H-index in medicine is driven by original research.

AIM: To investigate the contribution of selected types of articles to h-indices of medical researchers. METHODS: We used the Web of Science to export the publication records of various members from 26 scientific medical societies (13 European, 13 North American) associated with 13 medical specialties. Those included were presidents (n=26), heads of randomly chosen committees (n=52), and randomly selected members of those committees (n=52). Publications contributing to h-index were categorized as research articles, reviews, guidelines, meta-analyses, or other published work. RESULTS: Overall, 3259 items authored by 129 scholars were analyzed. The median h-index was 19.5. The median contribution of research articles to h-index was 84.4%. Researchers in the upper h-index tercile (≥28.5) had a larger share of research articles that contributed to h-index in comparison with those in the lower h-index tercile (≤12.5) (median 87.3% [1st-3rd quartile: 80.0%-93.1%] vs 80.0% [50.0%-88.9%], P=0.015). We observed an analogous difference with regard to guidelines (1.1% [0%-3.7%] vs 0% [0%-0%], P=0.007). CONCLUSIONS: Original research drives h-indices in medicine. Although guidelines contribute to h-indices in medicine, their influence is low. The specific role of randomized controlled trials in building h-index in medicine remains to be assessed.

Illuminating developmental biology through photochemistry.

Developmental biology has been continually shaped by technological advances, evolving from a descriptive science into one immersed in molecular and cellular mechanisms. Most recently, genome sequencing and 'omics' profiling have provided developmental biologists with a wealth of genetic and biochemical information; however, fully translating this knowledge into functional understanding will require new experimental capabilities. Photoactivatable probes have emerged as particularly valuable tools for investigating developmental mechanisms, as they can enable rapid, specific manipulations of DNA, RNA, proteins, and cells with spatiotemporal precision. In this Perspective, we describe optochemical and optogenetic systems that have been applied in multicellular organisms, insights gained through the use of these probes, and their current limitations. We also suggest how chemical biologists can expand the reach of photoactivatable technologies and bring new depth to our understanding of organismal development.

The evaluation of treatment plans in high-dose-rate endobronchial brachytherapy by utilizing 2D and 3D computed tomography imaging methods.

PURPOSE: To present comparison of treatment plans made by using 2D and 3D methods in the planning system, as well as to assess the quality of treatment plans using the 2D and 3D methods. MATERIAL AND METHODS: The studies involved a group of 31 patients with advanced lung cancer treated in the Brachytherapy Department of the Subcarpathian Cancer Center in Brzozów from 2011 to 2013. In total, 31 patients and 76 treatment plans were analyzed. We compared coverage of PTV planned in 3D and 2D. In the 3D method of treatment, three-dimensional images from computer tomography were used. In treatment plans performed using the 2D method, images from the simulator were used. RESULTS: The comparison of treatment plans made by using 2D and 3D methods is described. This comparison highlighted the significant differences between these two methods assessing reference dose coverage of the PTV by 100% and 85% isodose. CONCLUSIONS: Reference doses with 100% coverage of the PTV in treatment applied with the 3D method are 31% higher than when applied with the 2D method.

Individual applicator for brachytherapy for various sites of superficial malignant lesions.

The aim of this paper is to discuss brachytherapy treatment and individual applicators suitable for unfavorably localized superficial malignant lesions. Techniques for manufacturing an individual applicator and clinical examples of its use for various locations of cancer are presented. This techniques are based on individual size and shape of the tumour. CT-planning make the technique adequate for individual patient history and type of tumour. Featured techniques seems to be very useful and easy to performed.

Comparison of the GTV coverage by PTV and isodose of 90% in 2D and 3D planning during endobronchial brachytherapy in the palliative treatment of patients with advanced lung cancer. Pilot study.

PURPOSE: Endobronchial brachytherapy (EB) is one way of treatment of patients with advanced lung cancer. Technological progress and the introduction of computed tomography for use in 3D planning allows one to define the area being treated very precisely, which gives an opportunity to extend survival, even in groups of patients receiving palliative care. MATERIAL AND METHODS: In 2011, in the Brachytherapy Department of the Subcarpathian Oncological Center, a group of 12 consecutive patients with advanced cancer of the bronchus underwent palliative EB. We compared the coverage of GTV (gross tumor volume), seen in the computed tomography study with intravenous contrast, by the PTV (planning target volume) planned in 3D and 2D. RESULTS: In 2D planning GTV coverage ranged from 15% to 89%. By analyzing the isodose of 90%, it was found that 2D planning covered GTV in 15-35% of the dose. In 3D planning, this coverage changed positively, and ranged from 85% to 100%. The GTV coverage in 3D planning was 100% by definition. In addition, it should be noted that in the 3D planning one can spare critical organs or pacemakers. CONCLUSIONS: Planning for HDR brachytherapy in all locations should be based on dynamic imaging at present, especially in centers that are equipped with CT. Evaluation should be a routine test in treatment planning. The use of CT, even in palliative treatment planning, allows for much better coverage of GTV areas as well, which is very important to reduce radiation doses to critical organs and thereby reduce the toxic effects of treatment.

Surgical resection with adjuvant brachytherapy in soft tissue sarcoma of the extremity - a case report.

PURPOSE: Surgery is the major therapeutic method in soft tissue sarcomas of the extremity (E-STS). Treatment of large high-grade tumours, which resection cannot be performed with a wide safe margin, should include complementary radiation and/or chemo-therapy. Hopefully, the use of adjuvant brachytherapy will improve the prognosis of E-STS. CASE DESCRIPTION: After a long process of diagnosing a tumour in the medial compartment of the thigh, a 65-year-old woman with diagnosed synovial sarcoma underwent a surgery. Compartment resection was performed and the tumour was removed with a 10 mm safety margin of healthy tissue. Adjuvant brachytherapy was delivered with (192)Ir (MicroSelectron, Nucletron Electa Group, Stockholm, Sweden(®)) with 10 Ci of nominal activity to a dose of 55 Gy in 16 days because of large tumour size (99 × 78 × 73 mm) and its proximity to the neurovascular bundle. No complications were reported. The patient was discharged from the hospital on the 28(th) day after the surgery. The wound healed without any complications and the outpatient follow-up is being continued. DISCUSSION: Adjuvant brachytherapy is rarely used after surgical treatment due to its limited accessibility in hospitals with surgical and orthopaedic departments. There are numerous publications proving positive influence of brachytherapy on local control and decreased number of recurrences. The recurrence-free survival time also increased significantly, however no direct impact on the number of distant metastases was found. Treatment is well tolerated and short. The complication rate varies between centres from 5 to 30%. The most common adverse effects include: peripheral neuropathy, skin necrosis and osteonecrosis of the long bones. CONCLUSIONS: Treatment of large soft tissue sarcomas of the extremity (E-STS) should include combination of surgical intervention and external beam radiotherapy or brachytherapy. Adjuvant brachytherapy improves local control rate up to 78%, is well tolerated and rarely causes complications. We couldn't determine which type of adjuvant radiation therapy is more effective.

A search for factors specifying tonotopy implicates DNER in hair-cell development in the chick's cochlea.

The accurate perception of sound frequency by vertebrates relies upon the tuning of hair cells, which are arranged along auditory organs according to frequency. This arrangement, which is termed a tonotopic gradient, results from the coordination of many cellular and extracellular features. Seeking the mechanisms that orchestrate those features and govern the tonotopic gradient, we used expression microarrays to identify genes differentially expressed between the high- and low-frequency cochlear regions of the chick (Gallus gallus). Of the three signaling systems that were represented extensively in the results, we focused on the notch pathway and particularly on DNER, a putative notch ligand, and PTPζ, a receptor phosphatase that controls DNER trafficking. Immunohistochemistry confirmed that both proteins are expressed more strongly in hair cells at the cochlear apex than in those at the base. At the apical surface of each hair cell, the proteins display polarized, mutually exclusive localization patterns. Using morpholinos to decrease the expression of DNER or PTPζ as well as a retroviral vector to overexpress DNER, we observed disturbances of hair-bundle morphology and orientation. Our results suggest a role for DNER and PTPζ in hair-cell development and possibly in the specification of tonotopy.

Imaging electrical resonance in hair cells.

The mechanosensory hair cells of many auditory receptor organs are tuned by an electrical resonance that increases their responses to stimulation over a narrow band of frequencies. The small oscillations of membrane potential characteristic of this phenomenon have previously been detectable only through intracellular electrode measurements, which are laborious and preclude analysis at the level of an entire sensory organ. We used a voltage-sensitive dye to image hair-cell electrical resonance in an intact preparation of the bullfrog's sacculus, a receptor organ sensitive to low-frequency seismic and auditory stimuli. Imaging revealed distinct populations of hair cells whose resonant response varied with the frequency of transepithelial electrical stimulation. Most of the hair cells in the saccular epithelium in vitro were electrically tuned to stimulation at 25-50 Hz. The frequency dependence of the fluorescence signal was sensitive to pharmacological blockade of large-conductance Ca(2+)-sensitive K(+) channels and to enzymatic digestion. At an elevated concentration of Ca(2+), we observed transient fluorescence signals that probably represented action potentials. The stroboscopic imaging and analysis techniques described here present a general approach for studying subthreshold oscillations in electrically excitable cells.

HDR brachytherapy as a solution in recurrences of locally advanced prostate cancer.

PURPOSE: The object of this study was to analyze the outcome of salvage HDR brachytherapy treatment after local failure, for patients with prostate specific antigen (PSA) failure without distant metastasis, after external beam radiation and HDR brachytherapy treatment, or after radical prostatectomy, with or without hormonal therapy. MATERIAL AND METHODS: The group of 115 patients, without distant metastasis, after local failure and external beam radiation, followed by HDR brachytherapy treatment, or after radical prostatectomy, with hormonal therapy and without, have been enrolled to salvage HDR brachytherapy (SBR). All patients had minimum 3 months androgen deprivation therapy before salvage brachytherapy, which was continued until the next 9 months after SBR. Brachytherapy was administered in three 10 Gy fractions with 3 weeks gap between them. Each session of SBR was supported by trans-rectal USG real time pictures. The treatment planning was done on the base of Abacus system from Sauerwein® or with SWIFT system from Nucletron®. The following data were collected: Gleason score, clinical staging, the volume of the prostate, PSA before and after the initial treatment and periodically during the follow-up period. Also the time during which the PSA stays at the nadir level, patient's age and toxicity of treatments were taken into consideration. RESULTS: Doses from external radiotherapy or from HDR brachytherapy were recalculated to equivalent biological dose (EBD). The independence from biochemical progression in our group of patients after retreatment was 46% for patients with PSA ≤ 6 and 18% for patients with PSA > 6. Overall survival for patients with PSA ≤ 6 was 86% and 48% for patients with PSA > 6, respectively. CONCLUSIONS: Salvage prostate brachytherapy (SBR) can be safely performed with acceptable biochemical control and toxicity.

Domain-specific incorporation of noninvasive optical probes into recombinant proteins.

An integrated approach is described that allows the domain-specific incorporation of optical probes into large recombinant proteins. The strategy is the combination of two existing techniques, expressed protein ligation (EPL) and in vivo amino acid replacement of tryptophans with tryptophan (Trp) analogues. The Src homology 3 (SH3) domain from the c-Crk-I adaptor protein has been labeled with a Trp analogue, 7-azatryptophan (7AW), using Escherichia coli Trp auxotrophs. Structural, biochemical, and thermodynamic studies show that incorporation of 7AW does not significantly perturb the structure or function of the isolated domain. Ligation of the 7AW-labeled SH3 domain to the c-Crk-I Src homology 2 (SH2) domain, via EPL, generated the multidomain protein, c-Crk-I, with a domain-specific label. Studies of this labeled protein show that the biochemical and thermodynamic properties of the SH3 domain do not change within the context of a larger multidomain protein. The technology described here is likely to be a useful tool in enhancing our understanding of the behavior of modular domains in their natural context, within multidomain proteins.

Bacterial persistence as a phenotypic switch.

A fraction of a genetically homogeneous microbial population may survive exposure to stress such as antibiotic treatment. Unlike resistant mutants, cells regrown from such persistent bacteria remain sensitive to the antibiotic. We investigated the persistence of single cells of Escherichia coli with the use of microfluidic devices. Persistence was linked to preexisting heterogeneity in bacterial populations because phenotypic switching occurred between normally growing cells and persister cells having reduced growth rates. Quantitative measurements led to a simple mathematical description of the persistence switch. Inherent heterogeneity of bacterial populations may be important in adaptation to fluctuating environments and in the persistence of bacterial infections.