Genetic testing allows for identification of germline DNA variations which are associated with a significant increase in risk of developing breast and ovarian cancer. Detection of a BRCA1 or BRCA2 pathogenic variant triggers several clinical management actions, which may include increased surveillance and prophylactic surgery for healthy carriers or treatment with PARP inhibitor therapy for carriers diagnosed with cancer. Thus, standardized validated criteria for annotation of BRCA1 and BRCA2 variants according to their pathogenicity are necessary to support clinical decision making and ensure improved outcomes. Upon detection, variants whose pathogenicity can be inferred by the genetic code are typically classified as pathogenic, likely pathogenic, likely benign, or benign. Variants whose impact on function cannot be directly inferred by the genetic code are labeled as Variants of Uncertain Clinical Significance (VUS) and are evaluated by multifactorial likelihood models that use personal and family history of cancer, segregation data, prediction tools, and co-occurrence with a pathogenic BRCA variant. Missense variants, coding alterations that replace a single amino acid residue with another, are a class of variants for which determination of clinical relevance is particularly challenging. Here, we discuss current issues in variant classification by following a typical life cycle of a BRCA1 missense variant through detection, annotation and information dissemination. Advances in massively parallel sequencing have led to a substantial increase in VUS findings. Although comprehensive assessment and classification of missense variants according to their pathogenicity remains the bottle neck, new developments in functional analysis, high throughput assays, data sharing, and statistical models are rapidly changing this scenario.

(1) Background: The COVID-19 pandemic had a devastating impact on the world, causing widespread illness and death. It is essential to focus on prevention strategies to limit the spread of the disease. Despite the advent of vaccines, maintaining a vigilant approach to prevention remains paramount. While vaccines are essential, they do not guarantee absolute immunity, and their protective effect may diminish over time; (2) Methods: We reviewed effective strategies to prevent COVID-19 transmission. We focused on me-ta-analyses (MA), literature reviews (LR) and the health care context. Various prevention measures and interventions were reviewed. Both es-tablished practices and unresolved issues were considered; (3) Results: Standard precautions (SP) as the cornerstone of infection control, with hand hygiene and mask use as key components. Debate about the relative importance of droplet versus aerosol transmission led to differences in recommendations between agencies at the onset of the pandemic. We have clarified the role of personal protective equipment (PPE), including eye protection. The effectiveness of masks in pre-venting transmission is reviewed. The use of surgical masks is recommended to prevent droplet transmission, while eye protection is recommended in combination with masks. Although data show some risk reduction, the clear superiority of N95/FFP2 over surgical masks remains unproven. In terms of room occupancy, ventilation is critical in reducing the risk of transmission in poorly ventilated environments. The use of negative pressure isolation rooms (NPIRs) is being investigated. The presence of viral RNA on surfaces does not necessarily indicate infectivity, and the risk of transmission by surface contact is low if surfaces are properly maintained and hand hygiene is practised regularly. Testing for SARS-CoV-2 in asymptomatic persons in healthcare settings may help prevent transmission; (4) Conclusions: Prevention of SARS-CoV-2 transmission requires a multifaceted approach, including reducing particle emissions from infected persons by wearing masks, eliminating aerosols by ventilation, ensuring physical separation, and protecting exposed persons with masks and eye protection.

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic presumptive UTI patients and correlated them with detected levels of immune response biomarkers NGAL, IL-8, and IL-1β. The objective was to identify changes in immune response at different microbial densities and determine an optimal threshold for diagnosing symptomatic UTIs. Midstream clean-catch urine samples were analyzed for microbial identification and quantification using SUC and M-PCR, while NGAL, IL-8, and IL-1β levels were measured with ELISA. NGAL, IL-8, and IL-1β levels were all significantly higher in symptomatic subjects with microbial densities ≥ 10,000 cells/mL by M-PCR (p < 0.0069) or equivalent CFUs/mL by SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥ 10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable for diagnosing UTIs. These findings challenge the widely used threshold of 100,000 CFU per mL, which may overlook many active UTI cases.

The reported study was devoted to the investigation of viscoelastic behavior for solid and porous ultra-high-molecular-weight polyethylene (UHMWPE) under compression. The obtained experimental stress curves were interpreted using a two-term Prony series to represent the superposition of two coexisting activation processes corresponding to long molecular (~160 s) and short structural (~20 s) time scales, respectively, leading to good statistical correlation with the observations. In the case of porous polymer, the internal strain redistribution during relaxation was quantified using Digital Image Correlation (DIC) analysis. The strongly inhomogeneous deformation of the porous polymer was found not to affect the relaxation times. In order to generalize the results to three dimensions, X-ray tomography was used to examine the porous structure at the macro- and micro-scale levels. DIC analysis revealed positive correlation between the applied force and relative density. The apparent stiffness variation for UHMWPE foams with mixed open and closed cells was described using a newly proposed three-term expression. Furthermore, the in situ tensile loading and X-ray scattering study was applied for isotropic solid UHMWPE specimens to investigate their parameters of internal structure during orientation and stress relaxation process at another mode.

The COVID-19 pandemic has created huge damage to society and brought panics around the world. Such panics can be ascribed to the seemingly deceptive features of the COVID-19: compared to other deadly viral outspreads, it has medium transmission and mortality rates. As a result, the severity of the causative coronavirus, SARS-CoV-2, was deeply underestimated by the society at the beginning of the COVID-19 outbreak. Based on this, in this review, we define the viruses with features similar to those of SARS-CoV-2 as the Panic Zone viruses. To contain those viruses, accurate and fast diagnosis followed by effective isolation and treatment of patients are pivotal at the early stage of virus breakouts. This is especially true when there is no cure or vaccine available for a transmissible disease, which is the case for current COVID-19 pandemic. As of January 2021, more than two hundred kits for the COVID-19 diagnosis on the market are surveyed in this review, while emerging sensing techniques for SARS-CoV-2 are also discussed. It is of critical importance to rationally use these kits for the efficient management and control of the Panic Zone viruses. Therefore, we discuss guidelines to select diagnostic kits at different outbreak stages of the Panic Zone viruses, SARS-CoV-2 in particular. While it is of utmost importance to use nucleic acid-based detection kits with low false negativity (high sensitivity) at the early stage of an outbreak, the low false positivity (high specificity) gains its importance at later stages of the outbreak. When a society is set to reopen from the lock-down stage of the COVID-19 pandemic, it becomes critical to have antibody based immunoassay kits with high specificity to identify people who can safely return to the society after their recovery of SARS-CoV-2 infections. Given that the emergence of mutant viruses at the beginning of 2021 has complicated current battle against the COVID-19, we also discussed approaches and guidelines to detect viral mutants in the middle of the second wave of the pandemic that started at the end of 2020. Finally, since a massive attack from a viral pandemic requires a massive defense from the whole society, we urge both government and private sectors to research and develop more affordable and reliable point-of-care testing (POCT) kits, which can be used massively by the general public (and therefore called as massive POCT) to contain Panic Zone viruses in future.

The formation and propagation of cracks occurs through irreversible dislocation movements at notches, material defects and grain boundaries. Since this process is partly thermally controlled, the resistance to dislocation movements at low temperatures increases. This slows both fatigue initiation and fatigue crack propagation. From recent experimental data, it can be seen that fatigue crack growth is accelerated below the fatigue transition temperature (FTT) that correlates with the ductile-brittle transition temperature (DBTT) found by well-known fracture mechanics tests, i.e., Charpy impact, fracture toughness, and CTOD. Hence, this study investigates the relation between FTT and DBTT in S500 high-strength steel base material and welded joints at low temperatures using fatigue crack growth, fracture toughness tests as well as scanning electron microscopy. From the tests, an almost constant decrease in fatigue crack propagation rate is determined with decreasing test temperature even below the DBTT.