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Nevin Manimala Statistics

Safety and efficacy of autologous stem cell transplantation in dialysis-dependent myeloma patients-The DIADEM study from the chronic malignancies working party of the EBMT

Bone Marrow Transplant. 2023 Jan 21. doi: 10.1038/s41409-023-01915-7. Online ahead of print.

ABSTRACT

The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2 (82%), and >140 mg/m2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5-42.2) and the median OS 102 months (95% CI: 70.4-129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3-14%), 13% (6-20%), and 20% (12-29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.

PMID:36681775 | DOI:10.1038/s41409-023-01915-7

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Nevin Manimala Statistics

Stress-Sensitive Regulators of Fetal Neurodevelopment in HIV and Preeclampsia: An Immunocytochemical Appraisal of Placental OGT and T4 Levels

Arch Immunol Ther Exp (Warsz). 2023 Jan 21;71(1):3. doi: 10.1007/s00005-023-00668-x.

ABSTRACT

Preeclampsia and HIV are a significant burden to maternal health globally, especially in low-middle income countries such as South Africa. In the KwaZulu-Natal province, SA antenatal HIV prevalence is 41.1%, while PE is 12%. PE and HIV infections are maternal stress and inflammation that impact placental function and fetal development. Therefore, this study investigated the impact of the comorbidity of PE and HIV on placental stress and neurodevelopment. Placentae were obtained from four cohorts of pregnant women: normotensive HIV negative, normotensive HIV positive, preeclamptic HIV negative, and preeclamptic HIV positive. The placental tissue sections were immunostained for OGT and T4. Our findings showed that the maternal weight, diastolic, and systolic blood pressures (BP) were higher in PE vs. the normotensive groups, irrespective of HIV status. In addition, significant changes were noticed in the placental weight, fetoplacental ratio, and placental efficiency coefficient. Our findings showed that the maternal weight, diastolic, and systolic blood pressures (BP) were statistically higher in the PE compared to the normotensive. No significant differences were observed between HIV positive and HIV negative groups. In addition, significant changes were noticed in the placental weight, fetoplacental ratio, and placental coefficient. Furthermore, considerable upregulation in the placental expression of OGT in both the conducting and exchange villi of PE and concomitant downregulation in HIV-positive patients compared with Normotensive and HIV-negative individuals, respectively. Our results provide inferential evidence on the dysregulation of OGT in the comorbidity of PE and HIV. This may mediate a compromised programmed outcome of an adverse maternal environment during pregnancy and consequently affect fetal development.

PMID:36681768 | DOI:10.1007/s00005-023-00668-x

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Nevin Manimala Statistics

The characteristics and impact of small and medium forest enterprises on sustainable forest management in Ghana

Sci Rep. 2023 Jan 21;13(1):1208. doi: 10.1038/s41598-023-28403-8.

ABSTRACT

Small and Medium Forest Enterprises are considered promoters of local development and growth due to their contributions to over 50% of forest-based employment in some countries like Brazil, Uganda, and India. Despite the many potentials of these enterprises, their operations go unchecked, which poses a serious threat to the sustainability of tropical forests. This study highlights the characteristics of SMFEs and the impact of SMFEs on sustainable forest management in Ghana from a survey of 80 randomly sampled enterprises in seven communities in the Amenfi West Municipality in Ghana. Data was gathered using structured questionnaires and key informant interviews and analyzed with statistical tools in SPSS version 25. The findings show that 71.25% of the SMFEs are not registered with the appropriate authorities like the Registrar General’s department and the Municipal Assemblies. In addition, 55 (68.8%) of these enterprises have a direct dependency on the forest for raw materials with 21.8% of this number claiming to have obtained the needed permits/licenses to harvest the raw materials they need from the forests. For 91.25% of the enterprises, factors such as resource availability and profits drive their activities and 8.75% are driven by access to labor and job creation. The analysis showed that belonging to an association is a significant determinant of business registration at p = 0.001. Forest policies must seek to promote sustainable management of forest resources by enforcing registration and permit laws. SMFEs must be consistently monitored and supervised to ensure that their activities are guided by policy and their compliance rewarded through capacity building and government support.

PMID:36681764 | DOI:10.1038/s41598-023-28403-8

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Nevin Manimala Statistics

Predicting and elucidating the post-printing behavior of 3D printed cancer cells in hydrogel structures by integrating in-vitro and in-silico experiments

Sci Rep. 2023 Jan 21;13(1):1211. doi: 10.1038/s41598-023-28286-9.

ABSTRACT

A key feature distinguishing 3D bioprinting from other 3D cell culture techniques is its precise control over created structures. This property allows for the high-resolution fabrication of biomimetic structures with controlled structural and mechanical properties such as porosity, permeability, and stiffness. However, analyzing post-printing cellular dynamics and optimizing their functions within the 3D fabricated environment is only possible through trial and error and replicating several experiments. This issue motivated the development of a cellular automata model for the first time to simulate post-printing cell behaviour within the 3D bioprinted construct. To improve our model, we bioprinted a 3D construct using MDA-MB-231 cell-laden hydrogel and evaluated cellular functions, including viability and proliferation in 11 days. The results showed that our model successfully simulated the 3D bioprinted structure and captured in-vitro observations. We demonstrated that in-silico model could predict and elucidate post-printing biological functions for different initial cell numbers in bioink and different bioink formulations with gelatine and alginate, without replicating several costly and time-consuming in-vitro measurements. We believe such a computational framework will substantially impact 3D bioprinting’s future application. We hope this study inspires researchers to further realize how an in-silico model might be utilized to advance in-vitro 3D bioprinting research.

PMID:36681762 | DOI:10.1038/s41598-023-28286-9

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Nevin Manimala Statistics

Predicting mortality and visualizing health care spending by predicted mortality in Danes over age 65

Sci Rep. 2023 Jan 21;13(1):1203. doi: 10.1038/s41598-023-28102-4.

ABSTRACT

Health care expenditure in the last year of life makes up a high proportion of medical spending across the world. This is often framed as waste, but this framing is only meaningful if it is known at the time of treatment who will go on to die. We analyze the distribution of health care spending by predicted mortality for the Danish population over age 65 over the year 2016, with one-year mortality predicted by a machine learning model based on sociodemographics and use of health care services for the two years before entry into follow-up. While a reasonably good model can be built, extremely few individuals have high ex-ante probability of dying, and those with a predicted mortality of more than 50% account for only 2.8% of total health care expenditure. Decedents outspent survivors by a factor of more than ten, but compared to survivors with similar predicted mortality they spent only 2.5 times as much. Our results suggest that while spending in the last year of life is indeed high, this is nearly all spent in situations where there is a reasonable expectation that the patient can survive.

PMID:36681729 | DOI:10.1038/s41598-023-28102-4

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Nevin Manimala Statistics

Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches

Sci Rep. 2023 Jan 21;13(1):1188. doi: 10.1038/s41598-023-27928-2.

ABSTRACT

Staphylococcus aureus is a human commensal and also an opportunist pathogen causing life threatening infections. During S. aureus disease, the abscesses that characterise infection can be clonal, whereby a large bacterial population is founded by a single or few organisms. Our previous work has shown that macrophages are responsible for restricting bacterial growth such that a population bottleneck occurs and clonality can emerge. A subset of phagocytes fail to control S. aureus resulting in bacterial division, escape and founding of microabscesses that can seed other host niches. Here we investigate the basis for clonal microabscess formation, using in vitro and in silico models of S. aureus macrophage infection. Macrophages that fail to control S. aureus are characterised by formation of intracellular bacterial masses, followed by cell lysis. High-resolution microscopy reveals that most macrophages had internalised only a single S. aureus, providing a conceptual framework for clonal microabscess generation, which was supported by a stochastic individual-based, mathematical model. Once a threshold of masses was reached, increasing the number of infecting bacteria did not result in greater mass numbers, despite enhanced phagocytosis. This suggests a finite number of permissive, phagocyte niches determined by macrophage associated factors. Increased understanding of the parameters of infection dynamics provides avenues for development of rational control measures.

PMID:36681703 | DOI:10.1038/s41598-023-27928-2

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Nevin Manimala Statistics

Mapping nucleolus-associated chromatin interactions using nucleolus Hi-C reveals pattern of heterochromatin interactions

Nat Commun. 2023 Jan 21;14(1):350. doi: 10.1038/s41467-023-36021-1.

ABSTRACT

As the largest substructures in the nucleus, nucleoli are the sites of ribosome biogenesis. Increasing evidence indicates that nucleoli play a key role in the organization of 3D genome architecture, but systematic studies of nucleolus-associated chromatin interactions are lacking. Here, we developed a nucleolus Hi-C (nHi-C) experimental technique to enrich nucleolus-associated chromatin interactions. Using the nHi-C experiment, we identify 264 high-confidence nucleolus-associated domains (hNADs) that form strong heterochromatin interactions associated with the nucleolus and consist of 24% of the whole genome in HeLa cells. Based on the global hNAD inter-chromosomal interactions, we find five nucleolar organizer region (NOR)-bearing chromosomes formed into two clusters that show different interaction patterns, which is concordant with their epigenetic states and gene expression levels. hNADs can be divided into three groups that display distinct cis/trans interaction signals, interaction frequencies associated with nucleoli, distance from the centromeres, and overlap percentage with lamina-associated domains (LADs). Nucleolus disassembly caused by Actinomycin D (ActD) significantly decreases the strength of hNADs and affects compartment/TAD strength genome-wide. In summary, our results provide a global view of heterochromatin interactions organized around nucleoli and demonstrate that nucleoli act as an inactive inter-chromosomal hub to shape both compartments and TADs.

PMID:36681699 | DOI:10.1038/s41467-023-36021-1

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Nevin Manimala Statistics

Associations of parent-adolescent closeness with P3 amplitude, frontal theta, and binge drinking among offspring with high risk for alcohol use disorder

Alcohol Clin Exp Res. 2023 Jan 21. doi: 10.1111/acer.14973. Online ahead of print.

ABSTRACT

BACKGROUND: Parents impact their offspring’s brain development, neurocognitive function, risk, and resilience for alcohol use disorder (AUD) via both genetic and socio-environmental factors. Individuals with AUD and their unaffected children manifest low parietal P3 amplitude and low frontal theta (FT) power, reflecting heritable neurocognitive deficits associated with AUD. Likewise, children who experience poor parenting tend to have atypical brain development and greater rates of alcohol problems. Conversely, positive parenting can be protective and critical for normative development of self-regulation, neurocognitive functioning and the neurobiological systems subserving them. Yet, the role of positive parenting in resiliency toward AUD is understudied and its association with neurocognitive functioning and behavioral vulnerability to AUD among high-risk offspring is less known. Using data from the Collaborative Study on the Genetics of Alcoholism prospective cohort (N = 1256, mean age [SD] = 19.25 [1.88]), we investigated the associations of closeness with mother and father during adolescence with offspring P3 amplitude, FT power, and binge drinking among high-risk offspring.

METHODS: Self-reported closeness with mother and father between ages 12 and 17 and binge drinking were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism. P3 amplitude and FT power were assessed in response to target stimuli using a Visual Oddball Task.

RESULTS: Multivariate multiple regression analyses showed that closeness with father was associated with larger P3 amplitude (p = 0.002) and higher FT power (p = 0.01). Closeness with mother was associated with less binge drinking (p = 0.003). Among male offspring, closeness with father was associated with larger P3 amplitude, but among female offspring, closeness with mother was associated with less binge drinking. These associations remained statistically significant with father’s and mothers’ AUD symptoms, socioeconomic status, and offspring impulsivity in the model.

CONCLUSIONS: Among high-risk offspring, closeness with parents during adolescence may promote resilience for developing AUD and related neurocognitive deficits albeit with important sex differences.

PMID:36680783 | DOI:10.1111/acer.14973

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Nevin Manimala Statistics

Impact of Pilot Zones for Green Finance Reform and Innovations on green technology innovations: evidence from Chinese manufacturing corporates

Environ Sci Pollut Res Int. 2023 Jan 21. doi: 10.1007/s11356-023-25371-4. Online ahead of print.

ABSTRACT

Green technology innovation is a crucial factor in the global quest for sustainability. In 2017, China approved the establishment of Pilot Zones for Green Financial Reform and Innovations to build and improve the green financial system. Using a difference-in-difference (DID) model, this paper examines the impact of this pilot policy on corporate green technology innovation and its transmission mechanism based on the data of green patents of Chinese A-share listed manufacturing companies between 2014 and 2019. It is found that Pilot Zones for Green Financial Reform and Innovations have contributed to the growth of green technology innovations. This conclusion is confirmed after a series of robustness tests. The pilot policy’s promotion of green technology innovations is mainly reflected in the application of corporate green invention patents. However, it is more significant for non-heavy polluting enterprises, high-tech certified enterprises, and large enterprises. The paper also finds that the pilot policy promotes corporate green technology innovation by promoting social financing, talent support, and government financial support.

PMID:36680721 | DOI:10.1007/s11356-023-25371-4

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Nevin Manimala Statistics

Analyzing the effect of view factors on surface heat flux, surface temperature, and vegetation cover

Environ Sci Pollut Res Int. 2023 Jan 21. doi: 10.1007/s11356-023-25261-9. Online ahead of print.

ABSTRACT

With the increase in population in cities, economic, social, and environmental problems continue to increase, and it is thought that the microclimatic conditions created by these problems will cause more environmental problems. One of the factors affecting the urban climate in urban areas is urban geometry. The climate of a region changes due to the shape of the land surface, human activities, atmospheric movements, and latent and sensible heat fluxes. Sky view factor (SVF), building view factor (BVF), and tree view factor (TVF) are actively used in the determination of urban geometry. However, studies on how these factors affect the thermal state of the urban environment are insufficient. Determining the land surface changes and thermal condition characteristics (LST, NDVI, SHF, and LHF) depending on urban growth and examining how these properties affect thermal conditions are very important in the construction of sustainable urban planning. In the study, SVF, BVF, TVF, LST, NDVI, SHF, and LHF values of 55 points determined for three different areas with different urban geometries were calculated. How these values affect each other and their situation on urban outdoor thermal comfort is evaluated. In the study, statistical analysis was performed to evaluate the relationship between surface temperature, surface heat fluxes, different view factors, and vegetation. As a result of ANOVA analysis, it was determined as very significant (p > 0.01) in all regions. Both SHF and LHF values differ with SVF. The SHF value has a direct relationship with the SVF value. LHF is inversely proportional to the SVF value. The situation is reversed for SHF variation concerning vegetation. LHF and NDVI are directly related. SHF and NDVI are inversely proportional. SVF and NDVI values also vary according to the LST value. It has been observed that LST has a direct relationship with SVF and an inverse relationship with NDVI.

PMID:36680715 | DOI:10.1007/s11356-023-25261-9