Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants

PURPOSE To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first primary cancer types adjusting for family ascertainment. RESULTS BRCA1 PVs were associated with risks of male breast (RR = 4.30; 95% CI, 1.09 to 16.96), pancreatic (RR = 2.36; 95% CI, 1.51 to 3.68), and stomach (RR = 2.17; 95% CI, 1.25 to 3.77) cancers. Associations with colorectal and gallbladder cancers were also suggested. BRCA2 PVs were associated with risks of male breast (RR = 44.0; 95% CI, 21.3 to 90.9), stomach (RR = 3.69; 95% CI, 2.40 to 5.67), pancreatic (RR = 3.34; 95% CI, 2.21 to 5.06), and prostate (RR = 2.22; 95% CI, 1.63 to 3.03) cancers. The stomach cancer RR was higher for females than males (6.89 v 2.76; P = .04). The absolute risks to age 80 years ranged from 0.4% for male breast cancer to approximately 2.5% for pancreatic cancer for BRCA1 carriers and from approximately 2.5% for pancreatic cancer to 27% for prostate cancer for BRCA2 carriers. CONCLUSION In addition to female breast and ovarian cancers, BRCA1 and BRCA2 PVs are associated with increased risks of male breast, pancreatic, stomach, and prostate (only BRCA2 PVs) cancers, but not with the risks of other previously suggested cancers. The estimated age-specific risks will refine cancer risk management in men and women with BRCA1/2 PVs.
Plesiomonas shigelloides, an Atypical Enterobacterales with a Vibrio-Related Secondary Chromosome

Abstract About 10% of bacteria have a multichromosome genome with a primary replicon of bacterial origin, called the chromosome, and other replicons of plasmid origin, the chromids. Studies on multichromosome bacteria revealed potential points of coordination between the replication/segregation of chromids and the progression of the cell cycle. For example, replication of the chromid of Vibrionales (called Chr2) is initiated upon duplication of a sequence carried by the primary chromosome (called Chr1), in such a way that replication of both replicons is completed synchronously. Also, Chr2 uses the Chr1 as a scaffold for its partition in the daughter cells. How many of the features detected so far are required for the proper integration of a secondary chromosome in the cell cycle? How many more features remain to be discovered? We hypothesized that critical features for the integration of the replication/segregation of a given chromid within the cell cycle program would be conserved independently of the species in which the chromid has settled. Hence, we searched for a chromid related to that found in Vibrionales outside of this order. We identified one in Plesiomonas shigelloides, an aquatic and pathogenic enterobacterium that diverged early within the clade of Enterobacterales. Our results suggest that the chromids present in P. shigelloides and Vibrionales derive from a common ancestor. We initiated in silico genomic and proteomic comparative analyses of P. shigelloides, Vibrionales, and Enterobacterales that enabled us to establish a list of features likely involved in the maintenance of the chromid within the host cell cycle.
A Remote Monitoring System to Optimize the Home Management of Oral Anticancer Therapies (ONCO-TreC): Prospective Training–Validation Trial

Background A platform designed to support the home management of oral anticancer treatments and provide a secure web-based patient–health care professional communication modality, ONCO-TreC, was tested in 3 cancer centers in Italy. Objective The overall aims of the trial are to customize the platform; assess the system’s ability to facilitate the shared management of oral anticancer therapies by patients and health professionals; and evaluate system usability and acceptability by patients, caregivers, and health care professionals. Methods Patients aged ≥18 years who were candidates for oral anticancer treatment as monotherapy with an Eastern Cooperative Oncology Group performance status score of 0 to 1 and a sufficient level of familiarity with mobile devices were eligible. ONCO-TreC consisted of a mobile app for patients and a web-based dashboard for health care professionals. Adherence to treatment (pill count) and toxicities reported by patients through the app were compared with those reported by physicians in medical records. Usability and acceptability were evaluated using questionnaires. Results A total of 40 patients were enrolled, 38 (95%) of whom were evaluable for adherence to treatment. The ability of the system to measure adherence to treatment was high, with a concordance of 97.3% (95% CI 86.1%-99.9%) between the investigator and system pill count. Only 60% (3/5) of grade 3, 54% (13/24) of grade 2, and 19% (7/36) of grade 1 adverse events reported by physicians in the case report forms were also reported in the app directly by patients. In total, 94% (33/35) of patients had ≥1 app launch each week, and the median number of daily accesses per patient was 2. Approximately 71% (27/38) and 68% (26/38) of patients used the app for messages and vital sign entering, respectively, at least once during the study period. Conclusions ONCO-TreC is an important tool for measuring and monitoring adherence to oral anticancer drugs. System usability and acceptability were very high, whereas its reliability in registering toxicity could be improved. Trial Registration ClinicalTrials.gov NCT02921724; https://www.clinicaltrials. gov/ct2/show/NCT02921724
Assessment of microvascular rarefaction in human brain disorders using physiological magnetic resonance imaging

Cerebral microvascular rarefaction, the reduction in number of functional or structural small blood vessels in the brain, is thought to play an important role in the early stages of microvascular related brain disorders. A better understanding of its underlying pathophysiological mechanisms, and methods to measure microvascular density in the human brain are needed to develop biomarkers for early diagnosis and to identify targets for disease modifying treatments. Therefore, we provide an overview of the assumed main pathophysiological processes underlying cerebral microvascular rarefaction and the evidence for rarefaction in several microvascular related brain disorders. A number of advanced physiological MRI techniques can be used to measure the pathological alterations associated with microvascular rarefaction. Although more research is needed to explore and validate these MRI techniques in microvascular rarefaction in brain disorders, they provide a set of promising future tools to assess various features relevant for rarefaction, such as cerebral blood flow and volume, vessel density and radius and blood-brain barrier leakage.
Objective evaluation of stimulation artefact removal techniques in the context of neural spike sorting

Objective. We present a framework to objectively test and compare stimulation artefact removal techniques in the context of neural spike sorting. Approach. To this end, we used realistic hybrid ground-truth spiking data, with superimposed artefacts from in vivo recordings. We used the framework to evaluate and compare several techniques: blanking, template subtraction by averaging, linear regression, and a multi-channel Wiener filter (MWF). Main results. Our study demonstrates that blanking and template subtraction result in a poorer spike sorting performance than linear regression and MWF, while the latter two perform similarly. Finally, to validate the conclusions found from the hybrid evaluation framework, we also performed a qualitative analysis on in vivo recordings without artificial manipulations. Significance. Our framework allows direct quantification of the impact of the residual artefact on the spike sorting accuracy, thereby allowing for a more objective and more relevant comparison compared to indirect signal quality metrics that are estimated from the signal statistics. Furthermore, the availability of a ground truth in the form of single-unit spiking activity also facilitates a better estimation of such signal quality metrics.
PULSE CURRENT PARAMETER EVALUATION OF TYPICAL PARTIAL DISCHARGE MODELS IN OIL

According to the characteristics of partial discharge(PD)pulse waveform in tra nsformer oil and on the basis of combining multi-resolution analysis with soft -threshold, a novel wavelet de-noising algorithm for suppressing nois es is presented. The evaluated pulse parameters of discharge waveform are analyz ed and processed. The results from above analysis and processing show that the c ontradiction between partial characteristic and restraining noise can be settled well by soft threshold which is suitable for processing the waveform of single PD pulse. The partial characteristics of discharge pulse waveforms of different PD models are distinct. Evaluating the waveform characteristic parameters corres ponding to each discharge, the recognition of discharge type can be carried out well.
A Comparison of Vibrotactile Feedback and Electrical Muscle Stimulation (EMS) for Motor Response During Active Hand Movement

Wearable haptic technologies have garnered recent widespread attention due to increased accessibility, functionality, and affordability. These systems typically provide haptic feedback to augment the human ability to interact with their environment. This study compares two haptic feedback modalities, vibrotactile and EMS, against visual feedback to elicit a motor response during active hand movement. Forty-five participants, divided into three groups, performed a task to touch their face and received one of three possible sensory feedback cues, namely visual, vibrotactile, and electrical muscle stimulation (EMS), to interrupt their movement and avoid touching their face. Two quantitative performance measures are used in the comparison, the response time (time elapsed from stimulation to motor response) and the error rate (percentage that the user fails to avoid touching their face). Results showed that vibrotactile and EMS feedback yielded significantly faster response time than visual feedback, while no significant differences between vibrotactile and EMS were observed. Furthermore, the error rate was significantly lower for EMS compared to visual feedback, whereas no significant differences were observed between vibrotactile and visual feedback. In conclusion, it seems that EMS feedback is preferable for applications where errors are not tolerable (critical medical applications), whereas vibrotactile is superior for non-critical applications due to its low cost and higher usability (more pleasant compared to EMS).
Heart rate variability increases following automated acoustic slow wave sleep enhancement

Acoustic stimulation has been shown to enhance slow wave sleep and in turn, cognition, and now cardiac outcomes in young adults. With the emergence of commercial acoustic devices in the home, we sought to examine the impact of an acoustic, slow wave enhancing device on heart rate variability in healthy, middle‐aged males (n = 24, 39.92 ± 4.15 years). Under highly controlled conditions, the participants were randomised to receive closed‐loop brain state‐dependent stimulation in the form of auditory tones (STIM), or no tones (SHAM), in a crossover design, separated by a 1 week washout period. STIM and SHAM were compared on measures of heart rate variability for the whole night and over the first three sleep cycles. We found an increase in slow wave activity following STIM compared with SHAM. There was a significant increase in high frequency power and standard deviation of the normalised RR‐intervals (SDNN) during the STIM condition compared with SHAM (p < 0.05), due to changes observed specifically during N3. In conclusion, heart rate variability appears to improve following acoustic slow wave sleep enhancement.
Advances of research on parameterized dynamic models of magnetorheological dampers

Magnetorheological (MR) damper is a kind of intelligent actuator, which shows immense potential in the field of engineering structure. The researches on parameterized dynamic models of magnetorheological dampers are summarized. The advantages and disadvantages of every model are analyzed. And the problem of how to design the control law to make the dissipative ability of MR damper under fluctuating current be optimal is also discussed. The intelligent technology such as neural network and fuzzy logic may be an effective solution for practical applications.
eHealth Interventions to Support Self-Management in People With Musculoskeletal Disorders, “eHealth: It’s TIME”—A Scoping Review

Abstract Objective eHealth-mediated interventions have been proposed as one option to support self-management in those with musculoskeletal disorders (MSDs). This scoping review aimed to chart the evidence regarding eHealth modalities, musculoskeletal diagnosis, and outcomes of eHealth-mediated self-management support interventions in persons with MSDs and identify any gaps within the literature. Methods Six electronic databases (MEDLINE, CINAHL, PsycINFO, Embase, Scopus, and the Cochrane Database of Systematic Reviews), 7 grey literature sources (eg, OpenGrey), and reference and citation lists of included studies were searched from database inception to July 2020. Published studies of adult participants with a MSD utilizing an eHealth intervention to support self-management were included. Studies were limited to those published in English. Two reviewers independently screened all studies. Data were extracted by 1 reviewer and reviewed by another reviewer. Results After screening 3377 titles and abstracts followed by 176 full texts, 87 studies fulfilled the eligibility criteria. The majority were published in the last 5 years (n = 48; 55%), with almost one-third originating in the United States (n = 28; 32%). The most common eHealth modality type was internet based (n = 22; 35%), with almost one-half (n = 41; 47%) of the included studies involving participants with widespread musculoskeletal symptoms. The most commonly reported outcomes were related to body functions (ie, pain intensity) (n = 67; 45%), closely followed by activities and participation (ie, function) (n = 65; 44%), with environmental factors (ie, health care utilization) the least commonly reported (n = 17; 20%). Conclusions There is considerable variation within the eHealth-mediated self-management support intervention literature. Research is needed on the role of eHealth-mediated self-management support interventions across a broad range of MSDs to guide clinical practice. Impact This scoping review has identified gaps in the literature relating to specific eHealth modalities, musculoskeletal diagnoses, and health care utilization data, which should guide future research.
Single Entry Posterior Parasagittal Approach Radiofrequency Neurotomy of Cervical Medial Branch: A Feasible Alternative to Conventional Approaches in the Treatment of Cervical Facet Pain

Background Cervical facet joint pain is an important cause of chronic neck pain. The recommended treatment for this condition is radiofrequency (RF) neurotomy of the medial branch of dorsal rami. There have been attempts to find safe and effective ways to perform this procedure. The objective of this study is to describe the single entry posterior parasagittal approach and to evaluate the efficacy and safety of this approach compared to the conventional posterolateral approach of RF neurotomy of cervical medial branch. Methods The record of all patients with cervical facet pain who were treated with RF neurotomy medial branch of dorsal rami between January 2016 and December 2019 were reviewed retrospectively. Comparisons were made between patients who underwent RF neurotomy with multiple skin entry posterolateral approach and those who underwent RF neurotomy with single entry posterior parasagittal approach. The primary outcome was measured as the mean changes in numerical rating scale (NRS), and the secondary outcomes were duration and complications related to both approaches. Results Thirty-one patients who underwent RF neurotomy via posterolateral approach were compared with 40 patients who underwent the procedure via posterior parasagittal approach. Both approaches showed a significant decrease in the NRS from baseline values. However, the differences in the NRS lowering effect at 3 and 12 months between these 2 approaches were not statistically significant. The duration of the procedure was significantly shorter with posterior parasagittal approach (44.13 ± 4.72 minutes vs 54.68 ± 7.39 minutes; P < 0.001). There were no serious complications encountered in both approaches. Conclusions With comparable efficacy and safety profile between the posterior parasagittal and the conventional posterolateral approaches, the former single skin entry approach offers the added advantage of being less time-consuming. Further randomized prospective studies are necessary to validate these findings.
Identification of the Extracytoplasmic Function σ Factor σP Regulon in Bacillus thuringiensis

Antimicrobial resistance is major concern for public health. β-Lactams remain an important treatment option for many diseases. However, the spread of β-lactam resistance continues to rise. ABSTRACT Bacillus thuringiensis and other members of the Bacillus cereus family are resistant to many β-lactams. Resistance is dependent upon the extracytoplasmic function sigma factor σP. We used label-free quantitative proteomics to identify proteins whose expression was dependent upon σP. We compared the protein profiles of strains which either lacked σP or overexpressed σP. We identified 8 members of the σP regulon which included four β-lactamases as well as three penicillin-binding proteins (PBPs). Using transcriptional reporters, we confirmed that these genes are induced by β-lactams in a σP-dependent manner. These genes were deleted individually or in various combinations to determine their role in resistance to a subset of β-lactams, including ampicillin, methicillin, cephalexin, and cephalothin. We found that different combinations of β-lactamases and PBPs are involved in resistance to different β-lactams. Our data show that B. thuringiensis utilizes a suite of enzymes to protect itself from β-lactam antibiotics. IMPORTANCE Antimicrobial resistance is major concern for public health. β-Lactams remain an important treatment option for many diseases. However, the spread of β-lactam resistance continues to rise. Many pathogens acquire antibiotic resistance from environmental bacteria. Thus, understanding β-lactam resistance in environmental strains may provide insights into additional mechanisms of antibiotic resistance. Here, we describe how a single regulatory system, σP, in B. thuringiensis controls expression of multiple genes involved in resistance to β-lactams. Our findings indicate that some of these genes are partially redundant. Our data also suggest that the large number of genes controlled by σP results in increased resistance to a wider range of β-lactam classes than any single gene could provide.
The nuclear receptor Hr46/Hr3 is required in the blood brain barrier of mature males for courtship

The blood brain barrier (BBB) forms a stringent barrier that protects the brain from components in the circulation that could interfere with neuronal function. At the same time, the BBB enables selective transport of critical nutrients and other chemicals to the brain. Beyond these functions, another recently recognized function is even less characterized, specifically the role of the BBB in modulating behavior by affecting neuronal function in a sex-dependent manner. Notably, signaling in the adult Drosophila BBB is required for normal male courtship behavior. Courtship regulation also relies on male-specific molecules in the BBB. Our previous studies have demonstrated that adult feminization of these cells in males significantly lowered courtship. Here, we conducted microarray analysis of BBB cells isolated from males and females. Findings revealed that these cells contain male- and female-enriched transcripts, respectively. Among these transcripts, nuclear receptor Hr46/Hr3 was identified as a male-enriched BBB transcript. Hr46/Hr3 is best known for its essential roles in the ecdysone response during development and metamorphosis. In this study, we demonstrate that Hr46/Hr3 is specifically required in the BBB cells for courtship behavior in mature males. The protein is localized in the nuclei of sub-perineurial glial cells (SPG), indicating that it might act as a transcriptional regulator. These data provide a catalogue of sexually dimorphic BBB transcripts and demonstrate a physiological adult role for the nuclear receptor Hr46/Hr3 in the regulation of male courtship, a novel function that is independent of its developmental role.
Wearable Haptic Device Presenting Sensations of Fingertips to the Forearm

Several existing haptic displays used in virtual reality (VR) environments present haptic sensations generated by the fingertips in the VR to actual fingertips. However, these devices face certain challenges, such as physical interference between the devices, particularly when multi-degree-of-freedom (DOF) force needs to be presented to multiple fingers. To address this issue, we propose a haptic presentation method that transmits haptic sensations generated by the fingertips in the VR, including the direction of the force, to the forearm. We previously proposed a method to present both magnitude and direction of the force applied to the index finger using a five-bar linkage mechanism, which transmits the force sensation with two DOF to the forearm. In this study, the forces in the downward and left-right directions were obtained from the kinematics of a five-bar linkage mechanism for accurate force presentation. Additionally, we conducted a user study evaluating user grasping an object in the VR and performing task. The results verified the haptic sensation of the force transmitted by the proposed prototype to the user's forearm provides a sufficient comfort level. Furthermore, the task execution time and comfort level were comparable to those of a vibrotactile presentation presented directly to the fingertips.