Nevin Manimala

Bone Marrow Transplant. 2023 Aug 5. doi: 10.1038/s41409-023-02048-7. Online ahead of print.

ABSTRACT

In the setting of a first relapse of multiple myeloma (MM), a second autologous stem cell transplant (ASCT) following carfilzomib-lenalidomide-dexamethasone (KRd) is an option, although there is scarce data concerning this approach. We performed a retrospective study involving 22 EBMT-affiliated centers. Eligible MM patients had received a second-line treatment with KRd induction followed by a second ASCT between 2016 and 2018. Primary objective was to estimate progression-free survival (PFS) and overall survival (OS). Secondary objectives were to assess the response rate and identify significant variables affecting PFS and OS. Fifty-one patients were identified, with a median age of 62 years. Median PFS after ASCT was 29.5 months while 24- and 36-months OS rates were 92.1% and 84.5%, respectively. Variables affecting PFS were an interval over four years between transplants and the achievement of a very good partial response (VGPR) or better before the relapse ASCT. Our study suggests that a relapse treatment with ASCT after KRd induction is an effective strategy for patients with a lenalidomide-sensitive first relapse. Patients with at least four years of remission after a frontline ASCT and who achieved at least a VGPR after KRd induction appear to benefit the most from this approach.

PMID:37543712 | DOI:10.1038/s41409-023-02048-7

Sci Rep. 2023 Aug 5;13(1):12704. doi: 10.1038/s41598-023-38935-8.

ABSTRACT

Countries have pledged to different national and international environmental agreements, most prominently the climate change mitigation targets of the Paris Agreement. Accounting for carbon stocks and flows (fluxes) is essential for countries that have recently adopted the United Nations System of Environmental-Economic Accounting – ecosystem accounting framework (UNSEEA) as a global statistical standard. In this paper, we analyze how spatial carbon fluxes can be used in support of the UNSEEA carbon accounts in five case countries with available in-situ data. Using global multi-date biomass map products and other remotely sensed data, we mapped the 2010-2018 carbon fluxes in Brazil, the Netherlands, the Philippines, Sweden and the USA using National Forest Inventory (NFI) and local biomass maps from airborne LiDAR as reference data. We identified areas that are unsupported by the reference data within environmental feature space (6-47% of vegetated country area); cross-validated an ensemble machine learning (RMSE=9-39 Mg C [Formula: see text] and [Formula: see text]=0.16-0.71) used to map carbon fluxes with prediction intervals; and assessed spatially correlated residuals (<5 km) before aggregating carbon fluxes from 1-ha pixels to UNSEEA forest classes. The resulting carbon accounting tables revealed the net carbon sequestration in natural broadleaved forests. Both in plantations and in other woody vegetation ecosystems, emissions exceeded sequestration. Overall, our estimates align with FAO-Forest Resource Assessment and national studies with the largest deviations in Brazil and USA. These two countries used highly clustered reference data, where clustering caused uncertainty given the need to extrapolate to under-sampled areas. We finally provide recommendations to mitigate the effect of under-sampling and to better account for the uncertainties once carbon stocks and flows need to be aggregated in relatively smaller countries. These actions are timely given the global initiatives that aim to upscale UNSEEA carbon accounting.

PMID:37543683 | DOI:10.1038/s41598-023-38935-8

Sci Rep. 2023 Aug 5;13(1):12735. doi: 10.1038/s41598-023-40002-1.

ABSTRACT

Sleep disordered breathing (SDB), mainly obstructive sleep apnea (OSA), constitutes a major health problem due to the large number of patients. Intermittent hypoxia caused by SDB induces alterations in metabolic function. Nevertheless, metabolites characteristic for SDB are largely unknown. In this study, we performed gas chromatography-mass spectrometry-based targeted metabolome analysis using data from The Nagahama Study (n = 6373). SDB-related metabolites were defined based on their variable importance score in orthogonal partial least squares discriminant analysis and fold changes in normalized peak-intensity levels between moderate-severe SDB patients and participants without SDB. We identified 20 metabolites as SDB-related, and interestingly, these metabolites were frequently included in pathways related to fructose. Multivariate analysis revealed that moderate-severe SDB was a significant factor for increased plasma fructose levels (β = 0.210, P = 0.006, generalized linear model) even after the adjustment of confounding factors. We further investigated changes in plasma fructose levels after continuous positive airway pressure (CPAP) treatment using samples from patients with OSA (n = 60) diagnosed by polysomnography at Kyoto University Hospital, and found that patients with marked hypoxemia exhibited prominent hyperfructosemia and their plasma fructose levels lowered after CPAP treatment. These data suggest that hyperfructosemia is the abnormality characteristic to SDB, which can be reduced by CPAP treatment.

PMID:37543666 | DOI:10.1038/s41598-023-40002-1

J Ovarian Res. 2023 Aug 5;16(1):155. doi: 10.1186/s13048-023-01159-5.

ABSTRACT

BACKGROUND: Women with polycystic ovarian syndrome (PCOS) have increased hypothalamic-pituitary-adrenal (HPA) axis activation, pro-inflammatory mediators, and psychological distress in response to stressors. In women with PCOS, the corticotropin-releasing hormone (CRH) induces an exaggerated HPA response, possibly mediated by one of the CRH receptors (CRHR1 or CRHR2). Both CRHR1 and CRHR2 are implicated in insulin secretion, and variants in CRHR1 and CRHR2 genes may predispose to the mental-metabolic risk for PCOS.

METHODS: We phenotyped 212 Italian families with type 2 diabetes (T2D) for PCOS following the Rotterdam diagnostic criteria. We analyzed within CRHR1 and CRHR2 genes, respectively, 36 and 18 microarray-variants for parametric linkage to and/or linkage disequilibrium (LD) with PCOS under the recessive with complete penetrance (R1) and dominant with complete penetrance (D1) models. Subsequentially, we ran a secondary analysis under the models dominant with incomplete penetrance (D2) and recessive with incomplete penetrance (R2).

RESULTS: We detected 22 variants in CRHR1 and 1 variant in CRHR2 significantly (p < 0.05) linked to or in LD with PCOS across different inheritance models.

CONCLUSIONS: This is the first study to report CRHR1 and CRHR2 as novel risk genes in PCOS. In silico analysis predicted that the detected CRHR1 and CRHR2 risk variants promote negative chromatin activation of their related genes in the ovaries, potentially affecting the female cycle and ovulation. However, CRHR1- and CRHR2-risk variants might also lead to hypercortisolism and confer mental-metabolic pleiotropic effects. Functional studies are needed to confirm the pathogenicity of genes and related variants.

PMID:37543650 | DOI:10.1186/s13048-023-01159-5

Sci Rep. 2023 Aug 5;13(1):12718. doi: 10.1038/s41598-023-40036-5.

ABSTRACT

Diabetes mellitus (DM) has become the third chronic non-infectious disease affecting patients after tumor, cardiovascular and cerebrovascular diseases, becoming one of the major public health issues worldwide. Detection of early warning risk factors for DM is key to the prevention of DM, which has been the focus of some previous studies. Therefore, from the perspective of residents’ self-management and prevention, this study constructed Bayesian networks (BNs) combining feature screening and multiple resampling techniques for DM monitoring data with a class imbalance in Shanxi Province, China, to detect risk factors in chronic disease monitoring programs and predict the risk of DM. First, univariate analysis and Boruta feature selection algorithm were employed to conduct the preliminary screening of all included risk factors. Then, three resampling techniques, SMOTE, Borderline-SMOTE (BL-SMOTE) and SMOTE-ENN, were adopted to deal with data imbalance. Finally, BNs developed by three algorithms (Tabu, Hill-climbing and MMHC) were constructed using the processed data to find the warning factors that strongly correlate with DM. The results showed that the accuracy of DM classification is significantly improved by the BNs constructed by processed data. In particular, the BNs combined with the SMOTE-ENN resampling improved the most, and the BNs constructed by the Tabu algorithm obtained the best classification performance compared with the hill-climbing and MMHC algorithms. The best-performing joint Boruta-SMOTE-ENN-Tabu model showed that the risk factors of DM included family history, age, central obesity, hyperlipidemia, salt reduction, occupation, heart rate, and BMI.

PMID:37543637 | DOI:10.1038/s41598-023-40036-5

Sci Rep. 2023 Aug 5;13(1):12706. doi: 10.1038/s41598-023-39197-0.

ABSTRACT

Diabetes and hypertension are a serious public health problem worldwide. In the last decades, prevalence of these two metabolic diseases has dramatically increased in the Middle East and North Africa region, especially in Tunisia. This study aimed to determine the prevalence of type 2 diabetes (T2D) and High Blood Pressure (HBP) in Zaghouan, a North-East region of Tunisia. To this end, an exploratory study with stratified random sampling of 420 participants has been carried out. Various data were collected. Blood samples and urine were drawn for biochemical assay. Then, all data were analyzed using the statistical R software. Results showed an alarming situation with an inter-regional difference in prevalence of obesity (50.0%, CI 95.0%), HBP (39.0%, CI 95.0%) and T2D (32.0%, CI 95.0%). This study allowed the discovery of 24, 17 and 2 new cases of T2D, HBP and T2D&HBP respectively. The association of some socio-economic factors and biochemical parameters with these chronic diseases has been highlighted. To conclude, the health situation in the governorate of Zaghouan requires urgent interventions to better manage the growing epidemic of non-communicable diseases (NCD) in the region. This study demonstrated the importance of engaging health policy makers in road mapping and implementing national NCD prevention programs.

PMID:37543635 | DOI:10.1038/s41598-023-39197-0

Sci Rep. 2023 Aug 5;13(1):12716. doi: 10.1038/s41598-023-39939-0.

ABSTRACT

Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal disorder that causes syndromes characterized by physiological dysfunction in many organs and tissues. Despite the recognizable morphological and behavioral deficits associated with MPS I, neither the underlying alterations in functional neural connectivity nor its restoration following gene therapy have been shown. By employing high-resolution resting-state fMRI (rs-fMRI), we found significant reductions in functional neural connectivity in the limbic areas of the brain that play key roles in learning and memory in MPS I mice, and that adeno-associated virus (AAV)-mediated gene therapy can reestablish most brain connectivity. Using logistic regression in MPS I and treated animals, we identified functional networks with the most alterations. The rs-fMRI and statistical methods should be translatable into clinical evaluation of humans with neurological disorders.

PMID:37543633 | DOI:10.1038/s41598-023-39939-0

Arch Iran Med. 2022 Oct 1;25(10):682-690. doi: 10.34172/aim.2022.107.

ABSTRACT

BACKGROUND: The Herat province of Afghanistan is located on the Asian Esophageal Cancer Belt (AECB), a wide area in Central and Eastern Asia where very high rates of esophageal cancer (EC) have been observed. Several risk factors have been reported in the AECB Region by previous studies. Considering lack of information in Afghanistan on this issue, a study was conducted to determine the major risk factors related to EC in order to guide protective measures.

METHODS: A population-based case-control study was performed from July 2015 to August 2016 among 657 EC patients in the Herat Province and 180 histopathological confirmed cases and 189 controls were interviewed. A structured questionnaire was used and face-to-face interviews were conducted.

RESULTS: Low body mass index (BMI), low socio-economic status, family history of EC, consumption of dark tea, very hot beverage and qulurtoroosh were found to be statistically significant for EC and esophageal squamous cell carcinoma (ESCC) in univariate analyses. According to multivariate analyses, sex (OR=2.268; 95% CI=1.238-4.153), very hot beverages (OR=2.253; 95% CI=1.271- 3.996), qulurtoroosh (OR=5.679; 95% CI=1.787-18.815), dark tea (OR=2.757; 95% CI=1.531-4.967), high previous BMI (OR=0.215; 95% CI=0.117-0.431) and low socio-economic status (OR=1.783; 95% CI=1.007-3.177) were associated with ESCC. Being male was found to increase the risk of ESCC with OR=2.268 (95% CI=1.238-4.153).

CONCLUSION: Consuming very hot beverages dark tea and a local food, qulurtoroosh, were found as important risk factors for EC. Our findings warrant further studies and necessitate the implementation of protective measures for EC which is one of the leading cancers in the region.

PMID:37542400 | DOI:10.34172/aim.2022.107

Arch Iran Med. 2022 Oct 1;25(10):676-681. doi: 10.34172/aim.2022.106.

ABSTRACT

BACKGROUND: Iran was one of the first countries to become an epicenter of the coronavirus disease 2019 (COVID-19) epidemic. However, there is a dearth of data on the outcomes of COVID-19 and predictors of death in intensive care units (ICUs) in Iran. We collected extensive data from patients admitted to the ICUs of the one of the tertiary referral hospitals in Tehran, Iran, to investigate the predictors of ICU mortality.

METHODS: The study population included 290 COVID-19 patients who were consecutively admitted to the ICUs of the Sina hospital from May 5, 2021, to December 6, 2021, a period that included the peak of the epidemic of the delta (δ) variant. Demographic data, history of prior chronic diseases, laboratory data (including markers of inflammation), radiologic data, and medication data were collected.

RESULTS: Of the 290 patients admitted to the ICUs, 187 (64.5%) died and 103 (35.5%) survived. One hundred forty-one (141, 48.6%) were men, and the median age (10th percentile, 90th percentile) was 60 (41, 80). Using logistic regression models, older age, history of hypertension, high levels of inflammatory markers, low oxygen saturation, substantial lung involvement in computed tomography (CT) scans, and gravity of the disease as indicated by the WHO 8-point ordinal scale were primary predictors of mortality at ICU. The use of remdesivir and imatinib was associated with a statistically non-significant reduction in mortality. The use of tocilizumab had almost no effect on mortality.

CONCLUSION: The findings are consistent with and add to the currently existing international literature. The findings may be used to predict risk of mortality from COVID-19 and provide some guidance on potential treatments.

PMID:37542399 | DOI:10.34172/aim.2022.106

J Contemp Dent Pract. 2023 Jun 1;24(6):390-395. doi: 10.5005/jp-journals-10024-3518.

ABSTRACT

AIM: To compare the load-bearing capacity of three and four-unit fixed partial denture (FPD) with two different designs of pontics reinforced with industrial glass fibers at two different positions of the FPD.

MATERIALS AND METHODS: A total of 64 samples were made with Bis-acryl composite temporary material and reinforced with industrial glass fibers (E-glass). The specimens were divided into eight groups (groups I-VIII) depending on the number of units, type of pontic design and area of placement of fibers. A universal testing machine was used to evaluate and compare the load-bearing capacity of the specimens. The evaluated data were statistically analyzed using one-way ANOVA and Bonferroni post hoc tests (p ≤ 0.05).

RESULTS: Three-unit interim FPD and modified ridge lap pontic design showed greater load-bearing capacity after reinforcement with glass fibers than a four-unit interim FPD and hygienic pontic design, respectively. Fiber placement at the occlusal plus connector area as well as the cervical plus connector area had comparable results.

CONCLUSION: Industrial glass fibers (E-glass) could be used as a cheaper alternative but clinical performance and their safety are yet to be evaluated.

CLINICAL SIGNIFICANCE: Reinforcement with industrial-grade glass fibers can be a cheaper option for increasing the load-bearing capacity of interim partial dentures, but it needs to be studied in vivo through further studies.

PMID:37542386 | DOI:10.5005/jp-journals-10024-3518