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Breast malignancy is the most frequently diagnosed malignancy in women worldwide, and the diagnosis relies on invasive examinations. However, most clinical breast changes in women are benign, and invasive diagnostic approaches cause unnecessary suffering for the patients. Thus, a novel noninvasive approach for discriminating malignant breast lesions from benign lesions is needed.

We performed cell-free DNA (cfDNA) sequencing on plasma samples from 173 malignant breast lesion patients, 158 benign breast lesion patients, and 102 healthy women. We then analyzed the cfDNA-based nucleosome profiles, which reflect the various tissues of origin and transcription factor activities. Moreover, by using machine learning classifiers along with the cfDNA sequencing data, we built classifiers for discriminating benign from malignant breast lesions. Receiver operating characteristic curve analyses were used to evaluate the performance of the classifiers.

cfDNA-based nucleosome profiles reflected the various tissues of origin and transcription factor activities in benign and malignant breast lesions. The cfDNA-based transcription factor activities and breast malignancy-specific transcription factor-binding site accessibility profiles could accurately distinguish benign and malignant breast lesions, with area under the curve values of 0.777 and 0.824, respectively.

Our proof-of-principle study established a methodology for noninvasively discriminating benign from malignant breast lesions.

Our proof-of-principle study established a methodology for noninvasively discriminating benign from malignant breast lesions.Obesity is characterized by the excessive accumulation of the white adipose tissue (WAT), but healthy expansion of WAT via adipocyte hyperplasia can offset the negative metabolic effects of obesity. Thus, identification of novel adipogenesis regulators that promote hyperplasia may lead to effective therapies for obesity-induced metabolic disorders. Using transcriptomic approaches, we identified transmembrane BAX inhibitor motif-containing 1 (TMBIM1) as an inhibitor of adipogenesis. Gain or loss of function of TMBIM1 in preadipocytes inhibited or promoted adipogenesis, respectively. In vivo, in response to caloric excess, adipocyte precursor (AP)-specific Tmbim1 knockout (KO) mice displayed WAT hyperplasia and improved systemic metabolic health, while overexpression of Tmbim1 in transgenic mice showed the opposite effects. Moreover, mature adipocyte-specific Tmbim1 KO did not affect WAT cellularity or nutrient homeostasis. Mechanistically, TMBIM1 binds to and promotes the autoubiquitination and degradation of NEDD4, which is an E3 ligase that stabilizes PPARγ. Our data show that TMBIM1 is a potent repressor of adipogenesis and a potential therapeutic target for obesity-related metabolic disease.

To evaluate the incidence of vitreoretinal complications, treatment modalities, and the visual outcomes in a large cohort of eyes that underwent Boston Keratoprosthesis (KPro) implantation.

Retrospective, interventional case series.

132 eyes of 114 patients who underwent KPro implantation at the Centre Hospitalier de l’Université de Montréal from 2008 to 2017 were included with at least 1 year follow-up. Charts were reviewed and data was collected, including demographics, initial corneal indication for surgery, posterior segment complications, preoperative and postoperative visual acuity.

Mean follow-up was 68.2 months and 61.4% of eyes developed postoperative vitreoretinal complications (VRC). The most common VRC was RPM formation (38.6%, n=51) followed by RD (15.2%, n=20), CME (12.1%, n=16), ERM (9.8%, n=13), endophthalmitis (9.1%, n=12), sterile vitritis (7.6%, n=10), vitreous hemorrhage (6.8%, n=9), choroidal detachment (3.0%, n=4) and central retinal vein occlusion (0.7%, n=1). BCVA improved in the no VRC group from 1.74 ± 0.33 logMAR to 1.33±0.83 logMAR and in the VRC group from 1.74±0.36 logMAR to 1.52±0.83 logMAR, without any statistically significant intergroup differences (p=0.231). RD was the only significant complication associated with poorer visual outcomes (p=0.001).

Potentially blinding secondary complications occur in the majority of patients and frequent monitoring is necessary, specifically in the early and intermediate postoperative periods. This study evidenced significant improvements in visual outcomes of KPro eyes, including those that developed postoperative vitreoretinal complications.

Potentially blinding secondary complications occur in the majority of patients and frequent monitoring is necessary, specifically in the early and intermediate postoperative periods. This study evidenced significant improvements in visual outcomes of KPro eyes, including those that developed postoperative vitreoretinal complications.

To investigate the characteristics and rate of central visual field loss after optic disc hemorrhages (DH).

Prospective cohort study.

343 eyes of 220 subjects who had at least 3 years of follow-up with minimum of 5 visits with 10-2 and 24-2 visual field (VF) were recruited. Rates of 10-2 mean deviation (MD) loss in each hemifield and pre-defined zones were compared using linear mixed-effects model in DH and non-DH eyes. Clustered pointwise regression analysis was also used to define central VF progressors and compared to 24-2 VF loss using Guided Progression Analysis.

39 eyes with DH and 304 eyes without DH had a mean follow-up of 5.2 years. Eyes with DH had rates of 10-2 mean deviation (MD) loss that were 3 times faster than non-DH eyes (mean difference (95% CI) -0.36 dB/year(0.54, 0.18), p<0.001) and were 3.7 times more likely to progress (p=0.002). A larger proportion of glaucomatous eyes showed central VF progression rather than peripheral VF progression in DH group (30.8% vs. 20.5%) compared to non-DH group (10.9% vs. VX-765 mw 9.2%). In early glaucoma, the rate of 10-2 MD loss was 5.5 times faster in DH eyes than in non-DH eyes(p<0.001). Superonasal and superotemporal central VF regions progressed more rapidly than other regions, especially in DH eyes.

Central visual field loss is accelerated in glaucoma eyes with DH and it corresponds topographically to the DH location. In glaucoma patients with DH, one should consider supplementing 10-2 VFs with 24-2 VFS to monitor the disease.

Central visual field loss is accelerated in glaucoma eyes with DH and it corresponds topographically to the DH location. In glaucoma patients with DH, one should consider supplementing 10-2 VFs with 24-2 VFS to monitor the disease.