multifunctional adapter and signaling proteins, play a vital role in mediating the skeletal muscle effects of β2AR agonists. Carvedilol, classically defined as a βAR antagonist, is widely used for the treatment of chronic systolic heart failure and hypertension, and has been demonstrated to function as a β-arrestin-biased ligand for the β2AR, stimulating β-arrestin-dependent but not G protein-dependent signaling. In this study, we investigated whether treatment with carvedilol could enhance skeletal muscle strength via β-arrestin-dependent pathways. In a murine model, we demonstrate chronic treatment with carvedilol, but not other β-blockers, indeed enhances contractile force in skeletal muscle and this is mediated by β-arrestin 1. Interestingly, carvedilol enhanced skeletal muscle contractility despite a lack of effect on skeletal muscle hypertrophy. Our findings suggest a potential unique clinical role of carvedilol to stimulate skeletal muscle contractility while avoiding the adverse effects with βAR agonists. This distinctive signaling profile could present an innovative approach to treating sarcopenia, frailty, and secondary muscle wasting.
P38 MAPK Promotes Migration and Metastatic Activity of BRAF Mutant Melanoma Cells by Inducing Degradation of PMCA4b

Metastatic melanoma is the most aggressive type of skin cancer. Previously, we identified the plasma membrane Ca2+ pump isoform 4b (PMCA4b or ATP2B4) as a putative metastasis suppressor in BRAF mutant melanoma cells. Metastasis suppressors are often downregulated in cancer, therefore, it is important to identify the pathways involved in their degradation. Here, we studied the role of p38 MAPK in PMCA4b degradation and its effect on melanoma metastasis. We found that activation of p38 MAPK induces internalization and subsequent degradation of PMCA4b through the endo/lysosomal system that contributes to the low PMCA4b steady-state protein level of BRAF mutant melanoma cells. Moreover, BRAF wild type cell models including a doxycycline-inducible HEK cell system revealed that p38 MAPK is a universal modulator of PMCA4b endocytosis. Inhibition of the p38 MAPK pathway markedly reduced migration, colony formation and metastatic activity of BRAF mutant cells in vitro partially through an increase in PMCA4b and a decrease in β4 integrin abundance. In conclusion, our data suggest that the p38 MAPK pathway plays a key role in PMCA4b degradation and inhibition of this pathway—by increasing the stability of PMCA4b—may provide a potential therapeutic target for inhibition of melanoma progression and metastasis.
Ultrastructure and reconstruction of the flagellar apparatus in Chrysochromulina apheles sp. nov. (Prymnesiophyceae = Haptophyceae)

A new marine species of Chrysochromulina, C. apheles, is described from light and electron microscopy of a culture established from Danish coastal waters. The cells are among the smallest known in any species of Chrysochromulina, measuring ca. 4 μm in diameter. The general fine structure is illustrated and the structure of the haptonema and the flagellar apparatus is described in detail, based on serial sections. The flagellar root system, not previously examined in detail in any member of Chrysochromulina, is shown to consist of four microtubular roots, while cross-banded roots are lacking. Four cross-banded fibres were seen to interconnect the flagellar bases and the haptonema base. The haptonema belongs to the rather unusual six-stranded type. Two very similar looking types of small organic scales are present on the cell body. Unpublished data on the flagellar roots of the type species of Chrysochromulina, C. parva, are included. Chrysochromulina apheles is apparently cosmopolitan. It has presently bee.
Validation of an Automated Early Treatment Diabetic Retinopathy Study Low-contrast Letter Acuity Test.

SIGNIFICANCE Automated low-contrast letter acuity (LCLA) has several advantages: consistent luminance, reduced chance of individuals memorizing test letters, and convenient and accurate visual acuity reporting functions. Although automated LCLA might report slightly worse acuity than Sloan LCLA chart, considering its advantages, it may be a viable alternative to Sloan LCLA chart in clinical practice and research. PURPOSE The purpose of this study was to determine the repeatability of an automated LCLA measurement and its agreement with the Sloan LCLA chart test in normal participants and reduced-vision participants. METHODS Adult participants (n = 49) were measured with both automated Early Treatment Diabetic Retinopathy Study and Sloan LCLA tests, including normal and reduced-vision groups. Low-contrast letter acuity at two contrast levels (2.5 and 10%) was measured at 3 m in a random sequence with both LCLA tests. To test repeatability, participants were retested 1 week later. Repeatability of the two tests between two visits and agreement between automated and Sloan LCLA tests were evaluated using 95% limits of agreement. RESULTS In terms of the 95% limits of agreement, the repeatability of both tests was as follows: automated LCLA at 2.5%, ±0.26; automated LCLA at 10%, ±0.22; Sloan LCLA at 2.5%, ±0.23, and Sloan LCLA at 10%, ±0.16. The agreement of the two tests was as follows: ±0.19 at 2.5% and ±0.24 at 10%. The automated LCLA at 2.5 and 10% levels was generally reported one-half to one logMAR line lower than Sloan LCLA (mean differences, -0.04 at 2.5% and -0.13 at 10%; paired t test, P < .05). CONCLUSIONS The automated LCLA test shows fairly good test-retest repeatability at both 2.5 and 10% contrast levels. The agreement between the automated and the Sloan low-contrast letter acuity tests was comparable with test-retest agreement. Although the automated LCLA test reports slightly worse acuity than the Sloan LCLA test, it could be an appropriate alternative to the Sloan LCLA test.
Potential of the Volatile-Producing Fungus Nodulisporium sp. CF016 for the Control of Postharvest Diseases of Apple

In vitro and in vivo mycofumigation effects of the volatileproducing fungus Nodulisporium sp. CF016 isolated from stem of Cinnamomum loureirii and the role of its volatile compounds were investigated against phytopathogenic fungi. The volatile compounds produced by Nodulisporium sp. CF016 inhibited and killed a wide range of plant and storage pathogens including to Pythium ultimum, Rhizoctonia solani, Fusarium oxysporum, Phytophthora capsici, Sclerotinia sclerotiorum, Colletotrichum coccodes, Magnaporthe oryzae, Alternaria panax, Botrytis cinerea and Penicillium expansum. Mycofumigation with wheat bran-rice hull cultures of Nodulisporium sp. CF016 showed in vivo antifungal activity against gray mold caused by B. cinerea and blue mold caused by P. expansum of apple. The most abundant volatile compound produced by Nodulisporium sp. CF016 was β-elemene followed by 1-methyl-1,4-cyclohexadiene, β-selinene and α-selinene. Nodulisporium sp. CF016 could be an attractive mycofumigant in controlling postharvest diseases of various fruits including apple.