Miracle-dz/UniFAR-FTUs huggingface dataset:
How do parents frame their engagement experience in early intervention? A grounded theory study.

PURPOSE Parent and therapist engagement and partnership are critical in early intervention physiotherapy and occupational therapy for infants with cerebral palsy to improve outcomes. The main aim of this study was to understand how parents perceive their engagement experience in early intervention over time. METHODS Grounded theory methodology was used. Twenty parents of diverse backgrounds participated in 22 interviews (including some repeated longitudinally) to reflect on their engagement experience within the context of early intervention community services provided in the UK NHS. RESULTS The findings highlight how parents' perspectives of their engagement in EI change according to critical circumstances, including their preceding neonatal trauma, the at-risk CP label, firmer diagnosis of CP and their child's response to intervention. We theorise that this disrupted transition experience to parenthood becomes part of parental framing (or sense-making) of their engagement in EI. Overlapping frames of uncertainty, pursuit and transformation capture and explain nuances in parents' engagement patterns within EI over time. CONCLUSION This theorising has implications for early intervention therapists in how they engage in the lives of families and partner with parents to support healthier parental transition, wellbeing and subsequent improved infant outcomes.
Preoperative Disability Influences Effectiveness of MCID and PASS in Predicting Patient Improvement Following Lumbar Spine Surgery

Study Design: Retrospective cohort. Summary of Background Data: Although minimal clinically important difference (MCID) and patient acceptable symptom state (PASS) are utilized to interpret Oswestry Disability Index (ODI), it is unclear whether there is a clearly better metric between the two and if not, which metric should be utilized when. Objective: To compare the characteristics of MCID and PASS when interpreting ODI after lumbar spine surgery. Methods: Patients who underwent primary minimally invasive transforaminal lumbar interbody fusion or decompression were included. The ODI and global rating change data at 1 year were analyzed. The global rating change was collapsed to a dichotomous outcome variable—(a) improved, (b) not improved The sensitivity, specificity, positive predictive value and negative predictive value of MCID and PASS were calculated for the overall cohort and separately for patients with minimal, moderate, and severe preoperative disability. Two groups with patients who achieved PASS but not MCID and patients who achieved MCID but not PASS were analyzed. Results: Two hundred twenty patients (mean age 62 y, 57% males) were included. PASS (86% vs. 69%) and MCID (88% vs. 63%) had significantly greater sensitivity in patients with moderate and severe preoperative disability, respectively. Nineteen percent of patients achieved PASS but not MCID and 10% of patients achieved MCID but not PASS, with the preoperative ODI being significantly greater in the latter. Most of these patients still reported improvement with no significant difference between the 2 groups (93% vs. 86%). Conclusion: Significant postoperative clinical improvement is most effectively assessed by PASS in patients with minimal or moderate preoperative disability and by MCID in patients with severe preoperative disability. Adequate interpretation of ODI using the PASS and MCID metrics warrants individualized application as their utility is highly dependent on the degree of preoperative disability.
Making meaning of multimorbidity and severe mental illness: A viewpoint

People living with severe mental illness, such as schizophrenia and bipolar affective disorder, frequently experience poorer physical health compared to those without mental illness. This issue has hitherto been approached through the disease-centred construct of comorbidity, where subsequent conditions are viewed as secondary to an ‘index condition’. In contrast, this Viewpoint sets out to explain why multimorbidity, a patient-centred concept that instead refers to the coexistence of multiple chronic illnesses, is a more versatile and robust framework for tackling the issue of poor physical health in people with severe mental illness. In establishing this argument, this Viewpoint has sought to address three key areas. First, this article will discuss the epidemiology of both physical and psychiatric multimorbidity, with respect to how they manifest at greater frequency and at younger ages in people with severe mental illness. Second, the profound consequences of this multimorbidity burden will be explored, with respect to the ‘three D’s’ of death (premature mortality), disability (functional impacts) and deficit (health-economic impacts). Finally, the utility of multimorbidity as a framework will be illustrated through a proposal for a three-dimensional multimorbidity construct composed of (1) quantity, (2) severity and (3) duration of an individual’s chronic illnesses. Consequently, this Viewpoint aims to capture why it is necessary for modern psychiatry to grasp the concept of multimorbidity to facilitate holistic healthcare for people living with severe mental illness.
Performance Fatigability and Neuromuscular Responses Are Not Joint Angle Specific Following a Sustained Isometric Forearm Flexion Task Anchored to a High Perceptual Intensity in Women

Objectives: To examine the effects of joint angle (JA) on maximal voluntary isometric contractions (MVIC) and neuromuscular responses following a sustained, isometric forearm flexion task anchored to a rating of perceived exertion (RPE) of 8 (RPE=8). Methods: Nine women (age: 20.7±2.9 yrs; height: 168.8±7.2 cm; body mass: 66.3±6.8 kg) performed 2,3s forearm flexion MVICs at JAs of 75°, 100°, and 125° prior to and following a sustained, isometric forearm flexion task anchored to RPE=8 to task failure (torque reduced to zero) at JA100. Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from the biceps brachii. Results: The MVIC at JA100 (collapsed across Time) was significantly greater (p<0.05) than JA75 and JA125. The pre-test MVIC was significantly greater (p<0.001) than the post-test. For EMG amplitude (AMP) and EMG mean power frequency (MPF), pre-test values were significantly greater (p<0.05) than the post-test values, with no differences between JAs. For MMG AMP and MMG MPF, there were no significant (p>0.05) differences between Time or JAs. Pre-test neuromuscular efficiency (normalized MVIC/normalized EMG AMP) was significantly greater (p=0.005) than post-test. Conclusion: Following a sustained, isometric forearm flexion task anchored to RPE=8 at JA100, the fatigue-induced MVIC and neuromuscular responses were not affected by JA.
Predicting ICU Mortality in Acute Respiratory Distress Syndrome Patients Using Machine Learning: The Predicting Outcome and STratifiCation of severity in ARDS (POSTCARDS) Study*

OBJECTIVES: To assess the value of machine learning approaches in the development of a multivariable model for early prediction of ICU death in patients with acute respiratory distress syndrome (ARDS). DESIGN: A development, testing, and external validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: A total of 1,303 patients with moderate-to-severe ARDS managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed and tested prediction models in 1,000 ARDS patients. We performed logistic regression analysis following variable selection by a genetic algorithm, random forest and extreme gradient boosting machine learning techniques. Potential predictors included demographics, comorbidities, ventilatory and oxygenation descriptors, and extrapulmonary organ failures. Risk modeling identified some major prognostic factors for ICU mortality, including age, cancer, immunosuppression, Pao2/Fio2, inspiratory plateau pressure, and number of extrapulmonary organ failures. Together, these characteristics contained most of the prognostic information in the first 24 hours to predict ICU mortality. Performance with machine learning methods was similar to logistic regression (area under the receiver operating characteristic curve [AUC], 0.87; 95% CI, 0.82–0.91). External validation in an independent cohort of 303 ARDS patients confirmed that the performance of the model was similar to a logistic regression model (AUC, 0.91; 95% CI, 0.87–0.94). CONCLUSIONS: Both machine learning and traditional methods lead to promising models to predict ICU death in moderate/severe ARDS patients. More research is needed to identify markers for severity beyond clinical determinants, such as demographics, comorbidities, lung mechanics, oxygenation, and extrapulmonary organ failure to guide patient management.
TT U-Net: Temporal Transformer U-Net for Motion Artifact Reduction Using PAD (Pseudo All-Phase Clinical-Dataset) in Cardiac CT

Involuntary motion of the heart remains a challenge for cardiac computed tomography (CT) imaging. Although the electrocardiogram (ECG) gating strategy is widely adopted to perform CT scans at the quasi-quiescent cardiac phase, motion-induced artifacts are still unavoidable for patients with high heart rates or irregular rhythms. Dynamic cardiac CT, which provides functional information of the heart, suffers even more severe motion artifacts. In this paper, we develop a deep learning based framework for motion artifact reduction in dynamic cardiac CT. First, we build a PAD (Pseudo All-phase clinical-Dataset) based on a whole-heart motion model and single-phase cardiac CT images. This dataset provides dynamic CT images with realistic-looking motion artifacts that help to develop data-driven approaches. Second, we formulate the problem of motion artifact reduction as a video deblurring task according to its dynamic nature. A novel TT U-Net (Temporal Transformer U-Net) is proposed to excavate the spatiotemporal features for better motion artifact reduction. The self-attention mechanism along the temporal dimension effectively encodes motion information and thus aids image recovery. Experiments show that the TT U-Net trained on the proposed PAD performs well on clinical CT scans, which substantiates the effectiveness and fine generalization ability of our method. The source code, trained models, and dynamic demo will be available at https://github.com/ivy9092111111/TT-U-Net.
The LytS-type histidine kinase BtsS is a 7-transmembrane receptor that binds pyruvate

ABSTRACT LytS/LytTR-type histidine kinase/response regulator systems regulate crucial host-specific mechanisms during infection of human or plant hosts. Escherichia coli has two of them, and the histidine kinase BtsS is a high-affinity sensor for extracellular pyruvate that together with the response regulator BtsR activates the expression of btsT, which encodes a high-affinity pyruvate transporter. However, the molecular mechanism of how pyruvate binding triggers a response is still unclear. Here, we experimentally show that BtsS consists of seven transmembrane helices, with the N-terminus exposed on the periplasmic side. Using a site-directed mutagenesis-based screening assay, Arg72, Arg99, Cys110, and Ser113, all located on the periplasmic side in three transmembrane helices, were identified as critical for the binding of pyruvate to BtsS, a finding that was further confirmed by molecular dynamics simulation studies. In addition, Mn2+-dependent autophosphorylation of wild-type BtsS was demonstrated for the first time, and individual replacement of the four amino acids affected this process as well as dimerization and consequently btsT expression. This study demonstrates how binding of a metabolite to the membrane-integrated sensor domain triggers signaling in the cytoplasm. IMPORTANCE Here, we studied the LytS-type histidine kinase BtsS of E. coli and identified the pyruvate binding site within the membrane-spanning domains. It is a small cavity, and pyruvate forms interactions with the side chains of Arg72, Arg99, Cys110, and Ser113 located in transmembrane helices III, IV, and V, respectively. Our results can serve as a starting point to convert BtsS into a sensor for structurally similar ligands such as lactate, which can be used as biosensor in medicine. Here, we studied the LytS-type histidine kinase BtsS of E. coli and identified the pyruvate binding site within the membrane-spanning domains. It is a small cavity, and pyruvate forms interactions with the side chains of Arg72, Arg99, Cys110, and Ser113 located in transmembrane helices III, IV, and V, respectively. Our results can serve as a starting point to convert BtsS into a sensor for structurally similar ligands such as lactate, which can be used as biosensor in medicine.
Retinal stroke: research models, targets and experimental drugs

ABSTRACT Introduction Retinal artery occlusion (RAO), often caused by a microembolus and resulting in inner retinal ischemia, could be considered as the retinal analog to cerebral stroke. Although several therapeutic targets have been suggested in animal models of retinal ischemia and several potential treatments have been evaluated on small series of patients, central retinal artery occlusion (CRAO) is still rarely treatable in clinical practice. Areas covered Here, we review several animal models of RAO, including increased intraocular pressure, laser, vasoconstriction, embolization and clamp. We also review the pathogenic mechanisms that contribute to cell death cascades during ischemia, and the therapeutic strategies targeting these events. These strategies aim to restore blood flow by fibrinolysis, increase the oxygen or glucose supply, decrease the energy demands, restrict ionic leak fluxes or reduce the detrimental effects of glutamate, calcium and free radicals. The current literature suggests that tPA treatment could be effective for CRAO. Expert opinion Eye care professionals must make a rapid and accurate diagnosis and immediately refer patients with acute retinal stroke to specialized centers. CRAO management should also be facilitated by developing local networks to encourage collaboration among ophthalmologists, retina specialists and stroke neurologists.
Knowledge Gaps Regarding Indigenous Health in Occupational Therapy: A National Survey

Background. There is a need for the occupational therapy profession to respond to the Truth and Reconciliation Commission of Canada Calls to Action and work towards supporting the health and well-being of Indigenous Peoples. Purpose. (1) To determine the knowledge gaps of occupational therapists about Indigenous health and (2) to create recommendations to address identified gaps and inform responses from the profession. Method. A national needs survey was created and distributed to occupational therapists across Canada to determine the knowledge of occupational therapists about Indigenous health. Survey results were analyzed using thematic analysis and descriptive statistics. Findings. Data collected from 364 survey responses informed six distinct themes representing knowledge gaps of occupational therapists related to Indigenous health as follows: lack of foundational knowledge, power relations, lifelong learner, need for appropriate tools/approaches, respectful collaboration, and environmental influences. Implications. The project offers insight into the role of the occupational therapy profession in the process of reconciliation. Insights are focused on decolonizing occupational therapy practice, building trusting relationships with Indigenous Peoples, and the provision of appropriate training for occupational therapists to engage in culturally safer practices.
Population genetic testing and SERPINA1 sequencing identifies unidentified alpha-1 antitrypsin deficiency alleles and gene-environment interaction with hepatitis C infection

Alpha-1 antitrypsin deficiency (AATD), a relatively common autosomal recessive genetic disorder, is underdiagnosed in symptomatic individuals. We sought to compare the risk of liver transplantation associated with hepatitis C infection with AATD heterozygotes and homozygotes and determine if SERPINA1 sequencing would identify undiagnosed AATD. We performed a retrospective cohort study in a deidentified Electronic Health Record (EHR)-linked DNA biobank with 72,027 individuals genotyped for the M, Z, and S alleles in SERPINA1. We investigated liver transplantation frequency by genotype group and compared with hepatitis C infection. We performed SERPINA1 sequencing in carriers of pathogenic AATD alleles who underwent liver transplantation. Liver transplantation was associated with the Z allele (ZZ: odds ratio [OR] = 1.31, p<2e-16; MZ: OR = 1.02, p = 1.2e-13) and with hepatitis C (OR = 1.20, p<2e-16). For liver transplantation, there was a significant interaction between genotype and hepatitis C (ZZ: interaction OR = 1.23, p = 4.7e-4; MZ: interaction OR = 1.11, p = 6.9e-13). Sequencing uncovered a second, rare, pathogenic SERPINA1 variant in six of 133 individuals with liver transplants and without hepatitis C. Liver transplantation was more common in individuals with AATD risk alleles (including heterozygotes), and AATD and hepatitis C demonstrated evidence of a gene-environment interaction in relation to liver transplantation. The current AATD screening strategy may miss diagnoses whereas SERPINA1 sequencing may increase diagnostic yield for AATD, stratify risk for liver disease, and inform clinical management for individuals with AATD risk alleles and liver disease risk factors.
Lesion Dosimetry for [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy Combined with Stereotactic Body Radiotherapy in Patients with Oligometastatic Castration-Sensitive Prostate Cancer

Visual Abstract A single-institution prospective pilot clinical trial was performed to demonstrate the feasibility of combining [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) with stereotactic body radiotherapy (SBRT) for the treatment of oligometastatic castration-sensitive prostate cancer. Methods: Six patients with 9 prostate-specific membrane antigen (PSMA)–positive oligometastases received 2 cycles of [177Lu]Lu-PSMA-617 RPT followed by SBRT. After the first intravenous infusion of [177Lu]Lu-PSMA-617 (7.46 ± 0.15 GBq), patients underwent SPECT/CT at 3.2 ± 0.5, 23.9 ± 0.4, and 87.4 ± 12.0 h. Voxel-based dosimetry was performed with calibration factors (11.7 counts per second/MBq) and recovery coefficients derived from in-house phantom experiments. Lesions were segmented on baseline PSMA PET/CT (50% SUVmax). After a second cycle of [177Lu]Lu-PSMA-617 (44 ± 3 d; 7.50 ± 0.10 GBq) and an interim PSMA PET/CT scan, SBRT (27 Gy in 3 fractions) was delivered to all PSMA-avid oligometastatic sites, followed by post-PSMA PET/CT. RPT and SBRT voxelwise dose maps were scaled (α/β = 3 Gy; repair half-time, 1.5 h) to calculate the biologically effective dose (BED). Results: All patients completed the combination therapy without complications. No grade 3+ toxicities were noted. The median of the lesion SUVmax as measured on PSMA PET was 16.8 (interquartile range [IQR], 11.6) (baseline), 6.2 (IQR, 2.7) (interim), and 2.9 (IQR, 1.4) (post). PET-derived lesion volumes were 0.4–1.7 cm3. The median lesion-absorbed dose (AD) from the first cycle of [177Lu]Lu-PSMA-617 RPT (ADRPT) was 27.7 Gy (range, 8.3–58.2 Gy; corresponding to 3.7 Gy/GBq, range, 1.1–7.7 Gy/GBq), whereas the median lesion AD from SBRT was 28.1 Gy (range, 26.7–28.8 Gy). Spearman rank correlation, ρ, was 0.90 between the baseline lesion PET SUVmax and SPECT SUVmax (P = 0.005), 0.74 (P = 0.046) between the baseline PET SUVmax and the lesion ADRPT, and −0.81 (P = 0.022) between the lesion ADRPT and the percent change in PET SUVmax (baseline to interim). The median for the lesion BED from RPT and SBRT was 159 Gy (range, 124–219 Gy). ρ between the BED from RPT and SBRT and the percent change in PET SUVmax (baseline to post) was −0.88 (P = 0.007). Two cycles of [177Lu]Lu-PSMA-617 RPT contributed approximately 40% to the maximum BED from RPT and SBRT. Conclusion: Lesional dosimetry in patients with oligometastatic castration-sensitive prostate cancer undergoing [177Lu]Lu-PSMA-617 RPT followed by SBRT is feasible. Combined RPT and SBRT may provide an efficient method to maximize the delivery of meaningful doses to oligometastatic disease while addressing potential microscopic disease reservoirs and limiting the dose exposure to normal tissues.
Split or whole liver transplantation? Utilization and posttransplant survival

Background: Split liver transplantation (SLT), where a single donor liver is divided for transplantation to 2 recipients, has the potential to increase the availability of size-matched livers for pediatric candidates and expand the supply of donor organs available for adult candidates. Although SLT is a well-established technique, the number of SLTs has remained flat during the past 2 decades, partly due to concerns about the posttransplant survival of SLT recipients compared with whole liver transplantation (WLT) recipients. Prior work on SLT versus WLT survival analysis had limitations because, for pediatric recipients, it did not consider the correlations between donor age/weight and the allograft type, and for adult recipients, it may have included records where the donor livers did not meet the split liver criteria (splittable). Methods: Using the Organ Procurement and Transplantation Network’s database (2003–2019), this study analyzes and compares (i) key characteristics of donors and recipients, (ii) donor-recipient match dynamics (organ offers and accept/decline decisions), and (iii) recipient posttransplant survival, for SLT and WLT. Results and Conclusions: The results in this study show that the posttransplant survival of SLT and WLT recipients is similar (controlling for other confounding factors that may impact posttransplant survival), highlighting the importance of SLT for increasing the liver supply and potential benefits for both pediatric and adult candidates.
Estimating the Magnitude of Peak Flows for Steep Gradient Streams in New England

Estimates of flood events are used by the Federal, State, regional, and local officials to safely and economically design hydraulic structures as well as for effective floodplain management. The regression relationships developed to predict flows at ungauged sites do not always hold true for steep slope watersheds in New England. This study developed the regression relationships to predict peak flows for ungaged, unregulated steep streams in New England with recurrence intervals of 2, 5, 10, 25, 50, 100, and 500 years. For watersheds having a main channel slope that exceeds 50 ft per mile, peak flows are well estimated by the watershed drainage area and the mean annual precipitation. No metric of watershed steepness provided a statistically significantly improvement to prediction capability. For these steep watersheds, the series of regression equations was found to perform as well or better than the individual state regression equations.