Miracle-dz/UniFAR-FTUs huggingface dataset:
Poor Adherence to the Integrated Community Case Management of Newborn and Child Illness Protocol in Rural Ethiopia

ABSTRACT. Ethiopia has adopted the Integrated Community Case Management of Newborn and Child Illness (iCMNCI) strategy to expand access to neonatal and child health services. This study assessed compliance with the iCMNCI case management protocol at the primary care settings. A descriptive cross-sectional assessment was conducted in eight districts of Benishangul-Gumuz Region from April to December 2019, and 1,217 sick children aged 2 to 59 months and 43 sick young infants aged 0 to 2 months who sought clinical consultation at the 236 health posts were selected purposively. Trained supervisors reviewed the medical records of two most recent cases from each illness category to quantify the extent to which health workers correctly assessed, classified, treated, and followed up cases per the iCMNCI guidelines. A total of 32,981 children sought clinical consultation of whom 31,830 (96.5%) were aged 2 to 59 months, and 1,151 (3.5%) were young infants aged 0 to 2 months. Of the 1,217 selected children, 426 (35%) had pneumonia, 287 (23.6%) malaria, 501 (41.2%) diarrhea, and 3 (0.2%) had malnutrition. Nearly two-thirds 306 (72%) of pneumonia cases were correctly classified as having had the disease and 297 (70%) were correctly treated for pneumonia; 213 (74%) were correctly classified as having had malaria and 210 (73%) were correctly treated for malaria; and 393 (78%) were correctly classified as having had diarrhea and 297 (59%) were correctly treated for diarrhea. Generally, the current practices of child illness assessment, classification, and treatment have deviated from iCMNCI guidelines. Future interventions should support frontline health workers to comply strictly with case management protocols through training, mentorship, and supervision.
Kinematic function of knee implant designs across a range of daily activities

The aim of this randomized controlled trial was to measure and compare six‐degree‐of‐freedom (6‐DOF) knee joint motion of three total knee arthroplasty (TKA) implant designs across a range of daily activities. Seventy‐five TKA patients were recruited to this study and randomly assigned a posterior‐stabilized (PS), cruciate‐retaining (CR), or medial‐stabilized (MS) implant. Six months after surgery, patients performed five activities of daily living: level walking, step‐up, step‐down, sit‐to‐stand, and stand‐to‐sit. Mobile biplane X‐ray imaging was used to measure 6‐DOF knee kinematics and the center of rotation of the knee in the transverse plane for each activity. Mean 6‐DOF knee kinematics were consistently similar for PS and CR, whereas MS was more externally rotated and abducted, and lateral shift was lower across all activities. Peak‐to‐peak anterior drawer for MS was also significantly lower during walking, step‐up, and step‐down (p < 0.017). The center of rotation of the knee in the transverse plane was located on the medial side for MS, whereas PS and CR rotated about the lateral compartment or close to the tibial origin. The kinematic function of MS was more similar to that of the healthy knee than PS and CR based on reduced paradoxical anterior translation at low flexion angles and a transverse center of rotation located in the medial compartment. Overall, 6‐DOF knee joint motion for PS and CR were similar across all daily activities, whereas that measured for MS was appreciably different. The kinematic patterns observed for MS reflects a highly conforming medial articulation in the MS design.
Computational Modeling of Oddball Sequence Processing Exposes Common and Differential Auditory Network Changes in First-Episode Schizophrenia-Spectrum Disorders and Schizophrenia

Abstract Background and Hypothesis Differences in sound relevance filtering in schizophrenia are proposed to represent a key index of biological changes in brain function in the illness. This study featured a computational modeling approach to test the hypothesis that processing differences might already be evident in first-episode, becoming more pronounced in the established illness. Study Design Auditory event-related potentials to a typical oddball sequence (rare pitch deviations amongst regular sounds) were recorded from 90 persons with schizophrenia-spectrum disorders (40 first-episode schizophrenia-spectrum, 50 established illness) and age-matched healthy controls. The data were analyzed using dynamic causal modeling to identify the changes in effective connectivity that best explained group differences. Study Results Group differences were linked to intrinsic (within brain region) connectivity changes. In activity-dependent measures these were restricted to the left auditory cortex in first-episode schizophrenia-spectrum but were more widespread in the established illness. Modeling suggested that both established illness and first-episode schizophrenia-spectrum groups expressed significantly lower inhibition of inhibitory interneuron activity and altered gain on superficial pyramidal cells with the data indicative of differences in both putative N-methyl-d-aspartate glutamate receptor activity-dependent plasticity and classic neuromodulation. Conclusions The study provides further support for the notion that examining the ability to alter responsiveness to structured sound sequences in schizophrenia and first-episode schizophrenia-spectrum could be informative to uncovering the nature and progression of changes in brain function during the illness. Furthermore, modeling suggested that limited differences present at first-episode schizophrenia-spectrum may become more expansive with illness progression.
Effectiveness of antimalarial drug combinations in treating concomitant urogenital schistosomiasis in malaria patients in Lambaréné, Gabon: A non-randomised event-monitoring study

Background Urogenital schistosomiasis is prevalent in many malaria endemic regions of sub-Saharan Africa and can lead to long-term health consequences if untreated. Antimalarial drugs used to treat uncomplicated malaria have shown to exert some activity against Schistosoma haematobium. Here, we explore the efficacy on concomitant urogenital schistosomiasis of first-line recommended artemisinin-based combination therapies (ACTs) and investigational second-generation ACTs when administered for the treatment of uncomplicated malaria in Gabon. Methods Microscopic determination of urogenital schistosomiasis was performed from urine samples collected from patients with confirmed uncomplicated malaria. Egg excretion reduction rate and cure rate were determined at 4-weeks and 6-weeks post-treatment with either artesunate-pyronaridine, artemether-lumefantrine, artesunate-amodiaquine or artefenomel-ferroquine. Results Fifty-two (16%) out of 322 malaria patients were co-infected with urogenital schistosomiasis and were treated with antimalarial drug combinations. Schistosoma haematobium egg excretion rates showed a median reduction of 100% (interquartile range (IQR), 17% to 100%) and 65% (IQR, -133% to 100%) at 4-weeks and 6-weeks post-treatment, respectively, in the artesunate-pyronaridine group (n = 20) compared to 35% (IQR, −250% to 70%) and 65% (IQR, -65% to 79%) in the artemether-lumefantrine group (n = 18). Artesunate-amodiaquine (n = 2) and artefenomel-ferroquine combination (n = 3) were not able to reduce the rate of eggs excreted in this limited number of patients. In addition, cure rates were 56% and 37% at 4- and 6-weeks post-treatment, respectively, with artesunate-pyronaridine and no cases of cure were observed for the other antimalarial combinations. Conclusions Antimalarial treatments with artesunate-pyronaridine and artemether-lumefantrine reduced the excretion of S. haematobium eggs, comforting the hypothesis that antimalarial drugs could play a role in the control of schistosomiasis. Trial Registration This trial is registered with clinicaltrials.gov, under the Identifier NCT04264130.
Disordered regions endow structural flexibility to shell proteins and function towards shell–enzyme interactions in 1,2-propanediol utilization microcompartment

Abstract Intrinsically disordered regions in proteins have been functionally linked to the protein–protein interactions and genesis of several membraneless organelles. Depending on their residual makeup, hydrophobicity or charge distribution they may remain in extended form or may assume certain conformations upon biding to a partner protein or peptide. The present work investigates the distribution and potential roles of disordered regions in the integral proteins of 1,2-propanediol utilization microcompartments. We use bioinformatics tools to identify the probable disordered regions in the shell proteins and enzyme of the 1,2-propanediol utilization microcompartment. Using a combination of computational modelling and biochemical techniques we elucidate the role of disordered terminal regions of a major shell protein and enzyme. Our findings throw light on the importance of disordered regions in the self-assembly, providing flexibility to shell protein and mediating its interaction with a native enzyme. Communicated by Ramaswamy H. Sarma
I have decided about my COVID-19 vaccine, what about my child?

ABSTRACT Vaccination has been instrumental in controlling the COVID-19 pandemic, with numbers of new cases decreasing rapidly even as restrictions to control the spread of the virus were removed. The first stage of the vaccination campaign in Israel covered individuals aged 16 and older, following the U.S. Food and Drug Administration’s approval of the vaccine. While the campaign was later extended to those aged 12 and older, some parents continue to have doubts and concerns about the vaccine. Data were collected via an online questionnaire during April 2021; 516 parents participated. This research adopted a holistic approach that combines factors relating to vaccine acceptance previously reported in the literature. The acceptance of pediatric COVID-19 vaccination among parents varied by their children’s age groups, at 44.7%, 53.2%, and 66.4% among parents with children aged 0–6, 6–12, and 12–16, respectively. The results of this study indicate that different sets of variables affect the willingness of parents to vaccinate their children, depending on their child’s age. Moreover, a holistic approach is necessary in order to correctly verify the significant variables. Parents who evaluate the vaccine as more beneficial have a higher probability of being willing to vaccinate. In addition, for ages 12–16, parental willingness to vaccinate is associated with access to information, trust, and neighborhood norms. Those evaluating information about the vaccine as more fake news show higher probability to vaccinate their children. The timing of the survey is highly relevant, especially considering the uncertainty about the effectiveness and side effects of the vaccine.
Multiwavelength Observations of the 2002 Outburst of GX 339–4: Two Patterns of X-Ray-Optical/Near-Infrared Behavior

We report on quasi-simultaneous Rossi X-Ray Timing Explorer and optical/near-infrared (NIR) observations of the black hole candidate X-ray transient GX 339-4. Our observations were made over a time span of more than 8 months in 2002 and cover the initial rise and transition from a hard to a soft spectral state in X-rays. Two distinct patterns of correlated X-ray-optical/NIR behavior were found. During the hard state, the optical/NIR and X-ray fluxes correlated well, with a NIR versus X-ray flux power-law slope similar to that of the correlation found between X-ray and radio fluxes in previous studies of GX 339-4 and other black hole binaries. As the source went through an intermediate state, the optical/NIR fluxes decreased rapidly, and once it had entered the spectrally soft state, the optical/NIR spectrum of GX 339-4 was much bluer, and the ratio of X-ray to NIR flux was higher by a factor of more than 10 compared to the hard state. In the spectrally soft state, changes in the NIR preceded those in the soft X-rays by more than 2 weeks, indicating a disk origin of the NIR emission and providing a measure of the viscous timescale. A sudden onset of NIR flaring of ~0.5 mag on a timescale of 1 day was also observed during this period. We present spectral energy distributions, including radio data, and discuss possible sources for the optical/NIR emission. We conclude that, in the hard state, this emission probably originates in the optically thin part of a jet and that in none of the X-ray states is X-ray reprocessing the dominant source of optical/NIR emission. Finally, comparing the light curves from the all-sky monitor (ASM) and Proportional Counter Array (PCA) instruments, we find that the X-ray/NIR delay depends critically on the sensitivity of the X-ray detector, with the delay inferred from the PCA (if present at all) being a factor of 3-6 times shorter than the delay inferred from the ASM; this may be important in interpreting previously reported X-ray-optical/NIR lags.
Shock Dynamics in Stellar Outbursts. I. Shock Formation

Wave-driven outflows and non-disruptive explosions have been implicated in pre-supernova outbursts, supernova impostors, luminous blue variable eruptions, and some narrow-line and superluminous supernovae. To model these events, we investigate the dynamics of stars set in motion by strong acoustic pulses and wave trains, focusing on nonlinear wave propagation, shock formation, and an early phase of the development of a weak shock. We identify the shock formation radius, showing that a heuristic estimate based on crossing characteristics matches an exact expansion around the wave front and verifying both with numerical experiments. Our general analytical condition for shock formation applies to one-dimensional motions within any static environment, including both eruptions and implosions. We also consider the early phase of shock energy dissipation. We find that waves of super-Eddington acoustic luminosity always create shocks, rather than damping by radiative diffusion. Therefore, shock formation is integral to super-Eddington outbursts.
Inflammation in coronary artery disease-clinical implications of novel HDL-cholesterol–related inflammatory parameters as predictors

Coronary artery disease (CAD) is the leading cause of death worldwide. Inflammation and atherosclerotic plaques are the primary pathological mechanisms of CAD. Upon stimulation by deposited lipids and damaged endothelium, innate and adaptive immune cells are activated and recruited to initiate plaque development. Therefore, inflammatory cells and mediators are used to identify inflammatory risk in CAD patients. HDL-cholesterol (HDL-C) is demonstrated to have anti-inflammatory roles in atherosclerosis by interfering with plasma membrane lipid rafts of immune cells. Based on this, novel inflammatory parameters such as monocyte to HDL-C ratio are explored to improve the risk estimation of CAD prognosis. Moreover, with the advance in treatment strategies targeting the inflammatory process in atherosclerosis, identifying CAD patients with increased inflammatory risk by novel inflammatory parameters is of great importance in guiding CAD management. Therefore, this review aims to summarize the current information regarding inflammatory activation and HDL-C in atherosclerosis with a particular focus on the clinical implication of the novel HDL-C–related inflammatory parameters in CAD.
Serum Neutralization Against SARS-CoV-2 Variants Is Heterogenic and Depends on Vaccination Regimen

Abstract Omicron variants are still the dominant SARS-CoV-2 viruses worldwide, therefore determination of the level of protection from infection and severe disease is essential. Here, we investigated humoral and cellular immunity of individuals immunized by ChAdOx1, BNT162b2, and mRNA-1273 and our results show that IgG and neutralization titers wane over time. However, strongest neutralization against Omicron BA.1 and T-cell responses were detected in ChAdOx1 vaccinees 6 months after the second dose, while no long-lasting neutralization was shown against BA.2 in any cohort. Crucially, our investigation revealed that immunity against variants of concern is heterogenic and dependent on the immunization status.
Revisiting wormhole energy conditions in Riemann-Cartan spacetimes and under Weyl transformations

We show that the violation of the null energy condition by matter, required by traversable wormholes, can be removed in spacetimes with torsion. In addition, we show that this violation can also be removed in the conformal frame obtained by a Weyl transformation. This comes about because both conformally transformed wormholes and wormholes in spacetimes with torsion become sustained thanks to a combination of 'normal' matter, that satisfies the null energy condition, and an induced 'geometric' energy-momentum tensor that is able to greatly violate the null energy condition.
The MHC Motif Atlas: a database of MHC binding specificities and ligands

Abstract The highly polymorphic Major Histocompatibility Complex (MHC) genes are responsible for the binding and cell surface presentation of pathogen or cancer specific T-cell epitopes. This process is fundamental for eliciting T-cell recognition of infected or malignant cells. Epitopes displayed on MHC molecules further provide therapeutic targets for personalized cancer vaccines or adoptive T-cell therapy. To help visualizing, analyzing and comparing the different binding specificities of MHC molecules, we developed the MHC Motif Atlas (http://mhcmotifatlas.org/). This database contains information about thousands of class I and class II MHC molecules, including binding motifs, peptide length distributions, motifs of phosphorylated ligands, multiple specificities or links to X-ray crystallography structures. The database further enables users to download curated datasets of MHC ligands. By combining intuitive visualization of the main binding properties of MHC molecules together with access to more than a million ligands, the MHC Motif Atlas provides a central resource to analyze and interpret the binding specificities of MHC molecules.
Intact memory storage but impaired retrieval in visual memory in autism: New insights from an electrophysiological study

In a recent study on visual episodic memory (Desaunay, Clochon, et al., 2020), we have shown event‐related potentials (ERPs) differences associated with priming (150–300 msec), familiarity (350–470 msec), and recollection (600–700 msec), in young people with autism spectrum disorders (ASD) compared with typical development (TD). To go further into the study of the processes of storage and retrieval of the memory trace, we re‐analyzed Desaunay, Clochon, et al's data using time‐frequency analysis, that is, event‐related synchronization and desynchronization (ERS/ERD). This allows a decomposition of the spectral power within frequency bands associated with these ERPs. We focused both on the same time windows and the same regions of interest as previously published. We mainly identified, in ASD compared with TD, reduced ERS in low‐frequencies (delta, theta) in early time‐windows, and non‐significant differences in ERD in higher frequencies (alpha, beta1) in all time‐windows. Reduced ERS during recognition confirmed previously reported diminution of priming effects and difficulties in manipulation and retrieval of both semantic and episodic information. Conversely, preserved ERD corroborates a preservation of memory storage processes. These observations are consistent with a cognitive model of memory in ASD, that suggests difficulties in cognitive operations or executive demand at retrieval, subsequent to successful long‐term storage of information.
RNase L activation in the cytoplasm induces aberrant processing of mRNAs in the nucleus

The antiviral endoribonuclease, RNase L, is activated by the mammalian innate immune response to destroy host and viral RNA to ultimately reduce viral gene expression. Herein, we show that RNase L and RNase L-mediated mRNA decay are primarily localized to the cytoplasm. Consequently, RNA-binding proteins (RBPs) translocate from the cytoplasm to the nucleus upon RNase L activation due to the presence of intact nuclear RNA. The re-localization of RBPs to the nucleus coincides with global alterations to RNA processing in the nucleus. While affecting many host mRNAs, these alterations are pronounced in mRNAs encoding type I and type III interferons and correlate with their retention in the nucleus and reduction in interferon protein production. Similar RNA processing defects also occur during infection with either dengue virus or SARS-CoV-2 when RNase L is activated. These findings reveal that the distribution of RBPs between the nucleus and cytosol is dictated by the availability of RNA in each compartment. Thus, viral infections that trigger RNase L-mediated cytoplasmic RNA in the cytoplasm also alter RNA processing in the nucleus, resulting in an ingenious multi-step immune block to protein biogenesis.
Identification of key proteins of cytopathic biotype bovine viral diarrhoea virus involved in activating NF-κB pathway in BVDV-induced inflammatory response

ABSTRACT Bovine viral diarrhoea virus (BVDV) is the etiologic agent of bovine viral diarrhea-mucosal disease, one of the most important viral diseases in cattle, with inflammatory diarrhea, enteritis, and mucosa necrosis as the major clinical manifestations. NF-κB is an important transcription complex that regulates the expression of genes involved in inflammation and immune responses. NLRP3 inflammasome plays a key role in the development of inflammatory diseases. However, whether the activation of NF-κB is crucial for BVDV infection-induced inflammatory responses remains unclear. The results of our present study showed that BVDV infection significantly activated the NF-κB pathway and promoted the expression of NLRP3 inflammasome components (NLRP3, ASC, pro-caspase 1) as well inflammatory cytokine pro-IL-1β in BVDV-infected bovine cells, resulting in the cleavage of pro-caspase 1 and pro-IL-1β into active form caspase 1 and IL-1β. However, the levels of the NLRP3 inflammasome components and inflammatory cytokines were obviously inhibited, as well the cleavage of pro-caspase 1 and pro-IL-1β in the pre-treated bovine cells with NF-κB-specific inhibitors after BVDV infection. Further, cytopathic biotype BVDV (cpBVDV) Erns and NS5A proteins with their key functional domains contributed to BVDV-induced inflammatory responses via activating the NF-κB pathway were confirmed experimentally. Especially, the NS5A can promote cholesterol synthesis and accelerate its augmentation, further activating the NF-κB signalling pathway. Conclusively, our data elucidate that the activation of NF-κB signaling pathway plays a crucial role in cpBVDV infection-induced inflammatory responses.
Detecting primordial B-modes after Planck

We update the forecasts for the measurement of the tensor-to-scalar ratio r for various ground-based experiments (AdvACT, CLASS, Keck/BICEP3, Simons Array, SPT-3G), balloons (EBEX 10k and Spider) and satellites (CMBPol, COrE and LiteBIRD), taking into account the recent Planck data on polarized dust and using a component separation method. The forecasts do not change significantly with respect to previous estimates when at least three frequencies are available, provided foregrounds can be accurately described by few parameters. We argue that a theoretically motivated goal for future experiments is r∼2×10−3, and that this is achievable if the noise is reduced to ∼1 μK-arcmin and lensing is reduced to 10% in power. We study the constraints experiments will be able to put on the frequency and ℓ-dependence of the tensor signal as a check of its primordial origin. Futuristic ground-based and balloon experiments can have good constraints on these parameters, even for r∼2×10−3. For the same value of r, satellites will marginally be able to detect the presence of the recombination bump, the most distinctive feature of the primordial signal.