A hybrid positive unlabeled learning framework for uncovering scaffolds across human proteome by measuring the propensity to drive phase separation.

Scaffold proteins drive liquid-liquid phase separation (LLPS) to form biomolecular condensates and organize various biochemical reactions in cells. Dysregulation of scaffolds can lead to aberrant condensate assembly and various complex diseases. However, bioinformatics predictors dedicated to scaffolds are still lacking and their development suffers from an extreme imbalance between limited experimentally identified scaffolds and unlabeled candidates. Here, using the joint distribution of hybrid multimodal features, we implemented a positive unlabeled (PU) learning-based framework named PULPS that combined ProbTagging and penalty logistic regression (PLR) to profile the propensity of scaffolds. PULPS achieved the best AUC of 0.8353 and showed an area under the lift curve (AUL) of 0.8339 as an estimation of true performance. Upon reviewing recent experimentally verified scaffolds, we performed a partial recovery with 2.85% increase in AUL from 0.8339 to 0.8577. In comparison, PULPS showed a 45.7% improvement in AUL compared with PLR, whereas 8.2% superiority over other existing tools. Our study first proved that PU learning is more suitable for scaffold prediction and demonstrated the widespread existence of phase separation states. This profile also uncovered potential scaffolds that co-drive LLPS in the human proteome and generated candidates for further experiments. PULPS is free for academic research at http://pulps.zbiolab.cn.

APCs in sinus floor augmentation.

After tooth loss in the posterior area of the maxilla, sinus floor elevation is often required to compensate the vertical bone loss due to sinus pneumatization. This narrative review reports on the potential benefits of autologous platelet concentrates (APCs) during this procedure. As for transcrestal approach, APCs have been used as "sole" substitute/graft. However, because of the low number of clinical trials available with PRGF, and even none for PRP, no definitive conclusions can be made regarding their efficacy. The number of studies on the use of L-PRF were outnumbered indicating good feasibility for vertical bone gain, with a high implant survival rate and a low degree of complications. PRP and PRGF have not been studied as a "single/sole" substitute for a one-stage lateral window approach, probably because of the weak physical characteristics of the membranes. L-PRF alone appears to be a predictable grafting material for lateral maxillary sinus grafting and a reduced RBH should not be considered as a risk factor. Compared to a "standard" bone substitute L-PRF shows slightly less vertical bone gain (consider enough membrane application and use of bony window as new sinus floor roof over the implant apices), enhanced early resorption (first 6 months after application), but a similar stable bone gain afterward. For a two-stage lateral window approach, APCs "alone" cannot be recommended, due to their weak withstand to the sinus pneumatization forces. APCs combined with bone substitutes seem to accelerate bone formation, without any additional benefits on the long-term new bone gain. The use of L-PRF membranes for the treatment of perforations appears to be an effective treatment option, but further clinical studies are needed to confirm this. Even though the abovementioned statements are based on large numbers of studies, additional RCTs comparing APCs with different types of grafting procedures for sinus elevation are needed.

Unveiling the invisible: receivers use object weight cues for grip force planning in handover actions.

Handover actions are part of our daily lives. Whether it is the milk carton at the breakfast table or tickets at the box office, we usually perform these joint actions without much conscious attention. The individual actions involved in handovers, that have already been studied intensively at the level of individual actions, are grasping, lifting, and transporting objects. Depending on the object's properties, actors must plan their execution in order to ensure smooth and efficient object transfer. Therefore, anticipatory grip force scaling is crucial. Grip forces are planned in anticipation using weight estimates based on experience or visual cues. This study aimed to investigate whether receivers are able to correctly estimate object weight by observing the giver's kinematics. For this purpose, handover actions were performed with 20 dyads, manipulating the participant role (giver/receiver) and varying the size and weight of the object. Due to the random presentation of the object weight and the absence of visual cues, the participants were unaware of the object weight from trial to trial. Kinematics were recorded with a motion tracking system and grip forces were recorded with customized test objects. Peak grip force rates were used as a measure of anticipated object weight. Results showed that receiver kinematics are significantly affected by object weight. The peak grip force rates showed that receivers anticipate object weight, but givers not. This supports the hypothesis that receivers obtain information about the object weight by observing giver's kinematics and integrating this information into their own action execution.

Optimization of e-beam lithography parameters for nanofabrication of sub-50 nm gold nanowires and nanogaps based on a bilayer lift-off process.

Electron beam lithography (EBL) stands out as a powerful direct-write tool offering nanometer-scale patterning capability and is especially useful in low-volume R&D prototyping when coupled with pattern transfer approaches like etching or lift-off. Among pattern transfer approaches, lift-off is preferred particularly in research settings, as it is cost-effective and safe and does not require tailored wet/dry etch chemistries, fume hoods, and/or complex dry etch tools; all-in-all offering convenient, 'undercut-free' pattern transfer rendering it useful, especially for metallic layers and unique alloys with unknown etchant compatibility or low etch selectivity. Despite the widespread use of the lift-off technique and optical/EBL for micron to even sub-micron scales, existing reports in the literature on nanofabrication of metallic structures with critical dimension in the 10-20 nm regime with lift-off-based EBL patterning are either scattered, incomplete, or vary significantly in terms of experimental conditions, which calls for systematic process optimization. To address this issue, beyond what can be found in a typical photoresist datasheet, this paper reports a comprehensive study to calibrate EBL patterning of sub-50 nm metallic nanostructures including gold nanowires and nanogaps based on a lift-off process using bilayer polymethyl-methacrylate as the resist stack. The governing parameters in EBL, including exposure dose, soft-bake temperature, development time, developer solution, substrate type, and proximity effect are experimentally studied through more than 200 EBL runs, and optimal process conditions are determined by field emission scanning electron microscope imaging of the fabricated nanostructures reaching as small as 11 nm feature size.

Flexible light-stimulated artificial synapse based on detached (In,Ga)N thin film for neuromorphic computing.

Because of wide range of applications, the flexible artificial synapse is an indispensable part for next-generation neural morphology computing. In this work, we demonstrate a flexible synaptic device based on a lift-off (In,Ga)N thin film successfully. The synaptic device can mimic the learning, forgetting, and relearning functions of biological synapses at both flat and bent states. Furthermore, the synaptic device can simulate the transition from short-term memory to long-term memory successfully under different bending conditions. With the high flexibility, the excitatory post-synaptic current of the bent device only shows a slight decrease, leading to the high stability. Based on the experimental conductance for long-term potentiation and depression, the simulated three-layer neural network can achieve a high recognition rate up to 90.2%, indicating that the system comprising of flexible synaptic devices could have a strong learning-memory capability. Therefore, this work has a great potential for the development of wearable intelligence devices and flexible neuromorphic systems.

Predictors of recurrence and long-term patient reported outcomes following surgical repair of anal fistula, a retrospective analysis.

PURPOSE: Surgery for anal fistulas can result in devastating complications, including reoperations and fecal incontinence. There is limited contemporary evidence comparing outcomes since the adoption of the ligation of intersphincteric fistula tract procedure into mainstream practice. The purpose of this study is to compare recurrence rates and long-term outcomes of anal fistula following repair. METHODS: Data was collected from the electronic medical records or patient reported outcomes from patients aged 18 or older with a primary or recurrent cryptoglandular anal fistula. Primary outcome was recurrence defined as the identification of at least one fistula os or a high clinical suspicion of anal fistula. Secondary outcomes included fecal incontinence and postoperative quality of life. RESULTS: A total of 171 patients underwent definitive surgical repairs for their anal fistula. So 66.5% had a simple fistula, and 33.5% had a complex fistula. Of the 171 patients, 12.5% had a recurrence. The recurrence rates were 5.9% for simple fistula and 25.4% for complex fistula. Predictors of recurrence included diabetes mellitus, history of anorectal abscess, complex fistula, and sphincter sparing surgery. LIFT or plug/biologic procedures were both associated with a 50% or greater recurrence rate. No significant differences were found in fecal incontinence or associated quality of life between sphincter sparing or non-sphincter sparing surgical resections. CONCLUSION: The study provides insights into the long-term outcomes of surgical repair for anal fistula. We demonstrate that sphincter sparing operations are associated with increased recurrence, meanwhile, non-sphincter sparing surgeries did not increase the risk of fecal incontinence or worsen quality of life.

Long-term outcomes after cleft lift surgery for pilonidal sinus disease in post-pubertal adolescents: data from a prospective Danish cohort.

AIM: Pilonidal sinus disease (PSD) is a common condition. Despite a relatively large proportion of patients presenting as post-pubertal adolescents, only small cohorts focusing on this PSD subcategory have been published, and surgical treatment remains challenging. METHOD: The study is based on a prospective database established at Randers Regional Hospital in 2016. All patients undergoing Bascom's cleft lift (BCL) surgery from June 2016 until June 2020 were included in this study, focusing on patients ≤18 years of age comparing them to adult patients. Indications for BCL surgery were primary extensive manifestation, non-healing disease after previous elective surgery or disease recurrence. RESULTS: In total, n = 380 PSD patients were operated, of which n = 79 were post-pubertal adolescents with a median age at time of surgery of 17.2 years (interquartile range 16.3, 18.0). Sixty-six (84%) were boys. Twenty-seven (34%) presented with primary extensive manifestation, 34 (43%) due to non-healing wounds and 18 (23%) due to recurrence. Fifty-four patients (69%) healed uneventfully. There was no difference between the indications of surgery groups in terms of overall healing or time to healing if prolonged (P = 0.6). The median follow-up was 62 months (interquartile range 48, 73), with a 5-year recurrence rate of 19%, compared to 17% (P = 0.6) in the adult population. CONCLUSION: Our study is the first to investigate long-term clinical outcomes of BCL surgery for PSD in post-pubertal adolescent patients. Recurrences seem to occur more frequently compared to adults. However, we demonstrate that post-pubertal adolescent patients with advanced PSD can be treated with BCL surgery with acceptable outcomes.

Postoperative pain following laser fistula closure versus ligation of the intersphincteric fistula tract: A prospective double-blinded randomized controlled trial.

BACKGROUND: Prior studies focus primarily on surgical outcomes of anal fistula treatment, such as healing rates, rather than patient-reported outcomes, such as postoperative pain, which could influence surgical choice. OBJECTIVE: To compare pain scores at 6 and 24 h postoperatively between laser closure and ligation of the intersphincteric tract for anal fistula. DESIGN: Prospective, double-blinded randomized controlled trial. SETTINGS: A quaternary hospital in Malaysia. PATIENTS: Patients aged 18-75 years with high transsphincteric fistulas. INTERVENTION: Fistula laser closure versus ligation of the fistula tract (LIFT) treatment. MAIN OUTCOME MEASURES: Pain scores, continence, quality of life (QOL), operative time, and treatment failure were compared using chi-square, Fisher's exact test, student t-test, or Mann-Whitney with p < 0.05 denoting statistical significance. RESULTS: Fifty-six patients were recruited (laser, n = 28, LIFT, n = 28). Median pain scores for laser versus LIFT at 6 h postoperatively were 1.0 versus 2.0 (Rest, p = 0.213) and 3.0 versus 4.0 (Movement, p = 0.448), respectively. At 24 h, this reduced to 2.5 in both arms at rest (p = 0.842) but increased to 4.8 versus 3.5 on movement (p = 0.383). Median operative time for laser was significantly shorter (32.5 min) than LIFT (p < 0.001). Laser treated patients trended toward quicker return to work (10.5 vs. 14.0, p = 0.181) but treatment failure was similar (54% vs. 50%, p = 0.71). No patients developed postoperative incontinence. Mean SF-36 scores increased from baseline (67.1 ± 17.0; 95% CI 63.6-82.4 vs. 71.3 ± 11.4; 95% CI 64.0-75.0) to 6 months postoperatively (77.7 ± 21.0; 95% CI 57.0-80.3 vs. 74.0 ± 14.3; 95% CI 67.6-81.4) regardless of the type of surgery (P > 0.05). LIMITATIONS: Patients with prior fistula surgery (approximately 20%) led to heterogeneity. The total laser energy delivered varied depending on fistula anatomy. CONCLUSION: Laser fistula closure is an alternative to LIFT, with similar postoperative pain and shorter operative time despite more complex fistula anatomy in the laser arm, with a greater improvement in QOL. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06212739.

Supraperiosteal fat repositioning with midface lift in lower eyelid blepharoplasty: an 18-year experience.

PURPOSE: To assess the clinical outcomes of fat repositioning via supraperiosteal dissection with midface lift for correction of tear trough deformity in a large Asian patient population. METHODS: Retrospectively review 1152 Asian patients who underwent fat repositioning to the supraperiosteal plane with a midface lift between 2005 and 2022. Surgical technique, postoperative course, and complications were recorded. At the 6-month postoperative follow-up, the degree of patient satisfaction was assessed. RESULTS: A total of 2304 eyes from 1152 patients with an average follow-up of 10 months. These procedures were performed using a transforniceal approach in 185 patients (16%) or a transcutaneous skin excision approach in 967 patients (84%). Among the patients who underwent the transcutaneous technique, seven individuals (0.6%) experienced effective treatment of lower lid ectropion through lateral tarsal strip procedures. Nine patients (0.7%) required revision surgery to address the remaining lateral fat pad due to inadequate lateral orbital fat excision during the initial procedure. At the 6-month follow-up, most patients reported a high level of satisfaction, with 800 patients (78%) expressing extreme satisfaction and 196 patients (19.1%) reporting satisfaction with the improvement in their appearance. No one reported facial numbness, lower eyelid or cheek paralysis, newly developed diplopia or granuloma formation. CONCLUSION: The procedure of fat repositioning involving supraperiosteal dissection and a midface lift, whether performed using a transforniceal approach or a transcutaneous skin excision approach, in lower eyelid blepharoplasty proves to be a secure and auspicious surgical technique for rectifying tear trough deformity and attaining a pleasing aesthetic outcome.

The effect of power stretchers on occupational injury rates in an urban emergency medical services system.

BACKGROUND: To examine occupational injury rates in a dual-response emergency medical services (EMS) system before and after implementation of a power-lift stretcher system. METHODS: The seasonally-adjusted occupational injury rate was estimated relative to medical call volume (per 1000 calls) and workers (per 100 FTEs) from 2009 to 2019, and stratified by severity (lost-time, healthcare only), role (EMS, FIRE) and type (patient-handling). Power-lift stretchers were adopted between 2013 and 2015. Preinjury versus postinjury rates were compared using binomial tests. Interrupted time series (ITS) analysis was used to estimate the trend and change in injuries related to patient-handling, with occupational illnesses serving as control. RESULTS: Binomial tests revealed varied results, with reductions in the injury rate per 1000 calls (-14.0%) and increases in the rate per 100 FTEs (+14.1%); rates also differed by EMS role and injury severity. ITS analysis demonstrated substantial reductions in patient-handling injuries following implementation of power-lift stretchers, both in the injury rate per 1000 calls (-50.4%) and per 100 FTEs (-46.6%), specifically among individuals deployed on the ambulance. Injury rates were slightly elevated during the winter months (+0.8 per 100 FTEs) and lower during spring (-0.5 per 100 FTEs). CONCLUSIONS: These results support the implementation of power-lift stretchers for injury prevention in EMS systems and demonstrate advantages of ITS analysis when data span long preintervention and postintervention periods.