Successful management of primary splenic pregnancy: a case report and review of literature.

Ectopic pregnancy is defined as dislocation of a fertilized ovum anywhere other than in the cavity of uterus. Generally, the common site for dislocation is within fallopian tube, accounting for 95.5% of all ectopic gestations. Abdominal pregnancy is rare with a potentially life-threatening variation that resides within peritoneal cavity and the primary splenic pregnancy is even rarer. This report describes a patient with primary splenic pregnancy, who was successfully managed after splenectomy.

Unmet information needs and clinical characteristics in patients with precancerous oral lesions.

The purpose of this study was to investigate associated factors of the unmet information needs of patients with precancerous oral lesions. For this cross-sectional descriptive study, we recruited patients with precancerous oral lesions from the otolaryngology outpatient department of a single medical centre in central Taiwan. Patients were assessed using a set of structure questionnaires to measure patients' state anxiety levels, attitudes towards cancer prevention and need for information. Patients' anxiety and attitudes towards cancer prevention were evaluated based on unmet needs and associated factors were determined. Among the 106 subjects surveyed, the most prominent unmet information needs were about obtaining the test results as soon as possible. Patients with precancerous oral lesions who had high levels of state anxiety, long duration of time since quitting betel nut chewing and were without a history of oral cancer were more likely to have unmet information needs. A high level of anxiety about precancerous oral lesions was more prevalent among patients with unmet information needs than among those whose information needs were met. Health education and individual counselling should be provided to satisfy the information needs of this population.

[Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research].

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

CURB-65 score predicted mortality in community-acquired pneumonia better than IDSA/ATS minor criteria in a low-mortality-rate setting.

The CURB-65 scoring system performs well at identifying patients with pneumonia who have a low risk of death. Whether it predicts mortality in community-acquired pneumonia (CAP) better than the 2007 Infectious Disease Society of America (IDSA)/American Thoracic Society (ATS) minor criteria in low-mortality-rate settings is not clear. The purpose of this study was to determine the hypothesis.A total of 1,230 adult inpatients admitted to our hospital from 2005 to 2009 for CAP were reviewed retrospectively.The hospital mortality was 1.3 %. Percentage mortality increased significantly with CURB-65 score and the increasing number of IDSA/ATS minor criteria present. The number of CURB-65 criteria or IDSA/ATS minor criteria present had significant increased odds ratios for mortality of 7.547 and 2.711, respectively. The sensitivities of a CURB-65 score of ≥ 3 and the presence of ≥ 3 minor criteria in predicting mortality was 25 % and 37.5 %, which increased to 75 % and 62.5 %, while the cut-off values reduced to ≥ 2 criteria, respectively. The area under the receiver operating characteristic curve for CURB-65 was greater than the corresponding area for IDSA/ATS minor criteria in predicting hospital mortality (0.915 vs. 0.805, p = 0.0091).CURB-65 score predicted hospital mortality better than IDSA/ATS minor criteria, and a CURB-65 score of ≥ 2 or the presence of ≥ 2 minor criteria might be more valuable cut-off values for "severe" CAP in a low-mortality-rate setting.

Structural signature of plastic deformation in metallic glasses.

The structure feature of a model CuZr metallic glass during deformation is investigated by molecular dynamics simulations. A spatially heterogeneous irreversible rearrangement is observed in terms of nonaffine displacement. We find that regions with smaller nonaffine displacement have more Voronoi pentagons, while in those with larger nonaffine displacement other types of faces are more populated. We use the degree of local fivefold symmetry (LFFS) as the structural indicator to predict plastic deformation of local structures and find that the plastic events prefer to be initiated in regions with a lower degree of LFFS and propagate toward regions with a higher degree of LFFS.

RmpA regulation of capsular polysaccharide biosynthesis in Klebsiella pneumoniae CG43.

Sequence analysis of the large virulence plasmid pLVPK in Klebsiella pneumoniae CG43 revealed the presence of another mucoid factor encoding gene rmpA besides rmpA2. Promoter activity measurement indicated that the deletion of rmpA reduced K2 capsular polysaccharide (CPS) biosynthesis, resulting in decreased colony mucoidy and virulence in mice. Introduction of a multicopy plasmid carrying rmpA restored CPS production in the rmpA or rmpA2 mutant but not in the rcsB mutant. Transformation of the rmpA deletion mutant with an rcsB-carrying plasmid also failed to enhance CPS production, suggesting that a cooperation of RmpA with RcsB is required for regulatory activity. This was further corroborated by the demonstration of in vivo interaction between RmpA and RcsB using two-hybrid analysis and coimmunoprecipitation analysis. A putative Fur binding box was only found at the 5' noncoding region of rmpA. The promoter activity analysis indicated that the deletion of fur increased the rmpA promoter activity. Using electrophoretic mobility shift assay, we further demonstrated that Fur exerts its regulatory activity by binding directly to the promoter. As a result, the fur deletion mutant exhibited an increase in colony mucoidy, CPS production, and virulence in mice. In summary, our results suggested that RmpA activates CPS biosynthesis in K. pneumoniae CG43 via an RcsB-dependent manner. The expression of rmpA is regulated by the availability of iron and is negatively controlled by Fur.

Correlation between Klebsiella pneumoniae carrying pLVPK-derived loci and abscess formation.

Klebsiella pneumoniae-caused liver abscess (KLA) is an emerging infectious disease. However, factors other than K1-specific loci that contribute to the pathogenesis of this disease have not been identified. pLVPK is a 219,385-bp plasmid of K. pneumoniae CG43, an invasive K2 strain associated with KLA. We aimed in this study to evaluate the involvement of pLVPK in K. pneumoniae virulence and its clinical significance in abscess formation. A pLVPK-cured CG43 was isolated and its virulence was examined in a mouse model. The prevalence of pLVPK-derived loci terW, iutA, rmpA, silS, and repA was investigated in 207 clinical isolates by screening with specific primers. Loss of pLVPK abolished the ability of K. pneumoniae to disseminate into extraintestinal sites and, consequently, attenuated abscess formation in mice. Primary K. pneumoniae abscess isolates (n = 94) were more likely to be terW (+)-iutA (+)-rmpA (+)-silS (+) than those related to non-abscess infections (n = 113) (62% vs. 27%; p < 0.0001). Logistic regression analysis indicated that the presence of the terW-rmpA-iutA-silS loci was a significant risk factor (odds ratio, 4.12; 95% confidence interval, 2.02-8.4; p < 0.0001) for abscess formation. pLVPK is a determinant for K. pneumoniae virulence and infection with strains carrying the pLVPK-derived terW-rmpA-iutA-silS loci may predispose patients to abscess formation.

Determination of interatomic coupling between two-dimensional crystals using angle-resolved photoemission spectroscopy.

Lack of directional bonding between two-dimensional crystals like graphene or monolayer transition metal dichalcogenides provides unusual freedom in the selection of components for vertical van der Waals heterostructures. However, even for identical layers, their stacking, in particular the relative angle between their crystallographic directions, modifies properties of the structure. We demonstrate that the interatomic coupling between two two-dimensional crystals can be determined from angle-resolved photoemission spectra of a trilayer structure with one aligned and one twisted interface. Each of the interfaces provides complementary information and together they enable self-consistent determination of the coupling. We parametrise interatomic coupling for carbon atoms by studying twisted trilayer graphene and show that the result can be applied to structures with different twists and number of layers. Our approach demonstrates how to extract fundamental information about interlayer coupling in a stack of two-dimensional crystals and can be applied to many other van der Waals interfaces.

The association between subclass-specific IgG Fc N-glycosylation profiles and hypertension in the Uygur, Kazak, Kirgiz, and Tajik populations.

Hypertension results from the interaction of genetic and acquired factors. IgG occurs in the form of different subclasses, of which the effector functions show significant variation. The detailed differences between the glycosylation profiles of the individual IgG subclasses may be lost in a profiling method for total IgG N-glycosylation. In this study, subclass-specific IgG Fc glycosylation profile was investigated in the four northwestern Chinese minority populations, namely, Uygur (UIG), Kazak (KZK), Kirgiz (KGZ), and Tajik (TJK), composed of 274 hypertensive patients and 356 healthy controls. The results showed that ten directly measured IgG N-glycan traits (i.e., IgG1G0F, IgG2G0F, IgG2G1FN, IgG2G1FS, IgG2G2S, IgG4G0F, IgG4G1FS, IgG4G1S, IgG4G2FS, and IgG4G2N) representing galactosylation and sialylation are significantly associated with hypertension, with IgG4 consistently showing weaker associations of its sialylation, across the four ethnic groups. We observed a modest improvement on the AUC of ROC curve when the IgG Fc N-glycan traits are added into the glycan-based model (difference between AUCs, 0.044, 95% CI: 0.016-0.072, P = 0.002). The AUC of the diagnostic model indicated that the subclass-specific IgG Fc N-glycan profiles provide more information reinforcing current models utilizing age, gender, BMI, and ethnicity, and demonstrate the potential of subclass-specific IgG Fc N-glycosylation profiles to serve as a biomarker for hypertension. Further research is however required to determine the additive value of subclass-specific IgG Fc N-glycosylation on top of biomarkers, which are currently used.

A gain-of-function mutation in TNFRSF13B is a candidate for predisposition to familial or sporadic immune thrombocytopenia.

Essentials Positive family histories suggest the existence of hereditary immune thrombocytopenia (ITP). The predisposing gene for familial ITP was screened in two familial ITP patients. The G76S mutation on TNFRSF13B led to immune dysfunction and induced megakaryocyte apoptosis. The G76S mutation on TNFRSF13B is a gain-of-function mutation and a predisposing variant for ITP. SUMMARY: Background Most immune thrombocytopenia (ITP) is sporadic but a positive family history of ITP in some patients suggests that hereditary forms exist. Because of the rarity of familial ITP families available for study and the heterogeneity of sporadic ITP, family linkage analysis or genome-wide association studies are limited. Objectives Based on one ITP pedigree, we try to identify the predisposing gene in familial or sporadic ITP and reveal the way in which it causes thrombocytopenia. Methods Gene expression profiling analysis and whole-exome sequencing were performed on samples from family members with ITP, sporadic ITP cases and healthy individuals. We also evaluated the influence of potential pathogenic mutation on immune function and megakaryocyte apoptosis. Results Whole-exome sequencing identified a potential pathologic p.G76S heterozygous mutation on the TNFRSF13B gene in familial ITP patients. ITP patients harboring the G76S mutation displayed an upregulated 'cytokine-cytokine receptor interaction' signal, increased serum TNFα, IL-17α, IFNγ and BAFF levels, and enhanced binding capacity of APRIL ligand to B cells. Additionally, Epstein-Barr virus (EBV)-transformed B cells with the G76S mutation could induce human megakaryocyte line (Meg-01) apoptosis significantly. Conclusion p.G76S mutation on the TNFRSF13B gene is responsible for ITP, and is a genetic predisposing factor for familial or sporadic ITP.

Heterogeneous diffusion, viscosity, and the Stokes-Einstein relation in binary liquids.

We investigate the origin of the breakdown of the Stokes-Einstein relation (SER) between diffusivity and viscosity in undercooled melts. A binary Lennard-Jones system, as a model for a metallic melt, is studied by molecular dynamics. A weak breakdown at high temperatures can be understood from the collectivization of motion, seen in the isotope effect. The strong breakdown at lower temperatures is connected to an increase in dynamic heterogeneity. On relevant time scales some particles diffuse much faster than the average or than predicted by the SER. The van Hove self-correlation function allows one to unambiguously identify slow particles. Their diffusivity is even less than predicted by the SER. The time span of these particles being slow particles, before their first conversion to be a fast one, is larger than the decay time of the stress correlation. The contribution of the slow particles to the viscosity rises rapidly upon cooling. Not only the diffusion but also the viscosity shows a dynamically heterogeneous scenario. We can define a "slow" viscosity. The SER is recovered as the relation between slow diffusivity and slow viscosity.

Decoupled length scales for diffusivity and viscosity in glass-forming liquids.

The growth of the characteristic length scales both for diffusion and viscosity is investigated by molecular dynamics utilizing the finite-size effect in a binary Lennard-Jones mixture. For those quantities relevant to the diffusion process (e.g., the hydrodynamic value and the spatial correlation function), a strong system-size dependence is found. In contrast, it is weak or absent for the shear relaxation process. Correlation lengths are estimated from the decay of the spatial correlation functions. We find the length scale for viscosity decouples from the one of diffusivity, featured by a saturated length even in high supercooling. This temperature-independent behavior of the length scale is reminiscent of the unapparent structure change upon supercooling, implying the manifestation of configuration entropy. Whereas for the diffusion process, it is manifested by relaxation dynamics and dynamic heterogeneity. The Stokes-Einstein relation is found to break down at the temperature where the decoupling of these lengths happens.

Velocity autocorrelation function in supercooled liquids: Long-time tails and anomalous shear-wave propagation.

Molecular dynamic simulations are performed to reveal the long-time behavior of the velocity autocorrelation function (VAF) by utilizing the finite-size effect in a Lennard-Jones binary mixture. Whereas in normal liquids the classical positive t^{-3/2} long-time tail is observed, we find in supercooled liquids a negative tail. It is strongly influenced by the transfer of the transverse current wave across the period boundary. The t^{-5/2} decay of the negative long-time tail is confirmed in the spectrum of VAF. Modeling the long-time transverse current within a generalized Maxwell model, we reproduce the negative long-time tail of the VAF, but with a slower algebraic t^{-2} decay.

The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis.

Despite the pivotal role of MYC in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and many other cancers, the mechanisms underlying MYC-mediated tumorigenesis remain inadequately understood. Here we utilized a well-characterized zebrafish model of Myc-induced T-ALL for genetic studies to identify novel genes contributing to disease onset. We found that heterozygous inactivation of a tricarboxylic acid (TCA) cycle enzyme, dihydrolipoamide S-succinyltransferase (Dlst), significantly delayed tumor onset in zebrafish without detectable effects on fish development. DLST is the E2 transferase of the α-ketoglutarate (α-KG) dehydrogenase complex (KGDHC), which converts α-KG to succinyl-CoA in the TCA cycle. RNAi knockdown of DLST led to decreased cell viability and induction of apoptosis in human T-ALL cell lines. Polar metabolomics profiling revealed that the TCA cycle was disrupted by DLST knockdown in human T-ALL cells, as demonstrated by an accumulation of α-KG and a decrease of succinyl-CoA. Addition of succinate, the downstream TCA cycle intermediate, to human T-ALL cells was sufficient to rescue defects in cell viability caused by DLST inactivation. Together, our studies uncovered an important role for DLST in MYC-mediated leukemogenesis and demonstrated the metabolic dependence of T-lymphoblasts on the TCA cycle, thus providing implications for targeted therapy.

Cloning, sequencing and heterologous expression of a Klebsiella pneumoniae gene encoding an FAD-independent acetolactate synthase.

The gene encoding the valine-resistant and FAD-independent acetolactate synthase of Klebsiella pneumoniae was isolated and expressed in Escherichia coli. The nucleotide sequence of this gene was determined and it exhibited an open reading frame of 1680 bp in length. In vivo expression of the acetolactate synthase-encoding gene in E. coli revealed a single 60-kDa protein which is consistent with the molecular weight calculated from the deduced amino acid sequence of the gene product. The gene product shares about 20-30% homology with the acetolactate synthases of E. coli, yeast and higher plants.

Cloning of a human liver UDP-glucose pyrophosphorylase cDNA by complementation of the bacterial galU mutation.

A human liver cDNA clone which encodes the UDP-glucose pyrophosphorylase was isolated by complementation of a bacterial galU mutant. The deduced amino acid sequence of the human enzyme comprised 508 amino acids with a calculated molecular mass of 56,950. The human enzyme significantly resembles those of potato tuber and slime mold with a homology of 46.6% and 43.2%, respectively, in amino acid sequence. No homology was found between the eukaryotic and the prokaryotic enzymes. Northern blotting analysis revealed that the gene was expressed at the highest level in skeletal muscle, followed by liver, heart and kidney.

Nucleotide sequence and expression in Escherichia coli of the Klebsiella pneumoniae deaD gene.

The deaD gene of Klebsiella pneumoniae was isolated and its nucleotide sequence determined. The K. pneumoniae gene is highly homologous with the Escherichia coli analog throughout most of the coding region. The deduced primary sequence of the K. pneumoniae deaD gene product is 659 amino acids in length, in contrast with the 571 amino acids of the E. coli deaD product published previously. Sequence comparison revealed several differences near the 3' end of the deaD genes which result in the frame-shift effect. The 3' end sequence of the E. coli deaD gene was therefore analyzed to verify the discrepancy. Our result indicates that the E. coli deaD gene encodes a product of comparable size to the K. pneumoniae DeaD protein, and the carboxyl terminal sequences of the two proteins are highly homologous. In vivo expression of the K. pneumoniae deaD gene in E. coli yielded a 65-kDa protein. Primer extension analysis of the mRNA from K. pneumoniae identified a major transcription start site at an A residue 44 nt upstream of the first in-frame ATG codon.

Cloning and expression of the Klebsiella pneumoniae galactose operon.

The entire galactose (gal) operon of Klebsiella pneumoniae was isolated and functionally analyzed in Escherichia coli. The genes encoding galactokinase (galK), galactose-1-phosphate uridyltransferase (galT), and UDP-galactose-4-epimerase (galE) were mapped by complementation analysis. The gene order E-T-K was found to be identical to that of Salmonella spp. and E. coli. Analysis of the nucleotide sequence in the control region revealed significant homology with that of E. coli. Two major sites for transcriptional initiation, both mapped to a cytosyl residue, were identified by primer extension. When the operon is expressed in E. coli, the K. pneumoniae gal gene products make up about 30% of the total cellular proteins. The presence of a powerful promoter responsible for high level synthesis of the gal proteins was also demonstrated using beta-galactosidase as reporter.