Miracle-dz/UniFAR-FTUs huggingface dataset:
Low somatosensory cortex excitability in the acute stage of low back pain causes chronic pain

ABSTRACT BACKGROUND: Determining the mechanistic causes of complex biopsychosocial health conditions such as low back pain (LBP) is challenging, and research is scarce. Cross-sectional studies demonstrate altered excitability and organisation of the primary somatosensory and primary motor cortex in people with acute and chronic LBP, however, no study has explored these mechanisms longitudinally or attempted to draw causal inferences. METHODS: Prospective, longitudinal, cohort study including 120 people with an acute episode of LBP. Sensory evoked potential area measurements were used to assess primary and secondary somatosensory cortex excitability. Transcranial magnetic stimulation derived map volume was used to assess corticomotor excitability. Directed acyclic graphs identified variables potentially confounding the exposure-outcome relationship. The effect of acute-stage sensorimotor cortex excitability on six-month LBP outcome was estimated using multivariable regression modelling, with adjusted and unadjusted estimates reported. Sensitivity analyses were performed to explore the effect of unmeasured confounding and missing data. RESULTS: Lower primary (OR = 2.08, 95% CI = 1.22 to 3.57) and secondary (OR = 2.56, 95% CI = 1.37 to 4.76) somatosensory cortex excitability in the acute stage of LBP increased the odds of developing chronic pain at six-month follow-up. This finding was robust to confounder adjustment and unmeasured confounding (E-Value = 2.24 & 2.58, respectively). Corticomotor excitability in the acute stage of LBP was associated with higher pain intensity at 6-month follow-up (B = -0.15, 95% CI: -0.28 to -0.02) but this association did not remain after confounder adjustment. CONCLUSION: These data provide the first evidence that low somatosensory cortex excitability in the acute stage of LBP is a cause of chronic pain. Interventions designed to increase somatosensory cortex excitability in acute LBP may be relevant to the prevention of chronic pain.
5′-Cap sequestration is an essential determinant of HIV-1 genome packaging

Significance HIV-1 replication is critically dependent on the selective incorporation of viral RNA genomes into assembling virions. Although RNA elements that promote packaging have been identified, the determinants of authentic packaging fidelity and efficiency have until now remained unknown. The present studies show that genome selection is achieved by a bipartite mechanism that requires both dimerization-dependent exposure of packaging signals within the 5′ leader of the viral RNA and structural sequestration of the 5′ cap. Cap sequestration likely prevents capture by the cellular RNA processing and translation machinery, a mechanism that may help explain why some cellular RNA polymerase III transcripts that lack 5′ caps can parasitize virions. Cap sequestration may be commonly employed among RNA viruses that package 5′-capped genomes. HIV-1 selectively packages two copies of its 5′-capped RNA genome (gRNA) during virus assembly, a process mediated by the nucleocapsid (NC) domain of the viral Gag polyprotein and encapsidation signals located within the dimeric 5′ leader of the viral RNA. Although residues within the leader that promote packaging have been identified, the determinants of authentic packaging fidelity and efficiency remain unknown. Here, we show that a previously characterized 159-nt region of the leader that possesses all elements required for RNA dimerization, high-affinity NC binding, and packaging in a noncompetitive RNA packaging assay (ΨCES) is unexpectedly poorly packaged when assayed in competition with the intact 5′ leader. ΨCES lacks a 5′-tandem hairpin element that sequesters the 5′ cap, suggesting that cap sequestration may be important for packaging. Consistent with this hypothesis, mutations within the intact leader that expose the cap without disrupting RNA structure or NC binding abrogated RNA packaging, and genetic addition of a 5′ ribozyme to ΨCES to enable cotranscriptional shedding of the 5′ cap promoted ΨCES-mediated RNA packaging to wild-type levels. Additional mutations that either block dimerization or eliminate subsets of NC binding sites substantially attenuated competitive packaging. Our studies indicate that packaging is achieved by a bipartite mechanism that requires both sequestration of the 5′ cap and exposure of NC binding sites that reside fully within the ΨCES region of the dimeric leader. We speculate that cap sequestration prevents irreversible capture by the cellular RNA processing and translation machinery, a mechanism likely employed by other viruses that package 5′-capped RNA genomes.
A dissolved organic carbon (DOC) analyzer capable of detecting sub‐μM DOC differences in natural fresh waters: A proof of concept study

This study reports the development of a new type of organic carbon (OC) analyzer that combines flow through analysis and ultraviolet‐wet chemical oxidation (UV‐WCO). Total or dissolved OC (TOC or DOC, respectively) is determined through detection of CO2 as the oxidation product using a vibration insensitive nondispersive infrared (NDIR) gas analyzer. Aided by heat and UV, OC is oxidized by continuously pumping the liquid sample in‐line with a carbon‐free acidic persulfate reagent at a constant flow rate through the system. The CO2 produced from oxidation of OC is sparged from solution at a precise flow rate and is continuously detected, producing a stable signal plateau with high signal‐to‐noise ratio. A low carbon blank/baseline for the analysis is achieved by recycling persulfate reagent alone through the system until minimal CO2 is detected. We show progress in the optimization of this novel instrument that, unlike standard high temperature combustion (HTC) instrumentation that is subject to high blank variability and micromolar resolution (typical coefficient of variation (CV) ∼ 1–2%), has potential applications for studies of DOC net production and consumption by various mechanisms that typically require sub‐micromolar precision.
Glutamine promotes escape from therapy-induced senescence in tumor cells

Therapy-induced senescence (TIS) is a major cellular response to anticancer therapies. While induction of a persistent growth arrest would be a desirable outcome in cancer therapy, it has been shown that, unlike normal cells, cancer cells are able to evade the senescence cell cycle arrest and to resume proliferation, likely contributing to tumor relapse. Notably, cells that escape from TIS acquire a plastic, stem cell-like phenotype. The metabolic dependencies of cells that evade senescence have not been thoroughly studied. In this study, we show that glutamine depletion inhibits escape from TIS in all cell lines studied, and reduces the stem cell subpopulation. In line with a metabolic reliance on glutamine, escaped clones overexpress the glutamine transporter SLC1A5. We also demonstrate a central role of glutamine synthetase that mediates resistance to glutamine deprivation, conferring independence from exogenous glutamine. Finally, rescue experiments demonstrate that glutamine provides nitrogen for nucleotides biosynthesis in cells that escape from TIS, but also suggest a critical involvement of glutamine in other metabolic and non-metabolic pathways. On the whole, these results reveal a metabolic vulnerability of cancer stem cells that recover proliferation after exposure to anticancer therapies, which could be exploited to prevent tumor recurrence.
Nontuberculous mycobacterium: An emerging pathogen: Indian perspective

Nontuberculous mycobacteria (NTM), considered as mere contaminants, are off late, being reported as potential pathogens through various studies. The infections due to NTM range from pulmonary to extra pulmonary including skin and soft-tissue infections, traumatic and surgical wound infections, and catheter and implant-associated infections. Although extrapulmonary infections are extensively explored, pulmonary infections are scarcely reported due to their misdiagnosis as tuberculosis caused by M. tuberculosis (MTB). Appropriate detection methods are essential in order to facilitate the differential diagnosis of NTM from MTB infections. We aimed to collate the data available on NTM diagnosis and its epidemiology in India in this review. While diagnosis of MTB itself is more challenging in India, for appropriate treatment of NTM, special training and attention is needed for differential diagnosis of the former from latter. Currently, in India, in addition to the available techniques for identification of NTM, line probe assay (Hains life sciences) is proving to be a promising tool for the detection of NTM (common mycobacteria/additional species kit) and their antimicrobial resistance (Genotype NTM-DR VER 1.0). In future, with the price of sequencing steadily coming down, with proper monitoring, whole-genome sequencing could be the test of choice to predict the species, drug resistance, outbreaks in hospitals, and transmission dynamics.
The cardiovascular effects of amodiaquine and structurally related antimalarials: An individual patient data meta-analysis

Background Amodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial. Methods and findings Studies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression. The meta-analysis included 2,681 patients from 4 randomised controlled trials evaluating artemisinin-based combination therapies (ACTs) containing amodiaquine (n = 725), lumefantrine (n = 499), piperaquine (n = 716), and pyronaridine (n = 566), as well as monotherapy with chloroquine (n = 175) for uncomplicated malaria. Amodiaquine prolonged QTcS (mean = 16.9 ms, 95% CI: 15.0 to 18.8) less than chloroquine (21.9 ms, 18.3 to 25.6, p = 0.0069) and piperaquine (19.2 ms, 15.8 to 20.5, p = 0.0495), but more than lumefantrine (5.6 ms, 2.9 to 8.2, p < 0.001) and pyronaridine (−1.2 ms, −3.6 to +1.3, p < 0.001). In individuals aged ≥12 years, amodiaquine reduced heart rate (mean reduction = 15.2 beats per minute [bpm], 95% CI: 13.4 to 17.0) more than piperaquine (10.5 bpm, 7.7 to 13.3, p = 0.0013), lumefantrine (9.3 bpm, 6.4 to 12.2, p < 0.001), pyronaridine (6.6 bpm, 4.0 to 9.3, p < 0.001), and chloroquine (5.9 bpm, 3.2 to 8.5, p < 0.001) and was associated with a higher risk of potentially symptomatic sinus bradycardia (≤50 bpm) than lumefantrine (risk difference: 14.8%, 95% CI: 5.4 to 24.3, p = 0.0021) and chloroquine (risk difference: 8.0%, 95% CI: 4.0 to 12.0, p < 0.001). The effect of amodiaquine on the heart rate of children aged <12 years compared with other antimalarials was not clinically significant. Study limitations include the unavailability of individual patient-level adverse event data for most included participants, but no serious complications were documented. Conclusions While caution is advised in the use of amodiaquine in patients aged ≥12 years with concomitant use of heart rate–reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.
Perspectives from the patient: A content analysis of communication changes, impact, and strategies to facilitate communication in multiple sclerosis

Abstract Purpose: Communication changes in multiple sclerosis (MS) are under-explored and under-recognised. Persons with MS (PwMS) are experts in their condition and play a valuable role in informing clinicians and researchers of their condition. This study aimed to investigate the perspectives of PwMS on: (1) MS-related communication changes, (2) the impact of these communication changes across key aspects of a person’s life, including work/studies, relationships, and general quality of life, and (3) strategies used to facilitate communication in daily interactions. Method: Two-hundred and sixty PwMS were recruited internationally and completed an online questionnaire. Content analysis was used to analyse open-ended questionnaire responses. Result: One-hundred and ninety-seven (75.8%) participants reported communication changes, including language, cognitive, speech, voice, and fluency changes. Participants described a variety of personal and environmental factors that influence communication negatively, such as fatigue, stress, and heat. Communication changes were reported to impact on psychological wellbeing, interpersonal relationships, participation and identity in the workforce and career pathways, and tertiary studies. Around 40% of participants reported using a range of overt and covert strategies to manage communication changes. Only 11.2% (n = 22/197) of participants who reported communication changes accessed speech-language pathology (SLP) services. Conclusion: PwMS can experience a wide spectrum of communication changes. These communication changes can have a profound and far-reaching impact on psychological wellbeing and societal participation. Engagement with SLP services is limited compared to the reported prevalence of communication changes. There is a need to raise awareness of the role of SLP in service provision for PwMS to manage communication changes. This paper discusses and provides suggestions for SLP services for PwMS with communication changes. There is a timely need to develop evidence-based interventions to support PwMS manage communication changes and reduce their impact.
Does the Quality of Source Notes Matter? An Exploratory Study of Source-based Academic Writing

Integrated writing tasks have increased in popularity in second language writing classrooms. Extensive research on these tasks has examined the challenges that students face when completing such tasks. One significant challenge is the transformation of source language use when students integrate source information into their own essays. However, little is known about the relationship between students’ source notes and the quality of the essays that they produce. This exploratory study examined this issue by investigating the relationship between characteristics of English for academic purposes (EAP) students’ notes (N = 24) and their essay scores. The students’ notes were coded in terms of how they appropriated information from the source texts using four categories: copied, copied with changes, copied with gaps, and paraphrased. A multiple linear regression revealed that essay scores were predicted by the degree to which the students transformed source language and avoided copying. The implications of these findings for second language (L2) writing pedagogy and assessment are discussed.
Joint Planning of Network Slicing and Mobile Edge Computing: Models and Algorithms

Multi-access Edge Computing (MEC) facilitates the deployment of critical applications with stringent QoS requirements, latency in particular. This article considers the problem of jointly planning the availability of computational resources at the edge, the slicing of mobile network and edge computation resources, and the routing of heterogeneous traffic types to the various slices. These aspects are intertwined and must be addressed together to provide the desired QoS to all mobile users and traffic types still keeping costs under control. We formulate our problem as a mixed-integer nonlinear program (MINLP) and we define a heuristic, named Neighbor Exploration and Sequential Fixing (NESF), to facilitate the solution of the problem. The approach allows network operators to fine tune the network operation cost and the total latency experienced by users. We evaluate the performance of the proposed model and heuristic against two natural greedy approaches. We show the impact of the variation of all the considered parameters (viz., different types of traffic, tolerable latency, network topology and bandwidth, computation and link capacity) on the defined model. Numerical results demonstrate that NESF is very effective, achieving near-optimal planning and resource allocation solutions in a very short computing time even for large-scale network scenarios.
Improved Throughput for All-or-Nothing Multicommodity Flows with Arbitrary Demands

Throughput is a main performance objective in communication networks. This paper considers a fundamental maximum throughput routing problem-the all-or-nothing multicommodity flow (ANF) problem - in arbitrary directed graphs and in the practically relevant but challenging setting where demands can be (much) larger than the edge capacities. Hence, in addition to assigning requests to valid flows for each routed commodity, an admission control mechanism is required which prevents overloading the network when routing commodities.
Biomass accumulation, extraction and nutrient use efficiency by cover crops

The high biomass production of certain cover crops species is due to their high absorption capacity and nutrients use efficiency. Its potential for biomass production it is important to obtain productive plants using nutritional information especially in environments with low nutrient apport. The objective was to evaluate the biomass accumulation, extraction and nutrient use efficiency by cover crops growing in a soil of low fertility. The treatments were arranged in four randomized blocks, composed of seven cover crops: sunn hemp, spectabilis, pigeon pea forage, pigeon pea arbore, lab lab, jack bean and mucuna. To evaluate dry mass accumulation, crop growth rate and leaf area index, six plants were used in different times: 30, 45, 60, 75, 90 and 105 days after sowing. The cover crops differed in vegetative cycle, dry mass accumulation, yield, extraction and nutrient use efficiency, with better performance presented by pigeon pea arbore. The cover crops are good recyclers of nutrients, particularly nitrogen, potassium and calcium and have potential for use in the cultivation systems in the Northeast of Brazil.
Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials

Abstract Objective To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021. Study selection Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up. Data extraction and synthesis Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence. Results A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of −0.50 cm (95% CI −0.75 to −0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of −0.35 cm (−0.55 to −0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect). Conclusions Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. Systematic review registration https://osf.io/3pwn2
On Expanding the Definition and Use of Procedural Fidelity

Although our field has made significant progress in the measurement of procedural fidelity in research studies, we argue for a more nuanced and expansive perspective on procedural fidelity. Specifically, we review the status quo of procedural fidelity measurement in intervention research along with specific suggestions for increasing both precision and focused research on the levels of procedural fidelity that are needed to maximize outcomes for individual participants. Second, we offer an expanded example of procedural fidelity by examining the data on the influence of typical peers, particularly on how the data influence a broad range of skills for individuals with severe disabilities. Finally, we examine the need for multiple layers of procedural fidelity assessment if we are to fully understand the vast array of contextual variables that can influence both procedural fidelity and child outcomes, particularly in a progression of research from initial efficacy assessment through scale-up and replication. We utilize the program-wide implementation of the Pyramid Model for illustrative purposes.
Perceived Complexity of a Project’s Optimal Work Plan Influences Its Likelihood of Adoption by Project Managers

Project managers commonly adopt suboptimal work plans, even when optimal plans are readily accessible. This research identifies a factor that elicits this seemingly irrational behavior: the perceived complexity of the optimal work plan, as reflected in the plan’s Gantt chart representation. Four controlled experiments show that among experienced project managers presented with a work plan explicitly stated to be optimal, those who view a low-complexity plan are more likely to adopt the plan compared with project managers who view a high-complexity plan. Work-related stress triggered by exposure to the work plan is shown to mediate the effect.