Miracle-dz/UniFAR-FTUs huggingface dataset:
MANAGEMENT OF BRAIN INJURY AFTER CARDIAC ARREST

Cardiac arrest survivors are commonly admitted to an intensive care unit. Neurologic complications of cardiac arrest lead to significant morbidity in survivors. Advances in resuscitative efforts have led to an increase in the number of people who survive cardiac arrest, with a resultant increase in survivors suffering from postanoxic encephalopathy. The focus of resuscitation has shifted to emphasize interventions that restore adequate systemic circulation and those that will ameliorate brain injury after cardiac arrest resuscitation. Recent data about therapeutic hypothermia and other interventions have led to a shift in the role of the neurologist caring for these patients to promote more aggressive management of neurologic complications, including coma, encephalopathy, seizures and myoclonus, elevated intracranial pressure, and metabolic derangements. This chapter will review the neurologic complications of cardiac arrest and focus on the role of the neurologist in the management of such complications.
A Survey on Emotion and Sleep Status in Patients with Functional Constipation

Background: Functional constipation(FC) is prevalent in general population in China.Persistence of constipation symptoms may influence the emotion and sleep status.Aims: To investigate the emotion and sleep status of FC patients and their correlations with constipation.Methods: Consecutive FC patients fulfilling the Rome Ⅲ criteria and inclusion criteria were enrolled and a questionnaire was completed by face to face interview.The questionnaire contained constipation symptoms,emotion and sleep status and their correlations,diagnosis and management of constipation,and self-report of adverse impact of constipation on life.Results: A total of 228 valid questionnaires were analyzed.Of all the patients,60.5% reported "have felt tense" and 61.4% reported "have felt downhearted" in the past 3 months;feeling tense and/or downhearted in "a lot of the time" or "most of the time",which indicated an emotion disorder,occurred in about 39.9% of the patients.52. 6% of the patients reported sleep disorder in the past 3 months.Constipation occurred prior to emotion and sleep disorders was reported in majority of the patients.Number of medical visit was significantly higher in severe constipation patients co-morbid with emotion disorder when compared with those without emotion disorder(3.92 vs.2.57,P=0.013). Emotion and sleep disorders had no influence on patients' satisfaction to treatment(P=0.286). A high proportion of severe constipation patients reported that constipation had significant impact on daily life and health status.Conclusions: Patients with FC are often co-morbid with emotion and sleep disorders.Severity of constipation is the main influential factor for daily life and health status of FC patients.Emotion disorder may increase the number of medical visit for severe constipation patients.
Conformational ensembles of an RNA hairpin using molecular dynamics and sparse NMR data

Abstract Solution nuclear magnetic resonance (NMR) experiments allow RNA dynamics to be determined in an aqueous environment. However, when a limited number of peaks are assigned, it is difficult to obtain structural information. We here show a protocol based on the combination of experimental data (Nuclear Overhauser Effect, NOE) and molecular dynamics simulations with enhanced sampling methods. This protocol allows to (a) obtain a maximum entropy ensemble compatible with NMR restraints and (b) obtain a minimal set of metastable conformations compatible with the experimental data (maximum parsimony). The method is applied to a hairpin of 29 nt from an inverted SINEB2, which is part of the SINEUP family and has been shown to enhance protein translation. A clustering procedure is introduced where the annotation of base-base interactions and glycosidic bond angles is used as a metric. By reweighting the contributions of the clusters, minimal sets of four conformations could be found which are compatible with the experimental data. A motif search on the structural database showed that some identified low-population states are present in experimental structures of other RNA transcripts. The introduced method can be applied to characterize RNA dynamics in systems where a limited amount of NMR information is available.
TSLP Production in the Human Infant Airway Epithelium and Clinical Relevance during Viral Respiratory Infections.

Studies using human airway epithelial cells (AECs) derived from adults with asthma have confirmed that type 2 airway epithelial cytokines, such as TSLP (thymic stromal lymphopoietin), are key mediators in the pathogenesis of the disease (1), and this fundamental knowledge has led to the discovery of novel asthma therapies (2). In contrast, the airway epithelium of human infants has been remarkably understudied despite compelling evidence that asthma often begins in early life (3). In addition, prior studies have established that airway secretion of TSLP occurs during viral respiratory infections in young children (4, 5). Thus, our goal in this human-based study was to characterize the production of TSLP in vitro in primary infant AECs and in vivo during natural viral respiratory infections in human infants. This study was approved by the Institutional Review Board of Children’s National Health System and included parental informed consent.
Disentangling the Contributions of Plant Taxonomic and Functional Diversities in Shaping Aboveground Biomass of a Restored Forest Landscape in Southern China

Restoration is essential for supporting key ecosystem functions such as aboveground biomass production. However, the relative importance of functional versus taxonomic diversity in predicting aboveground biomass during restoration is poorly studied. Here, we used a trait-based approach to test for the importance of multiple plant diversity attributes in regulating aboveground biomass in a 30-years-old restored subtropical forest in southern China. We show that both taxonomic and functional diversities are significant and positive regulators of aboveground biomass; however, functional diversity (FD) was more important than taxonomic diversity (species richness) in controlling aboveground biomass. FD had the strongest direct effect on aboveground biomass compared with species richness, soil nutrients, and community weighted mean (CWM) traits. Our results further indicate that leaf and root morphological traits and traits related to the nutrient content in plant tissues represent the existence of a leaf and root economic spectrum, and the acquisitive resource use strategy influenced aboveground biomass. Our results suggest that both taxonomic and FD play a role in shaping aboveground biomass, but FD is more important in supporting aboveground biomass in this type of environments. These results imply that enhancing FD is important to restoring and managing degraded forest landscapes.
Degenerative Cervical Myelopathy in Higher-Aged Patients: How Do They Benefit from Surgery?

Background: Degenerative cervical myelopathy (DCM) is the most common reason for spinal cord disease in elderly patients. This study analyzes the preoperative status and postoperative outcome of higher-aged patients in comparison to young and elderly patients in order to determine the benefit to those patients from DCM surgery. Methods: A retrospective analysis of the clinical data, radiological findings, and operative reports of 411 patients treated surgically between 2007 and 2016 suffering from DCM was performed. The preoperative and postoperative neurological functions were evaluated using the modified Japanese Orthopedic Association Score (mJOA Score), the postoperative mJOA Score improvement, the neurological recovery rate (NRR) of the mJOA Score, and the minimum clinically important difference (MCID). The Charlson Comorbidity Index (CCI) was used to evaluate the impact of comorbidities on the preoperative and postoperative mJOA Score. The comparisons were performed between the following age groups: G1: ≤50 years, G2: 51–70 years, and G3: >70 years. Results: The preoperative and postoperative mJOA Score was significantly lower in G3 than in G2 and G1 (p < 0.0001). However, the mean mJOA Score’s improvement did not differ significantly (p = 0.81) between those groups six months after surgery (G1: 1.99 ± 1.04, G2: 2.01 ± 1.04, G: 2.00 ± 0.91). Furthermore, the MCID showed a significant improvement in every age-group. The CCI was evaluated for each age-group, showing a statistically significant group effect (p < 0.0001). Analysis of variance revealed a significant group effect on the delay (weeks) between symptom onset and surgery (p = 0.003). The duration of the stay at the hospital did differ significantly between the age groups (p < 0.0001). Conclusion: Preoperative and postoperative mJOA Scores, but not the extent of postoperative improvement, are affected by the patients’ age. Therefore, patients should be considered for DCM surgery regardless of their age.
“It’s Like a Death Sentence but It Really Isn’t” What Patients and Families Want to Know About Hospice Care When Making End-of-Life Decisions

Background: Hospice is underutilized, due to both lack of initiation from patients and late referral from clinicians. Prior research has suggested the reasons for underuse are multifactorial, including clinician and patient lack of understanding, misperceptions about the nature of hospice care, and poor communication during end-of-life discussions about hospice care. Little is known about the decisional needs of patients and families engaging in hospice decision-making. Objectives: To understand the decisional needs of patients and families making decisions about hospice care. Methods: We conducted focus groups with family caregivers and hospice providers and one-on-one interviews with patients considering or enrolled in hospice care. We identified participants through purposeful and snowball sampling methods. All interviews were transcribed verbatim and analyzed using a grounded theory approach. Results: Four patients, 32 family caregivers, and 27 hospice providers participated in the study. Four main themes around decisional needs emerged from the interviews and focus groups: (1) What is hospice care? ; (2) Why might hospice care be helpful? ; (3) Where is hospice care provided? ; and (4) How is hospice care paid for? Discussion: Hospice may not be the right treatment choice for all with terminal illness. Our study highlights where patients’ and families’ understanding could be enhanced to assure that they have the opportunity to benefit from hospice, if they so desire.
Differential Evolution for the Optimization of DMSO-free Cryoprotectants: Influence of Control Parameters.

This study presents the influence of control parameters including population size, mutation factor, crossover and four types of differential evolution algorithms including random, best, local-to-best and local-to-best with self-adaptive modification for the purpose of optimizing the compositions of DMSO-free cryoprotectants. Post-thaw recovery of Jurkat cells cryopreserved with two DMSO-free cryoprotectants displayed a non-linear, 4-dimensional structure with multiple saddle nodes, which was a suitable training model to tune the control parameters and select the most appropriate type of differential evolution algorithm. Self-adaptive modification presented better performance in terms of optimization accuracy and sensitivity of mutation factor and crossover among the four different types of algorithms tested. Specifically, the classical type of differential evolution algorithm exhibited a wide acceptance to mutation factor and crossover. The optimization performance is more sensitive to mutation than crossover and the optimization accuracy is proportional to the population size. Increasing population size also reduce the sensitivity of the algorithm to the value of the mutation factor and crossover. The analysis of optimization accuracy and convergence speed suggests larger population size with F>0.6 and Cr>0.3 are well suited for use with cryopreservation optimization purposes. The tuned differential evolution algorithm is validated through finding global maximums of other two DMSO-free cryoprotectant formulation data sets. The results of these studies can be used to help more efficiently determine the optimal composition of multicomponent DMSO-free cryoprotectants in the future.
Impact of Early Antiretroviral Therapy Initiation on HIV-Specific CD4 and CD8 T Cell Function in Perinatally Infected Children

Key Points HIV-specific T cell responses persist despite long-term viral suppression. Timing of ART initiation impacts the quality of the HIV-specific T cell responses. Baseline PBMC transcriptome is different in HIV-infected children treated early. Early initiation of antiretroviral therapy (ART) in vertically HIV-infected children limits the size of the virus reservoir, but whether the time of treatment initiation (TI) can durably impact host immune responses associated with HIV infection is still unknown. This study was conducted in PBMC of 20 HIV-infected virally suppressed children on ART (mean age 9.4 y), classified as early treated (ET; age at ART initiation ≤0.5 y, n = 14) or late treated (LT; age at ART initiation 1–10 y, n = 6). Frequencies and functions of Ag-specific CD4 (CD40L+) and CD8 (CD69+) T cells were evaluated by intracellular IL-2, IFN-γ, and TNF-α production with IL-21 in CD4 or CD107a, granzyme B and perforin in CD8 T cells following stimulation with HIV gp140 protein (ENV) or GAG peptides by multiparameter flow cytometry. ET showed a higher proportion of cytokine-producing ENV- and GAG-specific CD4 and CD8 T cells compared with LT. In particular, ET were enriched in polyfunctional T cells. RNA sequencing analysis showed upregulation of immune activation pathways in LT compared with ET. Our results suggest that timing of TI in HIV-infected children has a long-term and measurable impact on the quality of the HIV-specific T cell immune responses and transcriptional profiles of PBMC, reinforcing the importance of early TI.
Impact of Donor and Recipient CYP3A5*3 Genotype on Tacrolimus Population Pharmacokinetics in Chinese Adult Liver Transplant Recipients

Background: Tacrolimus (TAC) is widely used after liver transplantation, but the therapeutic window is narrow. Objective: The purpose was to study both donor and recipient CYP3A5*3 genotypes affecting TAC apparent clearance rate (CL/F) and investigate a TAC population pharmacokinetic (PPK) model in Chinese liver transplant recipients for potential starting-dose individualized medication. Methods: A data set of 721 TAC concentrations was obtained from 43 adult liver transplant recipients. The TAC PPK model was analyzed using nonlinear mixed-effects modeling. Potential covariates, including demographic characteristics, physiological and pathological data, concomitant medications, and CYP3A5*3 genotype, were evaluated. The final model was validated using normalized prediction distribution errors and bootstrapping. Results: A 2-compartment model with first-order absorption and elimination was used to describe TAC disposition. Population estimates of TAC, CL/F, apparent central distribution volume (V2/F), rate of absorption (Ka), and apparent peripheral distribution volume (V3/F) were 18.1 L/h (12%), 72.7 L (34%), 0.163 h−1 (17%), and 412 L (21%), respectively. The model and estimated parameters were found to be stable. Other covariates did not influence TAC CL/F. Both donor and recipient CYP3A5*1 genotypes were significantly correlated with TAC clearance, and CL/F was 1.70-fold higher in both donor and recipient CYP3A5*1 carriers than in noncarriers among Chinese liver transplant recipients. Conclusion and Relevance: A PPK model of TAC was established in Chinese adult liver transplantation recipients for starting-dose individualized medication, which can be expanded to optimize clinical efficacy and minimize toxicity with therapeutic drug monitoring.
Kif1c regulates osteoclastic bone resorption as a downstream molecule of p130Cas

Podosome formation in osteoclasts is an important initial step in osteoclastic bone resorption. Mice lacking c‐Src (c‐Src−/−) exhibited osteopetrosis due to a lack of podosome formation in osteoclasts. We previously identified p130Cas (Crk‐associated substrate [Cas]) as one of c‐Src downstream molecule and osteoclast‐specific p130Cas‐deficient (p130CasΔOCL−/−) mice also exhibited a similar phenotype to c‐Src−/− mice, indicating that the c‐Src/p130Cas plays an important role for bone resorption by osteoclasts. In this study, we performed a cDNA microarray and compared the gene profiles of osteoclasts from c‐Src−/− or p130CasΔOCL−/− mice with wild‐type (WT) osteoclasts to identify downstream molecules of c‐Src/p130Cas involved in bone resorption. Among several genes that were commonly downregulated in both c‐Src−/− and p130CasΔOCL−/− osteoclasts, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization. Reduced Kif1c expression was observed in both c‐Src−/− and p130CasΔOCL−/− osteoclasts compared with WT osteoclasts. Kif1c exhibited a broad tissue distribution, including osteoclasts. Knockdown of Kif1c expression using shRNAs in WT osteoclasts suppressed actin ring formation. Kif1c overexpression restored bone resorption subsequent to actin ring formation in p130CasΔOCL−/− osteoclasts but not c‐Src−/− osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas (191 words).
Large phenotypic enhancement of structured random RNA pools.

Laboratory evolution of functional RNAs has applications in many areas of chemical and synthetic biology. In vitro selections critically depend on the presence of functional molecules, such as aptamers and ribozymes, in the starting sequence pools. For selection of novel functions the pools are typically transcribed from random-sequence DNA templates, yielding a highly diverse set of RNAs that contain a multitude of folds and biochemical activities. The phenotypic potential-the frequency of functional RNAs-is very low, requiring large complexity of starting pools, surpassing 10E15 different sequences, to identify highly active isolates. Furthermore, the majority of random sequences is not structured and has a high propensity for aggregation; the in vitro selection process thus involves not just enrichment of functional RNAs, but also their purification from aggregation-prone "free-riders". We reasoned that purification of the non-aggregating, monomeric subpopulation of a random-sequence RNA pool will yield pools of folded, functional RNAs. We performed six rounds of selection for monomeric sequences and show that the enriched population is compactly folded. In vitro selections originating from various mixtures of the compact pool and a fully-random pool showed that sequences from the compact pool always dominate the population once a biochemical activity is detectable. A head-to-head competition of the two pools starting from a low (5E12) sequence diversity revealed that the phenotypic potential of the compact pool is about 1000-times higher than the fully-random pool. A selection for folded and monomeric RNA pools thus greatly increases the frequency of functional RNAs from that seen in random-sequence pools, providing a facile experimental approach to isolation of highly active functional RNAs from low-diversity populations.
Microfluidic Array Chip for Parallel Detection of Waterborne Bacteria

The polymerase chain reaction (PCR) is a robust technique used to make multiple copies of a segment of DNA. However, the available PCR platforms require elaborate and time-consuming operations or costly instruments, hindering their application. Herein, we introduce a sandwiched glass–polydimethylsiloxane (PDMS)–glass microchip containing an array of reactors for the real-time PCR-based detection of multiple waterborne bacteria. The PCR solution was loaded into the array of reactors in a single step utilising capillary filling, eliminating the need for pumps, valves, and liquid handling instruments. Issues of generating and trapping bubbles during the loading chip step were addressed by creating smooth internal reactor surfaces. Triton X-100 was used to enhance PCR compatibility in the chip by minimising the nonspecific adsorption of enzymes. A custom-made real-time PCR instrument was also fabricated to provide thermal cycling to the array chip. The microfluidic device was successfully demonstrated for microbial faecal source tracking (MST) in water.
Gut Microbial Metabolites and Biochemical Pathways Involved in Irritable Bowel Syndrome: Effects of Diet and Nutrition on the Microbiome

ABSTRACT The food we consume and its interactions with the host and their gut microbiota affect normal gut function and health. Functional gut disorders (FGDs), including irritable bowel syndrome (IBS), can result from negative effects of these interactions, leading to a reduced quality of life. Certain foods exacerbate or reduce the severity and prevalence of FGD symptoms. IBS can be used as a model of perturbation from normal gut function with which to study the impact of foods and diets on the severity and symptoms of FGDs and understand how critical processes and biochemical mechanisms contribute to this impact. Analyzing the complex interactions between food, host, and microbial metabolites gives insights into the pathways and processes occurring in the gut which contribute to FGDs. The following review is a critical discussion of the literature regarding metabolic pathways and dietary interventions relevant to FGDs. Many metabolites, for example bile acids, SCFAs, vitamins, amino acids, and neurotransmitters, can be altered by dietary intake, and could be valuable for identifying perturbations in metabolic pathways that distinguish a “normal, healthy” gut from a “dysfunctional, unhealthy” gut. Dietary interventions for reducing symptoms of FGDs are becoming more prevalent, but studies investigating the underlying mechanisms linked to host, microbiome, and metabolite interactions are less common. Therefore, we aim to evaluate the recent literature to assist with further progression of research in this field.
Housing situation and healthcare for patients in a psychiatric centre in Berlin, Germany: a cross-sectional patient survey

Objective To determine the housing situation among people seeking psychiatric treatment in relation to morbidity and service utilisation. Design Cross-sectional patient survey. Setting Psychiatric centre with a defined catchment area in Berlin, Germany, March–September 2016. Participants 540 psychiatric inpatients including day clinics (43.2% of all admitted patients in the study period (n=1251)). Main outcome measures Housing status 30 days prior the interview as well as influencing variables including service use, psychiatric morbidity and sociodemographic variables. Results In our survey, 327 participants (68.7%) currently rented or owned an own apartment; 62 (13.0%) reported to be homeless (living on the street or in shelters for homeless or refugees); 87 (18.3%) were accommodated in sociotherapeutic facilities. Participants without an own apartment were more likely to be male and younger and to have a lower level of education. Homeless participants were diagnosed with a substance use disorder significantly more often (74.2%). Psychotic disorders were the highest among homeless participants (29.0%). Concerning service use, we did neither find a lower utilisation of ambulatory services nor a higher utilisation of hospital-based care among homeless participants. Conclusions Our findings underline the need for effective housing for people with mental illness. Despite many sociotherapeutic facilities, a concerning number of people with mental illness is living in homelessness. Especially early interventions addressing substance use might prevent future homelessness.