Miracle-dz/UniFAR-FTUs huggingface dataset:
Preliminary Evaluation of the Safety and Probiotic Potential of Akkermansia muciniphila DSM 22959 in Comparison with Lactobacillus rhamnosus GG

In this study, for the first time, we examined some of the physico-chemical properties of the cell surface of Akkermansia muciniphila DSM 22959, comparing it with those of Lactobacillus rhamnosus GG—one of the most extensively studied probiotic microorganisms. In particular, hydrophobicity, auto-aggregation, co-aggregation, and biofilm formation were investigated. In addition, antibiotic susceptibility, co-culture, and antimicrobial activity of the two strains were compared. Hydrophobicity was evaluated using xylene and toluene, showing that A. muciniphila DSM 22959 possessed moderate hydrophobicity. A. muciniphila showed a faster and higher auto-aggregation ability than Lb. rhamnosus GG, but a lower aptitude in biofilm formation. In the co-aggregation test, the best performance was obtained by Lb. rhamnosus GG. Regarding the susceptibility to antibiotics, the differences between the two strains were remarkable, with A. muciniphila DSM 22959 showing resistance to half of the antibiotic tested. Interesting results were also obtained with regard to the stimulating effect of Lb. rhamnosus GG on the growth of A. muciniphila when co-cultured.
Newly diagnosed HIV positive children: a unique index case to improve HIV diagnosis and linkage to care of parents

ABSTRACT Newly diagnosed HIV positive children may be unique index cases to identify undiagnosed parents. Data was used from the Pediatric Urgent Start of HAART (NCT02063880) trial, which enrolled hospitalized, ART-naïve, HIV positive children ages 0–12 years in Kenya. Exact McNemar’s tests were used to compare proportions of mothers and fathers tested for HIV, linked to care, and on ART at baseline and 6 months. This analysis included 87 newly diagnosed children with HIV who completed 6 months of follow-up. Among 83 children with living mothers, there were improvements in maternal linkage to care and treatment comparing baseline to 6 months (36% vs. 78%; p < 0.0001 and 22% vs. 52%; p < 0.0001). Among 80 children with living fathers, there were increases from baseline to 6 months in the number of fathers who knew the child’s HIV status (34% vs. 78%; p < 0.0001), fathers ever tested for HIV (43% vs. 65%; p < 0.0001), fathers ever tested HIV positive (21% vs. 43%; p < 0.0001), fathers ever linked to care (15% vs. 35%; p < 0.0001), and fathers ever initiated on ART (11% vs. 23%; p = 0.0039). Newly diagnosed HIV positive children can be important index cases to identify parents with undiagnosed HIV or poor engagement in care.
A Daily Study Comparing Alcohol-Related Positive and Negative Consequences for Days With Only Alcohol Use Versus Days With Simultaneous Alcohol and Marijuana Use in a Community Sample of Young Adults.

BACKGROUND Alcohol and marijuana are psychoactive substances commonly used by young adults and are independently associated with numerous acute and long-term consequences. Many young adults engage in simultaneous alcohol and marijuana (SAM) use to cross-fade (i.e., to enhance the effects of intoxication), although the extent to which alcohol use and alcohol-related consequences increase on SAM occasions compared to alcohol-only occasions is unclear. This study examines daily data among a sample of SAM users comparing SAM days to other days when young adults only used alcohol. METHODS A sample of 409 young adults (age 18 to 25; Mage = 21.6, SD = 2.2; 50.9% women) who reported SAM use in the past month completed 2 bursts of 14 days of daily surveys (28 days in total) assessing alcohol use, alcohol-related consequences, and SAM use. RESULTS Multilevel models based on alcohol-only and SAM days (n = 3,016 days; 391 individuals) indicated young adults drank more alcohol on SAM days compared to alcohol-only days (with no marijuana use). Similarly, days with SAM use were associated with more alcohol-related positive and negative consequences. The daily association between SAM use and positive consequences was statistically significant, after accounting for the amount of alcohol consumed; in contrast, the association between SAM use and negative consequences was diminished and nonsignificant. CONCLUSIONS Among young adult SAM users, days with SAM use were associated with more alcohol use and positive consequences compared to days they only drank alcohol. Further examination of the motivational context for engaging in SAM use, as well as potential physiological interactions between alcohol and marijuana use on alcohol's effects, is warranted. Alcohol interventions might benefit from addressing increased alcohol use and alcohol-related consequences as risks associated with SAM use.
The chromatin bound proteome of the human malaria parasite

Proteins interacting with DNA are fundamental for mediating processes such as gene expression, DNA replication and maintenance of genome integrity. Accumulating evidence suggests that the chromatin of apicomplexan parasites, such as Plasmodium falciparum, is highly organized, and this structure provides an epigenetic mechanism for transcriptional regulation. To investigate how parasite chromatin structure is being regulated, we undertook comparative genomics analysis using 12 distinct eukaryotic genomes. We identified conserved and parasite-specific chromatin-associated domains (CADs) and proteins (CAPs). We then used the chromatin enrichment for proteomics (ChEP) approach to experimentally capture CAPs in P. falciparum. A topological scoring analysis of the proteomics dataset revealed stage-specific enrichments of CADs and CAPs. Finally, we characterized, two candidate CAPs: a conserved homologue of the structural maintenance of chromosome 3 protein and a homologue of the crowded-like nuclei protein, a plant-like protein functionally analogous to animal nuclear lamina proteins. Collectively, our results provide a comprehensive overview of CAPs in apicomplexans, and contribute to our understanding of the complex molecular components regulating chromatin structure and genome architecture in these deadly parasites.
On the aggregation of published prognostic scores for causal inference in observational studies

As real world evidence on drug efficacy involves nonrandomized studies, statistical methods adjusting for confounding are needed. In this context, prognostic score (PGS) analysis has recently been proposed as a method for causal inference. It aims to restore balance across the different treatment groups by identifying subjects with a similar prognosis for a given reference exposure (“control”). This requires the development of a multivariable prognostic model in the control arm of the study sample, which is then extrapolated to the different treatment arms. Unfortunately, large cohorts for developing prognostic models are not always available. Prognostic models are therefore subject to a dilemma between overfitting and parsimony; the latter being prone to a violation of the assumption of no unmeasured confounders when important covariates are ignored. Although it is possible to limit overfitting by using penalization strategies, an alternative approach is to adopt evidence synthesis. Aggregating previously published prognostic models may improve the generalizability of PGS, while taking account of a large set of covariates—even when limited individual participant data are available. In this article, we extend a method for prediction model aggregation to PGS analysis in nonrandomized studies. We conduct extensive simulations to assess the validity of model aggregation, compared with other methods of PGS analysis for estimating marginal treatment effects. We show that aggregating existing PGS into a “meta‐score” is robust to misspecification, even when elementary scores wrongfully omit confounders or focus on different outcomes. We illustrate our methods in a setting of treatments for asthma.
New phenolic acids from the whole herb of Elephantopus scaber Linn. and their anti-inflammatory activity

Abstract Two new phenolic acids, ethyl 3,3′,4,4′-tetrahydroxy-δ-truxinate (1), 3-O-p-coumaroyl-4-O-caffeoyl quinic acid methyl ester (2), together with three known compounds (3–5) were isolated from the whole plant of Elephantopus scaber Linn. The structures of the new compounds were elucidated using detailed spectroscopic analysis. Compound 3 was obtained and given its NMR data for the first time. All isolates were evaluated for their anti-inflammatory activity via inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells, and 1, 4 and 5 showed a moderate inhibition with IC50 values ranging from 11.85 to 20.62 μM. Graphical Abstract
Postburn leukoderma successfully treated with topical daylight psoralen UVA therapy

Postburn leukoderma is challenging to treat with different surgical and nonsurgical treatments resulting in variable outcomes. We report a case of a 56‐year‐old female with postburn leukoderma treated successfully with topical daylight psoralen UVA therapy for 6 months. The treatment was well tolerated and showed excellent improvement. In conclusion, we report the successful use of topical daylight PUVA for postburn leukoderma with almost complete repigmentation. This is a simple, convenient, and cheap nonsurgical treatment option.
Promise of Autologous CD34+ Stem/Progenitor Cell Therapy for Treatment of Cardiovascular Disease.

CD34+ cells are hematopoietic stem cells used therapeutically in patients undergoing radiation or chemotherapy due to their regenerative potential and ability to restore the hematopoietic system. In animal models, CD34+ cells have been associated with therapeutic angiogenesis in response to ischemia. Several trials have shown the potential safety and efficacy of CD34+ cell delivery in various cardiovascular diseases. Moreover, Phase III trials have now begun to explore the potential role of CD34+ cells in treatment of both myocardial and peripheral ischemia. CD34+ cells have been shown to be safe and well-tolerated in the acute myocardial infarction, heart failure, and angina models. Several studies have suggested potential benefit of CD34+ cell therapy in patients with coronary microvascular disease as well. In this review we will discuss the therapeutic potential of CD34+ cells, and describe the pertinent trials that have used autologous CD34+ cells in no-options refractory angina, acute myocardial infarction, and heart failure. Lastly, we will review the potential utility of autologous CD34+ cells in coronary endothelial and microvascular dysfunction.
A CLINICAL AUDIT OF HYSTERECTOMY IN BOWEN UNIVERSITY TEACHING HOSPITAL, OGBOMOSO, SOUTH WEST NIGERIA

Context: Hysterectomy is a major gynaecological surgical procedure which involves the removal of the uterus, occasionally structures in the adnexae are removed alongside depending on the need to do so. Hysterectomy can be approached Abdominally, vaginally or even with laparoscopic assistance. Objective: This study was embarked on to ascertain the prevalence, indication, pattern and outcome of hysterectomy over a four (4) year period. Study design, Settings and Subjects: This study is a four (4) year retrospective review of all cases of st hysterectomy either for gynaecological or obstetric reasons managed at BUTH from 1 January 2011 through 31st December 2014. Result: During the period under review a total of 127 hysterectomies were done for gynaecological and obstetrical indications, However, only 103 case records were available. Gynaecological indication was the reason for hysterectomy in 95 (92.2%) , while the remaining 8 (7.8%) had hysterectomy for Obstetrical indications. The mean age of patients in our study was 49.2±12.6 years; there was an age distribution of 18-90 years. The mean age of patients who had abdominal hysterectomy was 45.3±7.4 years, while the mean age for patients who had vaginal hysterectomy was 68.7±5.3 years. Abdominal hysterectomy accounted for 90( 87.4%) , while vaginal hysterectomy accounted for the remaining 13(12.6%) ; there was no case of laparoscopically assisted vaginal hysterectomy done. There were three(3) deaths following emergency hysterectomy performed on account of primary postpartum haemorrhage. Conclusion: Hysterectomy remains a major gynaecological procedure. Necessary steps are needed to ensure that gynaecologist acquire skills for hysterectomy especially vaginal hysterectomy and even laparoscopic assisted hysterectomy.
Let-7 microRNA is a critical regulator in controlling the growth and function of silk gland in the silkworm

ABSTRACT The silk gland is characterized by high protein synthesis. However, the molecular mechanisms controlling silk gland growth and silk protein synthesis remain undetermined. Here we demonstrated that CRISPR/Cas9-based knockdown of let-7 or the whole cluster promoted endoreduplication and enlargement of the silk gland, accompanied by changing silk yield, whereas transgenic overexpression of let-7 led to atrophy and degeneration of the silk gland. Mechanistically, let-7 controls cell growth in the silk gland through coordinating nutrient metabolism processes and energy signalling pathways. Transgenic overexpression of pyruvate carboxylase, a novel target of let-7, resulted in enlargement of the silk glands, which is consistent with the abnormal phenotype of the let-7 knockdown. Overall, our data reveal a previously unknown miRNA-mediated regulation of silk gland growth and physiology and shed light on involvement of let-7 as a critical stabilizer and booster in carbohydrate metabolism, which may have important implications for understanding of the molecular mechanism and physiological function of specialized organs in other species.
Translational studies within the TAMRAD randomized GINECO trial: evidence for mTORC1 activation marker as a predictive factor for everolimus efficacy in advanced breast cancer.

BACKGROUND Everolimus is an agent frequently associated with specific toxicities. Predictive markers of efficacy are needed to help define which patients could benefit from it. The goal of this exploratory study was to identify potential predictive biomarkers in the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) activation pathway using primary tumor samples collected during the phase II tamoxifen plus everolimus (TAMRAD) trial. PATIENTS AND METHODS Tumor tissues were collected retrospectively from the TAMRAD trial. Immunohistochemistry was carried out using specific antibodies directed toward proteins that result in mTORC1 activation [canonical phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mTOR or alternative pathways]. DNA was extracted from the tumor tissue; mutation screening in the PIK3CA gene (exons 9 and 20) and the KRAS gene (exons 2 and 3) was first carried out using Sanger direct sequencing, and then completed by next-generation sequencing for PIK3CA. An exploratory analysis of everolimus efficacy in terms of a time-to-progression (TTP) increase was carried out in each biomarker subgroup (high versus low expression referring to the median percentage of marked cells). RESULTS A total of 55 primary tumor samples from the TAMRAD trial-25 from the tamoxifen-alone group and 30 from the tamoxifen/everolimus group-were evaluated for biomarkers. The subgroups most likely to have an improvement in TTP with tamoxifen/everolimus therapy, compared with tamoxifen alone, were patients with high p4EBP1, low 4EBP1, low liver kinase B1, low pAkt, and low PI3K. Among the 45 samples screened for mutation status, nine samples (20%; 95% CI 9.6-34.6) had a PIK3CA mutation. KRAS mutation was observed in one patient. CONCLUSIONS A positive correlation between late effectors of mTORC1 activation, a positive correlation between Akt-independent mTORC1 activation, and an inverse correlation between canonical PI3K/Akt/mTOR pathway and everolimus efficacy were observed in this exploratory analysis. However, these correlations need to be validated in larger studies before applying the findings to routine clinical practice.
Fingerprint Voltammograms of Copper Single Crystals under Alkaline Conditions: A Fundamental Mechanistic Analysis.

A critical step towards the systematic development of electrocatalysts is the determination of the microscopic structure and processes at the electrified solid/electrolyte interface. The major challenges towards this end for experiment and computations are, respectively, achieving sufficient cleanliness and modelling the complexity of electrochemical systems. In this sense, benchmarks of well-defined model systems are sparse. This work presents a rigorous joint experimental-theoretical study on the single crystal (SC) Cu/aqueous interface. Within typical computational uncertainties, we find quantitative agreement between simulated and experimentally measured voltammograms, which allows to unequivocally identify the *OH adsorption feature in the fingerprint region of Cu (110), (100) and (111) SCs under alkaline conditions. We find the inclusion of hydrogen evolution reaction kinetics in the theoretical model to be crucial for an accurate steady-state description which gives rise to a negligible H* coverage. A purely thermodynamic description of the H* coverage through a Pourbaix analysis would incorrectly lead to a H* adsorption peak. The presented results establish a fundamental benchmark for all electrochemical applications of Cu.
Proportional Downscaling of Glutamatergic Release Sites by the General Anesthetic Propofol at Drosophila Motor Nerve Terminals

Visual Abstract Propofol is the most common general anesthetic used for surgery in humans, yet its complete mechanism of action remains elusive. In addition to potentiating inhibitory synapses in the brain, propofol also impairs excitatory neurotransmission. We use electrophysiological recordings from individual glutamatergic boutons in male and female larval Drosophila melanogaster motor nerve terminals to characterize this effect. We recorded from two bouton types, which have distinct presynaptic physiology and different average numbers of release sites or active zones. We show that a clinically relevant dose of propofol (3 μm) impairs neurotransmitter release similarly at both bouton types by decreasing the number of active release sites by half, without affecting release probability. In contrast, an analog of propofol has no effect on glutamate release. Coexpressing a truncated syntaxin1A protein in presynaptic boutons completely blocked this effect of propofol. Overexpressing wild-type syntaxin1A in boutons also conferred a level of resistance by increasing the number of active release sites to a physiological ceiling set by the number of active zones or T-bars, and in this way counteracting the effect of propofol. These results point to the presynaptic release machinery as a target for the general anesthetic. Proportionally equivalent effects of propofol on the number of active release sites across the different bouton types suggests that glutamatergic circuits that involve smaller boutons with fewer release sites may be more vulnerable to the presynaptic effects of the drug.
Biomechanical Comparison of 1-Level Corpectomy and 2-Level Discectomy for Cervical Spondylotic Myelopathy: A Finite Element Analysis

Background Anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) are effective treatments for cervical spondylotic myelopathy (CSM), but it is unclear which is better. In this study, we compared the biomechanical properties of 2-level ACDF and 1-level ACCF. Material/Methods An intact C3–C7 cervical spine model was developed and validated, then ACDF and ACCF simulation models were developed. We imposed 1.0 Nm moments and displacement-controlled loading on the C3 superior endplate. The range of motions (ROMs) of surgical and adjacent segments and von Mises stresses on endplates, fixation systems, bone-screw interfaces, and bone grafts were recorded. Results ACDF and ACCF significantly reduced the surgical segmental ROMs to the same extent. ACCF induced much lower stress peaks in the fixation system and bone-screw interfaces and higher stress peaks on the bone graft. ACDF induced much lower stress peaks on the C4 inferior endplate and equivalent stress on the C6 superior endplate. There was no difference in the ROMs of surgical and adjacent segments and the intradiscal stress of adjacent levels between ACDF and ACCF. Conclusions Both ACDF and ACCF can provide satisfactory spinal stability. ACDF may be beneficial for subsidence resistance due to the lower stress peaks on the endplate. The ACCF may perform better in long-term stability and bone fusion owing to the lower stress peaks in the fixation system and bone-screw interfaces, and higher stress peaks in the bone graft.
Metabolic tumor volume, cancer cell fraction, and prognosis – the case of T-cell/histiocyte-rich large B-cell lymphoma

Abstract T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare aggressive lymphoma characterized by a paucity of neoplastic B-cells and a majority of reactive T-cells with or without histiocytes. In the ‘Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin Lymphomas’ trial (clinicaltrials.gov NCT00554164; EudraCT 2006-001641-33), its frequency was less than 3%. While cancer cell content by quantitative histology was 10-times lower, baseline total metabolic tumor volume (TMTV) by 18-fluorodesoxyglucose positron emission tomography was 10-times higher in THRLBCL than in diffuse large B-cell lymphoma (DLBCL). When THRLBCL and DLBCL populations were matched for TMTV, the survival curves were superimposable. However, when the populations were matched for cancer cell volume by multiplying TMTV by cancer cell fraction, outcome in THRLBCL was worse than in DLBCL. Whether genetic differences between cancer cells, tumor-promoting properties of non-neoplastic cells, or both are responsible for inferior cancer cell volume-related outcome in THRLBCL, remains to be elucidated.
Clarification on chronic pain – a painfully persistent problem? A reply

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