Early intestinal obstruction after infliximab therapy in Crohn’s disease

There is scarce knowledge on early intestinal obstruction in Crohn’s disease (CD) after infliximab treatment. Therefore, we describe two cases of early intestinal obstruction in a series of 46 CD patients treated with infliximab. Both our two cases were 21-year-old men with newly diagnosed CD who were diagnosed with perianal disease 2 years previously. They were suffering from diarrhea and abdominal pain, but there were no symptoms indicating bowel obstruction. Radiographic studies revealed stenotic sites in the terminal ileum in both cases. In both cases, infliximab 300 mg was infused, after which their abnormal laboratory data as well as symptoms such as diarrhea and abdominal pain clearly improved. However, on the 11th or 13th day post-treatment, they presented abdominal distension with air-fluid levels on imaging studies. Ileocolonic resection was performed in both cases. Early intestinal obstruction after infliximab therapy is characterized by initial improvement of the symptoms and the laboratory data, which is soon followed by clinical deterioration. This outcome indicates that infliximab is so swiftly effective that the healing process tapers the stenotic site, resulting in bowel obstruction. Thus, although unpleasant and severe, the obstruction cannot be considered as a side effect but rather a consequence of infliximab’s efficacy. CD patients with intestinal stricture, particularly the penetrating type with stricture, should be well informed about the risk of developing intestinal obstruction after infliximab therapy and the eventual need for surgical intervention

A Countermeasure Method Using Poisonous Data Against Poisoning Attacks on IoT Machine Learning

In the modern world, several areas of our lives can be improved, in the form of diverse additional dimensions, in terms of quality, by machine learning. When building machine learning models, open data are often used. Although this trend is on the rise, the monetary losses since the attacks on machine learning models are also rising. Preparation is, thus, believed to be indispensable in terms of embarking upon machine learning. In this field of endeavor, machine learning models may be compromised in various ways, including poisoning attacks. Assaults of this nature involve the incorporation of injurious data into the training data rendering the models to be substantively less accurate. The circumstances of every individual case will determine the degree to which the impairment due to such intrusions can lead to extensive disruption. A modus operandi is proffered in this research as a safeguard for machine learning models in the face of the poisoning menace, envisaging a milieu in which machine learning models make use of data that emanate from numerous sources. The information in question will be presented as training data, and the diversity of sources will constitute a barrier to poisoning attacks in such circumstances. Every source is evaluated separately, with the weight of each data component assessed in terms of its ability to affect the precision of the machine learning model. An appraisal is also conducted on the basis of the theoretical effect of the use of corrupt data as from each source. The extent to which the subgroup of data in question can undermine overall accuracy depends on the estimated data removal rate associated with each of the sources described above. The exclusion of such isolated data based on this figure ensures that the standard data will not be tainted. To evaluate the efficacy of our suggested preventive measure, we evaluated it in comparison with the well-known standard techniques to assess the degree to which the model was providing accurate conclusions in the wake of the change. It was demonstrated during this test that when the innovative mode of appraisal was applied, in circumstances in which 17% of the training data are corrupt, the degree of precision offered by the model is 89%, in contrast to the figure of 83% acquired through the traditional technique. The corrective technique suggested by us thus boosted the resilience of the model against harmful intrusion

Measurement of a Phase of a Radio Wave Reflected from Rock Salt and Ice Irradiated by an Electron Beam for Detection of Ultra-High-Energy Neutrinos

We have found a radio-wave-reflection effect in rock salt for the detection of ultra-high energy neutrinos which are expected to be generated in Greisen, Zatsepin, and Kuzmin (GZK) processes in the universe. When an UHE neutrino interacts with rock salt or ice as a detection medium, a shower is generated. That shower is formed by hadronic and electromagnetic avalanche processes. The energy of the UHE neutrino shower converts to thermal energy through ionization processes. Consequently, the temperature rises along the shower produced by the UHE neutrino. The refractive index of the medium rises with temperature. The irregularity of the refractive index in the medium leads to a reflection of radio waves. This reflection effect combined with the long attenuation length of radio waves in rock salt and ice would yield a new method to detect UHE neutrinos. We measured the phase of the reflected radio wave under irradiation with an electron beam on ice and rock salt powder. The measured phase showed excellent consistence with the power reflection fraction which was measured directly. A model taking into account the temperature change explained the phase and the amplitude of the reflected wave. Therefore the reflection mechanism was confirmed. The power reflection fraction was compared with that calculated with the Fresnel equations, the ratio between the measured result and that obtained with the Fresnel equations in ice was larger than that of rock salt.Comment: 6 Pages, 5th International Workshop on Acoustic and Radio EeV Neutrino Detection Activitie

Sideward Peak of Intermediate Mass Fragments in High Energy Proton Induced Reactions

Intermediate mass fragment (IMF) formation in the 12 GeV proton induced reaction on Au target is analyzed by using a combined framework of a transport model (JAM/MF) and a newly developed non-equilibrium percolation (NEP) model. In this model, we can well reproduce the mass distribution of fragments. In addition, the sideward peaked angular distribution would emerge under the condition that the fragment formation time is very short, around 20 fm/c. Within this short time period, the un-heated part of the residual nucleus is kept to have doughnut shape, then the Coulomb repulsion from this shape strengthens the sideward peak of IMF.Comment: 22 pages, Latex, 6 embedded PS figure

ACTN1 Mutations Cause Congenital Macrothrombocytopenia

Congenital macrothrombocytopenia (CMTP) is a heterogeneous group of rare platelet disorders characterized by a congenital reduction of platelet counts and abnormally large platelets, for which CMTP-causing mutations are only found in approximately half the cases. We herein performed whole-exome sequencing and targeted Sanger sequencing to identify mutations that cause CMTP, in which a dominant mode of transmission had been suspected but for which no known responsible mutations have been documented. In 13 Japanese CMTP-affected pedigrees, we identified six (46%) affected by ACTN1 variants cosegregating with CMTP. In the entire cohort, ACNT1 variants accounted for 5.5% of the dominant forms of CMTP cases and represented the fourth most common cause in Japanese individuals. Individuals with ACTN1 variants presented with moderate macrothrombocytopenia with anisocytosis but were either asymptomatic or had only a modest bleeding tendency. ACTN1 encodes α-actinin-1, a member of the actin-crosslinking protein superfamily that participates in the organization of the cytoskeleton. In vitro transfection experiments in Chinese hamster ovary cells demonstrated that altered α-actinin-1 disrupted the normal actin-based cytoskeletal structure. Moreover, transduction of mouse fetal liver-derived megakaryocytes with disease-associated ACTN1 variants caused a disorganized actin-based cytoskeleton in megakaryocytes, resulting in the production of abnormally large proplatelet tips, which were reduced in number. Our findings provide an insight into the pathogenesis of CMTP

ABCC ゲンバク ショウガイ チョウサ イインカイ ブンショ オ ソザイ ニ シタ シリョウ ガゾウ デジタル アーカイビング モデル ノ サクセイ ニ カンスル ケンキュウ

研究報

Combined landscape of single-nucleotide variants and copy number alterations in clonal hematopoiesis

クローン性造血の臨床予後への影響を解明 --遺伝子変異とコピー数異常の統合的な知見--. 京都大学プレスリリース. 2021-07-09.Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11, 234 individuals without HM from the BioBank Japan cohort, including 672 individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH