Predicting habitual water intake from lifestyle questions.

OBJECTIVE: Previous studies have used selective recall and descriptive dietary record methods, requiring considerable effort for assessing food and water intake. This study created a simplified lifestyle questionnaire to predict habitual water intake (SQW), accurately and quickly assessing the habitual water intake. We also evaluated the validity using descriptive dietary records as a cross-sectional study. SUBJECTS AND METHODS: First, we used crowdsourcing and machine learning to collect data, predict water intake records, and create questionnaires. We collected 305 lifestyle-related questions as predictor variables and selective recall methods for assessing water intake as an outcome variable. Random forests were used for the machine learning models because of their interpretability and accurate estimation. Random forest and single regression correlation analysis were augmented by the synthetic minority oversampling that trained the model. We separated the data by sex and evaluated our model using unseen hold-out testing data, predicting the individual and overall habitual water intake from various sources, including non-alcoholic beverages, alcohol, and food. RESULTS: We found a 0.60 Spearman's correlation coefficient for total water intake between the predicted and the selective recall method values, reflecting the target value to be achieved. This question set was then used for feasibility tests. The descriptive dietary record method helped to obtain a ground-truth value. We categorized the data by gender, season, and source: non-alcoholic beverages, alcohol, food, and total water intake, and the correlation was confirmed. Consequently, our results showed a Pearson's correlation coefficient of 0.50 for total water intake between the predicted and the selective recall method values. CONCLUSIONS: We hypothesize that dissemination of SQW can lead to better health management by easily determining the habitual water intake.

Desarrollo y aplicación de un software educativo bidimensional para el proceso de enseñanza del diseño de Prótesis Parcial Removible / Validation of a two-dimensional educational software for the learning process of the design of Removable Partial Dentures

Objetivo: El objetivo de este estudio fue desarrollar e implementar un software educativo bidimensional para el proceso de aprendizaje del diseño de Prótesis Parciales Removibles.Materiales y métodos: Se utilizó el método científico y procedimientos de evaluación educativa para abordar las necesidades de la asignatura de Prótesis Parcial Removible en la Facultad de Odontología de la UNMSM de Perú en el año 2022. Se utilizó análisis, síntesis y encuestas. Se examinó la aplicabilidad del software y el cumplimiento de los requerimientos de enseñanza y aprendizaje, no sólo en la UNMSM sino en cualquier universidad con requerimientos y características similares. Resultados: La aplicación in-terna del software arrojó un valor final del 96%, mientras que la evaluación de alumnos y docentes mostró un 90% de aceptación, al considerar que el SEDUPPR es sencillo para instalar, sencillo en su manejo y funcionamiento, y es muy útil para aprender diseño de PPR. Conclusiones: El software educativo bidimensional diseñado para el proceso de aprendizaje de Prótesis Parcial Removible es aplicable y puede ser implementado en diferentes ámbitos educativos.

Objective: The objective of this study was to develop and implement a two-dimensional educational software for the learning process of designing Removable Partial Prostheses.Materials and Methods: The scientific method and educational evaluation procedures were utilized to address the needs of the Removable Partial Prosthesis subject in the Fa-culty of Dentistry at the UNMSM in Peru in 2022. Analysis, synthesis, and surveys were used. The software's applicability and fulfillment of teaching and learning requirements were examined, not only at the UNMSM but also in any university with similar require-ments and characteristics. Results: The internal application of the software yielded a final value of 96%, while the evaluation of students and teachers showed a 90% acceptance rate, considering that SEDUPPR is simple to install, easy to use and operate, and is very useful for learn PPR design. Conclusion: The two-dimensional educational software designed for the learning process of Removable Partial Prosthesis is applicable and can be implemented in different educational settings.

Favorable clinical response and drug retention of anti-IL-6 receptor inhibitor in rheumatoid arthritis with high CRP levels: the ANSWER cohort study.

OBJECTIVE: Currently, biological disease-modifying anti-rheumatic drugs (bDMARDs) with different modes of action [tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL-6Ri), or cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig)] are used in clinical practice to treat rheumatoid arthritis (RA). However, it is unclear which type of bDMARD is the most efficacious for a specific clinical situation. C-reactive protein (CRP) is an acute-phase reactant driven by IL-6 signalling. Here, we aimed to establish whether therapeutic efficacy differs between IL-6Ri and other bDMARDs with alternative modes of action in RA patients according to their CRP level. METHOD: RA patients treated with bDMARDs were enrolled from an observational multicentre registry in Japan. Patients were classified into three groups according to baseline CRP tertiles. The overall 3 year retention rates of each bDMARD category were assessed. The Clinical Disease Activity Index (CDAI) was also assessed before and 3, 6, and 12 months after bDMARD initiation. RESULTS: A total of 1438 RA patients were included and classified into three groups according to tertiles of baseline CRP levels (CRP1, 0-0.3; CRP2, 0.3-1.8; CRP3, 1.8-18.4 mg/dL). In CRP3, the overall 3 year drug retention rates were significantly higher for IL-6Ri than for TNFi and CTLA4-Ig (77.5 vs 48.2 vs 67.3, respectively). No significant difference was evident in terms of CDAI 12 months after bDMARD initiation in CRP1-CRP3. CONCLUSION: IL-6Ri may be a favourable therapeutic option over TNFi and CTLA4-Ig in RA patients with high CRP levels.

Structure of LRRK2 in Parkinson's disease and model for microtubule interaction.

Leucine-rich repeat kinase 2 (LRRK2) is the most commonly mutated gene in familial Parkinson's disease1 and is also linked to its idiopathic form2. LRRK2 has been proposed to function in membrane trafficking3 and colocalizes with microtubules4. Despite the fundamental importance of LRRK2 for understanding and treating Parkinson's disease, structural information on the enzyme is limited. Here we report the structure of the catalytic half of LRRK2, and an atomic model of microtubule-associated LRRK2 built using a reported cryo-electron tomography in situ structure5. We propose that the conformation of the LRRK2 kinase domain regulates its interactions with microtubules, with a closed conformation favouring oligomerization on microtubules. We show that the catalytic half of LRRK2 is sufficient for filament formation and blocks the motility of the microtubule-based motors kinesin 1 and cytoplasmic dynein 1 in vitro. Kinase inhibitors that stabilize an open conformation relieve this interference and reduce the formation of LRRK2 filaments in cells, whereas inhibitors that stabilize a closed conformation do not. Our findings suggest that LRRK2 can act as a roadblock for microtubule-based motors and have implications for the design of therapeutic LRRK2 kinase inhibitors.

The relationship between sucrose intake in coffee or tea, and root or coronal caries in an elderly Japanese population.

OBJECTIVES: Few studies have examined the effect of sucrose intake in coffee or tea (SCT) on dental caries, especially root caries, in elderly people. The purpose of the present study was to examine the associations between SCT and the prevalence of root or coronal caries in community-dwelling elderly Japanese. METHODS: Participants were 370 elders aged 75 years from a larger cohort study of elders in Niigata City, Japan. Dietary habits during the preceding month were assessed with a validated brief self-administered diet history questionnaire (BDHQ). The caries examination was conducted using mirror and ball-pointed periodontal probes under artificial light. Poisson regression analysis was performed to analyze the prevalence-rate ratios (PRRs) between SCT and the root or coronal caries. The number of root or coronal caries was selected as the dependent variable for the analysis. Then, SCT (tertiles labeled low, medium and high) and other 4 variables were selected as independent variables. RESULTS: The PRRs between the number of root caries lesions and SCT were signifi cantly higher in the second (medium intake, 1.38, p ⟨ 0.001) and third tertiles (high intake, 2.07, p ⟨ 0.001). Similar tendencies were seen for the number of coronal caries lesions (PRRs in the second and third tertiles 1.74 and 2.46, respectively, both p ⟨ 0.001). CONCLUSION: A significant positive relationship was observed between sucrose in coffee and tea and the number of coronal or root caries lesions in community-dwelling elderly Japanese.

Bendamustine-120 plus rituximab therapy for relapsed or refractory follicular lymphoma: a multicenter phase II study.

The optimal dose, schedule, and other aspects of bendamustine plus rituximab treatment remain unclear for patients with relapsed or refractory follicular lymphoma (FL). Herein, we analyzed the efficacy of bendamustine combined with rituximab (RB-120) treatment for Japanese patients with relapsed or refractory FL. This phase II clinical trial included patients with relapsed or refractory FL who received 375 mg/m2 rituximab on day 1 and 120 mg/m2 bendamustine on days 2 and 3 every 28 days for up to 6 cycles. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included the complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety. Thirty-seven patients were enrolled in the trial (median age 62 years, range 42-75 years). All patients were previously treated with rituximab-containing chemotherapy, and 83.8% were previously treated with the R-CHOP regimen. A median of 5 cycles (range 1-6) and 48.6% of patients completed 6 cycles. The ORR was 91.9% (95% confidence interval [CI] 78.1-98.3%), with a CR rate of 86.5% (95% CI 71.2-95.5%). The 3-year PFS and OS were 70.9% (95% CI 52.3-83.3%) and 88.9% (95% CI 73.1-95.7%), respectively, with the median 39.5 months follow-up duration. The most-frequently observed grade 3/4 adverse events were hematologic: lymphopenia (95%) and neutropenia (70%). No treatment-related deaths were observed. RB-120 showed a good efficacy with equivalent toxicities, compared with the bendamustine 120 mg/m2 monotherapy. However, the problem of high drop-out incidences cannot be ignored.

Deep-learning-based, computer-aided classifier developed with a small dataset of clinical images surpasses board-certified dermatologists in skin tumour diagnosis.

BACKGROUND: Application of deep-learning technology to skin cancer classification can potentially improve the sensitivity and specificity of skin cancer screening, but the number of training images required for such a system is thought to be extremely large. OBJECTIVES: To determine whether deep-learning technology could be used to develop an efficient skin cancer classification system with a relatively small dataset of clinical images. METHODS: A deep convolutional neural network (DCNN) was trained using a dataset of 4867 clinical images obtained from 1842 patients diagnosed with skin tumours at the University of Tsukuba Hospital from 2003 to 2016. The images consisted of 14 diagnoses, including both malignant and benign conditions. Its performance was tested against 13 board-certified dermatologists and nine dermatology trainees. RESULTS: The overall classification accuracy of the trained DCNN was 76·5%. The DCNN achieved 96·3% sensitivity (correctly classified malignant as malignant) and 89·5% specificity (correctly classified benign as benign). Although the accuracy of malignant or benign classification by the board-certified dermatologists was statistically higher than that of the dermatology trainees (85·3% ± 3·7% and 74·4% ± 6·8%, P < 0·01), the DCNN achieved even greater accuracy, as high as 92·4% ± 2·1% (P < 0·001). CONCLUSIONS: We have developed an efficient skin tumour classifier using a DCNN trained on a relatively small dataset. The DCNN classified images of skin tumours more accurately than board-certified dermatologists. Collectively, the current system may have capabilities for screening purposes in general medical practice, particularly because it requires only a single clinical image for classification.

Hybrid transgastric approach for the treatment of gastroesophageal junction pathologies.

Flexible endoscopy has evolved to the point that it includes many endoluminal procedures that once required open or laparoscopic surgery, for instance, antireflux surgery, pyloromyotomy, mucosal and submucosal tumor resections, and even full-thickness resection. However, these procedures remain technically demanding due to flexible technology issues: difficult imaging, limited energy devices, lack of staplers, unsatisfactory suturing abilities, and so on. Transgastric laparoscopy or hybrid laparoscopy/flex endoscopy has been described for almost two decades as an alternative to a pure endoluminal approach, mainly for pancreatic pseudocyst drainage and full-thickness and mucosal resection of various lesions. The approach has never been widely adopted mostly due to cumbersome and difficult to maintain methods of gastric access. We propose to expand the indications of transgastric laparoscopy by using novel endoscopically placed ports to replicate endoscopic procedures particularly in the difficult to access proximal stomach such as endoluminal antireflux surgery. Under general anesthesia, five female pigs (mean weight: 27.6 kg) had endoscopic placement of 3, 5 mm intragastric ports (Endo-TAGSS, Leakwood KS, USA) using a technique similar to percutaneous endoscopic gastrostomy. A 5-mm laparoscope was used for visualization. Laparoendoscopic-assisted plication of the gastroesophageal junction (GEJ) was performed using 3-0 interrupted sutures (Polysorb®, Covidien, Mansfield, MA, USA). A functional lumen imagine probe (EndoFLIP®, Crospon, Inc., Galway, Ireland) was used to measure diameter, cross sectional area (CSA), distensibility, and compliance of GEJ before and after intervention. Once the TAGSS ports were removed, the gastrotomies were closed by using endoscopic over-the-scope clips. At the end of the procedure, animals were euthanized. Five laparoendoscopic-assisted endoluminal plications were performed. The mean operative time was 65.6 min (Endoscopic evaluation: 3.2 min, TAGSS Insertion: 11 min, EndoFLIP evaluation + GEJ Plication: 43.25 min, gastric wall closure: 15 minutes). In all cases, this technique was effective and allowed to achieve an adequate GEJ plication by endoscopic grading and EndoFLIP measurements. Median pre-plication GEJ diameter (D) and median pre-plication GEJ cross-sectional area (CSA) were 11.42 mm (8.6-13.6 mm) and 104.8 mm2 (58-146 mm2). After the procedure, these values were decreased to 6.14 mm (5.7-6.6 mm) and 29.8 mm2 (25-34 mm2) respectively (p = 0.0079). Median pre-plication distensibility (d) and compliance (C) were 7.87 mm2/mmHg (2.4-22.69 mm2/mmHg) and 190.56 mm3/mmHg (70.9-502.8 mm3/mmHg). After the procedure, these values decreased to 1.5 mm2/mmHg (0.7-2.2 mm2/mmHg) and 52.17 mm3/mmHg (21.9-98.7 mm3/mmHg) respectively (p = 0.0317). No intraoperative events were observed. Endoscopically, all valves were felt to be transitioned from a Hill grade 3 (normal state for the animal model) to a Hill grade 1 at the procedure completion. A hybrid laparoendoscopic approach is a feasible alternative for performing intragastric procedures with the assistance of conventional laparoscopic instruments; especially in cases where the intervention location limits the access to standard endoscopy or where endoscopic technology is inadequate. Further evaluation is planned in survival models and clinical trials.

Assessment of the F wave technique for motor unit number estimation in normal dogs.

Motor unit number estimation (MUNE) is an electrophysiological technique to quantify the number of motor units in a muscle. A previous study examining MUNE in dogs used an incremental method. The purpose of this study was to examine the use of the F wave method in dogs and to provide information about this technique. Seven healthy laboratory dogs were examined using the F wave method by stimulating either a single site or multiple sites. In the multiple site stimulation F wave (MSS-F) method, the nerve was stimulated at several close sites along the deep peroneal nerve innervating the extensor digitorum brevis muscle. Test-retest was performed with a 1 week interval in all dogs using both techniques. In this preliminary study, median MUNE values were 88 (range 27-187) using the single site stimulation F wave (SSS-F) method and 68.5 (range 47-106) using the MSS-F method. The intra-class correlation coefficients between the two sets of data for each method were 0.20 and 0.09 for left and right SSS-F, respectively, and 0.77 and 0.69 for left and right MSS-F, respectively. MSS-F had less intra-individual variability of MUNE values and was more reproducible. These results indicate that MSS-F can be performed in dogs. MUNE using MSS-F might help with quantitative evaluation of motor neurone dysfunction and progression of diseases affecting motor neurones.