Search

Abstract Background Musculoskeletal ultrasound (MSUS) and the multi-biomarker disease activity (MBDA) score are outcome measures that may aid in the management of rheumatoid arthritis (RA) patients. This study evaluated tofacitinib response by MSUS/MBDA scores and assessed whether baseline MSUS/MBDA scores or their early changes predict later clinical response. Methods Twenty-five RA patients treated with tofacitinib were assessed at baseline, 2, 6 and 12-weeks. Power doppler (PDUS) and gray scale (GSUS) ultrasound scores, MBDA score, clinical disease activity index (CDAI), and disease activity score (DAS28) were obtained. Pearson correlations and multiple linear regression models were used to evaluate associations and identify predictors of response to therapy. Results MSUS, MBDA scores, CDAI, and DAS28 improved significantly over 12 weeks (p

We report 3 patients who presented with abnormal pancreatic contents that were initially nondiagnostic but were eventually found to have urate crystal deposition consistent with pancreatic tophaceous gout. Our first case involved an ICU patient who had fever of unknown origin and refractory pancreatic pseudocyst. The other 2 patients presented with abdominal pain associated with a pancreatic mass which mimicked malignancy. After further investigation, we were able to identify pancreatic tophaceous gout as the diagnosis. Initiation of therapy led to resolution of pancreatitis in the first patient and resolution of abdominal pain and decrease in size of a pancreatic mass in the other 2 patients. The recognition of clinical gout involving the pancreas has important implications in the evaluation and care of these patients who are at high risk for tophaceous gout. In addition, the importance of specimen preparation that preserves crystals for viewing is discussed.

Watermelon mosaic virus (WMV), a member of the genus Potyvirus, causes serious economic losses in cucurbit crops. For molecular biological studies of viruses, it is necessary to construct an infectious clone that can facilitate gene functional analysis. In this study, we constructed an infectious cDNA clone of WMV genomic RNA by Gibson assembly and evaluated its virulence and symptoms on a variety of host plants. A WMV isolate (WMV-IS-me2) collected from melon in Iksan, Jeonbuk Province, Korea in 2015 caused mosaic symptoms on leaves. Four overlapping PCR fragments of the full-length genome of this isolate and the pJL89 binary vector with overhanging ends of 40 bp were amplified by reverse transcription PCR and joined in a single isothermal reaction. The complete nucleotide sequence of the infectious cDNA clone of WMV was determined and the recombinant vector was transformed into Agrobacterium tumefaciens GV3101. Following agro-infiltration, an infectious clone (pWMV-M, KACC95145P) systemically induced mosaic symptoms on watermelon (Citrullus lanatus), zucchini (Cucurbita pepo), melon (Cucumis melo), and Nicotiana benthamiana plants. This infectious clone may be useful for screening cucurbit varieties resistant to WMV, as well as for studying viral gene function.

Summary: Cerebral cavernous malformations (CCMs) are neurovascular lesions caused by mutations in one of three genes (CCM1–3). Loss of CCM3 causes the poorest prognosis, and little is known about how it regulates vascular integrity. The C. elegans ccm-3 gene regulates the development of biological tubes that resemble mammalian vasculature, and in a genome-wide reverse genetic screen, we identified more than 500 possible CCM-3 pathway genes. With a phenolog-like approach, we generated a human CCM signaling network and identified 29 genes in common, of which 14 are required for excretory canal extension and membrane integrity, similar to ccm-3. Notably, depletion of the MO25 ortholog mop-25.2 causes severe defects in tube integrity by preventing CCM-3 localization to apical membranes. Furthermore, loss of MO25 phenocopies CCM3 ablation by causing stress fiber formation in endothelial cells. This work deepens our understanding of how CCM3 regulates vascular integrity and may help identify therapeutic targets for treating CCM3 patients. : Lant et al. use C. elegans genetics to better understand the human disease cerebral cavernous malformation (CCM). Through a whole-genome screen, and bioinformatics, they uncover a set of conserved genes that exhibit ccm-3 phenotypes. These targets may be able to inform therapeutic studies. Keywords: biological tubes, cerebral cavernous malformation, CCM3, C. elegans, endothelial cells, whole-genome screen, phenologs, bioinformatics

The functional specialization of CD4 T lymphocytes into various subtypes, including TH1 and TFH cells, is crucial for effective immune responses. TFH cells facilitate B cell differentiation within germinal centers, while TH1 cells are vital for cell-mediated immunity against intracellular pathogens. Integrin α4, a cell surface adhesion molecule, plays significant roles in cell migration and co-stimulatory signaling. In this study, we investigated the role of Integrin α4 in regulating TFH and TH1 cell populations during acute viral infection using CRISPR-Cas9 gene editing. To effectively delete the Itga4 in primary mouse CD4 T cells, we selected various combinations of crRNAs and generated ribonucleoprotein complexes with fluorochrome-conjugated tracrRNAs and Cas9 proteins. These crRNA pairs enhanced gene deletion by generating deletions in the gene. By analyzing the effects of Itga4 deficiency on TFH and TH1 cell differentiation during acute LCMV infection, we found that optimized crRNA pairs significantly increased the TH1 cell population. Our results highlight the importance of selecting and combining appropriate crRNAs for effective CRISPR-Cas9 gene editing in primary CD4 T cells. Additionally, our study demonstrates the role of Integrin α4 in regulating the differentiation of CD4 T cells, suggesting the potential molecular mechanisms driving T cell subset differentiation through integrin targeting.

Tailoring the pore structure in materials is a key to achieving efficient ion/molecular transportation. The interlayer space in graphitic materials can be expanded via the oxidation–exfoliation process. However, since the intercalation-mediated oxidation method does not work for carbon nanotubes (CNTs) that have semi-closed graphitic structures, mesoporous 1D nanostructure has been rarely prepared. In the present study, modified Hummers method-based oxidation was applied to cup-stacked carbon nanotubes (CSCNTs) with open-edge graphitic structure. The degree of oxidation was controlled by the weight ratio of the oxidant and added CNTs. The complete basal-plane oxidation was achieved when the oxidant was 5 times the weight of CSCNTs. Following thermal reduction further expanded the interlayer spaces of the CSCNTs resulting in the formation of mesoporous 1D nanostructure with alternating stacked–expanded graphene layers resembling honeycomb shape, indicating the importance of the unique nanostructure of CSCNTs for pore formation. Heat-treatment of the obtained mesoporous 1D structure helped improve the crystallinity, but at the same time deteriorated the porosity features as the heat-treatment temperature increased. Thermally induced defect repairing flattened the graphitic structure which also induced layer restacking; thus, this revealed the trade-off relationship between the crystallinity and porosity.

To investigate underlying mechanism of chondrogenic hypertrophy, we need proper in vitro hypertrophic model of mesenchymal stem cells (MSCs). This protocol describes our defined method for induction of in vitro chondrogenic hypertrophy of human umbilical cord blood-derived MSCs (hUCB-MSCs). By adding thyroid hormone (T3; triiodothyronine) and minimum osteogenic-inducing factors to culture medium, we could induce hypertrophy of hUCB-MSCs in vitro. Hypertrophic induction was validated using immunohistochemical analysis, Western blotting and reverse transcriptase polymerase chain reaction.

Background In breast reconstruction, synthetic meshes are frequently used to replace acellular dermal matrix (ADM), since ADM is expensive and often leads to complications. However, there is limited evidence that compares the types of substitutes. This study aimed to compare complications between materials via a network meta-analysis. Methods We systematically reviewed studies reporting any type of complication from 2010 to 2021. The primary outcomes were the proportion of infection, seroma, major complications, or contracture. We classified the intervention into four categories: ADM, absorbable mesh, nonabsorbable mesh, and nothing used. We then performed a network meta-analysis between these categories and estimated the odds ratio with random-effect models. Results Of 603 searched studies through the PubMed, MEDLINE, and Embase databases, following their review by two independent reviewers, 61 studies were included for full-text reading, of which 17 studies were finally included. There was a low risk of bias in the included studies, but only an indirect comparison between absorbable and non-absorbable mesh was possible. Infection was more frequent in ADM but not in the two synthetic mesh groups, namely the absorbable or nonabsorbable types, compared with the nonmesh group. The proportion of seroma in the synthetic mesh group was lower (odds ratio was 0.2 for the absorbable and 0.1 for the nonabsorbable mesh group) than in the ADM group. Proportions of major complications and contractures did not significantly differ between groups. Conclusion Compared with ADM, synthetic meshes have low infection and seroma rates. However, more studies concerning aesthetic outcomes and direct comparisons are needed.

Abstract Background Lung cancer surgery is reported as a risk factor for chronic pulmonary aspergillosis (CPA). However, limited data are available on its clinical impact. We aimed to determine the effect of developed CPA after lung cancer surgery on mortality and lung function decline. Methods We retrospectively identified the development of CPA after lung cancer surgery between 2010 and 2016. The effect of CPA on mortality was evaluated using multivariable Cox proportional hazard analyses. The effect of CPA on lung function decline was evaluated using multiple linear regression analyses. Results During a median follow-up duration of 5.01 (IQR, 3.41–6.70) years in 6777 patients, 93 developed CPA at a median of 3.01 (IQR, 1.60–4.64) years. The development of CPA did not affect mortality in multivariable analysis. However, the decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were greater in patients with CPA than in those without (FVC, − 71.0 [− 272.9 to − 19.4] vs. − 10.9 [− 82.6 to 57.9] mL/year, p

Abstract Background Due to the deep tissue penetration and reduced scattering, NIR-II fluorescence imaging is advantageous over conventional visible and NIR-I fluorescence imaging for the detection of bone growth, metabolism, metastasis, and other bone-related diseases. Methods Bone-targeted heptamethine cyanine fluorophores were synthesized by substituting the meso-carbon with a sulfur atom, resulting in a bathochromic shift and increased fluorescence intensity. The physicochemical, optical, and thermal stability of newly synthesized bone-targeted NIR fluorophores was performed in aqueous solvents. Calcium binding, bone-specific targeting, biodistribution, pharmacokinetics, and 2D and 3D NIR imaging were performed in animal models. Results The newly synthesized S-substituted heptamethine fluorophores demonstrated a high affinity for hydroxyapatite and calcium phosphate, which improved bone-specific targeting with signal-background ratios > 3.5. Particularly, P800SO3-PEG showed minimum nonspecific uptake, and most unbound molecules were excreted into the urinary bladder. Histological analyses demonstrated that P800SO3-PEG remained stable in the bone for over two weeks and was incorporated into bone matrices. Interestingly, the flexible thiol ethylene glycol linker on P800SO3-PEG induced a promising photothermal effect upon NIR laser irradiation, demonstrating potential theranostic imaging. Conclusions P800SO3-PEG shows a high affinity for bone tissues, deeper tissue imaging capabilities, minimum nonspecific uptake in the major organs, and photothermal effect upon laser irradiation, making it optimal for bone-targeted theranostic imaging.

In this paper, a novel helical antenna for high-power microwave is proposed. The proposed antenna is intended to demonstrate improved power handling capacity without any deterioration in matching characteristics, gain, and axial ratio. The proposed antenna with a long helix structure is investigated in order to achieve high gain and a relatively wide impedance bandwidth. By increasing the distance between the helix and the ground plane, an improved power handling capacity is obtained, and the impedance matching problem caused by the proposed method is addressed with the use of a feed-through insulator. In addition, a conical-shaped ground is used to compensate for the gain reduction by increasing the distance between the helix and the ground plane. As a result, the proposed antenna exhibits a gain exceeding 11 dBi and an axial ratio of less than 2 dB within the frequency range of 0.86–1.09 GHz. In addition, its power handling capacity exceeds 50 MW for a 0.7-ns input pulse length in air conditions.

Abstract Background Feeding jejunostomy was routinely placed during esophagectomy to ensure postoperative enteral feeding. Improved anastomosis technique and early oral feeding strategy after esophagectomy has led to question the need for the routine placement of feeding jejunostomy. The aim of this study is to evaluate role of feeding jejunostomy during Ivor Lewis operation. Methods We retrospectively reviewed 414 patients who underwent the Ivor Lewis operations from January 2015 to December 2018. Results 61 patients (14.7%) received jejunostomy insertion. The most common indication for jejunostomy was neoadjuvant concurrent chemoradiation therapy (CCRT). 48 patients (79%) had jejunostomy removed within 60 days after the surgery and the longest duration of jejunostomy inserted state was 121 days. About two-third of the patients with jejunostomy had never prescribed with an enteral feeding product. Among 353 patients without intraoperative feeding jejunostomy, 11(3.1%) received delayed jejunostomy insertion. Graft-related problems (6 patients), cancer progression (3 patients), acute lung injury (1 patient), and swallowing difficulty (1 patient) were reasons for delayed feeding jejunostomy insertion. Complication rate was relatively high as 24 patients (33.3%) out of 72 patients with jejunostomy insertion had complications and 7 patients (9.7%) visited ER more than twice with jejunostomy-related complications. Conclusion Only 3.6% patients who underwent the Ivor Lewis operation during 4-year span had anastomosis leakage. Although one-third of the patients with jejunostomy were benefited with alternative method of feeding after discharge, high complication rate regarding jejunostomy should be also considered. We believe feeding jejunostomy should not be applied routinely with prophylactic measures and should be reserved to very carefully selected patients with multiple high-risk factors.