Background: Axonal degeneration has been recognized as a key early contributor to the clinical presentation and pathogenesis of amyotrophic lateral sclerosis (ALS). Activation of the calcium-dependent cysteine protease calpain-2 is considered a critical effector of axonal degeneration. Based on evidence supporting a potential benefit of calpain-2 modulation in ALS and other neurodegenerative diseases, Amylyx developed AMX0114, an antisense oligonucleotide (ASO) inhibitor of calpain-2. This phase 1 study will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AMX0114 in people with ALS. Methods: LUMINA is planned to be conducted at ~15 sites in North America enrolling approximately 48 participants randomized 3:1 to receive AMX0114 or placebo. After study completion, an open-label extension study of AMX0114 will be implemented if data supports a positive benefit-risk profile. Results: The primary endpoints of the study include the incidence of adverse events (AEs), serious AEs, and dose-limiting toxicities. Secondary and tertiary endpoints include PK measurements (plasma and cerebrospinal fluid [CSF] levels of AMX0114), PD biomarkers, and functional measures of ALS progression. Conclusions: LUMINA is a first-in-human study evaluating the safety, tolerability, PK, and PD of AMX0114, the first ASO targeting calpain-2 in adult participants with ALS. Enrollment is planned to begin in Canada in early 2025.

Background: Amyotrophic Lateral Sclerosis (ALS) leads to progressive functional decline and reduced survival. Identifying clinical predictors like ALSFRS-R and FVC is essential for prognosis and disease management. Understanding progression profiles based on diagnostic characteristics supports clinical trial design and assessment of treatment response. This study evaluates disease progression and survival predictors in ALS patients from the CNDR. Methods: 1565 ALS patients in the CNDR were analyzed to assess baseline ALSFRS-R, FVC, time from symptom onset to diagnosis, and their association with disease progression and survival. Results: At diagnosis, ALSFRS-R was 44.7 (SD = 5.46), with 72.3% scoring ≥44. Mean FVC was 84.2% (SD = 23.3), with 78.3% of patients having FVC ≥65%. ALSFRS-R declined at 1.06 points/month (SD = 1.33), with faster progression in patients diagnosed within 24 months (1.61 points/month). Patients with ALSFRS-R ≥44 had a median survival of 41.8 months, compared to 30.9 months for those <44 (p < 0.001). Similarly, FVC ≥65% was associated with longer survival (35.4 vs. 29.5 months, p = 0.002). Conclusions: ALSFRS-R and FVC at diagnosis predict survival and inform clinical decision-making. These findings highlight the importance of early diagnosis and targeted interventions to slow disease progression and improve patient outcomes.

Background: ALS is a progressive neurodegenerative disease without a cure and limited treatment options. Edaravone, a free radical scavenger, was shown to slow disease progression in a select group of patients with ALS over 6 months; however, the effect on survival was not investigated in randomized trials. The objective of this study is to describe real-world survival effectiveness over a longer timeframe. Methods: This retrospective cohort study included patients with ALS across Canada with symptom onset up to three years. Those with a minimum 6-month edaravone exposure between 2017 and 2022 were enrolled in the interventional arm, and those without formed the control arm. The primary outcome of tracheostomy-free survival was compared between the two groups, accounting for age, sex, ALS-disease progression rate, disease duration, pulmonary vital capacity, bulbar ALS-onset, and presence of frontotemporal dementia or C9ORF72 mutation using inverse propensity treatment weights. Results: 182 patients with mean ± SD age 60±11 years were enrolled in the edaravone arm and 860 in the control arm (mean ± SD age 63±12 years). Mean ± SD time from onset to edaravone initiation was 18±10 months. Tracheostomy-free survival will be calculated. Conclusions: This study will provide evidence for edaravone effectiveness on tracheostomy-free survival in patients with ALS.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease resulting in muscle weakness, dysarthria and dysphagia, and ultimately respiratory failure leading to death. Half of the ALS patients survive less than 3 years, and 80% of the patients survive less than 5 years. Riluzole is the only approved medication in Canada with randomized controlled clinical trial evidence to slow the progression of ALS, albeit only to a modest degree. The Canadian Neuromuscular Disease Registry (CNDR) collects data on over 140 different neuromuscular diseases including ALS across ten academic institutions and 28 clinics including ten multidisciplinary ALS clinics. Methods: In this study, CNDR registry data were analyzed to examine potential differences in ALS care among provinces in time to diagnosis, riluzole and feeding tube use. Results: Significant differences were found among provinces, in time to diagnosis from symptom onset, in the use of riluzole and in feeding tube use. Conclusions: Future investigations should be undertaken to identify factors contributing to such differences, and to propose potential interventions to address the provincial differences reported.

Stored product insects show high adaption to hypoxia and hypercapnia, but the underlying mechanism is still unclear. Herein, a comparative transcriptome on 4th adzuki bean weevil (Callosobruchus chinensis) instar larvae was studied to clarify the response mechanisms to hypoxia (HA) and hypoxia/hypercapnia (HHA) using NextSeq500 RNA-Seq. Transcript profiling showed a significant difference in HA or HHA exposure both quantitatively and qualitatively. Compared with control, 631 and 253 genes were significantly changed in HHA and HA, respectively. Comparing HHA with HA, 1135 differentially expressed genes (DEGs) were identified. The addition of hypercapnia made a complex alteration on the hypoxia response of bean weevil transcriptome, carbohydrate, energy, lipid and amino acid metabolism were the most highly enriched pathways for genes significantly changed. In addition, some biological processes that were not significantly enriched but important were also discussed, such as immune system and signal transduction. Most of the DEGs related to metabolism both in HHA and HA were up-regulated, while the DEGs related to the immune system, stress response or signal transduction were significantly down-regulated or suppressed. This research reveals a comparatively full-scale result in adzuki bean weevil hypoxia and hypoxia/hypercapnia tolerance mechanism at transcription level, which might provide new insights into the genomic research of this species.

Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.

A fungal pathogen, Helminthosporium gramineum Rabehn f.sp. echinochloae (HGE), has been developed as a mycoherbicidal agent for the control of barnyardgrass in China. Under greenhouse conditions, the effect of the pathogen on disease incidence, mortality, and dry weight reduction of barnyardgrass was tested to determine the potential of this mycoherbicide. Field experiments during 2007 and 2008 showed that the conidia of HGE displayed excellent activity on barnyardgrass and good activity on a few other weed species. The HGE treatment increased the rice yield when compared with the untreated control and had no negative impact on the rice plant. In addition, the progression of HGE infection and the alteration of cellular ultrastructure in infected barnyardgrass were observed by using scanning and transmission electron microscopes. After infection, cell membranes of barnyardgrass leaves were found dramatically changed, and the ultrastructure of cells was severely deformed. This study clearly shows the scope of HGE as a potential mycoherbicide for control of barnyardgrass in agricultural cropping systems and has laid the groundwork for further studies on the mode of infection and the nosogenesis of HGE.

The middle to late Holocene history and early Anglo-European settlement impacts on Santa Rosa Island, California, were studied through the analysis of sediments in a small estuarine marsh. A 5.4-m-long sediment core produced a stratigraphic and pollen record spanning the last 5200 yr. Three major zones are distinguishable in the core. The lowermost zone (5200 to 3250 yr B.P.) represents a time of arid climate with predominantly marine sediment input and high Chenopodiaceae and Ambrosia pollen values. The intermediate zone (3250 yr B.P. to 1800 A.D.) is characterized by greater fresh water input and high values for Asteraceae and Cyperaceae pollen and charcoal particles. The uppermost zone (1800 A.D. to present) documents the unprecedented erosion, sedimentation, and vegetation change that resulted from the introduction of large exotic herbivores and exotic plants to the island during Anglo-European settlement. The identification of pollen grains of Torrey Pine (Pinus torreyana) documents the persistence of this endemic species on the island throughout the middle to late Holocene.

Pompe disease is a lysosomal storage disorder caused by a deficiency of theenzyme acid alpha-glucosidase. Patients have skeletal muscle and respiratoryweakness with or without cardiomyopathy. The objective of our review was tosystematically evaluate the quality of evidence from the literature toformulate evidence-based guidelines for the diagnosis and management ofpatients with Pompe disease. The literature review was conducted usingpublished literature, clinical trials, cohort studies and systematicreviews. Cardinal treatment decisions produced seven management guidelinesand were assigned a GRADE classification based on the quality of evidence inthe published literature. In addition, six recommendations were made basedon best clinical practices but with insufficient data to form a guideline.Studying outcomes in rare diseases is challenging due to the small number ofpatients, but this is in particular the reason why we believe that informedtreatment decisions need to consider the quality of the evidence.

The Chinese Spectral Radioheliograph (CSRH) is under construction in Mingantu station of NAOC in China. Now, CSRH-I which includes antenna, receiver and correlator in decimetric wave range has been established. This paper introduced calibration on CSRH and present some results of data processing.

This study was conducted to determine the effects of soy isoflavones on changes in body and tissue weight and on insulin-like factor I (IGF-I) and peroxisome proliferator-activated receptor-γ (PPARγ) gene and protein expression in muscle and adipose tissues in Chinese Guangxi minipig, as a model for studying human nutrition. A total of 72 male Chinese Guangxi minipigs were fed basal diet (control, Con), low dose of soy isoflavones and high dose of soy isoflavones (HSI). The results showed that HSI increased the body weight (BW) gain and fat percentage of minipigs (P < 0.05). In addition, the serum concentrations of IGF-I and interleukin-6 were increased by high levels of soy isoflavones (P < 0.05). Furthermore, a diet containing soy isoflavones enhanced IGF-I mRNA expression levels in longissimus muscle, but decreased these levels in perirenal fat. However, the mRNA and protein expression levels of PPARγ in longissimus muscle and subcutaneous adipose tissue were both increased when compared with the Con. The data indicated that soy isoflavones regulated the BW gain and fat percentage of Chinese Guangxi minipigs, which also showed changes in IGF-I system and PPARγ. However, further research is required to clarify the causative relationship.

Somatostatin (SS) is a hormone that inhibits the secretion of growth hormone. Immunization against SS can promote the growth of animals. A novel SS-VP22 fused vaccine, pEGS2SS-V, was constructed from pEGS2SS plasmid with a VP22 gene fragment. Two times of immunization with pEGS2SS-V-induced anti-SS antibodies in mice. Compared with mice immunized with pEGS2SS and 0.85% saline, the growth performance of mice immunized with pEGS2SS-V was increased by 14.1% (P < 0.05) and 48.4% (P < 0.01) on the 2nd week after the first vaccination, respectively. The results indicated that the effects of the somatostatin DNA vaccine could be improved effectively by VP22 gene adjuvant.