Miracle-dz/UniFAR-FTUs huggingface dataset:
The relationship between residential altitude and stunting: evidence from >26 000 children living in highlands and lowlands of Ethiopia

Abstract Little information is known about the influence of altitude on child growth in Ethiopia, where most people live in highlands. We investigated the relation of residential altitude with growth faltering (stunting) of infants and young children in Ethiopia. We also examined whether the altitude–growth relationship was independent of the influence of the dietary and non-dietary determinants of growth. We used the data of 26 976 under-5-year-old children included in the Ethiopian Demographic and Health Surveys, conducted from 2005 to 2016. The samples were recruited following a two-stage cluster sampling strategy. Stunting was defined by height-for-age <−2 z-scores. The relationship between residential altitude and stunting was examined by running multiple logistic regression analysis, controlling the effect of covariate dietary and non-dietary variables. The residential altitude of the study participants ranged from −116 to 4500 m above sea level (masl). There was a significant and progressive increase in the prevalence and odds of stunting with increasing altitude (P < 0·001), irrespective of the dietary and non-dietary predictors of stunting. The prevalence of stunting was lowest in lowlands (39 %) and highest in highlands (47 %). Compared with altitude <1000 masl, the odds of stunting was 1·41 times higher at altitude ≥2500 masl (OR 1·41, 95 % CI 1·16, 1·71) and 1·29 times higher at altitude 2000–2499 masl (OR 1·29, 95 % CI 1·11, 1·49). Children living in highlands might be at a higher risk of poor growth. Further studies are warranted to understand the mechanism behind the observed altitude–stunting link and identify strategies to compensate for the growth-faltering effect of living in highlands.
Sialic acids rather than glycosaminoglycans affect normal and sickle red blood cell rheology by binding to four major sites on fibrinogen

and corticosteroids would not have been considered without our patient's requests, and would not have been possible without our patient's intelligence, understanding and agreement. We could confidently manage her as an outpatient because she was reliable, she lived near to the medical center, and her family could help with her management and guarantee her safety. Also, we would not have considered this treatment if her thrombocytopenia had been severe or if she had any neurologic symptoms. But with all of these supportive circumstances, we were able to manage our patient successfully. Our experience illustrates the ability of caplacizumab and rituximab, without hospitalization, to achieve a remission in patients with TTP. More importantly, our experience illustrates the value of integrating shared decision-making into clinical practice and exemplifies how shared decision-making can facilitate changes of medical practice, including utilization of new treatments.
Long noncoding RNA VPS9D1-AS1 augments the malignant phenotype of non-small cell lung cancer by sponging microRNA-532-3p and thereby enhancing HMGA2 expression

We investigated the influence of the long noncoding RNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) on the malignant phenotype of non-small cell lung cancer (NSCLC) cells in vitro and in vivo. We also explored the mechanisms by which VPS9D1-AS1 exerts its oncogenic action during NSCLC progression. VPS9D1-AS1 expression was upregulated in NSCLC; the extent of its upregulation significantly correlated with patients’ adverse clinicopathological characteristics and shorter overall survival. When VPS9D1-AS1 was knocked down in NSCLC cells, their proliferation, colony-forming capacity, migration, and invasiveness were lower, whereas their apoptosis rate was higher, compared to the control. VPS9D1-AS1 knockdown attenuated tumor growth of NSCLC cells in vivo. Mechanistically, VPS9D1-AS1 directly interacted with microRNA-532-3p (miR-532-3p) in NSCLC cells; the impact of VPS9D1-AS1 knockdown on NSCLC cells was attenuated by miR-532-3p inhibition. Furthermore, VPS9D1-AS1 knockdown decreased the expression of high mobility group AT-hook 2 (HMGA2) in NSCLC cells via miR-532-3p sponging. Recovery of HMGA2 expression partially reversed the inhibitory effects of VPS9D1-AS1 knockdown on NSCLC cells. Thus, VPS9D1-AS1 functions as a competing endogenous RNA that positively regulates HMGA2 expression by sponging miR-532-3p in NSCLC cells, suggesting that the VPS9D1-AS1–miR-532-3p–HMGA2 pathway can be a potential diagnostic and/or therapeutic target in NSCLC.
Class-A penicillin binding proteins do not contribute to cell shape but repair cell-wall defects

Cell shape and cell-envelope integrity of bacteria are determined by the peptidoglycan cell wall. In rod-shaped Escherichia coli, two conserved sets of machinery are essential for cell-wall insertion in the cylindrical part of the cell: the Rod complex and the class-A penicillin-binding proteins (aPBPs). While the Rod complex governs rod-like cell shape, aPBP function is less well understood. aPBPs were previously hypothesized to either work in concert with the Rod complex or to independently repair cell-wall defects. First, we demonstrate through modulation of enzyme levels that aPBPs do not contribute to rod-like cell shape but are required for mechanical stability, supporting their independent activity. By combining measurements of cell-wall stiffness, cell-wall insertion, and PBP1b motion at the single-molecule level, we then present evidence that PBP1b, the major aPBP, contributes to cell-wall integrity by repairing cell wall defects.
Neural Machine Translation With GRU-Gated Attention Model

Neural machine translation (NMT) heavily relies on context vectors generated by an attention network to predict target words. In practice, we observe that the context vectors for different target words are quite similar to one another and translations with such nondiscriminatory context vectors tend to be degenerative. We ascribe this similarity to the invariant source representations that lack dynamics across decoding steps. In this article, we propose a novel gated recurrent unit (GRU)-gated attention model (GAtt) for NMT. By updating the source representations with the previous decoder state via a GRU, GAtt enables translation-sensitive source representations that then contribute to discriminative context vectors. We further propose a variant of GAtt by swapping the input order of the source representations and the previous decoder state to the GRU. Experiments on the NIST Chinese–English, WMT14 English–German, and WMT17 English–German translation tasks show that the two GAtt models achieve significant improvements over the vanilla attention-based NMT. Further analyses on the attention weights and context vectors demonstrate the effectiveness of GAtt in enhancing the discriminating capacity of representations and handling the challenging issue of overtranslation.
Enhancing Professional Reasoning through the Use of Evidence-Based Assessments, Robust Case Formulations and Measurable Goals

The value of therapists documenting their clinical reasoning and negotiating specific and measurable goals is widely acknowledged. However, the literature suggests that practitioners often encounter barriers when implementing best practice. This article details how occupational therapists in Derbyshire Healthcare NHS Foundation Trust entered an academic partnership, which transformed their communication of clinical and professional reasoning. Having adopted a conceptual model of practice, they established clearly defined processes for assessment, case formulation and goal setting. Service users, carers and team members confirmed that these initiatives enhanced person-centred practice, highlighted occupational issues and made treatment planning more effective for the whole team.
The domestication syndrome in vegetatively-propagated field crops.

BACKGROUND Vegetatively propagated crops are globally significant in terms of current agricultural production, as well as for understanding the long-term history of early agriculture and plant domestication. Today, significant field crops include sugarcane (Saccharum officinarum), potato (Solanum tuberosum), manioc (Manihot esculenta), bananas and plantains (Musa cvs.), sweet potato (Ipomoea batatas), yams (Dioscorea spp.) and taro (Colocasia esculenta). In comparison to sexually-reproduced crops, especially cereals and legumes, the domestication syndrome in vegetatively-propagated field crops is poorly defined. AIMS AND SCOPE Here, a range of phenotypic traits potentially comprising a syndrome associated with early domestication of vegetatively-propagated field crops is proposed, including: mode of reproduction, yield of edible portion, ease of harvesting, defensive adaptations, timing of production and plant architecture. The archaeobotanical visibility of these syndrome traits is considered with a view to the reconstruction of the geographical and historical pathways of domestication for vegetatively-propagated field crops in the past. CONCLUSIONS Although convergent phenotypic traits are identified, none are ubiquitous and some are divergent. In contrast to cereals and legumes, several traits seem to represent varying degrees of plastic response to growth environment and practices of cultivation, as opposed to solely morphogenetic 'fixation'.
Mechanisms of Change in Mindfulness-Based Cognitive Therapy in Adults With ADHD

Objective: Mindfulness-based cognitive therapy (MBCT) has been demonstrated to be effective in adults with ADHD. The aim of the current study was to examine its possible working mechanisms. Method: In the context of an randomized controlled trial (RCT), MBCT + TAU (treatment as usual) (n = 43) versus TAU (n = 51), we used mediation analyses to examine whether reduction of clinician-rated ADHD symptoms and improvement of positive mental health at 6-month follow-up had been mediated by change in mindfulness skills, self-compassion, and executive functioning over the course of MBCT. Results: Increase of self-compassion mediated improvement of positive mental health at 6-month follow-up. Improvement of mindfulness skills or self-compassion did not mediate the reduction in ADHD symptoms. Additional analyses suggest that self-reported inhibition did. Conclusion: The effect of MBCT on ADHD symptoms and positive mental health thus occurred via different mechanisms of change, that is, by improvements in inhibition and self-compassion, respectively.
An observational study of an approach to accommodate a fourth-year to third-year neurology clerkship curricular transition

ABSTRACT Background: Curricular transformation can result in bulges in students’ clinical placements. Objective: To report on learner outcomes associated with a competency-based opt-out approach for a required 4th-year neurology clerkship. Methods and Study Design: During Oregon Health & Science University’s recent undergraduate medical education curricular transformation, a 4-week required neurology clerkship transitioned from the fourth-year to the third-year in academic year 2016–17. Because this would have resulted in the neurology clerkship accommodating double enrollment for an entire academic year, 4th year medical students from the prior curriculum (graduating class of 2017) were offered the option of opting-out of the required neurology clerkship if they demonstrated competency by passing the USA National Board of Medical Examiners (US-NBME) clinical neurology subject examination and completing a neurology faculty-observed history and complete neurological examination. Results: Fifty-seven of 133 fourth-year students (42.9%) chose to complete the required neurology clerkship with 77 (57.9%) choosing to opt-out. All opt-out students passed the neurological exam assessment and scored similarly to the students who took the clerkship (US-NBME Neurology Subject Exam mean raw score in the opt-out group 76.9 vs, 77.6; p = 0.61). Students grades did not differ. Students who opted-out tended to pursue surgical careers (e.g., general surgery −10.8% opted-out vs 0% clerkship, OB/GYN – 6.8% opted-out vs 0% clerkship, orthopedic surgery 5.4% opted-out vs 0% clerkship) where those who took the clerkship tended to choose medical residency training disciplines (family medicine −16.1% clerkship vs 10.8% opting-out; internal medicine – 32.1% clerkship vs 14.9% opting-out; psychiatry 10.7% clerkship vs 2.7% opting-out (p = 0.042) Conclusion: While undertaking the neurology clerkship would have been the desired approach, students appear not to have been harmed by the opt-out approach regarding performance on the US-NBME clinical neurology subject exam. Choices regarding opting-out versus taking the neurology clerkship appear to be associated with career choice.
Anterior cingulate cortex differently modulates frontoparietal functional connectivity between resting‐state and working memory tasks

The brain frontoparietal regions and the functional communications between them are critical in supporting working memory and other executive functions. The functional connectivity between frontoparietal regions are modulated by working memory loads, and are shown to be modulated by a third brain region in resting‐state. However, it is largely unknown whether the third‐region modulations remain the same during working memory tasks or were largely modulated by task demands. In the current study, we collected functional MRI (fMRI) data when the subjects were performing n‐back tasks and in resting‐state. We first used a block‐designed localizer to define the frontoparietal regions that showed higher activations in the 2‐back than the 1‐back condition. Next, we performed physiophysiological interaction (PPI) analysis using left and right middle frontal gyrus (MFG) and superior parietal lobule (SPL) regions, respectively, in three continuous‐designed runs of resting‐state, 1‐back, and 2‐back conditions. No regions showed consistent modulatory interactions with the seed pairs in the three conditions. Instead, the anterior cingulate cortex (ACC) showed different modulatory interactions with the right MFG and SPL among the three conditions. While the increased activity of the ACC was associated with decreased functional coupling between the right MFG and SPL in resting‐state, it was associated with increased functional coupling in the 2‐back condition. The observed task modulations support the functional significance of the modulations of the ACC on frontoparietal connectivity.
MatchMixeR: a cross-platform normalization method for gene expression data integration

MOTIVATION Combining gene expression (GE) profiles generated from different platforms enables previously infeasible studies due to sample size limitations. Several cross-platform normalization methods have been developed to remove the systematic differences between platforms, but they may also remove meaningful biological differences among datasets. In this work, we propose a novel approach that removes the platform, not the biological differences. Dubbed as "MatchMixeR", we model platform differences by a linear mixed effects regression (LMER) model, and estimate them from matched GE profiles of the same cell line or tissue measured on different platforms. The resulting model can then be used to remove platform differences in other datasets. By using LMER, we achieve better bias-variance trade-off in parameter estimation. We also design a computationally efficient algorithm based on the moment method, which is ideal for ultra-high-dimensional LMER analysis. RESULTS Compared with several prominent competing methods, MatchMixeR achieved the highest after-normalization concordance. Subsequent differential expression analyses based on datasets integrated from different platforms showed that using MatchMixeR achieved the best trade-off between true and false discoveries, and this advantage is more apparent in datasets with limited samples or unbalanced group proportions. AVAILABILITY Our method is implemented in R-package, "MatchMixeR", freely available at: https://github.com/dy16b/Cross-Platform-Normalization.
Targeting Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐cell acute lymphoblastic leukemia

T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive hematological disorder that results from the clonal transformation of T‐cell precursors. Phosphatidylinositol 3‐kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) and canonical Wnt/β‐catenin signaling pathways play a crucial role in T‐cell development and in self‐renewal of healthy and leukemic stem cells. Notably, β‐catenin is a transcriptional regulator of several genes involved in cancer cell proliferation and survival. In this way, aberrations of components belonging to the aforementioned networks contribute to T‐ALL pathogenesis. For this reason, inhibition of both pathways could represent an innovative strategy in this hematological malignancy. Here, we show that combined targeting of Wnt/β‐catenin pathway through ICG‐001, a CBP/β‐catenin transcription inhibitor, and of the PI3K/Akt/mTOR axis through ZSTK‐474, a PI3K inhibitor, downregulated proliferation, survival, and clonogenic activity of T‐ALL cells. ICG‐001 and ZSTK‐474 displayed cytotoxic effects, and, when combined together, induced a significant increase in apoptotic cells. This induction of apoptosis was associated with the downregulation of Wnt/β‐catenin and PI3K/Akt/mTOR pathways. All these findings were confirmed under hypoxic conditions that mimic the bone marrow niche where leukemic stem cells are believed to reside. Taken together, our findings highlight potentially promising treatment consisting of cotargeting Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐ALL settings.
STARD1 and NPC1 expression as pathological markers associated with astrogliosis in post-mortem brains from patients with Alzheimer's disease and Down syndrome

Alzheimer´s disease (AD) is a progressive neurodegenerative disorder of complex etiology, while Down syndrome (DS) is considered a genetically determined form of AD. Alterations in cholesterol homeostasis have been linked to AD although the role in this association is not well understood. Increased expression of STARD1 and NPC1, which are involved in intracellular cholesterol trafficking, has been reported in experimental AD models but not in patients with AD. Here we analyzed endolysosomal/mitochondrial cholesterol homeostasis, expression of NPC1 and STARD1 and correlation with pathological markers of AD in cortex and hippocampus from post-mortem brains from patients with AD and DS. NPC1 expression was observed in hippocampus from patients with AD and DS. Moreover, STARD1 expression increased in hippocampus and cortex from patients with AD and DS, respectively, and its immunoreactivity discriminated controls from AD or DS with a better accuracy than Aβ42. Hippocampal areas stained with the recombinant GST-PFO probe showed increased mitochondrial cholesterol within astrocytes of brains from patients with AD and DS-brains compared to controls. Lysosomal cholesterol accumulation within hippocampal astrocytes was higher in DS than in AD. These data revealed increased intracellular cholesterol loading in hippocampus from patient with AD and DS and suggest that STARD1 could be a potential pre-clinical marker associated with early stages of AD pathology.
Electroconvulsive therapy treatment responsive multimodal brain networks

Electroconvulsive therapy is regarded as the most effective antidepressant treatment for severe and treatment‐resistant depressive episodes. Despite the efficacy of electroconvulsive therapy, the neurobiological underpinnings and mechanisms underlying electroconvulsive therapy induced antidepressant effects remain unclear. The objective of this investigation was to identify electroconvulsive therapy treatment responsive multimodal biomarkers with the 17‐item Hamilton Depression Rating Scale guided brain structure–function fusion in 118 patients with depressive episodes and 60 healthy controls. Results show that reduced fractional amplitude of low frequency fluctuations in the prefrontal cortex, insula and hippocampus, linked with increased gray matter volume in anterior cingulate, medial temporal cortex, insula, thalamus, caudate and hippocampus represent electroconvulsive therapy responsive covarying functional and structural brain networks. In addition, relative to nonresponders, responder‐specific electroconvulsive therapy related brain networks occur in frontal‐limbic network and are associated with successful therapeutic outcomes. Finally, electroconvulsive therapy responsive brain networks were unrelated to verbal declarative memory. Using a data‐driven, supervised‐learning method, we demonstrated that electroconvulsive therapy produces a remodeling of brain functional and structural covariance that was unique to antidepressant symptom response, but not linked to memory impairment.
Bridging inhaled aerosol dosimetry to physiologically based pharmacokinetic modeling for toxicological assessment: nicotine delivery systems and beyond

Abstract One of the challenges for toxicological assessment of inhaled aerosols is to accurately predict their deposited and absorbed dose. Transport, evolution, and deposition of liquid aerosols are driven by complex processes dominated by convection-diffusion that depend on various factors related to physics and chemistry. These factors include the physicochemical properties of the pure substance of interest and associated mixtures, the physical and chemical properties of the aerosols generated, the interplay between different factors during transportation and deposition, and the subject-specific inhalation topography. Several inhalation-based physiologically based pharmacokinetic (PBPK) models have been developed, but the applicability of these models for aerosols has yet to be verified. Nicotine is among several substances that are often delivered via the pulmonary route, with varied kinetics depending upon the route of exposure. This was used as an opportunity to review and discuss the current knowledge and state-of-the-art tools combining aerosol dosimetry predictions with PBPK modeling efforts. A validated tool could then be used to perform for toxicological assessment of other inhaled therapeutic substances. The Science Panel from the Alliance of Risk Assessment have convened at the “Beyond Science and Decisions: From Problem Formulation to Dose-Response Assessment” workshop to evaluate modeling approaches and address derivation of exposure-internal dose estimations for inhaled aerosols containing nicotine or other substances. The discussion involved PBPK model evaluation criteria, challenges, and choices that arise in such a model design, development, and application as a computational tool for use in human toxicological assessments.
PUMAH: Pan-Tilt Ultrasound Mid-Air Haptics for Larger Interaction Workspace in Virtual Reality

Mid-air haptic interfaces are promising tools for providing tactile feedback in Virtual Reality (VR) applications, as they do not require the user to be tethered to, hold, or wear any system or device. Currently, focused ultrasound phased arrays are the most mature solution for providing mid-air haptic feedback. They modulate the phase of an array of ultrasound emitters so as to generate focused points of oscillating high pressure, eliciting vibrotactile sensations when encountering a user's skin. While these arrays feature a reasonably large vertical workspace, they are not capable of displaying stimuli far beyond their horizontal limits, severely limiting their workspace in the lateral dimensions. In this paper, we propose an innovative low-cost solution for enlarging the workspace of focused ultrasound arrays. It features two degrees of freedom, rotating the array around the pan and tilt axes, thereby significantly increasing the usable workspace and enabling multi-directional feedback. Our hardware tests and human subject study in an ecological VR setting show a 14-fold increase in workspace volume, with focal point repositioning speeds over 0.85 m/s while delivering tactile feedback with positional accuracy below 18 mm. Finally, we propose a representative use case to exemplify the potential of our system for VR applications.