A proof of concept for a deep learning system that can aid embryologists in predicting blastocyst survival after thaw.

The ability to understand whether embryos survive the thaw process is crucial to transferring competent embryos that can lead to pregnancy. The objective of this study was to develop a proof of concept deep learning model capable of assisting embryologist assessment of survival of thawed blastocysts prior to embryo transfer. A deep learning model was developed using 652 labeled time-lapse videos of freeze-thaw blastocysts. The model was evaluated against and along embryologists on a test set of 99 freeze-thaw blastocysts, using images obtained at 0.5 h increments from 0 to 3 h post-thaw. The model achieved AUCs of 0.869 (95% CI 0.789, 0.934) and 0.807 (95% CI 0.717, 0.886) and the embryologists achieved average AUCs of 0.829 (95% CI 0.747, 0.896) and 0.850 (95% CI 0.773, 0.908) at 2 h and 3 h, respectively. Combining embryologist predictions with model predictions resulted in a significant increase in AUC of 0.051 (95% CI 0.021, 0.083) at 2 h, and an equivalent increase in AUC of 0.010 (95% CI -0.018, 0.037) at 3 h. This study suggests that a deep learning model can predict in vitro blastocyst survival after thaw in aneuploid embryos. After correlation with clinical outcomes of transferred embryos, this model may help embryologists ascertain which embryos may have failed to survive the thaw process and increase the likelihood of pregnancy by preventing the transfer of non-viable embryos.

The Utility of CONUT Score in Diffuse Large B Cell Lymphoma Patients.

BACKGROUND: Assessment of nutritional status is gaining more importance in cancer patients because nutritional status is associated with response to chemotherapy, side effects of cancer treatment and disease progression. Several studies that were performed on patients with solid malignancies have shown the clinical significance of CONUT score (Controlling nutritional status). AIMS: Therefore we tried to show the utility of CONUT score in newly diagnosed Diffuse Large B Cell Lymphoma (DLBCL) patients which is the most frequently seen B Cell Lymphoma type. METHODS: Data of the 81 patients diagnosed with DLBCL were retrospectively evaluated. The primary endpoint of our study was to evaluate and classify newly diagnosed DLBCL patients according to the CONUT score and secondary endpoint was to show any relationship with CONUT score and overall survival. Patients' demographics, treatment details, stages, extranodal involvements, the presence of bulky disease, response to treatment options and overall survivals were evaluated from medical recordings. RESULTS: Univariate cox regression analysis CONUT score was associated with overall survival (HR: 2.34-95% CI: 1.55-3.24 P = 0.040). On multivariate Cox regression analysis model CONUT score ≥5 was found to be an independent prognostic factor for overall survival (HR: 4.96-95% CI: 1.77-13.97- P = 0.002). CONCLUSION: The value of obtaining nutritional status in cancer patients is underestimated and CONUT score is simple, easily applicable and in our opinion is going to fill the gap especially in DLBCL patients.

Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

Square prism micropillars improve osteogenicity of poly(methyl methacrylate) surfaces.

Osteogenicity and osteointegration of materials is one of the key elements of the success of bone implants. Poly(methyl methacrylate) (PMMA) is the basic compound of bone cement and has been widely investigated for other orthopedic applications, but its poor osteointegration and the subsequent loosening of implant material limits its widespread use as bone implants. Micropillar features on substrate surfaces were recently reported to modulate cell behavior through alteration of cell morphology and promotion of osteogenesis. Utilization of this pillar-decorated topography may be an effective approach to enhance osteogenicity of polymeric surfaces. The aim of this study was to investigate the effect of cell morphology on the micropillar features on attachment, proliferation, and osteogenic activity of human osteoblast-like cells. A series of solvent cast PMMA films decorated with 8 µm high square prism micropillars with pillar width and interpillar distances of 4, 8 and 16 µm were prepared from photolithographic templates, and primary human osteoblast-like cells (hOB) isolated from bone fragments were cultured on them. Micropillars increased cell attachment and early proliferation rate compared to unpatterned surfaces, and triggered distinct morphological changes in cell body and nucleus. Surfaces with pillar dimensions and gap width of 4 µm presented the best osteogenic activity. Expression of osteogenic marker genes was upregulated by micropillars, and cells formed bone nodule-like aggregates rich in bone matrix proteins and calcium phosphate. These results indicated that micropillar features enhance osteogenic activity on PMMA films, possibly by triggering morphological changes that promote the osteogenic phenotype of the cells.

Biomass yield and feeding value of rye, triticale, and wheat straw produced under a dual-purpose management system.

Dual-purpose management of winter cereals for grazing and grain production provides highly nutritive forage for ruminants in the spring and may positively affect straw feeding value. A 2-yr study investigated the effect of spring defoliation of triticale, wheat, and rye at the tillering and stem elongation stages on total biomass, grain yields, and straw quality. Furthermore, straws of spring-defoliated and undefoliated (control) cereal crops were evaluated for nutritional value and voluntary intake as a means of assessing the efficiency of dual-purpose management systems from the winter feeding context as well. The feeding study consisted of 9 total mixed rations (TMR), each containing 35% triticale, rye, or wheat straw obtained under 3 spring-defoliation regimens. The TMR were individually fed to fifty-four 1-yr-old Anatolian Merino ewes for 28 d. Defoliation of the crops at tillering did not affect the total biomass production or grain yields. However, biomass and grain yields were reduced ( < 0.01) by 55 and 52%, respectively, in crops defoliated at stem elongation. Straw of spring-defoliated cereals had less NDF and ADF concentrations ( < 0.01) but greater CP ( < 0.01), nonfiber carbohydrates ( < 0.01), and ME concentrations ( < 0.01) compared with straw from undefoliated crops. The increase in the nutritive value of straw led to greater nutrient digestion ( < 0.01) and intake of DM and OM of ewes ( < 0.01). However, sheep live weight gain did not differ among treatments ( > 0.77). This study indicated that straw feeding value and digestibility can be increased through spring defoliation.

Nanomechanical motion of Escherichia coli adhered to a surface.

Nanomechanical motion of bacteria adhered to a chemically functionalized silicon surface is studied by means of a microcantilever. A non-specific binding agent is used to attach Escherichia coli (E. coli) to the surface of a silicon microcantilever. The microcantilever is kept in a liquid medium, and its nanomechanical fluctuations are monitored using an optical displacement transducer. The motion of the bacteria couples efficiently to the microcantilever well below its resonance frequency, causing a measurable increase in the microcantilever fluctuations. In the time domain, the fluctuations exhibit large-amplitude low-frequency oscillations. In corresponding frequency-domain measurements, it is observed that the mechanical energy is focused at low frequencies with a 1/fα -type power law. A basic physical model is used for explaining the observed spectral distribution of the mechanical energy. These results lay the groundwork for understanding the motion of microorganisms adhered to surfaces and for developing micromechanical sensors for bacteria.

Guided and magnetic self-assembly of tunable magnetoceptive gels.

Self-assembly of components into complex functional patterns at microscale is common in nature, and used increasingly in numerous disciplines such as optoelectronics, microfabrication, sensors, tissue engineering and computation. Here, we describe the use of stable radicals to guide the self-assembly of magnetically tunable gels, which we call 'magnetoceptive' materials at the scale of hundreds of microns to a millimeter, each can be programmed by shape and composition, into heterogeneous complex structures. Using paramagnetism of free radicals as a driving mechanism, complex heterogeneous structures are built in the magnetic field generated by permanent magnets. The overall magnetic signature of final structure is erased via an antioxidant vitamin E, subsequent to guided self-assembly. We demonstrate unique capabilities of radicals and antioxidants in fabrication of soft systems with heterogeneity in material properties, such as porosity, elastic modulus and mass density; then in bottom-up tissue engineering and finally, levitational and selective assembly of microcomponents.

Evaluation of epithelial chimerism after bone marrow mesenchymal stromal cell infusion in intestinal transplant patients.

Intestinal transplantation is the most effective treatment for patients with short bowel syndrome and small bowel insufficiencies. We evaluated epithelial chimerism after infusion of autologous bone marrow mesenchymal stromal cells (BMSCs) in patients undergoing cadaveric donor isolated intestinal transplantation (I-ITx). BMSCs were isolated from patients' bone marrow via iliac puncture and expanded in vitro prior to infusion. Two out of the 3 patients were infused with autologous BMSCs, and small intestine tissue biopsies collected post-operatively were analyzed for epithelial chimerism using XY fluorescent in situ hybridization and short tandem repeat polymerase chain reaction. We observed epithelial chimeric effect in conditions both with and without BMSC infusion. Although our results suggest a higher epithelial chimerism effect with autologous BMSC infusion in I-ITx, the measurements in multiple biopsies at different time points that demonstrate the reproducibility of this finding and its stability or changes in the level over time would be beneficial. These approaches may have potential implications for improved graft survival, lower immunosuppressant doses, superior engraftment of the transplanted tissue, and higher success rates in I-ITx.

Untethered micro-robotic coding of three-dimensional material composition.

Complex functional materials with three-dimensional micro- or nano-scale dynamic compositional features are prevalent in nature. However, the generation of three-dimensional functional materials composed of both soft and rigid microstructures, each programmed by shape and composition, is still an unsolved challenge. Here we describe a method to code complex materials in three-dimensions with tunable structural, morphological and chemical features using an untethered magnetic micro-robot remotely controlled by magnetic fields. This strategy allows the micro-robot to be introduced to arbitrary microfluidic environments for remote two- and three-dimensional manipulation. We demonstrate the coding of soft hydrogels, rigid copper bars, polystyrene beads and silicon chiplets into three-dimensional heterogeneous structures. We also use coded microstructures for bottom-up tissue engineering by generating cell-encapsulating constructs.

Clinical and prognostic importance of XIAP and USP8 in advanced stages of non-small cell lung cancer.

PURPOSE: To investigate the relationship of the apoptosis regulators X-linked inhibitor of apoptosis (XIAP) and ubiquitin specific protease 8 (USP8) with clinical parameters, survival and response to chemotherapy in patients with advanced stages of non-small cell lung cancer (NSCLC). METHODS: The study included 34 NSCLC patients (28 females, 6 males) and 44 healthy individuals (17 males, 27 females) as a control group. XIAP and USP8 levels were determined by ELISA. RESULTS: The median serum XIAP level of the patients and the control group showed no significant difference. USP8 level was higher in patients than in controls (p<0.0001). In univariate analysis, there was no significant relationship between XIAP and USP8 serum levels and age, sex, performance status, weight loss, stage of disease, histopatological type and response to chemotherapy. Response to chemotherapy did not differ between the high and low XIAP and USP8 groups . There was no significant difference in progression- free survival (PFS) (p=0.432 and p=0.50, respectively) and overall survival (OS) (p=0.989 and p=0.90, respectively) between the low and high XIAP and USP8 groups. CONCLUSION: No relationship was found in serum XIAP and USP8 levels with clinical parameters, response to chemotherapy, PFS and OS in patients with advanced stages of NSCLC.

Endocrine therapy alone vs. chemotherapy plus endocrine therapies for the treatment of elderly patients with endocrine-responsive and node positive breast cancer: a retrospective analysis of a multicenter study (Anatolian Society of Medical Oncology).

PURPOSE: The extra benefit of adding chemotherapy to effective endocrine therapy (ET) has not been clearly or consistently identified in patients older than 70 years with estrogen receptor (ER) positive and node positive breast cancer. The aim of this study was to evaluate the efficacy of adjuvant ET vs. chemotherapy plus endocrine therapies (Chemo/ET) in such patients. METHODS: In this retrospective multicenter study 191 patients ≥ 70 years with operated hormone receptor breast cancer, who were administered adjuvant ET or Chemo/ET were assessed. RESULTS: The median patient follow-up time was 29.0 months (range 1-252). Therefore disease free survival (DFS) and overall survival (OS) analysis was limited, due to the rather short median follow-up, and only 30-month cumulative percentages are reported herein. The 30-month DFS rates were 50.0% in the ET arm and 49.0% in the Chemo/ET arm (p=0.79). The 30-month OS rates were 86% in the ET arm and 96.0% in the Chemo/ET arm (p=0.08). Cox proportional hazard model showed that only surgery was independent prognostic factor for survival (p=0.047), while tumor size showed a strong trend for statistical significance (p=0.051). CONCLUSION: The addition of chemotherapy to endocrine therapy in older patients has no significant impact on DFS and OS.

Trabectedin in advanced soft tissue sarcoma: case series.

The prognosis of advanced soft tissue sarcomas (STS) is poor. The median overall survival (OS) is 6 months in unresectable and metastatic STS that progress after treatment with anthracyclines and ifosfamide. Trabectedin is an alkylating agent, effective in advanced STS, especially in leiomyosarcoma and liposarcoma. In the present study, the effectiveness and safety of trabectedin was retrospectively evaluated in 8 unresectable and metastatic STS patients. Their median age was 47 years. The median progression free survival (PFS) was 3.75 months and the median OS 15 months in relapse or progression after anthracyclines and/or ifosfamide. Toxicities were mainly hematologic. In the present study, trabectedin showed efficacy in different histological subtypes of sarcomas like liposarcoma and leiomyosarcoma.

Long term experience in high grade glial tumors with temozolomide.

PURPOSE: Temozolomide is used concurrently with radiotherapy (RT) and as consolidation therapy in high grade gliomas (HGGs). In the present study we present our experience of long-term efficacy and toxicity of temozolomide in HGGs. METHODS: After surgery, temozolomide was administered at 75 mg/m(2) daily concurrently with RT, followed by 6 courses of consolidation therapy (150-200 mg/m(2) for 5 days every 28 days). RESULTS: A total of 172 patients with either glioblastoma multiforme (GBM) (n= 142; 82.6%) or anaplastic astrocytoma (AA) (n= 30; 17.4%) were studied. The objective response rate (ORR) was 42.5%, including 12 (7%) complete responses (CRs) and 61 (35.5%) partial responses (PRs). In the GBM group, median progression free survival (PFS) and overall survival (OS) were 9 and 16 months, respectively. In the AA group, median PFS and OS were 16 and 24 months, respectively. Three-year OS was 18.2% for GBM, and 39.4% for AA. In elderly patients (14.5%), median PFS and OS were 8 and 11 months respectively for both HGGs. Serious toxicities were mainly hematologic. CONCLUSION: Temozolomide is an effective agent in HGGs with favorable outcome and low toxicity profile even in advanced age.

Mitomycin-C in combination with fluoropyrimidines in the treatment of metastatic colorectal cancer after oxaliplatin and irinotecan failure.

PURPOSE: To retrospectively evaluate the efficacy and tolerability of mitomycin-C (MMC) in combination with fluoropyrimidines as salvage 3rd -or 4th-line therapy in metastatic colorectal cancer (MCRC) patients. METHODS: All patients in this study had previously failed oxaliplatin and irinotecan-based chemotherapy. Patients were treated with MMC (6 mg/m(2) intravenously/i.v.) on day 1 in combination with either oral UFT (500 mg/m(2)) and oral leucovorin (LV) (30 mg) on days 1-14 every 3 weeks (group A) or infusional 5-fluorouracil (5-FU) by deGramont regimen with i.v. LV (200 mg/m(2)) on days 1 and 2, every 2 weeks (group B). RESULTS: Thirty-nine MCRC patients were analyzed. Twenty-two of them were in group A and 17 in group B. Thirty-three were evaluable for clinical efficacy. The clinical benefit in the intent-to-treat (ITT) population was 30.8%. Median progression free survival (PFS) was 6 months (95% confidence interval/ CI 4-8) and median overall survival (OS) 9 months (95% CI 6.5-11.5). Median PFS was 3 months (95% CI 2.4-3.6) in group A and 7 months (95% CI 5.1-8.9) in group B (p=0.009). Median OS was 7 months (95% CI 4.3-9.7) in group A and 12 months (95% CI 5.4-18.6) in group B (p=0.422). The combination of MMC and fluoropyrimidines was generally well tolerated. The most common severe toxicities were nausea and vomiting, neutropenia, hepatotoxicity and diarrhea. CONCLUSION: MMC in combination with fluoropyrimidines is safe and active in heavily-pretreated MCRC patients. This combination remains a viable option in these patients. However, better therapies are urgently needed.

Enhanced hydrogen release by catalyzed hydrolysis of sodium borohydride-ammonia borane mixtures: a solution-state 11B NMR study.

Hydrolysis of mixtures consisting of sodium borohydride NaBH(4) (SB) and ammonia borane NH(3)BH(3) (AB) was studied in the absence/presence of a Co catalyst. The kinetics of the H(2) evolutions was measured. The reactions were followed in situ by solution-state (11)B NMR and the hydrolysis by-products characterized by NMR, XRD and IR. It is demonstrated that the combination of the two compounds gives a synergetic effect. SB rapidly reduces the Co catalyst precursor and the NH(4)(+) ions from AB contribute in the dispersion of the in situ formed Co nanoparticles. As a result, the kinetics of H(2) evolution is greatly improved. For instance, a hydrogen generation rate of 29.6 L min(-1) g(-1)(Co) was found for a mixture consisting of 81 wt% NH(3)BH(3), 9 wt% NaBH(4) and 10 wt% CoCl(2). By (11)B NMR, it was showed that the reaction mechanisms are quite trivial. As soon as the Co catalyst forms in situ, SB, rather than AB, hydrolyzes until it is totally converted. Then, the overall hydrolysis continues with that of AB. Both reactions follow a bimolecular Langmuir-Hinshelwood mechanism; no reaction intermediates were observed during the process. In fact, SB and AB convert directly into B(OH)(4)(-), which comes in equilibrium with a polyborate compound identified as B(3)O(3)(OH)(4)(-). All of these results are discussed herein.

Cobalt in NaBH4 hydrolysis.

Cobalt-catalyzed hydrolysis of sodium borohydride (NaBH(4)) has attracted great attention since the hydride is believed to be promising hydrogen storage material. Cobalt is an efficient metal catalyst and has already proven to be a potential alternative to noble metals. Nevertheless it is not stable. Indeed it transforms into a Co- and B-based material when on contact with NaBH(4). Through ex situ characterizations (e.g. ICP, XRD, XPS and SEM), the Co- and B-based material has been supposed to be either a cobalt boride Co(x)B (with x from 1 to 3) or a Co-B alloy. This contradiction is the topic of the present paper. Herein, the literature dedicated to the Co-catalyzed NaBH(4) hydrolysis is exhaustively surveyed. The results of the ex situ characterizations are largely discussed, for example that: (i) the ex situ characterized Co(x)B or Co-B might be different from the in situ formed Co- and B-based catalyst; (ii) there is no clear evidence of the formation of either Co(x)B or Co-B; (iii) the in situ formed catalyst would change in accordance with a cycle in the course of the hydrolysis; and (iv) in situ characterizations are clearly required but their setting up is a challenge. These conclusions, among others, are argued.

A droplet-based building block approach for bladder smooth muscle cell (SMC) proliferation.

Tissue engineering based on building blocks is an emerging method to fabricate 3D tissue constructs. This method requires depositing and assembling building blocks (cell-laden microgels) at high throughput. The current technologies (e.g., molding and photolithography) to fabricate microgels have throughput challenges and provide limited control over building block properties (e.g., cell density). The cell-encapsulating droplet generation technique has potential to address these challenges. In this study, we monitored individual building blocks for viability, proliferation and cell density. The results showed that (i) SMCs can be encapsulated in collagen droplets with high viability (>94.2 +/- 3.2%) for four cases of initial number of cells per building block (i.e. 7 +/- 2, 16 +/- 2, 26 +/- 3 and 37 +/- 3 cells/building block). (ii) Encapsulated SMCs can proliferate in building blocks at rates that are consistent (1.49 +/- 0.29) across all four cases, compared to that of the controls. (iii) By assembling these building blocks, we created an SMC patch (5 mm x 5 mm x 20 microm), which was cultured for 51 days forming a 3D tissue-like construct. The histology of the cultured patch was compared to that of a native rat bladder. These results indicate the potential of creating 3D tissue models at high throughput in vitro using building blocks.