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Beacon Reconstruction Attack: Reconstruction of genomes in genomic data-sharing beacons using summary statistics.

MOTIVATION: Genomic data-sharing beacon protocol, developed by the Global Alliance for Genomics and Health, offers a privacy-preserving mechanism for querying genomic datasets while restricting direct data access. Despite their design, beacons remain vulnerable to privacy attacks. This study introduces a novel privacy vulnerability of the protocol: one can reconstruct large portions of the genomes of all beacon participants by only using the summary statistics reported by the protocol. RESULTS: We introduce a novel optimization-based algorithm that leverages beacon responses and SNP correlations for reconstruction. By optimizing for the SNP correlations and allele frequencies, the proposed approach achieves genome reconstruction with a substantially higher F1-score (70%) compared to baseline methods (45%) on beacons generated using individuals from the HapMap and OpenSNP datasets. We show that reconstructed genomes can be used by downstream applications such as in membership inference attacks against other beacons. Our findings reveal that beacons releasing allele frequencies substantially increase the reconstruction risk, underscoring the need for enhanced privacy-preserving mechanisms to protect genomic data. AVAILABILITY AND IMPLEMENTATION: Our implementation is available at https://github.com/ASAP-Bilkent/Beacon-Reconstruction-Attack.

Genomics

[Surgical treatment of calcanear fractures (103 cases). Reconstruction-arthrodesis, or reconstruction (author's transl)].

In a twelve-year period, 103 calcanear fractures (thalamus) were operated on, either by the Stulz procedure (calcanear Reconstruction-subtalar Arthrodesis [83 cases]), or by Reconstruction (20 cases). During the first seven years, the Stulz procedure had been performed systematically. During the following five years, indications were shaded between 28 reconstruction-arthrodesis and 20 reconstructions. A complete preoperative radiological study, including especially horizontal calcanear tomography enables to precise what type of injuries affects the four different parts of the calcaneus, and to choose between either procedure.

Adolescent

Use of plastipore for ossicular chain reconstruction: an evaluation.

With the exception of stapes prostheses, previous use of implantable alloplastic materials in reconstructing the sound conducting mechanism in middle ear surgery has been uniformly unsuccessful. A new material composed of ultra-high molecular weight polyethylene has been developed as a replacement for middle ear ossicles. This implant, called the Plastipore total ossicular replacement prosthesis (TORP), and the Plastipore drum to the stapes prosthesis were inserted in 87 patients, all of whom had a long history of extensive middle ear disease and/or surgery. One TORP patient was lost to follow-up. The overall average hearing gain was 14.8 db. The overall follow-up was 12.4 months with a range of from 3 to 25 months. Eleven of the 15 patients receiving the drum-to-stapes prosthesis had hearing gain; 55 of 71 patients receiving the TORP had hearing gain. Eight prostheses were extruded. Nine patients had no improvement in hearing. Eight patients had subsequent decrease in hearing after initial gains. All ears are now dry and aerated. Early evaluation appears to demonstrate that the Plastipore prosthesis shows promise for use in difficult reconstructive middle ear problems.

Ear Diseases

[Reconstruction of the injured flexor tendon in the proximal half of the "no man's land" by a modified method (tendon sheath reconstruction using a vein graft)].

On the basis of long years' experiences the "no man's land" has been divided by the author into 2 parts: the proximal and the distal part. For the treatment of the flexor tendon lesions occurred in the distal part of the author advocates his method already published: in the "tendon sheath" formed from the vein its "bridging" by free tendon transplant. If the lesion occurred in the proximal part, the formation of a long "tendon sheath" from a vein and then its "bridging" by long tendon transplant are advocated by the author.

Adult

Robustness of Ancestral Sequence Reconstruction to Among-site and Among-lineage Evolutionary Heterogeneity.

Ancestral sequence reconstruction is typically performed using homogeneous evolutionary models, which assume that the same substitution propensities affect all sites and lineages. These assumptions are routinely violated: heterogeneous structural and functional constraints favor different amino acids at different sites, and these constraints often change among lineages as epistatic substitutions accrue at other sites. To evaluate how violations of the homogeneity assumption affect ancestral sequence reconstruction under realistic conditions, we developed site-specific substitution models and parameterized them using data from deep mutational scanning experiments on three protein families; we then used these models to perform ancestral sequence reconstruction on the empirical alignments and on alignments simulated under heterogeneous conditions derived from the experiments. Extensive among-site and -lineage heterogeneity is present in these datasets, but the sequences reconstructed from empirical alignments are almost identical when heterogeneous or homogeneous models are used for ancestral sequence reconstruction. Using models fit to deep mutational scanning data from distantly related proteins in which mutational effects are very different also has a minimal impact on ancestral sequence reconstruction. The rare differences occur primarily where phylogenetic signal is weak-at fast-evolving sites and nodes connected by long branches. When ancestral sequence reconstruction is performed on simulated data, errors in the reconstructed sequences become more likely as branch lengths increase, but incorporating heterogeneity into the model does not improve accuracy. These data establish that ancestral sequence reconstruction is robust to unincorporated realistic forms of evolutionary heterogeneity, because the primary determinant of ancestral sequence reconstruction is phylogenetic signal, not the substitution model. The best way to improve accuracy is therefore not to develop more elaborate models but to apply ancestral sequence reconstruction to densely sampled alignments that maximize phylogenetic signal at the nodes of interest.

Phylogeny

Technical note: reconstructing dose distributions from manually planned electron boosts in breast radiotherapy.

PURPOSE: In breast radiotherapy, delivery of manually-calculated electron boosts limits retrospective dose-response analyses as dose distribution is unavailable. This work evaluates the feasibility of reconstructing dose distributions from manually planned electron boosts in breast-conserving radiotherapy. METHODS: Only 72 out of 198 breast cancer patients had complete stored dose distributions from sequential electron boosts in the REQUITE study. Arbitrary data from 70/72 patients were used to develop and validate dose reconstruction method. Twenty patients were used to determine optimal parameters for Monte-Carlo-based (MC) electron dose reconstruction on RayStation (v.11B-R), considering CT-calibration curve, MC-history number, andcalculation grid resolution. Remaining 50 patients were used to quantify dose reconstruction accuracy. The similarity between reconstructed and stored dose was evaluated using 3D-gamma index and dosimetric parameters extracted from breast and tumour bed contours. Dose difference location was evaluated using dose-location histogram. RESULTS: Calculation grid resolution significantly impacted electron dose distribution (p&#xa0;<&#xa0;0.01), where the finest grid (0.15&#xa0;cm) showed highest similarity to stored doses. CT-calibration curve and MC-history number had a negligible influence on dose reconstruction. Dosimetric difference between reconstructed and stored doses was&#xa0;<&#xa0;1&#xa0;Gy for breast and tumour bed. Reconstructed dose was achieved&#xa0;>&#xa0;90% gamma passing rate in the validation set. However, around 2.5&#xa0;Gy dose differences were observed at the skin and tissue interface regions. CONCLUSIONS: Retrospective electron boost dose reconstruction is feasible with acceptable accuracy, and could increase data completeness in large cohort studies. Caution is advised when assessing dose near tissue interface and further validation is needed outside the REQUITE dataset.

Electrons

Fault-tolerant pedigree reconstruction from pairwise kinship relations.

MOTIVATION: Pedigrees reconstructed from biologically related ancient genomes have revealed many insights into (pre)history. To our knowledge, all reported ancient pedigrees have been primarily manually reconstructed, as existing pedigree reconstruction methods are ill-suited for the quality and nature of ancient DNA data. RESULTS: We introduce repare, an open-source software method to automatically reconstruct pedigrees from inferred pairwise kinship relations, which are readily obtainable from ancient genomes. This method reconstructs pedigrees by iteratively incorporating pairwise kinship relations into a set of candidate pedigrees, with pruning and sampling to reduce its search space. It optionally considers supporting information such as haplogroups and skeletal age-at-death estimates. We evaluate this method on a variety of simulated pedigrees with varying error rates and missingness. We also use this method to reconstruct several published pedigrees that were originally manually reconstructed; for one, we present a potential alternative topology. repare optionally incorporates user-inferred pedigree constraints, enabling "human-in-the-loop" reconstruction workflows. Especially when used with these user-inferred constraints, we find that repare represents a powerful and flexible tool for ancient pedigree reconstruction. AVAILABILITY AND IMPLEMENTATION: repare is freely available at https://github.com/Narasimhan-Lab/repare. In addition, source code, benchmark scripts, and benchmark results used in this work are archived at https://doi.org/10.5281/zenodo.19716772.

Pedigree

Reconstruction of old radical cavities.

The methods as well as the primary and late results of 74 partial and 93 total reconstructions of old radical cavities were described. In partial reconstructions the tympanic cavity was reconstructed, but the cavity was not eliminated, as it was dry or could be kept dry. In total reconstructions the tympanic cavity and auditory canal were reconstructed, and in most cases the cavity was obliterated, either by muscle or by combined grafts of muscle, tragal cartilage, and homologous septal cartilage. On the basis of the late results, functionally 10--20% poorer than the primary ones, the indications for reconstruction of old radical cavities were discussed. If there is chronic aural discharge, and if the cavity is lined with granulations, the ear can be rendered dry by total reconstruction in 90% of the cases.

Cartilage

Mitral valve replacement versus reconstruction. An analysis of indications and results of mitral valve procedures in a consecutive series of 80 patients.

Case histories of 80 patients undergoing mitral valve procedures over a 2 year period were analyzed to determine the preoperative and intraoperative factors favoring reconstruction. Of 34 patients undergoing valve reconstruction, 31 (90 per cent) were women, and the average age of patients undergoing reconstruction was 41 versus 51 for patients who underwent replacement. Absence of calcification on fluoroscopic study and at operation favored reconstruction, as did the finding of good leaflet mobility by preoperative echocardiograms and operative assessment. Pure lesions, i.e., stenosis or insufficiency, favored reconstruction. In this regard, the use of new annuloplasty techniques has facilitated the surgeon's ability to reconstruct regurgitant mitral valves. No operative deaths and excellent functional and clinical results obtained in 80 per cent of patients undergoing mitral reconstruction justify the aggressive application of this technique in properly selected patients.

Adult

The preparation of graphical and three-dimensional reconstructions of the developing central nervous system.

In the development of the central nervous system morphogenesis and histogenesis are two strongly interdependent aspects. Since the histogenesis can only be investigated on microscopical sections the spatial relations of the various structures are lost. Thus the availability of reliable three-dimensional reconstructions is indispensible. The advantage of the bilateral symmetry of the central nervous system is that it creates the possibility to use the median plane as a natural plane of reference in the piling of the reconstructions, provided the material is sectioned perpendicular to that plane. Such a direction of sectioning is the more advisable, since during the histogenesis the outwards migration of the young neuroblasts mainly is radially orientated. The reconstruction method presented here is based upon a comparison of the median sections of two specimens, which are graphically reconstructed from two different series. Both series are sectioned at right angles to the median plane and also in mutually perpendicular direction. Each resulting optimalized graphically reconstructed median section is used as a reference in the correct piling of the three-dimensional reconstruction of the corresponding series, which consists of polystyrene plates. A prerequisite of the method is an exact orientation of the material during embedding, of which the procedure is described. Secondly the two specimens which yield both series must show a high degree of conformity. In embryological terms this means, that the various developmental stages must be accurately defined. The use of criteria which can only be appropriate when referring to the organ under investigation is argumented. In a discussion on the possibilities and limitations of the method a comparison is made with the reconstruction technique which is based upon the use of artificially introduced outer points of reference.

Animals

Display and visualization of three-dimensional reconstructed anatomic morphology: experience with the thorax, heart, and coronary vasculature of dogs.

A new method, termed reprojection, is used to visualize anatomic morphology contained within three-dimensional reconstructions made up of images of multiple parallel cross sections. This method involves the projection, either orthographically into a plane or radially onto a cylinder, of the volume picture elements (voxels) of the reconstruction. Orthographic reprojection images, formed by mathematically summing the magnitudes of the voxels along selected parallel paths through the reconstructed volume, are analagous to conventional radiographs formed by the passage of an X-ray beam through the volume. The reprojection image is a two-dimensional array of picture elements that is displayed on a television monitor using a digital-to-video scan converter. Also described are the techniques of noninvasive selective tissue dissolution and numerical dissection, whereby obscuring portions of the reconstructed volume are either partially "dissolved" or totally eliminated before reprojection. Utilizing these methods, anatomic information present in a three-dimensional reconstruction but not clearly seen in a reprojection image is rendered visible after removal of superposed structures. The usefulness of these methods is demonstrated utilizing three-dimensional reconstructions of the thorax, heart, and coronary arteries of dogs.

Animals

Study of pole assembly in Bacillus subtilis by computer reconstruction of septal growth zones seen in central, longitudinal thin sections of cells.

The septal growth of Bacillus subtilis 168/s has been studied by making a number of observations from thin sections of cells from exponentially growing cultures. The process was initiated by the formation of a new cross wall under a preexisting layer of cylindrical wall. An annular notch appeared to cut through the overlying wall and presumably allowed the cross wall to split into two layers of peripheral wall. During this initial notching process, two raised bands of wall material were produced which resembled those previously observed in morphological studies of Streptococcus faecalis. Through an improved fixation technique, it was possible to preserve the bands seen in B. subtilis to the extent that they were used as markers to study the subsequent stages of septal growth. These stages included (i) the continued displacement of the two bands from the cross wall (as the two nascent polar surfaces enlarged and as the diameter of the cross wall decreased), (ii) the closure of the cross wall, and (iii) the final severance of the common cross wall connection between two completed poles. To study this process in a more quantitative manner, three-dimensional reconstructions of the envelope observed between pairs of the raised bands were made from axial thin sections of cells. The process of reconstruction was based on a technique by which x, y coordinates were taken from thin sections and were rotated around the cell's central axis. These reconstructions were used to estimate the surface area or volume of the reconstructed zones or their parts. A round of septal growth was then simulated by arranging 118 reconstructions in order of increasing surface area or volume. The topology of the process was studied by noting how various measurements of septal thickness, length, surface area, and volume varied as a function of increasing septal zone size. This analysis was based on several assumptions, of which three of the most important are: (i) the bands produced by the initial notching process are markers which separate septal from cylindrical wall growth; (ii) a septal zone observed between pairs of bands is made up of two nascent poles and a single cross wall; and (iii) as septal zones develop in terms of relative age they increase in size (volume or surface area) or amount of wall. The data suggested that the S. faecalis model of surface growth (in which polar growth occurs through a regulated constrictive separation and expansion of a cross wall) also seems applicable to the pattern of septal growth observed here for B. subtilis. This was indicated from measurements which showed that increases in the size of nascent polar surfaces were correlated with decreases in cross wall diameter. An explanation of these observations may be that decreases in cross wall diameter were due to a progressive splitting of the cross wall that removed surface from the outer circumference of the cross wall and converted it into new polar surface. Calculations further suggested that if the poles of B. subtilis were made by this model a sizeable and variable increase in surface area of the cross wall would also be required to convert these separating cross wall layers into two curved polar structures. Measurements of wall thickness taken from various locations within septal zones indicated that while the thickness of the polar wall of B. subtilis was constant over its surface, the width of the cross wall varied considerably during a round of synthesis. Again, one of the simplest explanations compatible with these observations and those previously made in S. faecalis is that the B. subtilis cross wall is brought to a constant thickness (possibly by remodeling or precursor addition) before or during separation. Although most observations made from the reconstruction of the septal zones of B. subtilis may fit the S. faecalis model of surface growth, differences in the pattern of septal growth were seen when the two organisms were compared. These have been discussed in terms of differences in the regulation of their respective septal growth sites and basic mechanisms of wall assembly and modification.

Bacillus subtilis