Comprehensive analysis of key host gene-microbe networks in the cecum tissues of the obese rabbits induced by a high-fat diet.

The Cecum is a key site for cellulose digestion in nutrient metabolism of intestine, but its mechanisms of microbial and gene interactions has not been fully elucidated during pathogenesis of obesity. Therefore, the cecum tissues of the New Zealand rabbits and their contents between the high-fat diet-induced group (Ob) and control group (Co) were collected and analyzed using multi-omics. The metagenomic analysis indicated that the relative abundances of Corallococcus_sp._CAG:1435 and Flavobacteriales bacterium species were significantly lower, while those of Akkermansia glycaniphila, Clostridium_sp._CAG:793, Mycoplasma_sp._CAG:776, Mycoplasma_sp._CAG:472, Clostridium_sp._CAG:609, Akkermansia_sp._KLE1605, Clostridium_sp._CAG:508, and Firmicutes_bacterium_CAG:460 species were significantly higher in the Ob as compared to those in Co. Transcriptomic sequencing results showed that the differentially upregulated genes were mainly enriched in pathways, including calcium signaling pathway, PI3K-Akt signaling pathway, and Wnt signaling pathway, while the differentially downregulated genes were mainly enriched in pathways of NF-kappaB signaling pathway and T cell receptor signaling pathway. The comparative analysis of metabolites showed that the glycine, serine, and threonine metabolism and cysteine and methionine metabolism were the important metabolic pathways between the two groups. The combined analysis showed that CAMK1, IGFBP6, and IGFBP4 genes were highly correlated with Clostridium_sp._CAG:793, and Akkermansia_glycaniphila species. Thus, the preliminary study elucidated the microbial and gene interactions in cecum of obese rabbit and provided a basis for further studies in intestinal intervention for human obesity.

Prognostic implication and immunotherapy response prediction of a novel ubiquitination-related gene signature in liver cancer.

HCC, also known as hepatocellular carcinoma, is a frequently occurring form of cancer with an unfavorable prognosis. This research constructed a prognostic signature related to ubiquitination and investigated its correlation with the response to immunotherapy in HCC. The Molecular Signatures Database provided a compilation of genes associated with ubiquitination. A gene signature related to ubiquitination was obtained through Cox regression using the Least Absolute Shrinkage and Selection Operator method. The genetic factors CPY26B1, MCM10, SPINK4, and TRIM54 notably impacted the outcomes of HCC. The patients were divided into two groups: one group had a high risk of poor survival while the other had a low risk but a greater chance of controlling HCC progression. Both univariate and multivariate analyses using Cox regression found the risk score to be an independent predictor of HCC prognosis. Gene set enrichment analysis (GSEA) indicated enrichment in cell cycle and cancer-related microRNAs in high-risk groups. The tumor microenvironment (TME), response to immunotherapy, and effectiveness of chemotherapy medications positively correlated with the risk score. In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

HyperFace: A Deep Fusion Model for Hyperspectral Face Recognition.

Face recognition has been well studied under visible light and infrared (IR) in both intra-spectral and cross-spectral cases. However, how to fuse different light bands for face recognition, i.e., hyperspectral face recognition, is still an open research problem, which has the advantages of richer information retention and all-weather functionality over single-band face recognition. Thus, in this research, we revisit the hyperspectral recognition problem and provide a deep learning-based approach. A new fusion model (named HyperFace) is proposed to address this problem. The proposed model features a pre-fusion scheme, a Siamese encoder with bi-scope residual dense learning, a feedback-style decoder, and a recognition-oriented composite loss function. Experiments demonstrate that our method yields a much higher recognition rate than face recognition using only visible light or IR data. Moreover, our fusion model is shown to be superior to other general-purpose image fusion methods that are either traditional or deep learning-based, including state-of-the-art methods, in terms of both image quality and recognition performance.

Development and validation of a scoring system to predict esophagogastroduodenoscopy necessity.

OBJECTIVE: This study aimed to develop and validate a scoring system for predicting the need for esophagogastroduodenoscopy (EGD) in clinical practice to enhance accuracy and reduce misapplications. METHODS: From February 2021 to April 2022, outpatients scheduled for EGD at the Department of Gastroenterology in our hospital were recruited. Patients completed the system evaluation by providing clinical symptoms, relevant medical history, and endoscopic findings. Patients were randomly divided into the training and validation cohorts (at 2:1 ratio). The optimal algorithm was selected from five alternatives including a parallel test. Six physicians participated in a human-computer comparative validation. Sensitivity and negative likelihood ratio (-LR) were used as the primary indicators. RESULTS: Altogether 865 patients were enrolled, with 578 in the training cohort and 287 in the validation cohort. The scoring system comprised 21 variables, including age, 13 typical clinical symptoms, and seven medical history variables. The parallel test was selected as the final algorithm. Positive EGD findings were reported in 54.5% of the training cohort and 62.7% of the validation cohort. The scoring system demonstrated a sensitivity of 79.0% in the training cohort and 83.9% in the validation cohort, with -LR being 0.627 and 0.615, respectively. Compared to physicians, the scoring system exhibited higher sensitivity (84.0% vs 68.7%, P = 0.02) and a lower -LR (1.11 vs 2.41, P = 0.439). CONCLUSIONS: We developed a scoring system to predict the necessity of EGD using a parallel test algorithm, which was user-friendly and effective, as evidenced by single-center validation.

Analysis of Variables Associated with Positive Micro-Embolic Signals Detected by Transcranial Doppler in Patients with Atrial Fibrillation and Their Predictive Value for Embolic Risk.

Objective: This study examined the factors associated with positive micro-embolic signals (MES) on transcranial Doppler monitoring in patients with atrial fibrillation (AF), as well as the predictive value of MES for the risk of embolism in AF. Methods: Sixty-six patients who had micro emboli with AF were included in the positive group, and 75 patients who did not have micro emboli with AF served as the control group. The clinical data, congestive heart failure, hypertension, age ≥ 75 (doubled), diabetes mellitus, prior stroke or transient ischemic attack (doubled), vascular disease, age 65-74, female (CHA2DS2-VASc) score, D-dimer (D-d) level, echocardiography results, and brain magnetic resonance imaging (MRI) findings were compared between the two groups. Logistic regression models were used to analyze the relationship between positive micro emboli with CHA2DS2-VASc score, D-d, left atrial anteroposterior diameter (LAD), and silent cerebral ischemia (SCI) occurrence. Results: The CHA2DS2-VASc score, D-d level, and LAD were significantly higher in the positive group than in the control group (P < 0.05) and were accompanied by a higher detection rate of SCI by brain MRI (P < 0.01). Elevated D-d levels, increased LAD, and the detection rate of SCI were all highly positively correlated with positive micro emboli. Also, CHA2DS2-VASc score ≥ 2 showed a significant positive correlation with positive micro emboli, and the higher CHA2DS2-VASc score was associated with a stronger correlation. The multivariate regression analysis demonstrated that positive micro-embolic was independently associated with SCI and a CHA2DS2-VASc score of ≥ 4. Conclusion: Positive micro emboli in patients with persistent AF are consistent with an increased risk of embolism, and are independently associated with a higher CHA2DS2-VASc score and SCI, which can be used as an indicator of individual embolic risk in patients with AF.

[Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review].

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

Surgeon Variation in Perioperative Opioid Prescribing and Medium- or Long-term Opioid Utilization after Total Knee Arthroplasty: A Cross-sectional Analysis.

BACKGROUND: Whether a particular surgeon's opioid prescribing behavior is associated with prolonged postoperative opioid use is unknown. This study tested the hypothesis that the patients of surgeons with a higher propensity to prescribe opioids are more likely to utilize opioids long-term postoperatively. METHODS: The study identified 612,378 Medicare fee-for-service patients undergoing total knee arthroplasty between January 1, 2011, and December 31, 2016. "High-intensity" surgeons were defined as those whose patients were, on average, in the upper quartile of opioid utilization in the immediate perioperative period (preoperative day 7 to postoperative day 7). The study then estimated whether patients of high-intensity surgeons had higher opioid utilization in the midterm (postoperative days 8 to 90) and long-term (postoperative days 91 to 365), utilizing an instrumental variable approach to minimize confounding from unobservable factors. RESULTS: In the final sample of 604,093 patients, the average age was 74 yr (SD 5), and there were 413,121 (68.4%) females. A total of 180,926 patients (30%) were treated by high-intensity surgeons. On average, patients receiving treatment from a high-intensity surgeon received 36.1 (SD 35.0) oral morphine equivalent (morphine milligram equivalents) per day during the immediate perioperative period compared to 17.3 morphine milligram equivalents (SD 23.1) per day for all other patients (+18.9 morphine milligram equivalents per day difference; 95% CI, 18.7 to 19.0; P < 0.001). After adjusting for confounders, receiving treatment from a high-intensity surgeon was associated with higher opioid utilization in the midterm opioid postoperative period (+2.4 morphine milligram equivalents per day difference; 95% CI, 1.7 to 3.2; P < 0.001 [11.4 morphine milligram equivalents per day vs. 9.0]) and lower opioid utilization in the long-term postoperative period (-1.0 morphine milligram equivalents per day difference; 95% CI, -1.4 to -0.6; P < 0.001 [2.8 morphine milligram equivalents per day vs. 3.8]). While statistically significant, these differences are clinically small. CONCLUSIONS: Among Medicare fee-for-service patients undergoing total knee arthroplasty, surgeon-level variation in opioid utilization in the immediate perioperative period was associated with statistically significant but clinically insignificant differences in opioid utilization in the medium- and long-term postoperative periods.

Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study.

BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.

Prognostic significance of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in patients with primary T cell lymphomas.

OBJECTIVE: T cell lymphomas are associated with an aggressive worse prognosis. This study is designed to assess T cell lymphomas using 18F-FDG PET/CT. METHODS: Sixty-four patients with newly diagnosed T cell lymphomas underwent PET/computed tomography (PET/CT) scans, 47 cases who were fully followed up were retrospectively reviewed and analyzed. Overall survival (OS) and progression-free survival (PFS) were recorded for prognosis. We measured the maximum standardized uptake value (SUVmax) in all cases, analyzed the correlation between SUVmax and survival and other clinicopathologic parameters. Kaplan-Meier log-rank tests were then used to compare the survival of high and low PET/CT parameter groups, and multivariate Cox proportional hazards regression analysis was carried out to identify predictors of OS and PFS. RESULTS: With a median follow-up of 26.5 (range 0.7-117.5) months, the 1-, 2- and 3-year OS were 75.6, 61.7 and 49.2%, and PFS were 49.3, 39.9 and 29.9%, respectively in 47 patients. Among them, 33 cases progressed with a median time of 9.5 (0.7-115.0) months, and 26 patients died with a median survival time of 26.5 (0.7-117.5) months. Multivariate analysis showed the following independent prognostic factors for OS: age >60 years (P = 0.002), SUVmax >9.7 (P = 0.009) and extranodal involvement of more than one site (P = 0.018). In addition, lactate dehydrogenase level (P = 0.003) and B symptoms (P = 0.018) were independent risk factors for PFS. CONCLUSION: Pretherapy SUVmax may serve as an independent predictor of outcome in patients with newly diagnosed T cell lymphomas.

Food Insecurity Among Health Care Workers In The US.

Food insecurity, or the lack of access to an adequate supply of nutritious food, is associated with poor health outcomes including diabetes, heart disease, and depression. Food insecurity research has grown in the past two decades and has spurred efforts in the US health care system to "screen and intervene" for patient food insecurity. Using nationally representative data from the period 2013-18, this study is the first to our knowledge to investigate the prevalence of food insecurity for the health care workforce, an industry that ranges from low-skill, low-wage hourly jobs to highly specialized salaried positions. We found that relative to health diagnosing and treating practitioners, the odds of being food insecure were 5.1 times higher for health care support workers and 2.5 times higher for health technologists and technicians. The health care industry is the largest and fastest-growing US employer, and it is vital that leaders and policy makers address food insecurity among the health care workforce.

Monoclonal Immunoglobulin-Associated Renal Lesions in Patients with Newly Diagnosed Multiple Myeloma: A Report from a Single Center.

BACKGROUND: Monoclonal immunoglobulin-associated renal lesions in patients with newly diagnosed myeloma vary. We aimed to determine the pathological spectrum and analyze associated prognostic factors. METHODS: Fifty-six patients with newly diagnosed multiple myeloma and biopsy-proven renal lesions were enrolled. Kidney biopsies were reanalyzed, and the baseline clinical characteristics, treatments and outcomes were recorded. RESULTS: Fifty-one patients had monoclonal immunoglobulin-associated renal lesions, with myeloma cast nephropathy (MCN) being the most common pattern. We divided our cohort into pure MCN, MCN+ other pathologies and non-MCN. Patients with MCN had more severe renal injury than those with non-MCN. In our cohort, none of the patients with pure MCN or MCN + other pathologies presented with nephrotic syndrome. Patients with non-MCN had better renal and overall survival than those with pure MCN but similar survivals to those with MCN + other pathologies. Number of myeloma casts (HR 1.08, p = 0.012) was the only independent prognostic factor for renal survival. Male sex (HR: 3.64; p = 0.015) and number of casts (HR: 1.17; p = 0.001) were independent prognostic factors for overall survival. CONCLUSION: Patients with MCN had more severe renal injury than those with non-MCN. Patients with non-MCN had better renal and overall outcomes than those with pure MCN, but their outcomes were similar to those with MCN + other pathologies. The independent predictors of overall survival were male sex and number of myeloma casts.

Balancing Heterogeneous Image Quality for Improved Cross-Spectral Face Recognition.

Matching infrared (IR) facial probes against a gallery of visible light faces remains a challenge, especially when combined with cross-distance due to deteriorated quality of the IR data. In this paper, we study the scenario where visible light faces are acquired at a short standoff, while IR faces are long-range data. To address the issue of quality imbalance between the heterogeneous imagery, we propose to compensate it by upgrading the lower-quality IR faces. Specifically, this is realized through cascaded face enhancement that combines an existing denoising algorithm (BM3D) with a new deep-learning-based deblurring model we propose (named SVDFace). Different IR bands, short-wave infrared (SWIR) and near-infrared (NIR), as well as different standoffs, are involved in the experiments. Results show that, in all cases, our proposed approach for quality balancing yields improved recognition performance, which is especially effective when involving SWIR images at a longer standoff. Our approach outperforms another easy and straightforward downgrading approach. The cascaded face enhancement structure is also shown to be beneficial and necessary. Finally, inspired by the singular value decomposition (SVD) theory, the proposed deblurring model of SVDFace is succinct, efficient and interpretable in structure. It is proven to be advantageous over traditional deblurring algorithms as well as state-of-the-art deep-learning-based deblurring algorithms.

The link between health and economic preferences: Evidence from 22 OECD countries.

We study the link between health status and economic preferences using survey data from 22 Organisation for Economic Co-operation and Development (OECD) countries. We hypothesize that there is a relationship between poor health and the preferences that people hold, and therefore their choices and decisions. We find that individuals with a limiting health condition are more risk averse and less patient, and that this is true for physical and mental health conditions. The magnitudes of the health gap are approximately 60% and 70% of the gender gap in risk and time preferences, respectively. Importantly, the health gaps are large for males, females, young, old, school dropouts, degree holders, employed, nonemployed, rich, and poor. They also hold for countries with different levels of gross domestic product (GDP), inequality, social expenditure, and disease burden.

Myeloma cast nephropathy with diffuse amyloid casts without systemic amyloidosis: two cases report.

BACKGROUND: Multiple myeloma (MM) is a plasma-cell derived hematologic malignant disease. The malignant proliferating plasma cells secrete massive monoclonal immunoglobulins which lead to various pathologic types of renal injury. Myeloma cast nephropathy (MCN) is the most common histopathologic lesion with the worst renal prognosis. Rarely, the free light chains in the protein casts can form amyloid fibrils. Here, we reported two rare cases of MCN with diffuse amyloid casts. CASE PRESENTATION: Case 1: A 54-year-old Chinese man presented with a 4-year history of multiple myeloma, proteinuria and hematuria. He had monoclonal IgAλ plus free λ spike in both serum and urine. He had been on chemotherapy for 4 years and maintained normal serum creatinine until 11 months ago. Then, his renal function deteriorated and he went on hemodialysis 4 months before admission. Renal biopsy showed diffuse amyloid casts in the tubular lumens, without any obvious amyloid deposits in other kidney compartments or signs of extra-renal amyloidosis. The amyloid fibrils formed around mononuclear cells which were CD68 negative. According to the morphology and location, these mononuclear cells were considered as tubular epithelial cells. The patient was maintained on chemotherapy and hemodialysis. He died 8 months after renal biopsy. Case 2: A 58-year-old Chinese man presented with a one-and-a-half-year history of proteinuria and slowly rising serum creatinine. He had monoclonal IgDλ spike in both serum and urine. Amyloid casts were observed in the tubular lumens and mononuclear cells could be identified in the center of some casts. There were no amyloid deposits in other kidney compartments and no sign of systemic amyloidosis. The patient also had fine granular deposits along the tubular basement membrane with λ linear staining along tubular basement membrane suggesting light chain deposition disease. He was treated with bortezomib-based chemotherapy followed by lenalidomide-based chemotherapy and achieved very good partial remission (VGPR). After 27 months of follow-up, the patient still showed no signs of systemic amyloidosis. CONCLUSIONS: These 2 cases of MCN with diffuse amyloid casts have different histopathologic characteristics from the usual myeloma casts and tubular epithelial cells might play important roles in the pathogenesis.

Racial and Ethnic Disparities in COVID-19 Infections and Deaths Across U.S. Nursing Homes.

BACKGROUND/OBJECTIVES: To determine racial/ethnic disparities in weekly counts of new COVID-19 cases and deaths among nursing home residents or staff. DESIGN: Cross-sectional analysis of national nursing home COVID-19 reports linked to other data. Multivariable two-part models modeled disparities in count of cases or deaths, and logistic regressions modeled disparities in self-reported shortages in staff and personal protective equipment (PPE), across nursing home groups with varying proportions of racial/ethnic minority residents, defined as low-, medium-, medium-high-, and high-proportion groups. SETTING: A total of 12,576 nursing homes nationally. PARTICIPANTS: None. INTERVENTION: None. MEASUREMENTS: Numbers of incident COVID-19 confirmed cases among residents and staff, and incident COVID-19 related deaths among residents (primary outcomes); and nursing home reported shortages in staff and PPE (secondary outcomes). All outcomes were reported for the week of May 25, 2020. RESULTS: The number of weekly new COVID-19 confirmed cases among residents ranged from an average of 0.4 cases per facility (standard deviation (SD) = 2.5) for the low-proportion group (93.0% had zero new cases) to 1.5 cases per facility (SD = 6.3) for the high-proportion group (78.9% had zero new cases). Multivariable regression estimated that compared with the low-proportion group, the likelihood of having at least one new resident case was 76% higher (odds ratio = 1.76; 95% confidence interval = 1.38-2.25; P = .000) for the high-proportion group. Similar across-facility disparities were found for the weekly count of new COVID-19 deaths among residents (ranging from 0.1 deaths per facility (SD = 1.1) for the low-proportion group to 0.4 deaths (SD = 2.0) for the high-proportion group) and in the weekly count of new COVID-19 confirmed cases among staff (ranging from 0.3 cases (SD = 1.4] to 1.3 cases (SD = 4.4) per facility). No substantial disparities in self-reported shortages of staff or PPE were found. CONCLUSION: Nursing homes caring for disproportionately more racial/ethnic minority residents reported more weekly new COVID-19 confirmed cases and/or deaths. Immediate actions are needed to address these system-level disparities.

CDK5 inhibition in vitro and in vivo induces cell death in myeloma and overcomes the obstacle of bortezomib resistance.

The emergence of new drugs is a major feature of the treatment history of multiple myeloma (MM), which also reflects the current incurability of MM. As a unique member of cyclin dependent kinase (CDK) family, CDK5 participates in numerous tumorigenic or non­tumorigenic processes. The aim of this study is to investigate the effects of CDK5 on the viability of MM cells and bortezomib resistance using western blotting, immunohistochemistry, transient transfection, MTT assays, cell cycle analysis, apoptosis assays and a myeloma xenograft mouse model. The present study found that MM patients with high CDK5 expression in the bone marrow do not respond well to bortezomib, have higher DS stage and worse prognosis. Genetic and pharmacological (dinaciclib) inhibition of CDK5 triggers MM cell viability inhibition. Dinaciclib induces G2/M arrest and apoptosis of MM cells. In vivo experiments with myeloma xenograft mice indicate that dinaciclib significantly reduces the volume of tumors with good tolerance. Dinaciclib combined with bortezomib exerts a synergistic anti­myeloma activity accompanied by inhibiting the activation of the nuclear factor­κB pathway. This study demonstrates the important role of CDK5 in the pathogenesis, viability, prognosis and resistance to bortezomib of MM, laying a solid theoretical foundation for further clinical use of CDK5 inhibitors.

The predictive value of serum free light chain level early after allogeneic hematopoietic stem cell transplantation for chronic graft-versus-host disease, a preliminary study.

OBJECTIVE: Serum free light chain (FLC) level is closely associated with the functional state of B lymphocytes, and many studies have shown that delayed reconstitution of B lymphocytes contributed to chronic graft-versus-host disease (cGVHD). This study assessed the predictive value of FLC levels in serum collected early after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for cGVHD. METHODS: Sixty-two patients who had undergone allo-HSCT were retrospectively reviewed. The correlations between the FLC levels and the development of cGVHD were explored. RESULTS: Of the 62 patients, 33 cases developed cGVHD, with the prevalence of 53.2%. With Seattle classification, 19 cases had limited cGVHD while 14 cases contracted extensive cGVHD. While with NIH classification, 17 cases had mild cGVHD, 6 cases moderate cGVHD, and 10 cases severe cGVHD. Multivariant statistical analysis showed that the FLC levels were not associated with all severities of cGVHD but were correlated with the development of extensive or moderate to severe cGVHD (P = .01 and .038, respectively). CONCLUSIONS: Serum FLC levels early after HSCT may reflect the functional state of B-cell reconstitution. Patients with low serum FLC Level early post-allo-HSCT tend to develop extensive cGVHD or moderate to severe cGVHD.

Nursing Home Staff Turnover and Perceived Patient Safety Culture: Results from a National Survey.

BACKGROUND AND OBJECTIVES: We examined the association between turnover of registered nurses (RNs) and certified nurse assistants (CNAs) and perceived patient safety culture (PSC) in nursing homes (NHs). RESEARCH DESIGN AND METHODS: In 2017, we conducted PSC survey using the Agency for Healthcare Research and Quality- developed and -validated instrument for NHs. A random sample of 2,254 U.S. NHs was identified. Administrators, directors of nursing (DONs), and nurse unit leaders served as respondents. Responses were obtained for 818 facilities from 1,447 individuals. The instrument contained 42 items relating to 12 PSC domains and turnover rates. PSC domains were based on five-point Likert scale items. A positive response was defined as "agree" or "strongly agree" (4-5 on the Likert scale). For CNAs low turnover was defined as <35%, and for RNs <15%. Facility-level and market-competition characteristics were included. Bivariate comparisons employed analysis of variance and chi-square tests. In multivariable models, we fit separate linear regressions for the average positive PSC score and for each of the 12 PSC domains, including turnover rates, NH, and market factors. RESULTS: In NHs with low turnover, the overall PSC scores were 4.04% (RNs) and 6.28% (CNAs) higher than in NHs with high turnover. Teamwork, staffing, and training/skills were associated with CNA but not RN turnover. DISCUSSION AND IMPLICATIONS: The effect of turnover on PSC depends on who leaves and to a lesser extent on the organizational characteristics. In NHs, improvements in PSC may depend on the ability to retain a well-trained and skilled nursing staff.