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Evolutionary hypotheses on the ratio of males to females at birth posit that women terminate pregnancies with low likelihood of surviving and producing grandchildren. Thus, females are preferred to males under unfavorable conditions. Much of this literature has focused on catastrophic disruptions that induce maternal stress and result in fewer males. Diabetes may similarly affect the sex ratio.

A male bias at birth among infants born to women with GDM is widely recognized; mild hyperglycemia experienced early in pregnancy may signal favorable conditions and warrant investment in males. There are sparse data on women with pregestational diabetes, but some evidence for a female bias born to those with type 1 diabetes and severe hyperglycemia (i.e., requiring insulin). Disease-related maternal stress in these women may lead to the selective termination of male fetuses. Further examination of pregestational diabetes stands to contribute to scientific understanding of the sex ratio.

A male bias at birth among infants born to women with GDM is widely recognized; mild hyperglycemia experienced early in pregnancy may signal favorable conditions and warrant investment in males. There are sparse data on women with pregestational diabetes, but some evidence for a female bias born to those with type 1 diabetes and severe hyperglycemia (i.e., requiring insulin). Disease-related maternal stress in these women may lead to the selective termination of male fetuses. Further examination of pregestational diabetes stands to contribute to scientific understanding of the sex ratio.

Nowadays, several novel agents have been introduced in the treatment of multiple myeloma, not only resulting in high response rates and prolonged survival but also offering good quality of life. selleck chemicals llc However, the potential of cure, especially for patients with advanced or unfavorable disease features, remains elusive. Allogeneic hematopoietic stem cell transplantation, based mainly on the graft vs. myeloma effect, can offer prolonged disease control and probability of cure but unfortunately at the cost of considerable transplant-related toxicity rates. Therefore, the role of allogeneic hematopoietic stem cell transplantation in the treatment of multiple myeloma has been called into question. Recently, several studies, particularly those with long-term follow-up, demonstrated a trend of survival superiority for allografted patients with high-risk disease. These data fuel again the interest in allogeneic stem cell transplantation for selected patients with high-risk multiple myeloma, especially if the high remissiuperiority for allografted patients with high-risk disease. These data fuel again the interest in allogeneic stem cell transplantation for selected patients with high-risk multiple myeloma, especially if the high remission rates which can be achieved with the currently used treatment protocols could be long-life sustained through the additional exploitation of the long-lasting anti-multiple myeloma effect, originating from the allograft.Urban development has positive and negative effects on the evolution of enclosed lake water quality. This study aims to quantitatively analyze the water quality evolution of a typical urban lake, the Sha Lake, in the process of urban development. The land use degree comprehensive index (I) was calculated to reveal the level of urban development; water quality index (Smid) and eutrophication index (Tmid) were used to evaluate the water quality changes by fuzzy comprehensive-quantifying assessment (FCQA) method. The urban construction process and the water quality changes in 2000-2018 in the Sha Lake Basin were divided into three stages (1) in 2000-2006, with the slow urban development, water quality remained stable and the degree of eutrophication improved slightly; (2) in 2007-2009, I increased rapidly to reach 300, Smid and Tmid increased from 90.62 to 92.83 and 75.06 to 87.52, respectively. Water quality deteriorated because of the failure to implement environmental protection measures in time; (3) in 2010-2018, although urban development reached a high level (I > 300), the water network connection project, dredging project, exogenous pollutant control, and sewage pipe network renovation since 2009 were critical measures to improve water quality for a long time. Due to the lag effect on improving water quality, the implementation of environmental protection measures should be synchronized with or even before urban construction. The research results can provide a scientific basis for the urban lake water environment protection in the process of urban development.

Advanced colorectal cancer (CRC) is a heterogeneous disease, characterized by several subtypes with distinctive genetic and epigenetic patterns. During the last years, immune checkpoint inhibitors (ICIs) have revamped the standard of care of several tumors such as non-small cell lung cancer and melanoma, highlighting the role of immune cells in tumor microenvironment (TME) and their impact on cancer progression and treatment efficacy. An "immunoscore," based on the percentage of two lymphocyte populations both at tumor core and invasive margin, has been shown to improve prediction of treatment outcome when added to UICC-TNM classification. To date, pembrolizumab, an anti-programmed death protein 1 (PD1) inhibitor, has gained approval as first-line therapy for mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) advanced CRC. On the other hand, no reports of efficacy have been presented in mismatch-repair-proficient (pMMR) and microsatellite instability-low (MSI-L) or microsatellite smor core and invasive margin, has been shown to improve prediction of treatment outcome when added to UICC-TNM classification. To date, pembrolizumab, an anti-programmed death protein 1 (PD1) inhibitor, has gained approval as first-line therapy for mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) advanced CRC. On the other hand, no reports of efficacy have been presented in mismatch-repair-proficient (pMMR) and microsatellite instability-low (MSI-L) or microsatellite stable (MSS) CRC. This group includes roughly 95% of all advanced CRC, and standard chemotherapy, in addition to anti-EGFR or anti-angiogenesis drugs, still represents first treatment choice. Hopefully, deeper understanding of CRC immune landscape and of the impact of specific genetic and epigenetic alterations on tumor immunogenicity might lead to the development of new drug combination strategies to overcome ICIs resistance in pMMR CRC, thus paving the way for immunotherapy even in this subgroup.