A solvent-free, rapid and operationally simple method for the chlorination of pyrazoles with trichloroisocyanuric acid to access 4-chloropyrazole derivatives is described. This high-yielding protocol ...avoids tedious column chromatography and reduces solvent consumption. Mechanistic studies suggested an electrophilic aromatic substitution mechanism. This system also gives good green chemistry metrics.
Application of ball milling for the chlorination of pyrazoles to access 4-chloropyrazoles in an eco-friendly manner.
The clinicopathological significance of altered SWI/SNF complex has not been well evaluated in gastric cancer (GC). We examined SMARCA2, SMARCA4, SMARCB1 and ARID1A expression by immunohistochemistry ...in 1224 surgically resected GCs with subtyping into Epstein-Barr virus (EBV), microsatellite instability (MSI) and non-EBV/MSI Lauren histotypes. SWI/SNF mutations were investigated using the GC dataset of the TCGA Pan-Cancer Atlas. Clinicopathological association was assessed by statistical analysis. There were 427 cases (35%) of SWI/SNF-attenuated GC, including 344 SMARCA2 (28%), 28 SMARCA4 (2%), 11 SMARCB1 (1%) and 197 ARID1A (16%) cases. Simultaneous alterations of multiple subunits were observed. Compared to SWI/SNF-retained cases, SWI/SNF-attenuated GC exhibited a significant predilection to older ages, EBV and MSI genotypes, higher lymphatic invasion and less hematogenous recurrence (P < 0.05). SWI/SNF attenuation was an independent risk factor for short overall survival (P = 0.001, hazard ratio 1.360, 95% confidence interval 1.138-1.625). The survival impact stemmed from SMARCA2-attenuated GCs in stage III and non-EBV/MSI diffuse/mixed subtypes (P = 0.019 and < 0.001, respectively). ARID1A-lost/heterogeneous GCs were more aggressive in the EBV genotype (P = 0.016). SMARCB1 or SMARCA4 loss was not restricted to rhabdoid/undifferentiated carcinoma. In the TCGA dataset, 223 of 434 GCs (52%) harbored deleterious SWI/SNF mutations, including ARID1A (27%), SMARCA2 (9%), ARID2 (9%), ARID1B (8%), PBRM1 (7%), and SMARCA4 (7%). SWI/SNF-mutated GCs displayed a favorable outcome owing to the high percentage with the MSI genotype. In conclusion, SWI/SNF-altered GCs are common and the clinicopathological significance is related to the genotype.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
In this study, we examine the clinicopathological and molecular features of gastric cancer (GC) with SMARCA4 alterations.
Methods and results
We screened SMARCA4 alterations using ...immunohistochemistry on 1199 surgically resected GCs with information on Epstein–Barr virus (EBV), microsatellite instability (MSI) and other SWI/SNF subunits. SMARCA4, SMARCA2 and ARID1A mutations were investigated by targeted sequencing. The clinicopathological significance was determined by statistical analysis. Twenty‐seven cases (2%) with altered SMARCA4 expression were identified, exhibiting completely lost (six), reduced (nine) or heterogeneous (12) patterns. Frequent concomitant alterations of other SWI/SNF subunits were noted with an unusual discordant spatial heterogeneity. In comparison with SMARCA4‐retained GCs, SMARCA4‐lost GCs were observed more frequently in the non‐EBV/MSI subgroup (five of six) and reduced or heterogeneous SMARCA4 expression mainly occurred in EBV‐ or MSI‐associated cases (six of nine and six of 12, respectively; P < 0.001). Histologically, SMARCA4‐altered GC, irrespective of expression pattern, demonstrated divergent histomorphology, spanning tubular, poorly cohesive or mixed, neuroendocrine to solid and undifferentiated carcinoma, with a predilection to the latter two (P < 0.001). De‐differentiation‐like transition and rhabdoid features were noted in a minority of cases. For overall survival, altered SMARCA4 expression was an unfavourable prognostic factor in stage III, EBV‐associated GC and non‐EBV/MSI intestinal subtype (P ≤ 0.001). SMARCA4 or ARID1A mutations were detected mainly in SMARCA4‐lost or reduced GC, respectively.
Conclusions
SMARCA4‐altered GCs are rare and have intratumoral heterogeneity, histomorphological diversity, conditional prognostic significance and various genetic drivers. SMARCA4‐lost GC may represent a genuine SMARCA4‐deficient neoplasm, but most SMARCA4‐reduced/heterogeneous cases are secondary to ARID1A collapse or associated with different genotypes.
Aims and objectives
To assess the concurrent validity between logbooks and a single‐item rehabilitation adherence measurement for patients with stroke. Agreement between caregivers and patients and ...between caregivers and physical therapists regarding a single‐item measurement was investigated, and its predictive validity was explored.
Background
Adherence to therapy is a primary determinant of treatment success. There are no standard instruments for measuring rehabilitation adherence available for stroke patients.
Design
Prospective longitudinal study.
Methods
Seventy‐five patients with stroke were recruited, measured four times and followed for 6 months. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was used to ensure comprehensive reporting. Adherence was documented in logbooks, and single‐item measurements were compared. Predictive validity was explored by assessing associations between adherence levels, self‐care ability and health‐related quality of life. The Spearman's correlation coefficients, weighted kappa, and generalised estimating equations statistics were used to explore the concurrent validity, measurement agreement, and predictive validity, respectively.
Results
Logbook records had a fair correlation (rs = .23, p = .04) with the single‐item rehabilitation adherence measurements. There was moderate agreement (kappa = 0.42, p < .001) between caregiver and patient assessments and fair agreement (kappa = 0.29, p = .017) between caregiver and physical therapist assessments of patients' rehabilitation adherence levels. Perfect rehabilitation adherence, based on the logbook and single‐item measurements, predicted better scores for self‐care ability and quality of life than imperfect rehabilitation adherence during 6 months after inclusion.
Conclusions
There was fair concurrent validity between logbooks and single‐item rehabilitation adherence measurements and moderate and fair adherence measure agreement between caregivers and patients and caregivers and physical therapists, respectively. Logbooks and single‐item rehabilitation adherence measurements had adequate predictive validity.
Relevance to clinical practice
Single‐item rehabilitation adherence measurement is a workable and straightforward method to assess stroke patients' rehabilitation adherence in busy clinical care settings. Caregivers can represent stroke patients regarding their reported rehabilitation adherence.
Patient or public contribution
Patients were diagnosed with stroke in the study hospital. Rehabilitation physicians transferred patients to a research nurse who then screened them for the inclusion criteria and invited them and their family caregivers to participate in this study if they met the requirements. We also recruited seven physical therapists responsible for the physical therapy of the study participants. After participants signed informed consent, the research nurse encouraged participants to respond to research questions face to face, including rehabilitation adherence data, daily physical function, and quality of life. Each participant was measured four times at baseline and at 1, 3, and 6 months after inclusion in this study. Physical therapists had to score their patients' rehabilitation adherence levels before discharge.
Trial registration details
Not applicable.
This study compared changes in occlusal characteristics in patients with skeletal Class III malocclusion with surgery-first approach (SFA) and those with orthodontic-first approach (OFA) through ...digital occlusal analysis.
In this prospective study, 90 consecutive subjects were divided into control, OFA, and SFA groups (30 per group). Force discrepancy, occlusal time, tooth contact, center of force, and force–time graph pattern were calculated for all samples using the T-Scan III system. Between-group differences were analyzed using a 1-way analysis of variance and generalized estimating equations. These parameters were calculated at the following time points: preoperatively, 1-month postoperatively (T1), 4-months postoperatively, and 1-year postoperatively (T3).
No significant differences were observed in the parameters between the experimental groups. The force discrepancy of the OFA and SFA groups decreased, approaching the value of controls at T3. The occlusal time significantly increased at T1 and progressively decreased at T3. The initial contact and maximum force were most frequently observed on molars, and its maximum force significantly decreased by 5.72% and 7.40% in the OFA and SFA groups at T3, respectively. The number of tooth contact was significantly reduced at T1 and gradually increased at T3. Moreover, after surgery, the force–time graph pattern was normalized, and the center of force tended to be more centric; however, the most frequent trajectory revealed premature contact during closing.
No significant difference was found in all parameters between the OFA and SFA groups. Occlusion deteriorated at 1 month postoperatively but gradually improved at 1 year postoperatively, approaching the controls.
•Occlusal parameters were evaluated to differentiate postoperative outcomes between OFA and SFA.•Higher force distribution in some teeth partially remained postoperatively in all groups.•One year after surgery, improved balanced force and occlusal characteristics were observed.•Digital occlusal indicators improve occlusal diagnostic sensitivity during orthodontic therapy.
Recent studies have identified an association between perturbed type I interferon (IFN) responses and the severity of coronavirus disease 2019 (COVID-19). IFNα intervention may normalize the ...dysregulated innate immunity of COVID-19. However, details regarding its utilization and therapeutic evidence have yet to be systematically evaluated. The aim of this comprehensive review was to summarize the current utilization of IFNα for COVID-19 treatment and to explore the evidence on safety and efficacy. A comprehensive review of clinical studies in the literature prior to December 1st, 2021, was performed to identify the current utilization of IFNα, which included details on the route of administration, the number of patients who received the treatment, the severity at the initiation of treatment, age range, the time from the onset of symptoms to treatment, dose, frequency, and duration as well as safety and efficacy. Encouragingly, no evidence was found against the safety of IFNα treatment for COVID-19. Early intervention, either within five days from the onset of symptoms or at hospital admission, confers better clinical outcomes, whereas late intervention may result in prolonged hospitalization.
•A summary of the safety and efficacy of IFNα as a treatment for COVID-19.•No evidence was found against the safety of IFNα treatment for COVID-19.•Early intervention with IFNα within five days confers better clinical outcomes.
The recovery of diaphragmatic function is vital for successful extubation from mechanical ventilation. Recent studies have detected diaphragm atrophy in ventilated adults by using ultrasound, but no ...similar report has been conducted in children. In the current study, we hypothesized that mechanically ventilated children may also develop diaphragm atrophy and diaphragmatic dysfunction.
Children who were admitted to the pediatric intensive care unit and were newly intubated for mechanical ventilation were enrolled into this prospective case-control study. Diaphragm ultrasound assessments were performed daily to evaluate diaphragmatic function in the enrolled children until their discharge from the pediatric intensive care unit. Diaphragm thickness and the diaphragmatic thickening fraction (DTF) were measured through these assessments.
A total of 31 patients were enrolled, and overall, 1389 ultrasound assessments were performed. Immediately after intubation, the initial diaphragm thickness and DTF were measured to be 1.94 ± 0.44 mm and 25.85% ± 3.29%, respectively. In the first 24 hours of mechanical ventilation, diaphragm thickness and the DTF decreased substantially and decreased gradually thereafter. After extubation, the DTF was significantly different between the successful and failed extubation groups (P < 0.001), and a DTF value of <17% was associated with extubation failure.
Diaphragm ultrasound is a noninvasive method for measuring diaphragmatic function in mechanically ventilated children. In this study, significant diaphragm atrophy and a decreased DTF were observed within 24 hours of mechanical ventilation. The recovery of diaphragm thickness and the DTF may be a potential predictor of successful extubation from mechanical ventilation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A room temperature and solvent‐free β‐chlorination and β‐bromination protocol for meso‐tetraarylporphyrinato nickel(II) complexes to access the β‐octahalogenated derivatives by ball‐milling is ...communicated. Various ball‐milling parameters were systematically studied.
A green halogenation method employing no solvent and room temperature conditions for nickel(II) porphyrins is described.
To explore the impact of home environment on effects of a diabetes mellitus (DM)–specific care model among older adults following hip-fracture surgery.
A secondary analysis using the Home ...Environmental Barriers Scale assessed home environment (intervention group=81, control group=79) at 1- and 3-months post-discharge. Outcomes of physical functioning were assessed at 1-, 3-, 6-, and 12-months post-discharge.
The intervention group had better home environmental improvements compared with the control group. Participants were characterized as having good or poor environmental improvements. Those with good improvements and received the intervention had better activities of daily living compared with matched controls. Participants with poor improvements and received the intervention had better scores for hip range of motion and quadriceps muscle strength compared with matched controls.
A DM-specific home rehabilitation for older adults following hip-fracture surgery that includes assessment of the home environment can facilitate complex postoperative functional recovery.
•DM-specific care model can improve the home environment following hip fracture.•Home environment intervention can facilitate postoperative functional recovery.•Home modification with home rehabilitation was needed to improve recovery.
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