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PubMed2026

From Peaks to Power: Systematic Evaluation of Chromatographic Sampling Reveals Determinants of Quantification and Biological Discovery in DIA Proteomics.

Modern DIA proteomics increasingly emphasizes throughput and depth for large-cohort studies, but methods are often optimized using proxy metrics that can mask losses in quantifiable signal and statistical power. Here, we evaluate how data points per peak and other chromatographic features jointly contribute to quantification and downstream biological discovery. Using a matrix-matched calibration curve dataset, we checked how the number of data points per peak (DPPP) affects the limits of detection and quantification (LOD/LOQ). Reduced DPPP minimally affected LOD but substantially degraded LOQ. Feature modeling and nonparametric association analyses identified precursor peak area as the strongest feature-level predictor of LOQ, whereas DPPP showed weaker and context-dependent effects. Simulations of chromatographic peak integration recapitulated these trends, showing that increased sampling primarily improves integration precision, while quantitative accuracy is strongly governed by peak height and peak shape. Finally, when comparing 20 cancer vs 20 control plasma samples processed with Seer Proteograph, the decrease in DPPP led to a loss of statistical significance for proteins with low-abundance precursors. These findings argue that DIA optimization should prioritize LOQ and statistical power metrics─not identifications alone─by balancing sampling density with chromatographic peak height and quality to maximize useful biological signal.

Proteomics↗

PubMed1978

[Degenerative diabetic complications. Is persistent hyperglycemia more dangerous than wide glycemic fluctuations? (author's transl)].

Consistant data drawn from animal experiments and from clinical statistics have shown the diabetic specific complications (neuropathy and microangiopathy) to be closely related to the hyperglycemic component of diabetes mellitus. Working directly or through more complicated biochemical disorders, high levels of blood glucose interfer with the metabolism of the lens, the retina and the peripheral axon (leading to cataracts, retinopahy, and neuropathy). High blood sugar also alters the metabolism of endothelial and blood cells as well as the composition of plasma proteins. Wall and content of the minute vessels are both affected resulting in disturbed local blood flows and hypoxic areas. Various intertricated mechanisms have been discovered. Some of them initiate vicious circles leading to self-supported functional and later on, morphological abnormalities of diabetic microangiopathy (retinopathy, glomerulosclerosis, etc., etc.). High blood sugar exerts its influence (directly or not) in terms of duration and intensity (hours per day, days per year). There are good reasons to believe that persistent hyperglycemia uninterrupted throughout the day is much more harmful than high peaks alternating with periods of normo- and even hypoglycemia. There is no experimental nor clinical data pointing to glycemic instability as a risk factor for the minute vessels and the nerves, and opinion still often hold in some quarters. Although undesirable, frequent bouts of hypoglycemia associated with insulin treatment are indices that a rather good glycemic control has been achieved. And this can greatly delay the development of specific complications.

Diabetes Complications↗

PubMed1977

A comparison of the response to arm and leg work in patients with ischemic heart disease.

An exercise test based on arm work was evaluated in a series of 33 male patients, mean age 52 years, with ischemic heart disease. The responses to arm exercise on a modified table-mounted bicycle ergometer and to standard bicycle exercise were compared. Twenty six of 33 patients (79 per cent) had identical end-points with both tests. Three patients had an ischemic response, i.e., significant ST abnormality and/or angina pectoris during leg work only, and four patients during arm work only. 41 per cent of the peakload during leg exercise. Mean values were 181 and 439 kpm./min. (p less than 0.001). Comparison of individual data on peak load demonstrated only a weak correlation between arm and leg work capacity (r = 0.37, p less than 0.05). Peak heart rate was slightly higher during leg work, 129 compared to 122 beats/min. (p less than 0.05) but the mean heart rate-systolic blood pressure products were not significantly different. A subgroup of seven patients had a history of angina pectoris preferentially precipitated by arm work but their physiological responses did not differ significantly from those of patients without a history of arm work sensitivity. The data indicate that arm work is a satisfactory alternate diagnostic test method with respect to myocardial ischemia, but measurements of physical work capacity defined as aerobic capacity, cannot be based on arm work.

Adult↗

PubMed1979

The ability of ionizing radiations of different LET to induce chromosomal deletions in Aspergillus nidulans.

Conidia, derived from a strain of Aspergillus nidulans known to carry a specific chromosomal duplication, were irradiated. The duplicated segment had genetic markers, which, when eliminated from the genome, allowed the easy detection of deletion mutants. Survival curves derived following 15 MeV electron and gamma-ray irradiation were characterised by the presence of an appreciable shoulder, whilst 50 kvp X-rays gave a much smaller shoulder. Irradiation with beta-particles and alpha-particles gave rise to exponential survival curves. The RBE values for these radiations, based on the D37 value were for gamma-rays, 1.0, 15 MeV electrons 1.0, 50 kvp X-rays 1.9, beta-particles 2.1 and alpha-particles 3.4. With the exception of gamma-rays the radiations described were compared with respect to their ability to induce chromosomal deletions. When the number of deletants amongst survivors was plotted against dose, a linear relationship was found for electrons, X-rays and beta-particles. The response recorded for alpha-particles was essentially linear but with a biphasic component. The RBE values for the radiations, based on a value of unity for 15 MeV electrons were as follows: X-rays 1.3, beta-particles 0.8, alpha-particles above 7.5 krad 2.3 and below 7.5 krad 3.5. When these same data were re-plotted with number of deletants amongst survivors against log survival, electrons appeared the most efficient radiation at producing deletants amongst survivors, with an "m value" of 283 X 10(-5). Tritiated water was least efficient, the corresponding value being 182 X 10(-5). The number of deletants per 10(4) conidia plated, when plotted against dose yielded a curve which increased to a peak and then decreased linearly for all radiations. The peaks for electrons, X-rays and alpha-particles each had a value of about 14 deletants per 10(4) conidia plated and the peaks roughly corresponded with the point at which the survival curve became exponential and was clearly indicative of the accumulation of sub-lethal damage. However, for beta-particles the peak had a value of 7 deletants per 10(4) conidia plated. A non-DNA target has been implicated for cellular death following beta-particle irradiation.

Americium↗

PubMed1978

[Cerebro-vascular accident during pregnancy (author's transl)].

Cerebro-vascular accident is an uncommon but formidable complication of pregnancy. Faced with these cases, the neurosurgeon and obstetrician might differ in the planning of the treatment, when the interests of mother and child appear to conflict between them. From our clinical data of 5 cases and review of the literatures, the following points should be considered for the management of a cerebro-vascular accident during pregnancy. (1) The possibility of cerebro-vascular accident should be considered in any pregnant patients with neurological symptoms, and full investigation should be done if clini-indicated. (2) Aneurysm and angioma are most often encountered in pregnant patients with a cerebro-vascular accident. (3) Unless labour begins during investigation, a cerebral lesion should be treated before delivery, irrespective of the stage of pregnancy and the method of treatment should be decided primarily on neurosurgical grounds. (4) The time of onset of cerebro-vascular accident may be related to the hemodynamic and hormonal change. It occurs more frequently after the second trimester, when the blood volume and cardiac output reach their peak. (5) Pregnancy per se does not influence the mortality from a cerebro-vascular accident in pregnant patients.

Adult↗