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Aim: To evaluate the radiographic outcomes of lateral sinus floor elevation with simultaneous implant placement at sites without sinus membrane perforation (SMP) and sites with SMP managed with a resorbable membrane. Materials and Methods: One hundred and thirty‐nine patients and 170 implants (56 perforation, 114 non‐perforation) were included. Cone‐beam computed tomography (CBCT) images were taken before surgery (T0), immediately after surgery (T1) and 6 months after surgery (T2). Post‐operative augmentation parameters, including endo‐sinus bone gain (ESBG) along the implant axis, mean new bone height (NBH) surrounding the implant and augmentation volume (AV), were measured at T1 and T2. Results: At T1, there were no significant differences in ESBG, NBH and AV between the two groups. At T2, although ESBG did not significantly differ between the two groups, NBH (8.50 ± 1.99 mm vs. 9.99 ± 2.52 mm, p =.039) and AV (519.37 ± 258.38 mm3 vs. 700.99 ± 346.53 mm3, p <.001) were significantly lower in the perforation group. The shrinkage of graft material from T1 to T2, including ΔESBG (p =.002), ΔNBH (p <.001) and ΔAV (p <.001), was higher in the perforation group. Conclusions: SMP during LSFE with simultaneous implant placement is associated with greater resorption of the grafted area at a 6‐month follow‐up. [ABSTRACT FROM AUTHOR]

Purpose: Several hundreds of patients have been so far treated in clinical trials with boron neutron capture therapy (BNCT). Methods: This is a non-systematic review of clinical trials with BNCT, with special emphasis on the more recent trials. Results: The conducted trials have been relatively small single-arm studies and included mostly the patients with head and neck carcinomas resistant to traditional treatment modalities and glioblastomas. In general, the efficacy results have been promising and BNCT has been relatively well tolerated, even in the patients who have already been treated with conventional radiotherapy or chemoradiation. The most frequent adverse events have been similar to those associated with the conventional radiotherapy. At present, there is no evidence how the efficacy of BNCT would compare to the standard treatment modalities in earlier treatment lines. Conclusions: Most of the existing studies have been performed with reactor-based facilities, but there is now a rapidly increasing number of linear accelerator-based BNCT sites, and the clinical research is apparently activating again. This, combined with the increased knowledge on cancer biology and novel types of oncological therapies, opens possibilities to study innovative boron carriers and to combine BNCT with modern oncological therapies in the future clinical trials. To conduct larger phase III trials, multicenter approaches are encouraged to be applied, keeping in mind the importance of joint instructions and quality control measurements. [ABSTRACT FROM AUTHOR]

Background Objective Results Conclusion Use of permanent hair dyes causes unintended oxidative damage during the short time frame of the dyeing process that leads to perceivable changes in the feel, manageability and appearance of hair. Moreover, after hair has been dyed, regular exposure to the sun as a key environmental stressor continues to stimulate additional oxidative damage and to induce newly developed hair colours to fade prematurely or undergo changes in colour quality.To document the utility of acetyl zingerone methyl ether (MAZ) as a newly designed haircare ingredient to afford extra protection against oxidative damage and safeguard the integrity of hair colour.We demonstrate that MAZ is compatible chemically with the high alkaline conditions required for the colouring process and from theoretical calculations preferentially binds Fe and Cu ions relative to Ca or Zn ions. In model Fenton reactions MAZ effectively chelated active redox metals (Fe and Cu ions) in the presence of excess Ca+2 ions to inhibit the production of hydroxyl radicals, and in separate studies, MAZ neutralized singlet oxygen with greater efficiency than α‐tocopherol by a factor of 2.5. When mixed into permanent dyes prior to hair tress application, MAZ significantly reduced combing forces, and SEM images led to substantial reductions in visual signs of surface damage. In a 28‐day clinical study, relative to controls, mixing MAZ into hair dyes prior to application interfered neither with colour development nor with ability to cover grey hair and led to significant improvements in perceived attributes associated with hair's condition immediately following the dyeing process. Over a 28‐day maintenance phase, especially between Day 14 and Day 28, continued use of shampoo and conditioner containing MAZ significantly preserved gloss measurements and hair colour in terms of longevity and colour quality as remaining desired and fresh compared to use of control shampoo and conditioner.This work establishes MAZ as a next‐generation hair care ingredient for use in permanent dyes to attenuate oxidative damage and in shampoos and conditioners to promote longevity of hair colour and to maintain overall health and appearance of hair on a daily basis. [ABSTRACT FROM AUTHOR]

Background: Pulp stones are a type of pulp calcification, the presence of which tends to hinder endodontic treatment. Thus, this retrospective study aimed to analyze the distribution of pulp stones in the population in southwest China and identify the influencing factors. Materials: Cone-beam computed tomography (CBCT) scans of 5066 teeth of 200 patients (91 males and 109 females) aged 16–45 years were evaluated. Pulp stones were marked as either present or absent when distinct radiopaque masses were found in the pulp cavity, then evaluated the occurrence of pulp stones with regard to tooth type, sex, age group, and contact it with tooth status. The Pearson chi-square test and nonparametric test were used for statistical analysis. Results: Pulp stones were detected in 49.0% of patients and 7.4% of teeth, respectively. The incidence in females was 1.9 times higher than in males (OR = 1.9, 95% CI = 1.1–3.3, p = 0.001). Pulp stones were most prevalent in patients 36–45 years of age. Furthermore, in the age range of 16–45 years, the likelihood of finding pulp stones increased 1.1 times per year with age (OR = 1.1, 95% CI = 1.0–1.1, p = 0.032). A higher incidence of pulp stones was observed in the maxilla and molars. Of the 5066 teeth studied, pulp stones were more common in non-intact teeth. Conclusion: Nearly half of the population in southwest China had pulp stones. Pulp stones were found significantly more often in females, maxilla, and non-intact teeth, and their frequency increased with age. For dentists, understanding the distribution of pulp stones is crucial for the proper design of root canal treatment (RCT). Trial registration: This study was approved by the Ethics Committee of the Affiliated Hospital of Stomatology, Southwest Medical University (certificate number: 20220818001). [ABSTRACT FROM AUTHOR]

Deficits in N -methyl- d -aspartate receptor (NMDAR) signaling are implicated in the pathogenesis of schizophrenia. Luvadaxistat (TAK-831/NBI-1065844) is an investigational d -amino acid oxidase (DAAO) inhibitor that increases d -serine levels at NMDAR coagonist sites. INTERACT is a phase 2 randomized, placebo-controlled study that evaluated the efficacy and safety of three doses of luvadaxistat, covering a range of DAAO occupancy and d -serine levels, in patients with schizophrenia with persistent negative symptoms. The study included a 14-day, single-blinded placebo run-in period and a 12-week, double-blinded treatment period. The primary efficacy endpoint was the 12-week change from baseline in Positive and Negative Syndrome Scale—Negative Symptom Factor Score (PANSS NSFS). Secondary efficacy endpoints included the 12-week changes from baseline in Brief Assessment of Cognition in Schizophrenia (BACS) score and Schizophrenia Cognition Rating Scale (SCoRS) score. Safety endpoints included adverse event assessments. The full analysis set included all randomized patients (N = 256 [placebo, n = 87; luvadaxistat 50 mg, n = 58; 125 mg, n = 56; 500 mg, n = 55]); 228 patients completed the study. No significant improvements in PANSS NSFS were observed at any dose versus placebo at week 12. Improvements were observed with luvadaxistat 50 mg versus placebo in cognitive endpoints: BACS composite score (nominal one-sided p = 0.031) and SCoRS interviewer total score (nominal one-sided p = 0.011). Luvadaxistat did not significantly improve negative symptoms of schizophrenia. However, luvadaxistat 50 mg met the prespecified secondary endpoints for cognitive performance (BACS) and function (SCoRS), warranting further investigation in patients with cognitive impairment associated with schizophrenia. Luvadaxistat was well-tolerated in INTERACT, with no new safety signals observed. ClinicalTrials.gov : NCT03382639 [ABSTRACT FROM AUTHOR]

Sirtuins 6 (Sirt6) is a defatting acylase that protects against atherosclerosis and ischemic stroke. It has a high clinical reference value in predicting clinical outcomes such as cerebral hemorrhage, cerebral ischemia, and myocardial infarction. This study aimed to investigate the connection between serum Sirt6 levels and short-term prognosis among patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis with tissue-type plasminogen activator (rt-PA). This study involved AIS patients undergoing intravenous thrombolysis by rt-PA, and found that the serum Sirt6 level were significantly lower in the poor prognosis group than in the good prognosis group (p < 0.05), while the poor prognosis group's age, neutrophil count, atrial fibrillation, D-dimer level, and pre-thrombolysis National Institutes of Health Stroke Scale (NIHSS) score were significantly higher (p < 0.05). With a cut-off value of 689 ng/mL, receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) of serum sirt6 for predicting a poor prognosis following intravenous thrombolytic therapy in AIS patients was 0.841, with corresponding sensitivity and specificity of 90.74% and 70.06%. Poor outcome was independently influenced by age, pre-thrombolysis NIHSS score, platelet counts, D-dimer, and Sirt6 level (p < 0.05). A nomogram prediction model was created based on multivariate logistic regression results, and its AUC was 0.972. The Hosmer-Lemeshow test (χ² = 5.766, p = 0.673) and calibration curve analysis showed an acceptable fit for the prediction model. Decision analysis curves were also used to confirm the clinical utility of the model. In conclusion, Serum sirt6 was found to be a novel biomarker for predicting AIS patients treated with rt-PA, and sirt6-based nomograms may become a valuable tool for predicting AIS patients' long-term prognosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the postoperative clinical and functional outcomes of palatoplasty with three soft palate cleft repairs and analyse the factors potentially impacting these outcomes. A retrospective analysis was conducted on a consecutive series of 337 patients who underwent primary cleft palate repair by palatoplasty modified with either Furlow Z-plasty (P-FZP, n = 77), intravelar veloplasty (P-IVV, n = 110), or combined intravelar veloplasty–Furlow Z-plasty (P-IVV-FZP, n = 150). The postoperative outcomes evaluated included wound healing (complete closure/fistula) and velopharyngeal function. Demographic and surgical data were analysed using both univariate and multivariate analysis. There was no significant difference between the groups with regard to the sex distribution, age at repair, cleft width, cleft type, or follow-up duration. However, relaxing incisions were significantly more common with P-FZP (26.0%) and P-IVV (29.1%) compared to P-IVV-FZP (10%) (P = 0.002 and <0.001, respectively). The complete wound closure rate was significantly higher with P-IVV-FZP (97.3%) compared to P-FZP (88.3%) (P = 0.012) and P-IVV (90%) (P = 0.015). The normal velopharyngeal function rate was comparable for P-IVV-FZP (86.7%) and P-FZP (83.1%), and both rates were significantly better than the rate with P-IVV (73.6%) (P = 0.039 and 0.029, respectively). The cleft type and width were identified as factors influencing postoperative outcomes. In conclusion, it may be appropriate to prioritize the palatoplasty with combined intravelar veloplasty–Furlow Z-plasty whenever feasible. [ABSTRACT FROM AUTHOR]

To conceptualize a composite primary endpoint for parallel-group RCTs of exercise-based cardiac rehabilitation (CR) interventions and to explore its application and statistical efficiency. We conducted a statistical exploration of sample size requirements. We combined exercise capacity and physical activity for the composite endpoint (CE), both being directly related to reduced premature mortality in patients with cardiac diseases. Based on smallest detectable and minimal clinically important changes (change in exercise capacity of 15 W and change in physical activity of 10 min/day), the CE combines 2 dichotomous endpoints (achieved/not achieved). To examine statistical efficiency, we compared sample size requirements based on the CE to single endpoints using data from 2 completed CR trials. Cardiac rehabilitation phase III. Patients in cardiac rehabilitation. Not applicable. Exercise capacity (P max assessed by incremental cycle ergometry) and physical activity (daily minutes of moderate to vigorous physical activity assessed by accelerometry). Expecting, for example, a 10% between-group difference and improvement in the clinical outcome, the CE would increase sample size by up to 21% or 61%, depending on the dataset. When expecting a 10% difference and designing an intervention with the aim of non-deterioration, the CE would allow to reduce the sample size by up to 55% or 70%. Trialists may consider the utility of the CE for future studies in exercise-based CR to reduce sample size requirements. However, perhaps surprisingly at first, the CE could also lead to an increased sample size needed, depending on the observed baseline proportions in the trial population and the aim of the intervention. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is the main cause of death in middle-aged and older people and is characterized by high morbidity, high mortality, a high rehospitalization rate, and many high-risk groups. Nicotinamide adenine dinucleotide (NAD+) is widely present in the mitochondria of cardiomyocytes and maintains the redox balance in the body, which can effectively treat HF. We sought to evaluate whether NAD+ therapy has some clinical efficacy in patients with HF. Methods: Based on using conventional drugs to treat HF, patients (n = 60) were randomized 1:1 to saline and 50 mg NAD+ with 50 mL of normal saline for 7 days. The baseline characteristics of patients before and after treatment and cardiac function (N-terminal pro B-type natriuretic peptide (NT-proBNP) level and left ventricular ejection fraction (LVEF) value) were analyzed. Serological analysis (sirtuin-1 (SIRT1), sirtuin-3 (SIRT3), sirtuin-6 (SIRT6), reactive oxygen species (ROS), and endothelin) was also performed. Results: Among the 60 patients with HF who were treated with NAD+ for 7 days, the improvement rate in NT-proBNP levels and LVEF values was better than in the saline group, although not statistically significant. These patients were more likely to benefit from NAD+ because of higher levels of anti-oxidative stress (SIRT1, SIRT3, SIRT6, and ROS) and anti-endothelial injury (endothelin) than those in the saline control group. Conclusions: According to the results of this study, it is believed that 7 days of NAD+ injections has a positive effect on improving cardiac function, oxidative stress, and endothelial injury in patients with HF compared with the saline control. [ABSTRACT FROM AUTHOR]

Both cementless and cemented stems have exhibited favorable long-term outcomes in total hip arthroplasty. Nonetheless, in elderly patients, cemented hips offer an advantage due to their reduced risk of periprosthetic fractures. This study aimed to assess the initial outcomes of 28 patients who underwent unilateral cemented total hip arthroplasty utilizing a calcar-guided A2 stem (ARTIQO GmbH, Lüdinghausen, Germany). Various types of antibiotic-loaded bone cement were employed. During follow-up, we recorded demographic data and comorbidities and employed standardized clinical assessment tools, including the Harris Hip Score. Radiographic assessments included preoperative, postoperative, and follow-up imaging to evaluate subsidence, osteolysis, and bone resorption. The results indicated that among the 28 patients, 5 withdrew consent and 2 patients passed away from unrelated causes. Additionally, one prosthesis was explanted due to the undersizing of the cement stopper, which resulted in an inadequate cement mantle. As a result, 20 patients underwent a 1-year follow-up, revealing noteworthy enhancements in clinical scores, with no instances of radiolucent lines or osteolysis. No infections were detected. In summary, our short-term experience with this particular cemented short-stem design yielded promising results, exhibiting excellent functional outcomes, no aseptic loosening attributable to the stem, and no infections. Further clinical studies and registry data are essential to corroborate these findings. [ABSTRACT FROM AUTHOR]

Objective: The curve of Spee is deemed important characteristic of the dentition for a balanced occlusion and distribution of masticatory forces, while orthodontic levelling of an accentuated curve of Spee is generally included as a treatment goal for deepbite correction. However, relapse is often seen and can be problematic. Methods: A retrospective longitudinal study of predominantly young patients with a deep curve of Spee, who had been treated orthodontically with 0.018"‐slot Edgewise fixed appliances, was performed. The depth of the curve of Spee was digitally measured before treatment (T1), at debond (T2), and an average of 7 years post‐debond (T3) and analysed statistically at 5%. Results: A total of 157 patients were included (56.7% female; 11.6‐year‐old at T1), 16.6% of which were treated with premolars extractions. Non‐extraction treatment reduced the curve of Spee at the first premolar from 1.87 mm (T1) to 0.22 mm (T2), which relapsed 0.12 mm (T3; P =.04). The respective depths for the second premolar were 2.0 mm (T1), reduced to 0.80 mm (T2). No significant relapse was seen for the second premolar (0.08 mm; P >.05) or the first permanent molar (0.06 mm; P >.05). No overall significant differences in absolute relapse were seen between extraction and non‐extraction patients, but premolar extractions were associated with less clinically relevant relapse at the first molar (odds ratio 0.27; 95%‐confidence interval 0.08‐0.88; P =.003). Conclusion: Steep curves of Spee can be satisfactorily levelled orthodontically with satisfactory stability in the long term, while premolar extractions might be associated with less relapse. [ABSTRACT FROM AUTHOR]

This study investigates the feasibility of a novel brain–computer interface (BCI) device designed for sensory training following stroke. The BCI system administers electrotactile stimuli to the user's forearm, mirroring classical sensory training interventions. Concurrently, selective attention tasks are employed to modulate electrophysiological brain responses (somatosensory event-related potentials—sERPs), reflecting cortical excitability in related sensorimotor areas. The BCI identifies attention-induced changes in the brain's reactions to stimulation in an online manner. The study protocol assesses the feasibility of online binary classification of selective attention focus in ten subacute stroke patients. Each experimental session includes a BCI training phase for data collection and classifier training, followed by a BCI test phase to evaluate online classification of selective tactile attention based on sERP. During online classification tests, patients complete 20 repetitions of selective attention tasks with feedback on attention focus recognition. Using a single electroencephalographic channel, attention classification accuracy ranges from 70% to 100% across all patients. The significance of this novel BCI paradigm lies in its ability to quantitatively measure selective tactile attention resources throughout the therapy session, introducing a top-down approach to classical sensory training interventions based on repeated neuromuscular electrical stimulation. [ABSTRACT FROM AUTHOR]

This study investigates the impact of nonsurgical periodontal treatment (NSPT) on oral health-related quality of life (OHRQoL) in patients with periodontitis stages (S)2 and S3, and the factors associated with the prediction of patient-reported outcomes. Periodontitis patients (n = 68) with moderately deep periodontal pockets were recruited. Responses to the Oral Health Impact Profile (OHIP)-14 questionnaire and clinical parameters including plaque index, bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were recorded. All patients received supra- and subgingival professional mechanical plaque removal. All clinical parameters and questionnaire responses were recorded again 3 months after NSPT. Clinical parameters and OHIP-14 scores for both stages of periodontitis were significantly improved 3 months after treatment. However, participants with periodontitis S3 had significantly higher total OHIP-14, physical pain, and functional limitation domains scores than periodontitis S2 cases. Baseline CAL, BOP, and the presence of PPD in anterior teeth were positively associated with increased OHIP-14 scores after NSPT. NSPT improved OHRQoL in participants with periodontitis S2 and S3. This was more pronounced in participants having periodontitis S3 than S2. Poorer OHRQoL could be anticipated in people having severe CAL, high BOP, and presence of pockets in the anterior teeth. [ABSTRACT FROM AUTHOR]

Objective: To prove that the "sports rehabilitation bed" is a device aimed at improving the precision of stretching, which can help to reduce the difficulty of rehabilitation therapy, cut down the manpower input of rehabilitation therapy, and shorten the therapy duration as well. Methods: This was a clinical comparative study. Twenty patients who underwent stretching therapy in Sichuan Province Orthopedic Hospital from June 2020 to August 2020 were randomly selected to carry out a control study on both lower extremities. The experimental group was given sports rehabilitation bed to assist rehabilitation therapy, while the control group was given conventional bare-handed stretching rehabilitation therapy. The stretching angle, stretching value, and the effective rate of stretching therapy between the two groups to analyze the clinical value of the new sports rehabilitation therapy bed. Results: The stretching angle in the experimental group when using the sports rehabilitation therapy bed for stretching was lower than the conventional bare-handed stretching in the control group (T<0, P=0.05), with a statistically significant difference; the stretching values of the experimental group were lower than those of the control group(P<0.01), with a statistically significant difference. Moreover, the response rate of stretching therapy in the experimental group was lower than that in the control group(P<0.05), with a statistically significant difference. Conclusion: Sports rehabilitation therapy beds can results in the advantages of effectively preventing iatrogenic injury in the process of stretching, and providing a more accurate and convenient stretching therapy method than the current commonly used bare-handed stretching for sports rehabilitation and intervention. [ABSTRACT FROM AUTHOR]

Retifanlimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1 being investigated in several solid tumor types. We report final results from patients with recurrent microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) endometrial cancer treated with retifanlimab in a POD1UM-101 expansion cohort. Eligible patients (≥18 years; histologically proven/unresectable/recurrent, MSI-H/dMMR endometrial cancer; checkpoint inhibitor naive) received retifanlimab 500 mg intravenously every 4 weeks for ≤2 years. Primary endpoint was safety/tolerability. At data cutoff (May 17, 2023), 76 patients had received at least one retifanlimab dose. Median (range) age was 67 (49–88) years; 88.2% of patients had recurrent metastatic disease and 80.3% had visceral metastases. Seventy-five patients (98.7%) had received at least one prior systemic therapy. Median retifanlimab exposure was 10.0 (0.03–25.9) months; 23 patients completed treatment. 38 patients (50.0%) had grade ≥3 treatment-emergent adverse events (TEAEs), most commonly anemia (n = 10 [13.2%]). 63 patients (82.9%) had treatment-related AEs (TRAEs; grade ≥3, n = 14 [18.4%]); most common was fatigue (n = 14 [18.4%]). Two patients had TEAEs that led to death; no TRAEs were fatal. 39 patients had objective responses (51.3%; 95% CI, 39.6−63.0%); 19 patients (25.0%) had complete response and 20 (26.3%) had partial response. Median progression-free survival was 12.2 months; 30 patients (76.9%) had duration of response (DOR) ≥12 months. Median DOR was not reached after median follow-up time of 26.0 months. Retifanlimab was generally well tolerated and demonstrated encouraging anti-tumor activity in patients with pre-treated recurrent MSI-H/dMMR endometrial cancer. • We evaluated safety and anti-tumor activity of retifanlimab in patients with recurrent MSI-H/dMMR endometrial cancer. • Retifanlimab was generally well tolerated and demonstrated a safety profile typical of the PD-(L)1 inhibitor class. • Objective response rate of 51% (95% CI, 39.6–63.0%) was observed with retifanlimab; median DOR was not reached. • Retifanlimab represents a potential new treatment option for patients with recurrent MSI-H/dMMR endometrial cancer. [ABSTRACT FROM AUTHOR]

Purpose: High-dose methotrexate therapy (HD-MTX) is a standard treatment for various malignant tumors, but approximately 1–10% of patients experience delayed MTX elimination (DME) that can induce organ damage. Glucarpidase can hydrolyze MTX and thereby lower the level of active MTX in the blood. A multicenter, open-label, phase II investigator-initiated trial (CPG2-PII study) was conducted to evaluate glucarpidase rescue therapy in Japanese patients who showed DME after HD-MTX treatment. To confirm the robustness of this therapy, further corporate-sponsored clinical trial (OP-07-001 study) was conducted. Methods: The primary endpoint in the CPG2-PII study was to evaluate the proportion of patients of the percentage clinical important reduction (CIR) as an indicator of MTX concentration, which can be managed with leucovorin and supportive care. The primary endpoint of the OP-07-001 study was to evaluate the decreasing rate of plasma MTX concentration at 20 min after glucarpidase administration from the baseline for four patients. Glucarpidase was administered at a dose of 50 U/kg for 15 and 4 patients, respectively in the two studies, and safety was analyzed for each of them. Results: The rate of CIR was 76.9% (95% confidence interval, 46.2–95.0%) in the CPG2-PII study. The median reduction rate of plasma MTX was 98.83% in the OP-07-001 study. Hypersensitivity, blood bilirubin increased, and headache for each patient were the only study drug-related events. Conclusion: Glucarpidase showed an effect of reducing plasma MTX concentration in Japanese patients with DME as that observed in a previous US study, confirming its favorable safety and tolerability. [ABSTRACT FROM AUTHOR]

Background: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees. Objective: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function. Methods: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20–64. Subjects were allocated to receive either the WLE-derived ceramides and glucosylceramides (test group) or placebo for 12 weeks. The primary outcome was transepidermal water loss (TEWL), and secondary outcomes included skin hydration, visual analog scale (VAS) of itching sensation, and the Japanese Skindex-29. Results: One participant withdrew for personal reasons, resulting in 29 subjects for data analysis (placebo n = 15; test n = 14). The test group showed a tendency of lower TEWL compared to the placebo after 8 weeks (p = 0.07). Furthermore, after 12 weeks of administration, the test group had significantly lower TEWL than the placebo (p = 0.04). On the other hand, no significant differences were observed in the secondary outcome parameters. No adverse events related to the supplements were reported. Conclusions: Oral supplementation of WLE-derived ceramides and glucosylceramides is a prominent and safe approach to enhancing skin barrier function and health. Trial registration: (UMIN000050422). [ABSTRACT FROM AUTHOR]

Marella CE van Ruissen,1,2 Sebastiaan JW van Kraaij,1,2 Pim Gal,1,2 Wouter A Bakker,1,2 Hemme J Hijma,1,2 Geert Jan Groeneveld,1,2 Marieke L de Kam,1 Jacobus Burggraaf,1,2 Matthijs Moerland1,2 1Center for Human Drug Research, Leiden, The Netherlands; 2Leiden University Medical Center, Leiden, The NetherlandsCorrespondence: Matthijs Moerland, Center for Human Drug Research, Zernikedreef 8, Leiden, 2333CL, The Netherlands, Tel +31 71 524 6400, Fax +31 71 5246 499, Email mmoerland@chdr.nlAbstract: Dermal allyl isothiocyanate (AITC) administration and whole-body heat stress (WBHS) are two challenge models that are used to evaluate physiological mechanisms of vasodilation and pharmacological activity in humans. Their exact vasodilatory mechanisms in humans are not fully elucidated but are likely to be nitric oxide (NO)-mediated. This study aimed to evaluate whether there is overlap in the vasodilatory pathways of dermal AITC application and WBHS by combining the challenges. In this open-label interventional study, healthy volunteers underwent dermal administration of AITC twice: under basal conditions and during WBHS. Dermal blood flow (DBF) was non-invasively measured using laser speckle contrast imaging four times, once in each of the following situations: baseline, WBHS only, AITC only, and WBHS combined with AITC. A total of 12 male volunteers, aged 18– 61 years, participated in the study. Compared to baseline, following AITC application, their DBF increased by 63.43 AU (baseline: 32.55, 95% CI [17.78, 47.31] AU, AITC only: 95.97, 95% CI [81.21, 110.7] AU, p < 0.0001). During WBHS, the increase in DBF after AITC was 42.76 AU (WBHS only: 87.25, 95% CI [72.49, 102.0] AU, WBHS+AITC: 130.0, 95% CI [115.2, 144.8] AU, p < 0.0001). The combination of WBHS and AITC resulted in a lower DBF than the sum of the DBF responses to AITC and WBHS when applied separately (ED 20.67, 95% CI [− 3.532, 44.88], p = 0.0916). This might point towards the presence of an interaction in the vasodilatory mechanism of AITC application and WBHS, possibly indicating overlap in their NOS-driven vasodilatory pathways.Keywords: clinical study, vasodilatory pathways, laser speckle contrast imaging, pharmacological challenge models

Background Polycystic ovary syndrome with insulin resistance (PCOS-IR) is recognized as one of the most challenging subtypes of PCOS to treat due to its intricate pathogenesis and significant individual variability. Although Metformin, as a first-line medication, can ameliorate blood glucose levels and enhance insulin sensitivity, its efficacy in regulating hormonal imbalances and improving ovarian function is limited. Additionally, its gastrointestinal side effects often hinder patient adherence. Objective To evaluate the efficacy and safety of Yishen Quzhuo Formula compared to metformin in the treatment of PCOS-IR. Methods A prospective study enrolled 102 PCOS-IR patients from June 2022 to October 2023 at the Department of Gynecology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Patients were randomly assigned in a 2∶1 ratio to the experimental group (n=68) treated with Yishen Quzhuo Formula or the control group (n=34) treated with metformin. The comparison was made between the two groups in terms of ovulation rate, pregnancy rate, sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH ratio, testosterone (T), anti-Müllerian hormone (AMH) ], glucose and lipid metabolism indicators, BMI, waist-hip ratio (WHR), and incidence of adverse reactions. Results After treatment, the basal body temperature (BBT) ovulation rate in the experimental group increased compared to before treatment (P0.05). After treatment, both groups showed a decrease in LH/FSH compared to before treatment (P0.05). After treatment, the waist circumference of the control group was lower than that of the experimental group (P0.05). During treatment, adverse reactions such as hypoglycemia, fatigue, epigastric discomfort, and diarrhea occurred in patients, with a lower incidence of adverse reactions in the experimental group (5/68, 7.35%) than in the control group (15/31, 48.39%) (χ2=20.404, P

Background: Wearable sensors have been heralded as revolutionary tools for healthcare. However, while data are easily acquired from sensors, users still grapple with questions about how sensors can meaningfully inform everyday clinical practice and research. Summary: We propose a simple, comprehensive framework for utilizing sensor data in healthcare. The framework includes three key processes that are applied together or separately to (1) automate traditional clinical measures, (2) illuminate novel correlates of disease and impairment, and (3) predict current and future outcomes. We demonstrate applications of the Automate-Illuminate-Predict framework using examples from rehabilitation medicine. Key Messages: Automate-Illuminate-Predict provides a universal approach to extract clinically meaningful data from wearable sensors. This framework can be applied across the care continuum to enhance patient care and inform personalized medicine through accessible, noninvasive technology.

The nicotine pharmacokinetics (PK) of non-combustible tobacco and nicotine products, including e-cigarettes, have been extensively studied, with lower or similar nicotine exposure reported for most products compared with combustible cigarettes (CC). We conducted two clinical studies to evaluate nicotine PK and assess nicotine consumption when using two types of e-cigarettes with different flavor variants in U.S. healthy adults who smoke, under similar study protocols.

Abstract The objective of this study was to evaluate clinical outcomes for patients undergoing IVF treatment where an artificial intelligence (AI) platform was utilized by clinicians to help determine the optimal starting dose of FSH and timing of trigger injection. This was a prospective clinical trial with historical control arm. Four physicians from two assisted reproductive technology treatment centers in the United States participated in the study. The treatment arm included patients undergoing autologous IVF cycles between December 2022–April 2023 where the physician use AI to help select starting dose of follicle stimulating hormone (FSH) and trigger injection timing (N = 291). The control arm included historical patients treated where the same doctor did not use AI between September 2021 and September 2022. The main outcome measures were total FSH used and average number of mature metaphase II (MII) oocytes. There was a non-significant trend towards improved patient outcomes and a reduction in FSH with physician use of AI. Overall, the average number of MIIs in the treatment vs. control arm was 12.20 vs 11.24 (improvement = 0.96, p = 0.16). The average number of oocytes retrieved in the treatment vs. control arm was 16.01 vs 14.54 (improvement = 1.47, p = 0.08). The average total FSH in the treatment arm was 3671.95 IUs and the average in the control arm was 3846.29 IUs (difference = −174.35 IUs, p = 0.13). These results suggests that AI can safely assist in refining the starting dose of FSH while narrowing down the timing of the trigger injection during ovarian stimulation, benefiting the patient in optimizing the count of MII oocytes retrieved.

Abstract Background Pulp stones are a type of pulp calcification, the presence of which tends to hinder endodontic treatment. Thus, this retrospective study aimed to analyze the distribution of pulp stones in the population in southwest China and identify the influencing factors. Materials Cone-beam computed tomography (CBCT) scans of 5066 teeth of 200 patients (91 males and 109 females) aged 16–45 years were evaluated. Pulp stones were marked as either present or absent when distinct radiopaque masses were found in the pulp cavity, then evaluated the occurrence of pulp stones with regard to tooth type, sex, age group, and contact it with tooth status. The Pearson chi-square test and nonparametric test were used for statistical analysis. Results Pulp stones were detected in 49.0% of patients and 7.4% of teeth, respectively. The incidence in females was 1.9 times higher than in males (OR = 1.9, 95% CI = 1.1–3.3, p = 0.001). Pulp stones were most prevalent in patients 36–45 years of age. Furthermore, in the age range of 16–45 years, the likelihood of finding pulp stones increased 1.1 times per year with age (OR = 1.1, 95% CI = 1.0–1.1, p = 0.032). A higher incidence of pulp stones was observed in the maxilla and molars. Of the 5066 teeth studied, pulp stones were more common in non-intact teeth. Conclusion Nearly half of the population in southwest China had pulp stones. Pulp stones were found significantly more often in females, maxilla, and non-intact teeth, and their frequency increased with age. For dentists, understanding the distribution of pulp stones is crucial for the proper design of root canal treatment (RCT). Trial registration This study was approved by the Ethics Committee of the Affiliated Hospital of Stomatology, Southwest Medical University (certificate number: 20220818001).

Introduction: Segmental spinal deformity results from vertebral compression fracture (VCF) and progressive collapse of the fractured vertebral body (VB). The VB stenting (VBS) systemⓇ comprises a balloon-assisted, expandable, intrasomatic, metal stent that helps maintain the restored VB during balloon removal and cement injection, which minimizes cement leakage. We performed a prospective, multicenter, clinical trial of the VBS system in Japanese patients with acute VCF owing to primary osteoporosis. Methods: Herein, 88 patients, 25 men and 63 women aged 77.4±8.3 years, with low back pain, numerical rating scale (NRS) score of 4, and mean VB compression percentage (VBCP) of

Skin injuries are a global healthcare problem. Chronic ulcers do not heal in a timely fashion, so it is essential to help the body with skin repair. There are some treatments that have been applied to chronic ulcers. One of these treatments is growth factor (GF) therapy. Platelet-rich plasma (PRP) and Platelet-poor plasma (PPP) are two types of plasma derivatives containing many GFs important for wound healing. Several works have reported their application in wound healing and tissue regeneration. The use of autologous PRP is now an adequate alternative in regenerative medicine. It was also demonstrated that PPP is a hemostatic agent for wounds. This review has studied the latest clinical studies, which have applied PRP and PPP to patients with chronic wounds.

Introduction: For deep intrabony defects or Class II furcation involvements (FI), periodontal tissue regenerative therapy combined with bone graft materials and a barrier membrane is recommended. The objective of this study was to assess the safety and efficacy of using carbonate apatite (CO3Ap) granules and absorbable poly(lactic acid/caprolactone) (PLCL) membranes for periodontal regeneration in the treatment of intrabony defects and mandibular Class II FI. Methods: This prospective pilot clinical study, conducted at a single center with a single-arm design, aimed to assess the safety and efficacy of CO3Ap and PLCL membranes in patients with periodontitis. A total of 9 patients with 10 teeth, including seven deep intrabony defects and three Class II FI, were treated with CO3Ap granules and PLCL membranes. Clinical parameters such as probing pocket depth (PPD), clinical attachment level (CAL), bleeding on probing (BOP), tooth mobility (Mo), Plaque Index (PI), and Gingival Index (GI) were assessed at baseline, 6 and 12 months post-surgery. Radiographic analysis was performed using dental X-rays and cone beam computed tomography (CBCT) images taken at baseline, 6, and 12 months post-surgery. Results: Postoperative healing was uneventful in most of the cases. In some cases, membrane exposures were observed. However, there were no signs of inflammation, such as abnormal bleeding, pain, swelling, or pus. These exposures eventually healed well in the end. The mean reductions in PPD at 6 and 12 months were 4.5 ± 1.6 mm and 4.9 ± 1.4 mm, respectively, while the mean gains in CAL were 4.4 ± 1.7 mm at 6 months and 4.6 ± 1.2 mm at 12 months. Radiographic analysis showed improvements in linear bone height within intrabony defects and in the vertical subclassification of FI in Class II FI. Conclusions: Despite the limitations of this study, periodontal regenerative therapy using CO3Ap granules and a PLCL membrane demonstrated promising clinical safety and efficacy for treating intrabony defects and mandibular Class II furcation involvement.

The aim of this study is to investigate the correlation between the incidence of spontaneous tumours of various origins and the localisation in dogs with sex, breed, and age factors. A total of 360 tumours with various localisation were studied pathomorphologically. Histopathologic data sets from 360 dog tissue samples were processed and statistically examined. A chi-square test of independence was conducted to examine the relationships among the various levels of the specified variables. Logistic regression models were employed for dichotomous outcomes to ascertain the influence of certain explanatory variables on the tumour types. Characteristic pathomorphological changes observed during examination of dogs with oncologic diseases were determined. The most common neoplasms were mammary tumours, accounting for 43% of the cases. The mammary gland tumours were most common in mongrel dogs (25%), with German Shepherds (17.3%), Poodles, Dachshunds, Central Asian Shepherds (6.7% each), and Rottweilers (5.7%) following. The highest frequency of these tumours appeared at 8 years of age, predominantly originating from the ductal epithelium, which represented 46.4% of all the malignant cases.

Abstract Background To evaluate the effect of the low-viscosity Icon resin infiltrate application on the color change of white spot enamel lesions (WSLs) over 3-, 6-, and 12-m follow-up periods. Methods Ninety-six teeth diagnosis with WSLs using the ICDAS scoring system in 49 participants were assessed for their color change using the Icon resin infiltration technique. The Icon kit was applied to WSLs as instructed by the manufacturer. Icon-Etch (15% hydrofluoric acid) was applied to the lesions for 2 min, and then, it was rinsed off with copious amount of water for 30 s. Then, Icon-Dry (99% ethanol) was applied to the etched lesions for 30-s followed by the application of the Icon resin infiltrate that was light cured for 40 s. Color change assessment was performed using Vita Easyshade V spectrophotometer at baseline and immediately after Icon resin infiltration, then at 3-, 6-, and 12-m follow-up periods. Analysis of the data was performed using the test of repeated measure ANOVA and the paired sample t test. Results There was a statistically significant difference in ∆E between the different follow-up periods at immediate, 3-m, 6-m, and 12-m. The highest mean value was found in the immediate follow-up period, while the lowest mean value was found in 12-m follow-up period. Conclusions Low-viscosity Icon resin infiltration has the ability for immediate diffusion into the WSLs giving an immediate improvement in the esthetic outcome of the WSLs. However, its long-term outcomes might not be consistent for the color change of the WSLs.

Hiroyuki Ohbayashi, Mitsue Ariga, Kunihiro Ohta, Sahori Kudo, Osamu Furuta, Akinori Yamamoto Medical Corporation, Syureikai, Tohno Chuo Clinic, Mizunami City, Gifu, JapanCorrespondence: Hiroyuki Ohbayashi, Medical Corporation, Syureikai, Tohno Chuo Clinic, 1-14-1, Matsugase Cho, Mizunami City, Gifu, 509-6134, Japan, Tel +81-572-67-1118, Fax +81-572-67-2277, Email ohbayasi@nn.iij4u.or.jp; aims_reserve@yahoo.co.jpPurpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin’yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD).Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured.Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p< 0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p< 0.001, p< 0.001, p=0.004, p< 0.001, and p< 0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin’yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p < 0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively).Conclusion: Overall, Ninjin’yoeito significantly improved patients’ quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin’yoeito may improve frailty and sarcopenia in patients with COPD.Keywords: clinical study, frailty, Ninjin’yoeito, sarcopenia, therapeutic effect

Shi-hao Zhao,1 Wen-hui Wang,1 Yu-cong Liang,1 Kai-xin Zhang,1 Kuan Chen,1 Hong-ling Wang,2 Xiang-qi Wang2 1Acupuncture and Moxibustion Massage College, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 2Department of Oncology, Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, 450008, People’s Republic of ChinaCorrespondence: Xiang-qi Wang, Email wangxiangqi777@163.comAbstract: Baihe Gujin decoction is one of the most commonly used decoction in traditional Chinese medicine for the treatment of lung cancer. It can nourish yin and moisten the lung as well as prevent phlegm from forming and stop coughing. On the one hand, Baihe Gujin decoction is characterized with extensive application, proven efficacy, a long history, and high safety. On the other hand, Baihe Gujin decoction can induce apoptosis of tumor cells, improve immune function and inhibit inflammation. The main anti-tumor components of this include kaempferol, quercetin, isorhamnetin, glycyrrhizin and β-sitosterol. Clinically, Baihe Gujin decoction can improve the adverse reactions caused by radiotherapy, chemotherapy and immunotherapy for lung cancer, enhance the quality of life of patients, and prolong their survival time. At present, there are a large number of clinical and basic researches on the treatment of lung cancer with Baihe Gujin decoction. In this paper, we mainly discussed the treatment of lung cancer with Baihe Gujin decoction through analyzing basic and clinical researches at home and abroad in the past 20 years. Through the discussion, we aimed to probe deeper into Baihe Gujin decoction for the treatment of lung cancer, thereby providing a broader idea for clinical diagnosis and treatment of lung cancer.Keywords: Baihe Gujin decoction, lung cancer, traditional Chinese medicine, basic research, clinical study

Stroke is a primary cause of noncommunicable disease-related death and disability worldwide. The most common form, ischemic stroke, is increasing in incidence resulting in a significant burden on patients and society. Urgent action is thus needed to address preventable risk factors and improve treatment methods. This review examines emerging technologies used in the management of ischemic stroke, including neuroimaging, regenerative medicine, biology, and nanomedicine, highlighting their benefits, clinical applications, and limitations. Additionally, we suggest strategies for technological development for the prevention, diagnosis, and treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Areca nut (AN), the fruit or seed of Areca catechu Linn, has many uses, including chewing and medicinal purposes. It has sparked worries about health due to the presence of alkaloids. Chewing AN may have a variety of negative consequences; however, the medicinal use of AN has no notable adverse effects. To completely understand and effectively use AN, researchers have investigated its chemical makeup or biological activity, analyzed the variations between different AN species and different periods, and improved extraction and processing procedures. Today, an increasing number of researchers are exploring the underlying reasons for AN variations, as well as the molecular mechanisms of biosynthesis of chemical components, to comprehend and change AN at the genetic level. This review presents an overview of the clinical study, pharmacology, and detection of the main bioactive components in AN, and the main factors influencing their content, delving into the omics applications in AN research. On the basis of the discussions and summaries, this review identifies current research gaps and proposes future directions for investigation. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effect of the low-viscosity Icon resin infiltrate application on the color change of white spot enamel lesions (WSLs) over 3-, 6-, and 12-m follow-up periods. Methods: Ninety-six teeth diagnosis with WSLs using the ICDAS scoring system in 49 participants were assessed for their color change using the Icon resin infiltration technique. The Icon kit was applied to WSLs as instructed by the manufacturer. Icon-Etch (15% hydrofluoric acid) was applied to the lesions for 2 min, and then, it was rinsed off with copious amount of water for 30 s. Then, Icon-Dry (99% ethanol) was applied to the etched lesions for 30-s followed by the application of the Icon resin infiltrate that was light cured for 40 s. Color change assessment was performed using Vita Easyshade V spectrophotometer at baseline and immediately after Icon resin infiltration, then at 3-, 6-, and 12-m follow-up periods. Analysis of the data was performed using the test of repeated measure ANOVA and the paired sample t test. Results: There was a statistically significant difference in ∆E between the different follow-up periods at immediate, 3-m, 6-m, and 12-m. The highest mean value was found in the immediate follow-up period, while the lowest mean value was found in 12-m follow-up period. Conclusions: Low-viscosity Icon resin infiltration has the ability for immediate diffusion into the WSLs giving an immediate improvement in the esthetic outcome of the WSLs. However, its long-term outcomes might not be consistent for the color change of the WSLs. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the correlation between the incidence of spontaneous tumours of various origins and the localisation in dogs with sex, breed, and age factors. A total of 360 tumours with various localisation were studied pathomorphologically. Histopathologic data sets from 360 dog tissue samples were processed and statistically examined. A chi-square test of independence was conducted to examine the relationships among the various levels of the specified variables. Logistic regression models were employed for dichotomous outcomes to ascertain the influence of certain explanatory variables on the tumour types. Characteristic pathomorphological changes observed during examination of dogs with oncologic diseases were determined. The most common neoplasms were mammary tumours, accounting for 43% of the cases. The mammary gland tumours were most common in mongrel dogs (25%), with German Shepherds (17.3%), Poodles, Dachshunds, Central Asian Shepherds (6.7% each), and Rottweilers (5.7%) following. The highest frequency of these tumours appeared at 8 years of age, predominantly originating from the ductal epithelium, which represented 46.4% of all the malignant cases. [ABSTRACT FROM AUTHOR]

To observe the clinical study of biological wave early comprehensive rehabilitation therapy combined with different frequencies repetitive transcranial magnetic stimulation (rTMS) in the treatment of coma patients with severe craniocerebral injury. From January 2022 to April 2023, 90 coma patients with severe craniocerebral injury in the Third Hospital of Shandong Province were selected. According to the random number table method, patients were divided into group A and group B, 45 cases in each group, all patients were treated with biological wave early comprehensive rehabilitation therapy combine with rTMS, group A was given low frequency rTMS, and group B was given high frequency rTMS. The Disability Rating Scale (DRS) score, Glasgow Coma Scale (GCS) score, cerebral hemodynamic indexes [blood flow velocity (Vm), middle cerebral artery systolic peak velocity (Vs), pulsatility index (PI)], nerve cell factors[brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), S100-β, neuron-specific enolase (NSE)] and adverse reactions were compared in two groups before and after treatment. After treatment, the GCS score in group B was higher than that in group A, and the DRS score was lower than that in group A (P<0.05). After treatment, the Vm and Vs in group B were higher than those in group A, and the PI was lower than that in group A (P<0.05). After treatment, BDNF in group B was higher than that in group A, and GFAP, S100-β and NSE were lower than those in group A (P<0.05). The incidence of adverse reactions in group B was higher than that in group A (P<0.05). Biological wave early comprehensive rehabilitation therapy combined with rTMS in the treatment of coma patients with severe craniocerebral injury has a certain wake-up effect, among which high frequency wake-up effect is better, and it can effectively regulate the level of nerve cell factors,improve the body's cerebral hemodynamics, and improve GCS and DRS scores. But the adverse reactions of high-frequency rTMS treatment are greater than those of low-frequency rTMS, which is worthy of clinical attention. [ABSTRACT FROM AUTHOR]

Introduction: Senescent cells contribute to age‐related tissue deterioration, including the skin, which plays important roles in overall health and social interactions. This study aimed to assess the effects of the senotherapeutic peptide, OS‐01 (a.k.a. Pep 14), on skin. Methods: A 12‐week split‐face, double‐blinded, vehicle‐controlled study involving 22 participants was conducted. The OS‐01‐containing formulation was applied to one side of the face, while the other side received an identical control formulation lacking the peptide. Skin characteristics were assessed using instrumental measurements, expert clinical grading, and subjective questionnaires. Results: Results showed that the OS‐01 formulation significantly improved one aspect of skin barrier function, as evidenced by reduced trans‐epidermal water loss compared to both baseline and vehicle control. Expert grading and Antera 3D image analysis revealed a reduction in wrinkle appearance and indentation in the periorbital area, and improved skin texture and radiance on both sides of the face, with the OS‐01‐containing formulation demonstrating superior results. Participants also perceived improvements in skin hydration, smoothness, radiance, and overall appearance. Conclusion: The findings suggest that the OS‐01 formulation promotes skin health by strengthening the skin barrier, protecting against dehydration, reducing the appearance of wrinkles, and improving skin texture and radiance. These effects are likely attributed to the senotherapeutic properties of OS‐01 in reducing cellular senescence and its associated detrimental effects. [ABSTRACT FROM AUTHOR]

Introduction Conducting clinical studies is an integral part of the clinical research repertoire of university hospitals. A wealth of organizational competences must always be available in a central location and in an up-to-date form for appropriate administration. Information such as the number of ongoing studies, and the number of enrolled participants is required for tasks related to e.g. sponsor quality management and KPIs. A registry for clinical trials can answer these questions and enhance the exchange of information. Methods Requirements for an in-house registry for clinical trials were defined in a multidisciplinary task force. The requirements included interfaces and key abilities to create customized reports to fulfill the obligation to provide evidence. Results The study registry is productive since May 2020 and internal interfaces have been implemented to ensure consistency between systems and the documented studies. Manually recorded data is enhanced by interfaces to primary registers. The comprehensive data set in the study register enables the creation of individual queries at any time for a variety of questions. Discussion The UKSH study register has already demonstrated its usefulness in various applications and several projects. The extensive data set and the modular realization allows many current and future requirements to be met. [ABSTRACT FROM AUTHOR]

Sleep disorders associated with lifestyle changes and unhealthy habits are major public health concerns. Our previous study showed that Bifidobacterium adolescentis SBT2786 has a potent sleep-promoting effect on fruit flies. Fruit flies share many similarities with mammals, making them suitable model organisms for studying sleep. Thus, in the present study, we conducted a randomized, double-blind, placebo-controlled clinical trial to test whether SBT2786 has sleep-enhancing effects in humans. In this study, 61 participants in the SBT2786 group and 65 participants in the placebo group were analyzed. The results showed that SBT2786 increased sleep time; however, it predominantly increased light sleep and did not improve subjective sleep quality. Interestingly, mood improvement was observed. A subgroup analysis was conducted on participants with high stress levels, and results showed that these participants experienced an increase in sleep duration and an improvement in sleepiness upon waking up and reported feeling well-rested during the day. We concluded that SBT2786 may improve sleep quality, particularly in individuals experiencing high levels of stress, and that SBT2786 can be used as a dietary supplement to improve sleep and mood. [ABSTRACT FROM AUTHOR]

The skin is a barrier organ subjected to lifelong exposure to internal and external factors influencing both its biological response and appearance. A randomized split-face study was carried out on 22 adult female outdoor workers using an artichoke leaf extract (CynageTM). The product's efficacy was measured before and after 28 days of use. The following skin parameters were measured: wrinkle depth, skin roughness, and radiance, to assess the product's effect on the skin appearance; Ferric Reducing Antioxidant Power (FRAP), to assess the total antioxidant capacity; and tumor necrosis factor-alpha (TNF-α) levels, to assess the anti-inflammatory efficacy. These parameters were also integrated by the evaluation of the subjective perception of product efficacy. After 28 days of product use, the skin's appearance improved as follows: wrinkle depth and skin roughness decreased by 5.2% and 7.0%, respectively, while the skin radiance increased by 19.0%. The total antioxidant capacity of the skin increased by 20.2%. The skin's TNF-α levels decreased by 8.2%. The product efficacy was also perceived by the subjects participating in the study. The product was well tolerated. Our findings demonstrate the active role of the ingredient in decreasing the skin damage induced by the exposome. [ABSTRACT FROM AUTHOR]

This narrative review aims to examine the therapeutic potential and mechanism of action of plant extracts in preventing and treating alopecia (baldness). We searched and selected research papers on plant extracts related to hair loss, hair growth, or hair regrowth, and comprehensively compared the therapeutic efficacies, phytochemical components, and modulatory targets of plant extracts. These studies showed that various plant extracts increased the survival and proliferation of dermal papilla cells in vitro, enhanced cell proliferation and hair growth in hair follicles ex vivo, and promoted hair growth or regrowth in animal models in vivo. The hair growth-promoting efficacy of several plant extracts was verified in clinical trials. Some phenolic compounds, terpenes and terpenoids, sulfur-containing compounds, and fatty acids were identified as active compounds contained in plant extracts. The pharmacological effects of plant extracts and their active compounds were associated with the promotion of cell survival, cell proliferation, or cell cycle progression, and the upregulation of several growth factors, such as IGF-1, VEGF, HGF, and KGF (FGF-7), leading to the induction and extension of the anagen phase in the hair cycle. Those effects were also associated with the alleviation of oxidative stress, inflammatory response, cellular senescence, or apoptosis, and the downregulation of male hormones and their receptors, preventing the entry into the telogen phase in the hair cycle. Several active plant extracts and phytochemicals stimulated the signaling pathways mediated by protein kinase B (PKB, also called AKT), extracellular signal-regulated kinases (ERK), Wingless and Int-1 (WNT), or sonic hedgehog (SHH), while suppressing other cell signaling pathways mediated by transforming growth factor (TGF)-β or bone morphogenetic protein (BMP). Thus, well-selected plant extracts and their active compounds can have beneficial effects on hair health. It is proposed that the discovery of phytochemicals targeting the aforementioned cellular events and cell signaling pathways will facilitate the development of new targeted therapies for alopecia. [ABSTRACT FROM AUTHOR]

Introduction: TT-01025-CL is an oral, irreversible small molecule that potently inhibits vascular adhesion protein-1 (VAP-1) for the treatment of inflammation associated with non-alcoholic steatohepatitis (NASH). The objectives of this study were to evaluate the safety/tolerability, pharmacokinetics, and pharmacodynamics of TT-01025-CL, a VAP-1 inhibitor, in healthy Chinese volunteers. Methods: Double-blind, placebo-controlled, dose-escalation studies were conducted in subjects randomized to receive oral once-daily TT-01025-CL (ranges: 10-300 mg [single dose]; 20-100 mg for 7 days [multiple doses]) or placebo under fasting conditions. Safety and tolerability were monitored throughout the study. Pharmacokinetic (PK) parameters were determined using non-compartment analysis. The activity of semicarbazide-sensitive amine oxidase (SSAO)-specific amine oxidase and the accumulation of methylamine in plasma were evaluated as pharmacodynamic (PD) biomarkers. Results: A total of 36 (single-dose group) and 24 (multiple-dose group) subjects were enrolled in the study. No serious adverse events (AEs) were reported, and no subject discontinued due to an AE. All treatment-emergent adverse events (TEAEs) were mild and moderate in intensity. No dose-dependent increase in the intensity or frequency of events was observed. TT-01025-CL was rapidly absorbed after administration. In the single-ascending dose (SAD) study, median Tmax ranged from 0.5 to 2 h and mean t1/2z ranged from 2.09 to 4.39 h. PK was linear in the range of 100-300 mg. The mean Emax of methylamine ranged from 19.167 to 124.970 ng/mL, with mean TEmax ranging from 13.5 to 28.0 h. The complete inhibition (>90%) of SSAO activity was observed at 0.25-0.5 h post-dose and was maintained 48-168 h post-dose. In the multiple-ascending dose (MAD) study, a steady state was reached by day 5 in the 40 mg and 100 mg dose groups. Negligible accumulation was observed after repeated dosing. PK was linear in the range of 20-100 mg. Plasma methylamine appeared to plateau at doses of 20 mg and above, with mean Emax ranging from 124.142 to 156.070 ng/ mL and mean TEmax ranging from 14.2 to 22.0 h on day 7. SSAO activity in plasma was persistently inhibited throughout the treatment period. No evident change in methylamine and SSAO activity was observed in the placebo groups. Conclusion: TT-01025-CL was safe and well-tolerated at a single dose of up to 300 mg and multiple doses of up to 100 mg once daily for 7 consecutive days. Absorption and elimination occurred rapidly in healthy volunteers. Linearity in plasma exposure was observed. TT-01025-CL inhibited SSAO activity rapidly and persistently in humans. The profile of TT-01025-CL demonstrates its suitability for further clinical development. [ABSTRACT FROM AUTHOR]

Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX dry powder for inhalation (DPI) formulations were well-tolerated, showing a remarkable decline in overall bacterial burden compared to a placebo in bronchiectasis patients. Recent research using an inhalable powder combining Pseudomonas phage PEV20 with CFX exhibited a substantial reduction in bacterial density in mouse lungs infected with clinical P. aeruginosa strains and reduced inflammation. Currently, studies suggest that elevated biosynthesis of fatty acids could serve as a potential biomarker for detecting CFX resistance in LRTIs. Furthermore, inhaled CFX has successfully addressed various challenges associated with traditional CFX, including the incapacity to eliminate the pathogen, the recurrence of colonization, and the development of resistance. However, further exploration is needed to address three key unresolved issues: identifying the right patient group, determining the optimal treatment duration, and accurately assessing the risk of antibiotic resistance, with additional multicenter randomized controlled trials suggested to tackle these challenges. Importantly, future investigations will focus on the effectiveness of CFX DPI in bronchiectasis and COPD, aiming to differentiate prognoses between these two conditions. This review underscores the importance of CFX inhalable formulations against LRTIs in preclinical and clinical sectors, their challenges, recent advancements, and future perspectives. [ABSTRACT FROM AUTHOR]

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient‐centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography‐mass spectrometry (LC–MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient‐centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy. [ABSTRACT FROM AUTHOR]

Secondary use of health data has become an emerging topic in medical informatics. Many initiatives focus on clinical routine data, but clinical trial data has complementary strengths regarding highly structured documentation and mandatory data quality (DQ) reviews during the implementation. Clinical imaging trials investigate new imaging methods and procedures. Recently, DQ frameworks for structured data were proposed for harmonized quality assessments (QA). In this article, we investigate the application of these concepts to imaging trials and how a DQ framework could be defined for secondary use scenarios. We conclude that image quality can be assessed through both pixel data and metadata, and the latter can mostly be handled like structured study documentation in QA. For pixel data, typical quality indicators can be mapped to existing frameworks, but require additional image processing. Specific attention needs to be drawn to complete de-identification of imaging data, both on pixel data and metadata level. [ABSTRACT FROM AUTHOR]

The purpose of this randomized, split-mouth-designed controlled and single-blinded clinical study was to evaluate the 3-year clinical performance of Class I and Class II resin composite restorations placed with or without cavity lining with a flowable composite. Fifty patients with treatment needs in two premolars or molars were included. One of the teeth was restored using the nanohybrid composite (Grandio®SO, control group), in the test group a high viscosity flowable composite was additionally applied as a first layer. In both groups, the same self-etch adhesive system was applied. Clinical evaluation after 3 years was carried out using the modified USPHS/Ryge criteria. At the 3-year follow-up the recall rate was 92%. Four restorations failed in the test group (8.7%), three due to the loss of vitality and one after fracture. The control group exhibited a cumulative success rate of 100%, while the test group achieved a success rate of 91.3%. This led to significant differences in the annual failure rate (AFR) between the two groups, with rates of 0% and 2.9% (p < 0.05; Mann–Whitney U-test). After 3 years the cumulative survival rate including all restorations was 95.7%. Statistical analysis revealed significant differences for the parameters: tooth vitality, marginal discoloration, success rate, and AFR. The other parameters exhibited no significant differences. Consequently, the nanohybrid composite demonstrated excellent performance over a 3-year period, whereas the utilization of a flowable composite for the cavity lining did not appear to exert a beneficial influence on clinical outcomes. [ABSTRACT FROM AUTHOR]