bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Pengembangan Sumber Daya Manusia terhadap Kinerja Aparatur Sipil Negara (ASN) melalui Komitmen Afektif sebagai Variabel Intervening
Authors: Ahmad Fahrur Rizal , Wati Intan Ratna
Published: December 2024

ENGLISHEmployee performance is the most important factor, but there is a decline in performance at the Regional Financial and  Asset Management Agency (BPKAD) Pati Regency. This study aims to analyze the effect of human resource development on employee performance with affective commitment as an intervening variable. The population in this study were employees of BPKAD Pati Regency using purposive sampling with a sample size of 124 employees involved in this study. This study uses descriptive and quantitative methods, as well as multivariate analysis tools. Extensive variable analysis is provided by the Smart Partial Least Square (PLS) application program. The research results show that human resource development has a positive effect on affective commitment and employee performance. Affective commitment also has a positive effect on employee performance, and affective commitment can mediate the influence between HR development and performance. INDONESIAKinerja karyawan merupakan faktor terpenting, akan tetapi terjadi penurunan kinerja pada Badan Pengelolaan Keuangan Dan Aset Daerah (BPKAD) Kabupaten Pati.  Tujuan penelitian ini adalah untuk melihat bagaimana pengembangan sumber daya manusia berdampak pada kinerja karyawan dengan komitmen afektif sebagai variabel intervening. Populasi dalam penelitian ini adalah seluruh karyawan BPKAD Kabupaten Pati dengan menggunakan purposive sampling diperoleh sampel sebanyak 124 karyawan. Studi ini menggunakan metode deskriptif dan kuantitatif, serta alat analisis multivariat. Analisis variabel lebih mendalam diberikan dengan penggunaan model Structural Equation Modelling dan menggunakan program aplikasi Smart Partial Least Square (PLS). Penelitian ini memiliki hasil bahwa pengembangan SDM memiliki pengaruh positif pada komitmen afektif dan kinerja karyawan. Komitmen afektif juga memiliki pengaruh positif pada kinerja karyawan, dan komitmen afektif dapat memediasi pengaruh antara pengembangan SDM dan kinerja.
Effect of ethanol concentration as drying agent to the mechanical properties of oil palm lumber
Authors: Othman Ahmad Fauzi , Arshad Mohd Fadzil , Ahmad Zaki Junaiza , Nik Hashim Nik Hazlan , Abdul Latif Nur Hannani , Shafie Amran
Published: December 2024

This study includes the analysis of ethanol influence toward oil palm lumber as drying agent. The mechanical characteristics of oil palm timber were assessed. For ethanol soaking, the treatment was carried out utilizing 91%, 70%, 85%, 55%, and 49% concentration for both inner and outer layer of oil palm timber. The outer layer of oil palm lumber after treatment had more strength compared to control oil palm lumber. Meanwhile, the strength of treated core layer showed reduction compared to that of control oil palm lumber. Our finding demonstrates that the drying method of oil palm trunk using ethanol had been successful and showed that ethanol influenced mechanical properties of oil palm trunk in drying the outer and core layer of OPT for 24 hours with a temperature of 80℃ by using oven and only 55% of the ethanol concentration was suggested to obtain the best mechanical properties of OPT.
Synthesis, Antibacterial Properties and Molecular Docking of Nitrobenzoylthiourea Compounds and their Copper(II) Complex
Authors: MOHD YUNUS NURINA ASYURA BINTI , MOHAMAD ARIF MAYA ASYIKIN , MOHAMAD SINANG FAZIA
Published: December 2024

The rise of multidrug-resistant microbial pathogens has increased the demand for highly effective antibiotics. Five nitrobenzoylthiourea ligands (1–5) with amino acid side chains and their corresponding Cu(II) complexes (6–10) were synthesised with yields ranging from 43% to 90%. The successful synthesis of ligands 1-5 were confirmed by the absence of the ν(NCS) stretching band and the presence of the ν(NH) band, indicating the complete reaction of all (NCS) with a series of amino acids as well as the appearance of two N-H signals in the 1H NMR spectra of all the synthesised ligands. On the other hand, the shift of the (C=O) carboxylic peaks in the Cu(II) complexes suggested successful coordination of ligands to the metal ion via the carboxylate group. The antibacterial activities of these compounds were tested against six bacteria: Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa using the disc diffusion method. The Cu(II) complexes (6-10) exhibited enhanced antibacterial activity compared to the ligands  (1-5), especially against gram-negative bacteria (E. coli, K. pneumoniae, and P. aeruginosa). For example, compound 4 showed moderate activity against K. pneumoniae with a 14 mm inhibition zone while its Cu(II) complexes, 8 recorded better inhibition  against K. pneumoniae with a 16 mm inhibition zone. Molecular docking studies on all complexes (6-10) also revealed higher binding affinity with targeted proteins with binding energy between -10.4 kcal/mol to -9.0 kcal/mol, in comparison with ligand 2 and 4 with the binding energy of only -7.7 kcal/mol (against S. aureus) and -6.9 kcal/mol (against K. pneumoniae). The enhanced antibacterial activity of all complexes correlates with the higher binding affinity obtained for all complexes. Hence, this study concludes that the nitrobenzoylthiourea derivatives, and particularly their Cu(II) complexes can show potential as antibacterial agent although more thorough investigation are required to develop these compounds into useful drugs.
Pelatihan dan Implementasi Perencanaan Karir Siswa Pasca Lulus Sekolah Pada SMK
Authors: Setiadi Teguh , Fajri Laksamana Rajendra Haidar Azani , Ilhami Susanti Dwi
Published: December 2024

Pendidikan sekolah menengah kejuruan adalah sebagai jalur penting untuk membina para profesional terampil dengan skill sesuai dengan bidangnya dan semakin menarik perhatian di dunika pekerjaan. Pendidikan kejuruan lebih menekankan pada pengembangan keterampilan praktis dan kompetensi kejuruan siswa. Hal ini membekali mereka dengan kemampuan untuk beradaptasi dengan cepat terhadap tuntutan pasar dan berkontribusi pada pembangunan sosial dan ekonomi salah satunya di SMK Harapan Mulya Kendal. Seiring dengan kemajuan globalisasi dan teknologi, perencanaan karier telah berkembang lebih dari sekadar pemilihan karier; perencanaan karier telah berubah menjadi proses komprehensif yang memerlukan pertimbangan berbagai faktor seperti minat pribadi, nilai-nilai, keterampilan, dan persyaratan pasar kerja. Pada pengabdian kepada masyarakat ini bertujuan untuk implementasi penerapan aplikasi smart karir bagi siswa sekolah menengah kejuruan, dengan tujuan membantu mereka mengatasi tantangan di tempat kerja dengan lebih baik dan mewujudkan tujuan karier masing-masing sebelum lulus sekolah. Pelaksanaan kegiatan pengabdian kepada masyarakat menitikberatkan pada penyelesaian permasalahan yaitu sumber daya manusia siswa dan bimbingan konseling agar meningkatkan kualitas karir siswa, dan pemahaman terhadap potensi karir siswa SMK.
Reconstructing missing data of damaged buildings from post-hurricane reconnaissance data using XGBoost
Authors: Yang Hyunje , Lee Jun-Whan , Klepac Steven , Santos Cruz Armando Ulises , Subgranon Arthriya , Jiao Junfeng
Published: December 2024

Assessing building damage in coastal communities after a hurricane event is crucial for reducing both immediate and long-term disaster impacts, as well as for enhancing resilience planning and disaster preparedness. Despite the extensive data collection efforts of the post-hurricane reconnaissance teams, some information on the structural features of damaged buildings is often missing due to various reasons, like the absence of relevant documents or severe building damage, thereby limiting our comprehensive understanding of building resilience to natural disasters. This study introduces a machine learning approach based on extreme gradient boosting (XGBoost) to reconstruct missing structural features of the damaged buildings from four types of data (known structural, geospatial, hazard, and damage level information). XGBoost models were trained based on the reconnaissance datasets collected from four regions affected by Hurricanes. For each region, we analyzed the model’s performance depending on the missing structural features. We also demonstrated the importance of including geospatial, hazard, and damage level data by showing improved performance of XGBoost models compared to those trained only on known structural data. Furthermore, we examined how the accuracy of the XGBoost approach changes if multiple structural features are missing. This XGBoost approach has the potential to support post-hurricane building damage assessments by providing missing building details, enabling comprehensive post-disaster analysis.
Metyrapone single administration, as a possible predictive tool of its dosage and timing in Cushing’s syndrome
Authors: Tsujimoto Yasutaka , Yamamoto Naoki , Bando Hironori , Yamamoto Masaaki , Ohmachi Yuka , Motomura Yuma , Oi-Yo Yuka , Sasaki Yuriko , Suzuki Masaki , Urai Shin , Takahashi Michiko , Iguchi Genzo , Ogawa Wataru , Fukuoka Hidenori
Published: December 2024

Metyrapone is commonly used in the initial management of Cushing’s syndrome to reduce hypercortisolemia, but its optimal dosage and timing can vary significantly between patients. Currently, there are limited guidelines on adjustment methods for its administration to individual needs. This study aimed to evaluate responsiveness of each patient to metyrapone and identify the patient characteristics associated with the indices of cortisol responsiveness following a low-dose metyrapone. This single-center retrospective observational study included 15 treatment-naïve patients, 7 of whom had Cushing’s disease and 8 had adrenal Cushing’s syndrome. Serum cortisol levels were measured hourly from the time of administration of 250 mg of metyrapone up to four hours afterward. Parameters analyzed included the nadir of serum cortisol levels (Fnadir), the difference between basal and nadir serum cortisol levels (ΔF), the time to nadir, and the characteristics of the patients. As a result, cortisol suppression curves showed significant variability among patients, particularly in the time to nadir. While the median time to nadir was 2 hours, 20% of patients required 4 hours or more, and these responses were not associated with patient characteristics. Fnadir was positively correlated with early-morning serum cortisol levels, serum cortisol levels after low-dose dexamethasone suppression test (LDDST), and urinary free cortisol (UFC) levels, whereas ΔF was positively correlated with late-night serum cortisol levels, serum cortisol levels after LDDST, and UFC levels. In conclusion, the duration of response to metyrapone appeared unpredictable in patients with Cushing’s syndrome and did not correlate with patient characteristics at baseline. Tracking the effect of metyrapone following a single low-dose administration may explain this variability and provide insights for optimizing individual dosing regimens. Further studies are required to validate these findings and guide more personalized treatment adjustments.
Effectiveness of educational intervention in improving physical activity and nutritional performance among pregnant women: a pre-post quasi-experimental study using health belief model
Authors: Khani Jeihooni Ali , Razmjouie Fatemeh , Jormand Hanieh , Sedghi Jahromi Fariba , Afzali Harsini Pooyan , Kamyab Amirhossein , Ghalehgolab Farzaneh
Published: December 2024

Background

Physical activity and proper nutrition during pregnancy are crucial for maternal and fetal health. However, many pregnant women fail to meet recommended guidelines. This study aimed to assess the effectiveness of an educational intervention based on the Health Belief Model (HBM) in improving these behaviors.

Methods

A pre-post with control quasi-experimental study was conducted among 200 pregnant women (100 experimental and 100 control) in Shiraz, Iran. The intervention group attended eight weekly 50-minute educational sessions based on the HBM. Physical activity and nutritional performance were assessed using validated questionnaires at baseline and three months post-intervention. Data were analyzed using paired and independent t-tests, with effect sizes and 95% confidence intervals reported.

Results

The intervention significantly improved physical activity (mean score: 29.25 ± 4.42 vs. 12.28 ± 4.36, p < 0.001) and nutritional performance across all food groups (p < 0.001) in the experimental group compared to the control group. Key constructs of the HBM, including perceived sensitivity, severity, benefits, self-efficacy, and cues to action, showed significant increases with notable effect sizes and 95% confidence intervals, while perceived barriers significantly decreased (p < 0.001).

Conclusions

The educational intervention based on the HBM effectively improved physical activity and nutritional performance among pregnant women. Integrating such programs into routine prenatal care is recommended, with emphasis on personalized counseling, regular follow-ups, and spousal involvement to sustain behavioral changes and promote maternal and fetal health.
Efficacy and safety of chimeric antigen receptor T cells targeting BCMA and GPRC5D in relapsed or refractory multiple myeloma
Authors: Yang Xu , Wang Feiqing , Yuan Xiaoshuang , Yang Bo , Chen Juan , Cheng Jinyang , Liu Guangyang , Tang Dongxin , Xu Xiao , Wang Sanbin , He Zhixu , Liu Yang , Li Yanju
Published: December 2024

Background

Clinical studies have demonstrated the high efficacy of using chimeric antigen receptor (CAR)-T cells targeting B-cell maturation antigen (BCMA) and orphan G protein-coupled receptor, class C group 5 member D (GPRC5D) to treat relapsed or refractory multiple myeloma (RRMM). In this study, we compared the efficacy and safety of BCMA CAR-T-cell therapy (BCMA CAR-T) and GPRC5D CAR T-cell therapy (GPRC5D CAR-T) in patients with RRMM.

Methods

We retrieved and included eligible clinical trials of BCMA or GPRC5D CAR-T for RRMM patients. The primary outcomes for efficacy were overall response rate (ORR), complete response rate (CRR), minimal residual disease (MRD) negativity, and relapse rate. The primary outcomes for safety were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Results

We incorporated 18 early-phase, single-arm clinical trials, which included 503 and 133 patients receiving BCMA CAR-T and GPRC5D CAR-T, respectively. For the GPRC5D CAR-T cohort, the estimated ORR, CRR, MRD negativity rate, and relapse rate were found to be 89.8% [95% confidence interval (CI), 82.8%–96.9%], 50.5% (95% CI, 38.0%–62.9%), 78.8% (95% CI, 53.0%–100%), and 26.0% (95% CI, 7.4%–44.6%), respectively. In the BCMA CAR-T group, the ORR was 76.3% (95% CI, 67.9%–84.7%), the CRR was 34.3% (95% CI, 25.9%–42.7%), the MRD negativity rate was 76.5% (95% CI, 63.1%–90.0%), and the recurrence rate was 57.3% (95% CI, 47.7%–66.9%). These values were significantly lower than those observed in the GPRC5D CAR-T cohort. Both BCMA and GPRC5D CAR-T demonstrated acceptable safety. The estimated incidence of BCMA CAR-T resulting in grade 3–5 CRS and ICANS was only 5.4% (95% CI, 2.0%–10.4%) and 3.3% (95% CI, 0.6%–8.0%), respectively. The estimated incidence of GPRC5D CAR-T resulting in grade 3–5 CRS and ICANS was only 1.6% (95% CI, 0.0%–6.5%) and 2.7% (95% CI, 0.7%–6.2%), respectively.

Conclusion

GPRC5D CAR-T potentially demonstrates enhanced effectiveness relative to BCMA CAR-T in treating patients with RRMM. Therefore, GPRC5D CAR-T can be regarded as the preferred therapeutic option for RRMM, particularly among patients who have undergone relapse subsequent to BCMA CAR-T treatment.
Enhancing oncolytic virotherapy by extracellular vesicle mediated microRNA reprograming of the tumour microenvironment
Authors: Jennings Victoria A. , Rumbold-Hall Reah , Migneco Gemma , Barr Tyler , Reilly Katrina , Ingram Nicola , St Hilare Isabelle , Heaton Samuel , Alzamel Noura , Jackson David , Ralph Christy , Banerjee Susan , McNeish Iain , Bell John C. , Melcher Alan A. , Ilkow Carolina , Cook Graham P. , Errington-Mais Fiona
Published: December 2024

Background

There has been limited success of cancer immunotherapies in the treatment of ovarian cancer (OvCa) to date, largely due to the immunosuppressive tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are a major component of both the primary tumour and malignant ascites, promoting tumour growth, angiogenesis, metastasis, chemotherapy resistance and immunosuppression. Differential microRNA (miRNA) profiles have been implicated in the plasticity of TAMs. Therefore, delivering miRNA to TAMs to promote an anti-tumour phenotype is a novel approach to reverse their pro-tumour activity and enhance the efficacy of cancer immunotherapies. Oncolytic viruses (OVs) preferentially replicate in tumour cells making them ideal vehicles to deliver miRNA mimetics to the TME. Importantly, miRNA expressed by OVs get packaged within tumour-derived extracellular vesicles (TDEVs), and release of TDEV is augmented by OV infection, thus enhancing the dissemination of miRNA throughout the TME.

Method

Small RNA sequencing was used to identify differentially expressed miRNA during TAM generation and following LPS/IFNγ stimulation to induce an anti-tumour phenotype. Two differentially expressed miRNA identified, miR-155 and miR-19a, were cloned into oncolytic rhabdovirus (ORV), and anti-tumour efficacy was investigated using both in vitro and in vivo models of OvCa.

Results

This study demonstrates that ORV infection enhances TDEV production in OvCa cell lines both in vitro and in vivo and that TDEV are preferentially taken up by myeloid cells, including TAMs. Small RNA sequencing identified 23 miRNAs that were significantly upregulated in anti-tumour TAMs, including miR-155-5p. While 101 miRNAs were downregulated during pro-tumour TAM differentiation, including miR-19a-3p. Culturing TDEV expressing miR-155 or miR-19a with TAMs reversed their immunosuppressive activity, as measured by T cell proliferation. While ORV-miR-155 enhanced the generation of anti-tumour T cells, only ORV-miR19a significantly improved survival of mice bearing ovarian tumours.

Conclusion

This study demonstrates (i) that arming ORVs with immunomodulatory miRNA is an effective approach to deliver miRNA to myeloid cells within the TME and (ii) that miRNA have the capacity to reverse the tumour promoting properties of TAMs and improve the efficacy of cancer immunotherapies, such as OV.
Estimating fish stock biomass using a Bayesian state-space model: accounting for catchability change due to technological progress
Authors: Nishimoto Makoto , Aoki Yoshinori , Matsubara Naoto , Hamer Paul , Tsuda Yuichi
Published: December 2024

The assessment of trends in fish stocks using long-term time-series data is important for effective fisheries resource management. Despite technological advancements in recent decades, the resulting increase in fisheries catch potential with applied effort is often not adequately considered in stock assessments. To address this gap, we developed a framework for simultaneously estimating catchability and biomass using a state-space population model. This model allows for the flexible integration of the timing and functional form of the uptake of technological innovations that are assumed to influence catchability. Our objective was to test the effectiveness of this framework by applying it to 48 years of skipjack pole-and-line fishery data in Japanese waters. We utilized two population models, the Ricker-type and Gompertz-type, under three different scenarios of technology-driven catchability changes: constant, exponential, and S-shaped. The results indicate that the calculations converged for the constant and S-shaped scenarios, and that both the Ricker and Gompertz models performed almost equally well in terms of the goodness of fit and prediction accuracy under the S-shaped scenario, which assumes time-varying catchability. Although time-varying catchability poses challenges for accurate biomass estimation due to the large range of uncertainty, the decreasing trend in stock status is still detected. The estimated recent decline in the skipjack stock around Japan provides a warning for stock assessments that do not incorporate technological progress, despite the species’ high natural population growth rate and presumed stable stock status. Our methodology, based on publicly available archived catch records (catch and effort), can be applied to other species with known timelines of technological innovation.
Marine protected areas as a tool for environmental justice
Authors: Asokan Anupa
Published: December 2024

Overfishing, destructive industrial practices, and climate change are the biggest drivers of biodiversity loss in the ocean. Marine Protected Areas (MPAs), including through nature conservation initiatives like “30x30” and “America the Beautiful,” can be an effective solution to protect marine life and habitats, while making them more resilient to the pressures of extractive and destructive practices, as well as climate change impacts. There is general scientific consensus on the components that make MPAs ecologically effective, however, social context is often presented as burdensome—where protected spaces exclude communities from accessing nature. While this is a valid concern in top-down approaches to implementing protections around the world, under economic-driven systems of ocean management in countries like the United States, this narrative overlooks the potential opportunity of MPAs as a means to equity and environmental justice. In the U.S., the Magnuson-Stevens Fishery Conservation and Management Act (MSA) established a system that prioritizes the economic value of fisheries and centers power among Fishery Management Councils which are dominated by industry actors. Given this type of governance landscape, this perspective article presents MPAs as a step towards environmental justice in ocean management, whereby an MPA under the appropriate enabling conditions can be a tool to mitigate damage, distribute power, support other cultural value systems, and to advance our understanding of the ocean, climate change and diverse community impacts moving forward.
The effects of variable riverine inputs and seasonal shifts in phytoplankton communities on nitrate cycling in a coastal lagoon
Authors: Zilius Mindaugas , Barisevičiūtė Rūta , Bonaglia Stefano , Klawonn Isabell , Lorre Elise , Politi Tobia , Vybernaite-Lubiene Irma , Voss Maren , Overlinge Donata , Bukaveckas Paul A.
Published: December 2024

Estuarine systems, being situated at the interface between land and marine environments, are important sites for nitrate (NO3–) retention and processing due to large inputs, long retention time, and high biogeochemical activity. However, it remains uncertain how pelagic and benthic processes control NO3– cycling and how the relative importance of these processes is affected by seasonal changes in estuarine conditions. We measured the suite of processes governing NO3– cycling in the Curonian Lagoon (Southeast Baltic Sea) during two time periods representing spring and summer conditions. We show that in spring, benthic dissimilatory and assimilatory NO3– processes prevailed, while in summer, pelagic assimilatory processes dominated. During spring, warming temperatures and riverine nitrogen (N) inputs were associated with the onset of diatom blooms. N assimilation by diatoms resulted in the delivery of particulate organic N and organic matter to the benthos, resulting in greater denitrification in the sediments and a flux of NO3– from the water column to the sediments. In summer, phytoplankton blooms of buoyant cyanobacteria and high rates of assimilatory uptake dominated, resulting in greater particulate organic N export from the lagoon into the sea. Given the low dissolved inorganic N concentrations in summer, high uptake indicates that the pelagic community possessed a nutritional strategy to efficiently utilize multiple N forms at high rates. Overall, our findings show that diatom-dominated communities foster strong benthic-pelagic coupling, whereas cyanobacteria dominance is associated with pelagic-based N cycling. While this study sheds new light on mechanisms of NO3– retention in the Curonian Lagoon, further spatiotemporal resolution is recommended to better represent the variability in rates and to include other Baltic lagoons for a comprehensive understanding of N cycling in shallow estuarine systems.
Calorimetric measurement of energy and nutrient stimulation of microorganisms from the continental deep subsurface
Authors: Feyhl-Buska Jayme , Wu Fabai , Smith Isaiah E. , LaRowe Douglas E. , Robador Alberto , Kruger Brittany , Osburn Magdalena R. , Amend Jan P.
Published: December 2024

Microbial activity in the deep continental subsurface is difficult to measure due to low cell densities, low energy fluxes, cryptic elemental cycles and enigmatic metabolisms. Nonetheless, direct access to rare sample sites and sensitive laboratory measurements can be used to better understand the variables that govern microbial life underground. In this study, we sampled fluids from six boreholes at depths ranging from 244 m to 1,478 m below ground at the Sanford Underground Research Facility (SURF), a former goldmine in South Dakota, United States. The heat produced by microorganisms in these samples was measured in a nanocalorimeter as a proxy for activity. Heat flow measurements on unamended groundwater samples from five of the six boreholes comprising the Deep Underground Microbial Observatory (DeMMO) fell below the limit of detection, suggesting very low metabolic rates. Fluid samples from the borehole that registered a heat signal (DeMMO 6) from 1,478 m deep, were amended with a series of electron donors, electron acceptors, and amino acids before being introduced into the calorimeter. The addition of formate resulted in more than a ~500 nW increase in heat flow relative to the signal for unamended fluids during the first 100 h of incubation while the next highest heat flow arose from nitrate and acetate co-addition, at ~125 nW. Notably, both amendment conditions led to a ~1.5 orders of magnitude increase in cell density without causing major changes to community composition, suggesting that these electron donors and acceptors may be exploited by these communities in-situ. The addition of ~0.4 mM casamino acids resulted in a total heat flow of 2.25 μW within 35 h and a more than three orders of magnitude increase in cell density. In these experiments, Hydrogenophaga grew to dominate the amino acid amended borehole fluids. The strong microbial response to amino acid addition indicates a deep continental surface community that is limited by the availability of amino acids. A high potential for amino acid metabolism was proposed in genomic studies from this and similar sites but has not been shown in actively growing communities.
Isolation and characterization of cellulose-mineralizing haloalkaliphilic bacteria from Siberian soda lakes
Authors: Sorokin Dimitry Y. , Merkel Alexander Y. , Khizhniak Tatjana V.
Published: December 2024

Soda lakes are unique double-extreme habitats characterized by high salinity and soluble carbonate alkalinity, yet harboring rich prokaryotic life. Despite intensive microbiology studies, little is known about the identity of the soda lake hydrolytic bacteria responsible for the primary degradation of the biomass organic matter, in particular cellulose. In this study, aerobic and anaerobic enrichment cultures with three forms of native insoluble cellulose inoculated with sediments from five soda lakes in south-western Siberia resulted in the isolation of four cellulotrophic haloalkaliphilic bacteria and their four saccharolytic satellites. The final aerobic enrichment included a cellulotrophic bacteroidetes (strain ABcell3) related to Sporocytophaga accompanied by a hemicellulolytic Marinimicrobium strain ABcell2. The anaerobic enrichments resolved in three primary cellulotrophic bacteria and their three saccharolytic bacteroidetes satellites. The culture selected on amorphous cellulose (ac) included a new cellulotrophic member of the Chitinispirillaceae (Fibrobacterota)—strain ANBcel5, and two different saccharolytic satellites from the Marinilabiliales and Balneolales orders. The final enrichment selected on Sigma 101 cellulose consisted of an endospore-forming cellulotrophic strain ANBcel31 belonging to the genus Herbivorax (Acetivibrionales) and its saccharolytic satellite from the Balneolales order. The anaerobic enrichment on a filter paper yielded a binary consortium with the cellulotrophic endospore-forming Halanaerobiales strain ANBcel28 in obligate syntrophy with a cellobiose-utilizing Natronincola. A functional genome analysis of the cellulotrophic isolates confirmed the presence of a large repertoire of genes encoding excreted cellulases, mostly from the GH9 and GH5 families, and indicated that in the endospore-forming anaerobic strains, ANBcel28 and ANBcel31 most of their endo-glucanases are assembled in cellulosomes. Overall, this study showed that cellulose can be mineralized in soda lakes at moderately saline and highly alkaline conditions either by aerobic or fermentative haloalkaliphilic bacteria.
Exploring the therapeutic potential of precision medicine in rare genetic obesity disorders: a scientific perspective
Authors: Collet Tinh-Hai , Schwitzgebel Valerie
Published: December 2024

The prevalence of obesity is increasing worldwide, affecting both children and adults. This obesity epidemic is mostly driven by an increase in energy intake (abundance of highly palatable energy-dense food and drinks) and to a lesser degree a decrease in energy expenditure (sedentary lifestyle). A small proportion of individuals with obesity are affected by genetic forms of obesity, which often relate to mutations in the leptin-melanocortin pathway or are part of syndromes such as the Bardet-Biedl syndrome. These rare forms of obesity have provided valuable insights into the genetic architecture of obesity. Recent advances in understanding the molecular mechanisms that control appetite, hunger, and satiety have led to the development of drugs that can override genetic defects, enabling precision treatment. Leptin deficiency is uniquely treated with recombinant human metreleptin, while those with LEPR, PCSK1, or POMC deficiency can now be treated with the MC4R agonist setmelanotide. This review highlights the most frequent monogenic and syndromic forms of obesity, and the future outlook of precision treatment for these conditions.
Comprehensive review on neprilysin (NEP) inhibitors: design, structure-activity relationships, and clinical applications
Authors: Zhang Xinyue , Hu Chun , Tian Erkang , Shen Yanxin , Liu Wei , Li Juan
Published: December 2024

Neprilysin (NEP), a zinc-dependent membrane-bound metallopeptidase, regulates various bioactive peptides, particularly in kidneys, vascular endothelium, and the central nervous system. NEP’s involvement in metabolizing natriuretic peptides, insulin, and enkephalins makes it a promising target for treating cardiovascular and Alzheimer’s diseases. Several NEP inhibitors, such as sacubitril and omapatrilat, have been approved for clinical use, which inhibit NEP activity to prolong the bioactivity of beneficial peptides, thereby exerting therapeutic effects. However, despite the broad clinical application prospects of NEP inhibitors, they still have specific adverse reactions and side effects, such as hypotension, renal impairment, and a potentially increased risk of Alzheimer’s disease. This manuscript comprehensively reviews the progress on single-target and dual-target NEP inhibitors. Dual-target inhibitors often combine with other therapeutic targets, such as angiotensin receptors, to enhance therapeutic effects and reduce adverse reactions. The article also emphasizes these inhibitors' design strategies, structure-activity relationships (SAR), safety, and clinical performance.
Inhibition of the polyol pathway by Ducrosia anethifolia extract: plausible implications for diabetic retinopathy treatment
Authors: Ahmad Saheem , Ahmad Mohammad Faizan Ali , Khan Saif , Alouffi Sultan , Khan Mahvish , Khan Mohd Wajid Ali , Ansari Irfan Ahmad
Published: December 2024

Introduction

Diabetic retinopathy is a significant microvascular disorder and the leading cause of vision impairment in working-age individuals. Hyperglycemia triggers retinal damage through mechanisms such as the polyol pathway and the accumulation of advanced glycation end products (AGEs). Inhibiting key enzymes in this pathway, aldose reductase (AR) and sorbitol dehydrogenase (SD), alongside preventing AGE formation, may offer therapeutic strategies for diabetic retinopathy and other vascular complications. This study investigates the ability of Ducrosia anethifolia, an Arabian plant, to inhibit AR and SD enzymes.

Methods

Methanolic extracts of the plant were tested in enzyme assays and further analyzed using Lineweaver-Burk plots for kinetic insights. Additionally, the effects on AGE production and sorbitol accumulation in red blood cells were evaluated.

Results

The methanolic extract showed strong inhibitory effects on AR (IC50: 69.41 ± 3.59 μg/mL) and SD (IC50: 31.11 ± 5.58 μg/mL), acting through a mixed-inhibition mechanism. It also significantly reduced sorbitol accumulation and AGE formation.

Discussion

These findings suggest that the extract’s inhibition of the polyol pathway enzymes is due to its phytochemical content. Further isolation and identification of these active compounds could provide valuable insights for developing future pharmaceutical treatments for diabetic retinopathy.
Drought induced metabolic shifts and water loss mechanisms in canola: role of cysteine, phenylalanine and aspartic acid
Authors: Elferjani Raed , Pahari Shankar , Soolanayakanahally Raju , Ballantyne Krista , Nambara Eiji
Published: December 2024

Drought conditions severely curtail the ability of plants to accumulate biomass due to the closure of stomata and the decrease of photosynthetic assimilation rate. Additionally, there is a shift in the plant’s metabolic processes toward the production of metabolites that offer protection and aid in osmoadaptation, as opposed to those required for development and growth. To limit water loss via non-stomatal transpiration, plants adjust the load and composition of cuticle waxes, which act as an additional barrier. This study investigates the impact of soil water deficit on stomatal and epicuticular water losses, as well as metabolic adjustments in two canola (Brassica napus L.) cultivars—one drought-tolerant and the other drought-sensitive. Specifically, we examined the effect of a drought treatment, which involved reducing water holding capacity to 40%, on the levels of cysteine, sucrose, and abscisic acid (ABA) in the leaves of both cultivars. Next, we looked for potential differences in night, predawn, and early morning transpiration rates and the epicuticular wax load and composition in response to drought. A substantial rise in leaf cysteine was observed in both canola cultivars in response to drought, and a strong correlation was found between cysteine, ABA, and stomatal conductance, indicating that cysteine and sulfur may play a role in controlling stomatal movement during drought stress. Attributes related to CO2 diffusion (stomatal and mesophyll conductance) and photosynthetic capacity were different between the two canola cultivars suggesting a better management of water relations under stress by the drought-tolerant cultivar. Epicuticular waxes were found to adjust in response to drought, acting as an additional barrier against water loss. Surprisingly, both canola cultivars responded similarly to the metabolites (cysteine, sucrose, and ABA) and epicuticular waxes, indicating that they were not reliable stress markers in our test setup. However, the higher level of phenylalanine in the drought-tolerant canola cultivar is suggestive that this amino acid is important for adaptation to drier climates. Furthermore, a multitrait genotype-ideotype distance index (MGIDI) revealed the likely role of aspartic acid in sustaining nitrogen and carbon for immediate photosynthetic resumption after drought episodes. In conclusion, leveraging amino acid knowledge in agriculture can enhance crop yield and bolster resistance to environmental challenges.
Spatial heterogeneity of soil factors enhances intraspecific variation in plant functional traits in a desert ecosystem
Authors: Wang Yong-chang , Zhang Xue-ni , Yang Ji-fen , Tian Jing-ye , Song Dan-hong , Li Xiao-hui , Zhou Shuang-fu
Published: December 2024

Introduction

Functional traits of desert plants exhibit remarkable responsiveness, adaptability and plasticity to environmental heterogeneity.

Methods

In this study, we measured six crucial plant functional traits (leaf carbon, leaf nitrogen, leaf phosphorus, leaf thickness, chlorophyll concentration, and plant height) and employed exemplar analysis to elucidate the effects of soil environmental heterogeneity on intraspecific traits variation in the high-moisture-salinity and low-moisture-salinity habitats of the Ebinur LakeWetland National Nature Reserve.

Results

The results showed that (1) The soil moisture and electrical conductivity heterogeneity showed significant differences between the two moisture-salinity habitats. Moreover, soil nutrient in high moisture-salinity habitat exhibited higher heterogeneity than in low moisture-salinity habitat. The order of intraspecific trait variation among different life forms was herbs > shrubs > trees in both the soil moisture-salinity habitats. (2) At the community level, intraspecific variation of leaf carbon, nitrogen, plant height and chlorophyll content in high moisture-salinity habitat was higher than that in low moisture-salinity habitat, while the opposite was true for leaf thickness and leaf phosphorus content. (3) Our findings revealed a positive impact of soil heterogeneity on intraspecific traits variation. In high moisture-salinity habitat, the heterogeneity of soil organic carbon had the highest explanatory power for intraspecific traits variation, reaching up to 20.22%, followed by soil total nitrogen (9.55%) and soil total phosphorus (3.49%). By comparison, in low-moisture-salinity habitat, the heterogeneity of soil moisture alone contributes the highest explanatory power for intraspecific traits variation in community-level, reaching up to 13.89%, followed by the heterogeneity of soil total nitrogen (3.76%).

Discussion

This study emphasizes the differences in soil heterogeneity and intraspecific trait variation among plant life forms under various soil moisture-salinity habitats and confirms the significant promoting effect of soil heterogeneity on intraspecific trait variation of desert plant. Our findings provide valuable theoretical basis and reference for predicting plant adaptation strategies under environmental change scenarios.
Assembly and comparative analysis of the complete mitogenome of Rubus chingii var. suavissimus, an exceptional berry plant possessing sweet leaves
Authors: Shi Yujie , Chen Zhen , Jiang Jingyong , Wu Wenwu , Xin Yue , Zeng Wei
Published: December 2024

Rubus chingii var. suavissimus is a special berry plant of Rubus in the Rosaceae family. Its leaves contain high-sweetness, low-calorie, and non-toxic sweet ingredients, known as rubusoside. As a medicine and food biofunctional plant, it is a combination of “tea, sugar, and medicine.” In this study, the complete mitogenome of R. chingii var. suavissimus was successfully assembled and annotated based on PacBio HiFi sequencing technology. The mitogenome of R. chingii var. suavissimus was a typical master circle structure, spanning 432,483 bp and containing 34 unique protein-coding genes (PCGs), 20 tRNAs, and 3 rRNAs. The majority of these PCGs was subjected to purifying selection, and only one gene (ccmB) showed sign of positive selection. The mitogenome of R. chingii var. suavissimus contained a large number of repeats, and the homogeneous fragments transferring between plastid genome and mitogenome, with a total of 55 pairs of mitochondrial plastid sequences (MTPTs), and the total size was 56,913 bp. Comparative analysis showed that the non-coding region in the mitogenome of R. chingii var. suavissimus had undergone frequent rearrangements during evolution, but the coding region was still highly conserved. Furthermore, the maximum likelihood and Bayesian inference phylogenetic trees were reconstructed of 10 shared PCGs in 36 plant species. The topological structures of two phylogenetic trees were consistent with the APG IV classification system and had high support rates. In general, this study clarifies the mitogenome of R. chingii var. suavissimus and provides valuable insights into the genetic evolution of the Rosaceae family.
Machine learning analysis of factors affecting college students’ academic performance
Authors: Lu Jingzhao , Liu Yaju , Liu Shuo , Yan Zhuo , Zhao Xiaoyu , Zhang Yi , Yang Chongran , Zhang Haoxin , Su Wei , Zhao Peihong
Published: December 2024

This study aims to explore various key factors influencing the academic performance of college students, including metacognitive awareness, learning motivation, participation in learning, environmental factors, time management, and mental health. By employing the chi-square test to identify features closely related to academic performance, this paper discussed the main influencing factors and utilized machine learning models (such as LOG, SVC, RFC, XGBoost) for prediction. Experimental results indicate that the XGBoost model performs the best in terms of recall and accuracy, providing a robust prediction for academic performance. Empirical analysis reveals that metacognitive awareness, learning motivation, and participation in learning are crucial factors influencing academic performance. Additionally, time management, environmental factors, and mental health are confirmed to have a significant impact on students’ academic achievements. Furthermore, the positive influence of professional training on academic performance is validated, contributing to the integration of theoretical knowledge and practical application, enhancing students’ overall comprehensive competence. The conclusions offer guidance for future educational management and guidance, emphasizing the importance of cultivating students’ learning motivation, improving participation in learning, and addressing time management and mental health issues, as well as recognizing the positive role of professional training.
What are they all doing in that restaurant? Perspectives on the use of theory of mind
Authors: Gabbatore Ilaria , Bosco Francesca M. , Tirassa Maurizio
Published: December 2024

If “theory of mind” is conceived as reasoning in a strict sense, then it can be said to be useful only at certain times; however, this leaves the rest of social cognition hardly comprehensible. If “theory of mind” is used instead to refer to a mentalist ontology and the consequent awareness that we ourselves and the others function on mental states, then we need new approaches that explain the flow of social experience. To illustrate these points, we outline the general conceptual framework that underlies most empirical studies of theory of mind and discuss their pros and cons; then, we discuss the Theory of Mind Assessment Scale, a tool developed to investigate the complexity of theory of mind, which adopts a different perspective and has been successfully tested on numerous populations.
Case report: Clinical and genetic characterization of a novel ALDH7A1 variant causing pyridoxine-dependent epilepsy, developmental delay, and intellectual disability in two siblings
Authors: Salih Mustafa A. , AlBakheet Albandary , Almass Rawan , Hamed Ahlam A. A. , AlOdaib Ali , Kaya Namik
Published: December 2024

Background

Pathogenic variants in ALDH7A1 are associated with pyridoxine-dependent epilepsy (PDE), a rare autosomal recessive disorder characterized by epileptic seizures, unresponsiveness to standard antiseizure medications (ASM), and a response only to pyridoxine. Here, we report two patients (from a consanguineous family) with neonatal seizures and developmental delay.

Case presentation

Patient 1 (a 13-year-old girl) was born normally at term. Her pregnancy was complicated by antiphospholipid syndrome, and persistent vomiting was managed with several medications, including pyridoxine (40 mg daily). Seizures occurred 6 h after birth and did not respond to antiseizure medications. However, they ceased 2 days later when pyridoxine (40 mg daily) was administered. She continued her medications and had delayed early milestones. Phenobarbitone was discontinued at 18 months, and pyridoxine was increased to 100 mg daily at 8 years of age. She was able to join a regular school and performed well. Patient 2, a 12-year-old boy, was delivered normally at term. Seizures started 10 h after birth, and he immediately received 40 mg of pyridoxine. Seizures have been controlled since then, and he experienced delayed milestones. Pyridoxine was increased to 100 mg daily at 7 years of age. He is currently in fifth grade and has dyslexia. Whole exome sequencing (WES) revealed that both patients 1 and 2 harbor a novel homozygous missense variant in ALDH7A1 (NM_001202404: exon 12: c.1168G>C; (p.Gly390Arg)).

Conclusion

The present study reports a novel ALDH7A1 variant causing PDE and highlights the associated developmental delay and intellectual disability, despite early seizure control treatment.
The Southern Center for Maternal Health Equity (SCMHE): a multisector multifaceted community-based approach to reduce disparities in maternal morbidity and mortality in the Gulf South
Authors: Goldin Evans Melissa , Wallace Maeve , Bazzano Alessandra N. , Biggio Joseph R. , Cruz Kiara , Gamble Abigail , Green Carmen , Jah Zainab , Longo Sherri , Perez Susan , Reed Rachael N. , Shaffer Jeffrey G. , Shi Lizheng , Harville Emily
Published: December 2024

Introduction

The maternal mortality crisis in the United States disproportionately affects women who are Black, especially those living in the Gulf South. These disparities result from a confluence of healthcare, policy, and social factors that systematically place Black women at greater risk of maternal morbidities and mortality. This study protocol describes the Southern Center for Maternal Health Equity (SCMHE), a research center funded by the National Institutes of Health in 2023 to reduce preventable causes of maternal morbidity and mortality while improving health equity. This is a seven year program with pilot and implementation phases. SCMHE is co-led by three organizations: Reproductive Health Impact (a fiscally sponsored project of the Praxis Project), an advocacy community-based organization; Tulane University, an academic research institute; and Ochsner Health, a large regional nonprofit health system.

Methods

SCMHE applies a multilevel life course approach based on the Social Ecological Model to prevent maternal morbidity and mortality with interventions at individual, interpersonal, institutional, community, and societal levels. This community-focused research center uses an intersectional lens and the Reproductive Justice framework in its aims to improve maternal health and strengthen community-based maternal health research capacity in Louisiana and Mississippi.

Discussion

To advance the field of maternal health using participatory, community-centered, and radically equity-focused approaches previously underutilized and under-evaluated, the Center will lead three R01 projects to assess the implementation of existing evidence-based strategies and build the evidence base for translational research strategies.

Ethics and dissemination

By leveraging our team's existing network with local, regional, and national partners while continuing to build new, unique interdisciplinary partnerships, we will build upon our distinctive interdisciplinary strengths and community connections to bring our outreach and technical assistance efforts to diverse audiences.