Miracle-dz/UniFAR-FTUs huggingface dataset:
AGE, GROWTH, AND REPRODUCTIVE PATTERNS OF DALL'S PORPOISE (PHOCOENOIDES DALLI) IN THE CENTRAL NORTH PACIFIC OCEAN

Life history parameters were estimated for Dall's porpoise, Phocoenoides dalli, from biological specimens collected in the western Aleutian Islands, during 1981–1987. Of 2,033 males and 3,566 females examined, reproductive data were available for 1,941 males and 1,906 females; ages were determined for 813 males and 1,297 females. Female sexual maturity was based on the presence of one or more corpus on either ovary; 845 were sexually immature and 1,061 were sexually mature. Two estimates of female average age at sexual maturity (ASM) were 3.8 and 4.4 yr; average length at sexual maturity (LSM) was 172 cm. Males were considered sexually mature when evidence of spermatogenesis was detected; 1,136 were sexually immature and 805 were sexually mature. Two estimates of male ASM were 4.5 and 5.0 yr; LSM was 179.7 cm. Physical maturity was assessed for 246 males and 446 females by examining the degree of fusion in thoracic vertebral epiphyses. For both sexes, the average age at physical maturity was 7.2 yr. Average length at physical maturity was 202.6 cm for males and 192.7 cm for females. Average lengths of physically mature males (x= 198.1 cm, SE = 0.8566) and females (x= 189.7 cm, SE = 0.4002) were significantly different(P < 0.0001). Early postnatal growth was rapid in both sexes. A secondary growth spurt in both mass and length was characteristic for both sexes; the increase in length preceded the mass increase by 1–2 yr. Average length at birth (LOB) was approximately 100 cm; birth mass averaged 11.3 kg (SE = 0.0772). By the time the umbilicus had healed (<2 mo), the average length and mass had increased to 114.1 cm and 23.8 kg, respectively. Gestation period based on projections using LOB was 12 mo, but this was considered an overestimate. Calving was modal, centered in early July; an annual reproductive interval was indicated. Among the sexually mature females, 120 were pregnant, 55 were pregnant and lactating, 321 were pregnant with colostrum, and 33 were “resting. ” By 3 July (95% CI =x 1 d), 50% of births had occurred, during each of the seven years sampled. The ovulation rate was estimated at 0.914 ovulations per average reproductive year. Enlarged follicles and recent ovulations were observed in postpartum females in late July.
Cooperation of Fungal Laccase and Glucose 1-Oxidase in Transformation of Björkman Lignin and Some Phenolic Compounds

Summary A screening of wood-rotting basidiomycete fungi was conducted for glucose 1-oxidase (GOD) and laccase (LAC) production as well as for ligninolytic activity measured by a Rhemazol reaction. The results showed that genera rich in GOD are lignin degraders as well as effective producers of extracellular LAC. The fungi poor in GOD neither showed LAC, nor ligninolytic activity. The Björkman lignin and 3 phenolic compounds, hydroquinone and syringic and vanillic acids, were tested on the sequential activity of LAC and GOD. In the presence of LAC, quinoid intermediates formed from Björkman lignin and phenolic compounds were observed. The addition of GOD caused a diminution of the quinone level. During incubation of Björkman lignin with LAC and GOD depolymerization occurred, and in the experiments omitting GOD the quantities of low molecular products were markedly lower. Consequently, the consecutive ping-pong activity of LAC and GOD reduced the polymerization and improved the efficiency of depolymerization processes.
AMELIE speeds Mendelian diagnosis by matching patient phenotype and genotype to primary literature

An automated pipeline parses primary literature about Mendelian diseases to rank patient candidate causative genes, thereby accelerating diagnosis. Finding a gene in the stacks Genetic disease diagnosis can be time-consuming because of the extensive literature searching required. To speed this process, Birgmeier et al. developed AMELIE (Automatic Mendelian Literature Evaluation), an end-to-end machine learning approach with web interface that finds relevant literature supporting the disease causality of genetic variants and their association with different clinical presentations. The pipeline also parses the literature to rank the most likely candidate causative genes that best explain a given patient’s symptoms and outperformed similar algorithms when compared side by side. AMELIE could help clinicians narrow the field of possible causative genes, shortening the time required for expert diagnosis of Mendelian diseases. The diagnosis of Mendelian disorders requires labor-intensive literature research. Trained clinicians can spend hours looking for the right publication(s) supporting a single gene that best explains a patient’s disease. AMELIE (Automatic Mendelian Literature Evaluation) greatly accelerates this process. AMELIE parses all 29 million PubMed abstracts and downloads and further parses hundreds of thousands of full-text articles in search of information supporting the causality and associated phenotypes of most published genetic variants. AMELIE then prioritizes patient candidate variants for their likelihood of explaining any patient’s given set of phenotypes. Diagnosis of singleton patients (without relatives’ exomes) is the most time-consuming scenario, and AMELIE ranked the causative gene at the very top for 66% of 215 diagnosed singleton Mendelian patients from the Deciphering Developmental Disorders project. Evaluating only the top 11 AMELIE-scored genes of 127 (median) candidate genes per patient resulted in a rapid diagnosis in more than 90% of cases. AMELIE-based evaluation of all cases was 3 to 19 times more efficient than hand-curated database–based approaches. We replicated these results on a retrospective cohort of clinical cases from Stanford Children’s Health and the Manton Center for Orphan Disease Research. An analysis web portal with our most recent update, programmatic interface, and code is available at AMELIE.stanford. edu.
A High-Throughput Cellular Screening Assay for Small-Molecule Inhibitors and Activators of Cytoplasmic Dynein-1-Based Cargo Transport

Cytoplasmic dynein-1 (hereafter dynein) is a six-subunit motor complex that transports a variety of cellular components and pathogens along microtubules. Dynein’s cellular functions are only partially understood, and potent and specific small-molecule inhibitors and activators of this motor would be valuable for addressing this issue. It has also been hypothesized that an inhibitor of dynein-based transport could be used in antiviral or antimitotic therapy, whereas an activator could alleviate age-related neurodegenerative diseases by enhancing microtubule-based transport in axons. Here, we present the first high-throughput screening (HTS) assay capable of identifying both activators and inhibitors of dynein-based transport. This project is also the first collaborative screening report from the Medical Research Council and AstraZeneca agreement to form the UK Centre for Lead Discovery. A cellular imaging assay was used, involving chemically controlled recruitment of activated dynein complexes to peroxisomes. Such a system has the potential to identify molecules that affect multiple aspects of dynein biology in vivo. Following optimization of key parameters, the assay was developed in a 384-well format with semiautomated liquid handling and image acquisition. Testing of more than 500,000 compounds identified both inhibitors and activators of dynein-based transport in multiple chemical series. Additional analysis indicated that many of the identified compounds do not affect the integrity of the microtubule cytoskeleton and are therefore candidates to directly target the transport machinery.
Polyfluorochrome marking slows growth only during the marking month in the green sea urchin Strongylocentrotus droebachiensis

Used singly, the fluorochrome tags tetracycline and calcein have yielded important insights into sea urchin biology, especially regarding growth. We present a new method of tagging using sequential fluorochrome markers, as well as a more precise method of quantifying growth. Such polyfluorochromes enable repeated markings that allow measurement of multiple growth points and unique identification of individuals or groups. We marked sea urchins, Strongylocentrotus droebachiensis, with four fluorochromes: alizarin complexone, calcein, calcein blue, and tetracycline. All fluorochromes marked both by injection and immersion. We examined the clarity of the mark produced with low, metabolically scaled doses, and higher doses similar to those that have been previously used. We tested the effect of fluorochromes on survival, growth, jaw size, and gonad size by marking a size range (3.9–44.3 mm in diameter) of urchins with either one or all four fluorochromes. We quantified growth using a nominal diameter, that is a fitted constant, times the cube root of weight, which increased the precision of measurements by a factor of six relative to measured diameter. Growth rate was a decreasing function of diameter except for a growth lag in the smallest urchins. Growth rate data for all sizes were fitted using: gamma distributions; Tanaka functions; and, for larger sizes, straight lines (von Bertalanffy model). All treatments produced clear marks, with higher doses producing more reliably clear marks. Tetracycline marking did not affect growth; other treatments produced only transient slowing of growth in the marking month. Growth rate, survival, gonad production, and jaw weight did not differ between control and treatments during the following 6 months. Thus, polyfluorochromes produce reliable marks that do not significantly affect growth or gonad production.
Juvenile Coho Salmon Leaping Ability and Behavior in an Experimental Culvert Test Bed

Abstract As part of a research program aimed at identifying the culvert configurations and associated hydraulic conditions that foster the successful upstream movement of juvenile salmon, we investigated the ability of hatchery-raised juvenile coho salmon Oncorhynchus kisutch to leap into an experimental culvert under varying hydraulic conditions. Five outfall drops ranging from 0 to 32 cm were tested to represent differing degrees of culvert outfall drop. Trials were run at a culvert discharge of 0.028 m3/s and a tailwater pool depth of 30 cm. The median success rate was highest (85%) for the 0-cm drop, followed by 34% at 12 cm, 20% at 20 cm, 2% at 26 cm, and 0% at 32 cm. When overcoming the 0-cm (streaming flow) and 12-cm drops, fish predominantly used swimming behavior. For the outfall drops of 20 and 26 cm, leaping behavior predominated. In a typical leaping event, fish initiated the leap near the floor of the tailwater tank and used burst swimming to propel their bodies from near the standing wave (p.
Biophysical defects of an SCN5A V1667I mutation associated with epinephrine‐induced marked QT prolongation

The epinephrine infusion test (EIT) typically induces marked QT prolongation in LQT1, but not LQT3, while the efficacy of β‐blocker therapy is established in LQT1, but not LQT3. We encountered an LQT3 family, with an SCN5A V1667I mutation, that exhibited epinephrine‐induced marked QT prolongation.
Comparative blood and urine metabolomics analysis of healthy elderly and young male Singaporeans.

Comparative metabolomics analysis of biofluids could provide information about the metabolic alterations in aging. To investigate the signature of multiple metabolic profiles associated with aging in an Asian population, we performed a pilot study in healthy Singaporeans, including 33 elderly and 33 young males. Fasting whole bloods were analysed by routine haematology; the serum and urine metabolome profiles were obtained using NMR-based non-targeted metabolomics analysis and targeted lipoprotein analysis. Among the 90 identified compounds in serum and urine samples, 32 were significantly different between the two groups. The most obvious age-related metabolic signatures include decreased serum level of albumin lysyl, essential amino acids and derivatives, but increased level of N-acetyl glycoproteins and several lipids; elevated urine levels of TMAO, scyllo-inositol, citrate, and ascorbic acid, but decreased levels of several amino acids, acetate, etc. Among 112 lipoprotein subfractions, 65 were elevated, 2 were lower in the elderly group. These significantly age-varying metabolites, especially in the amino acid and fatty acid metabolism pathways, suggest the regulation of these pathways contributes to the aging process in Chinese Singaporeans. Further multi-omics studies including the gut microbiome and intervention studies in a larger cohort are needed to elucidate the possible mechanisms in the aging process.
EAACI Allergen Immunotherapy User's Guide

Abstract Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well‐defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.
Understanding Women’s Help-Seeking With Intimate Partner Violence in Tanzania

Intimate partner violence (IPV) is a serious global health problem affecting millions of women worldwide. Despite increased investments into its reduction, little research has been conducted into how women in low- and middle-income countries deal with IPV. This study seeks to explore this by looking in depth into help-seeking strategies utilized by abused women in Tanzania, using the 2015–2016 Tanzania Demographic and Health Survey. The prevalence of lifetime physical and/or sexual IPV was 41.6% in this study, but only half of all affected women sought help from anyone. The only clear association found with help-seeking was the severity of IPV.
Immunohistologic comparison and thrombus NET analysis in stroke and myocardial infarction

Despite extensive characterization of the role of platelet activation and the coagulation cascade in acute ischemic stroke (AIS), few studies have analyzed the immune cell composition of AIS thrombi. Recent articles describing a function of neutrophil-derived extracellular nucleosomes (NETs) in thrombus formation9 highlight the great need for clinical immunohistologic analyses in acute vascular disease. In this issue of Neurology®, Novotny et al.1 conduct a study comparing thrombus histology between AIS and acute myocardial infarction (AMI), with a focus on the role of immune cells and NETs.
Community Structure, Population Control, and Competition

In summary, then, our general conclusions are: (1) Populations of producers, carnivores, and decomposers are limited by their respective resources in the classical density-dependent fashion. (2) Interspecific competition must necessarily exist among the members of each of these three trophic levels. (3) Herbivores are seldom food-limited, appear most often to be predator-limited, and therefore are not likely to compete for common resources.
Occurrence and Risk Factors for Unplanned Catheter Removal in a PICU: Central Venous Catheters Versus Peripherally Inserted Central Venous Catheters

Objectives: We aimed to identify the occurrence and risk factors for unplanned catheter removal due to catheter-associated complications and the effects on catheter survival probability in a PICU. Design: Retrospective, single-center, observational study of cases involving conventional central venous catheters or peripherally inserted central venous catheters. Setting: The PICU of a tertiary children’s hospital. Patients: Consecutive PICU patients with central venous catheters between April 2016 and February 2019. Interventions: None. Measurements and Main Results: We identified unplanned catheter removals that were related to central line-associated bloodstream infection, thrombosis, and mechanical complications. During the study period, 582 central venous catheters and 474 peripherally inserted central venous catheters were identified. The median durations of catheter placement were 4.0 days for central venous catheters and 13.0 days for peripherally inserted central venous catheters (p < 0.001), and unplanned catheter removals due to catheter-associated complications were in 52 (8.9%) central venous catheter cases and 132 (27.8%) peripherally inserted central venous catheter cases (p < 0.001) (15.0 and 16.0 per 1,000 catheter-days, respectively [p = 0.75]). Unplanned catheter removal was associated with a peripheral catheter tip position among both central venous catheters and peripherally inserted central venous catheters (p < 0.001 and p = 0.001), and it was associated with surgical patient status among peripherally inserted central venous catheters (p = 0.009). In contrast, the use of ultrasound-guided insertion was associated with a lower occurrence of unplanned catheter removal among peripherally inserted central venous catheters (p = 0.01). With regard to catheter survival probability, there was no significant difference between central venous catheters and peripherally inserted central venous catheters (p = 0.23). However, peripherally inserted central venous catheters had a lower occurrence of central line-associated bloodstream infection than central venous catheters (p = 0.03), whereas there was no significant difference in the rates of thrombosis (p = 0.29) and mechanical complications (p = 0.84) between central venous catheters and peripherally inserted central venous catheters. Conclusions: In a PICU, peripherally inserted central venous catheters had lower occurrence of central line-associated bloodstream infection than central venous catheters; however, similar catheter survival probabilities were observed between both catheters. A central catheter tip position for both catheters and ultrasound-guided insertion for peripherally inserted central venous catheters may help limit unplanned catheter removal due to catheter-associated complications.
Diazoxide Preconditioning of Nonhuman Primate Pancreas Improves Islet Isolation Outcomes by Mitochondrial Protection

Objectives Previously, we showed that diazoxide (DZ), an effective ischemic preconditioning agent, protected rodent pancreas against ischemia-reperfusion injury. Here, we further investigate whether DZ supplementation to University of Wisconsin (UW) solution during pancreas procurement and islet isolation has similar cytoprotection in a preclinical nonhuman primate model. Methods Cynomolgus monkey pancreata were flushed with UW or UW + 150 μM DZ during procurement and preserved for 8 hours before islet isolation. Results First, a significantly higher islet yield was observed in UW + DZ than in UW (57,887 vs 23,574 IEq/pancreas and 5396 vs 1646 IEq/g). Second, the DZ treated islets had significantly lower apoptotic cells per islet (1.64% vs 9.85%). Third, DZ significantly inhibited ROS surge during reperfusion with a dose-response manner. Fourth, DZ improved in vitro function of isolated islets determined by mitochondrial potentials and calcium influx in responses to glucose and KCI. Fifth, the DZ treated islets had much higher cure rate and better glycemia control in diabetic mice transplant model. Conclusions This study showed a strong mitochondrial protection of DZ on nonhuman primate islets against ischemia-reperfusion injury that provides strong evidence for its clinical application in islet and pancreas transplantation.
Exposure‐Response Analysis of Vamorolone (VBP15) in Boys With Duchenne Muscular Dystrophy

Exposure‐response relationships of vamorolone, a novel dissociative steroidal anti‐inflammatory drug, were investigated in clinical trials in boys with Duchenne muscular dystrophy. Variables were clinical outcome measures, Fridericia‐corrected QT (QTcF) duration, and pharmacodynamic (PD) biomarkers. Exposure metrics were area under the plasma concentration time curve (AUC) and maximum plasma concentration (Cmax), with a sigmoid Emax model applied. Significant improvement in clinical efficacy outcomes was observed after 24 weeks of daily dosing. The primary outcome, time to stand from supine velocity, exhibited the highest sensitivity to vamorolone, with the lowest AUC value providing 50% of maximum effect (E50 = 186 ng·h/mL), followed by time to climb 4 stairs (E50 = 478 ng·h/mL), time to run/walk 10 m (E50 = 1220 ng·h/mL), and 6‐minute walk test (E50 = 1770 ng·h/mL). Week 2 changes of proinflammatory PD biomarkers showed exposure‐dependent decreases. The E50 was 260 ng·h/mL for insulin‐like growth factor‐binding protein 2, 1200 ng·h/mL for matrix metalloproteinase 12, 1260 ng·h/mL for lymphotoxin α1/β2, 1340 ng·h/mL for CD23, 1420 ng·h/mL for interleukin‐22‐binding protein, and 1600 ng·h/mL for macrophage‐derived chemokine/C‐C motif chemokine 22. No relationship was found between QTcF interval changes from baseline and Cmax in week 2 or 24. This analysis showed that improvements in clinical efficacy end points in week 24 and PD biomarkers in week 2 were achieved at typical vamorolone exposure of 2 mg/kg daily dose with a median AUC dose of 6 mg/kg (3651 ng·h/mL), corresponding to approximately 95% of maximum effects for most response variables.
[Expression and significance of follicular helper T cells and galactose-deficient IgA1 in children with Henoch-Schönlein purpura].

OBJECTIVE To study the role of follicular helper T (Tfh) cells and galactose-deficient IgA1 (Gd-IgA1) in the pathogenesis of childhood Henoch-Schönlein purpura (HSP) and the correlation between them. METHODS A total of 36 children with newly-diagnosed HSP were enrolled. They were divided into two groups: HSP nephritis (HSPN) group with 11 children and non-HSPN group with 25 children according to the presence or absence of HSPN. Another 15 children who underwent physical examination at the outpatient service were enrolled as the healthy control group. Flow cytometry was used to measure the proportion of Tfh cells (CD4+CXCR5+ICOS+) in peripheral blood. ELISA was used to measure the levels of interleukin-21 (IL-21) and interleukin-6 (IL-6) in peripheral blood and the serum levels of IgA1 and Gd-IgA1. A Pearson correlation analysis was used to investigate the correlation of serum Gd-IgA1 concentration with Tfh cells and related factors expression in the children with HSP. RESULTS Both the HSPN and non-HSPN groups had significantly higher proportion of Tfh cells and expression levels of IL-21 and IL-6 in peripheral blood than the healthy control group (P<0.05). The HSPN group had significant increases in the above indices compared with the non-HSPN group (P<0.05). Both the HSPN and non-HSPN groups had significantly higher serum levels of IgA1 and Gd-IgA1 than the healthy control group (P<0.05). The HSPN group had significantly higher serum levels of IgA1 and Gd-IgA1 than the non-HSPN group (P<0.05). In the children with HSP, serum Gd-IgA1 level was positively correlated with Tfh cells proportion and IL-21 and IL-6 levels (P<0.05). CONCLUSIONS Tfh cells and related cytokines and serum Gd-IgA1 are involved in the development of HSP/HSPN. Tfh cells may mediate the increased production of Gd-IgA1.