bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence From Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes, Transgenic Rabbits, and Patients
Authors: Crotti Lia , Neves Raquel , Dagradi Federica , Musu Giulia , Giannetti Federica , Bos J. Martijn , Barbieri Miriam , Cerea Paolo , Giovenzana Fulvio L.F. , Torchio Margherita , Mura Manuela , Gnecchi Massimiliano , Conte Giulio , Auricchio Angelo , Sala Luca , Odening Katja E. , Ackerman Michael J. , Schwartz Peter J.
Published: June 2024

BACKGROUND:

Despite major advances in the clinical management of long QT syndrome, some patients are not fully protected by beta-blocker therapy. Mexiletine is a well-known sodium channel blocker, with proven efficacy in patients with sodium channel–mediated long QT syndrome type 3. Our aim was to evaluate the efficacy of mexiletine in long QT syndrome type 2 (LQT2) using cardiomyocytes derived from patient-specific human induced pluripotent stem cells, a transgenic LQT2 rabbit model, and patients with LQT2.

METHODS:

Heart rate–corrected field potential duration, a surrogate for QTc, was measured in human induced pluripotent stem cells from 2 patients with LQT2 (KCNH2-p.A561V, KCNH2-p.R366X) before and after mexiletine using a multiwell multi-electrode array system. Action potential duration at 90% repolarization (APD
90
) was evaluated in cardiomyocytes isolated from transgenic LQT2 rabbits (KCNH2-p.G628S) at baseline and after mexiletine application. Mexiletine was given to 96 patients with LQT2. Patients were defined as responders in the presence of a QTc shortening ≥40 ms. Antiarrhythmic efficacy of mexiletine was evaluated by a Poisson regression model.

RESULTS:

After acute treatment with mexiletine, human induced pluripotent stem cells from both patients with LQT2 showed a significant shortening of heart rate–corrected field potential duration compared with dimethyl sulfoxide control. In cardiomyocytes isolated from LQT2 rabbits, acute mexiletine significantly shortened APD
90
by 113 ms, indicating a strong mexiletine-mediated shortening across different LQT2 model systems. Mexiletine was given to 96 patients with LQT2 either chronically (n=60) or after the acute oral drug test (n=36): 65% of the patients taking mexiletine only chronically and 75% of the patients who performed the acute oral test were responders. There was a significant correlation between basal QTc and ∆QTc during the test (
r
= −0.8;
P
<0.001). The oral drug test correctly predicted long-term effect in 93% of the patients. Mexiletine reduced the mean yearly event rate from 0.10 (95% CI, 0.07–0.14) to 0.04 (95% CI, 0.02–0.08), with an incidence rate ratio of 0.40 (95% CI, 0.16–0.84), reflecting a 60% reduction in the event rate (
P
=0.01).

CONCLUSIONS:

Mexiletine significantly shortens cardiac repolarization in LQT2 human induced pluripotent stem cells, in the LQT2 rabbit model, and in the majority of patients with LQT2. Furthermore, mexiletine showed antiarrhythmic efficacy. Mexiletine should therefore be considered a valid therapeutic option to be added to conventional therapies in higher-risk patients with LQT2.
The Central Eurasian Dawn of Everything
Authors: Atwood Christopher P.
Published: June 2024

The Scythian Empire is Beckwith’s latest effort to redefine the European civilizational legacy as Central Eurasian, from its feudal origins to the development of philosophy, science, politics, and religion. Beckwith proposes that a Scythian Empire, spanning from the Mediterranean to the Ganges to the Yellow River, played a central role in shaping ancient civilizations, challenging conventional views of history. The Scythian religion is interpreted, based on Herodotus’ accounts, as fundamentally monotheistic. Although it offers insightful points on the importance of Central Eurasia in shaping ancient civilizations, the book and its claims of a unified Scythian Empire and monotheistic Aryan religion remain controversial.
Anatomical Connectivity Constrains Dynamic Functional Connectivity among Neural Systems: Implications for Cognition and Behavior
Authors: Courtney Susan M. , Hinault Thomas
Published: June 2024

Leslie Ungerleider had a tremendous impact across many different areas of cognitive neuroscience. Her ideas and her approach, as well as her findings, will continue to impact the field for generations to come. One of the most impactful aspects of her approach was her focus on the ways that anatomical connections constrain functional communications among brain regions. Furthermore, she emphasized that changes in these functional communications, whether from lesions to the anatomical connections or temporary modulations of the efficacy of information transmission resulting from selective attention, have consequences for cognition and behavior. By necessity, this short review cannot cover the vast amount of research that contributed to or benefited from Leslie's work. Rather, we focus on one line of research that grew directly from some of Leslie's early work and her mentoring on these important concepts. This research and the many other lines of research that arose from these same origins has helped develop our understanding of the visual system, and cognitive systems more generally, as collections of highly organized, specialized, dynamic, and interacting subsystems.
Description of two new species of Dirhagini (Coleoptera, Eucnemidae, Melasinae) from Myanmar amber
Authors: HAN XIN-YU , MUONA JYRKI , ZHAO YAN-CHEN , REN DONG
Published: June 2024

Two new species of Dirhagini are described from Cretaceous Myanmar amber: Cenomana grandis sp. nov. and Protomicrorhagus latus sp. nov. Based on the new specimen, the diagnosis of the genus Protomicrorhagus Muona, 2020 is revised, and Protomicrorhagus brevis Muona, 2020 is re-described. An identification key to all Dirhagini species from Myanmar amber is provided. Prothoracic structures of Cretaceous and modern Dirhagini species are discussed.
Prevalence and Correlates of Substance Use and the Effects on the Young People in a Southwestern State of Nigeria
Authors: Daniel Ebenezer , Olawale Oluseyi , Avwerhota Michael , Tomori Michael , Popoola Israel , Bello Ahmed , Alewi Olukayode , Salami Aisha , Ogun Adebanke , Popoola Taiwo , Ekwuluo Celestine
Published: June 2024

In 2015, psychoactive substance use led to the deaths of 72 young people within a month across Ondo, Edo, and Rivers states in Nigeria, with Ondo being the most affected. The youth attributed these deaths to the wrath of the gods (Malokun) rather than alcohol consumption. This study aims to identify demographic factors influencing youth substance use in Ondo State. Using a cross-sectional, descriptive community study design, 500 participants aged 10 to 24 years were recruited. Data collected through a socio-demographic questionnaire and the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) were analyzed with Statistical Package for Social Science (SPSS) version 16. The findings revealed that alcohol was the most used substance, with a lifetime use prevalence of 69.6%, likely due to the availability and cultural acceptability of local alcoholic products like ogogoro and palm wine. Substance use was found to negatively impact social life. Significant correlates of substance use included gender, age, religion, and father’s relationship. Males had higher lifetime use than females (p = 0.008), and substance use prevalence was higher among late adolescents (p = 0.0034). Christian respondents reported higher lifetime use compared to Muslims (p = 0.010). These results highlight that alcohol is the predominant substance used by young people in Ondo State, with key correlates being male gender, religion, less friendly father relationships, and late adolescence, informing public health strategies to mitigate harmful effects of substance use.
Assessment of Removal Methylene Blue and Green Dye in Water by Adsorption in Aqueous Solution by the Pan Bottom from a Mining Waste from Betaré-Oya
Authors: Emmanuel Ngaha , Dilek Duranoğlu
Published: June 2024

This work focuses on the study of the adsorption of methylene blue (BM) and a green dye (CV) in aqueous solution by the pan bottom from a mining waste from Betaré-Oya. The aim is to recover mining waste as an adsorbent. The influence of physico-chemical parameters on the kinetics and isotherm of adsorption of these dyes on the pan bottom was determined. The UV/Visible spectroscopy technique was used for the analyses. The green dye was study at spectral wavelength 570 nm. Green. Adsorption equilibrium times are 15 minutes for these dyes. Experiments show that when the bottom mass of the pan increases, the quantities adsorbed decrease. In fact, it is the adsorption yields that increase from 60 to 80% for BM and from 30 to more than 90% for CV. Variations in pH showed greater adsorption of dyes in basic medium (pH ≥ 10) which indicates that the dyes are cationic. It was also observed that the amounts of BM and CV per unit of pan bottom increase with increasing initial concentration. The experimental data was analyzed by isotherm models. The value of the constant n of the Freundlich model for BM is 1.53, indicating that adsorption is unfavorable, whereas in the case of CV, adsorption is moderate. Langmuir and Temkin models better describe MB adsorption. The mechanism of adsorption of BM and CV is of chemical type. Pseudo-first-order, pseudo-second-order, Elovich and intra-particle kinetic models have been applied on data and the most suitable is the pseudo-second-order kinetic model.
Factors Associated with Unplanned Pregnancy Among Youth at a Selected Hospital in Lesotho
Authors: Maselinyane Tseko , Nyangu Isabel , Nyoni Champion
Published: June 2024

Unplanned pregnancy amongst youth is a fundamental health problem that affects both developing and developed countries globally. There are various factors associated with unplanned pregnancy amongst youth and these factors have differing propagators. Unplanned pregnancies account for over half of total pregnancies in Lesotho; youth pregnancies contribute vast percentage overall. This study aimed to assess which factors associated are with unplanned pregnancy among youths who sought antenatal and postnatal care services at a selected government hospital in Lesotho. A descriptive cross-sectional design was used, and data was collected from a sample of 100 participants using a structured questionnaire. The results revealed that unplanned pregnancy among youths was associated with age, unemployment, lack of contraceptive use, sexual abuse, living in rural areas and lack of unplanned pregnancy prevention campaigns. The findings of this study support socio-ecological model which postulates that variety of factors influence health outcomes. We conclude that more needs to be done to improve access to formal education, availability and accessibility of unplanned pregnancy prevention campaigns and sexual and reproductive services. Reduction in unplanned pregnancy has several benefits not only to sexual and reproductive health but to life holistically. Sexual and reproductive health benefits include reduced maternal and neonatal morbidity and mortality and reduced abortions.
Finite Element Axisymmetric Models for Conical Wedge Anchorage Used in the Production of Prestressed Steel Reinforced Concretes
Authors: Quang Pham
Published: June 2024

The anchor system plays a very important part of the prestressed structure, that contacts and transmits force to the cables when stretching to create residual stress. The operating conditions of the anchor system in general and the anchor core in particular are extremely harsh. In this paper, ABAQUS software was applied to model and numerically simulate the axisymmetric loading process of the anchor core in manufacturing prestressed concrete sleepers, to study the effects of tensile forces to the pressure resistance of the cylinder. To verify the analytical results, a Finite Element (FE)-model with the same material and geometrical properties was created. The diﬀerence is the assumption of plane stress in the analytical solution, can be solved using two - dimensional finite elements, which are most conveniently described in cylindrical (r, θ, z) coordinates. This articles also especially focused on calculating the change of stress on the edges of the anchor core teeth with different tensile forces. We also refered to experimental results to get data on traction force and working conditions to build a calculation model and select input parameters. Comparison of the stress generated on the teeth of the anchor core was performed with three different tensions of 171, 181 and 191 kN. The maximum and concentrated stress at the top and root of the anchor core when tensioning the cable has been calculated.
Geology and Geochemistry of Aberma and Its Environ Sheet 54se Gusau, Zamfara State, Nigeria
Authors: Aliyu Bello
Published: June 2024

The study area falls within the northwestern part of Nigeria and is underlain by crystalline rocks of the Basement Complex. Field mapping in Aberma and its environs were carried out using topographical map sheet of 54 SE Gusau on a scale 1: 25,000 with an area extends of about 30.8052km2. This field work was carried out using traverse method in conjunction with field equipment such as compass/clinometers, geologic hammer, sample bag and global positioning system. This study however, aims at producing a detail geological map, including the various rock geochemistry and petrography of the study area. The area is underlain by two major lithological rock type which is mica schist and granite gneiss. The granite gneiss is strongly foliated, caused by high temperature and pressure and the minerals observed in plane polarized light include quartz, orthoclase, plagioclase, muscovite, opaque mineral and biotite. The mica schists in the study area are mostly weathered in ditches below the ground surface, the rock is moderately weathered and show schistocyte. The minerals observed in plane polarized light include quartz and muscovite. The dominant structures observed include; joints, Quartz veins, foliation and pegmatite dyke. Structural analysis shows that the rocks have been affected by the Pan African orogeny with the joint’s orientation trending dominantly NNE-SSW and Quartz vein trending in somewhat E-W direction. The microscopic studies revealed that the mineralogical composition of the rocks types of the study area contain varying percentages of quartz, muscovite, plagioclase, orthoclase, opaque mineral and biotite as the major minerals. The geochemical analysis revealed the major and minor elemental distribution of the rock types of the study area. The chemical assay revealed that the granite gneiss and mica schist rock type of the study area are super-saturated with respect to silica, silica (SiO2) is the most abundant oxide with an average value of 78.12% in the rock sample. This implies that the rock analyzed is acidic in nature and must have formed from crystallization of an acidic magma because the silica content being greater than 65%.
Prospecting Tungsten (Scheelite) Mineralization in the Djouzami Area (Adamawa Cameroon) Using Ultra-Violet (UV) Fluorescence and Landsat-8 OLI Images
Authors: Raoul Yingyang , Emmanuel Nomo , Dagwaï Nguihdama , Mouhamed Ayiwouo , Bertrand Mbohou , Ismaïla Ngounouno
Published: June 2024

Remote sensing technology and X-rays fluorescence are largely used in the applied geology field. In this study, we combine field observations and petrography, remote sensing applications through the processing of the Landsat-8 OLI, and Ultra-violet fluorescence to map geological structures, hydrothermal alteration minerals, and characterize tungsten mineralization in the Djouzami area (Adamawa, Cameroon). Landsat-8 OLI satellite imagery, was processed to detect both hydrothermal alteration zones and regional structural lineaments associated with tungsten mineralization. Fieldworks and petrography revealed hydrothermal mineral assemblage made of muscovite, chlorite, tourmaline, hematite, calcite and sericite associated to metallic minerals including tungsten and pyrite hosted in quartz veins. This hydrothermal mineral assemblage is also identified in the gold-bearing quartz veins reported in several areas along the Lom group. Band Ratio (BR) and Principal component analysis (PCA) were implemented to extract spectral information related to alteration minerals. The Band Ratios 6/7, 4/2, and 6/5 have permits to map clay, iron oxide/hydroxides, and ferrous minerals, respectively. This study demonstrates the significant potential of fieldwork and multispectral remote sensing data processing for tungsten prospecting as a mineral exploration technique in the Djouzami region. The mapping led to the detection of 1334 lineaments which show four main directions. The ENE-WSW directions corresponds to the trending of the Sanaga shear zone; the NE-SW direction represents the trending of the Djouzami and the Bétaré-Oya shear zones or the main shear zone which underline the Lom group; the N-S and E-W directions are equivalent to the trending of the foliation in the Meiganga area. Most of the high hydrothermal zones and tungsten-bearing quartz veins are located along the NE-SW lineaments or shear zone. Gold-related NE-SW trending Djouzami shear zone is also proposed. The NE-SW structure constitute certainly pathway for mineralizing fluids and ground water circulation, and control tungsten mineralization. Results proposed in this work provide important information for research of characteristic hydrothermal minerals assemblage that accompany tungsten mineralization, and for identify structures that control this mineralization in the area.
Opinion: Differentiating Natural Threats and Hazards for Water and Wastewater Structures and Operations - Energetic Threats and Hazards for the Water Industry
Authors: Jr Lee , Richmond Scott , Spiewak Daryl
Published: June 2024

A novel approach is presented to view, discern, and to redefine dangerous threats and hazards from natural events that can impact water and wastewater systems. The intent of this approach is to minimize ambiguity while enhancing preparedness and operational awareness of water and wastewater facilities, each vital for sustainable public health. This new approach recognizes potential and kinetic energy sources to differentiate between the threats and hazards generated by natural events, such as hurricanes, tornadoes or landslides, which can impact the steady-state operations of essential water and wastewater recovery facilities, associated infrastructure, plus endanger workers and exposed personnel. To support thisrethinking, absent in current literature searches, “energetic models” for anticipating latent, partial or total disruption of water and wastewater facilities and related management operations from naturally occurring events, such as a hurricane, tornado, or landslide, are presented. The proposed “energetic models” are atypical, yet they have practical value and encourage the rethinking and reimagining of threats and hazards used by water professionals and related fields and professions. The proposed models can be applied clearly to multiple and complex natural, human-caused, technological and equally disruptive events for water enterprises, expanding to similar challenges in public health responses to disease outbreaks.
Sustainable Finance and Economical Profitability in Africa
Authors: Alim Ousmanou
Published: June 2024

African continent is facing a considerable demonstration of financial institutions and especially bank group which are dominating the banking environment. In the absence of developed financial markets, these bank organisations are at the centre of the economic activity. They are even the main financing source for companies, States, households and represent about 80% of African continent assets. This situation is encouraged by the organisational structure of those banks (subsidiary companies, representative offices, affiliated banks and branches) which permit a better representatively at the level of the continent. This research analyses the influence of sustainable finance principles on the economical profitability of 42 banking groups implanted in African continent between 2010 and 2020. Thus, data used are extracted from annual reports and were analysed through a time cross-sectional regression corrected for any latent heteroscedasticity and serial autocorrelation. At the end, the findings of this research are plural. firstly, green credits and transparency have a non-considerable impact on economical profitability. secondly, employee shareholding and gender diversity have a negative influence on economical profitability. thirdly, corporate environmental responsibility is negatively and highly correlated to bank economic profitability. Finally, philanthropy positively and highly affects economical profitability. One can therefore conclude that the profitability of sustainable finance is mitigated in Africa.
Men’s Involvement in Wives’ Contraceptive Choices: A Comparative Study in Rural and Urban Communities of Akure South Local Government Area
Authors: Daniel Ebenezer , Olawale Oluseyi , Bello Ahmed , Popoola Israel , Alewi Olukayode , Tomori Michael , Avwerhota Michael , Ogun Adebanke , Popoola Taiwo , Salami Aisha , Ekwuluo Celestine
Published: June 2024

In rural Nigerian communities, men play a crucial role in family planning decisions, often determining if and how their wives can practice contraception. This study aimed to examine the extent of husbands' influence on their wives' contraceptive choices, comparing rural and urban areas in Akure South local government area. The research included a sample of 360 men, using a researcher-developed questionnaire and interview guide for data collection. Descriptive statistics such as frequencies, percentages, means, and standard deviations were used to analyze the data, and chi-square inferential statistics tested the hypothesis at a 0.05 significance level using SPSS version 17. Findings revealed that only 46% of rural respondents participated in family planning practices. Men’s engagement in these activities showed low mean values (2.21, 2.11, 2.25), indicating minimal involvement, primarily due to lack of information (40.5%) and limited contraceptive options (34.8%). Most men used condoms (23.8%), a combination of condoms and withdrawal (27.5%), or vasectomy (13.1%). The study concluded that male participation in family planning was low. To improve this, communities need better access to information, education, and communication. Cultural and religious barriers hindering male involvement in family planning should be addressed, and more male contraceptive options should be made available.
How I treat iron overload in adult MDS
Authors: Leitch Heather A. , Buckstein Rena
Published: June 2024

Although clinical benefits of iron chelation therapy (ICT) in red blood cell (RBC) transfusion–dependent (TD) hereditary anemias such as α-thalassemia major are incontrovertible, the evidence supporting a similar benefit in patients with TD myelodysplastic neoplasms (MDS) and iron overload (IOL) is sometimes debated. MDS presents later in life, has a limited repertoire of life-extending therapies, and patients may have comorbidities acting as competing causes of death. However, refined prognostication identifies patients with MDS with a reasonable life expectancy, and because 50% of patients will ultimately become RBC TD and develop transfusional IOL, ICT should be considered in some. Using illustrative cases, we summarize mechanisms of iron toxicity, strategies for the identification of IOL, and propose definitions of IOL severity. We provide rationale for, and recommend which patients may benefit from, ICT. We discuss currently available chelators, their administration, monitoring, side effects, and their management. Given challenges with the use of iron chelators, we suggest the nuances to be considered when planning chelation initiation to include the rate of iron accumulation, the presence of organ iron and/or dysfunction, and detectable indicators of oxidative stress. Areas for future investigation are identified.
LMWH prevents thromboinflammation in the placenta via HBEGF-AKT signaling
Authors: Singh Kunal Kumar , Gupta Anubhuti , Forstner Désirée , Guettler Jacqueline , Ahrens Mirjam Susanne , Prakasan Sheeja Akshay , Fatima Sameen , Shamkeeva Saikal , Lia Massimiliano , Dathan-Stumpf Anne , Hoffmann Nikola , Shahzad Khurrum , Stepan Holger , Gauster Martin , Isermann Berend , Kohli Shrey
Published: June 2024

Low molecular weight heparins (LMWH) are used to prevent or treat thromboembolic events during pregnancy. Although studies suggest an overall protective effect of LMWH in preeclampsia (PE), their use in PE remains controversial. LMWH may convey beneficial effects in PE independent of their anticoagulant activity, possibly by inhibiting inflammation. Here, we evaluated whether LMWH inhibit placental thromboinflammation and trophoblast NLRP3 inflammasome activation. Using an established procoagulant extracellular vesicle–induced and platelet-dependent PE-like mouse model, we show that LMWH reduces pregnancy loss and trophoblast inflammasome activation, restores altered trophoblast differentiation, and improves trophoblast proliferation in vivo and in vitro. Moreover, LMWH inhibits platelet-independent trophoblast NLRP3 (NLR family pyrin domain containing 3) inflammasome activation. Mechanistically, LMWH activates via heparin-binding epidermal growth factor (HBEGF) signaling the PI3-kinase-AKT pathway in trophoblasts, thus preventing inflammasome activation. In human PE placental explants, inflammasome activation and PI3-kinase-AKT signaling events were reduced with LMWH treatment compared with those without LMWH treatment. Thus, LMWH inhibits sterile inflammation via the HBEGF signaling pathway in trophoblasts and ameliorates PE-associated complications. These findings suggest that drugs targeting the inflammasome may be evaluated in PE and identify a signaling mechanism through which LMWH ameliorates PE, thus providing a rationale for the use of LMWH in PE.
Genome-wide association analysis identify candidate genes for feed efficiency and growth traits in Wenchang chickens
Authors: Cai Keqi , Liu Ranran , Wei Limin , Wang Xiuping , Cui Huanxian , Luo Na , Wen Jie , Chang Yuxiao , Zhao Guiping
Published: June 2024

Background

Wenchang chickens are one of the most popular local chicken breeds in the Chinese chicken industry. However, the low feed efficiency is the main shortcoming of this breed. Therefore, there is a need to find a more precise breeding method to improve the feed efficiency of Wenchang chickens. In this study, we explored important candidate genes and variants for feed efficiency and growth traits through genome-wide association study (GWAS) analysis.

Results

Estimates of genomic heritability for growth and feed efficiency traits, including residual feed intake (RFI) of 0.05, average daily food intake (ADFI) of 0.21, average daily weight gain (ADG) of 0.24, body weight (BW) at 87, 95, 104, 113 days of age (BW87, BW95, BW104 and BW113) ranged from 0.30 to 0.44. Important candidate genes related to feed efficiency and growth traits were identified, such as PLCE1, LAP3, MED28, QDPR, LDB2 and SEL1L3 genes.

Conclusion

The results identified important candidate genes for feed efficiency and growth traits in Wenchang chickens and provide a theoretical basis for the development of new molecular breeding technology.
A bias-reduced generalized estimating equation approach for proportional odds models with small-sample longitudinal ordinal data
Authors: Tada Yukio , Sato Tosiya
Published: June 2024

Background

Longitudinal ordinal data are commonly analyzed using a marginal proportional odds model for relating ordinal outcomes to covariates in the biomedical and health sciences. The generalized estimating equation (GEE) consistently estimates the regression parameters of marginal models even if the working covariance structure is misspecified. For small-sample longitudinal binary data, recent studies have shown that the bias of regression parameters may result from the GEE and have addressed the issue by applying Firth’s adjustment for the likelihood score equation to the GEE as if generalized estimating functions were likelihood score functions. In this manuscript, for the proportional odds model for longitudinal ordinal data, the small-sample properties of the GEE were investigated, and a bias-reduced GEE (BR-GEE) was derived.

Methods

By applying the adjusted function originally derived for the likelihood score function of the proportional odds model to the GEE, we produced the BR-GEE. We investigated the small-sample properties of both GEE and BR-GEE through simulation and applied them to a clinical study dataset.

Results

In simulation studies, the BR-GEE had a bias closer to zero, smaller root mean square error than the GEE with coverage probability of confidence interval near or above the nominal level. The simulation also showed that BR-GEE maintained a type I error rate near or below the nominal level.

Conclusions

For the analysis of longitudinal ordinal data involving a small number of subjects, the BR-GEE is advantageous for obtaining estimates of the regression parameters of marginal proportional odds models.
Rational construction of a high-quality and high-efficiency biosynthetic system and fermentation optimization for A82846B based on combinatorial strategies in Amycolatopsis orientalis
Authors: Zhao Xinyi , Zhu Chenyang , Gao Wenli , Xie Huang , Lyu Zhongyuan , Zhao Qingwei , Li Yongquan
Published: June 2024

Background

Oritavancin is a new generation of semi-synthetic glycopeptide antibiotics against Gram-positive bacteria, which served as the first and only antibiotic with a single-dose therapeutic regimen to treat ABSSSI. A naturally occurring glycopeptide A82846B is the direct precursor of oritavancin. However, its application has been hampered by low yields and homologous impurities. This study established a multi-step combinatorial strategy to rationally construct a high-quality and high-efficiency biosynthesis system for A82846B and systematically optimize its fermentation process to break through the bottleneck of microbial fermentation production.

Results

Firstly, based on the genome sequencing and analysis, we deleted putative competitive pathways and constructed a better A82846B-producing strain with a cleaner metabolic background, increasing A82846B production from 92 to 174 mg/L. Subsequently, the PhiC31 integrase system was introduced based on the CRISPR-Cas12a system. Then, the fermentation level of A82846B was improved to 226 mg/L by over-expressing the pathway-specific regulator StrR via the constructed PhiC31 system. Furthermore, overexpressing glycosyl-synthesis gene evaE enhanced the production to 332 mg/L due to the great conversion of the intermediate to target product. Finally, the scale-up production of A82846B reached 725 mg/L in a 15 L fermenter under fermentation optimization, which is the highest reported yield of A82846B without the generation of homologous impurities.

Conclusion

Under approaches including blocking competitive pathways, inserting site-specific recombination system, overexpressing regulator, overexpressing glycosyl-synthesis gene and optimizing fermentation process, a multi-step combinatorial strategy for the high-level production of A82846B was developed, constructing a high-producing strain AO-6. The combinatorial strategies employed here can be widely applied to improve the fermentation level of other microbial secondary metabolites, providing a reference for constructing an efficient microbial cell factory for high-value natural products.
Diagnostic accuracy of an automated microscope solution (miLab™) in detecting malaria parasites in symptomatic patients at point-of-care in Sudan: a case–control study
Authors: Hamid Muzamil M. Abdel , Mohamed Abdelrahim O. , Mohammed Fayad O. , Elaagip Arwa , Mustafa Sayed A. , Elfaki Tarig , Jebreel Waleed M. A. , Albsheer Musab M. , Dittrich Sabine , Owusu Ewurama D. A. , Yerlikaya Seda
Published: June 2024

Background

Microscopic detection of malaria parasites is labour-intensive, time-consuming, and expertise-demanding. Moreover, the slide interpretation is highly dependent on the staining technique and the technician’s expertise. Therefore, there is a growing interest in next-generation, fully- or semi-integrated microscopes that can improve slide preparation and examination. This study aimed to evaluate the clinical performance of miLab™ (Noul Inc., Republic of Korea), a fully-integrated automated microscopy device for the detection of malaria parasites in symptomatic patients at point-of-care in Sudan.

Methods

This was a prospective, case–control diagnostic accuracy study conducted in primary health care facilities in rural Khartoum, Sudan in 2020. According to the outcomes of routine on-site microscopy testing, 100 malaria-positive and 90 malaria-negative patients who presented at the health facility and were 5 years of age or older were enrolled consecutively. All consenting patients underwent miLab™ testing and received a negative or suspected result. For the primary analysis, the suspected results were regarded as positive (automated mode). For the secondary analysis, the operator reviewed the suspected results and categorized them as either negative or positive (corrected mode). Nested polymerase chain reaction (PCR) was used as the reference standard, and expert light microscopy as the comparator.

Results

Out of the 190 patients, malaria diagnosis was confirmed by PCR in 112 and excluded in 78. The sensitivity of miLab™ was 91.1% (95% confidence interval [CI] 84.2–95.6%) and the specificity was 66.7% (95% Cl 55.1–67.7%) in the automated mode. The specificity increased to 96.2% (95% Cl 89.6–99.2%), with operator intervention in the corrected mode. Concordance of miLab with expert microscopy was substantial (kappa 0.65 [95% CI 0.54–0.76]) in the automated mode, but almost perfect (kappa 0.97 [95% CI 0.95–0.99]) in the corrected mode. A mean difference of 0.359 was found in the Bland–Altman analysis of the agreement between expert microscopy and miLab™ for quantifying parasite counts.

Conclusion

When used in a clinical context, miLab™ demonstrated high sensitivity but low specificity. Expert intervention was shown to be required to improve the device’s specificity in its current version. miLab™ in the corrected mode performed similar to expert microscopy. Before clinical application, more refinement is needed to ensure full workflow automation and eliminate human intervention.

Trial registration ClinicalTrials.gov: NCT04558515
Addressing anti-Black racism within public health in North America: a scoping review
Authors: Rakotovao Lucina , Simeoni Michelle , Bennett-AbuAyyash Caroline , Walji Taheera , Abdi Samiya
Published: June 2024

Objectives

The syndemic that is COVID-19 and the disproportionate policing of Black communities have recently generated mass social consciousness of the anti-Black racism (ABR) pervading health, social, and cultural institutions. However, little is known about the implementation of public health measures addressing ABR in an evolving pandemic context. The objective of this scoping review is to provide an overview of public health initiatives undertaken to address ABR across North American jurisdictions between December 2019 and June 2022.

Methods

A search for public health initiatives was conducted in June 2021 across MEDLINE, Ovid Embase, EBSChost, CINAHL, SocINDEX, and Google.ca. Included initiatives were those focussing on Black, African diasporic, or African American communities in the North American context. Community-led action, as well as initiatives in primary healthcare care, academic journals, and those broadly focused on racialized communities, were excluded from this review.

Synthesis

Seventy-five articles were included in this review, suggesting that ABR emerged as a public health priority. Strategies and action plans to address structural ABR were the most common types of initiatives observed (n = 21), followed by programs or interventions (n = 16), budget allocations or investments (n = 8), task forces (n = 7), guidance and recommendations for organizational capacity (n = 8), action-oriented declarations of ABR as a public health crisis (n = 8), and legislation and mandates (n = 7). Initiatives were largely cross-cutting of two or more socioeconomic themes (n = 23), while organizational change was also common (n = 16). Gaps in the current literature include a lack of community participation and outcome measurement for actions identified, which limit institutional accountability to communities of interest.

Conclusion

This research provides insights on public health accountability to social justice. This research outlines activities in upstream interventions, organizational transformation, and resource allocation in shaping anti-racist change, and require evaluation and input from those whom initiatives are intended to serve.
Comparing the effects of Pilates, corrective exercises, and Alexander’s technique on upper cross syndrome among adolescent girls student (ages 13–16): a six-week study
Authors: Shadi Nesa , Khalaghi Karim , Seyedahmadi Mohammad
Published: June 2024

Introduction

Upper Cross Syndrome is a pattern of muscle imbalance and postural dysfunction that can cause discomfort and pain. This study’s objective was to compare the effects of Pilates exercises, corrective exercises, and Alexander’s technique on upper cross syndrome in adolescent girls aged 13–16 years: a six-week intervention study.

Methods

The present study was Quasi-experimental, and its statistical population consisted of 13 to 16-year-old female students. Forty-five students who were diagnosed with upper cross syndrome were purposefully selected as samples and randomly assigned to three groups: Pilates exercises (N = 15), corrective exercises (N = 15), and Alexander’s technique (N = 15). The participants performed exercises for 60 min per session, three sessions per week, and six weeks. This study’s objective was to compare the effects of Pilates exercises, corrective exercises, and Alexander’s technique on upper cross syndrome in adolescent girls aged 13–16 years: a six-week intervention study. This study was retrospectively registered in the Iranian Registry of Clinical Trials (IRCT) on 2023-09-19 to comply with the journal’s policies. The assigned trial registration number is IRCT20230810059106N1.

Results

The results of the dependent t-test showed significant decreases in forward head angle (p = 0.0001), rounded shoulder (p = 0.001), and kyphosis (p = 0.0001) as a result of corrective exercises. There were also significant decreases in forward head angle (p = 0.0001), rounded shoulder (p = 0.002), and kyphosis (p = 0.001) after six weeks of practising Alexander’s technique. However, in the case of Pilates exercises, a significant decrease in forward head angle (p = 0.110), rounded shoulder (p = 0.598), and kyphosis (p = 0.371) was not observed. The one-way analysis of variance revealed a significant difference in the forward head angle (p = 0.012), rounded shoulders (p = 0.013), and kyphosis (p = 0.009).

Conclusions

The effect of Alexander’s technique and corrective exercises on forward head angle, rounded shoulder, and kyphosis abnormalities was almost similar and more effective than pilates exercises.
High-throughput screening carbon and nitrogen sources to promote growth and sporulation in Rhizopus arrhizus
Authors: Zhao Heng , Ju Xiao , Nie Yong , James Timothy Y. , Liu Xiao-Yong
Published: June 2024

Rhizopus arrhizus is a saprotrophic, sometimes clinically- and industrially-relevant mold (Mucorales) and distributed worldwide, suggesting it can assimilate a broad spectrum of substrates. Here, 69 strains of R. arrhizus were investigated by using the Biolog FF MicroPlate for the profiles of utilizing 95 carbon and nitrogen substrates. The study showed that most R. arrhizus strains were similar in average well color development (AWCD) and substrate richness (SR). Nevertheless, 13 strains were unique in principal component analyses, heatmap, AWCD, and SR analyses, which may imply a niche differentiation within R. arrhizus. The species R. arrhizus was able to utilize all the 95 carbon and nitrogen substrates, consistent with the hypothesis of a great metabolic diversity. It possessed a substrate preference of alcohols, and seven substrates were most frequently utilized, with N-acetyl-d-galactosamine and l-phenylalanine ranking at the top of the list. Eight substrates, especially l-arabinose and xylitol, were capable of promoting sporulation and being applied for rejuvenating degenerated strains. By phenotyping R. arrhizus strains in carbon and nitrogen assimilation capacity, this study revealed the extent of intra-specific variability and laid a foundation for estimating optimum substrates that may be useful for industrial applications.
A survey of machine learning techniques for improving Global Navigation Satellite Systems
Authors: Mohanty Adyasha , Gao Grace
Published: June 2024

Global Navigation Satellite Systems (GNSS)-based positioning plays a crucial role in various applications, including navigation, transportation, logistics, mapping, and emergency services. Traditional GNSS positioning methods are model-based, utilizing satellite geometry and the known properties of satellite signals. However, model-based methods have limitations in challenging environments and often lack adaptability to uncertain noise models. This paper highlights recent advances in machine learning (ML) and its potential to address these limitations. It covers a broad range of ML methods, including supervised learning, unsupervised learning, deep learning, and hybrid approaches. The survey provides insights into positioning applications related to GNSS, such as signal analysis, anomaly detection, multi-sensor integration, prediction, and accuracy enhancement using ML. It discusses the strengths, limitations, and challenges of current ML-based approaches for GNSS positioning, providing a comprehensive overview of the field.
Supply chain management of micro, small, and medium enterprises (MSMEs) in Africa: a bibliometric analysis
Authors: Wube Mulugeta Chane , Atwal Heena
Published: June 2024

This study examines the supply chain management of micro, small, and medium enterprises (MSMEs) in Africa, aiming to demonstrate the patterns of publication in this field. An extensive examination of bibliometric analysis has been conducted using 338 published works obtained from the Dimensions database over the last 20 years. The study was conducted based on publications, sources, authors, and institutions as the primary units of analysis. The study determined the leading journals, prolific authors, partnering countries, and organizations involved in research on supply chain management specifically focused on micro, small, and medium enterprises (MSMEs) in Africa. Furthermore, it has been uncovered that the investigation of supply chain management in MSMEs in Africa needs to be revised in comparison to that of larger organizations. Moreover, publications in the field are not only insufficiently accessible, but also authored by scholars who are not of African descent. Given the crucial role of MSMEs in the African economy, scholars in this field are encouraged to prioritize research on the supply chain management of MSMEs as a critical issue for the twenty-first century. Furthermore, researchers are recommended to do additional analyses utilizing alternative databases such as Web of Sciences and Scopus.
Driving gut microbiota enterotypes through host genetics
Authors: Larzul Catherine , Estellé Jordi , Borey Marion , Blanc Fany , Lemonnier Gaëtan , Billon Yvon , Thiam Mamadou Gabou , Quinquis Benoît , Galleron Nathalie , Jardet Deborah , Lecardonnel Jérôme , Plaza Oñate Florian , Rogel-Gaillard Claire
Published: June 2024

Background

Population stratification based on interindividual variability in gut microbiota composition has revealed the existence of several ecotypes named enterotypes in humans and various animal species. Enterotypes are often associated with environmental factors including diet, but knowledge of the role of host genetics remains scarce. Moreover, enterotypes harbor functionalities likely associated with varying abilities and susceptibilities of their host. Previously, we showed that under controlled conditions, 60-day-old pig populations consistently split into two enterotypes with either Prevotella and Mitsuokella (PM enterotype) or Ruminococcus and Treponema (RT enterotype) as keystone taxa. Here, our aim was to rely on pig as a model to study the influence of host genetics to assemble enterotypes, and to provide clues on enterotype functional differences and their links with growth traits.

Results

We established two pig lines contrasted for abundances of the genera pairs specifying each enterotype at 60 days of age and assessed them for fecal microbiota composition and growth throughout three consecutive generations. Response to selection across three generations revealed, per line, an increase in the prevalence of the selected enterotype and in the average relative abundances of directly and indirectly selected bacterial genera. The PM enterotype was found less diverse than the RT enterotype but more efficient for piglet growth during the post-weaning period. Shotgun metagenomics revealed differentially abundant bacterial species between the two enterotypes. By using the KEGG Orthology database, we show that functions related to starch degradation and polysaccharide metabolism are enriched in the PM enterotype, whereas functions related to general nucleoside transport and peptide/nickel transport are enriched in the RT enterotype. Our results also suggest that the PM and RT enterotypes might differ in the metabolism of valine, leucin, and isoleucine, favoring their biosynthesis and degradation, respectively.

Conclusion

We experimentally demonstrated that enterotypes are functional ecosystems that can be selected as a whole by exerting pressure on the host genetics. We also highlight that holobionts should be considered as units of selection in breeding programs. These results pave the way for a holistic use of host genetics, microbiota diversity, and enterotype functionalities to understand holobiont shaping and adaptation.
Attitudes and gaps in knowledge of the diagnosis, treatment, and psychopathology of eating disorders among different health professionals
Authors: Monteleone Alessio Maria , Carfagno Marco , Barone Eugenia , Cascino Giammarco , Pitocco Armando , Brandi Carlotta , Landolfi Lorenzo , Toni Claudia , Sampogna Gaia , Fiorillo Andrea
Published: June 2024

Background

Health professionals from different specialties in medical and psychological areas play an important role in diagnosis and treatment of eating disorders (EDs). This study aimed to identify gaps in knowledge about the diagnosis, etiology, and management of EDs and to assess health professionals’ attitudes towards these illnesses.

Methods

A new questionnaire was developed and validated. Residents and consultants working in disciplines involved in the management of EDs (namely, internal medicine, general practitioners, psychiatric area, psychological area, and surgical area) completed the questionnaire. Knowledge and attitudes were compared among the study groups through one-way ANCOVA and chi-square tests.

Results

The final version of the questionnaire consisted of 54 items assessing the following areas: stigma, treatment, physical complications, diagnosis, and aetiopathogenesis of EDs. For all health professionals the area of most deficiency was the aetiopathogenesis, while the best one was the management of physical complications. All medical professionals showed less knowledge than psychiatrists in terms of etiology, diagnosis, and treatment of EDs. A lack of knowledge about evidence-based psychotherapies, general psychopathology, and family members’ role in the management of EDs emerged among all health professionals. Stigma was found among non-mental health professionals who considered these patients to be different from others and responsible for their abnormal eating behaviors.

Conclusions

Clarifying the health professionals’ specific gaps occurring in the knowledge of EDs and in the attitudes towards these individuals may inform educational programs to improve early detection and management of EDs.