bluuebunny/crossref_metadata_2025 huggingface dataset:
The ‘Photosynthetic C1 pathway’ links carbon assimilation and growth in plants
Authors: Jardine Kolby , Gallo Luiza , Roth Melissa , Upadhyaya Shivani , Northen Trent , Kosina Suzanne , Tcherkez Guillaume , Eudes Aymerick , Domigues Tomas , Greule Markus , Keppler Frank
Published: April 2024

As atmospheric CO2 rises, increases in photosynthesis and plant growth are routinely documented across ecosystems globally. Although primarily studied in relation to photorespiration, serine metabolism in chloroplasts may play a key role in plant CO2 fertilization responses by linking CO2 assimilation with growth. However, little information is available on the in vivo activity of the plastidic phosphorylated serine pathway. Here, we show that the serine phosphate pathway is part of a ‘photosynthetic C1 pathway’ and demonstrate its high activity in foliage of a C3 tree where it rapidly integrates photosynthesis directly with C1 metabolism contributing to new biomass via methyl transfer reactions and imparting a large natural 13C-depleted signature. Using 13CO2-labelling, we show that leaf serine, the S-methyl group of leaf methionine, pectin methyl esters, and the associated methanol released during cell wall expansion during growth, are directly produced from photosynthetically-linked C1 metabolism, unrelated to photorespiration, within minutes of light exposure. We speculate that the photosynthetic C1 pathway and its key enzyme methionine synthase is highly conserved across the photosynthetic tree of life and may have evolved with oxygenic photosynthesis by providing a mechanism of directly linking carbon assimilation with growth. Although the rise in atmospheric CO2 inhibits major metabolic pathways like photorespiration in C3 plants, our results suggest that the photosynthetic C1 pathway may accelerate and represents a ‘missing link’ between enhanced photosynthesis and growth rates of modern plants and ecosystems during terrestrial CO2 fertilization under a changing climate.
The influence of anxiety sensitivity on observing in mindfulness among clinical populations with anxiety and/or depressive disorders
Authors: Diamond Danielle Moskow , Curtiss Joshua , Carpenter Joseph K. , Ito Masaya , Hofmann Stefan G.
Published: April 2024

Background: Many individuals who engage in mindfulness techniques experience decreased anxiety. Yet some who engage in mindfulness, particularly those with panic disorder (PD) or elevated anxiety sensitivity (AS) note heightened anxiety when focusing on particular sensations. The Five Facet Mindfulness Questionnaire (FFMQ) is the most widely utilized mindfulness questionnaire- however, the Observe facet has shown variability in the literature. This study therefore aimed to determine whether specific aspects of the Observe facet of the FFMQ differ in individuals with PD or elevated anxiety sensitivity (AS).
Methods: We examined a clinical sample of 1521 Japanese individuals who completed online self-report questionnaires, including the Five Facet Mindfulness Questionnaire (FFMQ).
Results: Several multiple indicator multiple cause (MIMIC) models investigated differential item functioning among the items in the Observe facet of the FFMQ, based on PD and/or AS. This process was repeated to examine the relationship between the Anxiety Sensitivity Index-3 (ASI-3) subscales and particular items of the Observe facet. Increased AS correlated with more observing generally, and increased AS was associated with greater scores on observing internal items and lower scores on observing external items. When PD and AS were analyzed simultaneously, only AS remained significant. The cognitive subscale showed the same pattern of results as the total ASI-3 subscale.
Conclusions: The findings of this study reveal that AS may modulate the mindfulness experience. The study sheds light on the importance of understanding where an individual observes in order to tailor mindfulness treatments for individuals.
The peripheral epigenome predicts white matter volume contingent on developmental stage: An ECHO study
Authors: Spencer Sophie. , Harker Samantha A. , Barry Fatoumata , Beauchemin Jennifer , Braden B. Blair , Burton Phoebe , D’sa Viren , Koinis-Mitchell Daphne , Mennenga Sarah E. , Deoni Sean C.L. , Lewis Candace R.
Published: April 2024

Epigenetic processes, including DNA methylation, are emerging as key areas of interest for their potential roles as biomarkers and contributors to the risk of neurodevelopmental, psychiatric, and other brain-based disorders. Despite this growing focus, there remains a notable gap in our understanding of how DNA methylation correlates with individual variations in brain function and structure. Additionally, the dynamics of these relationships during developmental periods, which are critical windows during which many disorders first appear, are still largely unexplored. The current study extends the field by examining if peripheral DNA methylation of myelination-related genes predicts white matter volume in a healthy pediatric population [N = 250; females = 113; age range 2 months-14 years; Mage = 5.14, SDage = 3.60]. We assessed if DNA methylation of 17 myelin-related genes predict white matter volume and if age moderates these relationships. Results highlight low variability in myelin-related epigenetic variance at birth, which rapidly increases non-linearly with age, and that DNA methylation, measured at both the level of a CpG site or gene, is highly predictive of white matter volume, in early childhood but not late childhood. These novel findings propel the field forward by establishing that DNA methylation of myelin-related genes from a peripheral tissue is a predictive marker of white matter volume in children and is influenced by developmental stage. The research underscores the significance of peripheral epigenetic patterns as a proxy for investigating the effects of environmental factors, behaviors, and disorders associated with white matter.
Elastogenesis Stimulation by Minoxidil or Nebivolol Reduces Premature Aging of the Aortic Wall in Diabetic Mice
Authors: Henry Auberi , Vanalderwiert Laetitia , Wahart Amandine , Berrio Daniel A Carvajal , Brauchle Eva M , Schenke-Layland Katja , Brinckmann Juergen , Steenbock Heiko , Debelle Laurent , Six Isabelle , Faury Gilles , Jaisson Stéphane , Gillery Philippe , Durlarch Vincent , Sartelet Hervé , Maurice Pascal , Bennasroune Amar , Martiny Laurent , Duca Laurent , Romier Béatrice , Blaise Sébastien
Published: April 2024

Background
The approximately fifteen-year reduction in life expectancy observed in diabetic patients, compared to non-diabetic individuals, is believed to be attributed to the early onset of cardiovascular diseases. Among the molecular actors involved in the occurrence of cardiovascular complications, the remodeling of elastic fibers (EFs) in favor of degradation rather than neosynthesis is significant.
Objective
This study aims to modulate the elastogenesis/elastolysis balance in the arterial wall of diabetic db/db mice (a diabetic model where the leptin receptor is deficient) to limit the premature aging of their EFs and aortic stiffening.
Methods
Mice are treated with two antihypertensive agents: minoxidil (an ATP-sensitive potassium (KATP) channel opener) or nebivolol (a β-blocker also active on KATP channels). The degree of wear and functionality of EF are assessed after these treatments. We complement this analysis by identifying molecular actors from smooth muscle cell cultures.
Results
Our data show that by applying these antihypertensive agents in cultured vascular smooth muscle cells in vitro and in diabetic mice, we efficiently stimulate elastogenesis and inhibit elastolysis. Therefore, treatments restore functional EFs and limit their degradation. This brings blood pressure values of diseased mice close to normal ones (as in unaffected mice). Elastogenesis pathway stimulation and elastolysis inhibition are induced by the opening of sensitive KATP channels and the regulation of the forkhead box transcription factor (FOXO1).
Conclusion
Monitoring these two pathways could, therefore, be sufficient to limit the premature aging of the aorta and to reduce the occurrence of hypertension, atherosclerosis, and aneurysms in diabetic patients.
Do the gait domains change in PD patients with freezing of gait during their ‘interictal’ period?
Authors: Zhao Jiahao , Liu Chen , Wan Ying , Zhu Xiaobo , Song Lu , Liu Zhenguo , Gan Jing
Published: April 2024

Objectives
Freezing of Gait (FOG) is one of the disabling symptoms in patients with Parkinson's Disease (PD). While it is difficult to early detect because of the sporadic occurrence of initial freezing events. Whether the characteristic of gait impairments in PD patients with FOG during the ‘interictal’ period is different from that in non-FOG patients is still unclear.
Methods
The gait parameters were measured by wearable inertial sensors. Exploratory factor analysis was used to investigate the inherent structure of diverse univariate gait parameters, with the aim of identifying shared characteristics among the gait variables.
Results
This cross-sectional study involved 68 controls and 245 PD patients (167 without FOG and 78 with FOG). The analysis yielded six distinct gait domains which were utilized to describe the impaired gait observed during the “interictal” period of FOG. Both PD-nFOG and PD-FOG groups exhibited significant impairments in the pace domain, kinematic domain, gait phase domain, and turning process domain compared to the healthy control. The gait phase domain was different in the PD-FOG group compared to the PD-nFOG group (p corrected = 0.004, Cohen's d = -0.46). And it was identified as independent risk factor for FOG (OR = 1.64, 95% CI = 1.05–2.55, p = 0.030), as well as other risk factors: gender (OR = 2.67, 95% CI = 1.19–5.99, p = 0.017), MDS-UPDRS IV score (OR = 1.23, 95% CI = 1.10–1.37, p < 0.001), and PIGD subscore (OR = 1.50, 95% CI = 1.30–1.73, p < 0.001). The model demonstrated a correct discrimination rate of 0.78 between PD-FOG and PD-nFOG, with an area under the receiver operating characteristic curve (AUC) of 0.87.
Conclusions
FOG was found to be associated with abnormal alterations in the gait phase domain during the interictal period. Models constructed using gait phase domain, PIGD subscore, gender, and severity of motor complications can better differentiate freezers from no-freezers during ‘interictal’ period.
Systematic Comparison Suggesting Intranasal Transplantation was the Best Route of Administration of Human Umbilical Cord Mesenchymal Stem Cells(hUC-MSCs) in Hypoxic-ischaemic brain damage (HIBD)Rat Model
Authors: Zhou Linyan , Zheng Kun , Zhang Ruibo , He Guangzhen , Xu Jinyun , Jiang Hao , Ren Lan , Zhou Miao , Zhao Liang , Liu Wenting , Gu Jiaowei
Published: April 2024

Aims: Hypoxic-ischaemic brain damage (HIBD) remains a common sequelae of various nervous system diseases. Human umbilical cord derived mesenchymal stem cells (hUC-MSCs) transplantation was considered to be promising in treating HIBD.
However, the best route of administration to transplant hUC-MSCs remains open. In this study, we systematically compared the three routes of administration —— the IntraVenous (IV)， IntraCerebral (IC) and IntraNasal (IN) administration for the first time to guide the best clinical practice.
Methods: The HIBD rat models were built on the 7th (PN7) day after birth of rats. The three routes of administration of hUC-MSCs were conducted on the 14th day (PN14) after birth of rats. And theses three groups (HIBD+IV, HIBD+IN, HIBD+IC) were compared with HIBD and sham group on motor function、learning and memory function improvement by hanging wire, vertical pole test, and Morris water maze (MWM) test on 10th (PN10) and 21st (PN21) day after birth of rats. Moreover, the pathological tests were used to compare the pathological repair effects of three routes of administration: the morphological changes of brain tissue were tested by Haematoxylin and Eosin staining (HE staining); the proliferation of reactive astrocytes were compared by detecting the expression of glial fibrillar acidic protein (GFAP) by immunohistochemistry; and the number of neuronal apoptosis in cortex and hippocampus were compared by TUNEL staining.
Results: The motor function of rats in HIBD group was significantly lower than that in sham group on the PN10, both in hanging wire and vertical pole tests (P< 0.0001). This shows the effectiveness of our HIBD model. All of the three routes of administration groups showed significant improvement of motor and learning function, reducing the liquefaction necrosis, GFAP expression, and apoptosis rate of nerve cells in cerebral cortex and hippocampus of HIBD rats. Among the three routes of administration groups, the functional improvement and pathological repair effect of intracerebral (IC) and intranasal (IN) administration were better than those of intravenous (IV) administration stem cells. And no significant difference between intracerebral and intranasal administration. As intranasal (IN) administration is more compliant and convenient in clinical practice than intracerebral (IC) administration, thus we suggest that intranasal (IN) administration is the best route of administration of hUC-MSCs on HIBD treatment.
A latent profile analysis of the functions of binge eating
Authors: O’Loghlen Elyse , Galligan Roslyn , Grant Sharon
Published: April 2024

Objective
The aim of this study was to identify naturally occurring groups of individuals experiencing binge eating (BE) symptoms based on their endorsement of varied functions of BE.
Method
Adults (N = 646) with self-reported BE symptoms were examined using latent profile analysis to identify differentiated profiles based on eight established functions of BE. Profiles were also compared on measures of BE symptoms, eating disorder psychopathology, internal shame, body shame, psychological distress, adverse childhood experiences, and demographic variables.
Results
A four-profile solution was selected balancing goodness-of-fit and interpretability. Profiles identified were Emotion Avoidance, Classic, Emotion Reactivity, and Complex, with profiles differing primarily on emotion- and trauma-related functions of BE, and varying on all associated characteristics examined, with the Complex profile showing the most adverse associations.
Discussion
The identification of these distinct profiles suggests that individuals present with differentiated, inter-related patterns or reasons for BE. These clinically relevant profiles may inform binge-eating disorder intervention choice and the targeting of specific maintenance factors within profiles. Further research is needed to examine the clinical utility of these profiles in informing the most suitable psychological treatment for an individual.
Effect of internet usage on the life satisfaction of the spousal caregivers of disabled elderly
Authors: Li Jia , Liang Nan , Wu Yue , Ma Xiangcao , Liao Zangyi
Published: April 2024

This empirical study assesses the impact of internet usage on the life satisfaction of the spousal caregivers responsible for disabled elderly. Drawing upon the data from the China Health and Retirement Longitudinal Study (CHARLS) (released in November 2023), we investigated the health status and life satisfaction of the spousal caregivers for disabled elderly with the recent rapid development of the internet employing a stratified Proportionate to Size Sampling (PPS) approach. We examined whether the life satisfaction of the elders’ spousal caregivers is associated with Internet use and whether Internet adoption can moderate intergenerational relationships, interpersonal interactions, and political-engagement of such caregivers. The study analyzed 760 samples (with an average age of 60.31 years, and rural households comprising 77.14%). We found there has a positive correlation between internet usage and the life satisfaction of the spousal caregivers. This finding enhances our understanding of the relationship between the internet usage and the life satisfaction of such individuals. Additionally, this study promotes the advancement of the internet to cater to the population aging, aids the elderly in bridging the digital divide, and offers a theoretical foundation for the government to establish targeted elderly-friendly internet policies.
The impact of education level on all-cause mortality in patients with atrial fibrillation
Authors: Sztaniszlav Aron , Björkenheim Anna , Magnuson Anders , Bryngelsson Ing-Liss , Edvardsson Nils , Poci Dritan
Published: April 2024

The association between socioeconomic status and cardiovascular morbidity and mortality is well known, but data on the influence of education level on mortality in individuals with atrial fibrillation (AF) are scarce. We investigated education level as a predictor of all-cause mortality in patients diagnosed with AF. This retrospective cohort study used a database created from several Swedish nationwide registries to identify all patients hospitalized with a diagnosis of AF from 1995 through 2008. Education level was categorized as primary, secondary, and academic. All-cause mortality risk was estimated in subpopulations defined by Charlson´s Comorbidity Index and several comorbidities. A total of 272,182 patients (56% male; mean age 72 ± 10 years) were followed over a five-year period. Cox regression models showed a reduction in all–cause mortality risk with increased education level. Hazard ratios (HR) relative to primary education remained significant after stratification and adjustment for several confounders: secondary education HR = 0.88; 95% CI: 0.86–0.89; p < 0.001; academic education HR = 0.70; 95% CI: 0.67–0.72; p < 0.001. Subpopulation analyses further confirmed that the relative risk reduction associated with a higher education level was statistically significant, regardless of comorbidity.
Bio-physical and socio-economic challenges, farmers’ perception of success and 14- year soil fertility trajectories in smallholder organic market gardens of North-East Zimbabwe
Authors: Tumbure Akinson , Chiduwa Mazvita , Mazuruse Gideon , Nyagadza Brighton , Kusena Kudzai
Published: April 2024

Some researchers have argued that organic agriculture does not yield intended benefits in African smallholder settings because of degraded soils and lack of organic resources. A multidisciplinary case study analysis of selected organic farming gardens in Makoni, Zimbabwe was done to explore farmer resources, perceptions, market access, preferences, and soil fertility status using survey and interview tools and soil analysis. Lack of agricultural water was identified as a major production challenge by 75% of respondents. Unavailable and unreliable transport and low income from sales were identified as the two main challenges (84 % of respondents) in selling organic produce. Roughly 95% of interviewed farmers currently sell their organic produce not marked as organic in the local district. We also reveal that 14-year organic management of soil fertility at MOFA has resulted in increased on average pH (range 0.6 – 2.1 units), and available P (range x6 – x26) compared to adjacent uncultivated areas. Soil organic matter either stayed the same or increased at 5 out of 6 sites and exchangeable Ca, Mg, and K increased by at least 157%, 21%, and 10%, respectively, all compared to uncultivated land. These improvements are likely the reason why 64% of farmers said they had observed yield increases. We conclude that 14 years of organic agriculture has led to the improvement of soil fertility in the initially low-fertility gardens as measured by pH, organic matter, and nutrient content. However, we recommend strengthening the market access to organic produce to sustain organic farming for smallholder farmers in Zimbabwe.
Crosstalk between mitochondrial and lysosomal co-regulators defines clinical outcomes of breast cancer by integrating multi-omics and machine learning
Authors: Chen Huilin , wang zhenghui , Shi Jiale , Peng Jinghui
Published: April 2024

Background
The impact of mitochondrial and lysosomal co-dysfunction on breast cancer patient outcomes is unclear. The objective of this study is to develop a predictive machine learning (ML) model utilizing mitochondrial and lysosomal co-regulators in order to enhance the prognosis for individuals with BC.
Methods
Differences and correlations of mitochondrial and lysosome related genes were screened and validated. WGCNA and univariate Cox regression were employed to identify prognostic mitochondrial and lysosomal co-regulators. ML was utilized to further selected these regulators as mitochondrial and lysosome-related model signature genes (mlMSGs)and constructed models. The association between the immune and mlMSGs score was investigated through scRNA-seq. Finally, the expression and function of the key gene SHMT2 were confirmed through in vitro experiments.
Results
According to the C-index, the coxboost+ Survivor-SVM model was identified as the most suitable for predicting outcomes in BC patients. Subsequently, patients were stratified into high and low risk groups based on the model, which demonstrated strong prognostic accuracy. While the overall immunoinfiltration of immune cells was decreased in the high-risk group, it was specifically noted that B cell mlMSGs activity remained diminished in high-risk patients. Additionally, the study found that SHMT2 promoted the proliferation, migration, and invasion of BC cells.
Conclusion
This study shows that the ML model accurately predicts the prognosis of BC patients. Analysis conducted through the model has identified decreased B-cell immune infiltration and reduced mlMSGs activity as significant factors influencing patient prognosis. These results may offer novel approaches for early intervention and prognostic forecasting in BC.
Detection and clinical analysis of human coronavirus infection with acute respiratory tract infection in children in the Xiamen area, China, in 2021-2023
Authors: Su Dequan , Xu Yong jun , Zhang Jinqiang , Ye Pingping , Ou Chunmei , Lin Xiaoyan , Su Wei , Zhuo Zhiqiang
Published: April 2024

Purpose:To investigate human coronavirus (HCoV) infection with acute respiratory tract infection in children in the Xiamen area, China, and to analyze the clinical features of HCoV infection in children.
Methods: A total of 15 283 children with acute respiratory tract infection were hospitalized in Xiamen City Children's Hospital from January 2021 to June 2023. Nasopharyngeal swabs from these children were assessed for the presence 13 respiratory tract-associated viruses, namely, Influenza A virus, adenovirus, bocavirus, rhinovirus, human coronavirus, influenza A virus H1N1, parainfluenza virus, chlamydia, metapneumovirus, influenza B virus, Mycoplasma pneumoniae, respiratory syncytial virus (RSV), and seasonal H3N2 virus using real-time fluorescence quantitative PCR. The clinical symptoms and signs of HCoV-positive children were analyzed and compared with those of RSV-infected children hospitalized during the same period.
Results:(1) Of the 15 283 children with acute respiratory infections, 8624 were positive for HCoV.(2) The HCoV detection rate was 0.87% (54/6230) during 2021, 0.82% (53/6439) during 2022, and 1.53% (40/2612) during 2023. The HCoV detection rates (%) for January to December were 0.98, 0.86, 0.83, 0.96, 0.67, 0.57, 0.66, 0.98, 1.02, 1.66, 1.89 and 1.23, respectively.(3) Eighty cases of acute respiratory tract infection with HCoV alone were hospitalized, including 33 cases of bronchopneumonia, 23 cases of acute bronchitis, 10 of acute tonsillitis, 10 of acute tonsillitis, and 4 of acute laryngitis.(4) The common clinical manifestations of HCoV-only infection were cough (72 cases), fever (64 cases), and wheezing (23 cases).(5) The proportion of wheezing in the RSV group was significantly higher than that in the HCoV group (P<0.05), but there were no significant differences observed in other clinical manifestations, the incidence of complications, and proportion of cases requiring mechanical ventilation between HCoV group and 103 RSV infected children (P>0.05).
Conclusion: Between January 2021 and June 2023, the detection rate of HCoV in Xiamen was 0.96%. The clinical manifestations and severity of acute respiratory tract infections due to HCoV were similar to those with respiratory syncytial virus infection.
The Brain’s First “Traffic Map” through Unified Structural and Functional Connectivity (USFC) Modeling
Authors: SILEMEK Arzu HAS , Chen Haitao , Sati Pascal , Gao Wei
Published: April 2024

The brain’s white matter connections are thought to provide the structural basis for its functional connections between distant brain regions but how our brain selects the best structural routes for effective functional communications remains poorly understood. In this study, we propose a Unified Structural and Functional Connectivity (USFC) model and use an “economical assumption” to create the brain’s first “traffic map” reflecting how frequently each structural connection segment of the brain is used to achieve the global functional communication system. The resulting USFC map highlights regions in the subcortical, default-mode, and salience networks as the most heavily traversed nodes and a midline frontal-caudate-thalamus-posterior cingulate-visual cortex corridor as the backbone of the whole brain connectivity system. Our results further revealed a striking negative association between structural and functional connectivity strengths in routes supporting negative functional connections as well as much higher efficiency metrics in the USFC connectome when compared to structural and functional ones alone. Overall, the proposed USFC model opens up a new window for effective brain connectome modeling and provides a considerable leap forward in brain mapping efforts for a better understanding of the brain’s fundamental communication mechanisms.
Statistical analysis for investigating determinants influencing diarrhea in Yemeni children under five: Insights from the 2022-2023 Multiple Indicator Cluster Survey
Authors: Satty Ali , Salih Mohyaldein , Abdalla Faroug A. , Mahmoud Ashraf F. A. , Gumma Elzain A. E. , Khamis Gamal Saad Mohammed , Adam Ahmed M. A. , Hassaballa Abaker A. , Hamed Omer M. A. , Mohammed Zakariya M. S.
Published: April 2024

Diarrheal disease remains a significant cause of preventable morbidity and mortality in the pediatric population, particularly among children below five years of age. Although the occurrence of diarrheal episodes is on the decline, its impact continues to escalate at a concerning rate among children under the age of five, especially in developing countries. The objective of this paper is to investigate the determinants associated with diarrhea in Yemeni children younger than five years, drawing on data from the latest edition of the Multiple Indicator Cluster Survey (MICS) Yemen conducted in 2022-2023. To investigate determinants associated with the occurrence of childhood diarrhea, bivariate analysis and multivariable logistic regression were utilized. The findings of this study suggest that age group 6-23, unimproved sanitation, and low-income households are associated with high risk of diarrhea in children under five years of age in Yemen. The study contributes additional evidence regarding determinants that should be prioritized in public health strategies geared towards reducing diarrheal prevalence among Yemeni children.
Recurrent Visceral Leishmaniasis in a Case with Interleukin-12 Receptor Beta-1 Deficiency
Authors: uygun hatice , oren Ayse Ceyda , Sahinoglu Esra Pekpak , akbayram sinan
Published: April 2024

Purpose In this study, we present the case of a children who was followed up for recurrent visceral leishmaniasis and diagnosed with IL-12Rβ1 deficiency.Methods A female patient who received Bacille Calmette-Guérin (BCG) vaccine 2 months after birth and developed visceral leishmaniasis at the age of 91 months was subsequently diagnosed with IL-12Rβ1 deficiency. The patient's diagnosis and treatment process were examined retrospectively.Results IL-12Rβ1 deficiency is an autosomal recessive disease characterized by susceptibility to recurrent and/or severe infections caused by weakly pathogenic mycobacteria and salmonella. Infections with other intramacrophagic organisms may also occur, although rarely. Based on this information, it is believed that the mutation in the IFN-γ/IL-12 axis in our patient predisposed her to recurrent Leishmania infections.Conclusion This study adds to the limited literature on IL12RB1 deficiency as a cause of VL. Patients diagnosed with VL should be evaluated immunologically, as recurrent Leishmania infections may occur in those with IL-12Rβ1 defects.
Reliability of beat-to-beat blood pressure variability in older adults
Authors: Lohman Trevor , Sible Isabel J. , Shenasa Fatemah , Engstrom Allison C. , Kapoor Arunima , Alitin John Paul M. , Gaubert Aimee , Thayer Julian F. , Ferrer Farrah , Nation Daniel A.
Published: April 2024

Blood pressure variability (BPV) is emerging as an important risk factor across numerous disease states, including cerebrovascular and neurodegenerative disease in older adults. However, there is no current consensus regarding specific use cases for the numerous available BPV metrics. There is also little published data supporting the ability to reliably measure BPV across metrics in older adults.
BPV metrics were derived from continuous beat-to-beat blood pressure monitoring data. Two sequential 7-minute waveforms were analyzed. Absolute and relative reliability testing was performed. Differences between antihypertensive medication users and non-users on BPV metric reliability was also assessed.
All sequence and dispersion based BPV metrics displayed good test-retest reliability. A measure of BP instability displayed only moderate reliability. Systolic and diastolic average real variability displayed the highest levels of reliability at ICC= .87 and .82 respectively. Additionally, systolic average real variability was the most reliable metric in both the antihypertensive use group, and the no antihypertensive use group.
Beat-to-beat dispersion and sequence-based metrics of BPV can be reliably obtained from older adults using noninvasive continuous blood pressure monitoring. Average real variability may be the most reliable and specific beat-to-beat blood pressure variability metric due to its decreased susceptibility to outliers and low frequency blood pressure oscillations.
Predicting relapsed/refractory disease in childhood hemophagocytic lymphohistiocytosis: A 13-year single-institute retrospective study in Thailand
Authors: Kusontammarat Pattranan , Choed-Amphai Chane , Sathitsamitphong Lalita , Sontichai Watchareewan , Natesirinilkul Rungrote , Charoenkwan Pimlak
Published: April 2024

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease. Relapsed/refractory disease is the main cause of death. This study is aimed to determine the prognostic indicators for relapsed/refractory disease in childhood HLH (R/R HLH).
Methods: Infants and children under 18 years of age who were diagnosed with HLH according to HLH-2004 criteria, MAS-HLH criteria for rheumatologic diseases, or H-score undergoing treatment in Chiang Mai University hospital between 2010 – 2022 were included. Demographic data, clinical characteristics, and laboratory parameters were retrospectively reviewed.
Results: Out of 86 childhood HLH cases, 30 patients (34.9%) experienced R/R HLH. All patients with primary HLH developed R/R HLH. The most common form of secondary HLH was infection-associated hemophagocytic syndrome (IAHS), comprising 43 cases. Of these, 37.2% had relapsed or refractory disease. Univariable analysis identified several potential risk factors for R/R HLH, including younger age, severe disease status, higher HLH-2004 criteria scores, higher H-scores, overt DIC, higher pSOFA scores, and increased levels of aspartate aminotransferase, total bilirubin, and direct bilirubin. Multivariable logistic regression analysis revealed that a pSOFA score of ≥ 8 and age < 3 years were independent risk factors for R/R HLH, with adjusted odds ratios of 6.35 (95% confidence interval [CI], 1.18 – 34.19; p = 0.032) and 3.62 (95% CI, 1.04 – 12.63; p = 0.044), respectively.
Conclusions: Children with HLH who have a pSOFA score of ≥ 8, or are younger than 3 years, are at a higher risk of relapsed or refractory disease. Further evaluation of management strategies in this context is warranted.
The Therapeutic Effect of Aerobic Exercise Training on Female Drug Addicts is Achieved by Improving the Community Structure of Intestinal
Authors: Wang Hangping , Bai Ruolan , Yuan Jixue , Shen Ruxuan , Yang Jiangping , Yuan Cunfeng
Published: April 2024

Background
This study aimed to investigate the effect of aerobic exercise on the gut microbiota structure of female drug addicts.
Results
Twelve weeks of aerobic exercise training may improve gut microbial diversity and increase the abundance of beneficial taxa. Following the exercise intervention, the operational taxonomic units(OTUs) counts in the exercise intervention groups increased with variable degrees when compared with the control groups. Furthermore, the OTU count of the MC group increased significantly. After the exercise intervention, principal component analysis revealed the following results: (1) at the phylum level, the dominant taxa, mainly composed of the phyla Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria, did not change significantly, suggesting that the composition of the gut microbiota may not be affected by exercise; (2) at the family or order levels, the MC group exhibited significantly higher abundance of Enterobacteriaceae and Enterobacterales when compared with the BC group (P < 0.05). Similarly, at the order level, when compared with the BX group, the MX group had a significantly higher abundance of Atopobiaceae, Porphyromonadaceae, Pasteurellaceae, and Pasteurellales (P < 0.05); (3) at the genus level, exercise significantly increased the abundance of Prevotella and Roseburia in the MC group when compared with the BC group (P < 0.05). Additionally, the abundance of Escherichia-Shigella and Megamonas was significantly lower in the MX group than in the BX group (P < 0.05). In summary, these beneficial bacteria can be used as new targets for targeted microbiota intervention in female drug addicts.
Conclusion
Female drug addicts who underwent 12 weeks of aerobic exercise training effectively improved their intestinal flora structure and had shifts in the intestinal microbial species. However, the impact of exercise on the gut microbiota of drug addicts varies by drug type. The mechanism of the effects of exercise intervention in drug addiction may be associated with the activation of the gut’s innate immunity.
Investigation of Aopp, Total Sulphydryl Group (T-sh), Seroplasmin Levels in Sheep Wi̇th Zoonotic Liver Parasitosis
Authors: OĞUZ Fatma ERTAŞ , KÖMÜROĞLU Ahmet Ufuk , AYAN Adnan , KILINÇ Özlem ORUNÇ , YÜKSEK Nazmi
Published: April 2024

The aim of inthe present study was to investigate aopp, total sulfhydryl group (t-sh) and seroplasmin levels in zoonotic liver parasitosis in sheep. this study was carried out in Iğdır province. For this purpose, 75 sheep were grouped as healthy, Fasciola spp., Echinococcus spp., Dicrocoelium spp., Echinococcus spp. + Dicrocoelium spp. The levels of the specified parameters were measured in these groups. According to the results, AOPP level in the fasciolosis group was remarkably higher than all other groups (p < 0.05). The serum AOPP level in the E + D group was found to be significantly higher compared to the control and dicrocoelium spp. groups (p < 0.05). Echinococcus spp. group was s remarkably higher than the dicrocoelium spp. group (p < 0.05). The ceruloplasmin level in the control group was found to be significantly lower compared to the Echinococcosis, fasciolosis and dicrocoeliosis groups (p < 0.05). Total sulfhydryl level was found to be lower in the patient groups compared to the healthy group, but this value was not significant. According to these results, it can be said that cellular damage occurs in liver parasitism. These parameters are thought to be valuable in terms of prognosis in parasitic infections. It is also thought that oxidative cell damage occurs in the attack of zoonotic liver parasites in which the immune response decreases. It is thought that this study will serve as a guide for future research.
Diversity, Bio-ecology and population dynamics of insect pests of pigeon pea in eastern India
Authors: CHINNASAMY SELVARAJ , PATRA SANDIP , SAMANTA ARUNAVA , SAMANTA SNIGDHA , SARKAR SURAJ
Published: April 2024

Field and laboratory experiments were conducted at Bidhan Chandra Krishi Viswavidyalaya (BCKV) to assess the diversity, bio-ecology and impact of weather variables on population dynamics of insect pests in pigeon pea during kharif season of 2016-2018. The results revealed that a total of 65 insect pest species were recorded in pigeon pea in the eastern India. Among them, 8, 30 and 27 numbers of species were classified as major, minor and negligible pests. Diversity study showed minimum variability between the two years. The average duration of life cycle of Helicoverpa armigera, Melanagromyza obtusa, Exelastis atomosa and Maruca vitrata were recorded at 43.16±0.74, 26.25±0.58, 36.5 ± 1.25 and 28.0 ± 1.50 days under relative humidity and temperature regime of 75 ± 2% and 28 ± 2°C, respectively. The population dynamics showed that H. armigera, M. vitrata, M. obtusa, E. atomosa and A. clavipes reached their peak during 8th standard meteorological week (SMW), 52nd SMW, 8th SMW, 7th SMW and 4th SMW with 1.40-1.66 larvae/plants, 14.73-15.60 larvae/plant, 208.33-212.33 maggot and pupae/plant, 9.73-10.53 larvae/plant and 43.00-47.0 grubs/plant during 2016-17 and 2017-18, respectively. The correlation analysis revealed that temperature (maximum and minimum) showed positive influence on larval population of H. armigera, M. obtusa, E. atomosa and A. clavipes whereas, maximum and minimum relative humidity and rainfall impacted negatively during both the years. In case of M. vitrata, maximum and minimum temperature demonstrated significant negative correlation, whereas maximum and minimum relative humidity showed positive and significant correlation during both the years. Whereas, rainfall showed non-significant negative correlation on pest population of all the pod borers of pigeon pea.
Efficacy of an AAV vector encoding a thermostable form of glucocerebrosidase in alleviating symptoms in a Gaucher disease mouse model
Authors: Futerman Anthony , Milenkovic Ivan , Blumenreich Shani , Hochfelder Ariel , Azulay Aviya , Biton Inbal , Zerbib Mirie , Oren Roni , Tsoory Michael , Joseph Tammar , Fleishman Sarel
Published: April 2024

Almost all attempts to date at gene therapy approaches for monogenetic disease have used the amino acid sequences of the natural protein. In the current study, we use a designed, thermostable form of glucocerebrosidase (GCase), the enzyme defective in Gaucher disease (GD), to attempt to alleviate neurological symptoms in a GD mouse that models type 3 disease, i.e. the chronic neuronopathic juvenile subtype. Upon injection of an AAVrh10 (adeno-associated virus, serotype rh10) vector containing the designed GCase (dGCase) into the left lateral ventricle of Gba-/-;Gbatg mice, a significant improvement in body weight and life-span was observed, compared to injection of the same mouse with the wild type enzyme (wtGCase). Moreover, a reduction in levels of glucosylceramide (GlcCer), and an increase in levels of GCase activity were seen in the right hemisphere of Gba-/-;Gbatg mice, concomitantly with a significant improvement in motor function, reduction of neuroinflammation and a reduction in mRNA levels of various genes shown previously to be elevated in the brain of mouse models of neurological forms of GD. Together, these data pave the way for the possible use of modified proteins in gene therapy for lysosomal storage diseases and other monogenetic disorders.
Integrated analysis of hepatocellular carcinoma reveals disparate subtype of prognosis significance
Authors: Jiang Feng-le , Jiang Xin , Zhang Zhe-ting , Wang Jian-min , Liu Jing-feng
Published: April 2024

Hepatocellular carcinoma (HCC) is a complex disease with various contributing factors. Most clinical biomarkers fall short in providing an accurate prognostic evaluation for HCC patients. This underscores the urgent need to gain insight into the role of key molecules in disease progression and to develop more dependable prognosis prediction models. Our study reported that molecular subtyping based on transcriptome profiling could serve as an independent predictor of HCC prognosis. The joint use of molecular subtyping and American Joint Committee on Cancer (AJCC) staging system was superior to each individual factor as a prognostic indicator. The multi-omics analysis revealed the activation of signal transduction, cytokines interaction, cell proliferation pathways in category A (CA) tumors, while organic compound metabolism pathways were enriched in category B (CB) tumors. These findings indicated significant and substantial molecular differences among prognostically relevant subtypes. This research highlighted the potential for widespread development and validation of molecular subtyping to improve clinical management of HCC patients. Through gaining a better understanding of the molecular variances among subtypes, such as different pathogenic pathways, this approach could guide more effective and tailored therapeutic strategies.
Contrast-enhanced ultrasound predicts surgical margin positivity in patients with breast cancer who underwent partial mastectomy
Authors: Shima Hiroaki , Satomi Fukino , Kondo Yuta , Nishikawa Noriko , Uno Satoko , Wada Asaka , Noda Ai , Kyuno Daisuke , Kameshima Hidekazu , Ohmura Tosei , Sugita Shintaro , Yama Naoya , Takemasa Ichiro
Published: April 2024

Background
The clinical disadvantage of positive margins in partial mastectomy for patients with operable breast cancer is clear and must be avoided; however, there is still room for improvement. The usefulness of contrast-enhanced ultrasound (CEUS) in diagnosing spread is currently well known. The CEUS-enhanced area for breast cancer tends to be wider than that observed in B-mode and probably includes cancer cells. This study aimed to analyze the correlation between characteristic findings and positive for margins in order to ultimately prove potential usefulness of CEUS in making the surgical margin negative.
Methods
We retrospectively evaluated the data of 142 patients with breast cancer who underwent partial mastectomy to explore the effect on positive margins when the CEUS staining area was smaller than the B-mode visualized mass (CEUS-B ≤ 0).
Results
CEUS-B ≤ 0 was associated with significantly more positive margins (p = 0.0467). CEUS-B was also extracted as an independent predictor on multivariate analysis.
Conclusions
The findings of no enhancement outside the area of visible tumor on CEUS but not visualized outside the area of visible tumor on B-mode might be a risk factor for a positive surgical margins.
Visual Tract Integrity before and after gene therapy in congenital Achromatopsia
Authors: Hillel Abramovitch , Bick Atira , Nitzan Guy , Deena Elul , Ayelet Mckyton , Eyal Banin , Netta Levin
Published: April 2024

CNGA3-achromatopsia is a rare hereditary syndrome caused by dysfunction of cone photoreceptors, resulting in low acuity, photoaversion and complete color blindness. Trials utilizing gene therapy have recently been initiated, but only limited clinical improvement has been observed. To explain this suboptimal outcome, we used diffusion tensor image (DTI) to assess visual pathway integrity in three CNGA3-achromatopsia patients before and after gene therapy, and compared them to 16 normally sighted adults. No significant differences from normal subjects in optic tract and radiation integrity were detected. Fiber integrity reduction was observed in the occipito-callosal fibers. These differences showed some normalization after treatment, but inter-subject variability was evident. Specifically, the observed changes were related to radial diffusivities, reflecting fiber myelination or glial cell alterations. Despite the fundamental role of cone photoreceptors in human sight, primary visual pathways in CNGA3-achromatopsia patients are comparable to those of healthy individuals. Nevertheless, splenial fibers, which are involved in a later phase of visual processing, appear to be affected by the altered cortical activity, being less cohesive in naïve patients. Following treatment, these fibers regain some integrity, suggesting that novel information is processed within the visual cortex and that integrity may be restored to better transmit this information.
Paramos in Peril: case study on a blue gold hotspot of central Colombia
Authors: Murad Cesar Augusto , Pearse Jillian , Huguet Carme
Published: April 2024

Paramos, unique and biodiverse ecosystems found solely in the high mountain regions of the tropics, are under threat. Despite their crucial role as primary water sources and significant carbon repositories in Colombia, they are deteriorating rapidly and garner less attention than other vulnerable ecosystems like the Amazon rainforest. Their fertile soil and unique climate make them prime locations for agriculture and cattle grazing, often coinciding with economically critical deposits such as coal which has led to a steady decline in paramo area. Anthropic impact was evaluated using multispectral images from Landsat and Sentinel over 37 years, on the Guerrero and Rabanal paramos in central Colombia which have experienced rapid expansion of mining and agriculture. Our analysis revealed that since 1984, the Rabanal and Guerrero paramos have lost 47.96% and 59.96% of their native vegetation respectively, replaced primarily by crops, pastures, and planted forests. We detected alterations in the spectral signatures of native vegetation near coal coking ovens, indicating a deterioration of paramo health and potential impact on ecosystem services. Consequently, human activity is reducing the extent of paramos and their efficiency as water sources and carbon sinks, potentially leading to severe regional and even global consequences.