Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of electrophysical agents in fibromyalgia: A systematic review and network meta-analysis

Objective To examine the effectiveness of electrophysical agents in fibromyalgia. Data sources CINAHL, Cochrane Library, Embase, Medline, PEDro, and Web of Science were searched from their inceptions to March 27, 2023. Methods This study was registered in PROSPERO (CRD42022354326). Methodological quality of included trials was assessed using PEDro scale, and the quality of evidence was determined according to the Grading of Recommendations Assessment, Development, and Evaluation system. The primary outcomes were pain, functional status, and mood. Results Fifty-four studies involving 3045 patients with fibromyalgia were eligible for qualitative synthesis and 47 (pain), 31 (functional status), and 26 (mood) for network meta-analysis. The network consistency model revealed that, when compared with true control, transcutaneous electrical nerve stimulation and microcurrent improved pain symptoms (P = 0.006 and P = 0.037, respectively); repetitive transcranial magnetic stimulation improved patient functional status (P = 0.018); and microcurrent (P = 0.001), repetitive transcranial magnetic stimulation (P = 0.022), and no treatment (P = 0.038) significantly improved mood after intervention. Surface under the cumulative ranking indicated that microcurrent was most likely to be the best for managing pain and mood (surface under the cumulative ranking: 70% and 100%, respectively); low-level laser therapy for pain and mood (80% and 70%, respectively); and repetitive transcranial magnetic stimulation for improving functional status and mood (80% and 70%, respectively). Conclusion This review found low to moderate quality evidence that microcurrent, laser therapy, and repetitive transcranial magnetic stimulation are the most effective electrophysical agents for improving at least one outcome in fibromyalgia.
Escalation to intensive care for the older patient. An exploratory qualitative study of patients aged 65 years and older and their next of kin during the COVID-19 pandemic: the ESCALATE study

Abstract Background older people comprise the majority of hospital medical inpatients so decision-making regarding admission of this cohort to the intensive care unit (ICU) is important. ICU can be perceived by clinicians as overly burdensome for patients and loved ones, and long-term impact on quality of life considered unacceptable, effecting potential bias against admitting older people to ICU. The COVID-19 pandemic highlighted the challenge of selecting those who could most benefit from ICU. Objective this qualitative study aimed to explore the views and recollections of escalation to ICU from older patients (aged ≥ 65 years) and next of kin (NoK) who experienced a COVID-19 ICU admission. Setting the main site was a large NHS Trust in London, which experienced a high burden of COVID-19 cases. Subjects 30 participants, comprising 12 patients, 7 NoK of survivor and 11 NoK of deceased. Methods semi-structured interviews with thematic analysis using a framework approach. Results there were five major themes: inevitability, disconnect, acceptance, implications for future decision-making and unique impact of the COVID-19 pandemic. Life was highly valued and ICU perceived to be the only option. Prior understanding of ICU and admission decision-making explanations were limited. Despite benefit of hindsight, having experienced an ICU admission and its consequences, most could not conceptualise thresholds for future acceptable treatment outcomes. Conclusions in this study of patients ≥65 years and their NoK experiencing an acute ICU admission, survival was prioritised. Despite the ordeal of an ICU stay and its aftermath, the decision to admit and sequelae were considered acceptable.
MicroRNA-708 emerges as a potential candidate to target undruggable NRAS

RAS, the most frequently mutated oncogene that drives tumorigenesis by promoting cell proliferation, survival, and motility, has been perceived as undruggable for the past three decades. However, intense research in the past has mainly focused on KRAS mutations, and targeted therapy for NRAS mutations remains an unmet medical need. NRAS mutation is frequently observed in several cancer types, including melanoma (15–20%), leukemia (10%), and occasionally other cancer types. Here, we report using miRNA-708, which targets the distinct 3’ untranslated region (3’UTR) of NRAS, to develop miRNA-based precision medicine to treat NRAS mutation-driven cancers. We first confirmed that NRAS is a direct target of miRNA-708. Overexpression of miRNA-708 successfully reduced NRAS protein levels in melanoma, leukemia, and lung cancer cell lines with NRAS mutations, resulting in suppressed cell proliferation, anchorage-independent growth, and promotion of reactive oxygen species-induced apoptosis. Consistent with the functional data, the activities of NRAS-downstream effectors, the PI3K-AKT-mTOR or RAF-MEK-ERK signaling pathway, were impaired in miR-708 overexpressing cells. On the other hand, cell proliferation was not disturbed by miRNA-708 in cell lines carrying wild-type NRAS. Collectively, our data unveil the therapeutic potential of using miRNA-708 in NRAS mutation-driven cancers through direct depletion of constitutively active NRAS and thus inhibition of its downstream effectors to decelerate cancer progression. Harnessing the beneficial effects of miR-708 may therefore offer a potential avenue for small RNA-mediated precision medicine in cancer treatment.
Effects of short birth interval on different forms of child mortality in Bangladesh: Application of propensity score matching technique with inverse probability of treatment weighting

Background The prevalence of Short Birth Interval (SBI) is higher in Low- and Middle-Income countries (LMICs), including Bangladesh. Previous studies in LMICs have estimated the effects of SBI on child mortality by comparing two unequal groups of mothers based on their socio-economic status. This approach may lead to overestimation or underestimation of the true effect of birth interval on child mortality, particularly when sample sizes are relatively small. Objective We determined the effects of SBI on several forms of child mortality in Bangladesh by comparing two equal groups created by applying the propensity score matching technique. Methods This study analyzed data from 5,941 mothers and 1,594 health facilities extracted from the 2017/18 Bangladesh Demographic and Health Survey and the 2017 Bangladesh Health Facility Survey. The exposure variable was SBI (defined as the interval between two subsequent births <33 months: yes, no), while the outcome variables were neonatal mortality (defined as mortality within 28 days of birth: yes, no), infant mortality (defined as mortality within 1 year of birth: yes, no), and under-five mortality (defined as mortality within 5 years of birth: yes, no). Multilevel Poisson regression based on inverse probability treatment weights was used to determine the association between exposure and outcome variables. Results The prevalence rates of neonatal, infant, and under-five mortality were 48.8, 30.8, and 23.1 per 1000 live births, respectively. Newborns of SBI mothers were found to have a 63% higher likelihood of neonatal mortality (aPR, 1.63; 95% CI, 1.08–2.46) compared to newborns of non-SBI mothers. Furthermore, the prevalence of infant mortality and under-five mortality was 1.45 times higher (aPR, 1.45; 95% CI, 1.01–2.08) and 2.82 times higher (aPR, 2.82; 95% CI, 2.16–3.70), respectively, among babies born in a short interval of their immediately preceding sibling as compared to babies born in a normal interval of their immediately preceding sibling. Conclusions Findings of this study indicate that SBI is an important predictor of child mortality. Consequently, around 1 million children born in a short interval every year in Bangladesh are at risk of dying before reaching their fifth birthday. This indicates a challenge for Bangladesh to achieve the SDG 3 target to reduce neonatal and under-five mortality to 12 and 25 deaths per 1000 live births, respectively. Hence, awareness-building programs about the adverse effects of SBI and strengthening existing healthcare facilities are important.
IRF4 rearrangement may predict favorable prognosis in children and young adults with primary head and neck large B‐cell lymphoma

Large B‐cell lymphoma with IRF4 rearrangement (LBCL, IRF4+) has been recently recognized as a specific entity that is frequently associated with young age and favorable prognosis. However, whether the good outcome of the disease is due to IRF4+ or other factors remains obscure. We thus analyzed 100 young patients with primary head and neck LBCL to see the clinicopathologic correlates of IRF4+.
A sting in the tail—are antibodies against the C‐terminus of Plasmodium falciparum circumsporozoite protein protective?

Malaria remains a huge burden on global public health. Annually there are more than 200 million cases with > 600,000 deaths worldwide, the vast majority of which occur within Sub‐Saharan Africa (WHO; World Malaria Report, 2021). Malaria disease is the consequence of infection by a protozoan parasite from the genus Plasmodium with most morbidity and mortality caused by P. falciparum. With rates of infection plateauing and rebounding in some areas (in particular, as a result of the disruption caused by the COVID‐19 pandemic), there have been increasing calls for new initiatives that can reduce malaria incidence towards local elimination or the hoped for goal of global eradication. In 2021, the World Health Organisation approved the first malaria vaccine RTS,S/AS01 (also called Mosquirix™), indicating it to be safe for use in young children and advocating its integration into routine immunisation programmes. Approval of this vaccine clearly represents a major landmark in global efforts towards malaria control and eradication aspirations. RTS,S modest efficacy, however, points at the need to better understand immune responses to the parasite if we hope to design next generation malaria vaccines with increased potency.
The Clinical Utility of Relative Bradycardia for Identifying Cases of Coronavirus Disease 2019 Pneumonia: A Retrospective Pneumonia Cohort Study

Objective Both coronavirus disease 2019 (COVID-19) pneumonia and relative bradycardia are common conditions among clinicians; however, the association between these has not been well studied. The present study assessed whether or not relative bradycardia on admission was more predominant in patients with COVID-19 pneumonia than in those with other infectious pneumonia. Methods For this single-center, retrospective cohort study, we collected data through electronic medical records and examined the occurrence of relative bradycardia on admission. We used logistic regression analyses to compare outcomes with and without relative bradycardia on admission. The primary outcome was COVID-19 pneumonia. The secondary outcome was hypoxemia during the hospital stay. We performed multivariable regression with adjusting for the effects of age, sex, healthcare-associated pneumonia, body mass index, Charlson comorbidity index, and bilateral infiltration on computed tomography (CT) as confounding factors. Patients Adult patients with new-onset hospitalized infectious pneumonia confirmed by CT between January 1, 2020, and July 31, 2021. Results This study included 395 participants. On admission, 87 (22.0%) participants exhibited relative bradycardia, and 302 (76.5%) participants had COVID-19. Relative bradycardia on admission was not significantly associated with COVID-19 pneumonia [adjusted odds ratio (OR) 1.32; 95% confidence interval (CI) 0.49-3.54, p=0.588] but was associated with hypoxemia (adjusted OR 4.74; 95%CI 2.64-8.52, p<0.001). Conclusion The study results showed that relative bradycardia on admission was not associated with COVID-19 in cases of infectious pneumonia. However, relative bradycardia may be associated with the incidence of hypoxemia in pneumonia.
Comparison and convergence of compartment syndrome techniques: a narrative review

ABSTRACT Introduction Compartment syndrome (CS) continues to be a legitimate orthopedic emergency as it leads to thousands of amputations and permanent nerve and tissue damage to undiagnosed patients for more than eight hours. In CS, intracompartmental pressure is elevated, causing reduced blood flow inside the limb compartments. An erroneous diagnosis may result in unnecessary fasciotomies, the only treatment for this condition. Areas Covered This review examines the previous and current diagnostic and therapeutic practices for compartment syndrome. It also performs a comparative analysis of each diagnostic technique and its foresights. Expert Opinion Currently, most clinicians rely on a physical examination of the patient to diagnose CS. The primary reason for the physical examination is the lack of a gold-standard device. The invasive intracompartmental pressure (ICP) measurement technique is still the most commonly used. On the other hand, many noninvasive approaches have the potential to be used as diagnostic tools; however, more research is needed before they can be accepted as standard clinical approaches.
Normal high-sensitivity cardiac troponin for ruling-out inpatient mortality in acute COVID-19

Introduction Assessment of inpatient mortality risk in COVID-19 patients is important for guiding clinical decision-making. High sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiac injury associated with a worse prognosis in COVID-19. We explored how hs-cTnT could potentially be used in clinical practice for ruling in and ruling out mortality in COVID-19. Method We tested the diagnostic value of hs-cTnT in laboratory-confirmed COVID-19 patients (≥18 years old) admitted to the Royal Berkshire Hospital (UK) between 1st March and 10th May 2020. A normal hs-cTnT was defined as a value within the 99th percentile of healthy individuals (≤14 ng/L), and an elevated hs-cTnT was defined as >14 ng/L. Adverse clinical outcome was defined as inpatient mortality related to COVID-19. Results A total of 191 COVID-19 patients (62% male; age 66±16 years) had hs-cTnT measured on admission. Of these patients, 124 (65%) had elevated hs-cTnT and 67 (35%) had normal hs-cTnT. On a group level, patients with elevated hs-cTnT had worse inpatient survival (p = 0.0014; Kaplan-Meier analysis) and higher risk of inpatient mortality (HR 5.84 [95% CI 1.29–26.4]; p = 0.02; Cox multivariate regression) compared to patients with normal hs-cTnT. On a per-patient level, a normal hs-cTnT had a negative predictive value of 94% (95% CI: 85–98%) for ruling out mortality, whilst an elevated hs-cTnT had a low positive predictive value of 38% (95% CI: 39–47%) for ruling in mortality. Conclusions In this study cohort of COVID-19 patients, the potential clinical utility of hs-cTnT appears to rest in ruling out inpatient mortality. This finding, if prospectively validated in a larger study, may allow hs-cTnT to become an important biomarker to facilitate admission-avoidance and early safe discharge.
Evaluating Outcomes and Time Delays of a Non-Trainee-Driven Hospitalist Procedure Service

Background and Objectives: Ultrasound guidance has become standard of care in hospital medicine for invasive bedside procedures, especially central venous catheter placement. Despite ultrasound-guided bedside procedures having a high degree of success, only a few hospitalists perform them. This is because these are usually performed by radiologists or in the setting of trainee-run procedure teams. We sought to determine the impact of a non-trainee driven, hospitalist-run procedure service relative to time from consult to procedure. Methods: The University of Alabama at Birmingham Hospital (UAB), Department of Hospital Medicine, trained 8 non-trainee hospitalist physicians (from existing staff) to implement the ultrasound-guided procedure service. This study examines consult to procedure completion time since the implementation of the procedure service (2014 to 2020). Univariate analyses are used to analyze pre-implementation (2012-2014), pilot (2014-2016), and post-implementation data (2016-2018 initial, and 2018-2020 sustained). Results: Results suggest a 50% reduction in time from consult to procedure completion when compared with the period before implementation of the nontrainee hospitalist procedure service. Conclusions: A hospitalist procedure service, which does not include trainees, results in less time lag from consult to procedure completion time, which could increase patient satisfaction and improve throughput. As such, this study has wide generalizability to community hospitals and other nonacademic medical centers that may not have trainees.
Contribution to Numerical Modeling of Water Flow in Variably Saturated, Heterogeneous Porous Media

Solutions to the Richards equation for water flow in variably saturated porous media are the focus of this paper. Working with field conditions, the extreme variability and complexity of soil, initial and boundary conditions can make the flow problem difficult to solve. This paper proposes to improve the computational efficiency of the mixed hybrid finite element (MHFE) method coupled with the variables transformation. The transform variables were introduced in order to simulate problems with convergence difficulty attributed to the presence of sharp wetting fronts. Furthermore, for better convergence behaviour, a technique that switches between the mixed-form and the pressure-head based form of the Richard’s equation was applied. Special attention was given to the top boundary conditions dealing with ponding or evaporation problems. In order to avoid non-physical oscillation problems, a mass condensation scheme was implemented in the model. Performance indicators in time and error of different options of the numerical model are defined, analyzed and classified. Thus, for each test case, a suitable numerical method that identifies which form of the Richards equation is best suited, the relevance of the switching technique as well as the utility of the transformation of the primary variable is possible. The results for the 1D Numerical test cases that have been performed matched those from the literature results. For evaporation and infiltration problem’s, the number of iterations needed to get the solution decrease when using the method of transformed pressure. Finally, knowing the soil heterogeneity, initial and boundary conditions, an agglomerative hierarchical clustering allows to analyze the need or not to transform variables and to use other options.
Zebrafish smarcc1a mutants reveal requirements for BAF chromatin remodeling complexes in distinguishing the atrioventricular canal from the cardiac chambers

Essential patterning processes transform the heart tube into a compartmentalized organ with distinct chambers separated by an atrioventricular canal (AVC). This transition involves the refinement of expression of genes that are first found broadly throughout the heart tube and then become restricted to the AVC. Despite the importance of cardiac patterning, we do not fully understand the mechanisms that limit gene expression to the AVC.
High-content synaptic phenotyping in human cellular models reveals a role for BET proteins in synapse assembly

Resolving fundamental molecular and functional processes underlying human synaptic development is crucial for understanding normal brain function as well as dysfunction in disease. Based upon increasing evidence of species-divergent features of brain cell types, coupled with emerging studies of complex human disease genetics, we developed the first automated and quantitative high-content synaptic phenotyping platform using human neurons and astrocytes. To establish the robustness of our platform, we screened the effects of 376 small molecules on presynaptic density, neurite outgrowth, and cell viability, validating six small molecules that specifically enhanced human presynaptic density in vitro. Astrocytes were essential for mediating the effects of all six small molecules, underscoring the relevance of non-cell-autonomous factors in synapse assembly and their importance in synaptic screening applications. Bromodomain and extraterminal (BET) inhibitors emerged as the most prominent hit class and global transcriptional analyses using multiple BET inhibitors confirmed upregulation of synaptic gene expression. Through these analyses, we demonstrate the robustness of our automated screening platform for identifying potent synaptic modulators, which can be further leveraged for scaled analyses of human synaptic mechanisms and drug discovery efforts.
NON-RELATIVISTIC TIME, EXISTENCE AND ADAPTATION

By using non-dimensional Navier–Stokes equations in systems where partial modelling complications can be avoided, it is shown that geometrically similar systems can exhibit identical behaviour but according to different time scales where the latter are also within our own control. These models indicate that the physical nature of time is not related to a fundamental constant, but the passage of time can have a different but still constant value in a particular system of our own choosing. This observation also adds to our knowledge relating to the dichotomy of interpreting time either as a flowing parameter or, alternatively, just accepting it as a part of space-time. The observation adds evidence in favour of both viewpoints. The conclusions also seem relevant to biological species, chemical processes in general and other branches of physics. Using earlier work of Prigogine and others, it also appears that instantaneous time has important properties dividing past and future time into two segments which differ fundamentally in physical characteristics. This seems to explain the ‘raison d’tre’ of the second law of thermodynamics and the necessarily asymmetrical nature of time in our own world where mathematical symmetry of physical laws is the norm. This entropic time barrier also seems to explain the physically intangible nature of past events and their possible natural importance as former lower entropy forms of existence. It is concluded that these physical features of time are necessary for the existence of any form of life and Darwinian evolution, in particular. The conclusions may also help to throw further light on other suggested theories and observations in physics and the role of quantum decoherence in life and its adaptive ability.
Time optimal control for a reaction diffusion system arising in cardiac electrophysiology – a monolithic approach

Motivated by the termination of undesirable arrhythmia, a time optimal control formulation for the monodomain equations is proposed. It is shown that, under certain conditions, the optimal solutions of this problem steer the system into an appropriate stable neighborhood of the resting state. Towards this goal, some new regularity results and asymptotic properties for the monodomain equations with the Rogers-McCulloch ionic model are obtained. For the numerical realization, a monolithic approach, which simultaneously optimizes for the optimal times and optimal controls, is presented and analyzed. Its practical realization is based on a semismooth Newton method. Numerical examples and comparisons are included.