Efficacy of Inclisiran in Patients Having Familial Hypercholesterolemia: Heterozygous Compared to Homozygous Trait, a Systematic Review and Meta-analysis.

OBJECTIVE: To find out whether inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. METHODS: We conducted the systematic review and meta-analysis of ORION clinical trials. PubMed, Embase, and Clinicaltrials.gov databases were searched for the relevant studies. Atheroscalerotic parameters considered for our objective were low-density lipoprotein cholesterol, total cholesterol, proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B, and nonhigh-density lipoprotein cholesterol. Primary outcomes were the percentage difference in atheroscalerotic parameters at follow-up relative to baseline values. Our study examined these primary outcomes to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by the Cochrane risk of bias tool. Meta-analysis was performed when at least 2 studies reported on the same variable. RESULTS: Four ORION clinical trials provided the data related to the mean difference in the atheroscalerotic parameters at follow-up relative to baseline, of HeFH and HoFH patient populations, after administration of 300 mg inclisiran subcutaneously. We pooled together these mean differences for each group and applied a statistical test to analyze if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in low-density lipoprotein cholesterol (HeFH: -48.62%; HoFH: -9.12%; P < 0.05), total cholesterol (HeFH: -30.31%; HoFH: -11.50%; P < 0.05), apolipoprotein (HeFH: -39.97%; HoFH: -14.68%; P < 0.05), and nonhigh-density lipoprotein (HeFH: -44.51%; HoFH: -12.22%; P < 0.05) between HeFH and HoFH groups. However, the difference in pooled mean difference in PCSK9 values (HeFH: -68.41%; HoFH: -56.25%; P = 0.2) between HeFH and HoFH groups was statistically insignificant. Studies were of high quality. CONCLUSIONS: There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.

Shattering and yield expression of sesame (Sesamum indicum L) genotypes influenced by paclobutrazol concentration under rainfed conditions of Pothwar.

Seed shattering is a critical challenge that significantly reduces sesame production by 50%. These shattering losses can be reduced by selecting shattering resistant genotypes or by incorporating modern agronomic management such as paclobutrazol, which can boost productivity and prevent seed shattering in sesame. Two-years of field trials were conducted to examine the effect of sesame genotypes, environment, and paclobutrazol (PBZ) concentrations. Twelve sesame genotypes were used in a four-way factorial RCBD with three replications and five PBZ concentrations (T0 = Control; T1 = 150; T2 = 300; T3 = 450; and T4 = 600 mg L- 1) under rainfed conditions of Pothwar. The findings revealed significant variations in the major effects of all examined variables (genotypes, locations, years, and PBZ levels). Sesame genotypes PI-154304 and PI-175907 had the highest plant height, number of capsule plant- 1, seed capsule- 1, 1000 seed weight, biological yield, and seed yield, while also having the lowest seed losses and shattering percentage. Regarding environments, NARC-Islamabad generated the highest plant height, number of capsule plant- 1, shattering percentage, and biological yield; however, the URF-Koont produced the highest seed yield with the lowest shattering percentage. Additionally, plant height, capsules plant- 1, and biological yield were higher in 2021, while seed capsule- 1, 1000 seed weight, seed losses, shattering percentage, and seed yield were higher in 2020. PBZ concentration affected all measured parameters; plant height and number of seed capsule- 1 decreased with increasing PBZ concentrations. 450 mg L- 1 PBZ concentration generated the highest biomass, number of capsules plant- 1, and seed yield. At the same time, PBZ concentration 600 mg L- 1 generated the smallest plant, the lowest seed capsules- 1, the greatest thousand seed weight, and the lowest shattering percentage. The study concluded that paclobutrazol could dramatically reduce shattering percentage and shattering losses while increasing economic returns through better productivity. Based on the findings, the genotypes PI-154304 and PI-175907 with paclobutrazol level 450 mgL- 1 may be suggested for cultivation in Pothwar farming community under rainfed conditions, as they showed promising shattering resistance as well as enhanced growth and yield.

Semiparametric estimation of cross-covariance functions for multivariate random fields.

The prevalence of spatially referenced multivariate data has impelled researchers to develop procedures for joint modeling of multiple spatial processes. This ordinarily involves modeling marginal and cross-process dependence for any arbitrary pair of locations using a multivariate spatial covariance function. However, building a flexible multivariate spatial covariance function that is nonnegative definite is challenging. Here, we propose a semiparametric approach for multivariate spatial covariance function estimation with approximate Matérn marginals and highly flexible cross-covariance functions via their spectral representations. The flexibility in our cross-covariance function arises due to B-spline-based specification of the underlying coherence functions, which in turn allows us to capture nontrivial cross-spectral features. We then develop a likelihood-based estimation procedure and perform multiple simulation studies to demonstrate the performance of our method, especially on the coherence function estimation. Finally, we analyze particulate matter concentrations (PM2.5 ) and wind speed data over the West-North-Central climatic region of the United States, where we illustrate that our proposed method outperforms the commonly used full bivariate Matérn model and the linear model of coregionalization for spatial prediction.

Desert Soil Microbes as a Mineral Nutrient Acquisition Tool for Chickpea (Cicer arietinum L.) Productivity at Different Moisture Regimes.

Drought is a major constraint in drylands for crop production. Plant associated microbes can help plants in acquisition of soil nutrients to enhance productivity in stressful conditions. The current study was designed to illuminate the effectiveness of desert rhizobacterial strains on growth and net-return of chickpeas grown in pots by using sandy loam soil of Thal Pakistan desert. A total of 125 rhizobacterial strains were isolated, out of which 72 strains were inoculated with chickpeas in the growth chamber for 75 days to screen most efficient isolates. Amongst all, six bacterial strains (two rhizobia and four plant growth promoting rhizobacterial strains) significantly enhanced nodulation and shoot-root length as compared to other treatments. These promising strains were morphologically and biochemically characterized and identified through 16sRNA sequencing. Then, eight consortia of the identified isolates were formulated to evaluate the growth and development of chickpea at three moisture levels (55%, 75% and 95% of field capacity) in a glass house experiment. The trend for best performing consortia in terms of growth and development of chickpea remained T2 at moisture level 1 > T7 at moisture level 2 > T4 at moisture level 3. The present study indicates the vital role of co-inoculated bacterial strains in growth enhancement of chickpea under low moisture availability. It is concluded from the results that the consortium T2 (Mesorhizobium ciceri RZ-11 + Bacillus subtilis RP-01 + Bacillus mojavensis RS-14) can perform best in drought conditions (55% field capacity) and T4 (Mesorhizobium ciceri RZ-11 + Enterobacter Cloacae RP-08 + Providencia vermicola RS-15) can be adopted in irrigated areas (95% field capacity) for maximum productivity of chickpea.

Thermodynamics and Kinetics Parameters of Eichhornia crassipes Biomass for Bioenergy.

BACKGROUND: Eichhornia crassipes is an aquatic plant well known for its role in soil reclamation due to the containment of valuable nutrients. Moreover, its biomass is an abundant and low-cost biological resource. Pyrolysis of a biomass offers one of the cleanest methods to harness the bioenergy stored in the biomass. OBJECTIVE: The present study was focused on evaluating the bioenergy potential of Eichhornia crassipes via pyrolysis. METHODS: Biomass of E. crassipes was collected from a municipal wastewater pond. Oven dried powdered biomass of E. crassipes was subjected to pyrolysis at three heating rates including 10, 30 and 50 °C min-1 in a simultaneous Thermogravimetry-Differential Scanning Calorimetry analyzer under an inert environment containing nitrogen. Data obtained were subjected to isoconversional models of Kissenger-Akahira-Sunose (KSA) and Flynn-Wall-Ozawa (FWO) to understand the reaction chemistry. RESULTS: Kinetic parameters have shown that the pyrolysis followed first-order reaction kinetics. The average values of activation energies (129.71-133.03 kJ mol-1) and thermodynamic parameters including high heating values (18.12 MJ kg-1), Gibb's free energies (171-180 kJ mol-1) and enthalpy of reaction (124-127 kJ mol-1) have shown the remarkable bioenergy potential of this biomass. CONCLUSION: This low-cost biomass may be used to produce liquids, gases, and biochar in a costefficient and environmentally friendly way via pyrolysis or co-pyrolysis in the future.

Kinetic analyses and pyrolytic behavior of Para grass (Urochloa mutica) for its bioenergy potential.

The biomass of Urochloa mutica was subjected to thermal degradation analyses to understand its pyrolytic behavior for bioenergy production. Thermal degradation experiments were performed at three different heating rates, 10, 30 and 50°Cmin-1 using simultaneous thermogravimetric-differential scanning calorimetric analyzer, under an inert environment. The kinetic analyses were performed using isoconversional models of Kissenger-Akahira-Sunose (KAS) and Flynn-Wall-Ozawa (FWO). The high heating value was calculated as 15.04MJmol-1. The activation energy (E) values were shown to be ranging from 103 through 233 kJmol-1. Pre-exponential factors (A) indicated the reaction to follow first order kinetics. Gibbs free energy (ΔG) was measured to be ranging from 169 to 173kJmol-1 and 168 to 172kJmol-1, calculated by KAS and FWO methods, respectively. We have shown that Para grass biomass has considerable bioenergy potential comparable to established bioenergy crops such as switchgrass and miscanthus.

Graphical dataset on important medicinal plants used for curing dental issues in Manoor Valley, Mansehra, Pakistan.

The graphical dataset in this paper is related to the research article entitled "A novel survey of the ethno medicinal knowledge of dental problems in Manoor Valley (Northern Himalaya), Pakistan" (I.U. Rahman, F. Ijaz, Z. Iqbal, A. Afzal, N. Ali, M. Afzal, M.A. Khan, S. Muhammad, G. Qadir, M. Asif, 2016) [1]. This article describes how the local community of Manoor Valley practices cultural / traditional knowledge for dental problems. For the recorded data of 25 medicinal plants, six quantitative ethnomedicinal statistical approaches / equations were used. Out of these indices, four were used to measure the most imported and cited medicinal plant species while two for the comparative analysis to evaluate the novelty of work.

A novel survey of the ethno medicinal knowledge of dental problems in Manoor Valley (Northern Himalaya), Pakistan.

ETHNOPHARMACOLOGICAL RELEVANCE: In the study area, the traditional knowledge and cultural practices of utilizing medicinal plants in the human healthcare is primarily restricted to the old age members of the community, while younger generation is mostly unaware of the natural wealth usage. AIM OF THE STUDY: We provide the first ever ethno medicinal insights into the management of dental disorders in Pakistan. The prime objective of the study was to explore novel knowledge of these local and remote community members and share it with rest of the world in documented form. MATERIALS AND METHODS: Field surveys were arranged for collection and documentation of medicinal plants of Manoor valley during 2015. Total 71 local inhabitants were interviewed randomly through questionnaire. The data obtained were quantitatively analyzed using the use value (UVi), relative frequency citations (RFCs), fidelity level index (FL%) and consensus index (CI%). For novel uses all plants were thoroughly checked with previously published articles on the same disorder and analyzed through Jaccard index (JI) and Sorensen's similarity index (QS). The collected specimens after confirmation were submitted to the Herbarium, Department of Botany, Hazara University, Mansehra, Pakistan (HUP). RESULTS: In present study 25 plants belonging to 17 families are reported, these plants were used commonly as ethno medicine. There were herbs (64%), shrubs (20%) and trees (16%) whereas, Lamiaceae with 4 species was the leading family. Majority of medicinal plant species were used in treatment of toothache (38%), wound healing (19%), gum infections (16%) whereas and lowest percentage of species were used for mouth ulcer as well as teeth powder (3%). Leaves were the most widely part used plant part in the treatment of different diseases (36%). Dominated medicinal plants with high used values were Juglans regia (UVi=0.94), Rumex dentatus (0.89) and Indigofera heterantha (0.88). Based on the RFC values, the most valuable and cited medicinal plant species used by the traditional drivers are Juglans regia having (RFCs=0.69) and Rumex dentatus (0.58). CI results show that most respondents percentage was for Juglans regia having CI%=69%, followed by Rumex dentatus (57.7%). Medicinal plants with high fidelity level and reported for one dental disorder were Berberis lycium, Geranium wallichianum, Lathyrus aphaca, Platanus orientalis, Sedum spp. and Urtica dioica for toothache. Further, new medicinal uses of Abies pindrow, Ajuga integrifolia, Berberis lycium, Urtica dioica, Indigofera heterantha were recorded for the first time from Pakistan and Astragalus grahamianus, Corydalis cornuta, Prunella vulgaris, Ranunculus muricatus, Rumex hastatus, Stellaria media, Tagetes minuta, Taraxacum officinale and Lathyrus aphaca, across the world for the current reported medicinal uses. All mentioned plant species are reported for the first time ever for dental disorders from Manoor Valley. Nonetheless, this is a novel study as no single ethno medicinal study on dental disorder up-till now has been reported from Pakistan. CONCLUSION: The present study is the first ever documentation of ethno medicinal practices aiming at the dental disorders in Pakistan, which resulted in 64% of medicinal uses new claims. So, the reported species of remote valley should be further evaluated for proper experimentation and pharmacological activities to authenticate their current traditional usage. Field observation revealed vegetation of the area was generally threatened due to its unwise use by the local communities. Trends like deforestation, over grazing, habitat fragmentation and introduction of the exotic taxa were the visible threats. So conservation of such an important natural God gifted treasure is mandatory.