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1.
Neural Regen Res ; 17(5): 1051-1058, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34558532

RESUMO

Repetitive transcranial magnetic stimulation (rTMS) has been shown to effectively improve impaired swallowing in Parkinson's disease (PD) patients with dysphagia. However, little is known about how rTMS affects the corresponding brain regions in this patient group. In this case-control study, we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy, Capital Medical University. The patients received high-frequency rTMS of the motor cortex once per day for 10 successive days. Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls. The results revealed that before treatment, PD patients with dysphagia showed greater activation in the precentral gyrus, supplementary motor area, and cerebellum compared with healthy controls, and this enhanced activation was weakened after treatment. Furthermore, before treatment, PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus, caudate nucleus, and left thalamus compared with healthy controls, and this activation increased after treatment. In addition, PD patients with dysphagia reported improved subjective swallowing sensations after rTMS. These findings suggest that swallowing function in PD patients with dysphagia improved after rTMS of the motor cortex. This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus. The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University (approval No. 2018bkky017) on March 6, 2018 and was registered with Chinese Clinical Trial Registry (registration No. ChiCTR 1800017207) on July 18, 2018.

2.
Bioengineered ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34719320

RESUMO

Previous studies on the mechanism of proliferation and cell cycle progression of gastric cancer cells have shown promising perspectives for the prevention and treatment of gastric cancer. The aim of the present study was to investigate the role of lemur tyrosine kinase 2 (LMTK2) in gastric cancer cell proliferation and cell cycle progression, as well as in tumor-bearing nude mouse models. The expression levels of LMTK2 were determined in gastric cancer cell lines. In addition, the effects of LMTK2 silencing or overexpression on cell proliferation were measured using Cell Counting Kit-8, BrdU and colony formation assays. Cell cycle progression was analyzed using flow cytometry and western blotting. The expression levels of proteins associated with the ß-catenin pathway were assessed using western blot analysis. A tumor-bearing nude mouse model was established by injecting gastric cancer cells, and the effect of LMTK2 knockdown or overexpression on tumor growth was examined. The expression levels of LMTK2 were found to be upregulated in all gastric cancer cell lines. Moreover, LMTK2 knockdown inhibited cell proliferation, colony formation and cell cycle progression. LMTK2 knockdown also inhibited the activation of GSK-3ß/ß-catenin signaling, as evidenced by reduced GSK-3ß phosphorylation and nuclear ß-catenin levels. LMTK2 knockdown also suppressed tumor growth, whereas overexpression accelerated this process. In conclusion, LMTK2 silencing can inhibit the proliferation of gastric cancer cells in vitro and tumor growth in vivo by regulating GSK-3ß phosphorylation and ß-catenin nuclear translocation.

3.
Mass Spectrom Rev ; : e21741, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34719806

RESUMO

Cancers are caused by accumulated DNA mutations. This recognition of the central role of mutations in cancer and recent advances in next-generation sequencing, has initiated the massive screening of clinical samples and the identification of 1000s of cancer-associated gene mutations. However, proteomic analysis of the expressed mutation products lags far behind genomic (transcriptomic) analysis. With comprehensive global proteomics analysis, only a small percentage of single nucleotide variants detected by DNA and RNA sequencing have been observed as single amino acid variants due to current technical limitations. Proteomic analysis of mutations is important with the potential to advance cancer biomarker development and the discovery of new therapeutic targets for more effective disease treatment. Targeted proteomics using selected reaction monitoring (also known as multiple reaction monitoring) and parallel reaction monitoring, has emerged as a powerful tool with significant advantages over global proteomics for analysis of protein mutations in terms of detection sensitivity, quantitation accuracy and overall practicality (e.g., reliable identification and the scale of quantification). Herein we review recent advances in the targeted proteomics technology for enhancing detection sensitivity and multiplexing capability and highlight its broad biomedical applications for analysis of protein mutations in human bodily fluids, tissues, and cell lines. Furthermore, we review recent applications of top-down proteomics for analysis of protein mutations. Unlike the commonly used bottom-up proteomics which requires digestion of proteins into peptides, top-down proteomics directly analyzes intact proteins for more precise characterization of mutation isoforms. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large-scale targeted detection and quantification of important protein mutations are discussed.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34813325

RESUMO

Global and phosphoproteome profiling has demonstrated great utility for the analysis of clinical specimens. One barrier to the broad clinical application of proteomic profiling is the large amount of biological material required, particularly for phosphoproteomics─currently on the order of 25 mg wet tissue weight. For hematopoietic cancers such as acute myeloid leukemia (AML), the sample requirement is ≥10 million peripheral blood mononuclear cells (PBMCs). Across large study cohorts, this requirement will exceed what is obtainable for many individual patients/time points. For this reason, we were interested in the impact of differential peptide loading across multiplex channels on proteomic data quality. To achieve this, we tested a range of channel loading amounts (approximately the material obtainable from 5E5, 1E6, 2.5E6, 5E6, and 1E7 AML patient cells) to assess proteome coverage, quantification precision, and peptide/phosphopeptide detection in experiments utilizing isobaric tandem mass tag (TMT) labeling. As expected, fewer missing values were observed in TMT channels with higher peptide loading amounts compared to lower loadings. Moreover, channels with a lower loading have greater quantitative variability than channels with higher loadings. A statistical analysis showed that decreased loading amounts result in an increase in the type I error rate. We then examined the impact of differential loading on the detection of known differences between distinct AML cell lines. Similar patterns of increased data missingness and higher quantitative variability were observed as loading was decreased resulting in fewer statistical differences; however, we found good agreement in features identified as differential, demonstrating the value of this approach.

5.
Br J Radiol ; : 20210279, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34813375

RESUMO

OBJECTIVES: To investigate the value of 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) combined with the platelet-lymphocyte ratio (PLR) in predicting the prognosis of nasopharyngeal carcinoma (NPC). METHODS: This was a retrospective analysis of the data of 73 patients with NPC who underwent 18F-FDG PET/CT before treatment from January 2010 to December 2014. The maximum standard uptake value (SUVmax) of NPC and the PLR within 1 week before treatment were both measured. The Mann-Whitney U-test was used to compare the differences between the SUVmax and PLR among the different clinical characteristics of patients with NPC and the 5-year progression-free survival (PFS) rate; according to the receiver operating characteristic (ROC) curve, the best cutoff values of the SUVmax and PLR were obtained and used to group patients. The Kaplan-Meier method and Log-rank test were used to conduct univariate analysis of 5-year PFS in patients with NPC, and Cox regression was used to conduct multivariate analysis; differences in the 5-year PFS of patients with different SUVmax values combined with the PLR were compared. RESULTS: The SUVmax and PLR of patients with disease progression within 5 years were higher than those of patients without disease progression (p = 0.006 and p = 0.026). SUVmax = 9.7 and PLR = 132.98 had the best prognostic diagnostic efficiency for patients. Cox multivariate analysis showed that the SUVmax and PLR are independent factors affecting the prognosis of NPC. The 5-year PFS of patients with SUVmax <9.7 was significantly higher than that of patients with SUVmax ≥9.7 in the high PLR group (PLR ≥132.98) and in the low PLR group (PLR <132.98) (59.3% vs 29.4%, p = 0.033 and 90.9% vs 42.9%, p = 0.006, respectively). For patients with SUVmax <9.7, the 5-year PFS of the high PLR group was significantly lower than the low PLR group (59.3% vs 90.9%, p = 0.016); for patients with SUVmax ≥9.7, there was no significant difference in 5-year PFS between the high PLR group and the low PLR group (29.4% vs 42.9%, p = 0.406). CONCLUSIONS: Both the SUVmax of the primary tumor and the PLR before treatment have an important influence on the prognosis of NPC. Combining the SUVmax and the PLR can more accurately predict the prognosis of patients with NPC. ADVANCES IN KNOWLEDGE: In this study, we evaluated the prognostic value of combining pretreatment tumor 18F-FDG uptake on PET/CT imaging and PLR in NPC patients. We found that both SUVmax and PLR are independent factors for the PFS of NPC patients, and a low SUVmax (SUVmax <9.7) combined with a low PLR (PLR <132.98) revealed significant PFS benefit.

6.
Front Endocrinol (Lausanne) ; 12: 759049, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803921

RESUMO

Purpose: To investigate the prognostic significance of extranodal extension (ENE) in papillary thyroid cancer (PTC). Methods: Seven hundred forty-three PTC patients were enrolled in the study from January 2014 to December 2017. The patients were dichotomized according to the presence of ENE. Logistic analysis was used to compare differences between the two groups. Kaplan-Meier (K-M) curve and propensity score matching (PSM) analyses were used for recurrence-free survival (RFS) comparisons. Cox regression was performed to analyze the effects of ENE on RFS in PTC. Results: Thirty-four patients (4.58%) had ENE. Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE. Further logistic regression analysis showed that age, extrathyroidal extension, and nodal stage remained statistically significant. Evaluation of K-M curves showed a statistically significant difference between the two groups before and after PSM. Cox regression showed that tumor size and ENE were independent risk factors for RFS. Conclusions: Age ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis were identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC.

7.
BMJ Open ; 11(11): e052557, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34810188

RESUMO

OBJECTIVES: Regular moderate-to-vigorous intensity recreational physical activity (PA) improves physical and cognitive functions. However, the age-associated relationships between non-recreational PA and functional ability remain less explored. We examined the associations between housework and functional health among younger and older Singaporean community-dwelling adults. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Younger (<65 years, n=249) and older (≥65 years, n=240) community-dwelling adults were randomly recruited from a large residential town in Singapore. OUTCOME MEASURES: Physical function was assessed using Short Physical Performance Battery (SPPB), repeated-chair-sit-to-stand and gait speed. Cognitive and sensorimotor functions were assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Physiological Profile Assessment (PPA), respectively. METHODS: Light housework (LH) and heavy housework (HH), recreational, and occupational and transport-related PAs were assessed using PA questionnaires. Participants were dichotomised into low-volume and high-volume LH and HH groups. Results were adjusted for level of recreational and other non-recreational PAs. RESULTS: Among older but not younger adults, RBANS scores were 8% and 5% higher in high HH and LH groups compared with low HH and LH groups, respectively (p=0.012 and p=0.016). Specifically, HH was associated with 14% higher attention score (p=0.014), and LH was associated with 12% and 8% higher immediate and delayed memory scores, respectively (p<0.001 and p=0.004). In older adults, sit-to-stand time and PPA scores were 8% and 23% lower in the high HH group than the low HH group, respectively (p=0.011 and p=0.040). SPPB and gait speed did not differ with age or HH. LH was not associated with physical or sensorimotor function. CONCLUSIONS: Among older adults, housework is associated with higher cognitive function, specifically in attention and memory. Associations of housework with physical function and sensorimotor performance were intensity dependent. Housework PA is positively associated with functional health among community-dwelling older adults, independent of recreation and other non-recreational PAs. Further longitudinal and intervention studies are needed to establish causality.

9.
Aging (Albany NY) ; 13(21): 24171-24191, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740994

RESUMO

Genomic instability (GIN) is pivotal in regulating tumor drug resistance, which blocked the treatment of triple negative breast cancer (TNBC). Although recent studies implied that non-coding RNA (ncRNA)-mediated autophagy abolishment promoted tumorigenesis by up-regulation of GIN, autophagy was known as a risk factor in tumor drug resistance. However, previous study also pointed that up-regulation of autophagy promoted GIN. Therefore, the relationship between autophagy and GIN is not clear, and more work is needed. And, if an ncRNA is identified to be a co-regulator of autophagy and GIN, it will be a potential therapy target of chemotherapy resistance in TNBC. In our study, we recognized both autophagy-GIN-associated microRNA (mi-26a-5p) by big data analysis, which was prognosis-correlated in breast cancer. Next, we identified the up-stream regulators (long non-coding RNA, lncRNA) and down-stream targets of miR-26a-5p by bioinformatics analysis (online public databases). Finally, we established lncRNA OTUD6B-AS1/miR-26a-5p/MTDH signaling pathway, and verified their functions by cytological, molecular biological and zoological experiments. In general, our study found (1) miR-26a-5p was a protective factor of breast cancer, while OTUD6B-AS1 and MTDH were risk factors; (2) OTUD6B-AS1 was the up-stream regulator of miR-26a-5p verified by luciferase; (3) up-regulation of miR-26a-5p and down-regulation of MTDH promoted cellular cytotoxicity of paclitaxel (PTX) in vitro and in vivo. (4) down-regulation of miR-26a-5p, overexpression of MTDH and OTUD6B-AS1 promoted autophagy and DNA damage; (5) up-regulation of OTUD6B-AS1 and MTDH inhibited DNA damage response (DDR) by inhibiting the phosphorylated activation of RAD51, ATR and ATM.

10.
Anal Chem ; 93(46): 15534-15542, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34747608

RESUMO

Currently, most of the electrochemical sensors were prepared based on the planar electrode (PE) and utilized in open circumstance. The accompanying issues include fixed and limited sensing area of PE, insufficient usage of the testing sample, tedious operation, and susceptibility to external environment. Herein, a novel tubular tip-like sensor (TTLS) platform was proposed, where a small tip accommodates all electrodes with a curved surface and also acts as a closed detection chamber. Teaming up with a commercial pipette and potentiostat, the TTLS is able to accomplish the whole assay procedure including sampling, detection, rinsing, and regeneration with a single hand. The electrochemical interface area can be easily tuned to adapting for different scenarios with varied sensitivity request. Moreover, two TTLS-based array systems were derived: one integrates multiple working electrodes in one tip for multicomponent quantification and the other assembles eight independent TTLSs for high-throughput analysis. The admirable sensing performance of the TTLS was fully proved by detecting several liver-related biomarkers in 5 µL of the serum sample. The proposed tubular sensor platform is superior to the traditional electrochemical sensor in the aspects of unique sensing surface, fast and simple operation, good portability, and great compatibility. The TTLS could be used as an ideal analytical tool in point-of-care testing and other fields.

11.
Br J Cancer ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34799695

RESUMO

BACKGROUND: Recently, a novel HOXB13 variant (X285K) was observed in men of African descent with prostate cancer (PCa) in Martinique. Little is known about this or other variants in HOXB13 which may play a role in PCa susceptibility in African-American (AA) men. METHODS: We sequenced HOXB13 in an AA population of 1048 men undergoing surgical treatment for PCa at Johns Hopkins Hospital. RESULTS: Seven non-synonymous germline variants were observed in the patient population. While six of these variants were seen only once, X285K was found in eight patients. In a case-case analysis, we find that carriers of this latter variant are at increased risk of clinically significant PCa (1.2% carrier rate in Gleason Score ≥7 PCa vs. 0% in Gleason Score <7 PCa, odds ratio, OR = inf; 95% Confidence Interval, 95%CI:1.05-inf, P = 0.028), as well as PCa with early age at diagnosis (2.4% carrier rate in patients <50 year vs. 0.5% carrier rate in patients ≥50 year, OR = 5.25, 95% CI:1.00-28.52, P = 0.03). CONCLUSIONS: While this variant is rare in the AA population (~0.2% MAF), its ancestry-specific occurrence and apparent preferential association with risk for the more aggressive disease at an early age emphasizes its translational potential as an important, novel PCa susceptibility marker in the high-risk AA population.

12.
Chemistry ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34791726

RESUMO

Rapid capture of 129 I with high volatility and toxicity in the environment has attracted much attention. Herein we reported a firstly synthesized nonporous material: pyridine N-oxides (NTPO and ATPO) as iodine adsorbent. Both of NTPO and ATPO exhibit remarkable performance on the adsorption of iodine in aqueous solution, vapor state and organic solvents. Upon the capture of iodine, pyridine N-oxides were transformed to binary cocrystals combined with the pyridine N-oxides and iodine which is driven by halogen bond between iodine and oxygen atoms. Moreover, pyridine N-oxides shows high chemical, thermal and moist stability.

13.
Nature ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795452

RESUMO

Nutrients are emerging regulators of adaptive immunity1. Selective nutrients interplay with immunological signals to activate mechanistic target of rapamycin complex 1 (mTORC1), a key driver of cell metabolism2-4, but how these environmental signals are integrated for immune regulation remains unclear. Here we use genome-wide CRISPR screening combined with protein-protein interaction networks to identify regulatory modules that mediate immune receptor- and nutrient-dependent signalling to mTORC1 in mouse regulatory T (Treg) cells. SEC31A is identified to promote mTORC1 activation by interacting with the GATOR2 component SEC13 to protect it from SKP1-dependent proteasomal degradation. Accordingly, loss of SEC31A impairs T cell priming and Treg suppressive function in mice. In addition, the SWI/SNF complex restricts expression of the amino acid sensor CASTOR1, thereby enhancing mTORC1 activation. Moreover, we reveal that the CCDC101-associated SAGA complex is a potent inhibitor of mTORC1, which limits the expression of glucose and amino acid transporters and maintains T cell quiescence in vivo. Specific deletion of Ccdc101 in mouse Treg cells results in uncontrolled inflammation but improved antitumour immunity. Collectively, our results establish epigenetic and post-translational mechanisms that underpin how nutrient transporters, sensors and transducers interplay with immune signals for three-tiered regulation of mTORC1 activity and identify their pivotal roles in licensing T cell immunity and immune tolerance.

14.
Cell Prolif ; : e13153, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34773310

RESUMO

'Human retinal pigment epithelial cells' is the first set of guidelines on human retinal pigment epithelial cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies technical requirements, test methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements and transportation requirements and waste disposal requirements for human retinal pigment epithelial cells, which is applicable to quality control during the process of manufacturing and testing of human retinal pigment epithelial cells. It was originally released by the Chinese Society for Cell Biology on 9 January 2021. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols and accelerate the international standardization of human retinal pigment epithelial cells for applications.

15.
Phys Rev Lett ; 127(18): 180502, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34767431

RESUMO

We report phase-programmable Gaussian boson sampling (GBS) which produces up to 113 photon detection events out of a 144-mode photonic circuit. A new high-brightness and scalable quantum light source is developed, exploring the idea of stimulated emission of squeezed photons, which has simultaneously near-unity purity and efficiency. This GBS is programmable by tuning the phase of the input squeezed states. The obtained samples are efficiently validated by inferring from computationally friendly subsystems, which rules out hypotheses including distinguishable photons and thermal states. We show that our GBS experiment passes a nonclassicality test based on inequality constraints, and we reveal nontrivial genuine high-order correlations in the GBS samples, which are evidence of robustness against possible classical simulation schemes. This photonic quantum computer, Jiuzhang 2.0, yields a Hilbert space dimension up to ∼10^{43}, and a sampling rate ∼10^{24} faster than using brute-force simulation on classical supercomputers.

16.
Asian J Surg ; 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34642052

RESUMO

PURPOSE: Currently, the early diagnosis of second primary cancers (SPCs) after gastric cancer (GC) remains a thorny problem. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been demonstrated to participate in the development of GC. Thus, we investigated diagnostic values of NLR and PLR in SPCs after GC. MATERIALS AND METHODS: 78 patients with SPCs after GC, 99 patients with single GC and 107 healthy controls were retrospectively analyzed between 2011 and 2021. We detected their hematological parameters, plotted receiver operating characteristic curves of NLR, PLR, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) alone or in combination for SPCs, and compared area under the curve (AUC). RESULTS: SPC patients had higher levels of NLR, PLR, CEA and CA19-9 than other groups, and all indicators increased synchronically with GC progression. Compared with single GC patients, SPC patients had higher NLR levels in each TNM stage and higher PLR levels in stage II-IV. Moreover, NLR and PLR levels in stage I of SPC patients were significantly higher than those in stage IV of single GC patients. The diagnostic efficiency of NLR (AUC = 0.845) and PLR (AUC = 0.796) was significantly higher than that of CEA (AUC = 0.672) and CA19-9 (AUC = 0.655) in SPCs. Pairwise combination had superior diagnostic performance for SPCs, with the largest being NLR combined with PLR (AUC = 0.881). CONCLUSIONS: Clinically, existing diagnostic methods can be combined with NLR and PLR in early diagnosing SPCs after GC.

17.
JTO Clin Res Rep ; 2(10): 100231, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34661178

RESUMO

Introduction: PARP inhibition may enhance antitumor responses in BAP1-associated mesothelioma by inducing synthetic lethality. Methods: A single-center, nonrandomized, phase 2 trial was conducted, in which patients with refractory mesothelioma were given olaparib 300 mg twice daily in a 21-day cycle until disease progression or intolerable toxicity. The primary objective was to determine the objective response rate on the basis of somatic or germline mutation status of DNA repair genes. The secondary objectives were to assess safety and tolerability and to determine progression-free survival (PFS) and overall survival (OS). Whole-exome sequencing was performed on blood and tumor. Results: A total of 23 previously treated patients with pleural and peritoneal mesothelioma were enrolled and treated (germline BAP1, n = 4; germline MRE11A, n = 1; somatic BAP1, n = 8 mutations). There was one (4%) partial response, 18 (78%) with stable disease at 6 weeks, and four (17%) with progressive disease. The median overall PFS and OS were 3.6 months (95% confidence interval [CI]: 2.7-4.2 mo) and 8.7 months (95% CI: 4.7 mo-not estimable), respectively. The median PFS of germline BAP1 mutants (n = 4) was 2.3 months (95% CI: 1.3-3.6 mo) versus 4.1 months (95% CI: 2.7-5.5 mo) for wild-type (n = 19; p = 0.019). The median OS was 4.6 months (95% CI: 3.1-4.9 mo) for germline BAP1 mutation versus 9.6 months (95% CI: 5.5 mo-not estimable) in no germline mutation (p = 0.0040). Olaparib was safe with no new safety concerns. Conclusions: Olaparib has limited activity in previously treated mesothelioma including patients with BAP1 mutations. Germline BAP1 mutations were associated with decreased PFS and OS.

18.
Prostate ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674288

RESUMO

BACKGROUND: Germline mutations in several genes, mainly DNA repair genes, have been associated with prostate cancer (PCa) progression. However, primarily due to the rarity of mutations, statistical evidence for these associations is not consistently established. The objective of this study is to synthesize evidence from multiple studies using a meta-analysis. METHODS: Genes analyzed were chosen based on National Comprehensive Cancer Network guidelines recommendations (10 genes) and a commonly reported gene (NBN). PCa progression in this analysis was defined as either having metastases or PCa-specific mortality. We searched PubMed for papers published before April 26, 2021, using selected keywords. Pooled odds ratio (OR) was estimated in all races and Caucasians-only using both fixed- and random-effect models. RESULTS: The search identified 1028 papers and an additional five from a manual review of references. After a manual process that excluded noneligible studies, 11 papers remained, including a total of 3944 progressors and 20,054 nonprogressors. Combining results from these eligible studies, mutation carrier rates were significantly higher in progressors than nonprogressors for NBN, BRCA2, ATM (under both fixed- and random-effect models), for CHEK2 (under fixed-effect model only), and for PALB2 (under random-effect model only), p < 0.05. Pooled OR (95% confidence interval) was 6.38 (2.25-18.05), 3.41 (2.31; 5.03), 1.93 (1.17-3.20), and 1.53 (1.00-2.33) for NBN, BRCA2, ATM, and CHEK2, respectively, under fixed-effect model and 2.63 (1.12-6.13) for PALB2 under random-effect model. No significant association was found for the six remaining genes. Certainty of evidence was low for many genes due primarily to the limited number of eligible studies and mutation carriers. CONCLUSIONS: Statistical evidence for five genes was obtained in this first meta-analysis of germline mutations and PCa progression. While these results may help urologists and genetic counselors interpret germline testing results for PCa progression, more original studies are needed.

19.
J Dairy Sci ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34696908

RESUMO

The physiological function of the reticulorumen plays an essential role in ruminant nutrition, and detailed knowledge of rumen motility can further advance understanding of ruminant nutrition and physiology. Rumen motility was simulated by setting different stirrer rotation speeds in a rumen simulation technique (RUSITEC) system. The aim of this study was to investigate the effects of rotation speeds on rumen fermentation, saturation factor of dissolved gases, hydrogen (H2) and methane (CH4) emissions, microbial protein synthesis, and selected microbial population using RUSITEC. The experiment was performed according to a balanced 3 × 3 Latin square design, and each period included 7 d for adaptation and 3 d for sampling. Three motility treatments included 5, 15, and 25 rpm rotation speeds. Daily total gas and H2 and CH4 emissions had quadratic responses to the increasing rotation speed and were highest at 15 rpm. Quadratic and linear responses (highest at 5 rpm) to increasing rotation speed were observed for saturation factors of H2 and CH4, liquid-dissolved H2 and CH4 concentrations, and headspace concentration of H2 in the gas phase, whereas increasing rotation speed linearly decreased saturation factors of CO2 and liquid-dissolved CO2 concentration. Quadratic and linear responses to increasing rotation speed were observed for molar percentages of acetate, ammonia, and microbial protein concentration, whereas increasing rotation speed quadratically increased pH and decreased total volatile fatty acid concentration and acetate-to-propionate ratio. The 15-rpm rotation speed had the highest values of total volatile fatty acids, acetate molar percentage, and microbial protein concentration. Quadratic and linear responses to increasing rotation speed were observed for copy numbers of solid-associated fungi and fluid-associated bacteria, fungi, and protozoa, while increasing rotation speed linearly increased copy numbers of solid-associated protozoa. Rotation at 15 rpm increased populations of fungi and protozoa in the solid rumen contents and the population of bacteria and fungi in the liquid rumen contents. In summary, this study provides insights on the biofunction of proper rumen motility (i.e., at a rotation speed of 15 rpm), such as improving feed fermentation, increasing gas emissions with decreased dissolved gas concentrations and saturation factors, and promoting microbial colonization and microbial protein synthesis, although further increase in rotation speed (i.e., to 25 rpm) decreases feed fermentation and microbial protein synthesis.

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