T-cell help in the tumor microenvironment enhances rituximab-mediated NK-cell ADCC.

ABSTRACT: Rituximab (RTX) and other monoclonal antibodies (mAbs) that bind directly to malignant cells are of great clinical value but are not effective for all patients. A major mechanism of action of RTX is antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells. Prior in vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic potential of NK cells activated by anti-CD20-coated target B cells. Here, we conducted studies using a novel mouse model and clinical correlative analysis to assess whether T-cell help contribute to RTX-mediated NK-cell ADCC in the tumor microenvironment (TME) in vivo. A humanized mouse model was developed using Raji lymphoma cells and normal donor peripheral blood mononuclear cells that allows for control of T-cell numbers in the lymphoma TME. In this model, NK-cell viability and CD16 and CD25 expression dropped after RTX in the absence of T cells but increased in the presence of T cells. RTX therapy was more effective when T cells were present and was ineffective when NK cells were depleted. In patients with indolent lymphoma, fine needle aspirates were obtained before and ∼1 week after treatment with a RTX-containing regimen. There was a strong correlation between CD4+ T cells as well as total T cells in the pretherapy TME and an increase in NK-cell CD16 and CD25 expression after RTX. We conclude that T-cell help in the TME enhances RTX-mediated NK-cell viability and ADCC.

Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours.

Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues. Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.

Effects of temperature fluctuations on the quality and microbial diversity of beef meatballs during simulated cold chain distribution.

BACKGROUND: Cold chain distribution with multiple links maintains low temperatures to ensure the quality of meat products, whereas temperature fluctuations during this are often disregarded by the industry. The present study simulated two distinct temperatures cold chain distribution processes. Quality indicators and high-throughput sequencing were employed to investigate the effects of temperature fluctuations on the quality and microbial diversity of beef meatballs during cold chain distribution. RESULTS: Quality indicators revealed that temperature fluctuations during simulated cold chain distribution significantly (P < 0.05) exacerbated the quality deterioration of beef meatballs. High-throughput sequencing demonstrated that temperature fluctuations affected the diversity and structure of microbial community. Lower microbial species abundance and higher microbial species diversity were observed in the temperature fluctuations group. Proteobacteria and Pseudomonas were identified as the dominant phylum and genus in beef meatballs, respectively, exhibiting faster growth rates and greater relative abundance under temperature fluctuations. CONCLUSION: The present study demonstrates that temperature fluctuations during simulated cold chain distribution can worsen spoilage and shorten the shelf life of beef meatballs. It also offers certain insights into the spoilage mechanism and preservation of meat products during cold chain distribution. © 2024 Society of Chemical Industry.

Dynamic changes of tenderness, moisture and protein in marinated chicken: the effect of different steaming temperatures.

BACKGROUND: The steam processing characteristics of chicken are a key factor in the simplicity and versatility of steamed chicken dishes. The aim of this study was to investigate in depth the changes in tenderness and water retention of marinated chicken at different slow steaming endpoint temperatures, and to further explore the effect of the evolution of protein conformations on the water status. RESULTS: The results showed that chicken samples' shear force peaked at 80 °C and decreased rapidly at 90 °C. As the steaming endpoint temperature increased between 50 and 90 °C, T21, T22, moisture content and centrifugal loss decreased, but P21, P22 and myofibril water-holding capacity showed regular changes. The electrophoretic bands and protein conformation changes showed that protein in marinated chicken underwent different degrees of denaturation, degradation and aggregation. And at 70 °C, with an increase of hydrophobic groups and crosslinking of disulfide bonds as well as an increase in the number of denatured sarcoplasmic proteins, the intermolecular network was enhanced, thus affecting the water retention. CONCLUSION: Water status of chicken meat heated at different steaming temperatures is closely related to the evolution of protein conformations. The present study serves as a robust theoretical foundation for enhancing the quality of steamed chicken products at an industrial scale. © 2024 Society of Chemical Industry.

Cancer germline predisposing variants and late mortality from subsequent malignant neoplasms among long-term childhood cancer survivors: a report from the St Jude Lifetime Cohort and the Childhood Cancer Survivor Study.

BACKGROUND: Carriers of cancer predisposing variants are at an increased risk of developing subsequent malignant neoplasms among those who have survived childhood cancer. We aimed to investigate whether cancer predisposing variants contribute to the risk of subsequent malignant neoplasm-related late mortality (5 years or more after diagnosis). METHODS: In this analysis, data were included from two retrospective cohort studies, St Jude Lifetime Cohort (SJLIFE) and the Childhood Cancer Survivor Study (CCSS), with prospective follow-up of patients who were alive for at least 5 years after diagnosis with childhood cancer (ie, long-term childhood cancer survivors) with corresponding germline whole genome or whole exome sequencing data. Cancer predisposing variants affecting 60 genes associated with well-established autosomal-dominant cancer-predisposition syndromes were characterised. Subsequent malignant neoplasms were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 with modifications. Cause-specific late mortality was based on linkage with the US National Death Index and systematic cohort follow up. Fine-Gray subdistribution hazard models were used to estimate subsequent malignant neoplasm-related late mortality starting from the first biospecimen collection, treating non-subsequent malignant neoplasm-related deaths as a competing risk, adjusting for genetic ancestry, sex, age at diagnosis, and cancer treatment exposures. SJLIFE (NCT00760656) and CCSS (NCT01120353) are registered with ClinicalTrials.gov. FINDINGS: 12 469 (6172 male and 6297 female) participants were included, 4402 from the SJLIFE cohort (median follow-up time since collection of the first biospecimen 7·4 years [IQR 3·1-9·4]) and 8067 from the CCSS cohort (median follow-up time since collection of the first biospecimen 12·6 years [2·2-16·6]). 641 (5·1%) of 12 469 participants carried cancer predisposing variants (294 [6·7%] in the SJLIFE cohort and 347 [4·3%] in the CCSS cohort), which were significantly associated with an increased severity of subsequent malignant neoplasms (CTCAE grade ≥4 vs grade <4: odds ratio 2·15, 95% CI 1·18-4·19, p=0·0085). 263 (2·1%) subsequent malignant neoplasm-related deaths (44 [1·0%] in the SJLIFE cohort; and 219 [2·7%] in the CCSS cohort) and 426 (3·4%) other-cause deaths (103 [2·3%] in SJLIFE; and 323 [4·0%] in CCSS) occurred. Cumulative subsequent malignant neoplasm-related mortality at 10 years after the first biospecimen collection in carriers of cancer predisposing variants was 3·7% (95% CI 1·2-8·5) in SJLIFE and 6·9% (4·1-10·7) in CCSS versus 1·5% (1·0-2·1) in SJLIFE and 2·1% (1·7-2·5) in CCSS in non-carriers. Carrying a cancer predisposing variant was associated with an increased risk of subsequent malignant neoplasm-related mortality (SJLIFE: subdistribution hazard ratio 3·40 [95% CI 1·37-8·43]; p=0·0082; CCSS: 3·58 [2·27-5·63]; p<0·0001). INTERPRETATION: Identifying participants at increased risk of subsequent malignant neoplasms via genetic counselling and clinical genetic testing for cancer predisposing variants and implementing early personalised cancer surveillance and prevention strategies might reduce the substantial subsequent malignant neoplasm-related mortality burden. FUNDING: American Lebanese Syrian Associated Charities and US National Institutes of Health.

Generalizability of "GWAS Hits" in Clinical Populations: Lessons from Childhood Cancer Survivors.

With mounting interest in translating genome-wide association study (GWAS) hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here, we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study, and we show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (n = 2,231; observed-to-expected replication ratio = 0.70, p = 6.2 × 10-8). An examination of five comparable phenotypes in a second independent cohort of survivors from the Childhood Cancer Survivor Study corroborated the overall limited generalizability of meta-GWAS hits to survivors (n = 4,212; observed-to-expected replication ratio = 0.55, p = 5.6 × 10-15). Finally, in direct comparisons of survivor samples against independent equivalently powered general population samples from the UK Biobank, we consistently observed lower meta-GWAS hit replication rates and poorer polygenic risk score predictive performance in survivor samples for multiple phenotypes. As a possible explanation, we found that meta-GWAS hits were less likely to be replicated in survivors who had been exposed to cancer therapies that are associated with phenotype risk. Examination of complementary DNA methylation data in a subset of survivors revealed that treatment-related methylation patterns at genomic sites linked to meta-GWAS hits may disrupt established genetic signals in survivors.

Enhancing underwater VLC with spatial division transmission and pairwise coding.

In this paper, we propose and evaluate two spatial division transmission (SDT) schemes, including spatial division diversity (SDD) and spatial division multiplexing (SDM), for underwater visible light communication (UVLC) systems. Moreover, three pairwise coding (PWC) schemes, including two one-dimensional PWC (1D-PWC) schemes, i.e., subcarrier PWC (SC-PWC) and spatial channel PWC (SCH-PWC), and one two-dimensional PWC (2D-PWC) scheme are further applied for signal-to-noise ratio (SNR) imbalance mitigation in the UVLC systems using SDD and SDM with orthogonal frequency division multiplexing (OFDM) modulation. The feasibility and superiority of applying SDD and SDM with various PWC schemes in a practical bandlimited two-channel OFDM-based UVLC system have been verified through both numerical simulations and hardware experiments. The obtained results show that the performance of SDD and SDM schemes are largely determined by both the overall SNR imbalance and the system spectral efficiency. Moreover, the experimental results demonstrate the robustness of SDM with 2D-PWC against bubble turbulence. Specifically, SDM with 2D-PWC can obtain bit error rates (BERs) under the 7% forward error correction (FEC) coding limit of 3.8 × 10-3 with a probability higher than 96% for a signal bandwidth of 70 MHz and a spectral efficiency of 8 bits/s/Hz, achieving an overall data rate of 560 Mbits/s.

Kikuchi disease with an exuberant proliferation of large T-cells: a study of 25 cases that can mimic T-Cell lymphoma.

Exuberant large T-cell proliferations in Kikuchi disease can potentially be misdiagnosed as lymphoma. In this study, we explore their clinicopathological features and summarize key points that can be used to distinguish them from T-cell lymphoma. The cohort consisted of 25 cases of Kikuchi disease with an exuberant large T-cell proliferation, which, in part, mimicked lymphoma. The median age was 25 years with a female:male ratio of 4:1. By B-scan ultrasonography, patients presented with either isolated lymphadenopathy (68%) involving the cervical and axillary regions or generalized lymphadenopathy (32%). Histologically, lymph nodes showed paracortical and interfollicular expansion by sheets of large cells associated with karyorrhectic debris. Histiocytes and plasmacytoid dendritic cells were present in the background. No case showed complete effacement of lymph node architecture. The large cells were CD8-positive cytotoxic T-cells with a high proliferation rate. These T-cells showed decreased BCL-2 in 17 (68%) cases. CD5 expression was decreased in 10 (40%) cases. Histiocytes in the background were positive for myeloperoxidase. Clonal TRG and/or TRB rearrangements were detected in 2 of 10 (20%) cases. In conclusion, large T-cell proliferations in Kikuchi disease can be alarming at the morphologic and immunophenotypic levels and need to be distinguished from T-cell lymphoma. Clinical features helpful in the differential diagnosis include young patients and lymphadenopathy involving the cervical and axillary regions. Major pathologic features helpful in this differential diagnosis include partial involvement of the lymph node and the presence of karyorrhectic debris, crescent-shaped histiocytes, and/or loose aggregates of plasmacytoid dendritic cells.

Ultra-sensitive UV solar-blind optical wireless communications with an SiPM.

In this Letter, an SiPM with a dedicated cooling system suitable for receiving ultra-low-power solar-blind wavelengths is reported. This is designed to decrease the temperature of the detector from 21°C to -10°C, and the corresponding dark count rate (DCR) is reduced by approximately 10 dB. A 275 nm optical wireless communication (OWC) system is established using on-off-keying (OOK) modulation. Transmission rates ranging from 100 kbit/s to 2 Mbit/s are demonstrated with this cooled SiPM. The received power is as low as 30 pW (corresponding to 41.5 photons per bit) at a data rate of 1 Mbit/s and a bit error rate of 2.4 × 10-3.

Association analysis identifies 65 new breast cancer risk loci.

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P < 5 × 10-8. The majority of credible risk single-nucleotide polymorphisms in these loci fall in distal regulatory elements, and by integrating in silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all single-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores for individualized screening and prevention.

T cells, particularly activated CD4+ cells, maintain anti-CD20-mediated NK cell viability and antibody dependent cellular cytotoxicity.

Anti-CD20 monoclonal antibody (mAb) therapy is a mainstay of therapy for B cell malignancies, however many patients fail to respond or eventually develop resistance. The current understanding of mechanisms responsible for this resistance is limited. When peripheral blood mononuclear cells of healthy donors were cultured with Raji cells for 7 days, rituximab (RTX) induced NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC), enhanced NK cell viability and increased or maintained NK expression of CD56, CD16, CD57 and KIR. T cells, mainly CD4+, mediated these changes in a contact-dependent manner, with local T cell production of IL2 playing a central role. Similar findings were found when autologous B cells were used as target cells demonstrating the need for T cell help was not due to allogenic reaction. Results with other anti-CD20 and anti-EGFR antibodies were consistent. Small numbers of T cells activated by anti-CD3/CD28 beads or bispecific antibody enhanced RTX-mediated NK cell ADCC, viability and phenotypical changes. Pathway analysis of bulk NK cell mRNA sequencing after activation by RTX with and without T cells was consistent with T cells maintaining the viability of the activated NK cells. These findings suggest T cell help, mediated in large part by local production of IL2, contributes to NK cell ADCC and viability, and that activating T cells in the tumor microenvironment, such as through the use of anti-CD3 based bispecific antibodies, could enhance the efficacy of anti-CD20 and other mAb therapies where NK-mediated ADCC is a primary mechanism of action.

Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE): a cloud-based platform for curating and classifying germline variants.

Variant interpretation in the era of massively parallel sequencing is challenging. Although many resources and guidelines are available to assist with this task, few integrated end-to-end tools exist. Here, we present the Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE), a web- and cloud-based platform for annotation, identification, and classification of variations in known or putative disease genes. Starting from a set of variants in variant call format (VCF), variants are annotated, ranked by putative pathogenicity, and presented for formal classification using a decision-support interface based on published guidelines from the American College of Medical Genetics and Genomics (ACMG). The system can accept files containing millions of variants and handle single-nucleotide variants (SNVs), simple insertions/deletions (indels), multiple-nucleotide variants (MNVs), and complex substitutions. PeCanPIE has been applied to classify variant pathogenicity in cancer predisposition genes in two large-scale investigations involving >4000 pediatric cancer patients and serves as a repository for the expert-reviewed results. PeCanPIE was originally developed for pediatric cancer but can be easily extended for use for nonpediatric cancers and noncancer genetic diseases. Although PeCanPIE's web-based interface was designed to be accessible to non-bioinformaticians, its back-end pipelines may also be run independently on the cloud, facilitating direct integration and broader adoption. PeCanPIE is publicly available and free for research use.

Application and comparison of active and transfer learning approaches for modulation format classification in visible light communication systems.

Automatic modulation classification (AMC) is a crucial part of adaptive modulation schemes for visible light communication (VLC) systems. However, most of the deep learning (DL) based AMC methods for VLC systems require a large amount of labeled training data which is quite difficult to obtain in practical systems. In this work, we introduce active learning (AL) and transfer learning (TL) approaches for AMC in VLC systems and experimentally analyze their performances. Experimental results show that the proposed novel AlexNet-AL and AlexNet-TL methods can significantly improve the classification accuracy with small sizes of training data. To be specific, using 60 labeled samples, AlexNet-AL and AlexNet-TL increase the classification accuracy by 6.82% and 14.6% compared to the result without AL and TL, respectively. Moreover, the use of data augmentation (DA) operation along with our proposed methods helps achieve further better performances.

Fluorescent concentrator based MISO-NOMA for visible light communications.

The experimental realization of multiple-input single-output (MISO) in visible light communication (VLC) has always been difficult due to dynamic channels, complex alignment, and limited capacity. We designed a quantum dot (QD) fluorescent concentrator combined with power domain multiplexing of a non-orthogonal multiple access (NOMA) scheme to provide an estimation-free MISO system. The system supports a large detection area of over 4 cm2 and a sum rate up to 120 Mbps over 2.3-m free space, providing a promising connection for the Internet of things (IoT). The concentrator was further implemented in an underwater environment under insufficient incident power. A record data rate of 120 Mbps has been achieved in a 1.5-m underwater MISO system, with a mean bit error rate of 3.24 × 10-3, which is below the forward error correction criterion.

THO-OFDM scheme for visible light communication with noise suppression and dimming control.

In recent years, visible light communication (VLC) has emerged as a dual-use technique for illumination as well as communication. In VLC system, dimming control is deemed to be an essential functionality for luminous intensity adjusting and energy saving. In this Letter, a noise-suppressed triple-layer hybrid optical orthogonal frequency division multiplexing (NSTHO-OFDM) is proposed and further combined with pulse width modulation (PWM) to achieve the functionality of dimming control. The proposed NSTHO-OFDM can attain a 4.28-dB maximum power gain compared with THO-OFDM with an overall bit error rate (BER) of 1 × 10-4. Moreover, the proposed dimming scheme can achieve a wide dimming range of 89.0% while maintaining a favorable BER below 3.8 × 10-3.

Quantum Energy Current Induced Coherence in a Spin Chain under Non-Markovian Environments.

We investigate the time-dependent behaviour of the energy current between a quantum spin chain and its surrounding non-Markovian and finite temperature baths, together with its relationship to the coherence dynamics of the system. To be specific, both the system and the baths are assumed to be initially in thermal equilibrium at temperature Ts and Tb, respectively. This model plays a fundamental role in study of quantum system evolution towards thermal equilibrium in an open system. The non-Markovian quantum state diffusion (NMQSD) equation approach is used to calculate the dynamics of the spin chain. The effects of non-Markovianity, temperature difference and system-bath interaction strength on the energy current and the corresponding coherence in cold and warm baths are analyzed, respectively. We show that the strong non-Markovianity, weak system-bath interaction and low temperature difference will help to maintain the system coherence and correspond to a weaker energy current. Interestingly, the warm baths destroy the coherence while the cold baths help to build coherence. Furthermore, the effects of the Dzyaloshinskii-Moriya (DM) interaction and the external magnetic field on the energy current and coherence are analyzed. Both energy current and coherence will change due to the increase of the system energy induced by the DM interaction and magnetic field. Significantly, the minimal coherence corresponds to the critical magnetic field which causes the first order phase transition.

The clinicopathological and molecular features of sinusoidal large B-cell lymphoma.

We report 17 cases of sinusoidal large B-cell lymphoma (SLBCL). Clinical, morphologic, immunophenotypic, and molecular features were detected and analyzed. All cases showed an obvious sinusoidal growth pattern, usually associated with residual atrophic lymphoid tissue. All tumors contained large pleomorphic lymphoid cells and one or more prominent nucleoli, with abundant amphophilic cytoplasms; 15/17 cases showed anaplastic morphologic features. The patient age ranged from 43 to 80 years (median 57 years), and 7 males and 10 females were included. Eleven of 15 (73.3%) patients had Ann Arbor stage III or IV disease, and 10/15 (66.6%) patients had an International Prognostic Index (IPI) score ≥3. Immunophenotypically, 16/17 (94.1%) cases displayed a nongerminal center B-cell (non-GCB) immunophenotype. Furthermore, 16/17 (94.1%) cases were positive for CD30, and p53 was expressed in 10/16 (62.5%) cases. In total, 12/14 (85.7%) cases expressed BCL2 and MYC simultaneously (double expression), and 11/14 (78.6%) cases showed PD-L1 positivity (6/11 had a PD-L1 tumor proportion score ≥50%). Cytogenetically, concurrent MYC and BCL2 and/or BCL6 abnormalities (break-apart or extra copy) were detected in 10/15 cases, and 7/13 (53.8%) cases harbored a PD-L1/L2 amplification. TP53 mutation was found in 7/13 (53.8%) cases by Sanger sequencing. Whole-exome and large-panel sequencing results revealed high mutation frequencies of TP53 (4/7), MYD88 (3/7), KMT2D (3/7), CREBBP (3/7), and PIM1 (3/7). Among the 13 patients with SLBCL treated with aggressive chemotherapy regimens, the median overall survival (OS) was 18 months, and the 2-year OS rate was 34.6%. The OS of patients with SLBCL was markedly worse than that of 35 control group patients with common diffuse large B-cell lymphoma (DLBCL) without sinusoidal features (P < 0.001). SLBCL may represent a specific type of DLBCL that has characteristic pathologic features. The cancer is aggressive in most clinical cases, and outcomes are poor. SLBCL and anaplastic DLBCL (A-DLBCL) have many overlapping clinicopathological and molecular features.

Short sleep duration and physical and psychological health outcomes among adult survivors of childhood cancer.

BACKGROUND: To examine associations between phenotypes of short sleep duration and clinically assessed health conditions in long-term survivors of childhood cancer. METHODS: Survivors recruited from the St. Jude Lifetime Cohort (n = 911; 52% female; mean age 34 years; 26 years postdiagnosis) completed behavioral health surveys and underwent comprehensive physical examinations. Sleep was assessed with the Pittsburgh Sleep Quality Index. Short sleep was defined as ≤6 h per night with phenotypes of short sleep including poor sleep efficiency (<85%), prolonged sleep onset latency (SOL; ≥30 min), and wake after sleep onset (≥3 times per week). Covariates included childhood cancer treatment exposures, demographics, body mass index, and physical inactivity. Separate modified Poisson regression models were computed for each health category to estimate relative risks (RR) and 95% confidence intervals (CI). Multinomial logistic regression models examined associations between sleep and an aggregated burden of chronic health conditions. RESULTS: Short sleep duration was reported among 44% (95% CI 41%-47%) of survivors. In multivariable models, short sleep duration alone was associated with pulmonary (RR = 1.35, 95% CI 1.08-1.69), endocrine (RR = 1.22, 95% CI 1.06-1.39) and gastrointestinal/hepatic conditions (RR = 1.46, 95% CI 1.18-1.79), and anxiety (RR 3.24, 95% CI 1.64-6.41) and depression (RR = 2.33, 95% CI 1.27-4.27). Short sleep with prolonged SOL was associated with a high/severe burden of health conditions (OR = 2.35, 95% CI 1.12-4.94). CONCLUSIONS: Short sleep duration was associated with multiple clinically ascertained adverse health conditions. Although the temporality of these associations cannot be determined in this cross-sectional study, sleep is modifiable and improving sleep may improve long-term health in survivors.

Effects of partial replacement of NaCl with KCl on bacterial communities and physicochemical characteristics of typical Chinese bacon.

This work aimed to determine the effects of partial substitution of NaCl with 0% (control), 30%, 50%, and 70% of KCl on the bacterial communities, proteolysis and lipid oxidation of Chinese bacon during processing. The proportion of genus Lactobacillus increased from 22.45% (fresh meat) to 72.78%, 81.64%, 76.53% and 85.63% at the end of processing for 0%, 30%, 50% and 70% KCl replacement samples, respectively. During the processing, Lactobacillus gradually became the dominant one, and higher the KCl ratio, more rapid was the process. After salting, the TBARS of control was markedly higher (P < 0.05) than that of the others, while a similar lipid oxidation level (P > 0.05) was observed at the end of processing for different groups. After salting, there was no difference in total free amino acids (TFAA) content among four treatments (P > 0.05), whereas KCl replacement samples shared significantly higher (P < 0.05) values than control at the end of processing. Redundancy analysis and Pearson correlation showed positive correlation between Lactobacillus versus TBARS and TFAA. Partial replacement of NaCl with KCl could, directly or subsequently by promoting the growth of Lactobacillus, influence proteolysis and lipid oxidation over the manufacturing process.

Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women.

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.