ACCURATE ALIGNMENT OF SEQUENCING READS FROM VARIOUS GENOMIC ORIGINS

Ph.DDOCTOR OF PHILOSOPH

Molecularly imprinted polymer based on MWCNTs-QDs as fluorescent biomimetic sensor for specific recognition of target protein

A novel molecularly imprinted optosensing material based on multi-walled carbon nanotube-quantum dots (MWCNT-QDs) has been designed and synthesized for its high selectivity, sensitivity and specificity in the recognition of a target protein bovine serum albumin (BSA). Molecularly imprinted polymer coated MWCNT-QDs using BSA as the template (BMIP-coated MWCNT-QDs) exhibits a fast mass-transfer speed with a response time of 25 min. It is found that the BSA as a target protein can significantly quench the luminescence of BMIP-coated MWCNT-QDs in a concentration-dependent manner that is best described by a Stem-Volmer equation. The K-SV for BSA is much higher than bovine hemoglobin and lysozyme, implying a highly selective recognition of the BMIP-coated MWCNT-QDs to BSA. Under optimal conditions, the relative fluorescence intensity of BMIP-coated MWCNT-QDs decreases linearly with the increasing target protein BSA in the concentration range of 5.0 x 10(-7)-35.0 x 10(-7) M with a detection limit of 80 nM

Counterproductive effects of anti-CD38 and checkpoint inhibitor for the treatment of NK/T cell lymphoma

IntroductionNatural killer/T cell lymphoma (NKTL) is an aggressive malignancy associated with poor prognosis. This is largely due to limited treatment options, especially for relapsed patients. Immunotherapies like immune checkpoint inhibitors (ICI) and anti-CD38 therapies have shown promising but variable clinical efficacies. Combining these therapies has been suggested to enhance efficacy.MethodsWe conducted a case study on a relapsed NKTL patient treated sequentially with anti-CD38 followed by ICI (anti-PD1) using cytometry analyses.Results and DiscussionOur analysis showed an expected depletion of peripheral CD38+ B cells following anti-CD38 treatment. Further analysis indicated that circulating anti-CD38 retained their function for up to 13 weeks post-administration. Anti-PD1 treatment triggered re-activation and upregulation of CD38 on the T cells. Consequently, these anti-PD1-activated T cells were depleted by residual circulating anti-CD38, rendering the ICI treatment ineffective. Finally, a meta-analysis confirmed this counterproductive effect, showing a reduced efficacy in patients undergoing combination therapy. In conclusion, our findings demonstrate that sequential anti-CD38 followed by anti-PD1 therapy leads to a counterproductive outcome in NKTL patients. This suggests that the treatment sequence is antithetic and warrants re-evaluation for optimizing cancer immunotherapy strategies

Characterizing Nodal Gamma-Delta T-Cell Lymphoma: Clinicopathological and Molecular Insights

Peripheral T-cell lymphomas with gamma-delta phenotype (GDTCL) are rare lymphoid malignancies. Beyond the well-recognized entities of extranodal lymphomas with gamma-delta phenotype as defined by the fifth edition of the World Health Organization Classification of Hematolymphoid Tumors and 2022 International Consensus Classification, there is a group of poorly defined gamma-delta T-cell lymphomas with predominantly nodal presentation, termed as nodal GDTCL (nGDTCL). In this study, we present a series of 12 cases of Epstein-Barr virus-negative nGDTCL, highlighting the clinical, histopathological, and molecular features of this rare entity. Seven cases reported in the literature were included in the analysis. Of the 12 cases, nGDTCL shows an increased incidence in elderly men, with a median age of 65.5 years. All cases presented primarily with enlarged lymph nodes, and 4 cases (4/12, 33.3%) showed involvement of extranodal sites, including skin, liver, spleen, and bone marrow. Histologically, 9 cases showed a diffuse and monomorphic proliferation of mostly medium-to-large lymphoid cells, whereas 3 cases demonstrated lymphoepithelioid morphology. All cases (12/12, 100%) were positive for CD3 and TCRgd. CD4, CD8, and CD56 were positive in 66.7% (8/12), 25% (3/12), and 8.3% (1/11) of cases, respectively. Most cases (8/12, 66.7%) showed a noncytotoxic phenotype. Using immunohistochemistry, the majority of cases (6/8, 75.0%) belonged to the peripheral T-cell lymphoma-GATA3 subtype with GATA3 and/or CCR4 expression and a noncytotoxic CD4-positive phenotype. Two cases (2/8, 25%) belonged to the peripheral T-cell lymphoma-TBX21 subtype, of which 1 displayed a cytotoxic CD8-positive phenotype. Next-generation sequencing was performed in 9 cases, and TP53 mutation was detected in 66.7% (6/9) of the cases. Mutations of ATM and KSR2 were identified in 2 cases each. It remains uncertain whether nGDTCL represents a distinct entity, and further studies are needed for better characterization. Nonetheless, nodal-based GDTCL should be distinguished from secondary nodal involvement by other extranodal GDTCL and Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases. (c) 2024 THE AUTHORS. Published by Elsevier Inc. on behalf of the United States & Canadian Academy of Pathology. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/)

Measurements of the pp → ZZ production cross section and the Z → 4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s = 13 TeV

Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013

DDX3X loss is an adverse prognostic marker in diffuse large B-cell lymphoma and is associated with chemoresistance in aggressive non-Hodgkin lymphoma subtypes.

Funder: addenbrooke's charitable trust, cambridge university hospital

Search for heavy resonances decaying to two Higgs bosons in final states containing four b quarks

A search is presented for narrow heavy resonances X decaying into pairs of Higgs bosons (H) in proton-proton collisions collected by the CMS experiment at the LHC at root s = 8 TeV. The data correspond to an integrated luminosity of 19.7 fb(-1). The search considers HH resonances with masses between 1 and 3 TeV, having final states of two b quark pairs. Each Higgs boson is produced with large momentum, and the hadronization products of the pair of b quarks can usually be reconstructed as single large jets. The background from multijet and t (t) over bar events is significantly reduced by applying requirements related to the flavor of the jet, its mass, and its substructure. The signal would be identified as a peak on top of the dijet invariant mass spectrum of the remaining background events. No evidence is observed for such a signal. Upper limits obtained at 95 confidence level for the product of the production cross section and branching fraction sigma(gg -> X) B(X -> HH -> b (b) over barb (b) over bar) range from 10 to 1.5 fb for the mass of X from 1.15 to 2.0 TeV, significantly extending previous searches. For a warped extra dimension theory with amass scale Lambda(R) = 1 TeV, the data exclude radion scalar masses between 1.15 and 1.55 TeV

Comparing public and private hospitals in China: Evidence from Guangdong

<p>Abstract</p> <p>Background</p> <p>The literature comparing private not-for-profit, for-profit, and government providers mostly relies on empirical evidence from high-income and established market economies. Studies from developing and transitional economies remain scarce, especially regarding patient case-mix and quality of care in public and private hospitals, even though countries such as China have expanded a mixed-ownership approach to service delivery. The purpose of this study is to compare the operations and performance of public and private hospitals in Guangdong Province, China, focusing on differences in patient case-mix and quality of care.</p> <p>Methods</p> <p>We analyze survey data collected from 362 government-owned and private hospitals in Guangdong Province in 2005, combining mandatorily reported administrative data with a survey instrument designed for this study. We use univariate and multi-variate regression analyses to compare hospital characteristics and to identify factors associated with simple measures of structural quality and patient outcomes.</p> <p>Results</p> <p>Compared to private hospitals, government hospitals have a higher average value of total assets, more pieces of expensive medical equipment, more employees, and more physicians (controlling for hospital beds, urban location, insurance network, and university affiliation). Government and for-profit private hospitals do not statistically differ in total staffing, although for-profits have proportionally more support staff and fewer medical professionals. Mortality rates for non-government non-profit and for-profit hospitals do not statistically differ from those of government hospitals of similar size, accreditation level, and patient mix.</p> <p>Conclusions</p> <p>In combination with other evidence on health service delivery in China, our results suggest that changes in ownership type alone are unlikely to dramatically improve or harm overall quality. System incentives need to be designed to reward desired hospital performance and protect vulnerable patients, regardless of hospital ownership type.</p