Nevin Manimala

Mol Inform. 2023 Apr 11. doi: 10.1002/minf.202200223. Online ahead of print.

ABSTRACT

The present work was devoted to explore the quantitative structure-property relationships for gas-to-ionic liquid partition coefficients (log K_ILA). A series of linear models were first established for the representative dataset ( IL01). The optimal model was a four-parameter equation (1Ed) consisting of two electrostatic potential-based descriptors ( Σ V s , ind – and V_s,max), one 2D matrix-based descriptor (J_D/Dt) and dipole moment (μ). All of the four descriptors introduced in the model can find the corresponding parameters, directly or indirectly, from Abraham’s linear solvation energy relationship (LSER) or its theoretical alternatives, which endows the model good interpretability. Gaussian process was utilized to build the nonlinear model. Systematical validations, including 5-fold cross-validation for the training set, the validation for test set, as well as a more rigorous Monte Carlo cross-validation were performed to verify the reliability of the constructed models. Applicability domain of the model was evaluated, and the Williams plot revealed that the model can be used to predict the log K_ILA values of structurally diverse solutes. The other 13 datasets were also processed in the same way, and all of the linear models with expressions similar to equation 1Ed were obtained. These models, whether linear of nonlinear, represent satisfactory statistical results, which confirms the universality of the method adopted in this study in QSPR modeling of gas-to-IL partition.

PMID:37040091 | DOI:10.1002/minf.202200223

J Natl Cancer Inst. 2023 Apr 11:djad046. doi: 10.1093/jnci/djad046. Online ahead of print.

ABSTRACT

BACKGROUND: Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies.

METHODS: This multi-center collaboration included patients with ICC or ECC treated at one of eight participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were two-sided.

RESULTS: Among 1,039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early-stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%), (all p < 0.00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%), (all p < 0.001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months, p < 0.001).

CONCLUSIONS: Patients with advanced ECC have low rates of molecular profiling, possibly in part due to insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.

PMID:37040087 | DOI:10.1093/jnci/djad046

J Natl Cancer Inst. 2023 Apr 11:djad064. doi: 10.1093/jnci/djad064. Online ahead of print.

ABSTRACT

BACKGROUND: WHO recommends a one- or two-dose human papillomavirus (HPV) vaccination schedule for females aged nine to twenty years. Studies confirming the efficacy of a single dose and of vaccine modifications are needed but randomized controlled trials (RCTs) are costly and face logistical and ethical challenges. We propose a resource-efficient single-arm trial design that uses untargeted and unaffected HPV types as controls.

METHODS: We estimated HPV vaccine efficacy (VE) from a single arm by comparing two ratios: the ratio of the rate of persistent incident infection with vaccine-targeted and cross-protected types (HPV16/18/31/33/45) to vaccine-unaffected HPV types (HPV35/39/51/52/56/58/59/66) versus the ratio of prevalences of these types at the time of trial enrollment. We compare VE estimates using only data from the bivalent HPV16/18 vaccine arm of the Costa Rica Vaccine Trial to published VE estimates that used both the vaccine and control arms.

RESULTS: Our single-arm approach among 3,727 women yielded VE estimates for persistent HPV16/18 infections similar to published two-arm estimates from the trial (according-to-protocol cohort: 91.0% (95% CI = 82.9%-95.3%) [single-arm] vs. 90.9% (95% CI: 82.0%-95.9%) [two arm]; intention-to-treat cohort: 41.7% (95% CI = 32.4%-49.8%) [single-arm] vs. 49.0% (95% CI = 38.1%-58.1%) [two-arm]). VE estimates were also similar in analytic sub-groups (number of doses received; baseline HPV serology status).

CONCLUSION: We demonstrate that a single-arm design yields valid VE estimates with similar precision to an RCT. Single-arm studies can reduce the sample size and costs of future HPV vaccine trials while avoiding concerns related to unvaccinated control groups.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00128661.

PMID:37040086 | DOI:10.1093/jnci/djad064

JNCI Cancer Spectr. 2023 Apr 11:pkad029. doi: 10.1093/jncics/pkad029. Online ahead of print.

ABSTRACT

BACKGROUND: Oral health is a key indicator of overall health, well-being, and quality of life. Several studies have provided new evidence about the role of oral diseases, specifically periodontitis, in generating risk for various forms of cancers including lung, colorectal, and pancreatic cancers.

METHODS: Incident lung cancer cases (n = 192) and matched controls (n = 192) were selected from participants of the CLUE I and CLUE II cohorts. Archived serum samples collected from participants in 1974 (in CLUE I) were analyzed using immunoblotting for IgG antibody levels to 13 bacteria of the periodontium. Associations between antibody levels and lung cancer were estimated using conditional logistic regression.

RESULTS: Most of the periodontal bacterial antibodies measured were inversely associated with lung cancer risk; of these, three were statistically significant (P. intermedia, A. naeslundii, and V. parvula). A statistically significant positive association was observed for one of the P. gingivalis strains after adjusting for P. intermedia. The sum of the logarithm of antibodies against the 13 measured bacteria was inversely associated with risk of lung cancer when the analysis was restricted to a longer follow-up (31-44 years after blood collection, highest vs lowest quartile: OR = 0.26, 95% CI = 0.08-0.84).

CONCLUSION: Findings from this study highlight the complexity of using serum IgG antibodies to periodontal bacteria to identify associations between oral pathogens and risk of lung cancer. The inverse associations observed for antibodies to periodontal bacteria suggest that these may represent markers of immunity that provide some advantage in reducing the development of lung cancer.

PMID:37040077 | DOI:10.1093/jncics/pkad029

Int J Cardiovasc Imaging. 2023 Apr 11. doi: 10.1007/s10554-023-02843-9. Online ahead of print.

ABSTRACT

BACKGROUND: The study aimed to assess the impact of percutaneous transcatheter atrial septal defect (ASD) closure on atrium and atrial appandage functions among patients with ostium secundum ASDs.

METHODS: A total of 101 patients (34,7% male, 65,3% female, 37,6 ± 12) with the diagnosis of ostium secundum type ASD underwent transthorasic (TTE) and transesophageal echocardiography (TEE) before and six months after percutaneous transcatheter ASD closure. Pulmonary venous flow and atrial appendage flow velocities were obtained from the TEE recordings. The offline evaluation of the global and segmental atrial appendage strains were evaluated with speckle tracking echocardiography (STE) via EchoPac 6,3 (GE Vingmed, Horten, Norway).

RESULTS: Mean values of pulmonary artery pressure, right ventricular, left atrium, left ventricular end-diastolic and end-systolic diameters were significantly decreased 6 months after ASD closure. Statistically significant changes were documented in pulmonary venous and left atrial appendage flow velocities after ASD closure. Both left and right atrial appendage flow velocities and global strains of atrial appandages were improved after ASD closure. The mean left atrial appendage global strain value was – 11.45 ± 4.13% before the procedure, this value was – 16.82 ± 3.78% sixth months after the procedure (P < 0.001).The mean right atrial appendage global strain was – 13.31 ± 4.84% before the procedure and – 18.53 ± 4.69% sixth months after the procedure (P < 0.001).

CONCLUSION: Left and right atrial appendage flow velocities and global strains of left and right atrial appandage can be improved after transcatheter ASD closure. Percutaneous transcatheter closure of ASDs not only improves atrial and left ventricular dimensions but also have a positive impact on left and right atrial appandage functions.

PMID:37040061 | DOI:10.1007/s10554-023-02843-9

Bull Exp Biol Med. 2023 Apr 11. doi: 10.1007/s10517-023-05754-w. Online ahead of print.

ABSTRACT

We analyzed the levels of LPO products and antioxidant defense components in women with the metabolic syndrome. Women with the metabolic syndrome had higher values of substrates with unsaturated double bonds and final TBA-reactive substances in comparison with the control group and higher levels of unsaturated double bonds, primary and end products of LPO, and retinol in comparison with the reference group (women with less than 3 signs of metabolic syndrome). No statistically significant differences between the groups were revealed while estimating the coefficient of oxidative stress; however, there was a tendency to an increase in the median value of this parameter in the group with metabolic syndrome. Thus, the results of the study indicate the activity of LPO reactions at different stages in women of reproductive age with the metabolic syndrome, which points to the necessity to evaluate and monitor the content of these metabolites in the patients of this cohort for the purpose of prevention and treatment.

PMID:37040040 | DOI:10.1007/s10517-023-05754-w

Int J Gynaecol Obstet. 2023 Apr 11. doi: 10.1002/ijgo.14777. Online ahead of print.

ABSTRACT

BACKGROUND: Protein neutrophil gelatinase-associated lipocalin (NGAL) has been associated with kidney injury and inflammatory conditions. In particular, several studies have found an association between maternal blood and urine levels and the development of pre-eclampsia.

OBJECTIVES: To examine whether maternal blood and urine levels of NGAL are good predictors of pre-eclampsia.

SEARCH STRATEGY: The authors searched MEDLINE databases via PubMed, Embase, Scopus, Scielo, Google Scholar, PROSPERO International Prospective Register of Systematic Reviews, and the Cochrane Central Register of Controlled Trials.

SELECTION CRITERIA: The authors included case-control observational clinical studies comparing protein levels of NGAL in serum and urine in women with pre-eclampsia with uncomplicated pregnancies. Only studies where the collection of blood or urine was peformed before the occurrence of pre-eclampsia were selected.

DATA COLLECTION AND ANALYSIS: The primary outcome was the difference in NGAL levels in blood or urine between women with and without pre-eclampsia.

RESULTS: Seven studies in total were included: five studies measuring NGAL in blood and two in urine. Regarding the serum studies, 315 patients were included as cases and 540 as controls. Higher NGAL in maternal blood during all three trimesters together was associated with pre-eclampsia; the standardized mean difference was 1.15 ng/mL (95% confidence interval, 0.92-1.39; P < 0.01). Regarding the urine studies, 39 patients were included as cases and 220 as controls. There was no statistically significant difference between patients with pre-eclampsia and controls regarding urine NGAL.

CONCLUSIONS: NGAL in maternal blood is higher in patients who later develop pre-eclampsia compared with controls and could be used as a potential predicting test in the routine clinical setting.

PMID:37040030 | DOI:10.1002/ijgo.14777

Int J Technol Assess Health Care. 2023 Apr 11;39(1):e20. doi: 10.1017/S0266462323000144.

ABSTRACT

BACKGROUND: Multi-stakeholder interactions have evolved at product and policy levels. There is a need to assess the current and future landscape of interactions between companies, and regulatory and HTA agencies to address challenges and identify areas for improvement.

OBJECTIVES: The aims of this study were to review the current interactions within and across regulatory and HTA agencies, and companies’ experiences in engaging in these activities; to assess the added value of interactions as well as limitations; to explore the future ecosystem for stakeholder interactions.

METHOD: Three separate questionnaires were developed for companies, regulators and HTA agencies, respectively, to assess their experiences and perceptions. The responses were analyzed using descriptive statistics and discussed at a multi-stakeholder workshop. Key outcomes from the surveys and workshop discussion were reported.

RESULTS: All seven regulators and seven HTA agencies in the survey indicated that they had stakeholder interactions. More formal collaboration occurred with regulators compared with HTA agencies. All nine companies have taken early advice but indicated the need for future prioritization. Success indicators can be built at the product and therapy levels, with the added value of faster patient access. Four principles were proposed for the future ecosystem: separate remit and functions between regulators and HTA; align processes; converge evidence requirements where possible; increase transparency.

CONCLUSIONS: This research brought together regulators, HTA agencies, companies to examine how they interact with one another. We propose measures of value and make recommendations on future evolution to enable better evidence generation and improve regulatory and HTA decision-making.

PMID:37039100 | DOI:10.1017/S0266462323000144

Expert Rev Anticancer Ther. 2023 Apr 11:1-9. doi: 10.1080/14737140.2023.2188196. Online ahead of print.

ABSTRACT

INTRODUCTION: Immunotherapy (IT) is showing promise in the treatment of breast cancer, but IT alone only benefits a minority of patients. Radiotherapy (RT) is usually included in the standard of care for breast cancer patients and is traditionally considered as a local form of treatment. The emerging knowledge of RT-induced systemic immune response, and the observation that the rare abscopal effect of RT on distant cancer metastases can be augmented by IT, have increased the enthusiasm for combinatorial immunoradiotherapy (IRT) for breast cancer patients. However, IRT largely follows the traditional sole RT and IT protocols and does not consider patient specificity, although patients’ responses to treatment remain heterogeneous.

AREAS COVERED: This review discusses the rationale of IRT for breast cancer, the current knowledge, challenges, and future directions.

EXPERT OPINION: The synergy between RT and the immune system has been observed but not well understood at the basic level. The optimal dosages, timing, target, and impact of biomarkers are largely unknown. There is an urgent need to design efficacious pre-clinical and clinical trials to optimize IRT for cancer patients, maximize the synergy of radiation and immune response, and explore the abscopal effect in depth, taking into account patients’ personal features.

PMID:37039098 | DOI:10.1080/14737140.2023.2188196

Psychogeriatrics. 2023 Apr 11. doi: 10.1111/psyg.12966. Online ahead of print.

ABSTRACT

BACKGROUND: Research has linked increased cognitive decline in a dementia care recipient to worsening caregiver burden, but the presence of positive aspects of caregiving is associated with better outcomes. As cognitive decline worsens, a lack of positive caregiving experiences could lead to burden for the caregiver. This study investigated relationships among dementia caregiver burden, cognitive decline, and positive aspects of caregiving in dementia, predicting an indirect effect of positive aspects of caregiving.

METHODS: Data from 724 patients of an outpatient memory clinic in Ohio were examined and dyads included based on clinically supported patient diagnoses on the dementia spectrum. Caregivers completed the Zarit Burden Interview (ZBI) and Positive Aspects of Caregiving (PAC) measures. The Montreal Cognitive Assessment and Mini-Mental State Examination were used to estimate cognitive decline, standardized to create a single variable. Multiple potential covariates were considered for inclusion in the model. A cross-sectional mediation analysis using the Hayes PROCESS macro explored the presence of an indirect effect of PAC on the relationship between cognitive decline and ZBI using 5000 bootstrap samples.

RESULTS: Only the potential covariate caregiver age was correlated with any of the primary variables; this variable was controlled in analyses. Significant relationships emerged between cognitive decline and ZBI (r = -0.12, P < 0.001), between PAC and ZBI (r = -0.23, P < 0.001), and between cognitive decline and PAC (r = -0.07, P < 0.05). An indirect effect of positive aspects of caregiving on the relationship between cognitive decline and ZBI was statistically significant (B = 0.0092, 95% bias-corrected confidence interval: 0.0008, 0.0185), accounting for 14.4% of the variance in the model.

CONCLUSIONS: A lack of positive aspects of caregiving could be partially responsible for development of dementia caregiver burden as cognitive decline worsens. Longitudinal examination of these relationships is needed to understand causality fully. Findings may help healthcare providers tailor treatment to alleviate caregiver burden.

PMID:37039090 | DOI:10.1111/psyg.12966