We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not ...occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.
•Positive DSA and crossmatch in ABOi combined liver-kidney transplantation has not been previously reported.•A patient with ABO and crossmatch incompatibilities underwent a successful combined liver-kidney transplantation following preoperative intervention.•We demonstrate that DSA/crossmatch positive and ABO-incompatible individuals could still be organ donor candidates.
The crystal structure and magnetoresponsive properties of Fe-doped MnCoGe alloys have been investigated using x-ray diffraction (XRD) and magnetic measurements. By alloying the Fe-containing ...isostructure compounds into MnCoGe, a magnetostructural transition from paramagnetic austenite to ferromagnetic martensite with large magnetization difference can be realized in a temperature window between the Curie temperatures of the austenite and martensite, resulting in a magnetic-field-induced martensitic transformation and large magnetic-entropy changes. A structural and magnetic phase diagram of Fe-doped MnCoGe alloys is presented.
► Isostructural alloying can manipulate structural stability of Fe-doped MnCoGe alloys. ► A magnetostructural transition was realized in a temperature window between TCA and TCM. ► The remarkable magnetoresponsive properties in Fe-doped MnCoGe alloys were found. ► A structural and magnetic phase diagram of Fe-doped MnCoGe alloys was proposed.
Context.
A link has finally been established between magnetars and fast radio burst (FRB) sources. Within this context, a major issue that remains unresolved pertains to whether sources of ...extragalactic FRBs exhibit X/
γ
-ray outbursts and whether this is correlated with radio activity. If so, the subsequent goal is to identify these sources.
Aims.
We aim to constrain possible X/
γ
-ray burst activity from one of the nearest extragalactic FRB sources currently known. This is to be done over a broad energy range by looking for bursts over a range of timescales and energies that are compatible with those of powerful flares from extragalactic magnetars.
Methods.
We followed up on the observation of the as-yet nearest extragalactic FRB source, located at a mere 149 Mpc distance, namely, the periodic repeater
FRB 180916.J0158+65
. This took place during the active phase between 4 and 7 February 2020, using the Insight–Hard X-ray Modulation Telescope (Insight–HXMT). By taking advantage of the combination of broad-band wavelengths, a large effective area, and several independent detectors at our disposal, we searched for bursts over a set of timescales from 1 ms to 1.024 s with a sensitive algorithm that had been previously characterised and optimised. Moreover, through simulations, we studied the sensitivity of our technique in the released energy-duration phase space for a set of synthetic flares and assuming a range of different energy spectra.
Results.
We constrain the possible occurrence of flares in the 1−100 keV energy band to
E
< 10
46
erg for durations Δ
t
< 0.1 s over several tens of ks exposure.
Conclusions.
We can rule out the occurrence of giant flares similar to the ones that were observed in the few cases of Galactic magnetars. The absence of reported radio activity during our observations prevents us from making any determinations regarding the possibility of simultaneous high-energy emission.
Stimulation of the host immune system is crucial in cancer treatment. In particular, nonspecific immunotherapies, when combined with other traditional therapies such as radiation and chemotherapy, ...may induce immunity against primary and metastatic tumors. In this study, we demonstrate that a novel, non-toxic immunoadjuvant, glycated chitosan (GC), decreases the motility and invasion of mammalian breast cancer cells in vitro and in vivo. Lung metastatic ratios were reduced in 4T1 tumor-bearing mice when intratumoral GC injection was combined with local high-intensity focused ultrasound (HIFU) treatment. We postulate that this treatment modality stimulates the host immune system to combat cancer cells, as macrophage accumulation in tumor lesions was detected after GC-HIFU treatment. In addition, plasma collected from GC-HIFU-treated tumor-bearing mice exhibited tumor-specific cytotoxicity. We also investigated the effect of GC on epithelial-mesenchymal transition-related markers. Our results showed that GC decreased the expression of Twist-1 and Slug, proto-oncogenes commonly implicated in metastasis. Epithelial-cadherin, which is regulated by these genes, was also upregulated. Taken together, our current data suggest that GC alone can reduce cancer cell motility and invasion, whereas GC-HIFU treatment can induce immune responses to suppress tumor metastasis in vivo.
In this paper, temporal and spatial analyses are employed to detect seismo‐ionospheric precursors (SIPs) in the ionospheric total electron content (TEC) during the 16 October 1999 Mw7.1 Hector Mine ...earthquake. To discriminate anomalies caused by global effects, such as solar radiations, magnetic storms, etc., and local effects, such as earthquake, we cross‐examine the GPS TECs and their gradients in the eastward and northward directions at epicenter/centers of the Hector Mine area and the other two reference areas at similar magnetic latitudes in Europe and Japan. Temporal variations of the northward TEC gradient suggest SIPs most likely appearing on days 6–5 before the earthquake. A global search by using the TEC of the global ionosphere map shows that the TEC increase and decrease anomalies continuously and specifically appear around the epicenter on day 5 before the earthquake.
Key Points
Temporal and spatial seismo‐ionospheric precursors
Lithosphere weather of GPS total electron content
Long lasting or duration of earthquake precursors
Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease with high heritability. Although several predisposing genes have been linked to IPAH, the genetic aetiology remains unknown for a ...large number of IPAH cases.
We conducted an exome-wide gene-based burden analysis on two independent case-control studies, including a total of 331 IPAH cases and 10 508 controls. Functional assessments were conducted to analyse the effects of genetic mutations on protein biosynthesis and function.
The gene encoding human bone morphogenetic protein 9 (
) was identified as a novel genetic locus displaying exome-wide association with IPAH in the discovery cohort (OR 18.8; p=1.9×10
). This association was authenticated in the independent replication cohort (p=1.0×10
). Collectively, the rare coding mutations in
occurred in 6.7% of cases, ranking this gene second to
, comprising a combined significance of 2.7×10
(OR 21.2). Intriguingly, the patients with
mutations had lower plasma levels of BMP9 than those without. Functional studies showed that the
mutations led to reduced BMP9 secretion and impaired anti-apoptosis ability in pulmonary arterial endothelial cells.
We identify
as an IPAH culprit gene.
The brown planthopper (BPH), Nilaparvata lugens (Stål) is a resurgent pest of rice crops throughout Asia. We recently discovered that octopamine (OA) and OA2B2 operate in the BPH mating system, where ...it mediates a wide range of molecular, physiological and behavioural changes. Here, we report on outcomes of experiments designed to test the hypothesis that OA/OA2B2 signalling mediates responses to three abiotic stressors, starvation, high temperature (37 °C), and induced oxidative stress. We found per os RNAi‐mediated OA2B2 silencing led to significantly decreased survival, measured in days, following exposure to each of these stressors. We selected a biologically costly process, reproductive biology, as a biotic stressor. Silencing of OA2B2 led to decreased total protein content in ovaries and fat bodies, downregulated expression of vitellogenin (Vg) and Vg receptor (VgR), inhibited fat body Vg protein synthesis, shortened the oviposition period, prolonged the preoviposition period, reduced the number of laid eggs, body weight and female longevity. In addition, the silencing treatments also led to inhibited ovarian development, and ovarian Vg uptake, reduced numbers of egg masses and offspring and lower hatching rates and population growth index. These data support our hypothesis that OA2B2 acts in mediating BPH resistance to biotic and abiotic stressors.
Starvation, high temperatures and oxidative stress‐induced OA2B2 expression in BPH.
Depletion of OA2B2 by RNAi reduced BPH stress resistance under abiotic stresses.
RNAi‐mediated OA2B2 led to reduced number of eggs laid, number of offspring.
Genome-wide association studies have identified over 100 genetic loci for atrial fibrillation (AF); recent work described an association between loss-of-function (LOF) variants in
and early-onset AF.
...We sought to determine the contribution of rare and common genetic variation to AF risk in the general population.
The UK Biobank is a population-based study of 500 000 individuals including a subset with genome-wide genotyping and exome sequencing. In this case-control study, we included AF cases and controls of genetically determined white-European ancestry; analyses were performed using a logistic mixed-effects model adjusting for age, sex, the first 4 principal components of ancestry, empirical relationships, and case-control imbalance. An exome-wide, gene-based burden analysis was performed to examine the relationship between AF and rare, high-confidence LOF variants in genes with ≥10 LOF carriers. A polygenic risk score for AF was estimated using the LDpred algorithm. We then compared the contribution of AF polygenic risk score and LOF variants to AF risk.
The study included 1546 AF cases and 41 593 controls. In an analysis of 9099 genes with sufficient LOF variant carriers, a significant association between AF and rare LOF variants was observed in a single gene,
(odds ratio, 2.71,
=2.50×10
). The association with AF was more significant (odds ratio, 6.15,
=3.26×10
) when restricting to LOF variants located in exons highly expressed in cardiac tissue (
). Overall, 0.44% of individuals carried
variants, of whom 14% had AF. Among individuals in the highest 0.44% of the AF polygenic risk score only 9.3% had AF. In contrast, the AF polygenic risk score explained 4.7% of the variance in AF susceptibility, while
variants only accounted for 0.2%.
Both monogenic and polygenic factors contribute to AF risk in the general population. While rare
variants confer a substantial AF penetrance, the additive effect of many common variants explains a larger proportion of genetic susceptibility to AF.
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