Category: Nevin Manimala

Geohealth. 2024 Jun 6;8(6):e2024GH001034. doi: 10.1029/2024GH001034. eCollection 2024 Jun.

ABSTRACT

The global COVID-19 outbreak severely hampered the growth of the global economy, prompting the implementation of the strictest prevention policies in China. Establishing a significant relationship between changes in nighttime light and COVID-19 lockdowns from a geospatial perspective is essential. In light of nighttime light remote sensing, we evaluated the spatiotemporal dynamic effects of COVID-19 city lockdowns on human activity intensity in the Zhengzhou region. Prior to the COVID-19 outbreak, nighttime light in the Zhengzhou region maintained a significant growth trend, even under regular control measures. However, following the October 2022 COVID-19 lockdown, nighttime light experienced a substantial decrease. In the central area of Zhengzhou, nighttime light decreased by at least 18% compared to pre-lockdown levels, while in the sub-center, the decrease was around 14%. The areas where nighttime light decreased the most in the central region were primarily within a 15 km radius, while in the sub-center, the decrease was concentrated within a 5 km radius. These changes in both statistical data and nighttime light underscored the significant impact of the COVID-19 lockdown on economic activities in the Zhengzhou region.

PMID:38855706 | PMC:PMC11156960 | DOI:10.1029/2024GH001034

Dent Mater J. 2024 Jun 7. doi: 10.4012/dmj.2023-274. Online ahead of print.

ABSTRACT

To study the biocompatibility of nanohydroxyapatite (nmHA)-SiO₂ fiber material and its efficacy in guided bone regeneration. ① The cytotoxicity of the nmHA-SiO₂ fiber material to MC3T3-E1 cells was determined by CCK-8 assay. The adhesion of cells on the surface of the material was observed. ② Bone defects were prepared in the skull of three groups of New Zealand white rabbits. The following treatments were administered: implantation of nmHA-SiO₂, implantation of Bio-Oss, and no treatment. The defects were then covered with nmHA-SiO₂ membrane or Hai’ao oral repair membrane. Animal samples were analyzed by gross observation, micro-computed tomography, hematoxylin-eosin staining and Masson staining. The data were statistically analyzed by multivariate analysis of variance to evaluate the repair of bone defects. ① The nmHA-SiO₂ fiber material has suitable biocompatibility. ② The nmHA-SiO₂ fiber material performed more effectively as a barrier membrane than other bone substitute materials in GBR model rabbits.

PMID:38853006 | DOI:10.4012/dmj.2023-274

Stat Med. 2024 Jun 9. doi: 10.1002/sim.10132. Online ahead of print.

ABSTRACT

We investigate the familywise error rate (FWER) for time-to-event endpoints evaluated using a group sequential design with a hierarchical testing procedure for secondary endpoints. We show that, in this setup, the correlation between the log-rank test statistics at interim and at end of study is not congruent with the canonical correlation derived for normal-distributed endpoints. We show, both theoretically and by simulation, that the correlation also depends on the level of censoring, the hazard rates of the endpoints, and the hazard ratio. To optimize operating characteristics in this complex scenario, we propose a simulation-based method to assess the FWER which, better than the alpha-spending approach, can inform the choice of critical values for testing secondary endpoints.

PMID:38852994 | DOI:10.1002/sim.10132

Stat Med. 2024 Jun 9. doi: 10.1002/sim.10090. Online ahead of print.

ABSTRACT

Multi-arm multi-stage (MAMS) platform trials efficiently compare several treatments with a common control arm. Crucially MAMS designs allow for adjustment for multiplicity if required. If for example, the active treatment arms in a clinical trial relate to different dose levels or different routes of administration of a drug, the strict control of the family-wise error rate (FWER) is paramount. Suppose a further treatment becomes available, it is desirable to add this to the trial already in progress; to access both the practical and statistical benefits of the MAMS design. In any setting where control of the error rate is required, we must add corresponding hypotheses without compromising the validity of the testing procedure.To strongly control the FWER, MAMS designs use pre-planned decision rules that determine the recruitment of the next stage of the trial based on the available data. The addition of a treatment arm presents an unplanned change to the design that we must account for in the testing procedure. We demonstrate the use of the conditional error approach to add hypotheses to any testing procedure that strongly controls the FWER. We use this framework to add treatments to a MAMS trial in progress. Simulations illustrate the possible characteristics of such procedures.

PMID:38852991 | DOI:10.1002/sim.10090

Korean J Fam Med. 2024 Jun 7. doi: 10.4082/kjfm.23.0246. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity is a significant health risk factor for cardiovascular diseases. Dyslipidemia, defined as a low high-density lipoprotein cholesterol (HDL-C) level, is associated with these risks. Recent bioelectrical impedance analysis (BIA) devices offer precise measurements of the percent body fat (PBF). We aimed to determine the association between PBF and HDL-C levels in middle-aged men in Korea.

METHODS: We conducted a cross-sectional sstudy of men aged 40-65 years who visited a health examination center. Body composition was analyzed using BIA. Health habits were assessed using a self-administered questionnaire. The participants were divided into four groups based on their PBF: group 1 (<21%), group 2 (21%-23.99%), group 3 (24%-28.99%), and group 4 (≥29%). Logistic regression was used to obtain the odds ratio (OR) between the PBF group and the low HDL-C level and adjusted for other variables.

RESULTS: In this study, 2,685 men were analyzed. The number of individuals diagnosed with low HDL-C levels increased significantly as the group-specific PBF increased. Group 4 showed a 5.5-fold greater association with low HDL-C compared to group 1 (P<0.01), whereas group 3 and group 2 showed an OR of 4.38 and 2.95 (P<0.01 and P<0.01), respectively.

CONCLUSION: These results suggest that if middle-aged men are able to decrease their body fat by <5%, their HDL-C levels will increase. We suggest that 3%-5% PBF is a useful guideline for general body fat reduction in Korean middle- aged men in primary care.

PMID:38852952 | DOI:10.4082/kjfm.23.0246

Korean J Fam Med. 2024 Jun 7. doi: 10.4082/kjfm.23.0269. Online ahead of print.

ABSTRACT

BACKGROUND: Establishing cost-effective informal care services for lonely older adults living at home in developing countries can be an innovative approach for improving their well-being. This study investigated the effectiveness of an informal home care support intervention program (HoSIP) reducing the loneliness and improving quality of life of lonely community-dwelling older adults.

METHODS: This quasi-experimental pre-post study employed a non-randomized control group design with a 12-week intervention period and three follow-up points at the end of the HoSIP. Questionnaires were used to measure feelings of loneliness (20-item UCLA Loneliness Scale), quality of life (Control, Autonomy, Self-Realization and Pleasure Scale), general health (12-item General Health Questionnaire), social network (six-item Lubben Social Network Scale), social support (12-item Multidimensional Scale of Perceived Social Support), and self-care ability (17-item Self-care Ability Scale for the Elderly). Repeated-measures analysis of variance was used to gauge the effect of the intervention program over time and in comparison to the control group. Data analyses were performed using the IBM SPSS Statistics software (IBM Corp., USA).

RESULTS: We found a significant relationship between the outcome variables, including feelings of loneliness (P<0.001) and quality of life (P<0.001), at different stages of measurement. Despite the positive feasibility results, the implementation of the HoSIP faced challenges due to a lack of facilities (e.g., place restriction for holding educational classes, educational facilities like computers, video projector, and whiteboard at daycare center) and the absence of supporting organizations.

CONCLUSION: Utilizing the existing capabilities of older adults to provide online and face-to-face care services can be a cost-effective way to improve their quality of life and reduce loneliness. The process of facilitating such informal care services for lonely older adults should be managed by either governmental or non-governmental organizations to reduce the rate of social isolation among this vulnerable population.

PMID:38852950 | DOI:10.4082/kjfm.23.0269

J Natl Cancer Inst. 2024 Jun 10:djae091. doi: 10.1093/jnci/djae091. Online ahead of print.

ABSTRACT

BACKGROUND: Breast cancer brain metastasis is a rising occurrence, necessitating a better understanding of the mechanisms involved for effective management. Breast cancer brain metastases diverge notably from the primary tumor, with gains in kinase and concomitant losses of steroid signaling observed. In this study, we explored the role of the kinase receptor RET in promoting breast cancer brain metastases and provide a rationale for targeting this receptor.

METHODS: RET expression was characterized in a cohort of patients with primary and brain metastatic tumors. RET functionality was assessed using pharmacological inhibition and gene silencing in patient-derived brain metastatic tumor explants and in vivo models, organoid models, and brain organotypic cultures. RNA sequencing was used to uncover novel brain metastatic relevant RET mechanisms of action.

RESULTS: A statistically significant enrichment of RET in brain metastases was observed in estrogen receptor-positive breast cancer, where it played a role in promoting cancer cell adhesion, survival, and outgrowth in the brain. In vivo, RET overexpression enhanced brain metastatic competency in patient-derived models. At a mechanistic level, RET overexpression was found to enhance the activation of gene programs involved in cell adhesion, requiring EGFR cooperation to deliver a pro-brain metastatic phenotype.

CONCLUSION: Our results illustrate, for the first time, the role of RET in regulating colonization and outgrowth of breast cancer brain metastasis and provide data to support the use of RET inhibitors in the management strategy for patients with breast cancer brain metastases.

PMID:38852945 | DOI:10.1093/jnci/djae091

Mol Phylogenet Evol. 2024 Jun 7:108117. doi: 10.1016/j.ympev.2024.108117. Online ahead of print.

ABSTRACT

The Least Nighthawk Chordeiles pusillus is widespread wherever there are savannas in the South American tropics, often in isolated patches, such as white-sands savannas in the Amazon rainforest realm. Here, we investigate genetic relationships between populations of the Least Nighthawk to understand historical processes leading to its diversification and to determine dispersal routes between northern and southern savannas by way of three hypothesized dispersal corridors by comparing samples from white-sand savannas to samples from other savannas outside of the Amazon rainforest region. We use 32 mtDNA samples from the range of C. pusillus to infer a dated phylogeny. In a subset of 17 samples, we use shotgun sequences to infer a distance-based phylogeny and to estimate individual admixture proportions. We calculate gene flow and shared alleles between white-sand and non-Amazonian populations using the ABBA-BABA test (D statistics), and Principal Component Analysis (PCA) to examine genetic structure within and between lineages. Finally, we use species distribution modelling (SDM) of conditions during the Last Glacial Maximum (LGM), currently, and in the future (2050-2080) to predict potential species occurrence under a climate change scenario. Two main clades (estimated to have diverged around 1.07 million years ago) were recovered with mtDNA sequences and Single Nucleotide Polymorphism (SNPs) and were supported by NGSadmix and PCA: one in the Amazon basin white-sand savannas, the other in the non-Amazonian savannas. Possible allele sharing between these clades was indicated by the D-statistics between northern non-Amazonian populations and the white-sand savanna population, but this was not corroborated by the admixture analyses. Dispersal among northern non-Amazonian populations may have occurred in a dry corridor between the Guianan and the Brazilian Shield, which has since moved eastward. Our data suggest that the lineages separated well before the Last Glacial Maximum, consequently dispersal could have happened at any earlier time during similar climatic conditions. Subsequently, non-Amazonian lineages became more divergent among themselves, possibly connecting and dispersing across the mouth of the Amazon River across Marajó island during favourable climatic conditions in the Pleistocene.

PMID:38852908 | DOI:10.1016/j.ympev.2024.108117

Mol Phylogenet Evol. 2024 Jun 7:108120. doi: 10.1016/j.ympev.2024.108120. Online ahead of print.

ABSTRACT

Ochrophyta is a photosynthetic lineage that crowns the phylogenetic tree of stramenopiles, one of the major eukaryotic supergroups. Due to their ecological impact as a major primary producer, ochrophytes are relatively well-studied compared to the rest of the stramenopiles, yet their evolutionary relationships remain poorly understood. This is in part due to a number of missing lineages in large-scale multigene analyses, and an apparently rapid radiation leading to many short internodes between ochrophyte subgroups in the tree. These short internodes are also found across deep-branching lineages of stramenopiles with limited phylogenetic signal, leaving many relationships controversial overall. We have addressed this issue with other deep-branching stramenopiles recently, and now examine whether contentious relationships within the ochrophytes may be resolved with the help of filling in missing lineages in an updated phylogenomic dataset of ochrophytes, along with exploring various gene filtering criteria to identify the most phylogenetically informative genes. We generated ten new transcriptomes from various culture collections and a single-cell isolation from an environmental sample, added these to an existing phylogenomic dataset, and examined the effects of selecting genes with high phylogenetic signal or low phylogenetic noise. For some previously contentious relationships, we find a variety of analyses and gene filtering criteria consistently unite previously unstable groupings with strong statistical support. For example, we recovered a robust grouping of Eustigmatophyceae with Raphidophyceae-Phaeophyceae-Xanthophyceae while Olisthodiscophyceae formed a sister-lineage to Pinguiophyceae. Selecting genes with high phylogenetic signal or data quality recovered more stable topologies. Overall, we find that adding under-represented groups across different lineages is still crucial in resolving phylogenetic relationships, and discrete gene properties affect lineages of stramenopiles differently. This is something which may be explored to further our understanding of the molecular evolution of stramenopiles.

PMID:38852907 | DOI:10.1016/j.ympev.2024.108120

Microbes Infect. 2024 Jun 7:105376. doi: 10.1016/j.micinf.2024.105376. Online ahead of print.

ABSTRACT

Host heterogeneity in pulmonary tuberculosis leads to varied responses to infection and drug treatment. The present portfolio of anti-TB drugs needs to be boosted with new drugs and drug regimens. Macozinone, a clinical-stage molecule targeting the essential enzyme, DprE1, represents an attractive option. Mice (I/St, B6, (AKRxI/St)F1, B6.I-100 and B6.I-139) genetically diverse susceptibility to M. tuberculosis (Mtb) H37Rv infection were subjected to aerosol- or intravenous infection to determine the efficacy of macozinone (MCZ). They were treated with macozinone or reference drugs (isoniazid, rifampicin). Lung and spleen bacterial burdens were measured at four and eight weeks post-infection. Lung histology was evaluated at four weeks of treatment. Treatment with macozinone resulted in a statistically significant reduction in the bacterial load in the lungs and spleen as early as four weeks after treatment initiation in mice susceptible or resistant to Mtb infection. In the TB hypoxic granuloma model, macozinone was more potent than rifampicin in reducing the CFU counts. However, histopathological analysis revealed significant lung changes in I/St mice after eight weeks of treatment initiation. Macozinone demonstrated efficacy to varying degrees across all mouse models of Mtb infection used. These results should facilitate its further development and potential introduction into clinical practice.

PMID:38852904 | DOI:10.1016/j.micinf.2024.105376