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Out of these, eight families were Israelis, they had a total of one sick child, 21 healthy children, and 21 miscarriages. Our observations support the previous knowledge that homozygosity for c.964-1G&gt;C in DHCR7 leads to a severe phenotype or early miscarriage. An unexpected observation was the excess of early miscarriages. This phenomenon is unclear and awaits further studies.Immune-checkpoint inhibitors (ICIs) are approved in the first-line and third-line settings for patients with extensive-stage or relapsed small-cell lung cancer (SCLC), respectively. In the first-line setting, the addition of the anti-programmed cell death 1 ligand 1 (PD-L1) antibody atezolizumab to chemotherapy improves overall survival (OS). In patients with relapsed disease, data from nonrandomized trials have revealed promising responses, although a significant improvement in OS over that obtained with conventional chemotherapy was not achieved in a randomized trial in this setting. Substantial research interest exists in identifying predictive biomarkers that could guide the use of ICIs in patients with SCLC. PD-L1 expression is typically low or absent in SCLC, which has precluded its use as a predictive biomarker. Tumour mutational burden might have some predictive value, although blood-based measures of tumour mutational burden did not have predictive value in patients receiving atezolizumab plus chemotherapy in the first-line setting. After three decades, ICIs have finally enabled an improvement in OS for patients with SCLC; however, a substantial amount of research remains to be done, including identifying the optimal therapeutic strategy and predictive biomarkers. In this Review, we describe the available data on clinical efficacy, the emerging evidence regarding biomarkers and ongoing clinical trials using ICIs and other immunotherapies in patients with SCLC.OBJECTIVES Accelerated gain in fat mass (FM) in early life increases the risk for adult diseases. Longitudinal data on infant body composition are crucial for clinical and research use, but very difficult to obtain due to limited measurement tools and unsuccessful measurements between age 6-24 months. We compared FM% by dual-energy X-ray absorptiometry (DXA), with cushion to reduce movement artifacts, with FM% by air-displacement plethysmography (ADP) and evaluated the reliability of this cushion during DXA by comparing FM% with and without cushion. Subsequently, we constructed sex-specific longitudinal body composition charts from 1-24 months. METHODS In 692 healthy, term-born infants (Sophia Pluto Cohort), FM% was measured by ADP from 1-6 months and DXA with cushion from 6-24 months. At 6 months, FM% was measured in triplicate by ADP and DXA with and without cushion(n = 278), later on in smaller numbers. RESULTS At 6 months, mean FM% by DXA with cushion was 24.1 and by ADP 25.0, mean difference of 0.9% (Bland-Altman p = 0.321, no proportional bias). Mean FM% by DXA without cushion was 12.5% higher compared to ADP (Bland-Altman p  less then  0.001). DXA without cushion showed higher mean FM% compared to DXA with cushion (+11.6%, p  less then  0.001) at 6 months. Longitudinally, FM% increased between 1-6 months and decreased from 6-24 months(both p  less then  0.001). CONCLUSIONS In infants, DXA scan with cushion limits movement artifacts and shows reliable FM%, comparable to ADP. [https://www.selleckchem.com/products/ipi-549.html see more] This allowed us to construct longitudinal body composition charts until 24 months. Our study shows that FM% increases from 1-6 months and gradually declines until 24 months.Germline mutations in PTEN account for ~10% of cases of autism spectrum disorder (ASD) with coincident macrocephaly. To explore the importance of nuclear PTEN in the development of ASD and macrocephaly, we previously generated a mouse model with predominantly cytoplasmic localization of Pten (Ptenm3m4/m3m4).Cytoplasmic predominant Pten localization results in a phenotype of extreme macrocephaly and autistic-like traits. Transcriptomic analysis of the Ptenm3m4/m3m4 cortex found upregulated gene pathways related to myeloid cell activation, myeloid cell migration, and phagocytosis. These transcriptomic findings were used to direct in vitro assays on Pten wild-type and Ptenm3m4/m3m4 microglia. We found increased Iba1 and C1q expression with enhanced phagocytic capacity in Ptenm3m4/m3m4 microglia, indicating microglial activation. Moreover, through a series of neuron-microglia co-culture experiments, we found Ptenm3m4/m3m4 microglia are more efficient at synaptic pruning compared with wild-type controls. In addition, we found evidence for neuron-microglia cross-talk, where Ptenm3m4/m3m4 neurons elicit enhanced pruning from innately activated microglia. Subsequent in vivo studies validated our in vitro findings. We observed a concurrent decline in the expression of Pten and synaptic markers in the Ptenm3m4/m3m4 cortex. At ~3 weeks of age, with a 50% drop in Pten expression compared with wild-type levels, we observed enhanced activation of microglia in the Ptenm3m4/m3m4 brain. Collectively, our data provide evidence that dysregulated Pten in microglia has an etiological role in microglial activation, phagocytosis, and synaptic pruning, creating avenues for future studies on the importance of PTEN in maintaining microglia homeostasis.Microscopic satellite metastases are an adverse prognostic feature in primary cutaneous melanoma patients. The prognostic significance of microsatellites, including their number, size and distance from the primary melanoma, using the 8th edition American Joint Committee on Cancer definition, has not previously been evaluated. This study sought to determine the prognostic significance of microsatellites in histopathologically reviewed cases. Eighty-seven cases of primary cutaneous melanoma with the presence of microsatellites documented in the original pathology report and all histopathology slides available were reviewed and the findings were correlated with clinical outcome. Matched control cases were selected for all confirmed microsatellites cases. The presence of microsatellites was confirmed in 69 cases. The microsatellite group had significantly worse prognosis, with 21% 5-year disease-free survival compared with 56% in the control group (p  less then  0.001). The 5-year melanoma-specific survival was 53% in the microsatellites group and 73% in the control group (p = 0.