Time Points Research Articles

Application of restorative neurostimulation for chronic mechanical low back pain in an older population with 2-year follow up

IntroductionData on the Medicare-aged population show that older patients are major consumers of low back pain (LBP) interventions. An effective approach for patients with mechanical LBP that has been refractory...

Development of pollinated and unpollinated ovules in Ginkgo biloba: unravelling pollen's role in ovule tissue maturation.

In gymnosperms such as Ginkgo biloba, the pollen's arrival plays a key role in ovule development, before fertilization occurs. Accordingly, G. biloba female plants geographically isolated from male plants aborted all their ovules after the pollination drop emission, which is the event that allows the ovule to capture pollen grains. To decipher the mechanism induced by pollination required to avoid ovule senescence and then abortion, we compared the transcriptomic of pollinated and unpollinated ovules at three time points after the end of the emission of pollination drops. Transcriptomic and in situ expression analyses revealed that several key genes involved in programmed cell death such as senescence and apoptosis, DNA replication, and cell cycle were differentially expressed in unpollinated ovules compared to pollinated ones. Interestingly, we provided evidence that the pollen captured by the pollination drop affects auxin local accumulation and might cause the deregulation of key genes required for ovule's programmed cell death and activating both the cell cycle and DNA replication genes.

Effects of re-vibration on mechanical properties and air-void characteristics of cement-stabilised macadam materials

ABSTRACT Layered continuous paving (LCP) technology is an effective choice for improving the integrity and construction efficiency of the thick cement-stabilised macadam (CSM) base course. However, the effects of re-vibration generated by construction equipment during the paving process are not well understood. In this investigation, the effects of re-vibration on mechanical properties and air-void characteristics were investigated by mechanical performance tests, chloride migration experiments and industrial computerised tomography tests. The results demonstrate that compared with the control group, the void characteristic parameters were reduced by applying re-vibration within 12 h, resulting in a more compact structure. Thus, the mechanical properties were improved. However, the improvement effect gradually weakened over the delay time. CSM interlayer bonding strength were related to the time point of applying re-vibration and the cement paste dosage sprinkled between the layers. It is suggested that12 h be used as the critical time point for the LCP.

Guideline for cleft lip and palate team approach management

Cleft lip and palate team approach management refers to the goal of achieving good appearance, normal function and mental health for patients with cleft lip and palate, through multidisciplinary cooperation, jointly formulating treatment plans, using surgical reconstruction as the main method, and performing the most appropriate treatment at the best time point. The team is a multidisciplinary medical team, and at least it is recommended to include oral and maxillofacial surgeons, orthodontists, pathological phoneticians, and psychological counselors. This guideline was formally applied by the Society of Cleft Lip and Palate and approved by Chinese Stomatological Association in 2019, and was officially released in 2022. This guideline describes the cleft lip and palate team approach management for Chinese, covering the primary and secondary surgical repair for cleft lip, cleft palate, and cleft alveolar, and orthodontic treatment, speech therapy, nursing, psychology, etc.

Persistence and emergence of new neuropsychological deficits following SARS-CoV-2 infection: A follow-up assessment of the Geneva COVID-COG cohort.

Despite numerous observations of neuropsychological deficits immediately following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, little is known about what happens to these deficits over time and whether they are affected by changes in fatigue and any psychiatric symptoms. We aimed to assess the prevalence of neuropsychological deficits at 6-9 months and again at 12-15 months after coronavirus disease 2019 (COVID-19) and to explore whether it was associated with changes in fatigue and psychiatric symptoms. We administered a series of neuropsychological tests and psychiatric questionnaires to 95 patients (mean age = 57.12 years, standard deviation (SD) = 10.68; 35.79% women) 222 (time point 1 (T1)) and 441 (time point 2 (T2)) days on average after infection. Patients were categorised according to the severity of their respiratory COVID-19 symptoms in the acute phase: mild (no hospitalisation), moderate (conventional hospitalisation), and severe (hospitalisation in intensive care unit (ICU) plus mechanical ventilation). We ran Monte-Carlo simulation methods at each time point to generate a simulated population and then compared the cumulative percentages of cognitive disorders displayed by the three patient subgroups with the estimated normative data. We calculated generalised estimating equations for the whole sample to assess the longitudinal associations between cumulative neuropsychological deficits, fatigue, and psychiatric data (anxiety, depressive symptoms, posttraumatic stress disorder, and apathy). Most participants (>50%) exhibited a decrease in their neuropsychological impairments, while approximately 25% showed an escalation in these cognitive deficits. At T2, patients in the mild subgroup remained free of accumulated neuropsychological impairments. Patients with moderate severity of symptoms displayed a decrease in the magnitude of cumulative deficits in perceptual and attentional functions, a persistence of executive, memory and logical reasoning deficits, and the emergence of language deficits. In patients with severe symptoms, perceptual deficits emerged and executive deficits increased, while attentional and memory deficits remained unchanged. Changes in executive functions were significantly associated with changes in depressive symptoms, but the generalised estimating equations failed to reveal any other significant effect. While most cumulative neuropsychological deficits observed at T1 persisted and even worsened over time in the subgroups of patients with moderate and severe symptoms, a significant proportion of patients, mainly in the mild subgroup, exhibited improved performances. However, we identified heterogeneous neuropsychological profiles both cross-sectionally and over time, suggesting that there may be distinct patient phenotypes. Predictors of these detrimental dynamics have yet to be identified.

Changes in functioning and health during the first 6-months of the COVID-19 pandemic among individuals with a spinal cord injury.

Single-cohort longitudinal survey design. To identify what ongoing impact the COVID-19 pandemic has on functioning and health in individuals with SCI. Using the ICF model as a guide, outcome measures were chosen to explore potential constructs and aspects of health and functioning which may have been affected by regulations. Online, Canada. Participants provided demographic and clinical characteristics at baseline. They completed standardized online measures at three time points, each roughly one month apart (June, July, and August of 2020). The measures assessed mental health, resilience, boredom, social support, technology use, life space, and participation. Repeated measures ANOVAs were used to identify longitudinal changes for each measure. We collected data from 21 participants with SCI (mean age 54 years, 12 male). We found a large effect size for participation (η2 = 0.20), which increased over time. We also found medium effect sizes in both anxiety (η2 = 0.12) and social network usage (η2 = 0.12). Anxiety decreased over time and social networking usage fluctuated slightly but with an increase from time point one to time point two. The results indicate that individuals with spinal cord injury appear to be staying relatively stable during the pandemic with improvements in a few key aspects, such as potentially increased participation and decreased anxiety. The results also suggest that it is important to continue fostering ways for individuals with spinal cord injury to stay connected, engaged, and informed.

Clinical characteristics of the "Gap" between the prevalence and incidence of hearing loss using National Health Insurance Service data.

Hearing loss is the inability to hear speech or sounds well, owing to a number of causes. This study aimed to simultaneously determine the prevalence, incidence, and the Gap between them in hearing loss in South Korean patients at the same point in time as well as to identify patients who have not recovered from hearing loss. We examined the prevalence and incidence of patients diagnosed with hearing loss in the National Health Insurance Service database over an 11-year period from 2010 to 2020. The difference between the prevalence and the incidence was defined in this study as the term "Gap". Gap is the number of patients converted into the number of patients per 100,000 people by subtracting the incidence from the prevalence. Clinical characteristics such as sex and age per 100,000 individuals were examined. As of 2020, the domestic prevalence obtained in this study was 1.84%, increasing annually, and the prevalence increased with age to 4.10% among those over 60. The domestic incidence was 1.57%, increasing annually, and the incidence increased with age to 3.36% for those over 60s. The Gap was 0.27%, showing a steady increase from 2011 to 2020 with a corresponding increase in insurance benefit expenses. To fully understand the burden of hearing loss and develop effective prevention and treatment strategies, it is important to measure the Gap between its prevalence and incidence. This Gap means a lot because hearing loss is an irreversible disease. Gap represents patients who have already been diagnosed with hearing loss and are being diagnosed every year, indicating that the number of patients who do not recover is increasing. In other words, the increase in Gap meant that there were many patients who constantly visited the hospital for diagnosis of hearing loss.

Effect of heat exposure on prostaglandin production and expression of COX-2, PGES, PGFS, ITGAV and LGALS15 mRNAs in endometrial epithelial cells of buffalo (Bubalus bubalis).

Early embryonic mortality is one of the major intriguing factors of reproductive failure that causes considerable challenge to the mammalian cell biologists. Heat stress is the major factor responsible for reduced fertility in farm animals. The present study aimed to investigate the influence of heat stress on prostaglandin production and the expression of key genes, including COX-2, PGES, PGFS, ITGAV and LGALS15, in buffalo endometrial epithelial cells. Buffalo genitalia containing ovaries with corpus luteum (CL) were collected immediately post-slaughter. The stages of the estrous cycle were determined based on macroscopic observations of the ovaries. Uterine lumens of the mid-luteal phase (days 6-10 of the estrous cycle) were washed and treated with trypsin to isolate epithelial cells, which were then cultured at control temperature (38.5°C for 24h) or exposed to elevated temperatures [38.5°C for 6h, 40.5°C for 18h; Heat Stressed (HS)]. The supernatant and endometrial epithelial cells were collected at various time points (0, 3, 6, 12, and 24h) from both the control and treatment groups. Although heat stress (40.5°C) significantly (P < 0.05) increased COX-2, PGES, and PGFS transcripts in epithelial cells but it did not affect the in vitro production of PGF2α and PGE2. The expression of ITGAV and LGALS15 mRNAs in endometrial epithelial cells remained unaltered under elevated temperature conditions. It can be concluded that elevated temperature did not directly modulate prostaglandin production but, it promoted the expression of COX-2, PGES and PGFS mRNA in buffalo endometrial epithelial cells.

Proteomic changes of botulinum neurotoxin injection on muscle growth in children with spastic cerebral palsy.

The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP). A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting. Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways. BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.

Effect of early preventive supplementation with calcium and phosphorus on metabolic bone disease in premature infants

ObjectiveThe objective was to study the effect of early preventive calcium and phosphorus supplementation on metabolic bone disease in preterm infants.MethodsA retrospective analysis of 234 preterm infants with a gestational age < 32 weeks or birth weight < 1500 g who were hospitalized in the Neonatology Department of the Second Hospital of Shandong University from 01.2018 to 12.2020 was conducted. One hundred thirty-two premature infants hospitalized from 01.2018 to 06.2019 did not receive prophylactic calcium and phosphorus supplementation in the early postnatal period. These infants received calcium or phosphorus supplementation at the time of hypocalcaemia or hypophosphatemia diagnosis. One hundred two premature infants hospitalized from 07.2019 to 12.2020 received early preventive calcium and phosphorus supplementation after birth. The levels of serum calcium and phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, calcitonin, and parathyroid hormone at different time points and growth indicators at six months of age were compared between the two groups of infants. The number of cases of metabolic bone disease and fracture between the two groups was compared.Results1) A total of 12 infants (5.13%) among the 234 preterm infants were diagnosed with metabolic bone disease, including 2 (1.96%) in the prophylactic supplementation group and 10 (7.58%) in the nonprophylactic supplementation group. Fractures occurred in 3 premature infants (25.0%) with metabolic bone disease, all of whom were in the group that did not receive prophylactic supplementation. 2) There was no significant difference in serum calcium and calcitonin levels between the two groups. The levels of serum phosphorus and 25 hydroxyvitamin D in the prophylactic supplementation group were higher than those in the nonprophylactic supplementation group (P < 0.05). In comparison, alkaline phosphatase and parathyroid hormone levels were lower in the prophylactic supplementation group than in the nonprophylactic supplementation group (P < 0.05). Preterm infants in the prophylactic supplementation group had higher weight, length, head circumference, and bone density values than those in the nonprophylactic supplementation group (P < 0.05).ConclusionPreventive supplementation with calcium and phosphorus after birth can effectively improve calcium and phosphorus metabolism, and reduce the incidence of metabolic bone disease and fractures in premature infants. This can be further publicized and used clinically.

A Novel Food Bore Protein Hydrogel with Silver Ions for Promoting Burn Wound Healing.

Hydrogels have emerged as a promising option for treating local scald wounds due to their unique physical and chemical properties. This study aims to evaluate the efficacy of ovalbumin/gelatin composite hydrogels in repairing deep II-degree scald wounds using a mouse dorsal skin model. Trauma tissues collected at various time points are analyzed for total protein content, hydroxyproline content, histological features, and expression of relevant markers. The results reveal that the hydrogel accelerates the healing process of scalded wounds, which is 17.27% higher than the control group. The hydrogel treatment also effectively prevents wound enlargement and redness of the edges caused by infection during the initial stage of scalding. The total protein and hydroxyproline content of the treated wounds are significantly elevated. Additionally, the hydrogel up-regulates the expression of VEGF (a crucial angiogenic factor) and down-regulates CD68 (a macrophage marker). In summary, this study provides valuable insights into the potential of multifunctional protein-based hydrogels in wound healing.

In vitro and in vivo study of antibacterial and anti-encrustation coating on ureteric stents.

To investigate the ability of propolis-coated ureteric stents to solve complications, especially urinary tract infections (UTIs) and crusting, in patients with long-term indwelling ureteric stents through antimicrobial and anti-calculus activities. Polyurethane (PU) ureteric stents were immersed in the ethanol extract of propolis (EEP), a well-known antimicrobial honeybee product, and subjected to chemical, hydrophilic, and seismic tests. The antimicrobial activity of the EEP coating was then examined by in vitro investigation. Proteus mirabilis infection was induced in rats within uncoated and EEP-coated groups, and the infection, stone formation, and inflammation were monitored at various time points. The characterisation results showed that the hydrophilicity and stability of the EEP surface improved. In vitro tests revealed that the EEP coating was biocompatible, could eliminate >90% of bacteria biofilms attached to the stent and could maintain bacteriostatic properties for up to 3 months. The in vivo experiment revealed that the EEP-coating significantly reduced the amount of bacteria, stones, and salt deposits on the surface of the ureteric stents and decreased inflammation in the host tissue. Compared with clinically used PU stents, EEP-coated ureteric stents could better mitigate infections and prevent encrustation. Thus, this study demonstrated that propolis is a promising natural dressing material for ureteric stents.

Change in body weight of older adults before and during the COVID-19 pandemic: longitudinal results from the Berlin Aging Study II

ObjectivesChange in body weight during the COVID-19 pandemic as an unintended side effect of lockdown measures has been predominantly reported for younger and middle-aged adults. However, information on older adults for which weight loss is known to result in adverse outcomes, is scarce. In this study we describe the body weight change in older adults before, during, and after the COVID-19 lockdown measures and explore putative associated factors with a focus on the period that includes the first six months of the COVID-19 containment measures. DesignProspective cohort study with three follow-up examinations over the course of 10 years. Setting and ParticipantsIn this study, we analyzed the longitudinal weight change of 472 participants of the Berlin Aging Study II (mean age of 67.5 years at baseline). MeasurementsBody weight was assessed at four time points. Additionally, differences between subgroups characterized by socio-economic, cognitive, and psychosocial variables as well as morbidity burden, biological age markers (epigenetic clocks, telomere length), and frailty were compared. ResultsOn average, women and men lost 0.87% (n = 227) and 0.5% (n = 245) of their body weight per year in the study period covering the first six months of the COVID-19 pandemic. Weight loss among men was particularly pronounced among groups characterized by change in physical activity due to COVID-19 lockdown, low positive affect, premature epigenetic age (7-CpG clock), diagnosed metabolic syndrome, and a more masculine gender score (all variables: p < 0.05, n = 245). ConclusionDuring the COVID-19 pandemic, older participants lost weight with a 2.5-times (women) and 2-times (men) higher rate than what is expected in this age.

Modern Hip Arthroscopy for FAIS May Delay the Natural History of Osteoarthritis in 25% of Patients: A 12-Year Follow-up Analysis.

Little is known about the effect of modern hip arthroscopy on the natural history of femoroacetabular impingement syndrome (FAIS) with respect to joint preservation. To (1) characterize the natural history of FAIS and (2) understand the effect of modern hip arthroscopy by radiographically comparing the hips of patients who underwent only unilateral primary hip arthroscopy with a minimum follow-up of 10 years. Cohort study; Level of evidence, 3. Between 2010 and 2012, 619 consecutive patients were reviewed from the practice of a single fellowship-trained hip arthroscopic surgeon. Inclusion criteria were FAIS, bilateral radiographic findings of femoroacetabular impingement, primary unilateral hip arthroscopy (labral repair, femoroplasty, or capsular closure), and minimum 10-year follow-up. The preoperative and minimum 10-year postoperative radiographs of patients were evaluated at each time point. Both operative and nonoperative hips were graded using the Tönnis classification or the presence of hip arthroplasty by 2 independent reviewers. Subgroup analyses were performed. A total of 200 hips from 100 patients were evaluated at a mean follow-up of 12.0 years. Preoperatively, 98% and 99% of operative and nonoperative hips were evaluated as Tönnis grades 0 and 1, respectively; 5% of nonoperative hips had worse Tönnis grades than operative hips. The nonoperative hip advanced to a worse Tönnis grade in 48% (48/100) of cases compared with 28% (28/100) among operative hips. At follow-up, Tönnis grades between hips were equal in 70% (70/100) of the cases, the operative hip had a better grade 25% (25/100) of the time, and the nonoperative hip had a better grade 5% (5/100) of the time. Modern hip arthroscopy was associated with a relative risk reduction of 42% in osteoarthritis progression. Impingement with borderline dysplasia, age, preoperative Tönnis grade, and alpha angle >65° were key risk factors in the radiographic progression of osteoarthritis. Although the majority of patients (70%) undergoing hip arthroscopy for FAIS did not experience differences between operative and nonoperative hips in terms of the radiographic progression of osteoarthritis, the natural history may be favorably altered for 25% of patients whose Tönnis grade was better after undergoing arthroscopic correction. Modern hip arthroscopy indications and techniques represent a valid joint-preservation procedure conferring a relative risk reduction of 42% in the progression of osteoarthritis. Arthroscopy for mixed patterns of impingement and instability were the fastest to degenerate.

Memory reactivation in slow wave sleep enhances relational learning in humans

Sleep boosts the integration of memories, and can thus facilitate relational learning. This benefit may be due to memory reactivation during non-REM sleep. We set out to test this by explicitly cueing reactivation using a technique called targeted memory reactivation (TMR), in which sounds are paired with learned material in wake and then softly played during subsequent sleep, triggering reactivation of the associated memories. We specifically tested whether TMR in slow wave sleep leads to enhancements in inferential thinking in a transitive inference task. Because the Up-phase of the slow oscillation is more responsive to cues than the Down-phase, we also asked whether Up-phase stimulation is more beneficial for such integration. Our data show that TMR during the Up-Phase boosts the ability to make inferences, but only for the most distant inferential leaps. Up-phase stimulation was also associated with detectable memory reinstatement, whereas Down-phase stimulation led to below-chance performance the next morning. Detection of memory reinstatement after Up-state stimulation was negatively correlated with performance on the most difficult inferences the next morning. These findings demonstrate that cueing memory reactivation at specific time points in sleep can benefit difficult relational learning problems.

Reciprocal association between pain and quality of life after newly acquired spinal cord injury.

Pain is highly prevalent in spinal cord injury (SCI) and a key determinant of quality of life (QoL). This is the first study to examine reciprocal associations between pain and QoL in patients undergoing their first inpatient rehabilitation after SCI. Longitudinal data, with three measurement time points (1month and 3months after SCI onset, and at discharge from inpatient rehabilitation) from the Inception Cohort of the Swiss Spinal Cord Injury Cohort Study. Participants were 381 individuals aged ≥ 16years with a newly diagnosed traumatic or non-traumatic SCI. 75.1% were male and the average age was 53.2years. Random intercept cross-lagged panel models were conducted to examine the reciprocal association between pain intensity and QoL, as measured with the International SCI QoL Basic Data Set three individual items (satisfaction with life, physical health, and psychological health) and total score (mean of the three individual items). Both item and total QoL scores increased over time. 1month: 5.3 (SD = 2.7), 3months: 5.9 (SD = 2.3), discharge: 6.6 (SD = 2.0). Participants reported relatively low levels of pain intensity that remained stable over the course of inpatient rehabilitation. 1month: 2.7 (SD = 2.3), 3months: 2.6 (SD = 2.4), discharge: 2.7 (SD = 2.5). There were no significant cross-lagged associations between QoL and pain intensity across time. Results indicate that pain intensity does not predict changes in QoL during first rehabilitation, and vice versa. Associations between pain intensity and QoL reported by previous studies may be attributable to individual characteristics and timely events that simultaneously influence pain and QoL.

Immunophenotypic characterization of leukemic stem cells in acute myeloid leukemia using single tube 10-colour panel by multiparametric flow cytometry: Deciphering the spectrum, complexity and immunophenotypic heterogeneity.

Despite extensive research, comprehensive characterization of leukaemic stem cells (LSC) and information on their immunophenotypic differences from normal haematopoietic stem cells (HSC) is lacking. Herein, we attempted to unravel the immunophenotypic (IPT) characteristics and heterogeneity of LSC using multiparametric flow cytometry (MFC) and single-cell sequencing. Bone marrow aspirate samples from patients with acute myeloid leukaemia (AML) were evaluated using MFC at diagnostic and post induction time points using a single tube-10-colour-panel containing LSC-associated antibodies CD123, CD45RA, CD44, CD33 and COMPOSITE (CLL-1, TIM-3, CD25, CD11b, CD22, CD7, CD56) with backbone markers that is, CD45, CD34, CD38, CD117, sCD3. Single-cell sequencing of the whole transcriptome was also done in a bone marrow sample. LSCs and HSCs were identified in 225/255 (88.2%) and 183/255 (71.6%) samples, respectively. Significantly higher expression was noted for COMPOSITE, CD45RA, CD123, CD33, and CD44 in LSCs than HSCs (p < 0.0001). On comparing the LSC specific antigen expressions between CD34+ (n = 184) and CD34- LSCs (n = 41), no difference was observed between the groups. More than one sub-population of LSC was demonstrated in 4.4% of cases, which further revealed high concordance between MFC and single cell transcriptomic analysis in one of the cases displaying three LSC subpopulations by both methods. A single tube-10-colour MFC panel is proposed as an easy and reproducible tool to identify and discriminate LSCs from HSCs. LSCs display both inter- and intra-sample heterogeneity in terms of antigen expressions, which opens the facets for single cell molecular analysis to elucidate the role of subpopulations of LSCs in AML progression.

SHAP value-based ERP analysis (SHERPA): Increasing the sensitivity of EEG signals with explainable AI methods.

Conventionally, event-related potential (ERP) analysis relies on the researcher to identify the sensors and time points where an effect is expected. However, this approach is prone to bias and may limit the ability to detect unexpected effects or to investigate the full range of the electroencephalography (EEG) signal. Data-driven approaches circumvent this limitation, however, the multiple comparison problem and the statistical correction thereof affect both the sensitivity and specificity of the analysis. In this study, we present SHERPA - a novel approach based on explainable artificial intelligence (XAI) designed to provide the researcher with a straightforward and objective method to find relevant latency ranges and electrodes. SHERPA is comprised of a convolutional neural network (CNN) for classifying the conditions of the experiment and SHapley Additive exPlanations (SHAP) as a post hoc explainer to identify the important temporal and spatial features. A classical EEG face perception experiment is employed to validate the approach by comparing it to the established researcher- and data-driven approaches. Likewise, SHERPA identified an occipital cluster close to the temporal coordinates for the N170 effect expected. Most importantly, SHERPA allows quantifying the relevance of an ERP for a psychological mechanism by calculating an "importance score". Hence, SHERPA suggests the presence of a negative selection process at the early and later stages of processing. In conclusion, our new method not only offers an analysis approach suitable in situations with limited prior knowledge of the effect in question but also an increased sensitivity capable of distinguishing neural processes with high precision.

Functional Laryngectomy and Quality of Life in Survivors of Head and Neck Cancer With Intractable Aspiration

Late effects of head and neck cancer (HNC) treatment include profound dysphagia, chronic aspiration, and death. Functional laryngectomy (FL) can improve patient survival and quality of life (QoL); however, removing a failing larynx for a noncancer reason is a difficult decision. Data regarding the ability of FL to improve self-perceptions of voice, swallowing, and QOL in survivors of HNC with intractable aspiration are inconclusive. To investigate the association of FL with changes in self-reported perceptions of voice, swallowing, oral intake, QoL, and mood in survivors of HNC experiencing profound dysphagia and intractable aspiration. This cohort study was conducted at a single academic institution and included survivors of HNC with profound swallowing dysfunction and intractable aspiration who underwent FL from July 2016 through March 2022. Of the initial 22 patients enrolled, 2 patients (15%) died of aspiration pneumonia before receiving FL. Data analyses were performed from July 2016 through March 2023. Self-reported measures of voice using the VHI (30-item Voice Handicap Index), swallowing using the EAT-10 (10-item Eating Assessment Tool), functional oral intake scale using the FOIS (Functional Oral Intake Scale), and quality of life using the FACT-H&N (Functional Assessment of Cancer Therapy-Head & Neck) were assessed before FL and at 1, 3, and 6 months after FL. Mood states were evaluated using the POMS (Profile of Mood States, second edition), before FL and at 6 months after FL. The study analyses included 20 patients (mean [SD] age, 72.4 (7.0) years; 19 [95%] males and 1 [5%] female) who underwent FL and had complete data across all time points. Among these, 12 patients (60%) had received chemoradiation for oropharyngeal, 7 (35%) for laryngeal, or 1 (5%) for nasopharyngeal cancer. The mean (SD) time from completion of oncologic treatment to FL was 15.5 (5.5) years. Mean (SD) score on the EAT-10 improved from 33.2 (7.4) to 23.1 (10.8) at 1 month; 12.1 (9.1) at 3 months; and 8.3 (7.4) at 6 months, with a large effect size (η2 = 0.72; 95% CI, 0.54-0.80). Mean (SD) score on the FOIS improved from 2.0 (1.5) to 2.9 (1.7) at 1 month; 4.8 (2.5) at 3 months; and 5.2 (1.7) at 6 months, with a large effect size (η2 = 0.6; 95% CI, 0.38-0.71). Improvement in oral intake was achieved in 19 patients (95%), and feeding tubes were removed in 10 of 16 patients (63%) who were feeding tube-dependent; 6 patients (27%) continued to require supplemental tube feedings. Mean (SD) score on the VHI improved from 63.6 (34.0) to 86.9 (33.7) at 1 month; 71.3 (36.1) at 3 months; and 39.7 (26.9) at 6 months, with a large effect size (η2 = 0.42; 95% CI, 0.19-0.56). Seventeen patients (85%) were able to use a tracheoesophageal voice prosthesis for alaryngeal communication. Mean (SD) score on the FACT-H&N improved from 86.2 (17.8) to 93.6 (18.4) at 1 month; 109.0 (18.4) at 3 months; and 121.0 (16.8) at 6 months, with a large effect size (η2 = 0.64; 95% CI, 0.42-0.74). Mean (SD) score on the POMS improved from 58.9 (13.2) at baseline to 44.5 (9.9) at 6 months, with a large effect size (Cohen d = 1.04; 95% CI, 0.48-1.57). None of the patients experienced major complications of FL; 1 patient (5%) had a postoperative pharyngocutaneous fistula. The findings of this cohort study indicate that FL was associated with marked improvements in self-perception of voice and swallowing, functional oral intake, QoL, and mood state among survivors of HNC. These findings can serve as a framework for FL counseling among HNC survivors experiencing profound dysphagia and intractable aspiration.

Identification of key differentially methylated genes in regulating muscle development and intramuscular fat deposition in chickens

Muscle development and intramuscular fat (IMF) deposition are intricate physiological processes characterized by multiple gene expressions and interactions. In this research, the phenotypic variations in the breast muscle of Jingyuan chickens were examined at three different time points: 42, 126, and 180 days old. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify differentially methylated genes (DMGs) responsible for regulating muscle development and IMF deposition. The findings indicate a significant increase in breast muscle weight (BMW), myofiber diameter, and cross-sectional area, as well as IMF content, in correlation with the progressive number of growing days in Jingyuan chickens. The findings also revealed that 380 hypo-methylated and 253 hyper-methylated DMGs were identified between the three groups of breast muscle. Module gene and DMG association analysis identified m6A methylation-mediated multiple DMGs associated with muscle development and fat metabolism. In vitro cell modeling analysis reveals stage-specific differences in the expression of CUBN, MEGF10, BOP1, and BMPR2 during the differentiation of myoblasts and intramuscular preadipocytes. Cycloleucine treatment significantly inhibited the expression levels of CUBN, BOP1, and BMPR2, and promoted the expression of MEGF10. These results suggest that m6A methylation-mediated CUBN, MEGF10, BOP1, and BMPR2 can serve as potential candidate genes for regulating muscle development and IMF deposition, and provide an important theoretical basis for further investigation of the functional mechanism of m6A modification involved in adipogenesis.