Miracle-dz/UniFAR-FTUs huggingface dataset:
Interpreting Mixture Profiles: Comparison Between Precision ID GlobalFiler™ NGS STR Panel v2 and Traditional Methods

Forensic investigation for the identification of offenders, recognition of human remains, and verification of family relationships requires the analysis of particular types of highly informative DNA markers, which have high discriminatory power and are efficient for typing degraded samples. These markers, called STRs (Short Tandem Repeats), can be amplified by multiplex-PCR (Polymerase Chain Reaction) allowing attainment of a unique profile through which it is possible to distinguish one individual from another with a high statistical significance. The rapid and progressive evolution of analytical techniques and the advent of Next-Generation Sequencing (NGS) have completely revolutionized the DNA sequencing approach. This technology, widely used today in the diagnostic field, has the advantage of being able to process several samples in parallel, producing a huge volume of data in a short time. At this time, although default parameters of interpretation software are available, there is no general agreement on the interpretation rules of forensic data produced via NGS technology. Here we report a pilot study aimed for a comparison between NGS (Precision ID GlobalFiler™ NGS STR Panel v2, Thermo Fisher Scientific, Waltham, MA, USA) and traditional methods in their ability to identify major and minor contributors in DNA mixtures from saliva and urine samples. A quantity of six mixed samples were prepared for both saliva and urine samples from donors. A total of 12 mixtures were obtained in the ratios of 1:2; 1:4; 1:6; 1:8; 1:10; and 1:20 between minor and major contributors. Although the number of analyzed mixtures is limited, our results confirm that NGS technology offers a huge range of additional information on samples, but cannot ensure a higher sensitivity in respect to traditional methods. Finally, the Precision ID GlobalFiler™ NGS STR Panel v2 is a powerful method for kinship analyses and typing reference samples, but its use in biological evidence should be carefully considered on the basis of the characteristics of the evidence.
Structure of substrate-bound SMG1-8-9 kinase complex reveals molecular basis for phosphorylation specificity

PI3K-related kinases (PIKKs) are large Serine/Threonine (Ser/Thr)-protein kinases central to the regulation of many fundamental cellular processes. PIKK family member SMG1 orchestrates progression of an RNA quality control pathway, termed nonsense-mediated mRNA decay (NMD), by phosphorylating the NMD factor UPF1. Phosphorylation of UPF1 occurs in its unstructured N- and C-terminal regions at Serine/Threonine-Glutamine (SQ) motifs. How SMG1 and other PIKKs specifically recognize SQ motifs has remained unclear. Here, we present a cryo-electron microscopy (cryo-EM) reconstruction of a human SMG1-8-9 kinase complex bound to a UPF1 phosphorylation site at an overall resolution of 2.9 Å. This structure provides the first snapshot of a human PIKK with a substrate-bound active site. Together with biochemical assays, it rationalizes how SMG1 and perhaps other PIKKs specifically phosphorylate Ser/Thr-containing motifs with a glutamine residue at position +1 and a hydrophobic residue at position -1, thus elucidating the molecular basis for phosphorylation site recognition.
Experimental studies on the regenerating lens and the eye in adult Triturus viridescens

In various species of larval and adult Triturus it has been definitely shown that tlie dorsal rim of the iris possesses the power to regenerate a new lens (Colucci, 1891; Wolff, 1895; Wadis, '14; Ogawa, '21; Sato, '30, '33 and '35; Stone, Zaur and Farthing, '34; Stone and Chace, '37). Concerning a similar phenomenon in other forms there have been both positive and negative claims reported in the literature which hare focused some interest on this peculiar method of lens regeneration. For a discussion of the latter claims the reader is referred to the experimental studies of Stone and Dinneaii ( '40) and Stone and Sapir ( '40). In the present paper, however, the problem for analysis is the growth of the regenerating lens in the adult Triturus eye and the relation of the size of the new lens to that of the eye possessing it. In the analysis we shall compare the results of several methods by which the regeneration of the lens is brought about. Lensectomy, grafting of the eye or the cutting of all the blood vessels to the eye effectively eliminate the original lens. This is followed by the formation of a new one. As we shall see later the eye as a whole is affected differently by various methods of operation. In any case it is
Fetal and Neonatal MRI Predictors of Aggressive Early Clinical Course in Vein of Galen Malformation

The authors aimed to identify brain MR imaging characteristics obtained from fetal and early neonatal scans that can predict the clinical presentation. A total of 32 neonatal patients (21 patients in the neonatal at-risk cohort, 11 in the infantile treatment cohort) were identified. Maximal mediolateral diameter and cross-sectional area at the narrowest point of the straight/falcine sinus were most predictive of clinical evolution into the neonatal at-risk cohort. This measurement clearly and unambiguously differentiated between high- and low-risk cohorts. The ability to accurately predict clinical evolution after birth based on fetal MR imaging can be of help for both caregivers and families, enabling better preparedness for urgent treatment and better planning for allocation of resources. BACKGROUND AND PURPOSE: Neonates with vein of Galen malformations are split into 2 cohorts: one needing urgent neonatal embolization, with relatively high mortality and morbidity even with expert care, and a cohort in which embolization can be deferred until infancy, with far better prognosis. We aimed to identify brain MR imaging characteristics obtained from fetal and early neonatal scans that can predict the clinical presentation. MATERIALS AND METHODS: Patients with vein of Galen malformations were stratified into a neonatal at-risk cohort if the patient needed urgent neonatal intervention or if neonatal death occurred; or an infantile treatment cohort if they were stable enough not to require treatment until >1 month of age. Twelve vascular MR imaging parameters, measured by 2 independent observers, were systematically correlated with the need for early neonatal intervention and/or neonatal mortality. RESULTS: A total of 32 neonatal patients (21 patients in the neonatal at-risk cohort, 11 in the infantile treatment cohort) were identified. Maximal mediolateral diameter (area under the curve = 0.866, P < .001) and cross-sectional area (area under the curve = 0.836, P = .002) at the narrowest point of the straight or falcine sinus were most predictive of clinical evolution into the neonatal at-risk cohort. There were 15 patients who had fetal MRIs (10 in the neonatal at-risk cohort and 5 in the infantile treatment cohort). Here too, maximal mediolateral diameter (area under the curve = 0.980, P = .003) and cross-sectional area (area under the curve = 0.941, P = .007) at the narrowest point of the straight or falcine sinus were highly predictive of the neonatal at-risk cohort. CONCLUSIONS: Early neonatal and fetal MR imaging can be readily used for accurate early risk stratification, assisting in directing resources, timing treatment decisions, and identifying appropriate cohorts for novel interventions.
Shell Growth of Large Benthic Foraminifera under Heavy Metals Pollution: Implications for Geochemical Monitoring of Coastal Environments

This study was promoted by the recent efforts using larger benthic foraminiferal (LBF) shells geochemistry for the monitoring of heavy metals (HMs) pollution in the marine environment. The shell itself acts as a recorder of the ambient water chemistry in low to extreme HMs-polluted environments, allowing the monitoring of recent-past pollution events. This concept, known as sclerochronology, requires the addition of new parts (i.e., new shell) even in extreme pollution events. We evaluated the physiological resilience of three LBF species with different shell types and symbionts to enriched concentrations of Cd, Cu, and Pb at levels several folds higher than the ecological criteria maximum concentration (CMC) (165–166, 33–43, 1001–1206 µg L−1, respectively), which is derived from aquatic organisms’ toxicity tests. The physiological response of the holobiont was expressed by growth rates quantified by the addition of new chambers (new shell parts), and by the chlorophyll a of the algal symbionts. The growth rate decrease varied between 0% and 30% compared to the unamended control for all HMs tested, whereas the algal symbionts exhibited a general non-fatal but significant response to Pb and Cu. Our results highlight that shell growth inhibition of LBF is predicted in extreme concentrations of 57 × CMC of Cu and 523 × CMC of Cd, providing a proof of concept for shell geochemistry monitoring, which is currently not used in the regulatory sectors.
Relationship Between Body Mass Index and Asthma Characteristics in a Group of Italian Children and Adolescents

The prevalence of asthma and obesity, two often associated conditions, is influenced not only by age and gender but also by lifestyle factors. This study aimed to determine whether, in a Mediterranean northern Italian region, Liguria, an increased prevalence of obesity could be detected in asthmatic children and adolescents and to evaluate the possible relationship between body mass index (BMI) and the characteristics and/or severity of asthma. BMI was determined in 554 asthmatic subjects (2.2–16.1 years) and 625 age-matched controls; BMI was expressed as a continuous variable in standard deviation score (SDS) units, determined as difference between the individual observed value and the reference mean for age and sex, divided by the corresponding standard deviation (BMI-SDS). Overweight/obesity was set at BMI-SDS of 2 or more. BMI-SDS was significantly higher in controls than in asthmatics (p = 0.04); however, the proportion of overweight/obesity subjects (BMI-SDS ≥ 2) was similar in controls and in asthmatic patients (p = 0.08). Evaluation of the asthmatic group revealed that BMI-SDS was independent of gender (p = 0.57), atopic sensitization (p = 0.69), and comorbidity with other allergic symptoms (p = 0.60). By contrast, BMI-SDS was lower in preschool-age children than in school-age children and adolescents (p < 0.0001), in subjects with a high rate of acute respiratory tract infections (p = 0.04), and in those not treated with inhaled corticosteroids (IGCs) (p = 0.02). Although an increase in the prevalence of overweight/obesity was not detected in asthmatic children and adolescents, the results reported here suggest a preventive surveillance of calorie intake and a promotion of physical activity in children requiring long-term treatment with inhaled glucocorticosteroids.
Effects of Anesthesia Techniques on Outcomes after Hip Fracture Surgery in Elderly Patients: A Prospective, Randomized, Controlled Trial

The superiority of distinct anesthesia methods for geriatric hip fracture surgery remains unclear. We evaluated high mobility group box-1 (HMGB1) and interleukin-6 (IL-6) with three different anesthesia methods in elderly patients undergoing hip fracture surgery. Routine blood test findings, postoperative morbidity, and mortality were assessed as secondary outcome. In total, 176 patients were randomized into desflurane (n = 60), propofol (n = 58), or spinal groups (n = 58) that received desflurane-based balanced anesthesia, propofol-based total intravenous anesthesia (TIVA), or spinal anesthesia, respectively. The spinal group required less intraoperative vasopressors (p < 0.001) and fluids (p = 0.006). No significant differences in HMGB1 (pgroup×time = 0.863) or IL-6 (pgroup×time = 0.575) levels were noted at baseline, postoperative day (POD) 1, or POD2. Hemoglobin, albumin, creatinine, total lymphocyte count, potassium, troponin T, and C-reactive protein were comparable among groups at all time-points. No significant differences in postoperative hospital stay, intensive care unit (ICU) stay, and ventilator use among groups were observed. Postoperative pulmonary, cardiac, and neurologic complications; and in-hospital, 30-day, and 90-day mortality were not significantly different among groups (p = 0.974). In conclusion, HMGB1 and IL-6, and all secondary outcomes, were not significantly different between desflurane anesthesia, propofol TIVA, and spinal anesthesia.
Diversity of nematode faunae under three vegetation types on a pallic soil in Otago, New Zealand

Abstract The mean numbers of nematodes in the upper 20 cm of soil in pasture, scrub, and podocarp forest were estimated to be, respectively, 4.2, 2.1, and 1.0 million/m2; including a total of 44 taxa. Plant‐feeding taxa dominated in the pasture soil. Soil from beneath scrub had the greatest proportion of fungal‐feeders; the Shannon‐Weaver index (H) was greatest at this site and, as many Dorylaimida were present, the value of the summed nematode maturity index (SMI) was also greatest here. Soil pH was lowest and C:N ratio highest under scrub. Bacterial‐feeding nematodes were the most abundant group in the forest soil. In addition to uncertainty in allocating nematodes to feeding groups, absence of information on nematodes in other forest types and on the incidence of mycorrhizae makes it difficult to reach firm conclusions about contributions by nematode functional groups, trends in diversity, and an integrated “soil quality” index.
Consecutive single-institution case series of primary central nervous system lymphoma treated by R-MPV or high-dose methotrexate monotherapy.

OBJECTIVE The optimal regimen for use of high dose-methotrexate-based chemotherapy in primary central nervous system lymphoma is still under debate. We conducted a retrospective study to evaluate the treatment outcome of a combination immunochemotherapy consisting of rituximab, methotrexate, procarbazine and vincristine followed by with or without whole brain radiotherapy and consolidation cytarabine, in comparison with high dose-methotrexate monotherapy followed by full dose whole brain radiotherapy. METHODS Newly diagnosed primary central nervous system lymphoma patients treated with either rituximab, methotrexate, procarbazine and vincristine or high dose-methotrexate in Kyorin University Hospital were identified, and the response rates and survival were compared. Toxicities, post-treatment transition of Mini-Mental State Examination, Karnofsky performance status score, Fazekas scale and prognostic factors were analysed in the rituximab, methotrexate, procarbazine and vincristine group. RESULTS Ninety-five patients treated with rituximab, methotrexate, procarbazine and vincristine (n = 39) or high dose-methotrexate (n = 56) were analysed. The complete response/complete response unconfirmed rate was significantly higher in the rituximab, methotrexate, procarbazine and vincristine group (74.4 vs. 15.4%, P < 0.001). Accordingly, both median progression-free survival and overall survival were significantly longer in the rituximab, methotrexate, procarbazine and vincristine group (median progression-free survival: unreached vs. 14.75 months, P < 0.001) (median overall survival: unreached vs. 63.15 months, P = 0.005). Although the rate of grade 3/4 hematologic toxicities was high both during rituximab, methotrexate, procarbazine and vincristine and consolidation cytarabine, the rate of grade 3/4 infections was low, and no treatment related deaths were observed. Deterioration in Karnofsky performance status or Mini-Mental State Examination was rare, except on disease recurrence. Although whole brain radiotherapy was associated with Fazekas scale deterioration, its association with Karnofsky performance status or Mini-Mental State Examination deterioration was not significant. CONCLUSIONS Rituximab, methotrexate, procarbazine and vincristine was apparently promising in comparison with high dose-methotrexate monotherapy with manageable toxicity in this retrospective study, and further investigation is warranted.
Necessity of routine chest radiograph in blunt trauma resuscitation: time to evaluate dogma with evidence.

C hest radiographs (CXR) have long been a cornerstone imaging adjunct during the primary evaluation of adult blunt trauma patients. Yet a CXR is not benign; portable radiography machines may disrupt temporal and spatial flow of the primary trauma evaluation to varying degrees, depending on institutional workflows. Historically, it was used for diagnosis of three potentially life-threatening injuries: pneumothorax, hemothorax, and aortic injury. We argue that just as the regular use of cervical spine radiographs has fallen by the wayside, so too should the CXR. Improved imaging modalities capable of diagnosing these same injuries, including thoracic ultrasonography and computed tomography (CT), have made routine CXR use during the primary survey obsolete (Table 1). In the modern era, interventions for the overwhelmingmajority of thoracic injuries are (1) needed urgently before any imaging, or (2) can be performed after a more accurate and rapid thoracic ultrasonography, or (3) can wait for CT.
Secondary Metabolites by Chemical Screening, 34. – Aspinolides and Aspinonene/Aspyrone Co‐Metabolites, New Pentaketides Produced by Aspergillus ochraceus

New 10-membered lactones, named aspinolide A–C (3, 4, 5), and the aspinonene/aspyrone co-metabolites, named trienediol (6), isoaspinonene (7), dihydroaspyrone (8), and dienetriol 9 were discovered by chemical screening methods in the cultures of Aspergillus ochraceus (DSM-7428) under altered fermentation conditions. The structures were established by detailed spectroscopic analysis. The polyketide origin of the skeleton and the biogenesis of the oxygen atoms were verified by feeding sodium [1,2-13C2]acetate and [18O2] gas, respectively, to growing cultures of the fungus. A comprehensive discussion of the supposed biosynthetic pathways draws the conclusion that two polyketide synthases (PKSα, PKSβ) exist, forming two different series of pentaketides in parallel. One pathway leads to branched-chain metabolites by a Favorski-like rearrangement of an epoxide intermediate, while the other involves detachment of the pentaketides from the PKSβ by lactonisation without any rearrangement of the carbon skeleton. The former pathway is affected by an inhibitor of cytochrome P450 dependent monooxygenases.
Cisplatin Protein Binding Partners and Their Relevance for Platinum Drug Sensitivity

Cisplatin is a widely used drug in the treatment of various solid tumors, such as ovarian cancer. However, while the acquired resistance significantly limits the success of therapy, some tumors, such as colorectal cancer, are intrinsically insensitive to cisplatin. Only a small amount of intracellular platinum binds to the target—genomic DNA. The fate of the remaining drug is largely obscure. This work aimed to identify the cytosolic protein binding partners of cisplatin in ovarian and colorectal cancer cells and to evaluate their relevance for cell sensitivity to cisplatin and oxaliplatin. Using the fluorescent cisplatin analog BODIPY-cisplatin, two-dimensional gel electrophoresis, and mass spectrometry, we identified the protein binding partners in A2780 and cisplatin-resistant A2780cis ovarian carcinoma, as well as in HCT-8 and oxaliplatin-resistant HCT-8ox colorectal cell lines. Vimentin, only identified in ovarian cancer cells; growth factor receptor-bound protein 2, only identified in colorectal cancer cells; and glutathione-S-transferase π, identified in all four cell lines, were further investigated. The effect of pharmacological inhibition and siRNA-mediated knockdown on cytotoxicity was studied to assess the relevance of these binding partners. The silencing of glutathione-S-transferase π significantly sensitized intrinsically resistant HCT-8 and HCT-8ox cells to cisplatin, suggesting a possible involvement of the protein in the resistance of colorectal cancer cells to the drug. The inhibition of vimentin with FiVe1 resulted in a significant sensitization of A2780 and A2780cis cells to cisplatin, revealing new possibilities for improving the chemosensitivity of ovarian cancer cells.
Pregnancy rates and serum progesterone levels of polar bears in western Hudson Bay

Blood samples were collected from 354 female polar bears (Ursus maritimus) on 476 occasions between 1982 and 1990. Serum progesterone concentrations were determined to evaluate reproductive status. Progesterone levels greater than 2.5 ng/mL were considered indicative of pregnancy in autumn. Of 85 females classified as pregnant that were seen the following year, 67% were with cubs and 33% were without cubs. Possible explanations for the large proportion of females with apparent reproductive failure include neonatal mortality, failure to implant, or abortion. The minimum weight of a confirmed pregnant female in autumn was 189 kg, but approximately 10% of the suspected pregnant females were below this and may have had insufficient fat stores to fast through the winter and produce cubs. Based on progesterone levels, implantation appeared to occur between mid-September and mid-October, likely followed by parturition from mid-November to mid-December. The annual pregnancy rate of solitary females, as determined.
Spawning Habitat and Geography Influence Population Structure and Juvenile Migration Timing of Sockeye Salmon in the Wood River Lakes, Alaska

Abstract The strict homing of sockeye salmon Oncorhynchus nerka results in reproductively isolated populations that often spawn in close proximity and share rearing habitat. High spawning fidelity enables these populations to adapt to local conditions, resulting in a wide range of life history characteristics and genetic variation within individual watersheds. The Wood River system in southwestern Alaska provides a pristine, well-studied system in which to examine fine-scale population structure and its influences on juvenile life histories. Adult sockeye salmon spawn in lake beaches, rivers, and small tributaries throughout this watershed, and juveniles rear in five nursery lakes. We genotyped 30 spawning populations and 6,066 migrating smolts at 45 single nucleotide polymorphism loci, two of which are candidates for positive selection in the study system. We show that there is significant genetic structure (F ST = 0.032) in the Wood River lakes and that divergence is generally related to spawning rather.
ASICs are required for immediate exercise-induced muscle pain and are downregulated in sensory neurons by exercise training.

Exercise training is an effective therapy for many pain-related conditions, and trained athletes have lower pain perception compared to unconditioned people. Some painful conditions, including strenuous exercise, are associated with elevated levels of protons, metabolites and inflammatory factors, which may activate receptors and/or ion channels, including acid-sensing ion channels (ASICs), on nociceptive sensory neurons. We hypothesized that ASICs are required for immediate exercise-induced muscle pain (IEIP), and that exercise training diminishes IEIP by modulating ASICs within muscle afferents. We found high-intensity interval training (HIIT) reduced IEIP in C57BL/6 mice, diminished ASICs mRNA levels in lumber dorsal root ganglia (DRG), and this downregulation of ASICs correlated with improved exercise capacity. Additionally, we found that ASIC3 -/- mice did not develop IEIP, however the exercise capacity of ASIC3 -/- was similar to wild-type mice. These results suggest that ASICs are required for IEIP, and that diminishment of IEIP after exercise training correlates with downregulation of ASICs in sensory neurons.