Miracle-dz/UniFAR-FTUs huggingface dataset:
Representation of Spatial and Feature Information in the Monkey Dorsal and Ventral Prefrontal Cortex

The primate prefrontal cortex (PFC) is critical for executive functions including working memory, task switching and response selection. The functional organization of this area has been a matter of debate over a period of decades. Early models proposed segregation of spatial and object information represented in working memory in the dorsal and ventral PFC, respectively. Other models emphasized the integrative ability of the entire PFC depending on task demands, not necessarily tied to working memory. An anterior-posterior hierarchy of specialization has also been speculated, in which progressively more abstract information is represented more anteriorly. Here we revisit this debate, updating these arguments in light of recent evidence in non-human primate neurophysiology studies. We show that spatial selectivity is predominantly represented in the posterior aspect of the dorsal PFC, regardless of training history and task performed. Objects of different features excite both dorsal and ventral prefrontal neurons, however neurons highly specialized for feature information are located predominantly in the posterior aspect of the ventral PFC. In accordance with neuronal selectivity, spatial working memory is primarily impaired by inactivation or lesion of the dorsal PFC and object working memory by ventral inactivation or lesion. Neuronal responses are plastic depending on task training but training too has dissociable effects on ventral and dorsal PFC, with the latter appearing to be more plastic. Despite the absence of an overall topography, evidence exists for the orderly localization of stimulus information at a sub-millimeter scale, within the dimensions of a cortical column. Unresolved questions remain, regarding the existence or not of a functional map at the areal and columnar scale, and the link between behavior and neuronal activity for different prefrontal subdivisions.
Motor imagery in chronic neglect: An fMRI pilot study

ABSTRACT Aim. Previous studies indicate the effectiveness of motor imagery training in stroke patients. To determine whether patients showing chronic visuospatial neglect symptoms may profit from motor imagery training, it is important to assess how the brain implements motor imagery when cortical systems involved in attentional control are impaired. Method. Therefore, in this pilot study, nine chronic neglect patients with right-hemispheric stroke performed motor imagery of a finger opposition task during functional magnetic resonance imaging (fMRI). Results. Imagery of unaffected hand movements was related to activations in the left primary somatosensory and premotor cortices as well as in the left supplementary motor area. During the imagery of the affected hand, patients displayed activations in the left premotor cortex and supplementary motor area as well as left dorsolateral prefrontal cortex. Furthermore, time since onset and visual imagery capacity were negatively related to activation in the supplementary motor area during the imagery of the affected hand. Conclusions. These initial results demonstrate motor imagery capacity in patients with chronic neglect via compensatory neural processing during motor imagery of the affected hand in ipsilateral brain regions, since we found that the supplementary motor area appears to be specifically related to neglect severity. Although our results must be treated with caution due to the small sample size and missing control group, they indicate that neglect is not necessarily an exclusion criterion for motor imagery training per se.
Epigenetics of fragile X syndrome and fragile X‐related disorders

The fragile X mental retardation 1 gene (FMR1)‐related disorder fragile X syndrome (FXS) is the most common heritable form of cognitive impairment and the second most common cause of comorbid autism. FXS usually results when a premutation trinucleotide CGG repeat in the 5′ untranslated region of the FMR1 gene (CGG 55–200) expands over generations to a full mutation allele (CGG >200). This expansion is associated with silencing of the FMR1 promoter via an epigenetic mechanism that involves DNA methylation of the CGG repeat and the surrounding regulatory regions. Decrease in FMR1 transcription is associated with loss of the FMR1 protein that is needed for typical brain development. The past decade has seen major advances in our understanding of the genetic and epigenetic processes that underlie FXS. Here we review these advances and their implications for diagnosis and treatment for individuals who have FMR1‐related disorders.
In which groups of pregnant women can the caesarean delivery rate likely be reduced safely in the USA? A multicentre cross-sectional study

Objectives To identify obstetrical subgroups in which (1) the caesarean delivery (CD) rate may be reduced without compromising safety and (2) CD may be associated with better perinatal outcomes. Design A multicentre cross-sectional study. Setting 19 hospitals in the USA that participated in the Consortium on Safe Labor. Participants 228 562 pregnant women in 2002–2008. Main outcome measures Maternal and neonatal safety was measured using the individual Weighted Adverse Outcome Score. Methods Women were divided into 10 subgroups according to a modified Robson classification system. Generalised estimated equation model was used to examine the relationships between mode of delivery and Weighted Adverse Outcome Score in each subgroup. Results The overall caesarean rate was 31.2%. Repeat CD contributed 29.5% of all CD, followed by nulliparas with labour induction (15.3%) and non-cephalic presentation (14.3%). The caesarean rates in induced nulliparas with a term singleton cephalic pregnancy and women with previous CD were 31.6% and 82.0%, respectively. CD had no clinically meaningful association with perinatal outcomes in most subgroups. However, in singleton preterm breech presentation and preterm twin gestation with the first twin in non-cephalic presentation, CD was associated with substantially improved maternal and perinatal outcomes. Conclusions Women with repeat CD, term non-cephalic presentation, term twins or other multiple gestation and preterm births may be the potential targets for safely reducing prelabour CD rate, while nulliparas or multiparas with spontaneous or induced labour, women with repeat CD, term non-cephalic presentation, term twins or other multiple gestation and preterm births are potential targets for reducing intrapartum CD rate without compromising maternal and neonatal safety in the USA. On the other hand, CD may still be associated with better perinatal outcomes in women with singleton preterm breech presentation or preterm twins with the first twin in non-cephalic presentation.
Integrated Epigenetics, Transcriptomics, and Metabolomics to Analyze the Mechanisms of Benzo[a]pyrene Neurotoxicity in the Hippocampus

Benzo[a]pyrene (B[a]P) is a common environmental pollutant that is neurotoxic to mammals, which can cause changes to hippocampal function and result in cognitive disorders. The mechanisms of B[a]P-induced impairments are complex . To date there have been no studies on the association of epigenetic, transcriptomic, and metabolomic changes with neurotoxicity after B[a]P exposure. In the present study, we investigated the global effect of B[a]P on DNA methylation patterns, noncoding RNAs (ncRNAs) expression, coding RNAs expression, and metabolites in the rat hippocampus. Male Sprague Dawley rats (SD rats) received daily gavage of B[a]P (2.0 mg/kg body weight [BW]) or corn oil for 7 weeks. Learning and memory ability was analyzed using the Morris water maze (MWM) test and change to cellular ultrastructure in the hippocampus was analyzed using electron microscope observation. Integrated analysis of epigenetics, transcriptomics, and metabolomics was conducted to investigate the effect of B[a]P exposure on the signaling and metabolic pathways. Our results suggest that B[a]P could lead to learning and memory deficits, likely as a result of epigenetic and transcriptomic changes that further affected the expression of CACNA1C, Tpo, etc. The changes in expression ultimately affecting LTP, tyrosine metabolism, and other important metabolic pathways.
Transcalibur: weight moving VR controller for dynamic rendering of 2D shape using haptic shape illusion

We introduce a dynamic weight moving VR controller for 2d haptic shape rendering using a haptic shape illusion. This allows users to perceive the feeling of various shapes in virtual space with a single controller. We designed a device that drives weight on a 2d planar area to alter mass properties of the hand-held controller. Our user study showed that the system succeeded in providing shape perception over a wide range.
Prereduction traction for the prevention of avascular necrosis before closed reduction for developmental dysplasia of the hip: a meta-analysis

Background and purpose Avascular necrosis (AVN) is one of the common complications after closed reduction and hip spica cast for developmental dysplasia of the hip (DDH). Prereduction traction has been used to reduce a dislocated hip or decrease the risk of AVN, but there are conflicting results in prevention effects on AVN. The purpose of this study was to systematically review the current literature and evaluate the effect of prereduction traction in preventing AVN in children with DDH treated by closed reduction through a meta-analysis. Materials and methods A systematic review of the literature was performed using PubMed and EMBASE with variations of three major terms: 1) hip dislocation; 2) closed reduction; and 3) avascular necrosis. Seven studies that could compare the incidence of AVN between the traction and no-traction group were included. Methodological quality was assessed, a heterogeneity test was done (p=0.008), and the pooled risk ratios were estimated. Results The association between traction and AVN was assessed, using data on 683 hips treated by closed reduction. The incidence of AVN in the traction and no-traction groups ranged from 5% to 47.7% and from 0% to 72.7%, respectively. A meta-analysis with a random effects model indicated no significant difference in the incidence of AVN between traction and no-traction groups (p=0.536). Conclusion There was insufficient evidence to decide the efficacy of prereduction traction before closed reduction in reducing the risk of AVN in patients with DDH in this meta-analysis. To recommend prereduction traction for the prevention of AVN, long-term follow-up studies considering age, severity of dislocation, and appropriate traction method are needed.
Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease

Chagasic heart disease develops in 30% of those infected with the protozoan parasite Trypanosoma cruzi, but can take decades to become symptomatic. Because of this, it has been difficult to assess the extent to which antiparasitic therapy can prevent the development of pathology. ABSTRACT Chagasic heart disease develops in 30% of those infected with the protozoan parasite Trypanosoma cruzi, but can take decades to become symptomatic. Because of this, it has been difficult to assess the extent to which antiparasitic therapy can prevent the development of pathology. We sought to address this question using experimental murine models, exploiting highly sensitive bioluminescent imaging to monitor curative efficacy. Mice were inoculated with bioluminescent parasites and then cured in either the acute or chronic stage of infection with benznidazole. At the experimental endpoint (5 to 6 months postinfection), heart tissue was removed and assessed for inflammation and fibrosis, two widely used markers of cardiac pathology. Infection of BALB/c and C3H/HeN mice with distinct T. cruzi lineages resulted in greatly increased myocardial collagen content at a group level, indicative of fibrotic pathology. When mice were cured by benznidazole in the acute stage, the development of pathology was completely blocked. However, if treatment was delayed until the chronic stage, cardiac fibrosis was observed in the BALB/c model, although the protective effect was maintained in the case of C3H/HeN mice. These experiments therefore demonstrate that curative benznidazole treatment early in murine T. cruzi infections can prevent the development of cardiac fibrosis. They also show that treatment during the chronic stage can block pathology but the effectiveness varies between infection models. If these findings are extendable to humans, it implies that widespread chemotherapeutic intervention targeted at early-stage infections could play a crucial role in reducing Chagas disease morbidity at a population level.
Closing the global ozone yield gap: Quantification and cobenefits for multistress tolerance

Increasing both crop productivity and the tolerance of crops to abiotic and biotic stresses is a major challenge for global food security in our rapidly changing climate. For the first time, we show how the spatial variation and severity of tropospheric ozone effects on yield compare with effects of other stresses on a global scale, and discuss mitigating actions against the negative effects of ozone. We show that the sensitivity to ozone declines in the order soybean > wheat > maize > rice, with genotypic variation in response being most pronounced for soybean and rice. Based on stomatal uptake, we estimate that ozone (mean of 2010–2012) reduces global yield annually by 12.4%, 7.1%, 4.4% and 6.1% for soybean, wheat, rice and maize, respectively (the “ozone yield gaps”), adding up to 227 Tg of lost yield. Our modelling shows that the highest ozone‐induced production losses for soybean are in North and South America whilst for wheat they are in India and China, for rice in parts of India, Bangladesh, China and Indonesia, and for maize in China and the United States. Crucially, we also show that the same areas are often also at risk of high losses from pests and diseases, heat stress and to a lesser extent aridity and nutrient stress. In a solution‐focussed analysis of these results, we provide a crop ideotype with tolerance of multiple stresses (including ozone) and describe how ozone effects could be included in crop breeding programmes. We also discuss altered crop management approaches that could be applied to reduce ozone impacts in the shorter term. Given the severity of ozone effects on staple food crops in areas of the world that are also challenged by other stresses, we recommend increased attention to the benefits that could be gained from addressing the ozone yield gap.
Galectins control MTOR and AMPK in response to lysosomal damage to induce autophagy

ABSTRACT The Ser/Thr protein kinase MTOR (mechanistic target of rapamycin kinase) regulates cellular metabolism and controls macroautophagy/autophagy. Autophagy has both metabolic and quality control functions, including recycling nutrients at times of starvation and removing dysfunctional intracellular organelles. Lysosomal damage is one of the strongest inducers of autophagy, and yet mechanisms of its activation in response to lysosomal membrane damage are not fully understood. Our recent study has uncovered a new signal transduction system based on cytosolic galectins that elicits autophagy by controlling master regulators of metabolism and autophagy, MTOR and AMPK, in response to lysosomal damage. Thus, intracellular galectins are not, as previously thought, passive tags recognizing damage to guide selective autophagy receptors, but control the activation state of AMPK and MTOR in response to endomembrane damage. Abbreviations: MTOR: mechanistic target of rapamycin kinase; AMPK: AMP-activated protein kinase / Protein Kinase AMP-Activated; SLC38A9: Solute Carrier Family 38 Member 9; APEX2: engineered ascorbate peroxidase 2; RRAGA/B: Ras Related GTP Binding A or B; LAMTOR1: Late Endosomal/Lysosomal Adaptor, MAPK and MTOR Activator 1; LGALS8: Lectin, Galactoside-Binding, Soluble, 8 / Galectin 8; LGALS9: Lectin, Galactoside-Binding, Soluble, 9 / Galectin 9; TAK1: TGF-Beta Activated Kinase 1 / Mitogen-Activated Protein Kinase Kinase Kinase 7 (MAP3K7); STK11/LKB1: Serine/Threonine Kinase 11 / Liver Kinase B1; ULK1: Unc-51 Like Autophagy Activating Kinase 1.
Marked Response of a Hypermutated ACTH-Secreting Pituitary Carcinoma to Ipilimumab and Nivolumab

Context Pituitary carcinoma is a rare and aggressive malignancy with a poor prognosis and few effective treatment options. Case A 35-year-old woman presented with an aggressive ACTH-secreting pituitary adenoma that initially responded to concurrent temozolomide and capecitabine prior to metastasizing to the liver. Following treatment with ipilimumab and nivolumab, the tumor volume of the dominant liver metastasis reduced by 92%, and the recurrent intracranial disease regressed by 59%. Simultaneously, her plasma ACTH level decreased from 45,550 pg/mL to 66 pg/mL. Molecular Evaluation Both prospective clinical sequencing with Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets and retrospective whole-exome sequencing were performed to characterize the molecular alterations in the chemotherapy-naive pituitary adenoma and the temozolomide-resistant liver metastasis. The liver metastasis harbored a somatic mutational burden consistent with alkylator-induced hypermutation that was absent from the treatment-naive tumor. Resistance to temozolomide treatment, acquisition of new oncogenic drivers, and subsequent sensitivity to immunotherapy may be attributed to hypermutation. Conclusion Combination treatment with ipilimumab and nivolumab may be an effective treatment in pituitary carcinoma. Clinical sequencing of pituitary tumors that have relapsed following treatment with conventional chemotherapy may identify the development of therapy-induced somatic hypermutation, which may be associated with treatment response to immunotherapy.
Risk Factors for Preoperative Anxiety and Depression in Patients Scheduled for Abdominal Aortic Aneurysm Repair

Background: Perioperative emotional disorders of patients underwent abdominal aortic aneurysm (AAA) repair is an emerging area of study, and preoperative mental distress of those patients remains poorly understood. The aim of this study was to investigate the prevalence and identify the risk factors of preoperative anxiety and depression in patients scheduled for AAA repair. Methods: A total of 189 patients who underwent elective AAA repair between 2015 and 2016 were included in this study. These patients were preoperatively evaluated by Hospital Anxiety and Depression Scale (HADS). Demographics and anxiety and depression scores of the patients were documented. Logistic regression was used to identify the independent risk factors of preoperative anxiety and depression. Results: A total of 150 AAA patients were included in final analysis. Of these 150 patients, 44 patients (29.3%) had borderline anxiety or clinical anxiety, and 42 patients (28.0%) were found to have borderline or clinical depression. Female (odds ratio [OR]: 2.81, 95% confidence interval [CI]: 1.08–7.26), the American Society of Anesthesiologists (ASA) Grade 3/4 (OR: 4.34, 95% CI: 1.13–16.68), higher education (OR: 1.44, 95% CI: 1.02–2.04), and abdominal or back pain (OR: 3.08, 95% CI: 1.20–7.87) were identified as significant independent risk factors of abnormal HADS-anxiety in overall patients; and higher level of education (OR: 1.87, 95% CI: 1.16–3.01) was predictive of anxiety in patients planned for endovascular aortic repair. Besides, higher body mass index (BMI) (OR: 1.18, 95% CI: 1.04–1.33) and abdominal or back pain (OR: 3.93, 95% CI: 1.70–9.11) were predictive of abnormal preoperative HADS-depression in overall patients. Conclusion: As for patients scheduled for AAA repair, female, higher ASA, higher level of education, and symptom may be independent risk factors for preoperative anxiety, and symptom and higher BMI may predict preoperative depression.
Human Lymphocyte-Protective Effects of an Ethanol Extract from Detarium microcarpum Guill. and Perr. (Caesalpiniaceae) Fruit Pulp

The current study aimed to evaluate, in vitro, the antioxidant capacity and the human lymphocyte-protective effect of the ethanolic extract from Detarium microcarpum fruit pulp against oxidative stress damage. Human lymphocytes were incubated with different concentrations of extract, followed by the addition of hydrogen peroxide or tert-butyl hydroperoxide. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, the antioxidant property of the extract was evaluated in vitro using hydrogen peroxide and nitric oxide radical-scavenging assays. Compared to the vehicle, the fruit pulp ethanol extract did not exhibit a cytotoxic effect on human lymphocytes. Furthermore, the cytotoxicity of hydrogen peroxide and tert-butyl hydroperoxide to human lymphocytes was significantly reduced by fruit extract pretreatment. The extract and ascorbic acid exhibited similar cytoprotective activity (p > 0.05). The fruit pulp extract showed more antioxidant activity than gallic acid in the hydrogen peroxide-scavenging model, while in the nitric oxide-quenching model, the fruit extract and gallic acid showed similar activity. The fruit pulp of D. microcarpum contains potent antioxidant and cell-protective compounds. The use of the fruit pulp of D. microcarpum as a food supplement could rescue cellular oxidative damage responsible for numerous pathologies.
Intestinal cryptosporidiosis in renal transplant recipients: Prevalence, species detection and comparative evaluation of SSU rRNA and Cryptosporidium oocyst wall protein genes

Context: Cryptosporidiosis is intestinal opportunistic infection commonly occurring in immunocompromised patients including renal transplant (RT) recipients receiving continuous immunosuppressive therapy. Knowledge about species of Cryptosporidium-infecting RT recipients is necessary to know about mode of its transmission (anthroponotic or zoonotic). Various genes such as small subunit rRNA (SSU rRNA) and Cryptosporidium oocyst wall protein (COWP) genes may help in species identification though their sensitivity and specificity are highly variable. Subjects and Methods: A total of 993 and 575 stool samples were examined for Cryptosporidium by microscopy from 358 RT recipients and 200 healthy controls, respectively. Stool samples of RT recipients and healthy controls were subjected to polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) for species identification. Results: Cryptosporidium was more commonly detected amongst RT recipients than healthy controls (30/358, 8.4% vs. 0/200, respectively; P < 0.001). The infection was more common amongst patients with diarrhoea than those without (26/162, 16.1% vs. 4/145, 2.8%; P < 0.001). Cryptosporidium parvum was identified in 10/30 (33.3%) and Cryptosporidium hominis in 20/30 (66.7%) samples. SSU gene PCR-RFLP proved to be more sensitive (100%) than COWP (90%); however, specificity of both was same (100%). Conclusions: Cryptosporidiosis is common amongst RT recipients, particularly those with diarrhoea. C. hominis is the most common species in the studied population. SSU rRNA PCR was more sensitive molecular method for the differentiation of Cryptosporidium species.