bluuebunny/crossref_metadata_2025 huggingface dataset:
Efektivitas Media Sosial Instagram dalam Penyebaran Informasi Covid-19 oleh Diskominfo Kota Kupang Provinsi NTT
Authors: Ajinegoro Dudy Obed , Kurniawan Kurniawan
Published: February 2024

Penyebaran COVID-19 tentunya membawa dampak bagi pola kehidupan kita. Masyarakat dituntut untuk selalu menjaga kesehatan untuk mencegah penularan COVID-19, untuk itu Diskominfo Kota Kupang sebagai lembaga pemerintah yang menaungi terkait penyebaran informasi COVID-19 melakukan berbagai upaya dalam rangka pencegahan dan penanggulangan COVID-19 berkaitan dengan penyebaran informasi berupa himbauan, anjuran, perintah maupun perkembangan terkait COVID-19. Masalah yang diangkat dalam penelitian ini adalah menentukan tingkat efektivitas penyebaran Informasi COVID- 19 di Kota Kupang melalui media social instagram. Penelitian yang dilakukan bertujuan untuk menganalisis dan mendeskripsikan efektivitas penggunaan media sosial instagram oleh diskominfo kota kupang dalam penyebaran informasi COVID-19 serta faktor yang menjadi kendala dan upaya dalam mengatasi kendala penyebaran informasi COVID-19 dan mengukur tingkat efektivitas dalam penyebaran COVID-19 yang dilakukan oleh Diskominfo Kota Kupang melalui media instagram sebagai media dengan pengikut terbesar. Metode Penelitian yang digunakan menggunakan metode Kualitatif deskriptif dengan melihat pola perilaku masyarakat melalui data wawancara berupa kuesioner dan data wawancara dari aparat pemerintah terkait serta data pendukung yang berkaitan dengan faktor-faktor dalam penyebaran informasi COVID-19 melalui media sosial instagram di Kota Kupang. Berdasarkan hasil dari penelitian bahwa diketahui proses penyebaran informasi COVID-19 yang dilakukan oleh Diskominfo Kota Kupang sudah mencapai standar efektif dengan kasus COVID-19 di kota Kupang yang cenderung menurun dan perubahan perilaku masyarakat yang semakin taat dengan protokol kesehatan rendah. Penyebaran Informasi terkait COVID-19 sudah maksimal dan diperlukan beberapa peningkatan agar proses penyebaran informasi menjadi lebih maksimal.
The Influence of Social Media on Public Administration
Authors: Sarjito Aris
Published: February 2024

Background: The increasing use of social media platforms has profoundly influenced various aspects of society, including public administration. Social media has become a powerful tool in communication, information sharing, and networking, and it can potentially transform how public administration operates. However, several challenges are associated with using social media in this context, such as cyber security risks and the potential for misinformation and fake news. Aim: This research aims to explore the influence of social media on public administration, including how social media platforms are being used in this context, the benefits and challenges associated with social media use, and how public administrators can effectively manage the risks and opportunities related to social media. Qualitative Method and Secondary Data: This research will use qualitative methods to collect and analyze data from secondary sources such as scholarly articles, government reports, and case studies. The data will be analyzed thematically to identify patterns and trends related to the research questions. Findings: The findings of this research suggest that public administrators are using social media platforms for a variety of purposes, including sharing information, receiving feedback, and engaging with citizens. Additionally, using social media has several benefits, such as increased transparency and accountability, greater citizen engagement, and faster communication. However, several challenges are associated with social media use, including cybersecurity risks, privacy concerns, and the potential for misinformation and fake news. Public administrators can effectively manage the risks and opportunities of social media use in their organizations by developing policies and procedures, training staff, and monitoring social media use.
Perlindungan Sosial Melalui Program Keluarga Harapan di Kelurahan Wagom Distrik Pariwari Kabupaten Fakfak
Authors: Uswanas Kristopel Philipus , Nuraida Ridla
Published: February 2024

Program Keluarga Harapan (PKH) merupakan perlindungan sosial dengan memberikan bantuan sosial bersyarat yang harus dipenuhi terlebih dahulu untuk keluarga kurang mampu yang telah ditetapkan sebagai keluarga penerima program keluarga harapan. Pertama kalinya dimulainya program keluarga pada tahun 2007 yang dilaksanakan oleh pemerintah Indonesia sebagai bantuan tunai bersyarat. Penelitian ini bertujuan untuk mengetahui Perlindungan Sosial melalui PKH di Kelurahan Wagom Distrik Pariwari Kabupaten Fakfak, persoalan yang terjadi dan upaya yang dilakukan oleh pemerintah untuk mengatasi persoalan yang ada di lapangan. Penelitian ini menggunakan pendekatan kualitatif yang bersifat deskriptif, teknik pengumpulan data menggunakan metode wawancara, observasi dan dokumentasi. Perlindungan Sosial melalui PKH di Kelurahan Wagom Distrik Pariwari Kabupaten Fakfak merupakan salah satu upaya pemerintah untuk mengurangi kemiskinan. Program ini memberikan bantuan kepada peserta PKH yang telah terpilih seperti keluarga miskin dengan anggota keluarga ibu hamil/nifas, anak (SD,SMP,SMA), Lansia dan disabilitas dengan ketentuan dan syarat yang harus dipenuhi oleh penerima bantuan. Hasil Penelitian ini mengungkapkan bahwa perlindungan sosial melalui PKH di Kelurahan Wagom sudah berjalan dengan baik, terlihat dari proses kegiatan pertemuan awal, sosialisasi pendamping, pencairan bantuan, pemutakhiran data dan verifikasi komitmen peserta. Serta persoalan yang dihadapi selama pelaksanaan PKH di lapangan, persoalan tersebut berdasarkan fasilitas pendidikan dan kesehatan, serta masalah dalam proses pendataan. Upaya yang dilakukan yaitu peningkatan sosialisasi,peningkatan pelayanan dan penyempurnaan data.
The Congruent Number Problem and Its Connection with Elliptic Curves
Authors: Khanra Palash
Published: February 2024

Number theory, a mathematical domain, centers on integers and their patterns. It often requires advanced methods to solve even simple problems. The Congruent Number Problem, unsolved for centuries, exemplifies this challenge. This survey article highlights how studying congruent numbers motivates exploring elliptic curves and how insights from these curves advance solving the Congruent Number Problem. The elegant connections between these subjects are striking.
Exploring the secretome of Corynebacterium glutamicum ATCC 13032
Authors: Balasubramanian Suvasini , Køhler Julie Bonne , Jers Carsten , Jensen Peter Ruhdal , Mijakovic Ivan
Published: February 2024

The demand for alternative sources of food proteins is increasing due to the limitations and challenges associated with conventional food production. Advances in biotechnology have enabled the production of proteins using microorganisms, thus prompting the exploration of attractive microbial hosts capable of producing functional proteins in high titers. Corynebacterium glutamicum is widely used in industry for the production of amino acids and has many advantages as a host organism for recombinant protein production. However, its performance in this area is limited by low yields of target proteins and high levels of native protein secretion. Despite representing a challenge for heterologous protein production, the C. glutamicum secretome has not been fully characterized. In this study, state-of-the-art mass spectrometry-based proteomics was used to identify and analyze the proteins secreted by C. glutamicum. Both the wild-type strain and a strain that produced and secreted a recombinant β-lactoglobulin protein were analyzed. A total of 427 proteins were identified in the culture supernatants, with 148 predicted to possess a secretion signal peptide. MS-based proteomics on the secretome enabled a comprehensive characterization and quantification (based on abundance) of the secreted proteins through label-free quantification (LFQ). The top 12 most abundant proteins accounted for almost 80% of the secretome. These are uncharacterized proteins of unknown function, resuscitation promoting factors, protein PS1, Porin B, ABC-type transporter protein and hypothetical membrane protein. The data can be leveraged for protein production by, e.g., utilizing the signal peptides of the most abundant proteins to improve secretion of heterologous proteins. In addition, secretory stress can potentially be alleviated by inactivating non-essential secreted proteins. Here we provide targets by identifying the most abundant, secreted proteins of which majority are of unknown function. The data from this study can thus provide valuable insight for researchers looking to improve protein secretion and optimize C. glutamicum as a host for secretory protein production.
ATP10A deficiency results in male-specific infertility in mice
Authors: Norris Adriana C. , Yazlovitskaya Eugenia M. , Yang Tzushan Sharon , Mansueto Alex , Stafford John M. , Graham Todd R.
Published: February 2024

Over 8% of couples worldwide are affected by infertility and nearly half of these cases are due to male-specific issues where the underlying cause is often unknown. Therefore, discovery of new genetic factors contributing to male-specific infertility in model organisms can enhance our understanding of the etiology of this disorder. Here we show that murine ATP10A, a phospholipid flippase, is highly expressed in male reproductive organs, specifically the testes and vas deferens. Therefore, we tested the influence of ATP10A on reproduction by examining fertility of Atp10A knockout mice. Our findings reveal that Atp10A deficiency leads to male-specific infertility, but does not perturb fertility in the females. The Atp10A deficient male mice exhibit smaller testes, reduced sperm count (oligozoospermia) and lower sperm motility (asthenozoospermia). Additionally, Atp10A deficient mice display testes and vas deferens histopathological abnormalities, as well as altered total and relative amounts of hormones associated with the hypothalamic-pituitary-gonadal axis. Surprisingly, circulating testosterone is elevated 2-fold in the Atp10A knockout mice while luteinizing hormone, follicle stimulating hormone, and inhibin B levels were not significantly different from WT littermates. The knockout mice also exhibit elevated levels of gonadotropin receptors and alterations to ERK, p38 MAPK, Akt, and cPLA2-dependent signaling in the testes. Atp10A was knocked out in the C57BL/6J background, which also carries an inactivating nonsense mutation in the closely related lipid flippase, Atp10D. We have corrected the Atp10D nonsense mutation using CRISPR/Cas9 and determined that loss of Atp10A alone is sufficient to cause infertility in male mice. Collectively, these findings highlight the critical role of ATP10A in male fertility in mice and provide valuable insights into the underlying molecular mechanisms.
Effect of on-pump vs. off-pump coronary artery bypass grafting in patients with non-dialysis-dependent severe renal impairment: propensity-matched analysis from the UK registry dataset
Authors: Fudulu Daniel P. , Argyriou Amerikos , Kota Rahul , Chan Jeremy , Vohra Hunaid , Caputo Massimo , Zakkar Mustafa , Angelini Gianni D.
Published: February 2024

Introduction

On-pump coronary artery bypass (ONCABG) grafting in patients with a pre-existing poor renal reserve is known to carry significant morbidity and mortality. There is limited controversial evidence on the benefit of off-pump coronary artery bypass (OPCABG) grafting in these high-risk groups of patients. We compared early clinical outcomes in propensity-matched cohorts of patients with non-dialysis-dependent pre-operative severe renal impairment undergoing OPCABG vs. ONCABG, captured in a large national registry dataset.

Methods

All data for patients with a pre-operative creatinine clearance of less than 50 mL/min who underwent elective or urgent isolated OPCABG or ONCABG from 1996 to 2019 were extracted from the UK National Adult Cardiac Surgery Audit (NACSA) database. Propensity score matching was performed using 1:1 nearest neighbor matching without replacement using several baseline characteristics. We investigated the effect of ONCABG vs. OPCABG in the matched cohort using cluster-robust standard error regression.

Results

We identified 8,628 patients with severe renal impairment undergoing isolated CABG, of whom 1,142 (13.23%) underwent OPCABG during the study period. We compared 1,141 propensity-matched pairs of patients undergoing OPCABG vs. ONCABG. The median age of the matched population was 78 years in both groups, with no significant imbalance post-matching in the rest of the variables. There was no difference between OPCABG and ONCABG in in-hospital mortality rates, post-operative dialysis, and stroke rates. However, the return to theatre for bleeding or tamponade was higher in ONCABG vs. OPCABG (P > 0.02); however, OPCABG reduced the total length of stay in the hospital by 1 day (P = 0.008). After double adjustment in the matched population using cluster-robust standard regression, ONCABG did not increase mortality compared to OPCABG (OR, 1.05, P = 0.78), postoperative stroke (OR, 1.7, P = 0.12), and dialysis (OR, 0.7, P = 0.09); however, ONCABG was associated with an increased risk of bleeding (OR, 1.53, P = 0.03).

Discussion

In this propensity analysis of a large national registry dataset, we found no difference in early mortality and stroke in patients with pre-operative severe renal impairment undergoing OPCABG or ONCABG surgery; however, ONCABG was associated with an increased risk of return to theatre for bleeding and an increased length of hospital stay.
Case report: Primary pericardial angiosarcoma, a rare cause of cardiac tamponade
Authors: Kong Ling-Yun , Cui Xiao-Zheng , Xiang Wei , Wang Xiu-Juan , Liu Fang
Published: February 2024

Primary pericardial angiosarcoma is a rare malignancy of the pericardium with variable clinical features and imaging characteristics. Herein, we report a case of histopathologically confirmed pericardial angiosarcoma in a 66-year-old man. The patient developed cardiac tamponade in a short time period. The transthoracic echocardiography showed the presence of multiple irregular echodensities, heterogeneous in echogenicity, encasing the apex of both ventricles in the pericardial space, initially misinterpreted as pericardial effusion. The patient died of cardiogenic shock despite undergoing a surgical pericardiectomy. Pericardial angiosarcoma can manifest as a mass obliterating the pericardial sac, rather than the typical pericardial effusion observed on echocardiography. Multimodality imaging studies aid in diagnosing primary pericardial angiosarcoma, but the final diagnosis relies on tissue histopathology.
Measuring mental health action competencies in school teachers: internal and external validity evidence
Authors: Kerry Matthew J. , Robin Dominik , Albermann Kurt , Dratva Julia
Published: February 2024

Introduction

Mental health literacy is receiving increasing research attention due to growing concerns for mental health globally. Among children, teachers have recently been recognized as playing a vital role in the recognition and reporting of potential mental health issues.

Methods

A nationally sampled cross-section of teachers was surveyed to examine the discriminant validity of the mental health literacy measure across levels of teaching. A survey collected a total of n = 369 teacher responses in Switzerland (Kindergarten = 76, Primary = 210, Secondary = 83). Item response theory (IRT) analyses were conducted.

Results

Inspection of psychometric properties indicated removal of two weak performing items. The 15-item measure exhibited a significant mean difference, such that class-responsibility function scored higher (M = 2.86, SD = .45) than non-responsible function (M = 2.68, SD = .45) teachers [t(309) = −2.20, p = .01]. It also exhibited a significant mean difference, such that more subjective experienced scored higher (M = 2.86, SD = .45) than less subjective experienced (M = 2.68, SD = .45) teachers [t(210) = −8.66, p < .01].

Discussion

Hypotheses regarding age and role tenure were in the expected direction, but non-significant. The MHL measure for teachers demonstrated sound measurement properties supporting usage across teaching levels.
Eliciting perspectives on remote healthcare delivery from service users with psychosis in the community: a cross-sectional survey study
Authors: Kuhn Ronja , Abdel-Halim Nadia , Healey Patrick , Bird Victoria , Elliot Kathryn , McNamee Philip
Published: February 2024

Introduction

The transition towards remote healthcare has been rapidly accelerated in recent years due to a number of factors, including the COVID-19 pandemic, however, few studies have explored service users' views of remote mental healthcare, particularly in community mental health settings.

Methods

As part of a larger study concerned with the development of a remotely delivered psychosocial intervention, a survey was conducted with service users with psychosis (N = 200) from six NHS trusts across England to gain cross-sectional data about service users' opinions and attitudes towards remote interventions and explore how digital access varies across different demographic groups and geographical localities.

Results

The majority of service users had access to technological devices and a quiet space to receive care. Age was a key factor in motivation to engage with remote care as older participants had less access to technological devices and the internet, and reported less confidence to learn how to use new technologies compared to younger participants. Differences in access and attitudes towards remote care were found across the different geographical localities. Over half of the participants (53.1%) preferred a hybrid model (i.e., mixture of face-to-face and remotely delivered treatment), with only 4.5% preferring remote treatment exclusively. Factors that both encourage and deter service users from engaging with remote care were identified.

Conclusions

The findings of this study provide important information about the environmental and clinical barriers that prevent, or limit, the uptake of remotely delivered care for people with psychotic disorders. Although service users often have the ability and capacity to receive remote care, providers need to be cognisant of factors which may exacerbate digital exclusion and negatively impact the therapeutic alliance.
Sedimentary characteristics and model of seasonal deltaic sandstone: a case study on the continental red bed from the Cretaceous Baxigai Formation, Tarim Basin, NW China
Authors: Wang Tong , Hu Yong , Li Bin , He Wenxiang , Gao Xiaoyang , Dou Luxing , Wang Jian
Published: February 2024

Seasonal delta is a sandy fan-shaped sedimentary system formed by seasonal river flooding in continental basins. Modern sedimentary finds that seasonal deltas mainly develop in an arid-semi-arid climate environment with gentle terrain. However, the study of seasonal deltas in ancient rock records is still insufficient, leading to misinterpretations as other sedimentary systems, which poses challenges to the correct understanding of the origin and spatial distribution of sand body deposits. In this study, the red bed deposits of the Cretaceous Baxigai Formation in the west of the Tabei Uplift were selected as the research object. Based on core observation and description, a comprehensive analysis of the sedimentary environment, sedimentary characteristics and sedimentary model of the Baxigai Formation was carried out using data such as well-logging and analytical testing, combined with modern depositional characteristics. Research shows that the sedimentary sequence of the Baxigai Formation red bed developed a seasonal delta sedimentary system in the arid climate. The seasonal delta deposits provide an opportunity to understand the influencing of river flow and total sedimentary loading vary greatly on the sedimentary model, sedimentary mechanism, and distribution of sand bodies in arid climates. The sedimentary process of the seasonal delta in the Baxigai Formation was controlled by the dual-stage sedimentation process in an arid paleoclimate. During the flood period, the supercritical flow sedimentary structures are widely developed in the major distributary channels, and the distributary channels migrate and bifurcate frequently. On the delta plain, crevasse channels are formed through the avulsion of major distributary channels. During the dry period, due to the consumption of water seepage and evaporation transfer, terminal distributary channels are abandoned, crevasse channels are not developed, and the sediment is exposed. The density of the distributary channels is reduced, and the total sedimentary loading is low. The distributary channels sand body is the skeleton sand body of the seasonal delta. This study is of great significance for accurately explaining the formation process of seasonal deltas and provides a useful reference for further exploration and deployment of oil and gas reservoirs and paleogeographic reconstruction in the study area.
Evaluating effectiveness of immersive virtual reality in promoting students’ learning and engagement: a case study of analytical biotechnology engineering course
Authors: Sánchez-López Angélica Lizeth , Jáuregui-Jáuregui Jesús Antonio , García-Carrera Nancy Anabel , Perfecto-Avalos Yocanxóchitl
Published: February 2024

We conducted an immersive virtual reality (IVR) intervention in an analytical biotechnology course to evaluate its effectiveness in promoting student learning and engagement. The objective was to assess the impact of an IVR tool on learning infrared (IR) spectroscopy and academic engagement. The IVR experience was integrated into the course sessions, which included theoretical framework, IR spectra exercises, an individual quiz, and competition games. Students were immersed in a first-person IVR experience simulating an analytical room, where they performed sample analysis and operated a virtual IR spectrometer. The quiz and survey assessed their understanding and perception of the IVR experience. When compared to control groups, IVR intervention group achieved higher scores on midterm exam questions related to IR spectroscopy and reported greater academic engagement according to the satisfaction survey. The findings highlighted the effectiveness of IVR in enhancing learning outcomes, curiosity, motivation, and engagement among students. Moreover, our research provides empirical evidence of IVR’s positive impact on student learning and engagement in the context of biotechnology engineering. Based on the study’s implications, educators in engineering fields should consider integrating IVR as an instructional tool, particularly for laboratory-related topics with limited equipment accessibility and overcrowded courses. Future research should explore the generalizability of these findings across different subjects and educational levels. Additionally, investigating the underlying factors influencing the effectiveness of IVR in promoting academic engagement would further enhance the understanding and implementation of this technology in educational settings.
The HBCU advantage: reimagining social capital among students attending black colleges
Authors: Johnson Jennifer M. , Jackson Elizabeth
Published: February 2024

Introduction

There is growing interest in exploring the ways Historically Black Colleges and Universities (HBCUs) mediate student outcomes.

Methods

Situating an HBCU education within the conceptual landscape of social capital, we follow the tenets of critical discourse analysis (CDA) to explore the narratives of ten early and mid-career HBCU alumni of eight 4-year colleges and universities. This framing allows for a nuanced analysis of the ways in which an HBCU education provides its students the opportunity to curate social capital in an environment that affirms racial identity and promotes continued service to the Black community.

Results

Findings support the notion that as purveyors of social capital, HBCUs facilitate the transmission of knowledge through relationships and networks that strengthen community ties and leads to educational and professional gains.

Discussion

These findings inform our understanding of the experiences, policies, and practices that promote community building and the successful career transitions among Black college graduates.
Hydrologic simulation of a neotropical alpine catchment influenced by conductive topsoils in the Ecuadorian Andes
Authors: Jarrin-Perez Fernando , Jeong Jaehak , Célleri Rolando , Crespo Patricio , Munster Clyde
Published: February 2024

Highly conductive topsoils in neotropical high-elevation grassland-dominated ecosystems, or so-called paramos in the Andean region, influence the local rainfall-runoff processes predominated by saturation-excess overland flow as the primary source of freshwater. The Soil and Water Assessment Tool (SWAT) model has shown limitations when applied to mountainous catchments with highly conductive soils that generate surface runoff as saturation-excess overland flow. In this study, we enhanced SWAT to simulate runoff as saturation-excess overland flow and examined the hydrological responses of an intensively monitored paramo catchment in Ecuador. The model setup considered a detailed representation of the hydro-physical properties of the soils at different depths, including high infiltration and lateral flow rates in the hillslopes and restricted groundwater interactions, a characteristic of the páramo catchments. SWAT reasonably reproduced the daily discharge during dry and wet periods and the cumulative occurrence of high and low flows. The performance metrics NSE, RSR, and PBIAS values during calibration/validation period were 0.86/0.84, 0.31/0.4, and −11.2/-7.58, respectively. The runoff ratio and partitioning of the total runoff into the lateral flow and surface runoff were physically meaningful. More significantly, SWAT was able to simulate saturation-excess overland flow, which is dominant compared to infiltration excess, and it is a distinctive characteristic of páramo catchments. Nevertheless, the model showed limitations in simulating low flows.
KNeXT: a NetworkX-based topologically relevant KEGG parser
Authors: Castaneda Everest Uriel , Baker Erich J.
Published: February 2024

Automating the recreation of gene and mixed gene-compound networks from Kyoto Encyclopedia of Genes and Genomes (KEGG) Markup Language (KGML) files is challenging because the data structure does not preserve the independent or loosely connected neighborhoods in which they were originally derived, referred to here as its topological environment. Identical accession numbers may overlap, causing neighborhoods to artificially collapse based on duplicated identifiers. This causes current parsers to create misleading or erroneous graphical representations when mixed gene networks are converted to gene-only networks. To overcome these challenges we created a python-based KEGG NetworkX Topological (KNeXT) parser that allows users to accurately recapitulate genetic networks and mixed networks from KGML map data. The software, archived as a python package index (PyPI) file to ensure broad application, is designed to ingest KGML files through built-in APIs and dynamically create high-fidelity topological representations. The utilization of NetworkX’s framework to generate tab-separated files additionally ensures that KNeXT results may be imported into other graph frameworks and maintain programmatic access to the originalx-yaxis positions to each node in the KEGG pathway. KNeXT is a well-described Python 3 package that allows users to rapidly download and aggregate specific KGML files and recreate KEGG pathways based on a range of user-defined settings. KNeXT is platform-independent, distinctive, and it is not written on top of other Python parsers. Furthermore, KNeXT enables users to parse entire local folders or single files through command line scripts and convert the output into NCBI or UniProt IDs. KNeXT provides an ability for researchers to generate pathway visualizations while persevering the original context of a KEGG pathway. Source code is freely available athttps://github.com/everest-castaneda/knext.
Metabolic clues to aging: exploring the role of circulating metabolites in frailty, sarcopenia and vascular aging related traits and diseases
Authors: Qian Zonghao , Huang Yuzhen , Zhang Yucong , Yang Ni , Fang Ziwei , Zhang Cuntai , Zhang Le
Published: February 2024

Background: Physical weakness and cardiovascular risk increase significantly with age, but the underlying biological mechanisms remain largely unknown. This study aims to reveal the causal effect of circulating metabolites on frailty, sarcopenia and vascular aging related traits and diseases through a two-sample Mendelian Randomization (MR) analysis.

Methods: Exposures were 486 metabolites analyzed in a genome-wide association study (GWAS), while outcomes included frailty, sarcopenia, arterial stiffness, atherosclerosis, peripheral vascular disease (PAD) and aortic aneurysm. Primary causal estimates were calculated using the inverse-variance weighted (IVW) method. Methods including MR Egger, weighted median, Q-test, and leave-one-out analysis were used for the sensitive analysis.

Results: A total of 125 suggestive causative associations between metabolites and outcomes were identified. Seven strong causal links were ultimately identified between six metabolites (kynurenine, pentadecanoate (15:0), 1-arachidonoylglycerophosphocholine, androsterone sulfate, glycine and mannose) and three diseases (sarcopenia, PAD and atherosclerosis). Besides, metabolic pathway analysis identified 13 significant metabolic pathways in 6 age-related diseases. Furthermore, the metabolite-gene interaction networks were constructed.

Conclusion: Our research suggested new evidence of the relationship between identified metabolites and 6 age-related diseases, which may hold promise as valuable biomarkers.
Complementary supramolecular drug associates in perfecting the multidrug therapy against multidrug resistant bacteria
Authors: Sahoo Pathik
Published: February 2024

The inappropriate and inconsistent use of antibiotics in combating multidrug-resistant bacteria exacerbates their drug resistance through a few distinct pathways. Firstly, these bacteria can accumulate multiple genes, each conferring resistance to a specific drug, within a single cell. This accumulation usually takes place on resistance plasmids (R). Secondly, multidrug resistance can arise from the heightened expression of genes encoding multidrug efflux pumps, which expel a broad spectrum of drugs from the bacterial cells. Additionally, bacteria can also eliminate or destroy antibiotic molecules by modifying enzymes or cell walls and removing porins. A significant limitation of traditional multidrug therapy lies in its inability to guarantee the simultaneous delivery of various drug molecules to a specific bacterial cell, thereby fostering incremental drug resistance in either of these paths. Consequently, this approach prolongs the treatment duration. Rather than using a biologically unimportant coformer in forming cocrystals, another drug molecule can be selected either for protecting another drug molecule or, can be selected for its complementary activities to kill a bacteria cell synergistically. The development of a multidrug cocrystal not only improves tabletability and plasticity but also enables the simultaneous delivery of multiple drugs to a specific bacterial cell, philosophically perfecting multidrug therapy. By adhering to the fundamental tenets of multidrug therapy, the synergistic effects of these drug molecules can effectively eradicate bacteria, even before they have the chance to develop resistance. This approach has the potential to shorten treatment periods, reduce costs, and mitigate drug resistance. Herein, four hypotheses are presented to create complementary drug cocrystals capable of simultaneously reaching bacterial cells, effectively destroying them before multidrug resistance can develop. The ongoing surge in the development of novel drugs provides another opportunity in the fight against bacteria that are constantly gaining resistance to existing treatments. This endeavour holds the potential to combat a wide array of multidrug-resistant bacteria.
Examining the effects of elevated CO2 on the growth kinetics of two microalgae, Skeletonema dohrnii (Bacillariophyceae) and Heterosigma akashiwo (Raphidophyceae)
Authors: Qin Jiahui , Jia Minjuan , Sun Jun
Published: February 2024

Carbon dioxide (CO2) serves as the primary substrate for the photosynthesis of phytoplankton, forming the foundation of marine food webs and mediating the biogeochemical cycling of C and N. We studied the effects of CO2 variation on the Michaelis-Menten equations and elemental composition of Skeletonema dohrnii and Heterosigma akashiwo. CO2 functional response curves were conducted from 100 to 2000 ppm. The growth of both phytoplankton was significantly affected by CO2, but in different trends. The growth rate of S. dohrnii increased as CO2 levels rose up to 400 ppm before reaching saturation. In contrast to S. dohrnii, the growth rate of H. akashiwo increased with CO2 increasing up to 1000 ppm, and then CO2 saturated. In addition, H. akashiwo showed a slower growth rate than S. dohrnii for all CO2 concentrations, aside from 1000 ppm, and the Michaelis-Menten equations revealed that the half-saturation constant of H. akashiwo was higher than S. dohrnii. An increase in CO2 concentration was seen to significantly affected the POC: Chl-a of both S. dohrnii and H. akashiwo, however, the effects on their elemental composition were minimal. Overall, our findings indicate that H. akashiwo had a more positive reaction to elevated CO2 than S. dohrnii, and with higher nutrient utilization efficiency, while S. dohrnii exhibited higher carbon fixation efficiency, which is in line with their respective carbon concentrating mechanisms. Consequently, elevated CO2, either alone or in combination with other limiting factors, may significantly alter the relative relationships between these two harmful algal blooms (HAB) species over the next century.
Insights into the rotational stability of toric intraocular lens implantation: diagnostic approaches, influencing factors and intervention strategies
Authors: Lin Xuanqiao , Ma Dongmei , Yang Jin
Published: February 2024

Toric intraocular lenses (IOLs) have been developed to enhance visual acuity impaired by cataracts and correct corneal astigmatism. However, residual astigmatism caused by postoperative rotation of the toric IOL is an important factor affecting visual quality after implantation. To decrease the rotation of the toric IOL, significant advancements have been made in understanding the characteristics of toric IOL rotation, the factors influencing its postoperative rotation, as well as the development of various measurement techniques and interventions to address this issue. It has been established that factors such as the patient’s preoperative refractive status, biological parameters, surgical techniques, postoperative care, and long-term management significantly impact the rotational stability of the toric IOL. Clinicians should adopt a personalized approach that considers these factors to minimize the risk of toric IOL rotation and ensure optimal outcomes for each patient. This article reviews the influence of various factors on toric IOL rotational stability. It discusses new challenges that may be encountered to reduce and intervene with rotation after toric IOL implantation in the foreseeable future.
Molecular insight into thymoquinone mechanism of action against Mycobacterium tuberculosis
Authors: Jankowski Grzegorz , Sawicki Rafał , Truszkiewicz Wiesław , Wolan Natalia , Ziomek Marcin , Hryć Benita , Sieniawska Elwira
Published: February 2024

Natural products are promising antimicrobials, usually having multiple and different cellular targets than synthetic antibiotics. Their influence on bacteria at various metabolic and functional levels contributes to higher efficacy even against drug-resistant strains. One such compound is a naturally occurring p-benzoquinone – thymoquinone. It is effective against different bacteria, including multidrug-resistant and extremely drug-resistant Mycobacterium tuberculosis. Its antibacterial mechanism of action was studied in several bacterial species except mycobacteria. To get an insight into the antimycobacterial activity of thymoquinone at the molecular level, we performed metabolomic and transcriptomic analyzes of bacteria exposed to this compound. The expression of genes coding stress-responsive sigma factors revealed that thymoquinone rapidly induces the production of sigE transcripts. At the same time, prolonged influence results in the overexpression of all sigma factor genes and significantly upregulates sigF. The metabolomic analysis confirmed that the antimycobacterial activity of thymoquinone was related to the depletion of NAD and ATP pools and the downregulation of plasma membrane lipids. This state was observed after 24 h and was persistent the next day, suggesting that bacteria could not activate catabolic mechanisms and produce energy. Additionally, the presence of a thymoquinone nitrogen derivative in the bacterial broth and the culture was reported.
Microbial divergence and evolution. The case of anammox bacteria
Authors: Cuecas Alba , Barrau M. Julia , Gonzalez Juan M.
Published: February 2024

Species differentiation and the appearance of novel diversity on Earth is a major issue to understand the past and future of microbial evolution. Herein, we propose the analysis of a singular evolutive example, the case of microorganisms carrying out the process of anammox (anaerobic ammonium oxidation). Anammox represents a singular physiology active on Earth from ancient times and, at present, this group is still represented by a relatively limited number of species carrying out a specific metabolism within the Phylum Planctomycetota. The key enzyme on the anammox pathway is hydrazine dehydrogenase (HDH) which has been used as a model in this study. HDH and rRNA (16S subunit) phylogenies are in agreement suggesting a monophyletic origin. The diversity of this singular phylogenetic group is represented by a few enriched bacterial consortia awaiting to be cultured as monospecific taxa. The apparent evolution of the HDH genes in these anammox bacteria is highly related to the diversification of the anammox clades and their genomes as pointed by phylogenomics, their GC content and codon usage profile. This study represents a clear case where bacterial evolution presents a paralleled genome, gene and species diversification through time from a common ancestor; a scenario that most times is masked by a web-like phylogeny and the huge complexity within the prokaryotes. Besides, this contribution suggests that microbial evolution of the anammox bacteria has followed an ordered, vertical diversification through Earth history and will present a potentially similar speciation fate in the future.
Pyrazinoic acid, the active form of the anti-tuberculosis drug pyrazinamide, and aromatic carboxylic acid analogs are protonophores
Authors: Fontes Fabio L. , Rooker Steven A. , Lynn-Barbe Jamie K. , Lyons Michael A. , Crans Debbie C. , Crick Dean C.
Published: February 2024

Pyrazinoic acid is the active form of pyrazinamide, a first-line antibiotic used to treat Mycobacterium tuberculosis infections. However, the mechanism of action of pyrazinoic acid remains a subject of debate, and alternatives to pyrazinamide in cases of resistance are not available. The work presented here demonstrates that pyrazinoic acid and known protonophores including salicylic acid, benzoic acid, and carbonyl cyanide m-chlorophenyl hydrazone all exhibit pH-dependent inhibition of mycobacterial growth activity over a physiologically relevant range of pH values. Other anti-tubercular drugs, including rifampin, isoniazid, bedaquiline, and p-aminosalicylic acid, do not exhibit similar pH-dependent growth-inhibitory activities. The growth inhibition curves of pyrazinoic, salicylic, benzoic, and picolinic acids, as well as carbonyl cyanide m-chlorophenyl hydrazone, all fit a quantitative structure–activity relationship (QSAR) derived from acid–base equilibria with R2 values > 0.95. The QSAR model indicates that growth inhibition relies solely on the concentration of the protonated forms of these weak acids (rather than the deprotonated forms). Moreover, pyrazinoic acid, salicylic acid, and carbonyl cyanide m-chlorophenyl hydrazone all caused acidification of the mycobacterial cytoplasm at concentrations that inhibit bacterial growth. Thus, it is concluded that pyrazinoic acid acts as an uncoupler of oxidative phosphorylation and that disruption of proton motive force is the primary mechanism of action of pyrazinoic acid rather than the inhibition of a classic enzyme activity.
Evaluation of the neuroprotective efficacy of the gramine derivative ITH12657 against NMDA-induced excitotoxicity in the rat retina
Authors: Di Pierdomenico Johnny , Gallego-Ortega Alejandro , Norte-Muñoz María , Vidal-Villegas Beatriz , Bravo Isaac , Boluda-Ruiz María , Bernal-Garro Jose Manuel , Fernandez-Bueno Iván , Pastor-Jimeno Jose Carlos , Villegas-Pérez María Paz , Avilés-Trigueros Marcelino , de los Ríos Cristobal , Vidal-Sanz Manuel
Published: February 2024

Purpose

The aim of this study was to investigate, the neuroprotective effects of a new Gramine derivative named: ITH12657, in a model of retinal excitotoxicity induced by intravitreal injection of NMDA.

Methods

Adult Sprague Dawley rats received an intravitreal injection of 100 mM NMDA in their left eye and were treated daily with subcutaneous injections of ITH12657 or vehicle. The best dose–response, therapeutic window study, and optimal treatment duration of ITH12657 were studied. Based on the best survival of Brn3a + RGCs obtained from the above-mentioned studies, the protective effects of ITH12657 were studied in vivo (retinal thickness and full-field Electroretinography), and ex vivo by quantifying the surviving population of Brn3a + RGCs, αRGCs and their subtypes α-ONsRGCs, α-ONtRGCs, and α-OFFRGCs.

Results

Administration of 10 mg/kg ITH12657, starting 12 h before NMDA injection and dispensed for 3 days, resulted in the best significant protection of Brn3a + RGCs against NMDA-induced excitotoxicity. In vivo, ITH12657-treated rats showed significant preservation of retinal thickness and functional protection against NMDA-induced retinal excitotoxicity. Ex vivo results showed that ITH12657 afforded a significant protection against NMDA-induced excitotoxicity for the populations of Brn3a + RGC, αRGC, and αONs-RGC, but not for the population of αOFF-RGC, while the population of α-ONtRGC was fully resistant to NMDA-induced excitotoxicity.

Conclusion

Subcutaneous administration of ITH12657 at 10 mg/kg, initiated 12 h before NMDA-induced retinal injury and continued for 3 days, resulted in the best protection of Brn3a + RGCs, αRGC, and αONs-RGC against excitotoxicity-induced RGC death. The population of αOFF-RGCs was extremely sensitive while α-ONtRGCs were fully resistant to NMDA-induced excitotoxicity.
Transcriptional precision in photoreceptor development and diseases – Lessons from 25 years of CRX research
Authors: Zheng Yiqiao , Chen Shiming
Published: February 2024

The vertebrate retina is made up of six specialized neuronal cell types and one glia that are generated from a common retinal progenitor. The development of these distinct cell types is programmed by transcription factors that regulate the expression of specific genes essential for cell fate specification and differentiation. Because of the complex nature of transcriptional regulation, understanding transcription factor functions in development and disease is challenging. Research on the Cone-rod homeobox transcription factor CRX provides an excellent model to address these challenges. In this review, we reflect on 25 years of mammalian CRX research and discuss recent progress in elucidating the distinct pathogenic mechanisms of four CRX coding variant classes. We highlight how in vitro biochemical studies of CRX protein functions facilitate understanding CRX regulatory principles in animal models. We conclude with a brief discussion of the emerging systems biology approaches that could accelerate precision medicine for CRX-linked diseases and beyond.
Endoscopic endonasal transsphenoidal surgery for unusual sellar lesions: eight cases and review of the literature
Authors: Wu Jiandong , Deng Peng , Qian Jinhong , Lu Yanli , Ding Zhiliang , Hu Xiaolong , Gong Yuhui , Tang Xiaoyu , Ma Mian
Published: February 2024

Background

Preoperative imaging for some unusual lesions in the sellar region can pose challenges in establishing a definitive diagnosis, impacting treatment strategies.

Methods

This study is a retrospective analysis of eight cases involving unusual sellar region lesions, all treated with endoscopic endonasal transsphenoidal surgery (EETS). We present the clinical, endocrine, and radiological characteristics, along with the outcomes of these cases.

Results

Among the eight cases, the lesions were identified as follows: Solitary fibrous tumor (SFT) in one case, Lymphocytic hypophysitis (LYH) in one case, Cavernous sinus hemangiomas (CSH) in one case, Ossifying fibroma (OF) in two cases; Sphenoid sinus mucocele (SSM) in one case, Pituitary abscess (PA) in two cases. All patients underwent successful EETS, and their diagnoses were confirmed through pathological examination. Postoperatively, all patients had uneventful recoveries without occurrences of diabetes insipidus or visual impairment.

Conclusion

Our study retrospectively analyzed eight unusual lesions of the sellar region. Some lesions exhibit specific imaging characteristics and clinical details that can aid in preoperative diagnosis and inform treatment strategies for these unusual sellar diseases.
Propofol anesthesia improves stroke outcomes over isoflurane anesthesia—a longitudinal multiparametric MRI study in a rodent model of transient middle cerebral artery occlusion
Authors: Franx Bart A. A. , van Tilborg Geralda A. F. , van der Toorn Annette , van Heijningen Caroline L. , Dippel Diederik W. J. , van der Schaaf Irene C. , Dijkhuizen Rick M. ,   on behalf of the CONTRAST consortium
Published: February 2024

General anesthesia is routinely used in endovascular thrombectomy procedures, for which volatile gas and/or intravenous propofol are recommended. Emerging evidence suggests propofol may have superior effects on disability and/or mortality rates, but a mode-of-action underlying these class-specific effects remains unknown. Here, a moderate isoflurane or propofol dosage on experimental stroke outcomes was retrospectively compared using serial multiparametric MRI and behavioral testing. Adult male rats (N = 26) were subjected to 90-min filament-induced transient middle cerebral artery occlusion. Diffusion-, T2- and perfusion-weighted MRI was performed during occlusion, 0.5 h after recanalization, and four days into the subacute phase. Sequels of ischemic damage—blood–brain barrier integrity, cerebrovascular reactivity and sensorimotor functioning—were assessed after four days. While size and severity of ischemia was comparable between groups during occlusion, isoflurane anesthesia was associated with larger lesion sizes and worsened sensorimotor functioning at follow-up. MRI markers indicated that cytotoxic edema persisted locally in the isoflurane group early after recanalization, coinciding with burgeoning vasogenic edema. At follow-up, sequels of ischemia were further aggravated in the post-ischemic lesion, manifesting as increased blood–brain barrier leakage, cerebrovascular paralysis and cerebral hyperperfusion. These findings shed new light on how isoflurane, and possibly similar volatile agents, associate with persisting injurious processes after recanalization that contribute to suboptimal treatment outcome.