Miracle-dz/UniFAR-FTUs huggingface dataset:
Weight gain and integrase inhibitors.

PURPOSE OF REVIEW Weight gain and obesity among people living with HIV (PLWH) is a serious problem that occurs often after initiation of antiretroviral therapy but may be worse with integrase strand transfer inhibitors (INSTIs). This article comprehensively reviews available data and summarizes our current understanding of the topic. RECENT FINDINGS Recent studies support the concept that weight gain and treatment emergent obesity are worse with INSTI-based regimens, particularly dolutegravir. Women and nonwhites appear to be the most at risk, and the accompanying nucleoside reverse transcriptase inhibitor may play a role. Lipohypertrophy, an abnormal accumulation of visceral fat and/or ectopic fat depots, continues to be a problem among PLWH, but the role of INSTIs is inconsistent. The pathogenesis of weight gain and changes in body composition in HIV, especially with INSTIs, is poorly understood but may lead to serious comorbidities, such as cardiovascular disease and diabetes. SUMMARY Although INSTI-based regimens are highly efficacious for viral suppression, they appear to cause more weight gain and treatment emergent obesity than non-INSTI-based regimens and may increase the risk of weight-related comorbidities. More studies are needed to understand the pathogenesis of weight gain with INSTIs in PLWH, in order to prevent this serious complication.
The use of missing values in proteomic data-independent acquisition mass spectrometry to enable disease activity discrimination

Abstract Motivation Data-independent acquisition mass spectrometry allows for comprehensive peptide detection and relative quantification than standard data-dependent approaches. While less prone to missing values, these still exist. Current approaches for handling the so-called missingness have challenges. We hypothesized that non-random missingness is a useful biological measure and demonstrate the importance of analysing missingness for proteomic discovery within a longitudinal study of disease activity. Results The magnitude of missingness did not correlate with mean peptide concentration. The magnitude of missingness for each protein strongly correlated between collection time points (baseline, 3 months, 6 months; R = 0.95–0.97, confidence interval = 0.94–0.97) indicating little time-dependent effect. This allowed for the identification of proteins with outlier levels of missingness that differentiate between the patient groups characterized by different patterns of disease activity. The association of these proteins with disease activity was confirmed by machine learning techniques. Our novel approach complements analyses on complete observations and other missing value strategies in biomarker prediction of disease activity. Supplementary information Supplementary data are available at Bioinformatics online.
Growing up with a rare genetic disease: an interpretative phenomenological analysis of living with Holt-Oram syndrome

Abstract Background Holt-Oram syndrome (HOS) is a rare genetic disease characterized by variable radial upper limb and cardiac defects. The aim of this research was to shed light on people’s subjective perceptions of their diseases, how these perceptions provide meaning, and the consequences the syndrome can have in daily life and across all life stages. Methods Semistructured interviews with ten participants diagnosed with HOS were conducted in France and analyzed using interpretative phenomenological analysis. Results Participants’ experiences fall under two main themes, namely, “stages of self-construction as different” and “when I am no longer the only one involved”, each of which has three subthemes. From childhood onwards, symptoms monopolize the physical and psychological spheres. The feeling of being different is unavoidable until the patient can appropriate his or her condition, and by the end of adolescence, the patient generally feels that he or she has adapted to the syndrome. In adulthood, other concerns arise, such as the fear of rejection, the need to better understand the genetic issues of the condition and the desire for offspring to not experience the same life difficulties. Conclusion The findings underscore the specific psychological issues associated with the syndrome at different life stages and the need for holistic genetic treatment with dedicated reference centers to improve care and further address these issues. IMPLICATIONS FOR REHABILITATION Holt-Oram syndrome is a genetic disease characterized by abnormalities of the upper limbs and shoulder girdle and associated with a congenital heart defect. Specific issues arise at different stages of life: the physical consequences of the syndrome arise during childhood, the self-construction of pervasive difference during adolescence, the fear of being rejected as a young adult, and concerns about future parenthood and the transmission of the syndrome and the desire that one’s child not be confronted with the same difficulties in adulthood. The complexity and entanglement of medical and existential issues related to HOS requires the development of multidisciplinary consultations that promote holistic care. The rarity of the syndrome and the lack of knowledge about HOS among health professionals and the general public make it necessary both to establish reference centers and to create patient associations to support patients.
N-glycosylation of Rim21 at an Unconventional Site Fine-tunes Its Behavior in the Plasma Membrane

The polytopic plasma membrane protein Rim21 senses both the elevation of ambient pH and alterations in plasma membrane lipid asymmetry in the Rim101 pathway in budding yeast. Rim21 is known to undergo N-glycosylation, but the site and function of the glycosylation modification is not known. Using a systematic mutation analysis, we found that Rim21 is N-glycosylated at an unconventional motif located in the N-terminal extracellular region. The Rim21 mutant protein that failed to receive N-glycosylation showed prolonged protein lifetime compared to that of WT Rim21 protein. Although both the WT and mutant Rim21 localized to the plasma membrane, they exhibited different biochemical fractionation profiles. The mutant Rim21, but not WT Rim21, was mainly fractionated into the heavy membrane fraction. Further, compared to WT Rim21, mutant Rim21 was more easily solubilized with digitonin but was conversely more resistant to solubilization with Triton X-100. Despite these different biochemical properties from WT Rim21, mutant Rim21 protein could still activate the Rim101 pathway in response to external alkalization. Collectively, N-glycosylation of Rim21 is not indispensable for its activity as a sensor protein, but modulates the residence of Rim21 protein to some microdomains within the plasma membrane with distinct lipid conditions, thereby affecting its turnover.
Bone Tissue Engineering in the Growing Calvarium Using Dipyridamole-Coated 3D Printed Bioceramic Scaffolds: Construct Optimization and Effects to Cranial Suture Patency.

BACKGROUND/PURPOSE 3D-printed bioceramic (3DBC) scaffolds composed of beta-tricalcium phosphate (β-TCP) delivering the osteogenic agent dipyridamole (DIPY) can heal critically-sized calvarial defects in skeletally mature translational models. However, this construct has yet to be applied to growing craniofacial models. In this study, we implanted 3DBC/DIPY scaffolds in a growing calvaria animal model and evaluated bone growth as a function of geometric scaffold design and DIPY concentration. Potential adverse effects on the growing suture were also evaluated. METHOD/DESCRIPTION Bilateral calvarial defects (10 mm) were created in 5-week-old (~1.1 kg) New Zealand White rabbits (n = 16 analyzed). 3DBC scaffolds were constructed in quadrant form composed of varying pore dimensions (220μm, 330μm, 500μm). Each scaffold was collagen coated and soaked in varying concentrations of DIPY (100μM, 1000μM, 10,000μM). Controls comprised empty defects. Animals were euthanized 8-weeks post-operatively. Calvaria were analyzed using micro-computed tomography (microCT), 3D reconstruction, and non-decalcified histologic sectioning. RESULTS Scaffold-induced bone growth was statistically greater than bone growth in empty defects (p=0.02). Large scaffold pores, 500μm, coated in 1,000μM DIPY yielded the most bone growth and lowest degree of scaffold presence within defect. Histology showed vascularized woven and lamellar bone along with initial formation of vascular canals within the scaffold lattice. MicroCT and histologic analysis revealed patent calvarial sutures without evidence of ectopic bone formation across all DIPY concentrations. CONCLUSION We present an effective pediatric bone tissue engineering scaffold design and dipyridamole concentration which is effective in augmentation of calvarial bone generation while preserving cranial suture patency.
Association between Red Blood Cell Distribution Width and Hemorrhagic Transformation in Acute Ischemic Stroke Patients

Background: Hemorrhagic transformation (HT) is a frequent complication of acute ischemic stroke (AIS). Red blood cell distribution width (RDW) is a cost-effective parameter associated with incidence and prognosis of cerebrovascular diseases. The purpose of this study was to assess whether RDW is associated with HT in AIS patients. Methods: AIS patients within 24 h from stroke onset between January 1, 2014, and December 31, 2018, were consecutively enrolled. Blood samples were collected. The primary outcome was HT, which was diagnosed by follow-up brain image and classified into hemorrhagic infarct (HI) and parenchymal hematoma (PH). Multivariate logistic regression analysis was performed to determine the relationship between RDW and HT as well as its subtypes. Potential effect modifier was identified by stratified logistic regression analysis. Results: Among the included 1383 patients, 220 (15.9%) developed HT (HI in 103 and PH in 117). Elevated RDW levels were associated with an increased risk of HT when 2 extreme tertiles were compared (OR 1.60, 95% CI 1.04–2.44, p = 0.031). The risk of HT increased stepwise across RDW tertiles (p for trend = 0.042). RDW significantly correlated with HI rather than PH. The association between RDW and HT could be modified by reperfusion therapy (p for interaction = 0.010), with no significant association between RDW and HT among patients underwent reperfusion therapy. Conclusions: Elevated RDW level was related to increased risk of HT among AIS patients without reperfusion therapy.
Automatic Anterior Chamber Angle Measurement for Ultrasound Biomicroscopy Using Deep Learning

Supplemental Digital Content is available in the text. Purpose: To develop a software package for automated measuring of the trabecular-iris angle (TIA) using ultrasound biomicroscopy. Methods: Ultrasound biomicroscopy images were collected and the TIA was manually measured by specialists. Different models were used as the convolutional neural network for the automatic TIA measurement. The root-mean-squared error, explained variance, and mean absolute percentage error were used to evaluate the performance of these models. The interobserver reproducibility, coefficient of variation, and intraclass correlation coefficient were calculated to evaluate the consistency between the manual measured and the model predicted values. Results: ResNet-18 had the best performance in root-mean-squared error, explained variance, and mean absolute percentage error among all 5 models. The average difference between the angles measured manually and by the model is −0.46±3.97 degrees for all eyes, −1.67±5.19 degrees for open angles, and 0.75±1.43 degrees for narrow angles. The coefficient of variation, intraclass correlation coefficient, and reproducibility of the total TIA measurements are 6.8%, 0.95, and 6.1 degrees for all angles; 6.4%, 0.99, and 7.7 degrees for open angles; and 8.8%, 0.93, and 4 degrees for narrow angles, respectively. Conclusions: Preliminary results show that this fully automated anterior chamber angle measurement method can achieve high accuracy and have good consistency with the manual measurement results, this has great significance for future clinical practice.
Acute Care, Prescription Opioid Use, and Overdose Following Discontinuation of Long-Term Buprenorphine Treatment for Opioid Use Disorder.

OBJECTIVE Although buprenorphine treatment reduces risk of overdose and death in opioid use disorder, most patients discontinue treatment within a few weeks or months. Adverse health outcomes following buprenorphine discontinuation were compared among patients who were successfully retained beyond 6 months of continuous treatment, a minimum treatment duration recently endorsed by the National Quality Forum. METHODS A retrospective longitudinal cohort analysis was performed using the MarketScan multistate Medicaid claims database (2013-2017), covering 12 million beneficiaries annually. The sample included adults (18-64 years of age) who received buprenorphine continuously for ≥180 days by cohorts retained for 6-9 months, 9-12 months, 12-15 months, and 15-18 months. For outcome assessment in the postdiscontinuation period, patients had to be continuously enrolled in Medicaid for 6 months after buprenorphine discontinuation. Primary adverse outcomes included all-cause emergency department visits, all-cause inpatient hospitalizations, opioid prescriptions, and drug overdose (opioid or non-opioid). RESULTS Adverse events were common across all cohorts, and almost half of patients (42.1%-49.9%) were seen in the emergency department at least once. Compared with patients retained on buprenorphine for 6-9 months (N=4,126), those retained for 15-18 months (N=931) had significantly lower odds of emergency department visits (odds ratio=0.75, 95% CI=0.65-0.86), inpatient hospitalizations (odds ratio=0.79, 95% CI=0.64-0.99), and filling opioid prescriptions (odds ratio=0.67, 95% CI=0.56-0.80) in the 6 months following discontinuation. Approximately 5% of patients across all cohorts experienced one or more medically treated overdoses. CONCLUSIONS Risk of acute care service use and overdose were high following buprenorphine discontinuation irrespective of treatment duration. Superior outcomes became significant with treatment duration beyond 15 months, although rates of the primary adverse outcomes remained high.
Successful rescue treatment of sepsis due to a pandrug-resistant, NDM-producing Klebsiella pneumoniae using aztreonam powder for nebulizer solution as intravenous therapy in combination with ceftazidime/avibactam

70% would seem appropriate. This is longer than the Gramnegative fT.MIC targets for cephalosporins of 30%–40% 7 and for carbapenems of 20%–35% and more similar to that for penicillins of 30%–60%. All the above data show the robustness of dilutional in vitro models in defining pharmacodynamic target sizes and their close alignment with animal models. Previous concerns about washout have also been shown to be baseless and indeed dilutional models may be superior to hollow-fibre systems in terms of cost-effectiveness, biofilm formation and modelled drug concentrations.
Associations among parental and romantic attachment, personality disorder symptoms, and physical health

The relations of parental and romantic attachment with physical health symptoms and the mediating role of personality disorder symptoms in those relations were examined in an online survey of US young adults. Latent class analysis identified two groups: occasionally sick and healthier. Insecure attachment was related to being occasionally sick and to personality disorder symptoms (poor reality testing, primitive defenses, and diffused identity). Primitive defenses/identity diffusion mediated relations between insecure parental attachment and physical symptoms. Maternal and paternal attachment each provided unique information about these relations. Romantic attachment was not associated with physical symptoms after adjusting for parental attachment and personality disorder symptoms.
Postoperative Care Pathways Following Lumbar Total Disc Replacement: Results of a Modified Delphi Approach.

STUDY DESIGN A modified Delphi method was used to establish consensus. Subject matter experts were invited to participate as the expert panel. Best practice statements were distributed to the panel. Panel members were asked to mark "agree" or "disagree" after a series of statements during several rounds until either consensus could be obtained or the practice method was deemed unable to achieve consensus. OBJECTIVE Lumbar total disc replacement (TDR) is acknowledged as an alternative to spinal fusion in appropriately selected patients. There is a lack of unanimity on the appropriate postoperative patient protocols and rehabilitation expectations for the procedure. The long-term viability of Lumbar TDR, further adoption in the community setting and specific patient outcomes are contingent on the existence of appropriate postoperative recovery programs. SUMMARY OF BACKGROUND DATA Currently there are no established methods for postoperative care following lumbar TDR. Establishing a postoperative clinical pathway algorithm may improve patient outcomes with respect to lumbar TDR. METHOD A lumbar TDR expert panel of 22 spine surgeons employed a modified Delphi method to drive consensus on postoperative care following single-level Lumbar TDR. The panel first reviewed literature and guidelines relevant to postoperative care following lumbar TDR. Panel members considered 21 survey questions intended to determine "standard-practice" postoperative care recommendations for patients who have undergone lumbar TDR for the initial recovery phase (0-4 wk) and rehabilitation (4-20 wk). Each panel member participated in a round of anonymous voting followed by a group discussion. Consensus was defined as 80% agreement or higher among the respondents. RESULTS Consensus was achieved in 11 of the 21 survey questions. There was a high degree of consensus around the key goals for both the initial recovery and rehabilitation phases, ceased use of narcotics for pain management by 4 weeks postoperative, unrestricted walking immediately following surgery, timelines for physical therapy (within 2-4 wk) and return to work based on level of activity (as early as 1 wk postoperative). Lack of agreement included the use of back bracing and timing of postoperative visits. Generally, panel members felt that patient expectations regarding return to function were different following lumbar TDR versus fusion and warrant further study. CONCLUSION Surgeon and patient alignment around postoperative expectations may significantly affect the long-term results of lumbar TDR. This surgeon consensus study found agreement for immediate postoperative ambulation, rapid reduction in opioids within the first month, and early return to work. When expectations are appropriately set with patients preoperatively, both provider and patient have shared goals in the return-to-function process. LEVEL OF EVIDENCE 5.
The Position of the Child in the Life Experiences of Immigrant Survivors of Intimate Partner Violence: A Study of Service Providers’ Perspectives in Spain

Intimate partner violence (IPV) is a global public health concern that has serious effects on the well-being of women and their children. Being a mother and an immigrant are critical factors that prevent women from seeking to end an abusive relationship. Evidence suggests that immigrant women see their children’s well-being and future as paramount while managing an abusive relationship. However, less is known about how women negotiate their children’s needs and interests when deciding whether to stay with or leave an abusive partner. Drawing on interviews with IPV service providers in Spain, this study aims to explore providers’ understandings of the position of the child in mothers’ reflections regarding whether to end an abusive relationship and of the implications of such positioning for mothers’ decision-making. The findings indicate that children hold two main positions in this process. In one, children are positioned as a trigger for mothers to stay with abusers. This occurs when women are economically dependent on their partner, when they think that their children need a father figure, or when the abuser plays a role in women’s migratory status within Spain. Second, children are positioned as a trigger for mothers to leave abusers when mothers see children as victims of violence or children in need of a mother figure. Framed by positioning theory, we discuss how we can understand the consequences of such positioning for immigrant women who are survivors of IPV and for service provision in this context. The implications of the findings for research, policy making, and professional decision-making are discussed.
Seeding of a Tumor in the Gastric Wall after Endoscopic Ultrasound-guided Fine-needle Aspiration of Solid Pseudopapillary Neoplasm of the Pancreas

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is widely used as a first-line procedure for the definitive diagnosis of pancreatic solid tumor. Adverse events associated with the EUS-FNA procedure include acute pancreatitis, bleeding, infection, and duodenal perforation. Rarely, pancreatic tumors disseminate in the peritoneal cavity or seed in the gastric wall via the biopsy needle tract after EUS-FNA. Such seeding has been noted primarily in cases of adenocarcinomas and has not been associated with solid pseudopapillary neoplasm (SPN), a rare and potentially malignant tumor of the pancreas. This is the first report of a case of tumor seeding in the gastric wall after EUS-FNA of pancreatic SPN.
Latino adolescents' daily bicultural stress and sleep: Gender and school context moderation.

OBJECTIVE Bicultural stress (i.e., challenge arising from navigating 2 cultural contexts) has significant consequences for Latino youth's health, but researchers have yet to examine the implications of bicultural stress for adolescents' sleep. The goals of this study were to examine whether individual and day-to-day (within-person) differences in bicultural stress were associated with Latino adolescents' sleep onset latency (i.e., time to fall asleep), sleep midpoint (i.e., sleep schedule), sleep duration (i.e., time asleep), and subjective sleep quality. METHOD Participants were 209 Latino late adolescents (Mage = 18.10 years; 64.4% female) attending over 90 different high schools who completed 7 daily diary surveys while wearing actigraph wristwatches (N = 1,320 daily observations). Participants also reported sleep problems in a standard survey. Statistical interactions were tested to assess moderation by gender and coethnic school composition. RESULTS On average, more bicultural stressors across the week were associated with lower average sleep duration and more sleep problems for male (compared to female) adolescents and youth attending schools with higher (compared to lower) Latino student enrollment. Regarding day-to-day differences, more daily bicultural stressors than usual predicted longer sleep onset latency that night for male adolescents, earlier sleep midpoint that night, and less sleep duration that night for youth attending higher Latino-enrollment schools. CONCLUSIONS Latino adolescents' everyday experiences of bicultural stress relate to differences in sleep duration, timing, and quality, with important variation by gender and school context. Results advance existing theory regarding social position factors that differentiate the health implications of bicultural stress for Latino youth. (PsycINFO Database Record (c) 2019 APA, all rights reserved).