Miracle-dz/UniFAR-FTUs huggingface dataset:
MiR-145 inhibits cell migration and increases paclitaxel chemosensitivity in prostate cancer cells

Objective(s): Prostate cancer (PC) is one of the most commonly diagnosed malignancies among men worldwide. Paclitaxel is a chemotherapeutic agent widely used to treat different types of cancer. Recent studies revealed miRNAs control various genes that influence the regulation of many biological and pathological processes such as the formation and development of cancer, chemotherapy resistance, etc. Materials and Methods: Between three PC cell lines (PC3, DU-145, LNCAP), PC3 showed the lowest miR-145 expression and was chosen for experiments. PC3 cells were treated with paclitaxel and miR-145 separately or in combination. To measure the cell viability, migratory capacity, autophagy, cell cycle progression, and apoptosis induction, the MTT assay, wound-healing assay, and Annexin V/PI apoptosis assay were used, respectively. Moreover, quantitative real-time PCR (qRT-PCR) was employed to measure the expression level of genes involved in apoptosis, migration, and stemness properties. Results: Obtained results illustrated that miR-145 transfection could enhance the sensitivity of PC3 cells to paclitaxel and increase paclitaxel-induced apoptosis by modulating the expression of related genes, including Caspase-3, Caspase-9, Bax, and Bcl-2. Also, results showed combination therapy increased cell cycle arrest at the sub-G1 phase. miR-145 and paclitaxel cooperatively reduced migration ability and related-metastatic and stemness gene expression, including MMP-2, MMP-9, CD44, and SOX-2. In addition, combination therapy can suppress MDR1 expression. Conclusion: These results confirmed that miR-145 combined with paclitaxel cooperatively could inhibit cell proliferation and migration and increase the chemosensitivity of PC3 cells compared to mono treatment. So, miR-145 combination therapy may be used as a promising approach for PC treatment.
Annually dated late Weichselian continental paleoclimate record from the Eifel, Germany

A record extending back to 23 220 calendar yr B.P. was obtained from varved sediments from Lake Holzmaar, Germany, by applying multiple dating methods and interlake comparison with Meerfelder Maar. Variations in the Weichselian inorganic carbon content resulting from intensified eolian activities coincide with proxy parameters of dust accumulation in Greenland. The timing for the end of the last glacial maximum at Holzmaar agrees with the Greenland Ice Sheet Project (GISP2) data but suggests dating discrepancies with the Greenland Ice Core Project data (GRIP). Assuming that periods of maximum dust deposition in the Eifel and Greenland coincide with ice advances in northeastern Germany, the Holzmaar record provides a means of dating three late Weichselian terminal moraines.
Effects of Impervious Cover at Multiple Spatial Scales on Coastal Watershed Streams 1

Abstract: The spatial scale and location of land whose development has the strongest influence on aquatic ecosystems must be known to support land use decisions that protect water resources in urbanizing watersheds. We explored impacts of urbanization on streams in the West River watershed, New Haven, Connecticut, to identify the spatial scale of watershed imperviousness that was most strongly related to water chemistry, macroinvertebrates, and physical habitat. A multiparameter water quality index was used to characterize regional urban nonpoint source pollution levels. We identified a critical level of 5% impervious cover, above which stream health declined. Conditions declined with increasing imperviousness and leveled off in a constant state of impairment at 10%. Instream variables were most correlated (0.77 ≤ |r| ≤ 0.92, p < 0.0125) to total impervious area (TIA) in the 100‐m buffer of local contributing areas (∼5‐km2 drainage area immediately upstream of each study site). Water and habitat quality had a relatively consistent strong relationship with TIA across each of the spatial scales of investigation, whereas macroinvertebrate metrics produced noticeably weaker relationships at the larger scales. Our findings illustrate the need for multiscale watershed management of aquatic ecosystems in small streams flowing through the spatial hierarchies that comprise watersheds with forest‐urban land use gradients.
The Use of Data and Models for Assessing the Equilibrium Partitioning Approach for Analysising Environmental Quality Standards in the Water Column and in the Sediments

An analysis of experimental and simulated data has been performed to study the relationships between EQS defined for surface waters in the Daughter Directive (COM (2006) 397) and possible EQS defined for sediments. From the above analysis of experimental and simulated data, it is clear that even though there is a coupling between water column and sediments, it is not possible to assess the chemical quality status of sediments based on water column data and viceversa. At the moment EQS have been defined for the water column and therefore these EQS will assess only the compliance with good chemical status of surface waters. If EQS were to be defined for sediments, these EQS will not reflect systematically the surface water quality and therefore they could not be used for this purpose, being the contrary is also true, i.e. compliance with EQS values for water column does not reflect sediment chemical status. However, it is clear that the good chemical quality of a water body will depend on having good chemical quality of surface water and sediments and that to assess both it is necessary to measure in both media. The same EQS developed for water could, in principle, be applied to porewater, hence, there is no need of developing another set of EQS. If porewater could not be measured, then the partitioning approach to pass to sediment concentrations should be applied. However, in this case an additional uncertainty is added to the procedure and therefore it is necessary to develop to develop new techniques and better databases since at the moment the predictions are between several orders of magnitude, which are not adequate for setting EQS. Additionally, the use of this approach would certainly require the characterization of the sediments in terms of its physical (grain size, material, temperature), chemical (organic matter content, black carbon, pH, redox, etc.) and biological (e.g. bioturbation), which at the moment are not obtained from standard environmental monitoring.
3D seismic interpretation of slump complexes: examples from the continental margin of Israel

This paper uses three‐dimensional (3D) seismic data from the continental margin of Israel (Eastern Mediterranean) to describe a series of slump deposits within the Pliocene and Holocene succession. These slumps are linked to the dynamics of subsidence and deformation of the transform margin of the eastern Mediterranean. Repeated slope failure occurred during the post‐Messinian, when a clay‐dominated progradational succession was forming. This resulted in large‐scale slump deposits accumulating in the mid‐lower slope region of the basin at different stratigraphic levels. It is probable that the slumps were triggered by a combination of slope oversteepening, seismic activity and gas migration.
Prevalence and outcome of acute kidney injury in burn victims at a tertiary centre in Cape Town, South Africa.

BACKGROUND Burn victims commonly experience acute kidney injury (AKI), which can lead to significant morbidity and mortality. OBJECTIVE To investigate the prevalence of AKI in burn patients, the causes of AKI and the rate of in-hospital mortality. METHODS A retrospective cohort study was conducted on patients admitted to the Tygerberg Hospital Burn Unit between 1 April 2018, and 31 March 2019. The study included all burn patients >18 years old, except for those with end-stage kidney disease or cold burn wounds, skin donors or readmissions. AKI was defined using the Kidney Disease Improving Global Outcomes criteria, and multivariable logistic regression was used to identify predictors of AKI and death, along with Kaplan-Meier survival analysis. RESULTS The prevalence of AKI was 27% (58/215). The most common causes of burns were open fires (37%) and shack fires (17%). Patients with AKI had higher scores on the abbreviated burn severity index (ABSI) (7 v. 5, p<0.01), required more mechanical ventilation (69% v. 33%, p<0.01) and experienced more sepsis (35% v. 12%, p<0.01). Predictors of AKI included ABSI score (adjusted odds ratio (aOR) 1.48, 95% confidence interval (CI) 1.21 - 1.80, p<0.01), mechanical ventilation (aOR 7.75, 95% CI 1.23 - 48.65, p=0.03) and high admission lactate (aOR 1.57, 95% CI 1.04 - 2.39, p=0.03). Mortality was higher in patients with AKI (34% v. 6%, p<0.01). ABSI score (aOR 2.16, 95% CI 1.56 - 2.99, p<0.01) and vasopressor use (aOR 7.71, 95% CI 2.15 - 27.60, p<0.01) were identified as predictors of death. The survival analysis revealed that AKI was associated with higher mortality (log rank, p<0.01). CONCLUSION The study highlights the high prevalence of AKI among burn victims requiring tertiary care and its association with high mortality rates. Improving living conditions in informal settlements could help prevent burns and their complications.
Confidence limits on fossil ranges that account for facies changes

Abstract A drawback to most existing methods of calculating confidence limits on fossil ranges is their assumption that the probability of collecting a taxon through a stratigraphic section is constant. Marshall (1997) described an approach that would circumvent this problem, but it requires knowing the probability of collection as a function of stratigraphic position. Multivariate paleoecological methods, such as detrended correspondence analysis (DCA), offer a means of estimating these probabilities. DCA axis 1 sample scores can be used to quantify facies change through a stratigraphic section, and to calculate the probability of collection of a taxon relative to DCA axis 1. From these two, the probability of collection of each taxon can be estimated for each horizon in the measured section. This approach is applied here to the Upper Ordovician Kope Formation of the Cincinnati, Ohio, area to distinguish between disappearances of taxa that are driven by facies change and taxon rarity and those that represent true regional extinction. This new approach to confidence limits could also be applied to test the synchroneity of extinction or origination at large-scale turnover events, such as mass extinctions and the turnover pulses that bound episodes of faunal stasis.
Contemporary global horizontal crustal motion

SUMMARY An analysis of Satellite Laser Ranging (SLR) data to the LAGEOS satellite has yielded improved estimates of the horizontal motion for a subset of 34 tracking sites within the global tracking network. The analysis, called SL8.3, utilized data acquired between 1980 January and 1993 June by the global network composed of 71 sites. The solution design provides for the simultaneous estimation of site positions and their velocities within a pre-defined kinematic frame. The solution is statistically rigorous and retains the full correlation information content. Least-squares estimates of relative poles of rotation, which are used to model the motion of one plate relative to another, were made based on the SLR estimated velocities for sites known to be well away from deformation zones. The resulting SLR-based relative rotation poles differ slightly from those of NUVEL-1, but in general, indicate that the magnitude of the SLR implied velocities is slower than those implied by NUVEL-1, consistent with the 4-5 per cent slowing in relative spherical rates noted in earlier comparisons. Spherical rates between sites in western North America support models of extension in the Basin and Range Province and the rotation of the Sierra Nevada microplate. An analysis of the spherical rates crossing the North Atlantic shows that SL8.3 estimated extension between North America-Eurasia sites is generally smaller than those implied by NUVEL-1; meanwhile SL8.3 rates between North America-Africa sites are in better agreement with NUVEL-1, although they are not so well determined. The maintenance and ongoing monitoring of global SLR site kinematics provides a well-defined global reference which will aid in combination global kinematic solutions where information from other technologies are merged (e.g. Very Long Baseline Interferometry and Global Positioning System) and in providing the context for densification studies of regional kinematics derived from terrestrial and Global Positioning System observations.
Leveraging stewardship to promote ceftriaxone use in severe infections with low- and no-risk AmpC Enterobacterales

ABSTRACT AmpC β-lactamases are associated with development of ceftriaxone resistance despite initial in vitro susceptibility, but the risk of AmpC derepression is not equal among Enterobacterales. The purpose of this study was to evaluate the impact of an AmpC stewardship intervention on the definitive treatment of low- and no-risk Enterobacterales. This was an IRB-approved, single pre-test, post-test quasi-experiment at a 5-hospital system. An AmpC stewardship intervention was implemented in July 2022 and included prescriber education, the removal of microbiology comments indicating potential for ceftriaxone resistance on therapy, and the modification of a blood PCR comment for Serratia marcescens to recommend ceftriaxone. Adults ≥18 years pre-intervention (July 2021 to December 2021) and post-intervention (July 2022 to December 2022) who received ≥72 hours of inpatient definitive therapy and had non-urine cultures growing low- and no-risk organisms (S. marcescens, Providencia spp., Citrobacter koseri, Citrobacter amalonaticus, or Morganella morganii) were included. The primary endpoint was definitive treatment with ceftriaxone. A total of 224 patients were included; 115 (51%) in pre-intervention and 109 (49%) in post-intervention. Definitive ceftriaxone therapy was prescribed more frequently after intervention [6 (5%) vs 72 (66%), P < 0.001]. After adjustment for critical illness, patients in the post-group were more likely to receive definitive ceftriaxone (adjOR, 34.7; 95% CI, 13.9–86.6). The proportion of patients requiring retreatment was 18 (15%) and 11 (10%) for pre- and post-intervention patients (P = 0.22), and ceftriaxone resistance within 30 days occurred in 5 (4%) and 2 (2%) patients in the pre- and post-group (P = 0.45). An antimicrobial stewardship intervention was associated with increased ceftriaxone prescribing and similar patient outcomes for low- and no-risk AmpC Enterobacterales.
Profile of human papillomavirus genotypes in breast and oesophageal cancer patients in Pretoria, South Africa.

BACKGROUND The association between human papillomavirus (HPV) and cervical cancer is well established, and cervical cancer can be prevented through HPV vaccination. Little has been reported on the association between HPV and breast carcinoma (BC) or oesophageal squamous cell carcinoma (OSCC) in Africa. It is possible that use of appropriate HPV vaccines against genotypes responsible for these cancers may also prevent their development. OBJECTIVES To investigate HPV genotype prevalence in BC and OSCC patients in Pretoria, South Africa (SA). METHODS A retrospective cross-sectional study of BC and OSCC patients managed at Steve Biko Academic Hospital from 2015 to 2019 was undertaken. Patient medical records were analysed, and DNA was extracted from their archived pathology material and amplified by polymerase chain reaction before hybridisation for HPV genotypes. RESULTS There were 101 patients with BC and 50 with OSCC. The prevalence of HPV infection in BC patients was 77.2%, with 35.6% high- risk (HR) genotypes, and that in OSCC patients 90.0%, with 56.0% HR genotypes. The most prevalent HPV genotypes (>20% each) were HPV 16, 70 and 51 for BC and HPV 51, 70, 16 and 82 for OSCC, with 31.7% and 60.0% of patients, respectively, having co-infection with ≥2 genotypes. CONCLUSION The high prevalence of infection with multiple HPV genotypes in BC and OSCC patients, with HPV 16, 51, 70, 35 and 82 the most common genotypes in these cancers, warrants expansion of the current SA bivalent HPV 16/18 vaccine for girls to include boys, and inclusion of HPV 51, 70, 35 and 82, in order to prevent BC and OSCC as well as cervical cancer.
A Theoretical Analysis of DeepWalk and Node2vec for Exact Recovery of Community Structures in Stochastic Blockmodels

Random-walk-based network embedding algorithms like DeepWalk and node2vec are widely used to obtain euclidean representation of the nodes in a network prior to performing downstream inference tasks. However, despite their impressive empirical performance, there is a lack of theoretical results explaining their large-sample behavior. In this paper, we study node2vec and DeepWalk through the perspective of matrix factorization. In particular, we analyze these algorithms in the setting of community detection for stochastic blockmodel graphs (and their degree-corrected variants). By exploiting the row-wise uniform perturbation bound for leading singular vectors, we derive high-probability error bounds between the matrix factorization-based node2vec/DeepWalk embeddings and their true counterparts, uniformly over all node embeddings. Based on strong concentration results, we further show the <italic>perfect</italic> membership recovery by node2vec/DeepWalk, followed by <inline-formula><tex-math notation="LaTeX">$K$</tex-math><alternatives><mml:math><mml:mi>K</mml:mi></mml:math><inline-graphic xlink:href="zhang-ieq1-3327631.gif"/></alternatives></inline-formula>-means/medians algorithms. Specifically, as the network becomes sparser, our results guarantee that with large enough window size and vertex number, applying <inline-formula><tex-math notation="LaTeX">$K$</tex-math><alternatives><mml:math><mml:mi>K</mml:mi></mml:math><inline-graphic xlink:href="zhang-ieq2-3327631.gif"/></alternatives></inline-formula>-means/medians on the matrix factorization-based node2vec embeddings can, with high probability, correctly recover the memberships of all vertices in a network generated from the stochastic blockmodel (or its degree-corrected variants). The theoretical justifications are mirrored in the numerical experiments and real data applications, for both the original node2vec and its matrix factorization variant.
Ocular manifestations of HIV infection at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.

BACKGROUND The pattern of HIV-associated eye disease has changed with ongoing advancements in highly active antiretroviral therapy (HAART). HIV-infected individuals now live longer, enabling us to observe the long-term effects of HIV and HAART on the eye. There are few recent studies on HIV-related ocular disease in sub-Saharan Africa. OBJECTIVES To describe the ocular manifestations of HIV in patients attending the Nthabiseng HIV clinic at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. METHODS A cross-sectional study was conducted in 2021 and 2022 using convenience sampling of patients at the HIV clinic. The participants' clinical history was taken, their files were reviewed, and they underwent ocular examination. Correlation between eyes was managed by taking disease in one eye as the presence of disease in the participant. Descriptive statistics were used to summarise participant characteristics. Univariate and multivariate logistic regression models were used to assess the odds ratio (OR) of developing HIV-associated ocular diseases, and a p-value of <0.05 was used to define statistical significance. RESULTS There were 182 participants (139 females and 43 males), with a mean (standard deviation) age of 48.9 (10.6) years. The most common anterior segment diagnoses were conjunctival microangiopathy (34.6%), pinguecula (31.3%) and cataracts (30.2%), while the most common posterior segment finding was peripheral retinal scarring with features in keeping of previous cytomegalovirus retinitis (24.2%). Notably, only 1.1% of patients had HIV retinopathy. A CD4 count <200 cells/μL showed an increased OR for cataracts (OR 4.24; p=0.003) and any anterior segment diagnoses (OR 10.05; p=0.029), while a CD4 count ≥200 cells/μL showed an increased risk of conjunctival microangiopathy (OR 2.14; p=0.017). CONCLUSION With the advent of HAART, ocular manifestations of HIV are changing and the incidence of severe ocular opportunistic infections and HIV retinopathy has decreased precipitously. Although this study has shown that patients with a CD4 count <200 cells/μL are at increased risk of developing anterior ocular manifestations of HIV, including cataracts, these diseases are relatively innocuous or easily treatable. Routine ocular screening of HIV patients seems to be substantially less important now than it was in the pre-HAART era.
Impacts of background field removal on CMIP5 projected changes in Pacific winter cyclone activity

Cyclones are responsible for much of the high impact weather in the extratropics, thus how they will change under global warming is of great concern. Several studies have used the multimodel climate simulations conducted under Phase 5 of the Coupled Model Intercomparison Project (CMIP5) to examine such changes. One study suggested that the frequency of strong cyclones is projected to decrease over the North Pacific, while another concluded that this frequency will increase. A single tracking algorithm has been used to derive cyclone statistics from 23 CMIP5 simulations using two different definitions of cyclones: cyclones as minima in total sea level pressure (SLP) or cyclones as minima in SLP perturbations about a large scale, low‐frequency background. When cyclones are defined by total SLP, the frequency of deep cyclones over the Pacific is projected to increase, while if cyclones are defined as perturbations, this frequency is projected to decrease. These differences are shown to be due to a projected deepening of the climatological mean Aleutian low. In view of these results, it is important to critically assess how cyclones should be defined. Preliminary results suggest that among CMIP5 simulations, over the Pacific, both the projected changes in the frequency of high wind events and mean available potential energy are better correlated with the projected changes in the frequency of cyclones defined as perturbations. It is concluded that more research should be done to quantify and understand the impacts of the different definitions of cyclones.
Etranacogene dezaparvovec for the treatment of adult patients with severe and moderately severe hemophilia B

ABSTRACT Introduction Etranacogene dezaparvovec is the first gene therapy approved for treatment of adults with severe and moderately severe hemophilia B. Areas covered This review describes the results of the clinical trial program of AMT-060 and etranacogene dezaparvovec, outlining the pharmacokinetic, clinical efficacy and safety data. With the entry of etranacogene dezaparvovec into the market, this review summarizes the treatment landscape in hemophilia B and discusses the current unknowns in the field. Expert opinion Gene therapy appears to be a feasible option for adults with severe and moderately severe hemophilia B. Etranacogene dezaparvovec enables most patients to reach stable factor IX (FIX) levels after a single intravenous infusion, eliminating the need for regular prophylaxis; thus, drastically reducing treatment burden and avoiding variable bleeding risk owing to fluctuating FIX activity levels. Efficacy of etranacogene dezaparvovec has been demonstrated even in the presence of preexisting neutralizing antibodies (up to a titer of 1:678), with a relative low risk of transaminitis and its associated potential loss of transgene expression. However, long-term data are required to ascertain the durability of FIX levels achieved and safety. The cost-effectiveness and adoption of innovative payment models for reimbursement are key in choosing gene therapy over existing treatments.