Ribonuclease, RNase A family, 9 (RNASE9) is a ribonuclease A superfamily member that is expressed only in the epididymis. It is a small, secreted polypeptide, it lacks ribonuclease activity, and its ...function(s) is unknown. However, epididymis-specific expression suggests a role in sperm maturation. We generated Rnase9−/− mice to study RNASE9 function in vivo. We confirm that RNASE9 expression is restricted to the epididymis. Within the epididymis, RNASE9 is first detected in midcaput, persists through the distal caput and corpus, and wanes in the cauda. Rnase9−/− mice are born at the expected Mendelian ratio, have normal postnatal growth and development, and have no outwardly apparent phenotype. Spermatogenesis is normal, and Rnase9-null sperm are morphologically normal. Rnase9−/− males have normal fertility in unrestricted mating trials, and fertilization rates in in vitro fertilization assays are indistinguishable from wild-type mice. Visual observations coupled with analyses of sperm velocities shortly after swim out from the corpus shows that motility of Rnase9-null sperm is significantly impaired. However, no differences between wild-type and Rnase9-null sperm are detected by computer-assisted sperm analysis 10–90 min after sperm isolation from the corpus or cauda. Assessment of capacitation-dependent signaling pathways in Rnase9-null sperm showed that, while levels of tyrosine phosphorylation of sperm proteins were normal, there was decreased phosphorylation of protein kinase A substrates upon capacitation compared to wild-type mice. In conclusion, RNASE9 is dispensable for fertility, but the absence of RNASE9 during epididymal transit results in impaired sperm maturation.
Abstract
Background
There is a limited number of treatment options for patients with corticosteroid refractory ulcerative colitis (UC). We aimed to evaluate tacrolimus for induction of remission in ...these patients.
Methods
MEDLINE, Embase, CENTRAL, Clinicaltrials.gov and ICTRP were searched up to October, 2021 to identify all relevant randomised contolled trials (RCTs). The authors independently reviewed potentially relevant studies to determine eligibility based on pre-specified criteria. A data extraction form was developed and used to extract data from included studies. Data were analysed using Review Manager. The primary outcomes were induction of remission and clinical improvement, as defined by the studies.
Results
Five RCTs were included with a total of, 347 participants with active UC. There is low certainty (oral and rectal) tacrolimus may be superior for clinical remission when compared to placebo (14/87 to, 1/61, RR, 3.76, 95% CI, 1.03 to, 13.73). There is low certainty (oral and rectal) tacrolimus may be superior for clinical improvement when compared to placebo (45/87 to, 7/61, RR, 4.47, 95% CI, 2.15 to, 9.29. The results on adverse events are of very low certainty and no conclusions can be drawn. There is low certainty there may be no difference in achievement of clinical remission when tacrolimus suppositories (16/44) were compared to beclomethasone (15/44) (RR, 1.07, 95% CI, 0.60 to, 1.88). There is low certainty there may be no difference in clinical improvement when tacrolimus suppositories (22/44) were compared to beclomethasone (22/44) (RR, 1.00, 95% CI, 0.66 to, 1.88). There is low cerainty there may be no difference in serious adverse events when tacrolimus suppositories (1/44) were compared to placebo suppositories (0/44) (RR, 1.00, 95% CI, 0.13 to, 71.70) and total adverse events (21/44 to, 14/44) (RR, 1.50, 95% CI, 0.88 to, 2.55). The evidence on the efficacy and safety of tacrolimus compared to cyclosporine is of very low quality and no conclusions can be drawn.
Conclusion
The cohorts studied are small, with missing data sets, short follow-up, and the clinical endpoints used are not in line with those suggested by regulatory bodies. No clinical practice conclusions can be made.This review highlights the need for further research that targets relevant clinical questions, uses appropriate trial methodology, and reports key findings in a systematic manner that facilitates future integration of findings with current evidence to better inform clinicians and patients. Future studies need to be adequately powered and of pertinent duration to capture the effectiveness of tacrolimus in the medium-to-long term. Well-structured efficacy studies need to be followed up by long-term phase, 4 extensions to provide key outputs and inform a real-world setting.
Abstract
Introduction
Due to the aging of the population we are confronting ourselves with an increased number of patients with chronic heart failure which stands a prevalence of over 37,7 million ...cases worldwide, being a major public health issue, first by the substantial morbidity and mortality that carries and second by the economic burden it brings annually upon the health-care system.
The main purpose of this study is to test a machine learning algorithm which can predict, through voice analysis the acutisation of heart failure, considering the particularities of the patient's voice.
Methods
The data we have used has been collected from a total of 16 patients, 9 men and 7 women, ages between 65 and 91 years old, who have agreed to take part in the study.
The selective criteria of inclusion has been the cause of hospitalization, selecting only the patients presented with cardiogenic acute pulmonary edema, regardless the precipitation cause or other known cardiovascular comorbidities. With the same electronic device we have recorded each patient's voice, twice a day, starting from the day one of hospitalization, when their general status was critical, until the day of discharge, when they were clinically stable.
Each voice recording containing specific keywords has been associated to the most used classification system for heart failure, the New York Heart Association Functional Classification and introduced into the machine learning algorithm.
Results
After integrating the information from 15 patients, the algorithm has classified correctly the 16th patient into the third NYHA stage, based only on his voice recording.
Conclusion
Voice is a cheap and easy way to monitor a patient's health status. The algorithm we have used for analyzing the voice provides high accuracy results, but for a larger dataset it might not be the best choice as it is computationally expensive. We are looking to obtain larger datasets and to compute more complex voice analyzer algorithms.
Funding Acknowledgement
Type of funding sources: None.
Ribonuclease, RNase A family, 9 (RNASE9) is a ribonuclease A superfamily member that is expressed only in the epididymis. It is a small, secreted polypeptide, it lacks ribonuclease activity, and its ...function(s) is unknown. However, epididymis-specific expression suggests a role in sperm maturation. We generated Rnase9(-/-) mice to study RNASE9 function in vivo. We confirm that RNASE9 expression is restricted to the epididymis. Within the epididymis, RNASE9 is first detected in midcaput, persists through the distal caput and corpus, and wanes in the cauda. Rnase9(-/-) mice are born at the expected Mendelian ratio, have normal postnatal growth and development, and have no outwardly apparent phenotype. Spermatogenesis is normal, and Rnase9-null sperm are morphologically normal. Rnase9(-/-) males have normal fertility in unrestricted mating trials, and fertilization rates in in vitro fertilization assays are indistinguishable from wild-type mice. Visual observations coupled with analyses of sperm velocities shortly after swim out from the corpus shows that motility of Rnase9-null sperm is significantly impaired. However, no differences between wild-type and Rnase9-null sperm are detected by computer-assisted sperm analysis 10-90 min after sperm isolation from the corpus or cauda. Assessment of capacitation-dependent signaling pathways in Rnase9-null sperm showed that, while levels of tyrosine phosphorylation of sperm proteins were normal, there was decreased phosphorylation of protein kinase A substrates upon capacitation compared to wild-type mice. In conclusion, RNASE9 is dispensable for fertility, but the absence of RNASE9 during epididymal transit results in impaired sperm maturation.
The paper presents an alternative Vold–Kalman filter order tracking (VKF_OT) method, i.e. adaptive angular-velocity VKF_OT technique, to extract and characterize order components in an adaptive ...manner for the condition monitoring and fault diagnosis of rotary machinery. The order/spectral waveforms to be tracked can be recursively solved by using Kalman filter based on the one-step state prediction. The paper comprises theoretical derivation of computation scheme, numerical implementation, and parameter investigation. Comparisons of the adaptive VKF_OT scheme with two other ones are performed through processing synthetic signals of designated order components. Processing parameters such as the weighting factor and the correlation matrix of process noise, and data conditions like the sampling frequency, which influence tracking behavior, are explored. The merits such as adaptive processing nature and computation efficiency brought by the proposed scheme are addressed although the computation was performed in off-line conditions. The proposed scheme can simultaneously extract multiple spectral components, and effectively decouple close and crossing orders associated with multi-axial reference rotating speeds.
•Adaptive angular-velocity VKFOT proposed as a counterpart of angular-displacement scheme.•Order/spectral waveforms recursively tracked by Kalman filtering based on the one-step state prediction.•Adaptive processing nature characterized and discussed although performed in off-line conditions.•Parameter investigation conducted through processing three synthesized signals.•Comprehensive comparison including computation efficiency among three OT schemes.
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