Miracle-dz/UniFAR-FTUs huggingface dataset:
Multimorbidity patterns and their relationship to mortality in the US older adult population

Background Understanding patterns of multimorbidity in the US older adult population and their relationship with mortality is important for reducing healthcare utilization and improving health. Previous investigations measured multimorbidity as counts of conditions rather than specific combination of conditions. Methods This cross-sectional study with longitudinal mortality follow-up employed latent class analysis (LCA) to develop clinically meaningful subgroups of participants aged 50 and older with different combinations of 13 chronic conditions from the National Health Interview Survey 2002–2014. Mortality linkage with National Death Index was performed through December 2015 for 166,126 participants. Survival analyses were conducted to assess the relationships between LCA classes and all-cause mortality and cause specific mortalities. Results LCA identified five multimorbidity groups with primary characteristics: “healthy” (51.5%), “age-associated chronic conditions” (33.6%), “respiratory conditions” (7.3%), “cognitively impaired” (4.3%) and “complex cardiometabolic” (3.2%). Covariate-adjusted survival analysis indicated “complex cardiometabolic” class had the highest mortality with a Hazard Ratio (HR) of 5.30, 99.5% CI [4.52, 6.22]; followed by “cognitively impaired” class (3.34 [2.93, 3.81]); “respiratory condition” class (2.14 [1.87, 2.46]); and “age-associated chronic conditions” class (1.81 [1.66, 1.98]). Patterns of multimorbidity classes were strongly associated with the primary underlying cause of death. The “cognitively impaired” class reported similar number of conditions compared to the “respiratory condition” class but had significantly higher mortality (3.8 vs 3.7 conditions, HR = 1.56 [1.32, 1.85]). Conclusion We demonstrated that LCA method is effective in classifying clinically meaningful multimorbidity subgroup. Specific combinations of conditions including cognitive impairment and depressive symptoms have a substantial detrimental impact on the mortality of older adults. The numbers of chronic conditions experienced by older adults is not always proportional to mortality risk. Our findings provide valuable information for identifying high risk older adults with multimorbidity to facilitate early intervention to treat chronic conditions and reduce mortality.
Structural Basis for the Shared Neutralization Mechanism of Three Classes of Human Papillomavirus Type 58 Antibodies with Disparate Modes of Binding

Cervical cancer primarily results from persistent infection with high-risk types of human papillomavirus (HPV). HPV type 58 (HPV58) is an important causative agent, especially in Asia. ABSTRACT Human papillomavirus type 58 (HPV58) is associated with cervical cancer and poses a significant health burden worldwide. Although the commercial 9-valent HPV vaccine covers HPV58, the structural and molecular-level neutralization sites of the HPV58 complete virion are not fully understood. Here, we report the high-resolution (∼3.5-Å) structure of the complete HPV58 pseudovirus (PsV58), determined by using cryo-electron microscopy (cryo-EM). Three representative neutralizing monoclonal antibodies (nAbs 5G9, 2H3, and A4B4) were selected through clustering from a panel of nAbs against HPV58. Bypassing the steric hindrance and symmetry mismatch in the HPV Fab-capsid immune complex, we present three different neutralizing epitopes in the PsV58 and show that, despite differences in binding, these nAbs share a neutralization mechanism. These results offer insight into HPV58 genotype specificity and broaden our understanding of HPV58 neutralization sites for antiviral research. IMPORTANCE Cervical cancer primarily results from persistent infection with high-risk types of human papillomavirus (HPV). HPV type 58 (HPV58) is an important causative agent, especially in Asia. Despite this, we still have limited data pertaining to the structural and neutralizing epitopes of HPV58, and this encumbers our in-depth understanding of the virus’ mode of infection. Here, we show that representative nAbs (5G9, 10B11, 2H3, 5H2, and A4B4) from three different groups share a neutralization mechanism that appears to prohibit the virus from associating with the extracellular matrix and cell surface. Furthermore, we determined that the nAbs engage via three different binding patterns: top-center binding (5G9 and 10B11), top-fringe binding (2H3 and 5H2), and fringe binding (A4B4). Our work shows that, despite differences in the pattern in binding, nAbs against HPV58 share a neutralization mechanism. These results provide new insight into HPV58 infection.
Newtonian Predictions Are Integrated With Sensory Information in 3D Motion Perception

Because the motions of everyday objects obey Newtonian mechanics, perhaps these laws or approximations thereof are internalized by the brain to facilitate motion perception. Shepard’s seminal investigations of this hypothesis demonstrated that the visual system fills in missing information in a manner consistent with kinematic constraints. Here, we show that perception relies on internalized regularities not only when filling in missing information but also when available motion information is inconsistent with the expected outcome of a physical event. When healthy adult participants (Ns = 11, 11, 12, respectively, in Experiments 1, 2, and 3) viewed 3D billiard-ball collisions demonstrating varying degrees of consistency with Newtonian mechanics, their perceptual judgments of postcollision trajectories were biased toward the Newtonian outcome. These results were consistent with a maximum-likelihood model of sensory integration in which perceived target motion following a collision is a reliability-weighted average of a sensory estimate and an internal prediction consistent with Newtonian mechanics.
Amelioration du transfert convectif de chaleur par l'écoulement pulse dans un fluide visqueux

Les effets de perturbations pulsatoires sur le transfert convectif de chaleur dans un fluide visqueux coule en regime laminaire ont ete etudies dans un ehangeur de chaleur a tubes cylindriques coaxiaux, la plage de temperature experimentale etant de 30°C a 45°C. Le fluide etudie dont la viscosite est douze fois superieure a celle de l'eau a la tempe5rature ambiante est une solution aqueuse de glycerol a 60% par poids, le nombre de Reynolds des ecoulements permanents varie de 150 a 1000. La presence des pulsations augmente de facon significative le transfert thermique, et ce a puissance mecanique dissipee identique. Nous avons en effet obtenu des ameliorations du coefficient de transfert de plus de 300% grâe h fortes perturbations pulsatoires. Ainsi, des pulsations imposees a l'ecoulement permanent representent un moyen simple et efficace pour ameliorer les echanges thermiques dans des fluides visqueux habituellement pompes en regime laminaire. Une correlation etablie a partir de nos donnees experimentales en ecoulement pulse permet d'evaluer le nombre de Nusselt avec une erreur moyenne de 10%. Pulsed perturbation effects on convective heat transfer in the laminar flow of a viscous fluid were studied in a co-axial cylindrical tube heat exchanger over the experimental temperature range 30 to 45°C. The fluid studied here, whose viscosity is twelve times larger than water at room temperature, is an aqueous solution of glycerol (60 wt %), and the Reynolds numbers of the steady flow are between 150 and 1000. The pulses significantly increase the thermal transfer at constant dissipated mechanical power. Indeed, enhancement of the heat transfer coefficient by more than 300% was obtained with strong pulsed perturbations. Therefore, pulses superimposed to a steady flow are a simple and efficient manner to improve thermal exchanges in viscous fluids that are usually pumped in the laminar regime. A correlation based on our experimental data on pulsatile flow is used to evaluate the Nusselt number with an average error of 10%.
Drivability Enhancement for AlGaN/GaN High-Electron Mobility Transistors with AlN Spacer Layer Using Si Ion Implantation Doping

Although a thin AlN spacer layer between the AlGaN barrier and GaN channel layers effectively increases electron mobility and sheet carrier concentration in a two-dimensional electron gas, the very wide bandgap AlN makes ohmic contacts difficult to form. We overcame this problem using Si ion implantation to attain contact resistance below 2.5×10-6 Ω cm2. Samples without ion implantation had poor ohmic properties. Inserting the thin AlN spacer layer dramatically improved the drain current of high-electron mobility transistors.
Predictive value of red blood cell distribution width in critically ill patients with atrial fibrillation: a retrospective cohort study.

BACKGROUND Atrial fibrillation (AF) is a leading cause of morbidity and mortality among elderly patients especially for patients in ICU. Previous studies revealed the impact of red blood cell distribution width (RDW) on predicting onset of AF. However, the prognostic value of RDW in critically ill patients with AF remains largely unknown. Thus, this study aims to explore the potential value on predicting in- and out-of-hospital mortality in critically ill patients with AF. METHODS Data were extracted from the Medical Information Mart for Intensive Care (MIMIC) III database and 7,867 critically ill patients with AF were enrolled. The association between RDW and inhospital mortality was evaluated using the multiple logistic regression analysis as a design variable. Shortand long-term outcomes were compared between the low RDW and high RDW groups in critically ill patients balanced by the propensity score matching (PSM) algorithm. RESULTS Analysis of the 7,867 patients revealed a linear relationship between RDW and in-hospital mortality. For critically ill patients with AF, the elevated level of RDW was associated with increased inhospital mortality, with the OR increasing from level 2 (OR: 1.75, 95% CI: 1.25 to 2.44) to level 5 (OR: 3.89, 95% CI: 2.55 to 5.93) with level 1 (RDW ≤13) as the reference group. 3841 enrolled patients with records in the CareVue systems were selected by PSM algorithm. The baseline characters were well balanced in 1,054 pairs of enrolled patients. A significant lower survival rate was observed in the high RDW group (P<0.001). CONCLUSIONS High levels of RDW are associated with increased in- and out-of-hospital mortality in critically ill patients with AF.
[Impact of Aperture Shape Controller on Knowledge-based VMAT Planning of Prostate Cancer].

PURPOSE Knowledge-based planning (KBP) has disadvantages of high monitor unit (MU) and complex multi-leaf collimator (MLC) motion. We investigated the optimal aperture shape controller (ASC) level for the KBP to reduce these factors in volumetric modulated arc therapy (VMAT) for prostate cancer. METHODS The KBP model was created based on 51 clinical plans (CPs) of patients who underwent the VMAT for prostate cancer. Another 10 CPs were selected randomly, and the KBPs with/without ASC, changed stepwise from very low (KBP-VL) to very high (KBP-VH), were performed with a single auto-optimization. The parameters of dose-volume histograms (DVHs) and MLC performance metrics were evaluated. We obtained the modulation complexity score for VMAT (MCSv), closed leaf score (CLS), small aperture score (SAS), leaf travel (LT), and total MU. RESULTS The ASC did not affect the DVH parameters negatively. The following comparisons of MLC performance were obtained (KBP vs. KBP-VL vs. KBP-VH, respectively): 0.25 vs. 0.27 vs. 0.30 (MCSv), 0.19 vs. 0.18 vs. 0.16 (CLS), 0.50 vs. 0.45 vs. 0.40 (SAS10 mm), 0.73 vs. 0.68 vs. 0.63 (SAS20 mm), 768.35 mm vs. 671.50 mm vs. 551.32 mm (LT), and 672.87 vs. 642.36 vs. 607.59 (MU). There were significant differences between KBP and KBP-VH for MCSv and LT (p<0.05). CONCLUSIONS The KBP using an ASC set to the very high level could reduce the complexity of MLC motion significantly more without deterioration of the DVH parameters compared with the KBP in VMAT for prostate cancer.
Classical Psychedelics as Therapeutics in Psychiatry – Current Clinical Evidence and Potential Therapeutic Mechanisms in Substance Use and Mood Disorders

Abstract Classical psychedelics, primarily psilocybin and lysergic acid diethylamide (LSD), have been used and extensively studied in Western medicine as part of substance-assisted psychotherapy in the 1950s and 1960s. Modern clinical research is currently gaining momentum and provides new evidence for the safety and efficacy of classical psychedelics (primarily psilocybin, but also LSD and ayahuasca) in the treatment of different psychiatric conditions, including substance use and mood disorders. In this review article, we outline common pathological mechanisms of substance use disorders (SUD) and unipolar depression. Next, the current literature on the effects of psychedelics is summarized in order to generate hypotheses regarding their potential therapeutic mechanisms of action in treating these psychiatric conditions. Finally, we review and discuss clinical trials published since 2011 investigating the effects of psychedelics in SUD and depression. While results from those modern clinical trials are promising, most of them do not meet the methodological requirements to allow firm conclusions on the clinical efficacy of psychedelics. Larger, blinded, randomized controlled trials (RCT) with clearly defined patient groups and well-defined primary endpoints are needed. Additionally, the therapeutic mechanisms of classical psychedelics are currently unknown. This review presents hypotheses derived from preclinical and human studies that need to be tested in future trials to better understand the clinical potential of psychedelic substances in modern psychiatry.
MEDICAL TREATMENT LANDSCAPE FOR ACTIVE ACROMEGALY IN A PITUITARY CENTER IN ISRAEL.

Objective: To evaluate current real-life experience with medical treatment for active acromegaly in a large cohort. Methods: Data on demographic parameters, blood tests, imaging studies, and treatments were extracted from the medical records. Results: The cohort included 87 patients (43 male) with active acromegaly. Mean age at diagnosis was 40.2±11.4 years, and mean duration of follow-up, 7.9±5.8 years. Seventy patients presented with a macroadenoma. Mean baseline IGF-1 (n=67) was 3.2±1.9 x ULN. Surgery was performed in 75 patients and radiotherapy in 10. Currently, 38 subjects receive somatostatin analogues, pegvisomant as monotherapy is given to 8 patients, pasireotide -17, cabegoline- 4, estrogen- 2 females, and SSAs combined with pegvisomant for 10 patients. Eight patients are not actively treated, including 4 following radiotherapy. Good biochemical control (IGF-1 ≤ 1.3 x ULN) was achieved in 76 patients (87%), and 11 patients (13%) are currently uncontrolled (IGF-1 > 1.3 x ULN). 78% of controlled patients are given one medication; 11% are on combination therapy; four patients are well controlled after radiotherapy and two are partially controlled without any treatment. The main adverse effects of treatment were diabetes mellitus in 7 patients (on pasireotide) and symptomatic cholelithiasis in 5. Conclusions: Active acromegaly can be controlled medically in most patients, with a low rate of adverse effects. This study displays the characteristic variety of treatment options available for active acromegaly.
Sleep phenotype of individuals with autism spectrum disorder bearing mutations in the PER2 circadian rhythm gene

The Per family of genes functions as a primary circadian rhythm maintenance in the brain. Mutations in PER2 are associated with familial advanced sleep‐phase syndrome 1 (FASPS1), and recently suggested in delayed sleep phase syndrome and idiopathic hypersomnia. The detection of PER2 variants in individuals with autism spectrum disorder (ASD) and without reported sleep disorders, has suggested a role of circadian‐relevant genes in the pathophysiology of ASD. It remains unclear whether these individuals may have, in addition to ASD, an undiagnosed circadian rhythm sleep disorder. The MSSNG database was used to screen whole genome sequencing data of 5,102 individuals with ASD for putative mutations in PER2. Families identified were invited to complete sleep phenotyping consisting of a structured interview and two standardized sleep questionnaires: the Pittsburgh Sleep Quality Index and the Morningness‐Eveningness Questionnaire. From 5,102 individuals with ASD, two nonsense, one frameshift, and one de novo missense PER2 variants were identified (0.08%). Of these four, none had a diagnosed sleep disorder. Three reported either a history of, or ongoing sleep disturbances, and one had symptoms highly suggestive of FASPS1 (as did a mutation carrier father without ASD). The individual with the missense variant did not report sleep concerns. The ASD and cognitive profiles of these individuals varied in severity and symptoms. The results support a possible role of PER2‐related circadian rhythm disturbances in the dysregulation of sleep overall and sometimes FASPS1. The relationship between dysregulated sleep and the pathophysiology of ASD require further exploration.
Developmental Pathways from Childhood Maltreatment to Young Adult Romantic Relationship Functioning

ABSTRACT Childhood abuse has been suggested to potentiate a maladaptive developmental trajectory, leaving adolescents and young adults at risk for mental health and romantic relationship problems. It has been suggested that mental health problems mediate the relationship between childhood abuse and young adult romantic relationship functioning; however, there are few prospective studies. The objective of the current study was to examine the effects of childhood physical, sexual, and emotional abuse on posttraumatic stress symptoms in adolescence, and relationship quality, intimacy, companionship, and conflict in young adult’s romantic relationships. Using data from the Longitudinal Studies of Childhood Abuse and Neglect (LONGSCAN), a sample of 313 racially diverse adolescents were used. Using structural equation modeling, it was found that dissociation mediated the relationship between physical abuse and relationship quality, but in the opposite direction of what was expected. Additionally, anger mediated the relationship from both physical and sexual abuse to conflict. Childhood abuse appears to influence young adult relationship functioning through mental health problems in mid-adolescence, particularly anger and dissociation. These results are consistent with the notion that children who were abused may struggle in romantic relationships in young adulthood and addressing mental health problems in adolescence may a point of intervention.
A 12-hour rapid titration method for cancer pain: a randomized, controlled, open-label study.

BACKGROUND Opioid titration is the best way to achieve a balance of pain relief and tolerable side effects for moderate-to-severe cancer pain. Rapid dose titration helps to achieve early analgesia. We explored the efficacy and safety of a 12-hour rapid dose titration in treating cancer pain. METHODS Opioid-naïve patients with moderate-to-severe cancer pain were randomly divided into oxycodone group and morphine group. The medicines were adjusted to oxycodone sustained-release tablets after 12 hours, and the dose of oxycodone sustained-release tablets was adjusted every 12 hours. The analgesic efficacy and adverse reactions during the treatment were observed until the 72nd hour. RESULTS A total of 106 patients were included in the analysis, with 51 patients in the oxycodone group and 55 in the morphine group. The pain control rate of all patients reached 96.2% 24 hours after treatment, and it was not significantly different between two groups (P=0.619). The proportion of Numeric Rating Scale (NRS) score that decreased by ≥50% was significantly higher in the oxycodone group than in the morphine group (P=0.013). In the first 12 hours and 24 hours, significantly lower proportions of patients in the oxycodone group experienced multiple episodes of breakthrough pain (BTP) than in the morphine group (P=0.032, P=0.021, respectively). The quality of life of the patients in the oxycodone group was significantly higher than that in the morphine group at the 24th hour (P=0.047), as was the degree to which the quality of life had improved (P<0.001). Only grade 1 or 2 adverse reactions were observed during the study period, and no significant difference between two groups. CONCLUSIONS The 12-hour rapid dose titration method can achieve early analgesia, with mild adverse reactions. In particular, the rapid titration method with background sustained-release oxycodone can reduce BTP episodes and achieve significant early pain relief.
A review on exploring better safety prospects in managing cancer using liposomal combinations of food bioactive compounds and anticancer drugs: Combisomes.

Nowadays, cancer is one of the deadliest diseases affecting an annually enormous number of people. Around 9.6 million people had died from different cancer types in 2018. Chemotherapy is considered to be a mainline treatment, and systemic administration of a single anticancer agent is also considered as vital clinical debacles of chemotherapy in cancer management. The formulators have been focusing currently onto procuring maximum benefit with the lowest aftereffects and maximum safety and efficacy for the patients undergoing chemotherapy. This review offers a perspective on the future developments of encapsulating food bioactive compounds with anticancer agents in a multifunctional single nanoliposomal delivery system. In the last decade, the paradigm shift was seen in formulating drug delivery systems for cancer treatment. Currently, food bioactive compounds are being taken as a hot subject by the researchers, especially for the treatment of cancer owing to both preventative and curative quality. This review collects the utilization of liposomes in the delivery of anticancer drugs by encapsulating with food bioactive compounds by the oral administration. The authors coined the name of this combination is "Combisomes" as a fourth generation liposomes. Authors opine that "Combisomes" can tackle cancer minimizing side effects encountered from the usual anticancer agents. "Combisomes" will purvey a safe platform for the delivery of food bioactive compounds and anticancer agents for managing cancer with better safety prospects.