Miracle-dz/UniFAR-FTUs huggingface dataset:
The response of culturally important plants to experimental warming and clipping in Pakistan Himalayas

The relative effects of climate warming with grazing on medicinally important plants are not fully understood in Hindukush-Himalaya (HKH) region. Therefore, we combined the indigenous knowledge about culturally important therapeutic plants and climate change with experimental warming (open-top chambers) and manual clipping (simulated grazing effect) and compared the relative difference on aboveground biomass and percent cover of plant species at five alpine meadow sites on an elevation gradient (4696 m-3346 m) from 2016–2018. Experimental warming increased biomass and percent cover throughout the experiment. However, the interactive treatment effect (warming x clipping) was significant on biomass but not on percent cover. These responses were taxa specific. Warming induced an increase of 1 ± 0.6% in Bistorta officinalis percent cover while for Poa alpina it was 18.7 ± 4.9%. Contrastingly, clipping had a marginally significant effect in reducing the biomass and cover of all plant species. Clipping treatment reduced vegetation cover & biomass by 2.3% and 6.26%, respectively, but that was not significant due to the high variability among taxa response at different sites. It was found that clipping decreased the effects of warming in interactive plots. Thus, warming may increase the availability of therapeutic plants for indigenous people while overgrazing would have deteriorating effects locally. The findings of this research illustrate that vegetation sensitivity to warming and overgrazing is likely to affect man–environment relationships, and traditional knowledge on a regional scale.
From neural stem cells to glioblastoma: A natural history of GBM recapitulated in vitro

Due to its aggressive and invasive nature glioblastoma (GBM), the most common and aggressive primary brain tumour in adults, remains almost invariably lethal. Significant advances in the last several years have elucidated much of the molecular and genetic complexities of GBM. However, GBM exhibits a vast genetic variation and a wide diversity of phenotypes that have complicated the development of effective therapeutic strategies. This complex pathogenesis makes necessary the development of experimental models that could be used to further understand the disease, and also to provide a more realistic testing ground for potential therapies. In this report, we describe the process of transformation of primary mouse embryo astrocytes into immortalized cultures with neural stem cell characteristics, that are able to generate GBM when injected into the brain of C57BL/6 mice, or heterotopic tumours when injected IV. Overall, our results show that oncogenic transformation is the fate of NSC if cultured for long periods in vitro. In addition, as no additional hit is necessary to induce the oncogenic transformation, our model may be used to investigate the pathogenesis of gliomagenesis and to test the effectiveness of different drugs throughout the natural history of GBM.
Machine learning of EEG spectra classifies unconsciousness during GABAergic anesthesia

In current anesthesiology practice, anesthesiologists infer the state of unconsciousness without directly monitoring the brain. Drug- and patient-specific electroencephalographic (EEG) signatures of anesthesia-induced unconsciousness have been identified previously. We applied machine learning approaches to construct classification models for real-time tracking of unconscious state during anesthesia-induced unconsciousness. We used cross-validation to select and train the best performing models using 33,159 2s segments of EEG data recorded from 7 healthy volunteers who received increasing infusions of propofol while responding to stimuli to directly assess unconsciousness. Cross-validated models of unconsciousness performed very well when tested on 13,929 2s EEG segments from 3 left-out volunteers collected under the same conditions (median volunteer AUCs 0.99-0.99). Models showed strong generalization when tested on a cohort of 27 surgical patients receiving solely propofol collected in a separate clinical dataset under different circumstances and using different hardware (median patient AUCs 0.95—0.98), with model predictions corresponding with actions taken by the anesthesiologist during the cases. Performance was also strong for 17 patients receiving sevoflurane (alone or in addition to propofol) (median AUCs 0.88—0.92). These results indicate that EEG spectral features can predict unconsciousness, even when tested on a different anesthetic that acts with a similar neural mechanism. With high performance predictions of unconsciousness, we can accurately monitor anesthetic state, and this approach may be used to engineer infusion pumps to intelligibly respond to patients’ neural activity.
Diverse changes in microglia morphology and axonal pathology during the course of 1 year after mild traumatic brain injury in pigs

Over 2.8 million people experience mild traumatic brain injury (TBI) in the United States each year, which may lead to long‐term neurological dysfunction. The mechanical forces that are caused by TBI propagate through the brain to produce diffuse axonal injury (DAI) and trigger secondary neuroinflammatory cascades. The cascades may persist from acute to chronic time points after injury, altering the homeostasis of the brain. However, the relationship between the hallmark axonal pathology of diffuse TBI and potential changes in glial cell activation or morphology have not been established in a clinically relevant large animal model at chronic time points. In this study, we assessed the tissue from pigs subjected to rapid head rotation in the coronal plane to generate mild TBI. Neuropathological assessments for axonal pathology, microglial morphological changes, and astrocyte reactivity were conducted in specimens out to 1‐year post‐injury. We detected an increase in overall amyloid precursor protein pathology, as well as periventricular white matter and fimbria/fornix pathology after a single mild TBI. We did not detect the changes in corpus callosum integrity or astrocyte reactivity. However, detailed microglial skeletal analysis revealed changes in morphology, most notably increases in the number of microglial branches, junctions, and endpoints. These subtle changes were most evident in periventricular white matter and certain hippocampal subfields, and were observed out to 1‐year post‐injury in some cases. These ongoing morphological alterations suggest persistent change in neuroimmune homeostasis. Additional studies are needed to characterize the underlying molecular and neurophysiological alterations, as well as potential contributions to neurological deficits.
Treatment challenges in adult female acne and future directions

ABSTRACT Introduction: Acne is a chronic, inflammatory, and immune-mediated disease of the pilosebaceous unit, highly prevalent in adolescents. However, an increasing number of adults over 25 years old with facial acne, particularly women, have been observed. It is considered a different disease when compared to acne vulgaris. Face is the mainly involved area with inflammatory lesions and more sensitive skin, pointing out the need of a holistic approach. Areas covered: We performed a comprehensive literature search on PubMed database, up to January 2021, regarding adult female acne. We synthesized data about pathogenesis; differences compared to acne vulgaris; and treatment, with focus in the management challenges and perspectives. Expert opinion: It is essential to value the negative impact on quality of life of adult female acne, independently of severity. The disease has prolonged evolution, and patient might be resilient once the improvement, regardless of the treatment option, will just be noticeable after 3 months. Aggravating factors should be clearly discussed, such as the need of changing many habits, especially lesions manipulation. The therapeutic regimen includes make-up and tailored skin care (considering proneness to sensitivity), while anti-acne drugs should be chosen in accordance with desire to be pregnant, presence of pregnancy or breastfeeding.
Examining rumination, devaluation of positivity, and depressive symptoms via community-based network analysis.

OBJECTIVE Components of rumination, including brooding and reflection, as well as devaluating prospective positivity, may help maintain depressive symptoms. We examined these components together for the first time using network analysis. METHODS We examined the robustness of rumination communities of closely related items in one network and then examined the interrelationships between rumination communities, devaluation of positivity, and depression, in a second network. RESULTS Three rumination communities emerged, replicating findings of Bernstein et al. Within a dense network, nodes representing brooding, reflective pondering, and difficulty trusting positive feelings were most influential. In addition, the node representing the depressive symptom negative self-views shared strong edges with nodes representing devaluation of positivity and brooding. CONCLUSION Brooding, reflective pondering, and elements of devaluing positivity are influential to depressive symptoms and may be important future experimental and therapeutic targets. Depressed individuals with negative self-views may engage in brooding and devalue their experience of positivity.
Pediatric high users of Canadian hospitals and emergency departments

Introduction Few studies have examined the most frequent pediatric users of hospital services. Our objective was to determine the clinical diagnoses, demographic characteristics, and medical severity of high-use pediatric patients in Canada. Methods We conducted a retrospective analysis of patients <18 years of age who either were admitted to hospital or visited an emergency department (ED) using the Canadian Institute for Health Information’s (CIHI) Dynamic Cohort of Complex, High System Users. The analysis of hospital admission data excluded Quebec and Manitoba. ED data was only available for Alberta and Ontario. Results 121 104 patients were identified as the most frequent hospital users and 459 998 patients as the most frequent ED users. High users were more likely to reside in a rural community, to be in a lower income quintile, and face more deprivation. The most frequent conditions for hospitalization for high use patients were disorders related to length of prematurity and fetal growth, respiratory and cardiovascular disorders specific to the perinatal period, and haemorrhagic and haematological disorders of fetus and newborn. For the most frequent ED users, the most common clinical diagnoses were acute upper respiratory infections, injuries to the head, and diseases of the middle ear and mastoid. Conclusion Pediatric high users by frequency of hospital and ED services are a distinct population. Better understanding their characteristics will allow for more appropriate planning of children’s health services and help identify areas for effective preventive or quality improvement initiatives.
Sexual conflict in a changing environment

Sexual conflict has extremely important consequences for various evolutionary processes including its effect on local adaptation and extinction probability during environmental change. The awareness that the intensity and dynamics of sexual conflict is highly dependent on the ecological setting of a population has grown in recent years, but much work is yet to be done. Here, we review progress in our understanding of the ecology of sexual conflict and how the environmental sensitivity of such conflict feeds back into population adaptivity and demography, which, in turn, determine a population's chances of surviving a sudden environmental change. We link two possible forms of sexual conflict – intralocus and interlocus sexual conflict – in an environmental context and identify major gaps in our knowledge. These include sexual conflict responses to fluctuating and oscillating environmental changes and its influence on the interplay between interlocus and intralocus sexual conflict, among others. We also highlight the need to move our investigations into more natural settings and to investigate sexual conflict dynamics in wild populations.
Combination therapy with tocilizumab and dexamethasone cost-effectively reduces Coronavirus disease 2019 mortality

Abstract Recent randomized trials suggest that interleukin-6 inhibitors like tocilizumab have mortality benefit for patients with severe coronavirus disease-2019. We employed a decision tree to investigate their cost-effectiveness and found that tocilizumab is cost-effective with an estimated incremental cost-effectiveness ratio of $16520 per quality-adjusted life year gained (95% credible interval 10760-51530).
Correlations between DW‐MRI and 18F‐FDG PET/CT parameters in head and neck squamous cell carcinoma following definitive chemo‐radiotherapy

Posttreatment diffusion–weighted magnetic resonance imaging (DW‐MRI) and 18F‐fluorodeoxygluocose (18F‐FDG) positron emission tomography (PET) with computed tomography (PET/CT) have potential prognostic value following chemo‐radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). Correlations between these PET/CT (standardized uptake value or SUV) and DW‐MRI (apparent diffusion coefficient or ADC) parameters have only been previously explored in the pretreatment setting.
Classes of drugs that target the cellular components of inflammation under clinical development for COPD

ABSTRACT Introduction The persistent inflammation that characterizes COPD and affects its natural course also impacting on symptoms has prompted research to find molecules that can regulate the inflammatory process but still available anti-inflammatory therapies provide little or no benefit in COPD patients. Consequently, numerous anti-inflammatory molecules that are effective in animal models of COPD have been or are being evaluated in humans. Areas covered In this article we describe several classes of drugs that target the cellular components of inflammation under clinical development for COPD. Expert opinion Although the results of many clinical trials with new molecules have often been disappointing, several studies are underway to investigate whether some of these molecules may be effective in treating specific subgroups of COPD patients. Indeed, the current perspective is to apply a more personalized treatment to the patient. This means being able to better define the patient’s inflammatory state and treat it in a targeted manner. Unfortunately, the difficulty in translating encouraging experimental data into human clinical trials, the redundancy in the effects induced by signal-transmitting substances and the nonspecific effects of many classes that are undergoing clinical trials, do not yet allow specific inflammatory cell types to be targeted.
Genome-wide association study of cardiac troponin I in the general population

Abstract Circulating cardiac troponin proteins are associated with structural heart disease and predict incident cardiovascular disease in the general population. However, the genetic contribution to cardiac troponin I (cTnI) concentrations and its causal effect on cardiovascular phenotypes are unclear. We combine data from two large population-based studies, the Trøndelag Health Study and the Generation Scotland Scottish Family Health Study, and perform a genome-wide association study of high-sensitivity cTnI concentrations with 48 115 individuals. We further use two-sample Mendelian randomization to investigate the causal effects of circulating cTnI on acute myocardial infarction (AMI) and heart failure (HF). We identified 12 genetic loci (8 novel) associated with cTnI concentrations. Associated protein-altering variants highlighted putative functional genes: CAND2, HABP2, ANO5, APOH, FHOD3, TNFAIP2, KLKB1 and LMAN1. Phenome-wide association tests in 1688 phecodes and 83 continuous traits in UK Biobank showed associations between a genetic risk score for cTnI and cardiac arrhythmias, metabolic and anthropometric measures. Using two-sample Mendelian randomization, we confirmed the non-causal role of cTnI in AMI (5948 cases, 355 246 controls). We found indications for a causal role of cTnI in HF (47 309 cases and 930 014 controls), but this was not supported by secondary analyses using left ventricular mass as outcome (18 257 individuals). Our findings clarify the biology underlying the heritable contribution to circulating cTnI and support cTnI as a non-causal biomarker for AMI in the general population. Using genetically informed methods for causal inference helps inform the role and value of measuring cTnI in the general population.
An exploratory, cross-sectional and multi-institutional study using three instruments to examine student perceptions of interprofessional education

ABSTRACT Interprofessional education (IPE) research needs to expand beyond single site, single event inquiry. Multi-institutional studies increase methodologic rigor and generalizability, advancing the pedagogical science of IPE. Four U.S. institutions used three different validated measures to examine early learner interprofessional outcomes. The three assessment tools included the Communication and Teamwork subscale of the University of West England Entry Level Interprofessional Questionnaire (UWE-ELIQ), the Self-Assessed Collaboration Skills (SACS), and the Interprofessional Teamwork and Team-based Practice factor of the Student Perceptions of Interprofessional Clinical Education-Revised, version 2 (SPICE-R2). Across the four institutions, 659 eligible participants, representing 19 programs completed the pre-survey, and 385 completed the post-survey. The UWE-ELIQ showed a statistically significant difference between the pre- and post-survey overall, but the effect size was small. One institution demonstrated a positive change in scores on the UWE-ELIQ with a small effect size, while the other institutions saw no significant change. Two institutions observed lower post-survey scores on the SPICE-R2. Cumulative results from the study indicated no statistically significant change from pre- to post- in total SACS or SPICE-R2 scores. Additional multi-site longitudinal research is needed to investigate use of validated instruments, as well as the impact of curricula and learning environment on educational outcomes.
Loss of function MPZ mutation causes milder CMT1B neuropathy

Mutations in Myelin Protein Zero (MPZ) cause CMT1B, the second leading cause of CMT1. Many of the >200 mutations cause neuropathy through a toxic gain of function by the mutant protein such as ER retention, activation of the Unfolded Protein Response (UPR) or disruption of myelin compaction. While there is extensive literature on the loss of function consequences of MPZ in heterozygous Mpz +/− null mice, there is little known of the consequences of MPZ haploinsufficiency in humans. We identified six patients from different families with p.Tyr68Ter or p.Asp104fs heterozygous mutations of MPZ that are predicted to cause a premature termination and nonsense mediated decay of the mutant allele. Five patients were evaluated in Milan and one in Iowa City; all should be haploinsufficient for MPZ. Patients were evaluated clinically and by electrophysiology. Sensory ataxia dominated the clinical presentation with only mild weakness present in five of the six patients. Symptoms presented in adulthood in all patients and only one individual had a CMTNSv2 >5. Deep tendon reflexes were absent in all patients. Patients with likely MPZ loss of function due to mutations that cause haplodeficiency in MPZ have a mild, predominantly large fiber sensory neuropathy that serves as a human equivalent to the neuropathy observed in heterozygous Mpz null mice. Successful therapeutic approaches in treating Mpz deficient mice may be candidates for trials in these and similar patients.
The impact of SARS-COV2 infection on people in residential care with Parkinson Disease or parkinsonisms: Clinical case series study

On March 2019 the World Health Organization declared Coronavirus disease (COVID-19) pandemic. Several recent reports disclose that the outcome of the infection is related to age, sex and can be influenced by underlying clinical conditions. Parkinson’s disease (PD) and other parkinsonisms are the most common chronic disease which can cause, directly or indirectly, the patient to be more exposed to other diseases, mostly respiratory system’s ones. Our primary outcome is to evaluate if PD patients are more susceptible than non-PD to take COVID-19 infection. Second, to detect if the infection course is worse in PD-COVID+ patients versus non-PD. This is a retrospective observational study on a cohort of 18 patients (13 PD– 5 non-PD), hospitalized in a Rehabilitative Unit during the occurrence of SARS-CoV2 epidemic outbreak. All patients performed laboratory tests, lung Computed Tomography (CT) and have been tested for COVID-19 thorough pharyngeal swab. PD and non-PD groups were comparable for age, gender and Hoehn and Yahr stage. Seventy-seven (77)% of PD and 60% of non-PD resulted positive for COVID-19. PD-COVID+ and PD-COVID- did not differ for age, disease duration and L-dopa daily dose. PD COVID-19+ subjects were mainly asymptomatic (50%) while non-PD ones were all symptomatic, mostly with respiratory difficulties. PD doesn’t seem to be a risk factor to take SARS-COV2 infection, even if our study is related to a limited sample size. Our results, together with those of other recent studies, highlight the need to evaluate the actual susceptibility of patients with Parkinson’s disease to develop COVID-19 disease, and how the infection may influence the risk of clinical worsening and increase of mortality.
Cross-Cultural Adaptation and Reliability Testing of Arabic Versions of Several Diabetic Foot Psychosocial Scales

The main aims of this study were cross-cultural adaptation and reliability testing of an Arabic version of Foot Care Confidence Scale (FCCS), Foot Care Outcomes Expectations Scale (FCOES), Patient Interpretation of Neuropathy Scales (PINS), Neuropathy-specific Quality of Life Scales (NQOLS), and offloading-related Visual Analog Scales (VAS). Two phases of translation and reliability testing were conducted in Jordan. Phase 1 included 2 forward and backward translations with 2 panel consensuses (translators, clinicians, and experts). In Phase 2, Cronbach’s alpha (α) and intraclass correlation coefficient (ICC) were used to test the internal consistency and stability (test–retest) of the Arabic scales in a sample of a total of 90 Jordanian participants with diabetic foot ulcers. Phase 1 resulted in Arabic translation and cross-cultural adaptation of the study scales. Phase 2 resulted in acceptable internal consistency of the translated scales (α = 0.74-0.91), except for the PIN “self/practitioner blame” and “acute ulcer onset” scales (α = 0.57, 0.49, respectively). Test–retest results (ICC) were: FCCS (0.85); FCOES (0.78); PINS (0.043-0.85); NQOLS (0.76-0.90); and offloading-related VAS (0.43-0.90). This study showed evidence of cultural appropriateness and reliability of most of the translated scales, for possible future implementation for the Arabic population.