bluuebunny/crossref_metadata_2025 huggingface dataset:
Unravelling the transcriptomic symphony of muscle ageing: key pathways and hub genes altered by ageing and caloric restriction in rat muscle revealed by RNA sequencing
Authors: Altab Gulam , Merry Brian J. , Beckett Charles W. , Raina Priyanka , Lopes Inês , Goljanek-Whysall Katarzyna , de Magalhães João Pedro
Published: January 2025

Age-related muscle wasting, sarcopenia is an extensive loss of muscle mass and strength with age and a major cause of disability and accidents in the elderly. Mechanisms purported to be involved in muscle ageing and sarcopenia are numerous but poorly understood, necessitating deeper study. Hence, we employed high-throughput RNA sequencing to survey the global changes in protein-coding gene expression occurring in skeletal muscle with age. Caloric restriction (CR) is a known prophylactic intervention against sarcopenia. Therefore, total RNA was isolated from the muscle tissue of both rats fed ad libitum and CR rats. RNA-seq data were subjected to Gene Ontology, pathway, co-expression, and interaction network analyses. This revealed the functional pathways most activated by both ageing and CR, as well as the key “hub” proteins involved in their activation.

RNA-seq revealed 442 protein-coding genes to be upregulated and 377 to be downregulated in aged muscle, compared to young muscle. Upregulated genes were commonly involved in protein folding and immune responses; meanwhile, downregulated genes were often related to developmental biology. CR was found to suppress 69.7% and rescue 57.8% of the genes found to be upregulated and downregulated in aged muscle, respectively. In addition, CR uniquely upregulated 291 and downregulated 304 protein-coding genes. Hub genes implicated in both ageing and CR included Gc, Plg, Irf7, Ifit3, Usp18, Rsad2, Blm and RT1-A2, whilst those exclusively implicated in CR responses included Alb, Apoa1, Ambp, F2, Apoh, Orm1, Mx1, Oasl2 and Rtp4. Hub genes involved in ageing but unaffected by CR included Fgg, Fga, Fgb and Serpinc1. In conclusion, this comprehensive RNA sequencing study highlights gene expression patterns, hub genes and signalling pathways most affected by ageing in skeletal muscle. This data may provide the initial evidence for several targets for potential future therapeutic interventions against sarcopenia.
Improving natural red pigment production by Streptomyces phaeolivaceus strain GH27 for functionalization of textiles with in silico ADME prediction
Authors: Sayed Gehad H. El , Fadel Mohamed , Fouad Rasha , Ahmed Hend M. , Hamed Ahmed A.
Published: January 2025

The red pigment was recovered from the S. phaeolivaceus GH27 isolate, which was molecularly identified using 16S rRNA gene sequencing and submitted to GenBank as OQ145635.1. The ideal growth conditions included 1% (w/v) starch, diammonium citrate, dibasic sodium phosphate, 5% (v/v) inoculum, pH 8, a rotation speed of 150 rpm, a temperature of 37 °C, and an incubation period of 9 days. Using ethanol as a solvent, the red pigment was effectively recovered. Data indicates that pigment content remained steady at 40 and 50 °C. Heating the pigment extract to 60, 70, 80, 90, and 100 °C for one hour results in pigment retention of 98%, 96.5%, 95.5%, 94.6%, and 92.6% of its pigment density, respectively. Studies indicate that the pigment extracts exhibited optimal stability at alkaline pH levels. The findings demonstrate that the red pigment extract has a peak absorbance range of 280–340 nm, with a λmax of 300 nm. GC/MS analysis revealed that the primary components of the pigment extract were linolenic acid methyl ester and oleic acid methyl ester, constituting 26.41% and 25.25%, respectively. Fabrics dyed with extracted red pigment exhibit excellent fastness when using the comprehensive green method. In comparison to conventional and nanotechnological attributes, printed samples exhibit significant color strength without environmental repercussions. The treatment of cotton, wool, and polyester samples suppressed pathogen growth to differing extents. Polyester had the most important inhibitory effects on Staphylococcus aureus (50.03%) and Bacillus cereus (39.49%). The ADME physicochemical properties of the predominant medication were assessed, together with its bioavailability. The radar plot demonstrated ideal parameters for size, polarity, lipophilicity, solubility, and saturation, excluding flexibility. It exhibited intermediate synthetic accessibility, exceptional permeability and absorption, elevated gastrointestinal absorption, and blood–brain barrier penetration; nonetheless, it did not adhere to the medicinal chemistry rule of three.

Graphical Abstract
Associations between changes in the gut microbiota and liver cirrhosis: a systematic review and meta-analysis
Authors: Liu Ye , Chen Ziwei , Li Chang , Sun Tianhan , Luo Xuanmei , Jiang Boyue , Liu Meilan , Wang Qing , Li Tong , Cao Jianfu , Li Yayu , Chen Yuan , Kuai Lu , Xiao Fei , Xu Hongtao , Cui Hongyuan
Published: January 2025

Objective

Summaries of the relationships between the microbiota and liver cirrhosis and their conclusions are not consistent. This study describes microbial differences in patients with liver cirrhosis by performing a meta-analysis.

Methods

We searched PubMed, Embase, Web of Science, and the Cochrane Library and collected related articles published before March 10, 2024. Ratio of autochthonous to non-autochthonous taxa was calculated as the cirrhosis dysbiosis ratio (CDR). Using a random-effects model, the standard mean deviation (SMD) and 95% confidence interval (CI) were calculated. We subsequently performed subgroup, sensitivity, and publication bias analyses. cirrhosis dysbiosis ratio.

Results

A total of 53 eligible papers including 5076 participants were included. The pooled estimates revealed a moderately significant reduction in gut microbiome richness in patients with liver cirrhosis compared with controls, including the Shannon, Chao1, observed species, ACE, and PD indices, but no significant difference was observed for the Simpson index. Over 80% of the studies reported significant differences in β diversity. Families Enterobacteriaceae and Pasteurellaceae, belonging to the phylum Proteobacteria, along with the family Streptococcaceae and the genera Haemophilus, Streptococcus, and Veillonella, were significantly associated with liver cirrhosis compared to the control group. In contrast, the healthy group exhibited a higher abundance of the class Clostridia, particularly the families Lachnospiraceae and Ruminococcaceae, which are known for their diversity and role as common gut commensals. Furthermore, the class Bacilli, predominantly represented by the genus Streptococcus, was markedly enriched in the cirrhosis group.

Conclusions

The microbiota richness of liver cirrhosis patients was lower than that of healthy controls. Alterations in gut microbiota linked to liver cirrhosis were characterized by a decrease in Lachnospiraceae, Ruminococcaceae, and Clostridia and an enrichment of Enterobacteriaceae, Pasteurellaceae, Streptococcaceae, Bacilli, and Streptococcus.
Relationship between kidney function and healthy life expectancy: A historical cohort study
Authors: Ogura Hisayuki , Toyama Tadashi , Samuta Hikaru , Hirako Kohei , Itatani Tomoya , Nakagawa Shiori , Oshima Megumi , Kitajima Shinji , Hara Akinori , Sakai Norihiko , Shimizu Miho , Takura Tomoyuki , Wada Takashi , Iwata Yasunori
Published: January 2025

Background

The impact of chronic kidney disease (CKD) on healthy life expectancy and healthcare costs requires research. This study examined associations between CKD and healthy life expectancy, and its economic burden.

Methods

This study of community-dwelling adults residing in Hakui City, Ishikawa Prefecture, Japan used data from the National Health Insurance database between 2012 and 2022. Participants were grouped by baseline estimated glomerular filtration rate (eGFR) (< 45, ≥ 45 to < 60, ≥60 to < 75, ≥75 to < 90, and ≥ 90 mL/min/1.73 m²). The primary endpoint was a composite of becoming a care level ≥ 2 or death. Multivariable Cox proportional hazards models were used to calculate the risk regarding time to the primary endpoint. Secondary endpoints were the annual medical and long-term care costs.

Results

The 5,592 participants had a mean follow-up of 6.4 years. The hazard ratio was 1.86 (95% confidence interval [CI]: 1.35 to 2.55) for the eGFR < 45 group and 1.60 (95% CI: 1.13 to 2.25) for the eGFR ≥ 90 group, both compared with the eGFR ≥ 60 to < 75 group. Both annual costs were significantly higher in the lower eGFR groups than in the higher eGFR groups. For the eGFR < 45 group, the median medical care cost was 0.38 million yen/year in all participants and the median long-term care cost was 0.40 million yen/year in primary endpoint achievers. A lower eGFR was correlated with longer unhealthy years of life.

Conclusions

Higher and lower eGFRs were associated with increased risks of reduced healthy life expectancy. A lower eGFR was associated with higher medical and long-term care costs.
Visible and invisible cultural patterns influencing women’s use of maternal health services among Igala women in Nigeria: a focused ethnographic study
Authors: Opara Uchechi Clara , Iheanacho Peace Njideka , Petrucka Pammla
Published: January 2025

Background

Explicit and implicit cultural patterns are critical cultural norms, beliefs, and practices that determine women’s health-seeking behaviour. These cultural patterns could limit women’s use of maternal health services, resulting in maternal health complications. The study aims to provide an in-depth understanding of explicit and implicit cultural patterns, their meanings and how they influence women’s use of maternal health services among Igala women in Nigeria.

Methods

Roper and Shapira’s (2000) focused ethnography was employed with 43 women aged 18–43 years recruited using the purposive and snowballing technique. The study was conducted with 21 women for one-on-one interviews and two focus group discussions with six women in the rural area and seven women in the urban area. In addition, participant observation of nine women from the third trimester to birth was conducted, yielding 189 h of observation in two primary healthcare facilities in rural and urban areas. Data analysis was conducted using Roper and Shapira’s (2000) method.

Result

Three themes were generated using the PEN3 cultural model: perceptions, enabler, and nurturers. Subthemes generated under the theme of perception were, Belief in witchcraft, Pregnancy announces itself, I cannot tell people I am in labour, and Unspoken acquiescence to the culture. Under the theme of nurturer, Home birth was found to limit access to maternal health services. The theme of enabler yielded subthemes such as You are not woman enough; I want my placenta and Rising matriarchs.

Conclusion

Implicit and explicit cultural patterns significantly influence women’s use of maternal health services. Given the complexity of culture and its influence on women’s use of maternal health services, multifaceted strategies tailored to the cultural needs of communities are needed to enhance the realization of Sustainable Development Goal #3:1 in Nigeria.
Nurse worry as a trigger for rapid response team activation improving outcomes: a retrospective cohort study in non-critical units
Authors: Gentil Luana L.S. , Nascimento Milena S. , Jaures Michele , de Carvalho Leonardo P. , Laselva Claudia R. , Brandi Simone
Published: January 2025

Background

Patients hospitalized outside of monitored environments may experience sudden clinical worsening requiring transfer to the Intensive Care Unit. Early detection based on the clinical nurse’s identification of the risk of clinical deterioration represents an opportunity to prevent serious adverse events. Nurse worry is defined as the use of clinical reasoning combined with intuition that precedes the patient’s clinical deterioration.

Objective

The objective of this study was to evaluate nurse worry as a trigger for rapid response team activation in patients hospitalized in non-critical units and its association with the need in ICU admission.

Methods

This retrospective cohort study utilized data retrieved from an anonymized institutional database used to monitor the actions of the rapid response team. Data collected from January 2021 to December 2022 were analyzed, encompassing patients over 18 years old admitted to non-critical units and evaluated by the rapid response team. Analyzed variables included demographic characteristics, MEWS score, and causes for activating the rapid response team, such as changes in vital signs and nurse worry. Main outcomes assessed were transfer to the ICU, medical procedures, and drug administration. Patients were divided into three groups for analysis: those triggered for RRT assessment exclusively by changes in vital signs, those triggered exclusively by nurse worry and those triggered by the nurse worry combined with changes in vital signs.

Results

A total of 4634 rapid response team consultations were included, with 1574 triggered by changes in vital signs, 1263 triggered by nurse worry and 1797 triggered by the nurse worry associated with changes in vital signs. The group with nurse concern showed a lower need for transfers to the ICU (40%) compared to the group with changes in vital signs (50%) p < 0.001 although there was no difference in relation to the need for medical procedures,17% in both groups.

Conclusion

The NW emerges as a relevant factor in triggering RRT and may be associated with improved outcomes, such as reduced need for ICU transfers. However, the observational design of the study does not allow for establishing causal relationships.
Neighborhood environment associations with cognitive function and structural brain measures in older African Americans
Authors: Chaar Dima L. , Tu Le , Moore Kari , Du Jiacong , Opsasnick Lauren A , Ratliff Scott M , Mosley Thomas H , Kardia Sharon L. R. , Zhao Wei , Zhou Xiang , Diez Roux Ana V , Faruque Fazlay S , Butler Kenneth R , Smith Jennifer A
Published: January 2025

Background

Since older adults spend significant time in their neighborhood environment, environmental factors such as neighborhood socioeconomic disadvantage, high racial segregation, low healthy food availability, low access to recreation, and minimal social engagement may have adverse effects on cognitive function and increase susceptibility to dementia. DNA methylation, which is associated with neighborhood characteristics as well as cognitive function and white matter hyperintensity (WMH), may act as a mediator between neighborhood characteristics and neurocognitive outcomes.

Methods

In this study, we examined whether DNA methylation in peripheral blood leukocytes mediates the relationship between neighborhood characteristics and cognitive function (N = 542) or WMH (N = 466) in older African American (AA) participants without preliminary evidence of dementia from the Genetic Epidemiology Network of Arteriopathy (GENOA).

Results

For a 1-mile buffer around a participant’s residence, each additional fast food destination or unfavorable food store with alcohol per square mile was nominally associated with a 0.05 (95%CI: 0.01, 0.09) and a 0.04 (0.00, 0.08) second improvement in visual conceptual tracking score, respectively. Also, each additional alcohol drinking place per square mile was nominally associated with a 0.62 (0.05, 1.19) word increase in delayed recall score, indicating better memory function (all p < 0.05). Neighborhood characteristics were not associated with WMH. We did not find evidence that DNA methylation mediates the observed associations between neighborhood characteristics and cognitive function.

Conclusions

The presence of fast food destinations and unfavorable food stores with alcohol was associated cognitive measures, possibly due to greater social interaction provided in these venues. However, replication of these findings is necessary. Further examination of the potential pathways between the neighborhood environment and cognitive function/WMH may allow the development of potential behavioral, infrastructural, and pharmaceutical interventions to facilitate aging in place and healthy brain aging in older adults, especially in marginal populations that are most at risk.
Drug-target binding affinity prediction based on power graph and word2vec
Authors: Hu Jing , Hu Shuo , Xia Minghao , Zheng Kangxing , Zhang Xiaolong
Published: January 2025

Background

Drug and protein targets affect the physiological functions and metabolic effects of the body through bonding reactions, and accurate prediction of drug-protein target interactions is crucial for drug development. In order to shorten the drug development cycle and reduce costs, machine learning methods are gradually playing an important role in the field of drug-target interactions.

Results

Compared with other methods, regression-based drug target affinity is more representative of the binding ability. Accurate prediction of drug target affinity can effectively reduce the time and cost of drug retargeting and new drug development. In this paper, a drug target affinity prediction model (WPGraphDTA) based on power graph and word2vec is proposed.

Conclusions

In this model, the drug molecular features in the power graph module are extracted by a graph neural network, and then the protein features are obtained by the Word2vec method. After feature fusion, they are input into the three full connection layers to obtain the drug target affinity prediction value. We conducted experiments on the Davis and Kiba datasets, and the experimental results showed that WPGraphDTA exhibited good prediction performance.
Echocardiographic phenotypes of diabetic myocardial disorder: evolution over 15 months follow-up in the ARISE-HF trial
Authors: Marwick Thomas H. , Lam Carolyn , Liu Yuxi , Del Prato Stefano , Rosenstock Julio , Butler Javed , Ezekowitz Justin , Ibrahim Nasrien E. , Tang W. H. Wilson , Zannad Faiez , Perfetti Riccardo , Januzzi James L.
Published: January 2025

Background

Diabetic myocardial disorder (DbMD, evidenced by abnormal echocardiography or cardiac biomarkers) is a form of stage B heart failure (SBHF) at high risk for progression to overt HF. SBHF is defined by abnormal LV morphology and function and/or abnormal cardiac biomarker concentrations.

Objective

To compare the evolution of four DbMD groups based on biomarkers alone, systolic and diastolic dysfunction alone, or their combination.

Methods

The Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial was a Phase 3 randomised trial of an aldose reductase inhibitor in patients with well-controlled type 2 diabetes mellitus (T2DM). The 1858 potential participants (age 67 ± 7 years; 50% women) were screened for SBHF based on abnormal echocardiography or biomarkers (N-terminal pro-B-type natriuretic peptide ≥ 40 ng/L or high sensitivity cardiac troponin T ≥ 10 ng/L [women] and ≥ 16 ng/L [men]). Exercise capacity (peak VO2) was reduced in 669 with DbMD (age 68 ± 7, 50% women), and peak VO2 was reassessed at 15 months.

Results

The 1463 (79%) participants with DbMD were allocated to four clusters; 907 (49%) showed isolated elevation of cardiac biomarkers, 301 (16%) with systolic dysfunction/hypertrophy, 162 (9%) with diastolic dysfunction and 93 (5%) comprised an overlap cluster (combined diastolic, systolic or LV geometric abnormalities). Reduced VO2 (< 75% predicted) was present in 669 (46%); 72% of those with both systolic and diastolic dysfunction, 56% of those with systolic dysfunction and LVH, 53% of those with diastolic dysfunction and 38% with biomarkers alone (p < 0.0001). In 669 patients followed over 15 months, there was a similar small decrement in VO2 in all groups.

Conclusions

Among individuals with T2DM and SBHF, reduced functional capacity is most prevalent in those with multiple physiological disturbances. However, there was no difference between phenogroups in the evolution of exercise intolerance.

Trial Registration: ARISE-HF, NCT04083339.
Improving 10-year cardiovascular risk prediction in patients with type 2 diabetes with metabolomics
Authors: Xie Ruijie , Seum Teresa , Sha Sha , Trares Kira , Holleczek Bernd , Brenner Hermann , Schöttker Ben
Published: January 2025

Background

Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MACE) in these patients.

Methods

Data from 10,257 to 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation. A total of 249 metabolites were measured with nuclear magnetic resonance (NMR) spectroscopy. Sex-specific LASSO regression with bootstrapping identified significant metabolites. The enhanced model’s predictive performance was evaluated using Harrell’s C-index.

Results

Seven metabolomic biomarkers were selected by LASSO regression for enhanced MACE risk prediction (three for both sexes, three male- and one female-specific metabolite(s)). Especially albumin and the omega-3-fatty-acids-to-total-fatty-acids-percentage among males and lactate among females improved the C-index. In internal validation with 30% of the UKB, adding the selected metabolites to the SCORE2-Diabetes model increased the C-index statistically significantly (P = 0.037) from 0.660 to 0.678 in the total sample. In external validation with ESTHER, the C-index increase was higher (+ 0.043) and remained statistically significant (P = 0.011).

Conclusions

Incorporating seven metabolomic biomarkers in the SCORE2-Diabetes model enhanced its ability to predict MACE in patients with type 2 diabetes. Given the latest cost reduction and standardization efforts, NMR metabolomics has the potential for translation into the clinical routine.

Graphical abstract
The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy
Authors: Ma Qinglong , Zhang Wenyang , Wu Kongming , Shi Lei
Published: January 2025

KRAS is one of the most mutated genes, driving alternations in metabolic pathways that include enhanced nutrient uptaking, increased glycolysis, elevated glutaminolysis, and heightened synthesis of fatty acids and nucleotides. However, the beyond mechanisms of KRAS-modulated cancer metabolisms remain incompletely understood. In this review, we aim to summarize current knowledge on KRAS-related metabolic alterations in cancer cells and explore the prevalence and significance of KRAS mutation in shaping the tumor microenvironment and influencing epigenetic modification via various molecular activities. Given that cancer cells rely on these metabolic changes to sustain cell growth and survival, targeting these processes may represent a promising therapeutic strategy for KRAS-driven cancers.
The role of luteinizing hormone activity in spermatogenesis: from physiology to clinical practice
Authors: Esteves Sandro C. , Humaidan Peter
Published: January 2025

The production of spermatozoa, a process known as spermatogenesis, is primarily controlled by follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-driven testosterone. LH acts on the Leydig cells, stimulating steroid production, predominantly testosterone, and activating critical inter-related spermatogenesis regulatory pathways. Despite evidence that exogenous gonadotropins containing LH activity can effectively restore spermatogenesis in males with hypogonadotropic hypogonadism, the use of these drugs to treat other forms of male infertility is the subject of an ongoing debate. In this review, we delve into the molecular properties and functions of LH activity in spermatogenesis regulation and explore available preparations for therapeutic use. We also examine the evidence regarding the effectiveness of LH-containing drugs in treating specific male infertility conditions and identify the main areas for future research. Our review highlights the critical role of LH in spermatogenesis and emphasizes the potential of LH-containing drugs in treating male infertility. However, further research is required to completely elucidate the mechanisms underlying the effects of LH activity on sperm production and to establish the most effective dosages and treatment durations.
Characterization of a chitinase from Trichinella spiralis and its immunomodulatory effects on allergic airway inflammation in mice
Authors: Xu Jia , Yao Ye , Zhuang Qisheng , Li Zixuan , Zhang Min , Wang Shouan , Hu Hongxin , Ye Jianbin
Published: January 2025

Background

A fundamental tenet of the hygiene theory is the inverse association between helminth infections and the emergence of immune-mediated diseases. Research has been done to clarify the processes by which helminth-derived molecules can inhibit immunological disorders. This study aimed to evaluate the ability of Trichinella spiralis chitinase (Ts-chit) to ameliorate the symptoms of allergic airway inflammation.

Methods

Recombinant Trichinella spiralis chitinase (rTs-chit) was expressed in Escherichia coli BL21, and its structural homology to murine acidic mammalian chitinase (AMCase) was comprehensively analyzed. The expression of Ts-chit was examined across all T. spiralis life stages. To explore its immunomodulatory potential, a murine model of allergen-induced airway inflammation was established. The effects of rTs-chit were evaluated by assessing airway hyperresponsiveness and cytokine profiles in bronchoalveolar lavage fluid and performing detailed histopathological and immunohistochemical analyses.

Results

Recombinant Ts-chit (rTs-chit) was successfully expressed in E. coli BL21, showing strong structural similarity to murine acidic mammalian chitinase (AMCase). Expression profiling revealed that Ts-chit is present throughout all stages of the T. spiralis life cycle. In an allergic airway inflammation model, rTs-chit reduced weight loss and lung inflammation, lowering inflammatory cell infiltration and Th2 cytokines (IL-4, IL-5, IL-13) while increasing the immunosuppressive cytokine IL-10. Additionally, rTs-chit treatment decreased the expression of GATA3, arginase-1, MCP-1, CCL-11, and AMCase, along with reducing OVA-specific IgE, IgG, and IgG1 levels, suggesting its potential as an immunomodulatory agent.

Conclusions

This study highlights rTs-chit’s potential as a therapeutic agent for allergic airway diseases, leveraging its structural similarity to host chitinases to regulate Th2 responses and inflammatory pathways. The findings provide new insights into helminth-derived proteins as promising candidates for immune-based therapies.

Graphical Abstract
Pathogen delivery route impacts disease severity in experimental Mycoplasma ovipneumoniae infection of domestic lambs
Authors: Jacobson Bryan Tegner , DeWit-Dibbert Jessica , Zanca LaShae , Sonar Sobha , Hardy Carol , Throolin Michael , Brewster Patricia C. , Andujo Kaitlyn , Jones Kerri , Sago Jonathon , Smith Stephen , Bowen Lizabeth , Bimczok Diane
Published: January 2025

M. ovipneumoniae is a respiratory pathogen that can cause mild to moderate pneumonia and reduced productivity in domestic lambs. However, studies on both natural and experimental M. ovipneumoniae infection have reported highly variable clinical signs and pathology. Here, we assessed the impact of administering M. ovipneumoniae to the upper respiratory tract (URT) or to the lower respiratory tract (LRT) of two-month-old specific pathogen-free lambs. Lambs were inoculated with PBS (control) or with ceftiofur-treated nasal wash fluid obtained from sheep with natural M. ovipneumoniae infection, monitored for eight weeks, and subsequently euthanized. All lambs in the URT and LRT groups developed a stable infection with M. ovipneumoniae. M. ovipneumoniae infection led to lower weight gains and mild respiratory disease, with significantly greater effects following LRT inoculation compared to URT inoculation. At necropsy, lambs inoculated via the LRT showed consolidation of the cranial lung lobes. In addition, histological signs of  alveolar, bronchiolar, and interstitial inflammation were significantly more severe in the LRT compared to the URT group. M. ovipneumoniae loads in the trachea and bronchi also were significantly higher after LRT than URT inoculation. Interestingly, 9/10 inoculated lambs also tested positive for M. haemolytica in nasal swab but not in bronchial swab samples. In summary, our study suggests that bypassing protective mechanisms of the URT by delivering respiratory pathogens to the LRT leads to more severe respiratory disease and lung damage than delivery to the URT.
Optimization and characterization studies of poultry waste valorization for peptone production using a newly Egyptian Bacillus subtilis strain
Authors: Saeed Hajar , Ragaey Anthony , Samy Ziad , Ashraf Viola , ElMostafa Aly , Ahmad Norhan , Bebawy Enjy , Sorour Nour ElHoda M. , El-Sayed Salwa M. , Bakry Ashraf , Ebeed Naglaa , Elhariry Hesham , El-Noby Thanaa , Abu-Hussien Samah H.
Published: January 2025

Valorization of poultry waste is a significant challenge addressed in this study, which aimed to produce cost-effective and sustainable peptones from poultry waste. The isolation process yielded the highly potent proteolytic B.subtilis isolate P6, identified through 16S rRNA gene sequencing to share 94% similarity with the B.subtilis strain KEMET024 (GenBank accession number PP694485.1) and deposited in MIRCEN culture collection, Cairo, Egypt as EMCC 998871. It reached optimal production levels during 24 h of incubation, with biomass at 2.5 g/L, protease activity at 455 U/mL, and total amino acid (TAA) concentration at 208 mg/mL. For screening the most significant factors for peptone production, the Plackett–Burman design identified meat and bone meal concentration as the main significant factor influencing total amino acid reaching 420 mg/mL. BOX-Behnken design optimized peptone production increasing its production level by twofold to reach 2850 U/mL of protease activity and 580 mg/mL of total amino acids. The produced peptone demonstrated a superior amino acid profile compared to commercial peptones, with a remarkably higher total amino acid content of 621.556 mg/g and elevated levels of essential amino acids like aspartic acid (37.745%), glutamic acid (90.876%), glycine (117.272%), and alanine (50.373%). Characterization revealed optimal pH and temperature conditions of around pH 8 and 50–60°C, respectively, for the proteolytic activity. The Michaelis–Menten and Lineweaver–Burk plots determined a Km of 0.5 mg/mL and Vmax of 174.08 U/mL suggesting cooperative substrate binding and providing insights into the enzyme’s maximum rate and affinity. The produced peptone exhibited minimal cytotoxicity at lower concentrations (≤ 1 mg/mL), with cell viability exceeding 94% against normal human skin fibroblast (HSF) cells. However, higher concentrations (≥ 3 mg/mL) displayed increased cytotoxic effects. Moreover, the results strongly indicate that the produced peptone, particularly at 0.5% concentration, is an effective nitrogen source for B. subtilis cultivation, demonstrating its potential for biotechnological applications. This study successfully valorized poultry waste by developing a sustainable and cost-effective alternative to commercial peptones, contributing to waste valorization and sustainable biotechnological processes.

Graphical abstract
Trends in Israel's Medical Administration subspecialty, 1987–2022
Authors: Angel Yoel , Goldshtein Hadar , Barel Nevo , Fire Gil , Halberthal Michael , Niv-Yagoda Adi
Published: January 2025

Background

Israel is unique in offering a formal subspecialty in Medical Administration and mandating it for physicians applying for senior roles. Data on the prevalence and characteristics of these specialists are limited.

Methods

The national registry of licensed physicians was used to identify all living physicians who completed the Medical Administration subspecialty by December 31, 2022. Data on year of medical licensing, city of residence, and list of additional recognized specialties along with their respective date of completion were extracted. Websites of key public health organizations were sampled to identify qualifications of persons in senior leadership positions.

Results

Since 1987, 277 physicians have completed the Medical Administration subspecialty, with a significant increase in annual certifications from 4.5 in 2015 (interquartile range [IQR] 4–6) to 13 (IQR 10.5–15) in 2022 (p < 0.001). Specialists completed the subspecialty a median of 18 years (IQR 13–21) post-licensing, with 269 physicians (97.1%) holding additional specialties, primarily in Internal Medicine, Pediatrics, Family Medicine, or Public Health. Compared to the general physician population, some base specialties like Public Health are over-represented while others, like Anesthesiology, are under-represented. Only 40 (14.4%) specialists reside outside major metropolitan areas. Nineteen (61.3%) general hospital CEOs, 2 (20%) psychiatric hospital CEOs, 13 (35.1%) Ministry of Health and 4 (7.8%) Sick Fund executives are specialists in Medical Administration (p < 0.005).

Conclusions

The steady growth in the number of specialists in Medical Administration demonstrates the sustainability and scalability of this model, which may serve as a template for other healthcare systems. However, the limited representation of these specialists in senior roles of some organizations, and their concentration within certain specialties and regions, indicates areas for policy attention to enhance leadership diversity and reduce healthcare disparities.
Evidence Communication Rules for Policy (ECR-P) critical appraisal tool
Authors: Danopoulos Evangelos , Aston John A. D. , Shah Aarushi , Schneider Claudia R.
Published: January 2025

Background

Scientific papers increasingly put forward scientific-based policy recommendations (SPRs) as a means of closing the circle of science, policy and practice. Assessing the quality of such SPRs is crucial, especially within the context of a systematic review. Here, we present ECR-P (Evidence Communication Rules for Policy)—a critical appraisal tool that we have developed, which can be used in assessing not only the quality of SPRs but also the quality of their evidence base and how effectively these have both been communicated.

Methods

The rationale behind ECR-P centres on three dimensions of quality; two are the well-established concepts of internal and external validity. Here, we introduce a third—evidence communication—encompassing both evidence veracity and quality of communication. Elements of the three dimensions of quality are considered within the context of the five rules of evidence communication. These are as follows: inform, not persuade; offer balance, not false balance; disclose uncertainties; state evidence quality and pre-empt misunderstandings.

Results

Development of ECR-P has been carried out by an interdisciplinary team and was piloted with a systematic review reported more fully elsewhere. ECR-P comprises a set of preliminary considerations which capture key aspects for the assessment, leading on to the main tool whose structure is domain-based, each domain mapping to one of the five rules of evidence communication. The domains include 25 signalling questions designed to obtain essential information for the critical appraisal. The questions focus on either the study’s evidence or the policy recommendations. Domain-based judgement is derived from responses to the signalling questions and an accompanying algorithm, followed by an overall quality judgement.

Conclusions

ECR-P has been designed to provide a standardised and transparent approach to assess the quality and communication of SPRs and their evidence base. The tool, which could be applied across all scientific fields, has been developed to fit primarily with the systematic reviewing process but could also serve as a stand-alone tool. Besides review assessors, it can also be used by policymakers, researchers, peer reviewers, editors and any other stakeholders interested in evidence-based policymaking and high-quality evidence communication. We encourage further independent testing of the tool in real-world evidence-based research.
Health symptoms and associated factors in times of a pandemic: a population-based study
Authors: Gerbecks J. , Plevier C. , Yzermans C. J. , Dückers M. L. A. , Baliatsas C.
Published: January 2025

Background

Non-specific symptoms, such as headaches and sleep problems, are more common after disasters. They can become chronic, and impact emotional and physical functioning. However, limited research has focused on such symptoms in the context of a pandemic. This study investigated the association between perceived impact of the COVID-19 pandemic, and prevalence, duration, and severity of health symptoms.

Methods

A cross-sectional survey using validated questionnaires was conducted shortly after the first COVID-19 wave in 2020, with nearly 46,000 adult participants from Utrecht, the Netherlands. Negative binomial regression analyses were performed to assess the relationship between pandemic-related factors and symptom reports, adjusting for demographics, chronic conditions, lifestyle, and socio-economic status.

Results

Perceived impact of the pandemic on stress levels, loneliness, anxiety and depression was consistently and significantly associated with symptom report, duration, and perceived severity. Incidence rate ratio’s (IRR) varied from 1.17 to 1.29. Delayed care during the pandemic was associated with severity of symptoms (IRR = 1.63; 99% confidence intervals (CI): 1.20–2.20). People that (suspected) got COVID-19 infected were at higher risk of symptom report, duration, and perceived severity (IRR around 1.20–1.28).

Conclusion

As with other disasters, the perceived impact of an immediate threat such as a pandemic can influence health symptoms, independent of health or socio-demographic factors. Understanding symptom patterns and risk factors can assist healthcare professionals and policymakers in identifying vulnerable groups, symptoms profiles, and improving care and support during and after pandemics.
Overexpression of multiple cytochrome P450 genes with and without knockdown resistance mutations confers high resistance to deltamethrin in Culex quinquefasciatus
Authors: Chamnanya Saowanee , Kiddela Benyapa , Saingamsook Jassada , Nachaiwieng Woottichai , Lumjuan Nongkran , Somboon Pradya , Yanola Jintana
Published: January 2025

Background

The cytochrome P450s-mediated metabolic resistance and the target site insensitivity caused by the knockdown resistance (kdr) mutation in the voltage-gated sodium channel (vgsc) gene were the main mechanisms conferring resistance to deltamethrin in Culex quinquefasciatus from Thailand. This study aimed to investigate the expression levels of cytochrome P450 genes and detect mutations of the vgsc gene in deltamethrin-resistant Cx. quinquefasciatus populations in Thailand.

Methods

Two field-collected strains of Cx. quinquefasciatus, Cq_SP and Cq_NiH, were selected with deltamethrin to generate the resistant strains Cq_SP-R and Cq_NiH-R, respectively. Bioassays were tested on larvae and adults of each strain according to WHO methods. Eight cytochrome P450 genes were analyzed for the expression level using quantitative real time-PCR. The cDNA of mosquitoes was amplified and sequenced for four fragments of vgsc gene. The kdr L1014F mutation and the haplotype of the CYP9M10 gene were detected in survivor and dead mosquitoes after exposure to the deltamethrin WHO test paper. Statistical analyses were performed using Fisher’s exaction test.

Results

Bioassay tests revealed a significantly higher resistance level in Cq_SP-R than in Cq_NiH-R strains in both larvae and adults. All eight cytochrome P450 genes were significantly overexpressed in larvae of Cq_NiH-R strain compared to the parent and susceptible Cq_Sus strains. The CYP6AA7 and CYP9J34 genes had the highest expression ratios, exceeding 24-fold in Cq_NiH-R larvae. In Cq_SP-R strain, the CYP4H34 and CYP9J34 genes were overexpressed in both stages. The kdr L1014F mutation was found in Cq_SP-R and its parent Cq_SP strains with a significantly higher mutant allele frequency in the survivor mosquitoes than in dead mosquitoes (P < 0.0001). The V240M and novel L925F mutations were found only in Cq_SP-R strain. Heterozygous genotype for the D-Cu( +)/Cu(–) of CYP9M10 gene was detected in Cq_NiH and Cq_NiH-R strains but other strains were mostly homozygous for the Cu(–)/Cu(–).

Conclusions

Overexpression of multiple cytochrome P450 genes alone has a relatively minor impact on resistance. The combined mechanisms of cytochrome P450- and kdr-mediated resistance result in significantly higher resistance to deltamethrin in Cx. quinquefasciatus. This study supports sustainable public health initiatives in Thailand to address the evolving challenges of insecticide resistance.
Boswellic acid synergizes with low-dose ionizing radiation to mitigate thioacetamide-induced hepatic encephalopathy in rats
Authors: Saad Dina E. , Mansour Somaya Z. , Kandil Eman I. , Hassan Asmaa , Moawed Fatma S. M. , Elbakry Mustafa M. M.
Published: January 2025

Hepatic encephalopathy (HE) is a syndrome that arises from acute or chronic liver failure. This study was devised to assess the impact of a combination of boswellic acid (BA) and low doses of gamma radiation (LDR) on thioacetamide (TAA)-induced HE in an animal model. The effect of daily BA treatment (175 mg/kg body weight, for four weeks) and/or fractionated low-dose γ-radiation (LDR; 0.25 Gy, twice the total dose of 0.5 Gy) was evaluated against TAA (200 mg/kg, intraperitoneal) twice-weekly for four weeks to induce liver damage and HE in rats. TAA-exposed rats exhibited a significant elevation in serum activities of liver enzymes (GGT, ALP) and plasma ammonia levels at P < 0.05 (Duncan’s test) compared to the control group. Moreover, there was an increase in the levels of proinflammatory cytokines (IL6, IL12, IL18) in the TAA-exposed animals accompanied by a depletion in the activities of paraoxonase-1 and neurotransmitter contents compared with normal control rats (P < 0.05). However, the administration of BA alone or in combination with LDR led to improvements in liver and brain parameter indices. Furthermore, the histopathological assessments of liver and brain tissues supported the findings of the biochemical investigations. From the statistical analysis, it can be concluded that the combined administration of BA and exposure to LDR may possess potential hepatoprotective effects against hepatic encephalopathy-associated hyperammonemia and the consequent damage to the liver and brain. This study proposes that a combination of therapeutic approaches, LDR and BA could be a new therapeutic candidate for the management of hepatic encephalopathy.
Impact of hyper- and hypothermia on cellular and whole-body physiology
Authors: Iba Toshiaki , Kondo Yutaka , Maier Cheryl L. , Helms Julie , Ferrer Ricard , Levy Jerrold H.
Published: January 2025

The incidence of heat-related illnesses and heatstroke continues to rise amidst global warming. Hyperthermia triggers inflammation, coagulation, and progressive multiorgan dysfunction, and, at levels above 40 °C, can even lead to cell death. Blood cells, particularly granulocytes and platelets, are highly sensitive to heat, which promotes proinflammatory and procoagulant changes. Key factors in heatstroke pathophysiology involve mitochondrial thermal damage and excessive oxidative stress, which drive apoptosis and necrosis. While the kinetics of cellular damage from heat have been extensively studied, the mechanisms driving heat-induced organ damage and death are not yet fully understood. Converse to hyperthermia, hypothermia is generally protective, as seen in therapeutic hypothermia. However, accidental hypothermia presents another environmental threat due to arrhythmias, cardiac arrest, and coagulopathy. From a cellular physiology perspective, hypothermia generally supports mitochondrial homeostasis and enhances cell preservation, aiding whole-body recovery following resuscitation. This review summarizes recent findings on temperature-related cellular damage and preservation and suggests future research directions for understanding the tempo-physiologic axis.
Investigating continuous intention to use metaverse in higher education institutions: a dual-staged structural equation modeling-artificial neural network approach
Authors: Ali Reham Adel , Soliman Mohamed , Weahama Muhammad Roflee , Assalihee Muhammadafeefee , Mahmud Imran
Published: January 2025

The current study explores metaverse adoption among higher education institutions (HEIs) in the light of a theoretical framework to empower future perspectives of the metaverse as a learning platform. Even though this technology was just recently introduced to the higher education sector, very few attempts have been made to evaluate its impact. The purpose of this research is to analyze the elements that influence the continuous intention (CI) to utilize the metaverse technology in learning. The technology acceptance model (TAM) and the self-determination theory (SDT) are both included in this study. A questionnaire was developed and distributed to students attending private universities in order to obtain the data that was needed for the proposed model. Using a hybrid approach that consists of partial least squares structural equation modeling (PLS-SEM) and an artificial neural network (ANN) model, which combines a linear PLS model with compensation and a nonlinear ANN model without compensation, the effect of CI on using the metaverse as a learning platform is investigated. This approach was chosen because it contains both of these types of models. When it comes to explaining the use of metaverse technology among students attending higher education institutions in Egypt, the research findings suggested that autonomy and perceived usefulness (PU) are major determinants. Nevertheless, the continuing intention was unaffected by the perceived ease of use (PEOU) of the product. Furthermore, according to the data provided by the ANN model, the most significant predictors are relatedness, PEOU, autonomy, and PU. It has been determined that the results obtained from the PLS-SEM and ANN modes are identical. Additionally, both theoretical and practical implications are discussed in this article.
Tuning electronic structure and carrier transport properties through crystal orientation control in two-dimensional Dion-Jacobson phase perovskites
Authors: Kim Byunggeol , Park Jeehong , Kang Donghee , Jung Na Eun , Kim Kitae , Ryu Hongsun , Jang Joon Ik , Park Soohyung , Yi Yeonjin
Published: January 2025

Two-dimensional halide perovskites are attracting attention due to their structural diversity, improved stability, and enhanced quantum efficiency compared to their three-dimensional counterparts. In particular, Dion-Jacobson (DJ) phase perovskites exhibit superior structural stability compared to Ruddlesden-Popper phase perovskites. The inherent quantum well structure of layered perovskites leads to highly anisotropic charge transport and optical properties. Therefore, controlling the preferred crystal orientation (parallel or perpendicular) is crucial for optimizing device performance. This work presents a rational strategy to control parallel and perpendicular crystal growth in C6N2H16PbI4 (4AMPPbI4)-based DJ phase perovskite thin films. We demonstrate that crystal orientation depends on crystal growth rates, which can be controlled by varying the solvent composition, antisolvent, and annealing temperature. Direct and inverse photoelectron spectroscopy reveals that the electronic structure of 4AMPPbI4, including its work function, ionization energy, and electron affinity, is orientation-dependent. Different orientations significantly affect carrier transport as confirmed by single-carrier devices. This study highlights the critical role of crystal orientation in DJ phase perovskites for designing high-performance optoelectronic devices.

Graphical Abstract