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Porous Nitinol with a three-dimensional anisotropic interconnective open pore structure has been successfully produced by the combustion synthesis (CS) of elemental Ni and Ti powders. The resulting product can be tailored to closely match the stiffness of cancellous bone to minimize stress shielding. The average elastic modulus was approximately 1 GPa for a porosity of 60 vol% and the average pore size of 100-500 µm. The low elastic modulus meets the basic demand for orthopedic bone ingrowth applications. Furthermore, porous Nitinol was composed of cubic (austenitic) and monoclinic (martensitic) NiTi compounds without the presence of Ni metal or Ni-rich phases. The resulting product exhibits excellent corrosion resistance with breakdown potentials above 750mV. An ovine study in cortical sites of the tibia demonstrated rapid osseointegration into the porous strucutre as early as two weeks and complete bone growth across the implant at six weeks. A separate ovine study showed complete through-growth of bone at four months using a lumbar interbody fusion model, substantiating the use of porous Nitinol as an implant material for applications in the spine. Porous Nitinol is thus a promising biomaterial with proven biocompatibility and exceptional osseointegration performance which may enhance the healing process and promote long-term fixation, making it a strong candidate for a wide range of orthopedic implant applications.

Introduction: In our former study, we had validated the previously developed predictive model for in-hospital falls (Saga fall risk model) using eight simple factors (age, sex, emergency admission, department of admission, use of hypnotic medications, history of falls, independence of eating, and Bedriddenness ranks [BRs]), proving its high reliability. We found that only admission to the neurosurgery department, history of falls, and BRs had significant relationships with falls. In the present study, we aimed to clarify whether each of these three items had a significant relationship with falls in a different group of patients. Methods: This was a single-center based, retrospective study in an acute care hospital in a rural city of Japan. We enrolled all inpatients aged 20 years or older admitted from April 2015 to March 2018. We randomly selected patients to fulfill the required sample size. We performed multivariable logistic regression analysis using forced entry on the association between falls and each of the eight items in the Saga fall risk model 2. Results: A total of 2932 patients were randomly selected, of whom 95 (3.2%) fell. The median age was 79 years, and 49.9% were men. Multivariable analysis showed that female sex (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.39-0.93, p = 0.022), having a history of falls (OR 1.9, 95% CI 1.16-2.99, p = 0.010), requiring help with eating (OR 1.9, 95% CI 1.12-3.35, p = 0.019), BR of A (OR 6.6, 95% CI 2.82-15.30, p < 0.001), BR of B (OR 7.5, 95% CI 2.95-19.06, p < 0.001), and BR of C (OR 4.1, 95% CI 1.53-11.04, p = 0.005 (were significantly associated with falls. Conclusion: History of falls and BRs were independently associated with in-hospital falls. Keywords: bedridden, Bedriddenness ranks, fall, predictive model, validation, Saga fall risk model 2

Background: It is unclear how much effort Japanese university general medicine (GM) departments, which teach basic medical skills and have a high affinity for clinical practice, devote to medical education, particularly undergraduate education. This study aimed to clarify the contribution of GM departments of Japanese universities to medical education. Patients and Methods: This was a questionnaire-based descriptive study of GM departments of Japanese universities. We sent the questionnaire created using Google Forms by email, and the universities responded by Internet. The department chairperson of the universities' main hospital was responsible for completing the questionnaire. It covered the number of staff, inpatients over the previous 3 years, affiliated hospitals, classroom lectures, and practical training sessions per year for each academic year in medical faculty and students accepted for clinical clerkship. Items also included the effort for clinical training, research, and education and the effort for undergraduate, initial clinical residency, and specialty program training. Results: In all, 46 of 71 universities responded, and we included 43 in our analysis. The median number of medical staff was 7; the median number of inpatients over the previous 3 years was 76. The median number of classroom lectures of the GM department was 1 for 1st-year, 5 for 3rd-year, 9 for 4th-year, and 0 for 2nd-, 5th-, and 6th-year students. The median total number of accepted students for clinical clerkship was 120. The median educational effort of the GM department was 30. With total educational effort set at 100, the median effort for undergraduate education was 45, for postgraduate residency 30, and for specialty program training 20. Conclusion: The undergraduate medical education by GM departments of Japanese universities was provided mainly in clinical settings for almost all medical students. A focus on exposing students to GM in early academic years would improve the educational environment. Keywords: clinical clerkship, general medicine, medical education, specialty program, university

Site-specific DNA recombination is important for basic cellular functions including viral integration, control of gene expression, production of genetic diversity and segregation of newly replicated chromosomes, and is used by bacteriophage λ to integrate or excise its genome into and out of the host chromosome. λ recombination is carried out by the bacteriophage-encoded integrase protein (λ-int) together with accessory DNA sites and associated bending proteins that allow regulation in response to cell physiology. Here we report the crystal structures of λ-int in higher-order complexes with substrates and regulatory DNAs representing different intermediates along the reaction pathway. The structures show how the simultaneous binding of two separate domains of λ-int to DNA facilitates synapsis and can specify the order of DNA strand cleavage and exchange. An intertwined layer of amino-terminal domains bound to accessory (arm) DNAs shapes the recombination complex in a way that suggests how arm binding shifts the reaction equilibrium in favour of recombinant products.

The educational effects of a hands-on clinical clerkship on medical students at the Department of General medicine of Japanese university hospitals remain to be clarified. This study aimed to determine how such education affects medical students' self-evaluation of their clinical skills. We enrolled 5th-year-grade students at the Department of General Medicine, Saga University Hospital, Japan in 2017. The students were divided into those who were going to have Japanese traditional-style observation-based training mainly in the outpatient clinic (Group O) and those in the 2018, new-style, hands-on clinical clerkship as one of the group practice members in outpatient and inpatient clinics (Group H). A questionnaire survey using the 4-point Likert scale for self-evaluation of the students' clinical skills at the beginning and the end of their training was conducted in both groups. The pre- and post-training scores of each item in both groups were compared and analyzed using the Mann-Whitney test. All 99 students in Group O and 121 of 123 students in Group H answered the questionnaires. The response rate was 99%. Two items regarding the abilities of \"can perform a systemic physical examination quickly and efficiently\" and \"can clearly explain the current medical condition, therapeutic options, or risks associated with treatment, and discuss the process for obtaining informed consent\" showed higher scores in the post-training survey in Group H than in Group O. There were no differences in these scores in the pre-training survey between the two groups. A hands-on clinical clerkship at the Department of General medicine in a university hospital in Japan provided medical students with higher self-confidence in their skills of performing a physical examination and better understanding of patients' treatment options and the process of informed consent than observation-based training.

Recently, successful predictions using machine learning (ML) algorithms have been reported in various fields. However, in traumatic brain injury (TBI) cohorts, few studies have examined modern ML algorithms. To develop a simple ML model for TBI outcome prediction, we conducted a performance comparison of nine algorithms: ridge regression, least absolute shrinkage and selection operator (LASSO) regression, random forest, gradient boosting, extra trees, decision tree, Gaussian naïve Bayes, multi-nomial naïve Bayes, and support vector machine. Fourteen feasible parameters were introduced in the ML models, including age, Glasgow Coma Scale (GCS), systolic blood pressure (SBP), abnormal pupillary response, major extracranial injury, computed tomography (CT) findings, and routinely collected laboratory values (glucose, C-reactive protein [CRP], and fibrin/fibrinogen degradation products [FDP]). Data from 232 patients with TBI were randomly divided into a training sample (80%) for hyperparameter tuning and validation sample (20%). The bootstrap method was used for validation. Random forest demonstrated the best performance for in-hospital poor outcome prediction and ridge regression for in-hospital mortality prediction: the mean statistical measures were 100% sensitivity, 72.3% specificity, 91.7% accuracy, and 0.895 area under the receiver operating characteristic curve (AUC); and 88.4% sensitivity, 88.2% specificity, 88.6% accuracy, and 0.875 AUC, respectively. Based on the feature selection method using the tree-based ensemble algorithm, age, Glasgow Coma Scale, fibrin/fibrinogen degradation products, and glucose were identified as the most important prognostic factors for poor outcome and mortality. Our results indicate the relatively good predictive performance of modern ML for TBI outcome. Further external validation is required for more heterogeneous samples to confirm our results.

Crystal structures of human APOBEC3A and a chimera of APOBEC3B and APOBEC3A bound to ssDNA reveal an unanticipated ‘U-shaped’ binding mode and provide insight into target selectivity. APOBEC-catalyzed cytosine-to-uracil deamination of single-stranded DNA (ssDNA) has beneficial functions in immunity and detrimental effects in cancer. APOBEC enzymes have intrinsic dinucleotide specificities that impart hallmark mutation signatures. Although numerous structures have been solved, mechanisms for global ssDNA recognition and local target-sequence selection remain unclear. Here we report crystal structures of human APOBEC3A and a chimera of human APOBEC3B and APOBEC3A bound to ssDNA at 3.1-Å and 1.7-Å resolution, respectively. These structures reveal a U-shaped DNA conformation, with the specificity-conferring −1 thymine flipped out and the target cytosine inserted deep into the zinc-coordinating active site pocket. The −1 thymine base fits into a groove between flexible loops and makes direct hydrogen bonds with the protein, accounting for the strong 5′-TC preference. These findings explain both conserved and unique properties among APOBEC family members, and they provide a basis for the rational design of inhibitors to impede the evolvability of viruses and tumors.

A bstract We present measurements of the branching fractions for the decays B → Kμ + μ − and B → Ke + e − , and their ratio ( R K ), using a data sample of 711 fb − 1 that contains 772 × 10 6 B B ¯ events. The data were collected at the ϒ(4 S ) resonance with the Belle detector at the KEKB asymmetric-energy e + e − collider. The ratio R K is measured in five bins of dilepton invariant-mass-squared ( q 2 ): q 2 ∈ (0 . 1 , 4 . 0) , (4 . 00 , 8 . 12) , (1 . 0 , 6 . 0), (10 . 2 , 12 . 8) and ( > 14 . 18) GeV 2 /c 4 , along with the whole q 2 region. The R K value for q 2 ∈ (1 . 0 , 6 . 0) GeV 2 /c 4 is 1.03 − 0.24 + 0.28 ± 0 . 01. The first and second uncertainties listed are statistical and systematic, respectively. All results for R K are consistent with Standard Model predictions. We also measure CP -averaged isospin asymmetries in the same q 2 bins. The results are consistent with a null asymmetry, with the largest difference of 2.6 standard deviations occurring for the q 2 ∈ (1 . 0 , 6 . 0) GeV 2 /c 4 bin in the mode with muon final states. The measured differential branching fractions, d ℬ /dq 2 , are consistent with theoretical predictions for charged B decays, while the corresponding values are below the expectations for neutral B decays. We have also searched for lepton-flavor-violating B → Kμ ± e ∓ decays and set 90% confidence-level upper limits on the branching fraction in the range of 10 − 8 for B + → K + μ ± e ∓ , and B 0 → K 0 μ ± e ∓ modes.

A bstract Charged lepton flavor violation is forbidden in the Standard Model but possible in several new physics scenarios. In many of these models, the radiative decays τ ± → ℓ ± γ ( ℓ = e, μ ) are predicted to have a sizeable probability, making them particularly interesting channels to search at various experiments. An updated search via τ ± → ℓ ± γ using full data of the Belle experiment, corresponding to an integrated luminosity of 988 fb − 1 , is reported for charged lepton flavor violation. No significant excess over background predictions from the Standard Model is observed, and the upper limits on the branching fractions, B ( τ ± → μ ± γ ) ≤ 4 . 2 × 10 − 8 and B ( τ ± → e ± γ ) ≤ 5 . 6 × 10 − 8 , are set at 90% confidence level.

Hyper-Kamiokande consists of two identical water-Cherenkov detectors of total 520 kt, with the first one in Japan at 295 km from the J-PARC neutrino beam with 2.5$^\\circ$ off-axis angles (OAAs), and the second one possibly in Korea at a later stage. Having the second detector in Korea would benefit almost all areas of neutrino oscillation physics, mainly due to longer baselines. There are several candidate sites in Korea with baselines of 1000–1300 km and OAAs of 1$^\\circ$–3$^\\circ$. We conducted sensitivity studies on neutrino oscillation physics for a second detector, either in Japan (JD $\\times$ 2) or Korea (JD + KD), and compared the results with a single detector in Japan. Leptonic charge–parity (CP) symmetry violation sensitivity is improved, especially when the CP is non-maximally violated. The larger matter effect at Korean candidate sites significantly enhances sensitivities to non-standard interactions of neutrinos and mass ordering determination. Current studies indicate the best sensitivity is obtained at Mt. Bisul (1088 km baseline, $1.3^\\circ$ OAA). Thanks to a larger (1000 m) overburden than the first detector site, clear improvements to sensitivities for solar and supernova relic neutrino searches are expected.