Neoadjuvant immunochemotherapy in the treatment of nonmetastatic muscle-invasive bladder cancer: a systematic review.

Introduction: Multiple trials are currently studying the additional effect of immunotherapy on neoadjuvant chemotherapy (NAC) in nonmetastatic muscle-invasive bladder cancer. Methods: We performed a systematic review of the literature that summarizes all ongoing trials, with their results when available. Results: From an initial 269 trials identified, 17 were included. Pathological response and pathological complete response rates of the immunotherapy + NAC combination in the cisplatin-eligible population varied between 56.6-75% and 34.0-66.7%, respectively. Two studies published their results in the cisplatin-ineligible population, with pathological complete response rates of 18 and 45.2%. Conclusion: Neoadjuvant immunochemotherapy in platinum-eligible patients results in response rates higher than those reported for NAC alone. Strong preliminary results are still lacking in the platinum-ineligible population.

When possible, chemotherapy containing cisplatin is recommended before patients undergo radical surgery for bladder cancer. Multiple studies are currently evaluating the additional effect of immunotherapy (drugs that activate the immune system). We reviewed all ongoing studies and found an apparent better control of bladder cancer with the chemotherapy + immunotherapy combination. Stronger studies are needed, however, to confirm these preliminary results. In patients who cannot receive cisplatin, different chemotherapy + immunotherapy combinations were used, but with inconclusive results.

A 174.7-dB FoM, 2nd-Order VCO-Based ExG-to-Digital Front-End Using a Multi-Phase Gated-Inverted-Ring Oscillator Quantizer.

This paper presents a second-order voltage-controlled oscillator (VCO)-based front-end for the direct digitization of biopotential signals. This work addresses the non-linearity of VCO-based ADC architectures with a mismatch resilient, multi-phase quantizer, a gated-inverted-ring oscillator (GIRO), achieving >110-dB SFDR. Leveraging the time-domain encoding of the first integrator, the ADC's power is dynamically scaled with the input amplitude enabling up to 35% power savings in the absence of motion artifacts or interference. An auxiliary input-impedance booster increases the ADC's input impedance to 50 MΩ across the entire bandwidth. Fabricated in a 65-nm CMOS process, this ADC achieves 92.3-dB SNDR in a 1 kHz BW while consuming 5.8 µW for a 174.7 dB Schreier FoM.

Biocatalytic synthesis of planar chiral macrocycles.

Macrocycles can restrict the rotation of substituents through steric repulsions, locking in conformations that provide or enhance the activities of pharmaceuticals, agrochemicals, aroma chemicals, and materials. In many cases, the arrangement of substituents in the macrocycle imparts an element of planar chirality. The difficulty in predicting when planar chirality will arise, as well as the limited number of synthetic methods to impart selectivity, have led to planar chirality being regarded as an irritant. We report a strategy for enantio- and atroposelective biocatalytic synthesis of planar chiral macrocycles. The macrocycles can be formed with high enantioselectivity from simple building blocks and are decorated with functionality that allows one to further modify the macrocycles with diverse structural features.