Machine learning in electronic-quantum-matter imaging experiments.

For centuries, the scientific discovery process has been based on systematic human observation and analysis of natural phenomena1. Today, however, automated instrumentation and large-scale data acquisition are generating datasets of such large volume and complexity as to defy conventional scientific methodology. Radically different scientific approaches are needed, and machine learning (ML) shows great promise for research fields such as materials science2-5. Given the success of ML in the analysis of synthetic data representing electronic quantum matter (EQM)6-16, the next challenge is to apply this approach to experimental data-for example, to the arrays of complex electronic-structure images17 obtained from atomic-scale visualization of EQM. Here we report the development and training of a suite of artificial neural networks (ANNs) designed to recognize different types of order hidden in such EQM image arrays. These ANNs are used to analyse an archive of experimentally derived EQM image arrays from carrier-doped copper oxide Mott insulators. In these noisy and complex data, the ANNs discover the existence of a lattice-commensurate, four-unit-cell periodic, translational-symmetry-breaking EQM state. Further, the ANNs determine that this state is unidirectional, revealing a coincident nematic EQM state. Strong-coupling theories of electronic liquid crystals18,19 are consistent with these observations.

A study of hospitalized COVID-19 patients with AKI in a setting of multiracial developing country.

BACKGROUND: The commonest indication for hospitalization in COVID-19 patients is hypoxemia or severe respiratory symptoms. However, COVID-19 disease may result in extrapulmonary complications including kidney-related pathology. The reported incidence of renal involvement related to COVID infection varies based on geographical location. OBJECTIVE: This study aimed to assess the incidence rate of AKI in hospitalized COVID-19 patients and identify risk factors and prognostic predictors. METHOD: In this retrospective study, we recruited hospitalized COVID-19 patients from January 2021 until June 2021 at the University Malaya Medical Center. The inclusion criteria were hospitalized for ≥ 48 h with confirmed COVID-19 infection and at least 18 years old. Patient demographic and clinical data were collected from electronic medical records. The staging of AKI was based on criteria as per KDIGO guidelines. RESULTS: One thousand five hundred twenty-nine COVID patients fulfilled the inclusion criteria with a male-to-female ratio of 759 (49.6%) to 770 (50.3%). The median age was 55 (IQR: 36-66). 500 patients (32.7%) had diabetes, 621 (40.6%) had hypertension, and 5.6% (n = 85) had pre-existing chronic kidney disease (CKD). The incidence rate of AKI was 21.1% (n = 323). The percentage of COVID patients in different AKI stages of 1,2 and 3 were 16.3%, 2.1%, and 2.7%, respectively. Fifteen hospitalized patients (0.98%) required renal replacement therapy. 58.8% (n = 190) of AKI group had complete recovery of kidney function. Demographic factors included age (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.012), CKD (p < 0.001), and vaccination status (p = 0.042) were associated with an increased risk of developing AKI. We found that the AKI cohort had statistically significant lower platelet counts and higher ferritin levels than the non-AKI cohort. AKI is a risk predictor of prolonged hospitalization (p < 0.001) and higher mortality rates (P < 0.001). CONCLUSION: AKI is a common clinical complication among hospitalized COVID-19 patients. The etiology of AKI is multifactorial and may have an adverse impact on patient morbidity and mortality.

Early Postoperative Activities of Daily Living Do Not Adversely Affect Joint Torques or Translation Regardless of Capsular Condition: A Cadaveric Study.

PURPOSE: To evaluate the impact of capsular management on joint constraint and femoral head translations during simulated activities of daily living (ADL). METHODS: Using 6 (n = 6) cadaveric hip specimens, the effect of capsulotomies and repair was then evaluated during simulated ADL. Joint forces and rotational kinematics associated with gait and sitting, adopted from telemeterized implant studies, were applied to the hip using a 6-degrees of freedom (DOF) joint motion simulator. Testing occurred after creation of portals, interportal capsulotomy (IPC), IPC repair, T-capsulotomy (T-Cap), partial T-Cap repair, and full T-Cap repair. The anterior-posterior (AP), medial-lateral (ML), and axial compression DOFs were operated in force control, whereas flexion-extension, adduction-abduction, and internal-external rotation were manipulated in displacement control. Resulting femoral head translations and joint reaction torques were recorded and evaluated. Subsequently, the mean-centered range of femoral head displacements and peak signed joint restraint torques were calculated and compared. RESULTS: During simulated gait and sitting, the mean range of AP femoral head displacements with respect to intact exceeded 1% of the femoral head diameter after creating portals, T-Caps, and partial T-Cap repair (Wilcoxon signed rank P < .05); the mean ranges of ML displacements did not. Deviations in femoral head kinematics varied by capsule stage but were never very large. No consistent trends with respect to alterations in peak joint restrain torques were observed. CONCLUSIONS: In this cadaveric biomechanical study, capsulotomy and repair minimally affected resultant femoral head translation and joint torques during simulated ADLs. CLINICAL RELEVANCE: The tested ADLs appear safe to perform after surgery, regardless of capsular status, because adverse kinematics were not observed. However, further study is required to determine the importance of capsular repair beyond time-zero biomechanics and the resultant effect on patient-reported outcomes.

Hip Circumferential Labral Reconstruction Provides Similar Distractive Stability to Labral Repair After Cam Over-Resection in a Biomechanical Model.

PURPOSE: To evaluate the change in hip distractive stability after a cam over-resection, labral tear, repair, labrectomy, or circumferential 6- or 10-mm labral reconstruction in a biomechanical model. METHODS: Ten fresh-frozen matched-pair human cadaveric hips were analyzed using a materials testing system to measure the force and distance required to disrupt the suction seal of the hip (1) with an intact capsule and labrum; (2) after a capsulectomy and labral repair; (3) after a capsulectomy, 5-mm cam over-resection and labral repair; (4) after a capsulectomy, 5-mm cam over-resection and labral tear; (5) after a capsulectomy, 5-mm cam over-resection and labrectomy; and (6) after a capsulectomy, 5-mm cam over-resection and a 6- or 10-mm circumferential labral reconstruction with iliotibial band (5 hips each). Each specimen was retested at 0° flexion, 45° flexion, and 45° flexion and at 15° internal rotation and analyzed using nonparametric statistical methods. RESULTS: The Friedman test of differences was significant among structural conditions and hip positions (P = .001). In all positions, the resistive force that opposed the disruption of the suction seal in an intact hip was significantly greater compared with all other conditions. The resistive force for the capsulectomy, 5-mm cam over-resection and labrectomy condition was significantly less compared with almost all other conditions and hip positions. A qualitative suction seal was achieved in 20% of hip specimens with a 6-mm labral reconstruction, whereas a seal was in achieved 60% of specimens with a 10-mm labral reconstruction. CONCLUSIONS: After a cam over-resection, a circumferential labral reconstruction improves the distractive stability of a labral deficient hip, comparable to a labral repair or tear in a biomechanical model. CLINICAL RELEVANCE: Circumferential labral reconstruction may be a viable treatment option for patients with ongoing symptoms after hip arthroscopy with evidence of a cam over-resection and a deficient labrum.

Hip Labral and Capsular Repair Are Unable to Restore Distractive Stability in a Biomechanical Model.

PURPOSE: To evaluate the change in hip distractive stability after a capsulotomy, labral tear, and simultaneous repair of both the capsule and the labrum in a biomechanical model. METHODS: Ten fresh-frozen human cadaveric hips were analyzed using a materials testing system to measure the distractive force and distance required to disrupt the hip suction seal under the following conditions: (1) native intact capsule and labrum, (2) 2- or 4-cm interportal capsulotomy (IPC), (3) labral tear, (4) T extension, (5) labral repair, (6) T extension repair, and (7) IPC repair. Each specimen was retested at 0° of flexion, 45° of flexion, and 45° of flexion with 15° of internal rotation. RESULTS: A significantly higher distractive force was required to rupture the suction seal in the intact condition compared with IPC (P = .012; 95% confidence interval [CI], 4.9-42.4); IPC and labral tear (P = .002; 95% CI, 11.3-49.4); IPC, labral tear, and T extension (P = .001; 95% CI, 13.9-51.5); IPC, labral repair, and T extension (P < .001; 95% CI, 20.8-49.7); IPC, labral repair, and T extension repair (P = .002; 95% CI, 12.5-52.4); and IPC repair, labral repair, and T extension repair (P = .01; 95% CI, 5.8-46.1). The IPC condition required a higher distractive force in isolation than when combined with a labral tear (P = .14; 95% CI, 1.2-12.0), T extension (P = .005; 95% CI, 2.8-15.3), or labral repair (P = .002; 95% CI, 4.4-18.8). CONCLUSIONS: The distractive resistance of an intact hip capsule and labrum was not restored once the soft tissues were violated, despite labral repair with a loop technique and capsular repair with interrupted figure-of-8 sutures. CLINICAL RELEVANCE: Time-zero complete capsular repair with concomitant labral repair may not be adequate to restore distractive hip stability after hip arthroscopy, reinforcing the use of postoperative precautions in the early postoperative period.

Lymph node ratio prognosticates overall survival in patients with stage IV colorectal cancer.

BACKGROUND: Lymph node ratio (LNR) is suggested to address the shortcomings of using only lymph node yield (LNY) or status in colorectal cancer (CRC) prognosis. This study explores how LNR affects survival in patients with metastatic colorectal cancer (mCRC), seeking to provide clearer insights into its application. METHODS: This observational cohort study investigated stage IV patients with CRC (1995-2021) who underwent an upfront resection of their primary tumour at Concord Hospital, Sydney. Clinicopathological data were extracted from a prospective database, and LNR was calculated both continuously and dichotomously (LNR of 0 and LNR > 0). The primary endpoint was overall survival (OS). The associations between LNR and various clinicopathological variables were tested using regression analyses. Kaplan-Meier and Cox regression analyses estimated OS in univariate and multivariate survival models. RESULTS: A total of 464 patients who underwent a primary CRC resection with clear margins (mean age 68.1 years [SD 13.4]; 58.0% M; colon cancer [n = 339,73.1%]) had AJCC stage IV disease. The median LNR was 0.18 (IQR 0.05-0.42) for colon cancer (CC) resections and 0.21 (IQR 0.09-0.47) for rectal cancer (RC) resections. A total of 84 patients had an LNR = 0 (CC = 66 patients; RC = 18 patients). The 5-year OS for the CC cohort was 10.5% (95% CI 8.7-12.3) and 11.5% (95% CI 8.4-14.6) for RC. Increasing LNR demonstrated a decline in OS in both CC (P < 0.001) and RC (P < 0.001). In patients with non-lymphatic dissemination only (LNR = 0 or N0 status), there was better survival compared with those with lymphatic spread (CC aHR1.50 [1.08-2.07;P = 0.02], RC aHR 2.21 [1.16-4.24;P = 0.02]). CONCLUSIONS: LNR is worthy of consideration in patients with mCRC. An LNR of 0 indicates patients have a better prognosis, underscoring the need for adequate lymphadenectomy to facilitate precise mCRC staging.

Glycaemic control and microvascular complications among paediatric type 2 diabetes mellitus patients in Hong Kong at 2 years after diagnosis.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is becoming increasingly common among children and adolescents worldwide, including those in Hong Kong. This study analysed the characteristics and prevalence of microvascular complications among paediatric T2DM patients in Hong Kong at diagnosis and 2 years after diagnosis. METHODS: All patients aged <18 years who had been diagnosed with DM at public hospitals in Hong Kong were recruited into the Hong Kong Childhood Diabetes Registry. Data collected at diagnosis and 2 years after diagnosis were retrospectively retrieved from the Registry for patients diagnosed from 2014 to 2018. RESULTS: Median haemoglobin A1c (HbA1c) levels were 7.5% (n=203) at diagnosis and 6.5% (n=135) 2 years after diagnosis; 59.3% of patients achieved optimal glycaemic control (HbA1c level <7%) at 2 years. A higher HbA1c level at diagnosis was associated with worse glycaemic control at 2 years (correlation coefficient=0.39; P<0.001). The presence of dyslipidaemia (adjusted odds ratio [aOR]=3.19; P=0.033) and fatty liver (aOR=2.50; P=0.021) at 2 years were associated with suboptimal glycaemic control. Diabetic neuropathy and retinopathy were rare in our cohort, but 18.6% of patients developed microalbuminuria (MA) within 2 years after diagnosis. Patients with MA had a higher HbA1c level at 2 years (median: 7.2% vs 6.4%; P=0.037). Hypertension was a risk factor for MA at 2 years, independent of glycaemic control (aOR=4.61; P=0.008). CONCLUSION: These results highlight the importance of early diagnosis and holistic management (including co-morbidity management) for paediatric T2DM patients.

Refractive error and amblyopia among primary school children in remote islands of East Coast of Peninsular Malaysia.

INTRODUCTION: Little is known about the prevalence of refractive errors and amblyopia among school children on the islands of East Coast Malaysia. This study aimed to investigate the prevalence of these conditions and their associated factors in this unique and remote geographical location. MATERIALS AND METHODS: This multicentre cross-sectional school-based study included 480 children aged 7 to 12 year from primary schools on the islands of the East Coast of Malaysia. All children underwent visual acuity assessment, orthoptic evaluation, anterior and posterior segment examinations and manifest refraction. Demographic data, history of parental refractive error, parental education level, duration of digital screen time and time spent outdoors were documented in a questionnaire distributed to the parents. RESULTS: The mean age was 9.53 ± 1.69 years, with an equal distribution of genders. The ethnic composition of the subjects was 99.4% Malay and 0.6% Orang Asli. The overall prevalence of refractive errors was 11.9% (95% CI: 9.1 to 15.1%), with myopia at 7.1% (95% CI: 5.0 to 9.8%), hyperopia at 2.5% (95% CI: 1.3 to 4.3%), astigmatism at 2.3% (95% CI: 1.1 to 4.1%) and amblyopia at 2.5% (95% CI: 1.3 to 4.3%). Older age, an absence of parental history of refractive error and reduced daily outdoor time were significantly associated with refractive errors (p < 0.05). CONCLUSION: The prevalence of refractive error is 11.9% and amblyopia is 2.5% among primary school children on the islands of the East Coast of Peninsular Malaysia. Older age, an absence of parental history of refractive error and reduced daily outdoor time are associated with refractive error.

Prophylactic intravenous tranexamic acid and thromboembolism in non-cardiac surgery: a systematic review, meta-analysis and trial sequential analysis.

Tranexamic acid is an antifibrinolytic drug that is widely used during surgery, but there are concerns about its thromboembolic effects. We aimed to investigate the effect of prophylactic intravenous tranexamic acid on thromboembolic outcomes in patients undergoing non-cardiac surgery. The MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched. Randomised controlled trials comparing intravenous tranexamic acid with placebo or no treatment in patients undergoing non-cardiac surgery were included. The primary outcome was a composite of peri-operative cardiovascular thromboembolic events, defined as any deep vein thrombosis, pulmonary embolism, myocardial ischaemia/infarction or cerebral ischaemia/infarction. A total of 191 randomised controlled trials (40,621 patients) were included in the review. The primary outcome occurred in 4.5% of patients receiving intravenous tranexamic acid compared with 4.9% of patients in the control group. Our analysis showed that there was no difference between groups for composite cardiovascular thromboembolic events (risk ratio 1.02, 95%CI 0.94-1.11, p = 0.65, I2 0%, n = 37,512). This finding remained robust when sensitivity analysis was performed with continuity correction and in studies with a low risk of bias. However, in trial sequential analysis, our meta-analysis only achieved 64.6% of the required information size. There was no association between intravenous tranexamic acid and seizure rate or mortality rate within 30 days. Intravenous tranexamic acid was associated with a reduced blood transfusion rate compared with control (9.9% vs. 19.4%, risk ratio 0.46, 95%CI 0.41-0.51, p < 0.0001). It was encouraging to see the evidence that the administration of intravenous tranexamic in patients undergoing non-cardiac surgery was not associated with an increased risk of thromboembolic outcomes. However, our trial sequential analysis demonstrated that currently available evidence is not yet sufficient to reach a firm conclusion.

Major low anterior resection syndrome has equivalent health-related quality of life implications as having a permanent colostomy.

BACKGROUND: The literature is inconclusive when comparing health-related quality of life following restorative anterior resection (AR) compared with abdominoperineal resection (APR). Consideration of functional outcomes may explain this inconsistency. The aim of this study was to compare health-related quality of life in patients post-anterior resection, stratified by low anterior resection syndrome score, and post-abdominoperineal resection patients. METHODS: A cross-sectional study of consecutive patients post APR and AR for rectal or sigmoid adenocarcinoma at a tertiary centre in Sydney, Australia (Jan 2012- Dec 2021) was performed. HRQoL outcomes (SF36v2 physical [PCS] and mental component summary [MCS] scores) were compared between APR and AR patients, with subgroup analyses stratifying AR patients according to LARS score (no/minor/major). Age- and gender-adjusted comparisons were performed by linear regression. RESULTS: Overall, 248 post-AR patients (57.3% male, mean age 70.8 years, SD 11.6) and 64 post-APR patients (62.5% male, mean age 68.1 years, SD 13.1) participated. When stratified by LARS, 'major LARS' had a similar negative effect on age-and sex-adjusted PCS scores as APR. 'No LARS' (p < 0.001) and 'minor LARS' (p < 0.001) patients had higher PCS scores compared to post-APR patients. 'Major LARS' had a similarly negative effect on MCS scores compared with post-APR patients. MCS scores were higher in 'no LARS' (p = 0.006) compared with APR patients. CONCLUSIONS: Postoperative bowel dysfunction significantly impacts health-related quality of life. Patients with 'major LARS' have health-related quality of life as poor as those following APR. This requires consideration when counselling patients on postoperative health-related quality of life, especially where poor postoperative bowel function is anticipated following restorative surgery.

Five-year retrospective review of ultrasound-guided manual vacuum aspiration for first-trimester miscarriage.

INTRODUCTION: Manual vacuum aspiration is increasingly accepted as an alternative to medical or surgical evacuation of the uterus after first-trimester miscarriage. This study aimed to assess the efficacy of ultrasound-guided manual vacuum aspiration (USG-MVA) in the management of first-trimester miscarriage. METHODS: This retrospective analysis included adult women with first-trimester miscarriage who underwent USG-MVA in Hong Kong between July 2015 and February 2021. The primary outcome was the efficacy of USG-MVA in terms of complete evacuation of the uterus, without the need for further medical or surgical intervention. Secondary outcomes included tolerance of the entire procedure, the success rate of karyotyping using chorionic villi, and procedural safety (ie, any clinically significant complications). RESULTS: In total, 331 patients were scheduled to undergo USG-MVA for first-trimester miscarriage or incomplete miscarriage. The procedure was completed in 314 patients and well-tolerated in all of those patients. The complete evacuation rate was 94.6% (297/314), which is similar to the rate (98.1%) achieved by conventional surgical evacuation in a previous randomised controlled trial in our unit. There were no major complications. Samples from 95.2% of patients were suitable for karyotyping, which is considerably higher than the rate of suitable samples (82.9%) obtained via conventional surgical evacuation in our previous randomised controlled trial. CONCLUSION: Ultrasound-guided manual vacuum aspiration is a safe and effective method to manage first-trimester miscarriage. Although it currently is not extensively used in Hong Kong, its broader clinical application could avoid general anaesthesia and shorten hospital stay.

Cross-sectional study to assess the psychological morbidity of women facing possible miscarriage.

INTRODUCTION: Threatened miscarriage is a common complication of pregnancy. This study aimed to assess psychological morbidity in women with threatened miscarriage, with the goal of identifying early interventions for women at risk of anxiety or depression. METHODS: Women in their first trimester attending an Early Pregnancy Assessment Clinic were recruited between July 2013 and June 2015. They were asked to complete the 12-item General Health Questionnaire (GHQ-12), the Beck Depression Inventory (BDI), Spielberger's State Anxiety Inventory State form (STAI-S), the Fatigue Scale-14 (FS-14), and the Profile of Mood States (POMS) before consultation. They were also asked to rate anxiety levels before and after consultation using a visual analogue scale (VAS). RESULTS: In total, 1390 women completed the study. The mean ± standard deviation of GHQ-12 (bi-modal) and GHQ-12 (Likert) scores were 4.04 ± 3.17 and 15.19 ± 5.30, respectively. Among these women, 48.4% had a GHQ-12 (bi-modal) score ≥4 and 76.7% had a GHQ-12 (Likert) score >12, indicating distress. The mean ± standard deviation of BDI, STAI-S, and FS-14 scores were 9.35 ± 7.19, 53.81 ± 10.95, and 2.40 ± 0.51, respectively. The VAS score significantly decreased after consultation (P<0.001). Compared with women without a history of miscarriage, women with a previous miscarriage had higher GHQ-12, BDI, and POMS scores (except for fatigue-inertia and vigour-activity subscales). A higher bleeding score was strongly positively correlated with GHQ-12 (Likert) score. There were weak correlations between pain score and the GHQ-12 (bi-modal) ≥4, BDI >12, and POMS scores (except for confusion-bewilderment subscale which showed a strong positive correlation). CONCLUSION: Women with threatened miscarriage experience a considerable psychological burden, emphasising the importance of early recognition for timely management.

Risks and impacts of thromboembolism in patients with pancreatic cancer.

INTRODUCTION: Patients with pancreatic cancer have a high risk of thromboembolism (TE), which may increase mortality. Most relevant studies have been conducted in Western populations. We investigated risk factors for TE in a predominantly Chinese population of patients with pancreatic cancer, along with effects of TE on overall survival. METHODS: This retrospective cohort study included patients diagnosed with exocrine pancreatic cancer in Prince of Wales Hospital in Hong Kong between 2010 and 2015. Data regarding patient demographics, World Health Organization performance status, stage, treatment, TE-related information, and time of death (if applicable) were retrieved from electronic medical records. Univariate and multivariable logistic regression analyses were performed to identify risk factors for TE. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: In total, 365 patients were included in the study. The overall incidence of TE (14.8%) was lower than in Western populations. In univariate logistic regression analysis, stage IV disease and non-head pancreatic cancer were significantly associated with TE (both P=0.01). Multivariable logistic regression analysis showed that stage IV disease was a significant risk factor (odds ratio=1.08, 95% confidence interval [CI]=1.00-1.17; P=0.046). Median overall survival did not significantly differ between patients with and without TE (4.88 months vs 7.80 months, hazard ratio=1.08, 95% CI=0.80-1.49; P=0.58) and between patients with TE who received anticoagulation treatment or not (5.63 months vs 4.77 months, hazard ratio=0.72, 95% CI=0.40-1.29; P=0.27). CONCLUSION: The incidence of TE was low in our Chinese cohort. Stage IV disease increased the risk of TE. Overall survival was not affected by TE or its treatment.

Implementation of ovarian tissue cryopreservation in Hong Kong.

INTRODUCTION: Worldwide, >130 babies have been born from ovarian tissue cryopreservation (OTC) and ovarian tissue transplantation (OTT). Ovarian tissue cryopreservation can improve quality of life among young female cancer survivors. Here, we assessed the feasibility of OTC and subsequent OTT in Hong Kong via xenografts in nude mice. METHODS: This pilot study was conducted in a university-affiliated tertiary hospital. Fifty-two ovarian tissues were collected from 12 patients aged 29 to 41 years during ovarian surgery, then engrafted into 34 nude mice. The efficacies of slow freezing and vitrification were directly compared. In Phase I, non-ovariectomised nude mice underwent ovarian tissue engraftment. In Phase II, ovariectomised nude mice underwent ovarian tissue engraftment, followed by gonadotrophin administration to promote folliculogenesis. Ovarian tissue viability was assessed by gross anatomical, histological, and immunohistochemical examinations before and after OTC. Follicular density and morphological integrity were also assessed. RESULTS: After OTC and OTT, grafted ovarian tissues remained viable in nude mice. Primordial follicles were observed in thawed and grafted ovarian tissues, indicating that the cryopreservation and transplantation protocols were both effective. The results were unaffected by gonadotrophin stimulation. CONCLUSION: This study demonstrated the feasibility of OTC in Hong Kong as well as primordial follicle viability after OTC and OTT in nude mice. Ovarian tissue cryopreservation is ideal for patients who cannot undergo the ovarian stimulation necessary for oocyte or embryo freezing as well as prepubertal girls (all ineligible for oocyte freezing). Our findings support the clinical implementation of OTC and subsequent OTT in Hong Kong.

Results From Finland's 2022 Para Report Card on Physical Activity for Children and Adolescents With Disabilities.

Finland's 2022 Para Report Card on Physical Activity for Children and Adolescents With Disabilities includes a summary of results and grades for 10 physical activity indicators and highlights how these grades are interpreted by stakeholders. The disability classification was based on the UNICEF/Washington Group on Disability Statistics measure, Generalized Anxiety Disorder (GAD7) measure, or education status. Data between 2017 and 2021 were reviewed by 24 physical activity specialists using benchmarks adapted for data on disabilities from the Active Healthy Kids Global Alliance. The grades were assigned as follows: Overall Physical Activity, C+; Organized Sport, C; Active Play, D; Active Transportation, B; Family and Peers, C+; School, B; Community and Environment, C-; Government, A-; sedentary behavior and physical fitness were graded as incomplete. Stakeholder focus-group discussions highlighted the need for multidisciplinary cooperation and increasing competence of specialists working with children to promote a physically active lifestyle for all children.

A mutation panel comprising BRAFV600E, NRASQ61R, and NRASQ61H replicated retrospective histopathological examination findings in differentiating benign goitre from malignant papillary thyroid cancer in a cohort of Malaysian patients.

Thyroid malignancy status is usually confirmed through histopathological examination (HPE) following thyroidectomy. In Malaysia, the application of molecular markers in pre-operative diagnosis of thyroid cancer remains unexplored. In this study, BRAF and NRAS gene mutation panel was assessed, and the results were compared with retrospective HPE findings. Malaysian patients with benign goitre (BTG: n=33) and papillary thyroid cancer (PTC: n=25; PTCa: n=20, PTCb: n=5) were recruited at Universiti Malaya Medical Centre from September 2019 to December 2022. PCR-direct DNA sequencing of BRAFV600, NRASG12, NRASG13, and NRASQ61 was conducted on DNA extracted from the patients' thyroid tissue specimens following thyroidectomy and HPE. BRAFV600E and NRASQ61R mutations showed absolute PTC-specificity with PTC-sensitivity of 32% and 28%, respectively. NRASQ61H demonstrated lower PTC-specificity (94%) but higher PTC-sensitivity (72%) compared to the BRAFV600E and NRASQ61R mutations. Although the NRASG12 and NRASG13 variants were absent in this study, a novel NRASV14D mutation was detected in a PTCa patient. Unlike PTCb, coexistence of BRAFV600E and NRASQ61 variants was commonly observed among the PTCa patients. Notably, all PTCb patients had NRASQ61H mutation with one patient carried both the NRASQ61H and BRAFV600E mutations. Association analysis revealed potential link between gender, BRAFV600E mutation and lymph node metastasis. In conclusion, mutation panel comprising BRAFV600E, NRASQ61R, and NRASQ61H did not discriminate the two PTC subtypes but replicated the retrospective HPE findings in differentiating BTG from PTC. The application of this mutation panel in pre-operative diagnosis of thyroid nodules requires further validation in a larger sample size, preferably incorporating fineneedle aspirate biopsies.

The age-dependent association of risk factors with pancreatic cancer.

BACKGROUND: Pancreatic cancer presents as advanced disease in >80% of patients; yet, appropriate ages to consider prevention and early detection strategies are poorly defined. We investigated age-specific associations and attributable risks of pancreatic cancer for established modifiable and non-modifiable risk factors. PATIENTS AND METHODS: We included 167 483 participants from two prospective US cohort studies with 1190 incident cases of pancreatic cancer during >30 years of follow-up; 5107 pancreatic cancer cases and 8845 control participants of European ancestry from a completed multicenter genome-wide association study (GWAS); and 248 893 pancreatic cancer cases documented in the US Surveillance, Epidemiology, and End Results (SEER) Program. Across different age categories, we investigated cigarette smoking, obesity, diabetes, height, and non-O blood group in the prospective cohorts; weighted polygenic risk score of 22 previously identified single nucleotide polymorphisms in the GWAS; and male sex and black race in the SEER Program. RESULTS: In the prospective cohorts, all five risk factors were more strongly associated with pancreatic cancer risk among younger participants, with associations attenuated among those aged >70 years. The hazard ratios comparing participants with three to five risk factors with those with no risk factors were 9.24 [95% confidence interval (CI) 4.11-20.77] among those aged ≤60 years, 3.00 (95% CI 1.85-4.86) among those aged 61-70 years, and 1.46 (95% CI 1.10-1.94) among those aged >70 years (Pheterogeneity = 3×10-5). These factors together were related to 65.6%, 49.7%, and 17.2% of incident pancreatic cancers in these age groups, respectively. In the GWAS and the SEER Program, the associations with the polygenic risk score, male sex, and black race were all stronger among younger individuals (Pheterogeneity ≤0.01). CONCLUSIONS: Established risk factors are more strongly associated with earlier-onset pancreatic cancer, emphasizing the importance of age at initiation for cancer prevention and control programs targeting this highly lethal malignancy.

Development, implementation and initial feasibility testing of the MediEmo mobile application to provide support during medically assisted reproduction.

STUDY QUESTION: Is it possible to develop a patient smartphone application for medically assisted reproduction (MAR) that is acceptable to patients and fertility staff? SUMMARY ANSWER: Staff and patients responded positively to the MediEmo smartphone application, perceiving it to be acceptable and feasible to implement in a busy clinic. WHAT IS KNOWN ALREADY: Digital tools are increasingly popular to provide practical, administrative and psychological support alongside medical treatments. Apps and other digital tools have been developed for use alongside MAR but there is very limited research on the development or acceptability and feasibility of these tools. STUDY DESIGN, SIZE, DURATION: Mixed methods research. This article outlines the development phase of the MediEmo smartphone app, which was guided by the Medical Research Council development framework for complex interventions. The resulting MediEmo app was then implemented into a single centre for MAR in the UK, acceptability evaluated and feasibility explored among 1106 potential participants undertaking IVF cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS: Consultation and data collection took part at a single mid-sized urban fertility clinic. Development of the MediEmo smartphone application took place during 2013 to 2017. Implementation of the MediEmo took place from June 2017 to September 2020. The MediEmo app comprises three functions (six features) namely medication management (medication timeline, messaging), mood management (emotional tracking, coping support) and functional support (frequently asked questions, symptom checker). Data on age, fertility diagnosis, anti-Müllerian hormone level were collected about the users of the MediEmo in addition to MediEmo usage data and attitudes towards the MediEmo smartphone application. MAIN RESULTS AND THE ROLE OF CHANCE: Informed by the developmental process described, MediEmo is an app combining patient medication diary management and ease of integration into clinic systems with emotional support, emotional tracking and data capture. This study demonstrates acceptability and feasibility of MediEmo, with good uptake (79.8%), mood data sensitivity and reliability and positive feedback. LIMITATIONS, REASONS FOR CAUTION: Single centre, small number of users in questionnaire studies. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest smartphone apps can contribute to fertility care and that patient engagement is high. Evaluation of any apps introduced into clinical pathways should be encouraged to promote development of the most useful digital tools for fertility patients. STUDY FUNDING/COMPETING INTEREST(S): This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. Outside of the submitted work, J.B. reports personal speaker fees from Merck KGaA, Darmstadt, Germany, Merck AB an affiliate of Merck KGaA, Darmstadt Germany, Theramex, MedThink China, Ferring Pharmaceuticals A/S, grant from Merck Serono Ltd, outside the submitted work and that she is co-developer of Fertility Quality of Life (FertiQoL) and MediEmo app; N.M and C.Y are minority shareholders and J.B.'s University (Cardiff University) owns one third of shares. None of the shareholders benefitted financially from MediEmo. I.R., C.H. and K.Y.B.N. declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Multimodality imaging of developmental splenic anomalies: tips and pitfalls.

Anomalies in number and location may occur during splenic development. This review aims to offer a brief overview of splenic function and embryology and a detailed account of the imaging appearances using different imaging techniques of the normal spleen and various congenital splenic anomalies including (1) abnormal viscero-atrial situs, (2) splenogonadal fusion, (3) intrapancreatic accessory spleen, (4) wandering spleen, and (5) splenosis. Emphasis is placed on the salient features that help radiologists recognise important associations (e.g., asplenia/polysplenia in situs abnormalities), avoid diagnostic pitfalls (e.g., mistaking intrapancreatic accessory spleen as pancreatic neoplasms), and potential complications (e.g., acute torsion in wandering spleen). The correct identification of the said anomalies from more sinister causes, such as malignancies, are essential, where early intervention is necessary.

Biomechanics of Cam Femoroacetabular Impingement: A Systematic Review.

PURPOSE: To assess how biomechanical gait parameters (kinematics, kinetics, and muscle force estimations) differ between patients with cam-type femoroacetabular impingement (FAI) and healthy controls, through a systematic search. METHODS: A systematic review of the literature from PubMed, Scopus, and Medline and EMBASE via OVID SP was undertaken from inception to April 2020 using PRISMA guidelines. Studies that described kinematics, kinetics, and/or estimated muscle forces in cam-type FAI were identified and reviewed. RESULTS: The search strategy identified 404 articles for evaluation. Removal of duplicates and screening of titles and abstracts resulted in full-text review of 37 articles, with 12 meeting inclusion criteria. The 12 studies reported biomechanical data on a total of 173 cam-FAI (151 cam-specific, 22 mixed-type) patients and 177 healthy age-, sex-, and body mass index-matched controls. Patients with cam FAI had reduced hip sagittal plane range of motion (mean difference -3.00° [-4.10, -1.90], P < .001), reduced hip peak extension angles (mean difference -2.05° [-3.58, -0.53] , P = .008), reduced abduction angles in the terminal phase of stance, and reduced iliacus and psoas muscle force production in the terminal phase of stance compared to the control groups. Cam FAI cohorts walked at a slower speed compared with controls. CONCLUSIONS: In conclusion, patients with cam-type FAI exhibit altered sagittal and frontal plane kinematics as well as altered muscle force production during level gait compared to controls. These findings will help guide future research into gait alterations in FAI and how such alterations may contribute to pathologic progression and furthermore, how such alterations can be modified for therapeutic benefit. LEVEL OF EVIDENCE: Systematic review of Level III studies.