Miracle-dz/UniFAR-FTUs huggingface dataset:
Long‐term histological analysis of innervation and macrophage infiltration in a mouse model of intervertebral disc injury–induced low back pain

Low back pain (LBP) is a leading cause of global disability. Multiple anatomical, cellular, and molecular factors are implicated in LBP, including the degeneration of lumbar intervertebral discs (IVDs). We previously described a mouse model that displays behavioral symptoms of chronic LBP. Here, we investigated the development of pathological innervation and macrophage infiltration into injured IVDs following a puncture injury in mice over 12 months. 2‐month old CD1 female mice underwent a single puncture of the ventral L4/5 IVD using a 30G needle, and were sacrificed 4 days and 0.5‐, 3‐, 6‐ and 12‐months post‐injury. Severity of disc degeneration was assessed using colorimetric staining. IVD innervation was measured by PGP9.5‐immunoreactivity (‐ir) and calcitonin gene‐related peptide‐ir (CGRP‐ir). Macrophage accumulation into IVDs was detected by F4/80‐ir. Mechanical IVD injury resulted in severe degeneration and increased PGP9.5‐ir nerve fiber density starting at 4 days that persisted for up to 12 months and dorsal herniations began to occur at 3 months. CGRP‐ir was also upregulated in injured IVDs, with the largest increase at 12 months after injury. Infiltration of F4/80‐ir macrophages was observed in injured IVDs by day 4 both dorsally and ventrally, with the latter diminishing in the later stage. Persistent LBP is a complex disease with multiple underlying pathologies. By highlighting pathological changes in IVD innervation and inflammation, our study suggests that strategies targeting these mechanisms might be useful therapeutically.
Primary Care Practitioner Training in Child and Adolescent Psychiatry (PTCAP): A Cluster-Randomized Trial

Objectives Rural primary care practitioners (PCPs) have a pivotal role to play in frontline pediatric mental health care, given limited options for referral and consultation. Yet they report a lack of adequate training and confidence to provide this care. The aim of this study was to test the effectiveness of the Practitioner Training in Child and Adolescent Psychiatry (PTCAP) program, which was designed to enhance PCPs’ pediatric mental health care confidence. The program includes brief therapeutic skills and practice guidelines PCPs can use to address both subthreshold concerns and diagnosable conditions, themselves. Methods The study design was a pilot, cluster-randomized, multicenter trial. Practices were randomly assigned to intervention (n practices = 7; n PCPs = 42) or to wait-list control (n practices = 6; n PCPs = 34). The intervention involved 8 hr of training in practice guidelines and brief therapeutic skills for depression, anxiety, attention deficit hyperactivity disorder, and behavioral disorders with case discussion and video examples, while the control practiced as usual. A linear random-effects model controlling for clustering and baseline was carried out on the individual-level data to examine between-group differences in the primary (i.e., confidence) and secondary (i.e., attitude and knowledge) outcomes at 1-week follow-up. Results Findings were a statistically significant difference in the primary outcomes. Compared to the control group, the intervention group indicated significantly greater confidence in managing diagnosable conditions (d = 1.81) and general concerns (d = 1.73), as well as in making necessary referrals (d = 1.27) and obtaining consults (d = 0.74). While the intervention did not significantly impact secondary outcomes (attitudes and knowledge), regression analysis indicated that the intervention may have increased confidence, in part, by ameliorating the adverse impact of negative mental health care attitudes. Conclusion PTCAP enhances PCPs’ child/youth mental health care confidence in managing both general and diagnosable concerns. However, an 8-hr session focused on applying brief therapeutic skills was insufficient to significantly change attitudes and knowledge. Formal testing of PTCAP may be warranted, perhaps using more intensive training and including outcome assessments capable of determining whether increased PCP confidence translates to more effective management and better patient outcomes.
The Effect of Operator Position on the Quality of Chest Compressions Delivered in a Simulated Ambulance

Abstract Background: Ambulances are where patient care is often initiated or maintained, but this setting poses safety risks for paramedics. Paramedics have found that in order to optimize patient care, they must compromise their own safety by standing unsecured in a moving ambulance. Hypothesis/Problem: This study sought to compare the quality of chest compressions in the two positions they can be delivered within an ambulance. Methods: A randomized, counterbalanced study was carried out with 24 paramedic students. Simulated chest compressions were performed in a stationary ambulance on a cardiopulmonary resuscitation (CPR) manikin for two minutes from either: (A) an unsecured standing position, or (B) a seated secured position. Participants’ attitudes toward the effectiveness of the two positions were evaluated. Results: The mean total number of chest compressions was not significantly different standing unsecured (220; SD = 12) as compared to seated and secured (224; SD = 21). There was no significant difference in mean compression rate standing unsecured (110 compressions per minute; SD = 6) as compared to seated and secured (113 compressions per minute; SD = 10). Chest compressions performed in the unsecured standing position yielded a significantly greater mean depth (52 mm; SD = 6) than did seated secured (26 mm; SD = 7; P < .001). Additionally, the standing unsecured position produced a significantly higher percentage (83%; SD = 21) for the number of correct compressions, as compared to the seated secured position (8%; SD = 17; P < .001). Participants also believed that chest compressions delivered when standing were more effective than those delivered when seated. Conclusions: The quality of chest compressions delivered from a seated and secured position is inferior to those delivered from an unsecured standing position. There is a need to consider how training, technologies, and ambulance design can impact the quality of chest compressions.
Adaptive Liquid Interfacially Assembled Protein Nanosheets for Guiding Mesenchymal Stem Cell Fate

There is a growing interest in the development of dynamic adaptive biomaterials for regulation of cellular functions. However, existing materials are limited to two‐state switching of the presentation and removal of cell‐adhesive bioactive motifs that cannot emulate the native extracellular matrix (ECM) in vivo with continuously adjustable characteristics. Here, tunable adaptive materials composed of a protein monolayer assembled at a liquid–liquid interface are demonstrated, which adapt dynamically to cell traction forces. An ultrastructure transition from protein monolayer to hierarchical fiber occurs through interfacial jamming. Elongated fibronectin fibers promote formation of elongated focal adhesion structures, increase focal adhesion kinase activation, and enhance neuronal differentiation of stem cells. Cell traction force results in spatial rearrangement of ECM proteins, which feeds back to alter stem cell fate. The reported biomimetic adaptive liquid interface enables dynamic control of stem cell behavior and has potential translational applications.
Echocardiography-Guided Dual-Lumen Venovenous Extracorporeal Membrane Oxygenation Cannula Placement in the ICU-A Retrospective Review.

OBJECTIVE The most effective method of image guidance for venovenous extracorporeal membrane oxygenation is not known. The authors' objectives were to define the frequency of successful initial cannulation using echocardiographic guidance in the intensive care unit, as well as to determine the frequency of subsequent adjustments. Additional aims were to illustrate cannula malposition problems and to describe features associated with difficult cannulation. DESIGN Retrospective consecutive case series analysis. SETTING Single tertiary care university hospital. PARTICIPANTS Forty-five patients treated with venovenous extracorporeal membrane oxygenation. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The most common causes of respiratory failure were pneumonia, aspiration, and inhalational burn injury. Sixty-two percent survived to discharge. Initial cannulation was successful in 39 cases (87%). Adverse events included 5 cases of cannula malposition and 1 case of hemorrhagic shock. During the course of extracorporeal membrane oxygenation, 17 patients (38%) required echo-guided cannula position adjustments. There were no fatal complications. Factors associated with difficult cannulation included extremes of size, a prominent Eustachian valve, and an anterior guidewire bending in the right atrium. Younger age was associated positively with survival. There was no significant association between adverse events during cannulation and survival. CONCLUSIONS Dual-lumen venovenous extracorporeal membrane oxygenation cannulation in the intensive care unit under echo guidance has a high initial success rate, but many patients require subsequent repositioning. Echocardiography can define cannula position in sufficient detail to identify malposition precisely and to guide repositioning.
Current RNA-seq methodology reporting limits reproducibility

Abstract Ribonucleic acid sequencing (RNA-seq) identifies and quantifies RNA molecules from a biological sample. Transformation from raw sequencing data to meaningful gene or isoform counts requires an in silico bioinformatics pipeline. Such pipelines are modular in nature, built using selected software and biological references. Software is usually chosen and parameterized according to the sequencing protocol and biological question. However, while biological and technical noise is alleviated through replicates, biases due to the pipeline and choice of biological references are often overlooked. Here, we show that the current standard practice prevents reproducibility in RNA-seq studies by failing to specify required methodological information. Peer-reviewed articles are intended to apply currently accepted scientific and methodological standards. Inasmuch as the bias-less and optimal RNA-seq pipeline is not perfectly defined, methodological information holds a meaningful role in defining the results. This work illustrates the need for a standardized and explicit display of methodological information in RNA-seq experiments.
Neurogranin Regulates Alcohol Sensitivity through AKT Pathway in the Nucleus Accumbens

Dysfunction of glutamate neurotransmission in the nucleus accumbens (NAc) has been implicated in the pathophysiology of alcohol use disorders (AUD). Neurogranin (Ng) is exclusively expressed in the brain and mediates N‐methyl‐d‐aspartate receptor (NMDAR) hypo‐function by regulating the intracellular calcium‐calmodulin (Ca2+‐CaM) pathway. Ng null mice (Ng–/– mice) demonstrate increased alcohol drinking compared to wild‐type mice, while also showing less tolerance to the effect of alcohol. To identify the molecular mechanism related to alcohol seeking, both in vivo microdialysis and label‐free quantification proteomics comparing Ng genotype and effects of alcohol treatment on the NAc are utilized. There is significant difference in glutamate and gamma‐aminobutyric acid (GABA) neurotransmission between genotypes; however, alcohol administration normalizes both glutamate and GABA levels in the NAc. Using label‐free proteomics, 427 protein expression changes are identified against alcohol treatment in the NAc among 4347 total proteins detected. Bioinformatics analyses reveal significant molecular differences in Ng null mice in response to acute alcohol treatment. Ingenuity pathway analysis found that the AKT network is altered significantly between genotypes, which may increase the sensitivity of alcohol in Ng null mice. The pharmacoproteomics results presented here illustrate a possible molecular basis of the alcohol sensitivity through Ng signaling in the NAc.
Recapturing disease response: A phase 2 study of carfilzomib 56 mg/m2 in patients with relapsed or refractory multiple myeloma who have progressed on carfilzomib 27 mg/m2

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The prevalence of musculoskeletal disorders among pre-adolescent agricultural workers of West Bengal, India : research article

In India, particularly in West Bengal, pre-adolescents are primarily associated with agricultural works in rural areas mostly due to their socio-economic disadvantage. They are compelled to carry out a considerable amount of manual, rigorous tasks in the agricultural field. For this they have to adopt some undesirable postures that may lead to musculoskeletal disorder (MSD) in the near future. The main aim of the present investigation was to assess the prevalence of MSD among the pre-adolescent agricultural workers (both male and female) of West Bengal. For this study three groups of subjects, an experimental group engaged in hand intensive jobs, control group-I performing lesser amount of hand intensive job and control group-II pursuing only education were selected. A modified Nordic questionnaire was used for all groups. It is evident from this study that these very young agricultural workers who are required to constantly bend and twists during work will experience transient fatigue, pain and eventually MSDs.
Trends in mortality, cardiovascular complications, and risk factors in type 2 diabetes.

BACKGROUND Quality of diabetes care in the Netherlands ranked second in the Euro Diabetes Index 2014, but data on outcomes are lacking. We assessed trends in cardiovascular disease and mortality among type 2 diabetes (T2DM) patients in the context of risk factor control. METHODS Annual cohorts of adult T2DM patients were constructed from the PHARMO Database Network. Age-standardised mortality rates and incidence rates (IR) of hospitalisations for acute myocardial infarction (AMI), stroke, and congestive heart failure (CHF) were compared with a diabetes-free population matched on age, sex, and general practitioner. Life years lost (LYL) to T2DM or cardiovascular disease were determined by comparing life expectancy between matched groups. Proportions attaining glycated haemoglobin (HbA1c), blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) goals were assessed annually. RESULTS Among 53,602 T2DM patients, slight increases in IR between 2008 and 2016 were proportional to those in diabetes-free controls; on average T2DM increased the risk of mortality by 86%, hospitalisation for AMI 69%, stroke 57%, and CHF 185%. At age 55, LYL to T2DM averaged 3.5 years and established CVD added 1.8 years, irrespective of sex. HbA1c goal attainment increased from 58% to 65%, LDL-C from 56% to 65%, and systolic BP from 57% to 72%. CONCLUSION Despite highly organised diabetes care, excess incident cardiovascular events and mortality due to T2DM did not decrease over the study period. Life expectancy of T2DM patients is significantly reduced and risk factor control is suboptimal. This suggests there is considerable room for improvement of diabetes care in the Netherlands.
Molecular Dynamics Study on the Effect of Defects upon Shear Properties of Graphene

Abstract—We investigated the shear properties of graphene containing point defects, such as vacancies, nitrogen atoms, and interlayer sp carbons via molecular dynamics (MD) simulations. In the MD simulation, we used three types of potential functions: the second–generation reactive empirical bond order (REBO) potential for covalent C–C bonds, the Tersoff potential for covalent C–N bonds, and the Lennard-Jones potential for interlayer interactions in bilayer graphene. It was found that graphene is more sensitive to vacancy than sp carbon or nitrogen atom unless these defects cluster in graphene.
Evaluation of the Probation Results of 2010 in Samsun Mental Health Hospital and the Compliance with Treatment in Individuals Referred from the Centers Outside of the City Center of Samsun

Aim: In this study, we aimed at evaluating the probations results and compliance with treatment in patients referred to the Samsun Mental Health Hospital from the centers outside of the city of Samsun. Method: The study data were collected retrospectively from the records of the year 2010. The data concerning age and sex, compliance with treatment and the centers from where the patients were referred, were reviewed. Results: In 2010, a total of 491 persons were referred to Samsun Mental Health Hospital in accordance with a probation measures. Four applicants (0.9%) were female and 487 applicants (99.1%) were male. The mean age of the subjects was 32.5±9.8 years (range: 17-70). The treatment was completed in 376 (77.6%) patients, and 115 (22.4%) were noncompliant. When compared to the referrals from the other centers, treatment compliances in patients referred from the center of the Samsun City were found similar. However significant differences were found between the patients referred from the districts of Vezirkopru and Carsamba and those referred from the cities of Sinop, Trabzon, Gumushane and Rize in compliance with treatment. Conclusions: 376 (77.6%) patients completed the treatment in the community without being imprisoned. The contribution of probation was apparent. However, if these individuals are provided more easily accessible treatment programs in their own centers, this may increase the effectiveness of that practice. Then, it will provide a significant contribution to reducing substance abuse.
Anthocyanin accumulation and differential gene expression in wild-typeand mutant Syzygium malaccense fruits during their growth and ripening

Ripe wild-type Malay apple (Syzygium malaccense) cv. Saraek fruit epidermis is red, whereas a mutant has a white skin. Wild-type and mutant fruit were used as a fruit model to study the regulation and gene expression patterns of anthocyanin biosynthesis and a myeloblastosis (MYB) transcription factor during growth and development. Fruit size, color, anthocyanin composition, and the expression of genes involved in anthocyanin biosyntheses were determined during fruit growth and ripening. Wild-type ripe fruit had a greater diameter and fruit mass than the mutant. The total anthocyanin content was approximately nine-fold higher in wild-type red fruit than in mutant white fruit. The major anthocyanin in the fruit skin of the wild-type was cyanidin-3-O-glucoside with minor amounts of pelargonidin-3-O-glucoside, peonidin-3-O-glucoside, and cyanidin-3,5-O-diglucoside. No anthocyanin was found in mutant fruit. The accumulation of cyanidin-3-O-glucoside during fruit growth and ripening was correlated with red color development and activities of phenylalanine ammonia lyase (PAL) and UDP-glucose:flavonoid-3-O-glucosyltransferase (UFGT). We cloned fragments and characterized seven genes involved in anthocyanin biosynthesis pathway namely phenylalanine ammonia lyase (SmPAL), chalcone synthase (SmCHS), chalcone isomerase (SmCHI), flavanone-3-hydroxylase (SmF3H), dihydroflavonol 4-reductase (SmDFR), leucoanthocyanidin dioxygenase (SmLDOX), and UDP glucose-flavonoid-3-O-glucosyl transferase (SmUFGT), as well as a MYB transcription factor (SmMYB). The expressions of all the genes were determined by semi-quantitative reverse transcription (RT)-PCR and quantitative real-time RT-PCR. The skin of wild-type fruit contained transcripts of all above mentioned genes, whereas the mutant fruit showed no SmUFGT and SmMYB expressions, which correlated with the absence of anthocyanin accumulation during fruit growth and ripening. These results suggest that lack of anthocyanin biosynthesis in mutant fruit may be via the regulation of UFGT and MYB transcription factor expressions.