Greater toe grip and gentler heel strike are the strategies to adapt to slippery surface

This study investigated the plantar pressure distribution during gait on wooden surface with different slipperiness in the presence of contaminants. Fifteen Chinese males performed 10 walking trials on a 5-m wooden walkway wearing cloth shoe in four contaminated conditions (dry, sand, water, oil). A pressure insole system was employed to record the plantar pressure data at 50 Hz. Peak pressure and time-normalized pressure-time integral were evaluated in nine regions. In comparing walking on slippery to non-slippery surfaces, results showed a 30% increase of peak pressure beneath the hallux (from 195.6 to 254.1 kPa), with a dramatic 79% increase in the pressure time integral beneath the hallux (from 63.8 to 114.3 kPa) and a 34% increase beneath the lateral toes (from 35.1 to 47.2 kPa). In addition, the peak pressure beneath the medial and lateral heel showed significant 20–24% reductions, respectively (from 233.6–253.5 to 204.0–219.0 kPa). These findings suggested that greater toe grip and gentler heel strike are the strategies to adapt to slippery surface. Such strategies plantarflexed the ankle and the metatarsals to achieve a flat foot contact with the ground, especially at heel strike, in order to shift the ground reaction force to a more vertical direction. As the vertical ground reaction force component increased, the available ground friction increased and the floor became less slippery. Therefore, human could walk without slip on slippery surfaces with greater toe grip and gentler heel strike as adaptation strategies

Probing the Nature of High-z Short GRB 090426 with Its Early Optical and X-ray Afterglows

GRB 090426 is a short duration burst detected by Swift ($T_{90}\sim 1.28$ s in the observer frame, and $T_{90}\sim 0.33$ s in the burst frame at $z=2.609$). Its host galaxy properties and some $\gamma$-ray related correlations are analogous to those seen in long duration GRBs, which are believed to be of a massive-star origin (so-called Type II GRBs). We present the results of its early optical observations with the 0.8-m TNT telescope at Xinglong observatory, and the 1-m LOAO telescope at Mt. Lemmon Optical Astronomy Observatory in Arizona. Our well-sampled optical afterglow lightcurve covers from $\sim 90$ seconds to $\sim 10^4$ seconds post the GRB trigger. It shows two shallow decay episodes that are likely due to energy injection, which end at $\sim 230$ seconds and $\sim 7100$ seconds, respectively. The decay slopes post the injection phases are consistent with each other ($\alpha\simeq 1.22$). The X-ray afterglow lightcurve appears to trace the optical, although the second energy injection phase was missed due to visibility constraints introduced by the {\em Swift} orbit. The X-ray spectral index is $\beta_X\sim 1.0$ without temporal evolution. Its decay slope is consistent with the prediction of the forward shock model. Both X-ray and optical emission is consistent with being in the same spectral regime above the cooling frequency ($\nu_c$). The fact that $\nu_c$ is below the optical band from the very early epoch of the observation provides a constraint on the burst environment, which is similar to that seen in classical long duration GRBs. We therefore suggest that death of a massive star is the possible progenitor of this short burst.Comment: 7 pages, 1 figures, 2 tables, revised version, MNRAS, in pres

Radiomics in urolithiasis: Systematic review of current applications, limitations, and future directions

Radiomics is increasingly applied to the diagnosis, management, and outcome prediction of various urological conditions. Urolithiasis is a common benign condition with a high incidence and recurrence rate. The purpose of this scoping review is to evaluate the current evidence of the application of radiomics in urolithiasis, especially its utility in diagnostics and therapeutics. An electronic literature search on radiomics in the setting of urolithiasis was conducted on PubMed, EMBASE, and Scopus from inception to 21 March 2022. A total of 7 studies were included. Radiomics has been successfully applied in the field of urolithiasis to differentiate phleboliths from calculi and classify stone types and composition pre-operatively. More importantly, it has also been utilized to predict outcomes and complications after endourological procedures. Although radiomics in urolithiasis is still in its infancy, it has the potential for large-scale implementation. Its greatest potential lies in the correlation with conventional established diagnostic and therapeutic factors

The identification of novel Mycobacterium tuberculosis DHFR inhibitors and the investigation of their binding preferences by using molecular modelling

It is an urgent need to develop new drugs for Mycobacterium tuberculosis (Mtb), and the enzyme, dihydrofolate reductase (DHFR) is a recognised drug target. The crystal structures of methotrexate binding to mt- and h-DHFR separately indicate that the glycerol (GOL) binding site is likely to be critical for the function of mt-DHFR selective inhibitors. We have used in silico methods to screen NCI small molecule database and a group of related compounds were obtained that inhibit mt-DHFR activity and showed bactericidal effects against a test Mtb strain. The binding poses were then analysed and the influence of GOL binding site was studied by using molecular modelling. By comparing the chemical structures, 4 compounds that might be able to occupy the GOL binding site were identified. However, these compounds contain large hydrophobic side chains. As the GOL binding site is more hydrophilic, molecular modelling indicated that these compounds were failed to occupy the GOL site. The most potent inhibitor (compound 6) demonstrated limited selectivity for mt-DHFR, but did contain a novel central core (7H-pyrrolo[3,2-f]quinazoline-1,3-diamine), which may significantly expand the chemical space of novel mt-DHFR inhibitors. Collectively, these observations will inform future medicinal chemistry efforts to improve the selectivity of compounds against mt-DHFR

Therapeutic and Tumor-specific Immunity Induced by Combination of Dendritic Cells and Oncolytic Adenovirus Expressing IL-12 and 4-1BBL

Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12- and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12- and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12- and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic

Association of maternal Vitamin D status with glucose tolerance and caesarean section in a multi-ethnic Asian cohort: the growing up in Singapore towards healthy outcomes study

10.1371/journal.pone.0142239PLoS ONE10111-16GUSTO (Growing up towards Healthy Outcomes

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN