Does obstructive sleep apnea-induced intermittent hypoxia increase the incidence of solitary pulmonary nodules, thyroid nodules, and other disorders? A retrospective study based on 750 cardiovascular disease patients.

BACKGROUND: Obstructive sleep apnea (OSA) has been shown to be an important risk factor for cardiovascular disease (CVD), and intermittent hypoxia is an important pathogenetic factor for it. In the clinic, it was found that most CVD patients combined with OSA were also combined with solitary pulmonary nodules (SPN) or thyroid nodules (TN). Are these disorders related to intermittent hypoxia? One study showed that intermittent hypoxia is a pathogenic factor for lung cancer in mice, but there have been no clinical reports. So we conducted a retrospective study to explore whether intermittent hypoxia caused by OSA increases the incidence of SPN, TN, and other disorders. METHODS: We selected 750 patients with cardiovascular disease (CVD), who were divided into the control group and the OSA group according to the result of portable sleep monitoring. Retrospectively analyzed the comorbidities that patients with OSA are prone to and explored the correlation between OSA and those comorbidities. RESULTS: The incidence of SPN, TN, cervical spondylosis, and carotid-artery plaques was higher in the OSA group than in the control group. These diseases are significantly associated with OSA (p < 0.05), and their incidence increased with an elevated apnea-hypopnea index. After excluding interference from age, gender, BMI, smoking history, history of lung disease, and history of tumors, OSA showed a significant correlation with SPN. After excluding age, gender, BMI, and thyroid disease, OSA was associated with TN. Patients with comorbidities have lower nocturnal oxygen saturation and more extended periods of apnea. Logistic multiple regression results revealed that male, advanced age, obesity, CS, and nasal septum deviation were independent risk factors for OSA. CONCLUSIONS: Patients combined with OSA may further develop more comorbidities, such as SPN, TN, and carotid-artery plaques. It may be related to intermittent hypoxia caused by OSA.

BCL10 correlates with bad prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma.

It has been reported that B-cell CLL-lymphoma 10 (BCL10) serves as an oncogene in cervical cancer. However, the roles of BCL10 in hepatocellular carcinoma (HCC), especially involved in immune infiltration remain not clear. This study aims to explore the relationship between BCL10 and the prognosis and clinical significance, and immune infiltration in HCC. The expression of BCL10 was analyzed between HCC samples and non-tumor samples in the multiple datasets. In addition, the prognostic values of BCL10 and its methylation in HCC were also investigated. The clinical significance of BCL10 has also been explored. Furthermore, the correlation between BCL10 and immune infiltration in HCC microenvironment was assessed. Finally, the biological behaviors of BCL10 in HCC were verified by cell function experiments. It was found that the expression levels of BCL10 were increased in HCC patients in multiple datasets. Moreover, the increased BCL10 and its reduced methylation were associated with the poor survival. BCL10 was significantly associated with immune infiltration. When BCL10 was knocked down in HCC cells, their proliferation ability was significantly inhibited, their migration was significantly decreased, their apoptosis was significantly increased, and AKT signaling pathway was inhibited. In conclusion, BCL10 is a potential prognostic and diagnostic biomarker related to immune infiltration in HCC microenvironment.

Safety and feasibility of destination care for bariatric surgery: a single institution retrospective study.

INTRODUCTION: Increasing emphasis on value-based healthcare has prompted both employers and healthcare organizations to develop innovative strategies to supply high quality care to patients. One such strategy is through the bundled care payment model (BCPM). Through this model, our institution partnered with employers from across the country to provide quality care for their members. Patients traveling greater than 2 h driving time from the bariatric center were considered "destination" patients. To properly care for our destination patients, our institution created a "destination bariatric program." We sought to investigate comparative outcomes for the first 100 patients who completed the program. We hypothesized that there would be no difference in patient outcomes or complications between destination and local patient groups undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). METHODS AND PROCEDURES: A retrospective cohort analysis of patients undergoing bariatric surgery at a MBSAQIP-accredited bariatric surgery center between May 2019 and October 2021 was conducted. Patients were divided into destination or local patient groups based on participation in the established destination surgery program. Patient demographics, perioperative clinical outcomes, and complications were compared and statistically analyzed using two-sample t-tests, Chi-square tests, Fisher's exact tests, and univariate logistic regressions. RESULTS: This study identified 296 patients, which consisted of destination (n = 110) and local (n = 186) patient cohorts. Patients in the destination group had higher rates of diabetes mellitus (29.1% vs 24.2%, p = 0.029), but otherwise cohorts had similar basic demographics and comorbidities. Outcomes revealed no statistically significant associations between patient cohort (destination versus local) and ED admission (p = 0.305), hospital readmission (p = 0.893), surgical reintervention (p = 0.974), endoscopic-reintervention (p = 0.714), and patient complications in the postoperative period (30 days). CONCLUSION: Participation in destination care programs for bariatric surgery was found to be both safe and feasible. These destination programs represent an opportunity to provide a broader patient population access to complex surgical care.

National assessment of obstetrics and gynecology and family medicine residents' experiences with CenteringPregnancy group prenatal care.

OBJECTIVE: To examine family medicine (FM) and obstetrician-gynecologist (OB/GYN) residents' experiences with CenteringPregnancy (CP) group prenatal care (GPNC) as a correlate to perceived likelihood of implementing CP in future practice, as well as knowledge, level of support, and perceived barriers to implementation. METHODS: We conducted a repeated cross-sectional study annually from 2017 to 2019 with FM and OB/GYN residents from residency programs in the United States licensed to operate CP. We applied adjusted logistic regression models to identify predictors of intentions to engage with CP in future practice. RESULTS: Of 212 FM and 176 OB/GYN residents included in analysis, 67.01% of respondents intended to participate as a facilitator in CP in future practice and 51.80% of respondents were willing to talk to decision makers about establishing CP. Both FM and OB/GYN residents who spent more than 15 h engaged with CP and who expressed support towards CP were more likely to participate as a facilitator. FM residents who received residency-based training on CP and who were more familiar with CP reported higher intention to participate as a facilitator, while OB/GYN residents who had higher levels of engagement with CP were more likely to report an intention to participate as a facilitator. CONCLUSION: Engagement with and support towards CP during residency are key factors in residents' intention to practice CP in the future. To encourage future adoption of CP among residents, consider maximizing resident engagement with the model in hours of exposure and level of engagement, including hosting residency-based trainings on CP for FM residents.

Post-Operative Outcomes of Pre-Thoracic Surgery Respiratory Muscle Training vs Aerobic Exercise Training: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To compare the postoperative outcomes of preoperative respiratory muscle training (RMT) with a device to preoperative aerobic exercise training (AET) in patients undergoing thoracic surgeries (cardiac and lung). DATA SOURCES: PubMed, EMBASE, Cochrane, and Web of Science were comprehensively searched upon inception to 9/2020. STUDY SELECTION: All randomized control studies, including preoperative RMT and preoperative AET compared with a non-training control group, were included. DATA EXTRACTION: The meta-analysis was performed for outcomes including postoperative pulmonary complications (PPC), pneumonia, postoperative respiratory failure (PRF), hospital length of stay (HLOS), and mortality. We performed a network meta-analysis based on Bayesian random-effects regression models. DATA SYNTHESIS: A total of 25 studies, 2070 patients were included in this meta-analysis. Pooled data for the patients who performed RMT with a device showed a reduction in PPCs, pneumonia, PRF with odds ratio (OR) of 0.35 (P value .006), 0.38 (P value .002), and 0.22 (P value .008), respectively. Pooled data for the patients who performed AET showed reduction in PPC, pneumonia with a OR of 0.33 (P value <.00001) and OR of 0.54 (P value .01), respectively. HLOS was decreased by 1.69 days (P value <.00001) by performing RMT and 1.79 days (P value .0008) by performing AET compared with the usual group. No significant difference in all-cause mortality compared with usual care in both RMT and AET intervention groups. No significant difference in the incidence of PRF compared with usual group in RMT + AET and AET alone intervention groups (OR 0.32; P=.21; OR 0.94; P=.87). Based on rank probability plots analysis, on network meta-analysis, RMT and AET ranked similarly on the primary outcome of PPC and secondary outcomes of pneumonia, PRF and HLOS. CONCLUSIONS: In thoracic surgeries, preoperative RMT is comparable with preoperative AET to prevent PPC, pneumonia, and PRF and reduce HLOS. It can be considered in patients in resource-limited settings.

Comparison of left atrial and left atrial appendage mechanics in the recurrence of atrial fibrillation after radiofrequency catheter ablation.

OBJECTIVES: Although radiofrequency catheter ablation (RFCA) has become an important treatment strategy for paroxysmal or persistent atrial fibrillation (AF), AF recurrence after RFCA remains an important issue that plagues clinicians and patients. This study aimed to investigate the association of left atrial (LA) and left atrial appendage (LAA) mechanics with AF recurrence after RFCA and to compare their prognostic values in patients with AF undergoing RFCA. METHODS: A total of 160 patients with non-valvular AF who underwent RFCA for the first time were included in this study. All patients underwent transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) before the procedure. All patients were followed up for one year after RFCA, and AF recurrence was recorded. Speckle-tracking echocardiography was used to measure LA and LAA global longitudinal strain (GLS). LA and LAA mechanical dispersion (MD) were defined as the standard deviation of time to peak strain at each segment standardized by the R-R interval. Logistic regression analysis was used to analyze independent contributors for AF recurrence after RFCA. The prediction efficiency of factors associated with the presence of AF recurrence was evaluated by the receiver operating characteristic (ROC) curve with area under curve (AUC). RESULTS: During 1-year follow-up, 45 (28%) patients had recurrence, and 115 (72%) patients had no recurrence. The age, CHA2 DS2 -VASc score, NT-proBNP, LA volume index (LAVI), LA MD, and LAA MD of patients in recurrence group were significantly higher than those in no recurrent group (p < .05). The LAA emptying fraction (LAAEF), LA GLS, and LAA GLS in recurrence group were significantly lower than those in no recurrent group (p < .05). Logistic regression analysis showed that LA and LAA GLS were independent contributors for AF recurrence (p < .05), providing incremental values. The AUCs of LA and LAA GLS in predicting AF recurrence were higher than that of other factors, and the LA GLS+LAA GLS joint model had higher prediction efficiency. CONCLUSION: This study demonstrated the LA and LAA GLS were independent contributors for AF recurrence after RFCA and provided incremental values. LA and LAA GLS can be used as the predictor of AF recurrence after RFCA, and they may be beneficial for the risk stratification of AF recurrence.

A Fully Conjugated Covalent Organic Framework with Oxidative and Reductive Sites for Photocatalytic Carbon Dioxide Reduction with Water.

Constructing a powerful photocatalytic system that can achieve the carbon dioxide (CO2 ) reduction half-reaction and the water (H2 O) oxidation half-reaction simultaneously is a very challenging but meaningful task. Herein, a porous material with a crystalline topological network, named viCOF-bpy-Re, was rationally synthesized by incorporating rhenium complexes as reductive sites and triazine ring structures as oxidative sites via robust -C=C- bond linkages. The charge-separation ability of viCOF-bpy-Re is promoted by low polarized π-bridges between rhenium complexes and triazine ring units, and the efficient charge-separation enables the photogenerated electron-hole pairs, followed by an intramolecular charge-transfer process, to form photogenerated electrons involved in CO2 reduction and photogenerated holes that participate in H2 O oxidation simultaneously. The viCOF-bpy-Re shows the highest catalytic photocatalytic carbon monoxide (CO) production rate (190.6 µmol g-1 h-1 with about 100 % selectivity) and oxygen (O2 ) evolution (90.2 µmol g-1 h-1 ) among all the porous catalysts in CO2 reduction with H2 O as sacrificial agents. Therefore, a powerful photocatalytic system was successfully achieved, and this catalytic system exhibited excellent stability in the catalysis process for 50 hours. The structure-function relationship was confirmed by femtosecond transient absorption spectroscopy and density functional theory calculations.

Tumor-associated mononuclear cells in the tumor bed of triple-negative breast cancer associate with clinical outcomes in the post-neoadjuvant chemotherapy setting.

PURPOSE: To evaluate the clinical role of tumor-associated macrophages, including foamy (FM) and hemosiderin-laden macrophages (HLM) in the tumor bed (TB) of triple-negative breast cancer (TNBC) post-neoadjuvant chemotherapy (NACT). METHODS: We conducted a pathologic review of 129 women, diagnosed with TNBC between 2002 and 2016 at our institute. The residual cancer burden (RCB) was calculated. We estimated the percentage of tumor-infiltrating lymphocytes (TILs) in the core needle biopsy (CNB), and FM, HLM, and TILs (in TB) [the combined cells are designated as tumor-associated mononuclear cells (TAMNC)]. The information on patient demographics, chemotherapy regimen, recurrence-free survival (RFS), and overall survival (OS) was extracted from the medical records. RESULTS: Pathologic complete response (pCR) was achieved in 34.1% of the women. TILs (10% increment in CNB) only were associated with pCR in the multivariable analysis [odds ratio 1.04 (1.02, 1.06) (p = 0.0003)]. Immune cells associated with better OS included TAMNC (≤ 30%) [hazard ratio (HR) 4.32 (1.93, 9.66) (p = 0.0004)], and FM (0%) [HR 2.30 (1.06, 4.98) (p = 0.036)]. While increased HLM (10% increment) was statistically significant with HR 0.93 and 95% CI (0.88 to 0.98) (p = 0.0061), using a cutoff of 0%, HLM (0%: negative vs. ≥ 1%: positive) achieved only borderline significance with HR 2.05 (0.98, 4.31) (p = 0.058). Similarly, these immune cells were also associated with better RFS: TAMNC (≤ 30%) [HR 4.57 (2.04, 10.21) (p = 0.0002)], FM (0%) [HR 2.80 (1.23, 6.35) (p = 0.014)], and HLM (0%) [HR 2.34 (1.07, 5.11) (p = 0.03)]. TILs (in TB) were not associated with any clinical outcomes. CONCLUSIONS: Although TILs may play a role in the response to NACT, they may not be critical to the prognosis after NACT. Instead, FM and HLM may assume this role. More studies are warranted.

Oncologic outcome of radical prostatectomy versus radiotherapy as primary treatment for high and very high risk localized prostate cancer.

OBJECTIVE: To compare the oncologic outcomes of radical prostatectomy (RP) versus external beam radiotherapy (EBRT) ± androgen deprivation therapy for primary treatment of high risk localized prostate cancer (CaP). METHODS: We retrospectively reviewed a prospectively-populated database for cases who underwent primary treatment for high risk localized CaP, had more than 2 years follow-up, and were treated since 2006. A total of 335 cases were studied of whom 291 underwent RP and 44 underwent EBRT. Clinical characteristics, biochemical progression-free survival (BPFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were compared. RESULTS: EBRT cases were older (p < .01; mean 71 years vs. 61 years) and had longer PSA doubling time (PSADT) (p = .03; median 4.8 years vs. 3.5 years) than RP. Race, pretreatment PSA and biopsy Gleason score were similar. Median follow-up was 5.1 (range: 2.3-12.8) years for RP versus 3.3 (range: 2-12.4) years for EBRT. Three- and 5-year BPFS were 42% and 36% after RP versus 86% and 75% after EBRT (p < .01). The rate of adjuvant/salvage therapy was 58% after RP versus 20% after EBRT (p < .01). Three- and 5-year MFS were 80% and 77% after RP versus 91% and 91% after EBRT (p = .11). Three-year CSS was 98% in both groups and OS was 97% after RP versus 94% after EBRT (p = .73). CONCLUSIONS: RP had higher rates of biochemical failure and adjuvant or salvage treatment versus EBRT in high risk localized CaP. MFS trended toward benefit after EBRT, but CSS and OS remained high in both groups.

Comparative efficacy of chemoimmunotherapy versus immunotherapy for advanced non-small cell lung cancer: A network meta-analysis of randomized trials.

BACKGROUND: To the authors' knowledge, in the absence of head-to-head trials, it is unclear whether chemoimmunotherapy provides an additional overall survival (OS) benefit compared with immunotherapy alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors conducted a systematic literature review and network meta-analysis (NMA) to compare the efficacy of chemoimmunotherapy versus ICI. METHODS: MEDLINE, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to April 2020. Phase 3 trials evaluating the efficacy of first-line ICI or chemoimmunotherapy and reporting efficacy outcomes (OS, progression-free survival [PFS], and the overall response rate [ORR]) stratified by programmed death-ligand 1 (PD-L1) status were included. NMA with a Bayesian random effects model was performed. RESULTS: A total of 12 eligible trials comprising 7845 patients were included. In patients who were negative for PD-L1 (tumor proportion score [TPS] <1%), NMA comparing chemoimmunotherapy with dual-agent ICI failed to demonstrate a statistically significant difference with regard to OS, PFS, or the ORR. In patients with low PD-L1 (TPS 1%-49%), there was no statistically significant difference observed between chemoimmunotherapy compared with either single-agent ICI or dual-agent ICI with regard to OS or the ORR. In patients with high PD-L1 (TPS ≥50%), chemoimmunotherapy was found to be associated with an improved PFS and ORR compared with single-agent ICI, but not with dual-agent ICI. No differences in OS were observed with chemoimmunotherapy when compared with either single-agent or dual-agent ICIs. CONCLUSIONS: Although chemoimmunotherapy appears to improve the ORR and PFS in patients with PD-L1-high tumors when compared with single-agent ICI, it does not appear to confer an OS benefit over single-agent or dual-agent ICI for patients with advanced NSCLC regardless of PD-L1 status. Prospective trials are needed to validate these findings.

Prognostic Significance of Complete Pathologic Response Obtained with Chemotherapy Versus Chemoradiotherapy in Gastric Cancer.

BACKGROUND: Few studies have compared the survival advantage of complete pathologic response (cPR) achieved through neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) in gastric adenocarcinoma. Our study utilizes a large national cancer database to address this question. PATIENTS AND METHODS: This is a retrospective review of patients with clinical stage I to III gastric adenocarcinoma from 2004 to 2013 who received nCT or nCRT. Patients who achieved cPR were selected. Associations were evaluated using Mann-Whitney U and Fisher's exact tests. Survival information was summarized using standard Kaplan-Meier methods, where estimates of the median and 5-year survival rates were estimated with 95% confidence intervals. RESULTS: A total of 413 patients who had cPR were identified. Eighty-four patients received nCT and 329 patients received nCRT. Patients in the nCRT group had higher clinical stage (88.4% vs. 75.0%) and more proximal location of tumors (95.4% vs. 45.2%). The nCT group (n = 84) had a 94% 5-year survival rate, while the nCRT group's (n = 329) rate was 60% (p < 0.001). On Cox regression modeling using a propensity-weighted approach, nCT treatment was an independent predictor of improved overall survival (nCRT vs. nCT; HR 10.44, p < 0.001). CONCLUSIONS: The use of nCT leads to a significant increase in overall survival in patients when compared with nCRT for those who achieved cPR in gastric adenocarcinoma. While this study is limited in identifying the cause for this difference in overall survival, this important finding nonetheless requires further investigation and should be considered in the development of future gastric cancer trials.

Thrombotic complications and anticoagulation in COVID-19 pneumonia: a New York City hospital experience.

Infection with SARS-CoV-2 (COVID-19) can cause prothrombotic complications. We aim to study the frequency of thrombotic complications and impact of anticoagulation on outcomes in hospitalized patients. We conducted a retrospective chart review of 921 consecutive patients admitted to our hospital with COVID-19. Patients were divided into four groups depending on whether they were on anticoagulation prior to admission, started anticoagulation during the admission, received prophylactic anticoagulation, or did not receive any anticoagulation. At the time of analysis, 325 patients (35.3%) had died, while 544 patients (59%) had been discharged resulting in inpatient mortality of 37.3%. Male sex, age > 65 years, and high D-dimer at admission were associated with higher mortality. Sixteen patients (1.7%) had venous thromboembolism confirmed with imaging, 11 patients had a stroke, and 2 patients developed limb ischemia. Treatment with therapeutic anticoagulation was associated with improved inpatient mortality compared with prophylactic anticoagulation alone (63% vs 86.2%, p < 0.0001) in patients requiring mechanical ventilation. Other outcomes such as rates of liberation from mechanical ventilation and duration of mechanical ventilation were not significantly impacted by the type of anticoagulation.

Primary and secondary breast angiosarcoma: single center report and a meta-analysis.

BACKGROUND: Primary and secondary breast angiosarcoma is a rare and aggressive malignancy with limited published literature. Optimal management is mostly based on expert opinion. Our study aims to describe a single institution experience with breast angiosarcoma and evaluate other publications on this topic to further clarify prognostic outcomes and treatment modalities in this disease. METHODS: Twenty two cases of breast angiosarcoma from Roswell Park Comprehensive Cancer Center were retrospectively analyzed. Additionally, a systemic review and meta-analysis was conducted to study the association between survival outcomes, overall survival (OS), and recurrence-free survival (RFS) in both primary (PAS) and secondary breast angiosarcoma (SAS). RESULTS: 9 PAS patients (41%) and 13 SAS patients (59%) were retrospectively analyzed. No significant differences were noted in tumor characteristics and survival outcomes between PAS and SAS. Treatment modality had no significant effects on survival outcomes although adjuvant chemotherapy demonstrated a trend towards improved RFS in high grade tumors. 380 PAS and 595 SAS patients were included in the outcome meta-analysis. Survival outcomes were significantly worse with high grade tumors and tumor size of > 5 cm. Adjuvant radiation therapy demonstrated significantly better RFS, while adjuvant chemotherapy had no effect on survival outcomes. CONCLUSION: Tumor size and grade seem to be reliable predictors of survival in both PAS and SAS. Mastectomy does not seem to be adding any additional benefit to BCS. Adjuvant radiation therapy showed statistically significant RFS benefit, while adjuvant chemotherapy can be beneficial in high grade tumors.

Icaritin inhibits the invasion and epithelial-to-mesenchymal transition of glioblastoma cells by targeting EMMPRIN via PTEN/AKt/HIF-1α signalling.

Icaritin, a hydrolytic product of icariin from the Epimedium genus, exerts anti-tumour effects on a variety of tumour cell types, mainly by inhibiting cell proliferation and inducing apoptosis. However, little is known about the role of icaritin in cancer invasion and epithelial-to-mesenchymal transition (EMT). In the present study, the glioblastoma (GBM) cell line U87MG was used as a model to investigate the effects of icaritin on the invasion and EMT of cancer cells. The results showed that icaritin significantly inhibited the invasion and EMT of GBM cells by targeting extracellular matrix metalloproteinase (EMMPRIN). Furthermore, the findings strongly indicate that the modulatory effect of icaritin on EMMPRIN is mediated via the PTEN/Akt/HIF-1α signalling pathway. The data provide the first experimental evidence of the inhibitory effect of icaritin on cancer cell invasion and EMT, thus highlighting the potential of icaritin to be employed as a promising anti-cancer agent in the treatment of GBM.

Self-assembled DNA nanoclews for the efficient delivery of CRISPR-Cas9 for genome editing.

CRISPR-Cas9 represents a promising platform for genome editing, yet means for its safe and efficient delivery remain to be fully realized. A novel vehicle that simultaneously delivers the Cas9 protein and single guide RNA (sgRNA) is based on DNA nanoclews, yarn-like DNA nanoparticles that are synthesized by rolling circle amplification. The biologically inspired vehicles were efficiently loaded with Cas9/sgRNA complexes and delivered the complexes to the nuclei of human cells, thus enabling targeted gene disruption while maintaining cell viability. Editing was most efficient when the DNA nanoclew sequence and the sgRNA guide sequence were partially complementary, offering a design rule for enhancing delivery. Overall, this strategy provides a versatile method that could be adapted for delivering other DNA-binding proteins or functional nucleic acids.

[Comparative metabolomics analysis of metabolic pathways in the high-yielding mutant strain of avilamycin].

Avilamycin (AVI) is an oligosaccharide antibiotic that has strong inhibitory effect on Gram-positive bacteria. It is widely used in livestock and poultry farming. However, the use of traditional breeding techniques and immature fermentation process have become the key factors limiting its commercialization. In this study, we used comparative metabolomics techniques to examine the difference in intracellular metabolism between a high-yield AVI mutant strain modified by ribosome engineering technology and the parental strain. GC-MS analysis was conducted on mycelia samples taken on days 4, 6, and 8 of fermentation, resulting in the detection of a total of 112 compounds. After comparison with the NIST library, 29 intracellular metabolites were accurately identified. Two-dimensional principal component analysis (PCA) revealed significant differences in metabolites between the mutant strain and the parental strain at different time points. Orthogonal partial least squares-discriminant analysis (OPLS-DA) identified 11 intracellular metabolites that were closely related to AVI biosynthesis. KEGG metabolic pathway enrichment analysis showed that avilamycin synthesis was closely related to carbohydrate metabolism and amino acid metabolism. Six key differential metabolites were selected: L-valine, L-serine, L-alanine, D-galactose, D-cellobiose, and D-glucose. Upregulation of these metabolites in the mutant strain enhanced its metabolic flow for AVI synthesis. After 8 days of fermentation, the mutant strain produced 76.86% more AVI than the parental strain. The findings of this study serve as reference for the future rational optimization of avilamycin fermentation.

Periodontal Pocket Therapy Using a Class IV Dental Diode Laser in Dogs: A Retrospective Analysis.

Class IV dental diode lasers have been introduced as a nonsurgical therapy for periodontal pockets in veterinary and human dentistry. This retrospective case series evaluates the use of Class IV dental diode laser therapy for abnormal periodontal pockets in a specialty veterinary dental practice. A hypothesis that the Class IV diode dental laser is a useful adjuvant modality in canine periodontal pocket therapy in the reduction of clinical pocket depth was made. This article discusses and demonstrates diode laser use in periodontal pocket therapy in a specialty veterinary dental practice and reviews the current literature. Inclusion in this study was limited to client-owned dogs with noted periodontal pocketing on any tooth type between 3 and 6 mm, which were treated with closed root planing (RP/C) and laser therapy who returned in 6 to 7 months for recheck of the pockets from the years 2017 to 2020. Twelve patients met the inclusion criteria. A total of 128 periodontal pockets were included in the study. Each periodontal pocket was a case receiving therapy. The mean periodontal pocket depth before the treatment is measured as 3.35 mm. The mean pocket depth of the periodontal pockets following treatment was 0.59 mm. The mean improvement in periodontal pocket depths after diode laser therapy when considering patient and tooth number using linear mixed-effects modeling was 2.63 mm (95% confidence interval [CI]: 1.81-3.46, P < .0001). No statistically significant results were observed for pocket type, as P values were greater than .05.

Interventional analytics in skilled nursing facilities associated with reduced readmissions.

OBJECTIVE: To assess differences in longitudinal profiles for 30-day risk-adjusted readmission rates in skilled nursing facilities (SNFs) associated with Penn Medicine's Lancaster General Hospital (LGH) that implemented an interventional analytics (IA) platform vs other LGH facilities lacking IA vs other SNFs in Pennsylvania vs facilities in all other states. STUDY DESIGN: Retrospective longitudinal analysis of CMS readmissions data from 2017 through 2022, and cross-sectional analysis using CMS quality metrics data. METHODS: CMS SNF quality performance data were aggregated and compared with risk-adjusted readmissions by facility and time period. Each SNF was assigned to a cohort based on location, referral relationship with LGH, and whether it had implemented IA. Multivariable mixed effects modeling was used to compare readmissions by cohort, whereas quality measures from the fourth quarter of 2022 were compared descriptively. RESULTS: LGH profiles differed significantly from both state and national profiles, with LGH facilities leveraging IA demonstrating an even greater divergence. In the most recent 12 months ending in the fourth quarter of 2022, LGH SNFs with IA had estimated readmission rates that were 15.24, 12.30, and 13.06 percentage points lower than the LGH SNFs without IA, Pennsylvania, and national cohorts, respectively (all pairwise P < .0001). SNFs with IA also demonstrated superior CMS claims-based quality metric outcomes for the 12 months ending in the fourth quarter of 2022. CONCLUSIONS: SNFs implementing the studied IA platform demonstrated statistically and clinically significant superior risk-adjusted readmission rate profiles compared with peers nationally, statewide, and within the same SNF referral network (P < .0001). A more detailed study on the use of IA in this setting is warranted.

Impact of the COVID-19 pandemic on routine vaccination coverage under varying prevalence Conditions: A cohort study in Beijing, China.

BACKGROUND: The COVID-19 pandemic has experienced various phases including outbreaks, a global health crisis, and eventual de-escalation from a public health emergency of international concern, significantly affecting the delivery and utilization of healthcare services. This study aimed to evaluate the impact of the COVID-19 pandemic on the coverage rate of routine immunization in children under varying prevalence conditions. METHODS: We conducted a retrospective, population-based cohort study in Beijing, China, utilizing stratified random sampling by birthdate to obtain a sample of 29,811 participants. Subjects were categorized into four cohorts based on when they became eligible for vaccination: the Pre-COVID Period cohort, the COVID-19 Low Epidemic Period cohort, the COVID-19 Surging Period cohort, and the COVID-19 Slowing Down Period cohort. A one-month follow-up was conducted. Cox proportional hazards model was employed to examine associations between the COVID-19 epidemic status and timely vaccination. RESULTS: Participants age-eligible for vaccination during the COVID-19 Low Epidemic Period demonstrated higher rates of timely vaccination (HR 1.18, 95% CI 1.15-1.22) compared to those eligible during the Pre-COVID Period. Conversely, those eligible during the COVID-19 Surging Period displayed lower rates (HR 0.73, 95% CI 0.66-0.82). No significant difference in vaccination timeliness was observed for those eligible during the COVID-19 Slowing Down Period in comparison to the Pre-COVID Period (HR 0.99, 95% CI 0.91-1.09). By the end of May 2023, DTP3 rate among eligible children during the COVID-19 Surging Period had surpassed 90%. CONCLUSIONS: Significantly declining rates of timely vaccination were observed during the COVID-19 Surging Period, which lasted two months, but not during the nearly three-year-long COVID-19 Low Epidemic Period. An upward trend in vaccination timeliness followed, culminating in a return to baseline levels over the subsequent 3-4 months. Our findings suggested that the pandemic exerted a decreasing and recoverable impact on the coverage rate of routine immunizations in China.

Prospective evaluation of patient-reported outcomes of invisible ink tattoos for the delivery of external beam radiation therapy: the PREFER trial.

Introduction: Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation. Methods and materials: In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests. Results: Of 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively). Discussion: In the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered.