Miracle-dz/UniFAR-FTUs huggingface dataset:
Propensity score-integrated composite likelihood approach for incorporating real-world evidence in single-arm clinical studies

ABSTRACT In medical product development, there has been an increased interest in utilizing real-world data which have become abundant with recent advances in biomedical science, information technology, and engineering. High-quality real-world data may be analyzed to generate real-world evidence that can be utilized in the regulatory and healthcare decision-making. In this paper, we consider the case in which a single-arm clinical study, viewed as the primary data source, is supplemented with patients from a real-world data source containing both clinical outcome and covariate data at the patient-level. Propensity score methodology is used to identify real-world data patients that are similar to those in the single-arm study in terms of the baseline characteristics, and to stratify these patients into strata based on the proximity of the propensity scores. In each stratum, a composite likelihood function of a parameter of interest is constructed by down-weighting the information from the real-world data source, and an estimate of the stratum-specific parameter is obtained by maximizing the composite likelihood function. These stratum-specific estimates are then combined to obtain an overall population-level estimate of the parameter of interest. The performance of the proposed approach is evaluated via a simulation study. A hypothetical example based on our experience is provided to illustrate the implementation of the proposed approach.
The relationship between parenting stress and maternal responsiveness among mothers of children with developmental problems

by FRIDA PERALES MAHONEY This study explored the relationship between parenting stress and mother-child interaction style among mothers of children with pervasive developmental disorders (PDD) and developmental disabilities (DD) who participated in a Relationship Focused (RF) intervention over a period of one year. Associations between children’s diagnoses, severity, parenting stress, and mother-child interaction style were analyzed by secondary data analysis. Correlation and hierarchical regression statistical procedures were used with two groups of mothers of 44 children, ages 11-54 months who completed pre and post treatment group only. Results indicated that mothers of children with PDD experienced more parenting stress than mothers of children with DD. Also, the severity of children’s disabilities was a significant predictor of the level of parenting stress mothers reported. In addition, children’s diagnosis of PDD and parent-child interaction style prior to intervention predicted change in the style of parent-child interactions at post treatment, and parenting stress prior to intervention was a statistically significant predictor of parenting stress after intervention. Findings have two major implications for early intervention practice. First, they confirmed the generally reported results that
Digital PCR-An Emerging Technology with Broad Applications in Microbiology.

BACKGROUND The PCR and its variant, quantitative PCR (qPCR), have revolutionized the practice of clinical microbiology. Continued advancements in PCR have led to a new derivative, digital PCR (dPCR), which promises to address certain limitations inherent to qPCR. CONTENT Here we highlight the important technical differences between qPCR and dPCR, and the potential advantages and disadvantages of each. We then review specific situations in which dPCR has been implemented in clinical microbiology and the results of such applications. Finally, we attempt to place dPCR in the context of other emerging technologies relevant to the clinical laboratory, including next-generation sequencing. SUMMARY dPCR offers certain clear advantages over traditional qPCR, but these are to some degree offset by limitations of the technology, at least as currently practiced. Laboratories considering implementation of dPCR should carefully weigh the potential advantages and disadvantages of this powerful technique for each specific application planned.
Prescribing, Recording, and Reporting Photon-Beam Intensity-Modulated Radiation Therapy (IMRT)

3 Executive Summary . 5
Microvascular blood flow during vascular occlusion tests assessed by diffuse correlation spectroscopy

What is the central question of this study? What are the characteristics of the time courses of blood flow in the brachial artery and microvascular beds of the skin and skeletal muscle following transient ischaemia? What is the main finding and its importance? Skeletal muscle blood flow was significantly slower than the transient increase in the cutaneous tissue, suggesting mechanistic differences between cutaneous and muscular blood flow distribution after transient ischaemia. These results challenge the use of the cutaneous circulation as globally representative of vascular function.
Autonomous 3D Exploration of Large Structures Using an UAV Equipped with a 2D LIDAR

This paper addressed the challenge of exploring large, unknown, and unstructured industrial environments with an unmanned aerial vehicle (UAV). The resulting system combined well-known components and techniques with a new manoeuvre to use a low-cost 2D laser to measure a 3D structure. Our approach combined frontier-based exploration, the Lazy Theta* path planner, and a flyby sampling manoeuvre to create a 3D map of large scenarios. One of the novelties of our system is that all the algorithms relied on the multi-resolution of the octomap for the world representation. We used a Hardware-in-the-Loop (HitL) simulation environment to collect accurate measurements of the capability of the open-source system to run online and on-board the UAV in real-time. Our approach is compared to different reference heuristics under this simulation environment showing better performance in regards to the amount of explored space. With the proposed approach, the UAV is able to explore 93% of the search space under 30 min, generating a path without repetition that adjusts to the occupied space covering indoor locations, irregular structures, and suspended obstacles.
Development of a Reporter System Monitoring Regulated Intramembrane Proteolysis of the Transmembrane bZIP Transcription Factor ATF6α

When endoplasmic reticulum (ER) functions are perturbed, the ER induces several signaling pathways called unfolded protein response to reestablish ER homeostasis through three ER transmembrane proteins: inositol-requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Although it is important to measure the activity of ATF6 that can indicate the status of the ER, no specific cell-based reporter assay is currently available. Here, we report a new cell-based method for monitoring ER stress based on the cleavage of ATF6α by sequential actions of proteases at the Golgi apparatus during ER stress. A new expressing vector was constructed by using fusion gene of GAL4 DNA binding domain (GAL4DBD) and activation domain derived from herpes simplex virus VP16 protein (VP16AD) followed by a human ATF6α N-terminal deletion variant. During ER stress, the GAL4DBD-VP16AD(GV)-hATF6α deletion variant was cleaved to liberate active transcription activator encompassing GV-hATF6α fragment which could translocate into the nucleus. The translocated GV-hATF6α fragment strongly induced the expression of firefly luciferase in HeLa Luciferase Reporter cell line containing a stably integrated 5X GAL4 site-luciferase gene. The established double stable reporter cell line HLR-GV-hATF6α(333) represents an innovative tool to investigate regulated intramembrane proteolysis of ATF6α. It can substitute active pATF6(N) binding motif-based reporter cell lines.
Cutting Edge Neurosurgery

Palese and Infanti (2006) examined the experiences of nurses who took part in craniotomies where the patients were initially anaesthetised but woken during the procedure to test specific responses, before being reanaesthetised for the remainder of the procedure. Their research revealed that dealing with this affected the way in which the instrument practitioners (scrubbed person) communicated with the rest of the team and with the patient. They sometimes had to explain to the patient what the surgeon required them to do.
PRACTICING HOSPITAL PHARMACISTS MENTORING PHARMACY STUDENTS IN CLINICAL PHARMACY: AN EXPERIENCE FRO M DOW UNIVERSITY OF HEALTH SCIENCES (DUHS) PAKISTAN

Pharmacy education has been an important and in tegral part of the education system of a country. Pharmacy education in Pakistan has grown significantly through the ag es and there are quite a few number of pharmacy schools provi ding education to the students. The a cademia and practice had always been disjointed in the country . Dow College of Pharmacy (DCOP) at DUHS was established in the year 2008, with the v ision to pr ovide exemplary pharmacy education to the students and bridging the gap between education and practice . Th e intervention was made by the c ollege through appointing practicing faculty members , working at Dow University Hospital as clinical pharmacists and t each ing clinical pharmacy to the students at DCOP. Since no other pharmacy school in the country had jointly appointed faculty of pharmacy, this intervention provided opportunity to DCOP to produce quality clinical pharmacists for the country. Under the s upervision of clinical pharmacist pharmacy students were regularly rotated to hospital and were trained to take medication history, review patient profiles, gather & interpret laboratory data, and identifying potential drug related problems. Students were required to present their findings and intervention s in patient profile as case studies to clinical pharmacists and interactive discussions we re carried out by the mentors to enhance their clinical skills. The experiment of mentoring pharmacy students thro ugh p racticing clinical pharmacist proved to be an efficient tool to develop and strengthen clinical skills of pharmacy graduates and could serve as a role model for other pharmacy schools in the country.
Walking Green: Developing an Evidence Base for Nature Prescriptions

Although the health benefits of exercise and exposure to nature are well established, most evidence of their interaction comes from acute observations of single sessions of activity. However, documenting improved health outcomes requires ongoing interventions, measurement of multiple outcomes, and longitudinal analyses. We conducted a pilot study to guide the development of a protocol for future longitudinal studies that would assess multiple physiological and psychological outcomes. Herein, we report psychological outcomes measured from thirty-eight participants before and after three conditions: a 50 min walk on a forest path, a 50 min walk along a busy road, and a period of activities of daily living. Changes in positive and negative affect, anxiety, perceived stress, and working memory are reported. We benchmark these results to existing studies that used similar protocols and also identify elements of the protocol that might impair recruitment or retention of subjects in longer-term studies. Linear mixed-models regression revealed that walking improved psychological state when compared to activities of daily living, regardless of walk environment (p < 0.05). Comparison of mean differences showed that forest walks yielded the largest and most consistent improvements in psychological state. Thus, despite a protocol that required a 3.5 h time commitment per laboratory visit, the beneficial effects of walking and exposure to a forested environment were observed.
Zebrafish etv2 knock‐in line labels vascular endothelial and blood progenitor cells

ETS transcription factor Etv2/Etsrp is one of the earliest markers for vascular and hematopoietic progenitors and functions as a key regulator of hematovascular development in multiple vertebrates, including zebrafish. Therefore, transgenic etv2 reporter lines provide a valuable tool to study vasculogenesis and hematopoiesis. However, previously generated zebrafish reporter lines do not fully recapitulate the endogenous pattern of etv2 expression.
Neutrophils promote VLA-4–dependent B cell antigen presentation and accumulation within the meninges during neuroinflammation

Significance A distinct murine model of multiple sclerosis used to examine factors involved in ectopic lymphoid tissue formation during central nervous system autoimmunity reveals that infiltration and aggregation of B cells within the leptomeninges is dependent upon B cell expression of VLA-4 and is preceded by neutrophil migration. This finding establishes the early mechanisms involved in the establishment of chronic inflammatory changes within the meninges during autoimmune inflammation that promote the formation of ectopic lymphoid tissue associated with disease progression and disability in multiple sclerosis. The success of B cell depletion therapies and identification of leptomeningeal ectopic lymphoid tissue (ELT) in patients with multiple sclerosis (MS) has renewed interest in the antibody-independent pathogenic functions of B cells during neuroinflammation. The timing and location of B cell antigen presentation during MS and its animal model experimental autoimmune encephalomyelitis (EAE) remain undefined. Using a new EAE system that incorporates temporal regulation of MHCII expression by myelin-specific B cells, we observed the rapid formation of large B cell clusters in the spinal cord subarachnoid space. Neutrophils preceded the accumulation of meningeal B cell clusters, and inhibition of CXCR2-mediated granulocyte trafficking to the central nervous system reduced pathogenic B cell clusters and disease severity. Further, B cell-restricted very late antigen-4 (VLA-4) deficiency abrogated EAE dependent on B cell antigen presentation. Together, our findings demonstrate that neutrophils coordinate VLA-4–dependent B cell accumulation within the meninges during neuroinflammation, a key early step in the formation of ELT observed in MS.
Baicalein as a Potential Inhibitor against BACE1 and AChE: Mechanistic Comprehension through In Vitro and Computational Approaches

One of the major neurodegenerative features of Alzheimer’s disease (AD) is the presence of neurotoxic amyloid plaques composed of amyloid beta peptide (Aβ). β-Secretase (BACE1) and acetylcholinesterase (AChE), which promote Aβ fibril formation, have become attractive therapeutic targets for AD. P-glycoprotein (P-gp), the major efflux pump of the blood-brain barrier (BBB), plays a critical role in limiting therapeutic molecules. In pursuit of discovering a natural anti-AD candidate, the bioactivity, physicochemical, drug-likeness, and molecular docking properties of baicalein, a major compound from Scutellaria baicalensis, was investigated. Baicalein exhibited strong BACE1 and AChE inhibitory properties (IC50 23.71 ± 1.91 µM and 45.95 ± 3.44 µM, respectively) and reacted in non-competitive and competitive manners with substrates, respectively. in Silico docking analysis was in full agreement with the in vitro results, demonstrating that the compound exhibited powerful binding interaction with target enzymes. Particularly, three continuous hydroxyl groups on the A ring demonstrated strong H-bond binding properties. It is also noteworthy that baicalein complied with all requirements of Lipinski’s rule of five by its optimal physicochemical properties for both oral bioavailability and blood–brain barrier permeability. Overall, the present study strongly demonstrated the possibility of baicalein having in vivo pharmacological efficacy for specific targets in the prevention and/or treatment of AD.
Confidence intervals for the ratio of two independent Poisson rates: Parametric bootstrap, modified asymptotic, and approximate-estimate approaches

We propose four confidence intervals for the ratio of two independent Poisson rates. We apply a parametric bootstrap approach, two modified asymptotic results, and we propose an ad-hoc approximate-estimate method to construct confidence intervals. We justify the correctness of the proposed methods asymptotically in the case of non-rare events (when the Poisson rates are large). We also compare the proposed confidence intervals with some recommended ones in the case of rare events (when the Poisson rates are small) via an extensive simulation study. The results show that the proposed modified asymptotic and the approximate-estimate confidence intervals perform reasonably well in terms of coverage probability and average length.
Seminal SIRT1‐oxidative stress relationship in infertile oligoasthenoteratozoospermic men with varicocele after its surgical repair

This work assessed seminal SIRT1‐oxidative stress (OS) relationship in infertile oligoasthenoteratozoospermic (OAT) men after varicocele repair. Overall, thirty OAT men with varicocele were investigated. Inclusion criteria were infertile males (males who were unable to initiate a pregnancy within 1 year of regular unprotected intercourse), confirmed OAT and normal female factor. These cases were subjected to history taking, clinical checkup and semen analysis. In their semen, seminal SIRT1, malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were assessed. These men were subjected to varicocele surgical repair and were followed up for 3 months. Post‐operatively, the mean seminal SIRT1, GPx levels showed significant increases and the mean MDA level showed significant decrease compared to the pre‐operative levels linked to improved sperm parameters. The mean seminal SIRT1, GPx, MDA levels showed more significant improvement in grade III varicocele cases compared to grade II cases after surgical repair. Seminal SIRT1 levels showed significant positive correlations with sperm concentration, sperm motility, sperm normal morphology, seminal GPx levels and a significant negative correlation with seminal MDA levels. It could be concluded that seminal SIRT1 is significantly decreased in infertile OAT men with varicocele after its surgical repair linked to improved sperm parameters as well as seminal OS.
Enhanced effects of electrospun collagen-chitosan nanofiber membranes on guided bone regeneration

Abstract It was aim to study the physicochemical features and biocompatibility of electrospun collagen-chitosan membranes, and its potential in guided bone regeneration. Electrospinning technology was applied in the fabrication of electrospun collagen membranes and electrospun collagen-chitosan membranes following observation of scanning electron microscope. Physicochemical properties including tensile strength, elongation rate, porosity, degradation rate, and biocompatibility of membranes were measured then. In vivo, calvarial bone defects created on rats were covered with two kinds of membranes respectively. In the 4th and 8th week, enzyme-linked immunosorbent assay testing bone alkaline phosphatase and osteocalcin, Micro CT analyzing bone volume, bone volume/total volume, trabecular number and trabecular spacing values, and histological staining were carried out for evaluating the potentials of the membranes on bone regeneration. We found that regular and highly-porous structure favoring the adhesion and proliferation of periodontal ligament cells was observed in all electrospinning groups. Compared with electrospun collagen membranes, electrospun collagen-chitosan membranes performed better physiochemical features including higher tensile strength and more stable degradation rate. In the animal model, compared with the other groups, higher levels of bone alkaline phosphatase in the 4th week and osteocalcin in the 8th week were observed in the electrospun collagen-chitosan membrane. Meanwhile, both of the radiographical and histological results further confirmed that the new bone formation (with higher bone volume, bone volume/total volume, Trabecular number, and lower Trabecular spacing) were more active in the electrospun collagen-chitosan membrane. In conclusion, Electrospun collagen-chitosan membranes perform excellent physicochemical properties, biocompatibility, and great effects on guided bone regeneration, which as the membrane has good application prospect in tissue regeneration.
Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration

The cardiac lymphatic vascular system and its potentially critical functions in heart patients have been largely underappreciated, in part due to a lack of experimentally accessible systems. We here demonstrate that cardiac lymphatic vessels develop in young adult zebrafish, using coronary arteries to guide their expansion down the ventricle. Mechanistically, we show that in cxcr4a mutants with defective coronary artery development, cardiac lymphatic vessels fail to expand onto the ventricle. In regenerating adult zebrafish hearts the lymphatic vasculature undergoes extensive lymphangiogenesis in response to a cryoinjury. A significant defect in reducing the scar size after cryoinjury is observed in zebrafish with impaired Vegfc/Vegfr3 signaling that fail to develop intact cardiac lymphatic vessels. These results suggest that the cardiac lymphatic system can influence the regenerative potential of the myocardium.
Acute lower leg hot water immersion protects macrovascular dilator function following ischaemia–reperfusion injury in humans

• What is the central question of this study? What is the effect of lower leg hot water immersion on vascular ischaemia–reperfusion injury induced in the arm of young healthy humans? • What is the main finding and its importance? Lower leg hot water immersion successfully protects against vascular ischaemia–reperfusion injury in humans. This raises the possibility that targeted heating of the lower legs may be an alternative therapeutic approach to whole‐body heating that is equally efficacious at protecting against vascular ischaemia–reperfusion injury.
Growing up with Gay Parents: What is the Big Deal? *

A very large body of social science research going back decades has documented the vital and unique role of mothers and of fathers in childhood development. These studies have also demonstrated the negative psychological, educational, and social effects on children who have been deprived of growing up in a home with both biological parents who are married to each other. A very brief summary of findings on the mothers’ unique and crucial role in childhood development would include these points:
Pregnant Patient Perceptions of Provider Detection and Treatment of Insomnia

ABSTRACT Objective: To survey pregnant patients about whether their health care providers assessed insomnia, the types of treatment recommendations providers made, and the types of treatments patients utilized. Participants: Participants were 423 English-speaking pregnant women. Methods: In this cross-sectional study, participants self-reported insomnia symptoms on the Insomnia Severity Index and indicated whether they discussed their sleep with a health care provider, whether they received any recommendations to improve their sleep, and whether they utilized any interventions or aids to improve their sleep during their current pregnancy. Results: Approximately one-third (39%) of participants reported that they discussed their sleep with a health care provider at some point during their pregnancy. Among participants who reported moderate to severe insomnia symptoms (Insomnia Severity Index>14), 57% reported that they had discussed their sleep with a health care provider, and 28% reported receiving an insomnia diagnosis. Over-the-counter medication was the most commonly recommended (53%) and utilized (39%) sleep intervention among women with moderate to severe insomnia symptoms. Conclusions: According to patient report, insomnia may be under-detected during pregnancy. When insomnia is recognized, treatment recommendations do not match clinical practice guidelines or women’s preferences for receiving cognitive behavior therapy for insomnia. Taken together with previous research on the prevalence and consequences of prenatal insomnia, these findings suggest the need for an increased focus on the importance of sleep during pregnancy.