Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Characteristics of Nocardiosis: a Multicenter Retrospective Study in Korea

Background Nocardiosis is a rare, but potentially life-threatening condition. It is difficult to diagnose, and bacterial culture identification can be time consuming. We investigated the characteristics of nocardiosis and the suitability of the treatment approach in Korea. Materials and Methods This retrospective study was conducted at 5 medical institutions between 2011 and 2021. We reviewed the medical records of patients with microbiologically confirmed nocardiosis. Appropriate antibiotic selection was defined as follows: (1) selecting antibiotics according to the species, (2) if the species of Nocardia was unknown, trimethoprim-sulfamethoxazole-based therapy or linezolid-based therapy was administered, and (3) selection of antibiotics using the antibiotic susceptibility test. The appropriate treatment periods for antibiotics were defined as treatment maintained from 3 to 12 months, depending on involvement of the organs. Descriptive analysis and Fisher exact test were used. Statistical significance was set at P-values of <0.05. Results Thirty patients were enrolled. Of these patients, 18 (60.0%) were male. The median age was 70.5 years. Among the diagnosed patients, 12 (40.0%) had an immunocompromised status. Eight (30.0%) patients received optimal treatment for the appropriate treatment period. Appropriate dosing duration was observed in 3 of the 12 (25.0%) immunocompromised patients. There was no significant difference between the presence or absence of immunosuppression and the adequacy of treatment for nocardiosis (P = 1.000). Skin and soft tissue (14 patients) were most frequently involved in this study. Nocardia species (spp.) were isolated from culture at a median of 6.0 days. There were 7 cases with N. farcinica (23.3%). Conclusion We found that 60.0% of the patients with nocardiosis did not have an immunocompromised status. Further, 26.7% of the total patients received adequate treatment for nocardiosis. The reasons for suboptimal management of nocardiosis in Korea are presumed to be diagnostic difficulties, lack of awareness about nocardiosis, and difficulties in selecting antibiotics for Nocardia spp. among clinicians. The lack of antibiotic susceptibility tests for Nocardia spp. could be the source of these problems. Nocardiosis should be suspected in cases of recurrent infections with skin and soft tissue, musculoskeletal, or respiratory system involvement with or without an immunocompromised status. Clinical microbiological support is required for the diagnosis and selection of antibiotics in Korea. High clinical index of suspicion and clinical microbiological support are required for the accurate diagnosis of nocardiosis in Korea.
Complex evolutionary history of photosynthesis in Bradyrhizobium

Bradyrhizobium comprises a diverse group of bacteria with various lifestyles. Although best known for their nodule-based nitrogen-fixation in symbiosis with legumes, a select group of bradyrhizobia are also capable of photosynthesis. This ability seems to be rare among rhizobia, and its origin and evolution in these bacteria remain a subject of substantial debate. Therefore, our aim here was to investigate the distribution and evolution of photosynthesis in Bradyrhizobium using comparative genomics and representative genomes from closely related taxa in the families Nitrobacteraceae, Methylobacteriaceae, Boseaceae and Paracoccaceae. We identified photosynthesis gene clusters (PGCs) in 25 genomes belonging to three different Bradyrhizobium lineages, notably the so-called Photosynthetic, B. japonicum and B. elkanii supergroups. Also, two different PGC architectures were observed. One of these, PGC1, was present in genomes from the Photosynthetic supergroup and in three genomes from a species in the B. japonicum supergroup. The second cluster, PGC2, was also present in some strains from the B. japonicum supergroup, as well as in those from the B. elkanii supergroup. PGC2 was largely syntenic to the cluster found in Rhodopseudomonas palustris and Tardiphaga . Bayesian ancestral state reconstruction unambiguously showed that the ancestor of Bradyrhizobium lacked a PGC and that it was acquired horizontally by various lineages. Maximum-likelihood phylogenetic analyses of individual photosynthesis genes also suggested multiple acquisitions through horizontal gene transfer, followed by vertical inheritance and gene losses within the different lineages. Overall, our findings add to the existing body of knowledge on Bradyrhizobium ’s evolution and provide a meaningful basis from which to explore how these PGCs and the photosynthesis itself impact the physiology and ecology of these bacteria.
A standardised protocol for relative SARS-CoV-2 variant severity assessment, applied to Omicron BA.1 and Delta in six European countries, October 2021 to February 2022

Several SARS-CoV-2 variants that evolved during the COVID-19 pandemic have appeared to differ in severity, based on analyses of single-country datasets. With decreased testing and sequencing, international collaborative studies will become increasingly important for timely assessment of the severity of new variants. Therefore, a joint WHO Regional Office for Europe and ECDC working group was formed to produce and pilot a standardised study protocol to estimate relative case-severity of SARS-CoV-2 variants during periods when two variants were co-circulating. The study protocol and its associated statistical analysis code was applied by investigators in Denmark, England, Luxembourg, Norway, Portugal and Scotland to assess the severity of cases with the Omicron BA.1 virus variant relative to Delta. After pooling estimates using meta-analysis methods (random effects estimates), the risk of hospital admission (adjusted hazard ratio (aHR) = 0.41; 95% confidence interval (CI): 0.31−0.54), admission to intensive care unit (aHR = 0.12; 95% CI: 0.05−0.27) and death (aHR = 0.31; 95% CI: 0.28−0.35) was lower for Omicron BA.1 compared with Delta cases. The aHRs varied by age group and vaccination status. In conclusion, this study demonstrates the feasibility of conducting variant severity analyses in a multinational collaborative framework and adds evidence for the reduced severity of the Omicron BA.1 variant.
Evaluation of sequence hybridization for respiratory viruses using the Twist Bioscience Respiratory Virus Research panel and the OneCodex Respiratory Virus sequence analysis workflow

Respiratory viral infections are a major global clinical problem, and rapid, cheap, scalable and agnostic diagnostic tests that capture genome-level information on viral variation are urgently needed. Metagenomic approaches would be ideal, but remain currently limited in that much of the genetic content in respiratory samples is human, and amplifying and sequencing the viral/pathogen component in an unbiased manner is challenging. PCR-based tests, including those which detect multiple pathogens, are already widely used, but do not capture information on strain-level variation; tests with larger viral repertoires are also expensive on a per-test basis. One intermediate approach is the use of large panels of viral probes or ‘baits’, which target or ‘capture’ sequences representing complete genomes amongst several different common viral pathogens; these are then amplified, sequenced and analysed with a sequence analysis workflow. Here we evaluate one such commercial bait capture method (the Twist Bioscience Respiratory Virus Research Panel) and sequence analysis workflow (OneCodex), using control (simulated) and patient samples head-to-head with a validated multiplex PCR clinical diagnostic test (BioFire FilmArray). We highlight the limited sensitivity and specificity of the joint Twist Bioscience/OneCodex approach, which are further reduced by shortening workflow times and increasing sample throughput to reduce per-sample costs. These issues with performance may be driven by aspects of both the laboratory (e.g. capacity to enrich for viruses present in low numbers), bioinformatics methods used (e.g. a limited viral reference database) and thresholds adopted for calling a virus as present or absent. As a result, this workflow would require further optimization prior to any implementation for respiratory virus characterization in a routine diagnostic healthcare setting.
Metabolic syndrome increases the risk for premature employment exit: A longitudinal study among 60 427 middle-aged and older workers from the Lifelines Cohort Study and Biobank

Objectives This study aimed to examine whether (i) metabolic syndrome (MetS) increases the risk for premature employment exit and (ii) a dose–response relationship exists between an increasing number of MetS components and premature employment exit among middle-aged and older workers. Methods A sample of N=60 427 Dutch workers (40–64 years old) from the Lifelines Cohort Study and Biobank were examined using data from five measurement waves during a total median follow-up time of 4.2 years. MetS components were based on physical measures, blood markers, and medication use. Premature employment exit types (ie, unemployment, work disability, and early retirement) were determined using questionnaires. MetS and number of MetS components were examined as risk factors for premature employment exit using competing risk regression analysis. Results MetS significantly increased the risk for work disability [adjusted sub distribution hazard ratio (SHR) 1.78, 95% confidence interval (CI) 1.54–2.05] and unemployment (adjusted SHR 1.16, 95% CI 1.06–1.26). A clear dose–response relationship was found for an increasing number of MetS components and work disability. No associations were found between MetS (components) and early retirement after adjusting for sociodemographic factors. Conclusions MetS was identified as a modifiable early-stage cardio-metabolic risk factor especially for work disability and, to a lesser extent, for unemployment. Further, a clear dose–response relationship was found between an increasing number of MetS components and work disability. MetS interventions and prevention might help to prolong working lives. More awareness is needed among employers and occupational health professionals about the premature employment exit risk faced by middle-aged and older workers with MetS.
Sexual and reproductive healthcare utilisation and affordability for South Sudanese refugees and host populations in Northern Uganda: A mixed methods study

Given Uganda’s increasing refugee population, the health financing burden on refugee and host populations is likely to increase because Uganda’s integrated health system caters to both populations. We used sexual, reproductive, and maternal health (SRMH) as a lens to assess the utilisation and user cost of health services in Northern Uganda to identify potential gaps in SRMH services and their financing. We conducted a cross-sectional survey among 2,533 refugee and host women and girls in Arua and Kiryandongo districts. We conducted 35 focus group discussions and 131 in-depth interviews with host and South Sudanese refugees, community members, health workers, NGO and governmental actors. Qualitative data were analysed thematically using a framework approach. Quantitative data were analysed using t-test, chi-square tests, multivariate logistical regression, and a two-part model. We found high levels of access to maternal care services among refugee and host communities in Northern Uganda, but lower levels of met need for family planning (FP). Refugees had higher uptake of delivery care than host communities due to better-resourced refugee facilities, but incurred higher costs for delivery kits and food and less for transport due to facilities being closer. FP uptake was low for both groups due to perceived risks, cultural and religious beliefs, and lack of agency for most women. Host communities lack access to essential maternal healthcare services relative to refugees, especially for delivery care. Greater investment is needed to increase the number of host facilities, improve the quality of SRMH services provided, and further enhance delivery care access among host communities. Ongoing funding of delivery kits across all communities is needed and new financing mechanisms should be developed to support non-medical costs for deliveries, which our study found to be substantial in our study. All populations must be engaged in co-designing improved strategies to meet their FP needs.
Revisiting the concept of drug‐resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force

Despite progress in the development of anti‐seizure medications (ASMs), one third of people with epilepsy have drug‐resistant epilepsy (DRE). The working definition of DRE, proposed by the International League Against Epilepsy (ILAE) in 2010, helped identify individuals who might benefit from presurgical evaluation early on. As the incidence of DRE remains high, the TASK1 workgroup on DRE of the ILAE/American Epilepsy Society (AES) Joint Translational Task Force discussed the heterogeneity and complexity of its presentation and mechanisms, the confounders in drawing mechanistic insights when testing treatment responses, and barriers in modeling DRE across the lifespan and translating across species. We propose that it is necessary to revisit the current definition of DRE, in order to transform the preclinical and clinical research of mechanisms and biomarkers, to identify novel, effective, precise, pharmacologic treatments, allowing for earlier recognition of drug resistance and individualized therapies.
The Arf-GAP Age2 localizes to the late-Golgi via a conserved amphipathic helix

Arf GTPases are central regulators of the Golgi complex, which serves as the nexus of membrane-trafficking pathways in eukaryotic cells. Arf proteins recruit dozens of effectors to modify membranes, sort cargos, and create and tether transport vesicles, and are therefore essential for orchestrating Golgi trafficking. The regulation of Arf activity is controlled by the action of Arf-GEFs which activate via nucleotide exchange, and Arf-GAPs which inactivate via nucleotide hydrolysis. The localization dynamics of Arf GTPases and their Arf-GAPs during Golgi maturation have not been reported. Here we use the budding yeast model to examine the temporal localization of the Golgi Arf-GAPs. We also determine the mechanisms used by the Arf-GAP Age2 to localize to the Golgi. We find that the catalytic activity of Age2 and a conserved sequence in the unstructured C-terminal domain of Age2 are both required for Golgi localization. This sequence is predicted to form an amphipathic helix and mediates direct binding of Age2 to membranes in vitro. We also report the development of a probe for sensing active Arf1 in living cells and use this probe to characterize the temporal dynamics of Arf1 during Golgi maturation.
Emotion regulation of social pain: double dissociation of lateral prefrontal cortices supporting reappraisal and distraction

Abstract The dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) are both crucial regions involved in voluntary emotion regulation. However, it remains unclear whether the two regions show functional specificity for reappraisal and distraction. This study employed transcranial magnetic stimulation (TMS) to explore, in a real social interactive scenario, whether different lateral prefrontal regions play relatively specific roles in downregulating social pain via reappraisal and distraction. Participants initially took part in a social interactive game, followed by receiving either active (the DLPFC- or VLPFC-activated group, n = 100 per group) or control (the vertex-activated group, n = 100) TMS session. They were then instructed to use both distraction and reappraisal strategies to downregulate any negative emotions evoked by the social evaluation given by their peers who interacted with them previously. Results demonstrated that the TMS-activated DLPFC has a greater beneficial effect during distraction, whereas the activated VLPFC has a greater beneficial effect during reappraisal. This result investigated the direct experience of social pain and extended previous findings on empathy-related responses to affective pictures while also controlling for confounding factors such as empathic concern. Therefore, we are now confident in the double dissociation proposal of the DLPFC and VLPFC in distraction and reappraisal.
Favorable Patient-Reported, Clinical, and Functional Outcomes 2 Years After ACL Repair and InternalBrace Augmentation Compared With ACL Reconstruction and Healthy Controls

Background: Recently, interest in anterior cruciate ligament (ACL) preservation and repair after proximal ACL tears has been resurrected. Although good clinical outcomes have been reported in the literature with adequate patient selection, to date detailed scientific evidence for the functional benefit of primary ACL repair with ligament augmentation is scarce. Purpose: To compare patient-reported, clinical, and functional outcomes in patients 2 years after ACL repair and InternalBrace augmentation (ACL-IB) with age- and sex-matched patients 2 years after ACL reconstruction (ACL-R) and with matched healthy controls. Study Design: Cohort study; Level of evidence, 3. Methods: In total, 29 patients 2 years after ACL-IB, 27 sex- and age- matched patients 2 years after ACL-R (hamstring autografts), and 29 matched healthy controls were included. Patient-reported outcomes were assessed using the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, EQ-5D-5L, Tegner Activity Scale, and Anterior Cruciate Ligament Return to Sports after Injury scale. Surgery time was recorded. For clinical outcomes, range of motion and thigh and shank circumference were measured, and passive anterior translation was determined using the Rolimeter. Isokinetic muscle strength was measured using a Biodex dynamometer. The limb symmetry index (operated/contralateral or nondominant/dominant × 100), side-to-side differences (operated – contralateral, nondominant – dominant), and hamstring-quadriceps ratios were calculated for functional parameters. Failure and reoperation rates were not compared. Results: Two years after surgery, patients treated with ACL-IB showed good to excellent patient-reported outcomes comparable with those of patients after ACL-R. Surgery time, including concomitant surgeries, was significantly shorter in the ACL-IB group (mean, 81 minutes) compared with the ACL-R group (mean, 97 minutes) (P = .024). Isokinetic muscle strength was comparable between patient groups without significant differences in extensor and flexor strength or in hamstring-quadriceps ratios. Conclusion: These results suggest that ACL-IB achieves comparable patient-reported, clinical, and functional outcomes with ACL-R at 2 years postoperatively and, after careful patient selection, should be considered as a valuable early treatment alternative for proximal ACL tears. Registration: NCT04429165 (ClinicalTrials.gov identifier).
Estimating causal effects in observational studies for survival data with a cure fraction using propensity score adjustment

In observational studies, covariates are often confounding factors for treatment assignment. Such covariates need to be adjusted to estimate the causal treatment effect. For observational studies with survival outcomes, it is usually more challenging to adjust for the confounding covariates for causal effect estimation because of censoring. The challenge becomes even thornier when there exists a nonignorable cure fraction in the population. In this paper, we propose a causal effect estimation approach in observational studies for survival data with a cure fraction. We extend the absolute treatment effects on survival outcomes—including the restricted average causal effect and SPCE—to survival outcomes with cure fractions, and construct the corresponding causal effect estimators based on propensity score stratification. We prove the asymptotic properties of the proposed estimators and conduct simulation studies to evaluate their performances. As an illustration, the method is applied to a stomach cancer study.
A Computationally Lightweight Safe Learning Algorithm

Safety is an essential asset when learning control policies for physical systems, as violating safety constraints during training can lead to expensive hardware damage. In response to this need, the field of safe learning has emerged with algorithms that can provide probabilistic safety guarantees without knowledge of the underlying system dynamics. Those algorithms often rely on Gaussian process inference. Unfortunately, Gaussian process inference scales cubically with the number of data points, limiting applicability to high-dimensional and embedded systems. In this paper, we propose a safe learning algorithm that provides probabilistic safety guarantees but leverages the Nadaraya-Watson estimator instead of Gaussian processes. For the Nadaraya-Watson estimator, we can reach logarithmic scaling with the number of data points. We provide theoretical guarantees for the estimates, embed them into a safe learning algorithm, and show numerical experiments on a simulated seven-degrees-of-freedom robot manipulator.
Hyperbolic lattices and two-dimensional Yang-Mills theory

Hyperbolic lattices are a new type of synthetic quantum matter emulated in circuit quantum electrodynamics and electric-circuit networks, where particles coherently hop on a discrete tessellation of two-dimensional negatively curved space. While real-space methods and a reciprocal-space hyperbolic band theory have been recently proposed to analyze the energy spectra of those systems, discrepancies between the two sets of approaches remain. In this work, we reconcile those approaches by first establishing an equivalence between hyperbolic band theory and $U(N)$ topological Yang-Mills theory on higher-genus Riemann surfaces. We then show that moments of the density of states of hyperbolic tight-binding models correspond to expectation values of Wilson loops in the quantum gauge theory and become exact in the large-$N$ limit.
Adjacency Sketches in Adversarial Environments

An adjacency sketching or implicit labeling scheme for a family $\cal F$ of graphs is a method that defines for any $n$ vertex $G \in \cal F$ an assignment of labels to each vertex in $G$, so that the labels of two vertices tell you whether or not they are adjacent. The goal is to come up with labeling schemes that use as few bits as possible to represent the labels. By using randomness when assigning labels, it is sometimes possible to produce adjacency sketches with much smaller label sizes, but this comes at the cost of introducing some probability of error. Both deterministic and randomized labeling schemes have been extensively studied, as they have applications for distributed data structures and deeper connections to universal graphs and communication complexity. The main question of interest is which graph families have schemes using short labels, usually $O(\log n)$ in the deterministic case or constant for randomized sketches. In this work we consider the resilience of probabilistic adjacency sketches against an adversary making adaptive queries to the labels. This differs from the previously analyzed probabilistic setting which is ``one shot". We show that in the adaptive adversarial case the size of the labels is tightly related to the maximal degree of the graphs in $\cal F$. This results in a stronger characterization compared to what is known in the non-adversarial setting. In more detail, we construct sketches that fail with probability $\varepsilon$ for graphs with maximal degree $d$ using $2d\log (1/\varepsilon)$ bit labels and show that this is roughly the best that can be done for any specific graph of maximal degree $d$, e.g.\ a $d$-ary tree.