Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective Safety Study of Intrathecal Gadobutrol in Different Doses

The present study adds to the accumulating evidence that intrathecal gadobutrol in doses up to 0.50 mmol is safe. BACKGROUND AND PURPOSE: In our clinical practice, we increasingly use intrathecal contrast-enhanced glymphatic MR imaging to assess CSF disturbances. However, because intrathecal MR imaging contrast agents such as gadobutrol (Gadovist; 1.0 mmol/mL) are used off-label, a thorough understanding of the safety profile is required. MATERIALS AND METHODS: We performed a prospective safety study from August 2020 to June 2022 of intrathecal gadobutrol, including consecutive patients who received either 0.50, 0.25, or 0.10 mmol. Serious and nonserious adverse events were recorded systematically at 1–3 days, 4 weeks, and >6 months after the intrathecal administration. RESULTS: The study included 196 patients who received intrathecal gadobutrol, including patients assessed for idiopathic normal pressure hydrocephalus (iNPH, n = 144) or patients examined for other CSF disorders (non-iNPH cohort; n = 52). The intrathecal gadobutrol doses were either 0.50 mmol (n = 56), 0.25 mmol (n = 111), or 0.10 mmol (n = 29). No serious adverse events were observed. Nonserious adverse events on days 1–3 after intrathecal gadobutrol were, to some degree, dose-dependent but mild-to-moderate, including severe headache, nausea, and/or dizziness in 6/196 (6.3%) patients, and they were more common in the non-iNPH than in the iNPH cohort. At 4 weeks, none reported severe nonserious adverse events, and 9/179 (5.0%) patients had mild-to-moderate symptoms. After >6 months, 2 patients reported mild headache. CONCLUSIONS: The present study adds to the accumulating evidence that intrathecal gadobutrol in doses up to 0.50 is safe.
Functional imaging and neurochemistry identify in vivo neuroprotection mechanisms counteracting excitotoxicity and neurovascular changes in the hippocampus and visual cortex of obese and type 2 diabetic animal models

Functional MRI (fMRI) with 1H‐MRS was combined on the hippocampus and visual cortex of animal models of obesity (high‐fat diet, HFD) and type 2 diabetes (T2D) to identify the involved mechanisms and temporal evolution of neurometabolic changes in these disorders that could serve as potentially reliable clinical biomarkers. HFD rats presented elevated levels of N‐acetylaspartylglutamate (NAAG) (p = 0.0365 vs. standard diet, SD) and glutathione (GSH) (p = 0.0494 vs. SD) in the hippocampus. NAAG and GSH levels in this structure proved to be correlated (r = 0.4652, p = 0.0336). This mechanism was not observed in diabetic rats. Combining MRS and fMRI‐evaluated blood‐oxygen‐level‐dependent (BOLD) response, elevated taurine (p = 0.0326 vs. HFD) and GABA type A receptor (GABAAR) (p = 0.0211 vs. SD and p = 0.0153 vs. HFD) were observed in the visual cortex of only diabetic rats, counteracting the elevated BOLD response and suggesting an adaptative mechanism against hyperexcitability observed in the primary visual cortex (V1) (p = 0.0226 vs. SD). BOLD amplitude was correlated with the glutamate levels (r = 0.4491; p = 0.0316). Therefore, here we found evidence for several biological dichotomies regarding excitotoxicity and neuroprotection in different brain regions, identifying putative markers of their different susceptibility and response to the metabolic and vascular insults of obesity and diabetes.
Dry eye disease and risk factors for corneal complications in chronic ocular graft-versus-host disease

Purpose: The current study was carried out to evaluate the clinical features and management outcomes of dry eye disease (DED) in chronic ocular GvHD following allogenic hematopoietic stem cell transplantation (HSCT). Methods: A retrospective review of consecutive patients diagnosed with chronic ocular GvHD between 2011 and 2020 was performed at a tertiary eye care network. Multi-variate regression analysis was carried out for identifying risk factors associated with progressive disease. Results: A total of 34 patients (68 eyes) with a median age of 33 years [inter-quartile range (IQR) 23–40.5] were studied. The most common indication for HSCT was acute lymphocytic leukemia (26%). Ocular GvHD developed at a median of 2 years (IQR 1–5.5 years) after HSCT. Aqueous tear deficiency was present in 71% of the eyes, of which 84% had a Schirmer value of <5 mm. The median visual acuity at presentation and that after a median follow-up of 6.9 months were comparable at 0.1 log minimum angle of resolution (logMAR) (P = 0.97). Topical immunosuppression was required in 88% of cases, and with this, improvement in corneal (53%, P = 0.003) and conjunctival staining scores (45%, P = 0.43) was noted. A progressive disease was present in 32% with persistent epithelial defects being the most common complication. Grade 2 conjunctival hyperemia [odds ratio (OR): 2.6; P = 0.01] and Schirmer's value <5 mm (OR: 2.7; P = 0.03) were found to be associated with progressive disease. Conclusion: Aqueous deficient DED is the most common ocular manifestation of chronic ocular GvHD, and the risk of the disease progression is greater in eyes with conjunctival hyperemia and severe aqueous deficiency. Awareness among ophthalmologists of this entity is essential for its timely detection and optimal management.
Numerical Study of Surfactant-Laden Drop-Drop Interactions

In this paper, we numerically investigate the effects of surfactant on drop-drop interactions in a 2D shear flow using a coupled level-set and immersed interface approach proposed in (Xu et al., J. Comput. Phys., 212 (2006), 590-616). We find that surfactant plays a critical and nontrivial role in drop-drop interactions. In particular, we find that the minimum distance between the drops is a non-monotone function of the surfactant coverage and Capillary number. This non-monotonic behavior, which does not occur for clean drops, is found to be due to the presence of Marangoni forces along the drop interfaces. This suggests that there are non-monotonic conditions for coalescence of surfactant-laden drops, as observed in recent experiments of Leal and co-workers. Although our study is two-dimensional, we believe that drop-drop interactions in three-dimensional flows should be qualitatively similar as the Maragoni forces in the near contact region in 3D should have a similar effect.
Advantages and drawbacks associated with the use of endosonography in sarcoidosis

ABSTRACT Introduction Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a real-time, minimally invasive procedure for sampling intrathoracic lymph nodes. Herein, we discuss EBUS-guided procedures, their benefits, and drawbacks in diagnosing sarcoidosis. Areas covered We first describe the utility of various endosonographic imaging techniques like B-mode, elastography, and doppler imaging. We then review the diagnostic yield and safety of EBUS-TBNA and compare it with the other available diagnostic modalities. Subsequently, we discuss the technical aspects of EBUS-TBNA influencing the diagnostic yield. Recent advances in EBUS-guided diagnostics like EBUS-guided intranodal forceps biopsy (EBUS-IFB) and EBUS-guided transbronchial mediastinal cryobiopsy (EBMC) are reviewed. Finally, we summarize the advantages and disadvantages associated with EBUS-TBNA in sarcoidosis and provide an expert opinion on the optimal use of this procedure in patients with suspected sarcoidosis. Expert opinion EBUS-TBNA is a minimally invasive, safe procedure with a good diagnostic yield, and should be the preferred diagnostic modality for sampling intrathoracic lymph nodes in patients with suspected sarcoidosis. For optimal diagnostic yield, EBUS-TBNA should be combined with endobronchial biopsy (EBB) and transbronchial lung biopsy (TBLB). Newer endosonographic techniques like EBUS-IFB and EBMC might obviate the need for EBB and TBLB due to their superior diagnostic yield.
Risk factors for psychiatric symptoms in patients with long COVID: A systematic review

Prolonged symptoms of COVID-19 have been found in many patients, often known as Long COVID. Psychiatric symptoms are commonly seen in Long COVID patients and could last for weeks, even months, after recovery. However, the symptoms and risk factors associated with it remain unclear. In the current systematic review, we provide an overview of psychiatric symptoms in Long COVID patients and risk factors associated with the development of those symptoms. Articles were systematically searched on SCOPUS, PubMed, and EMBASE up to October 2021. Studies involving adults and geriatric participants with a confirmed previous COVID-19 diagnosis and reported psychiatric symptoms that persist for more than four weeks after the initial infection were included. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies. Prevalence rates and risk factors associated with psychiatric symptoms were collected. This present study was registered at PROSPERO (CRD42021240776). In total, 23 studies were included. Several limitations in this review were the heterogeneity of studies’ outcomes and designs, studies limited to articles published in English, and the psychiatric symptoms mainly were assessed using self-report questionnaires. The most prevalent reported psychiatric symptoms, from the most to the least reported, were anxiety, depression, post-traumatic stress disorder (PTSD), poor sleep qualities, somatic symptoms, and cognitive deficits. Being female and having previous psychiatric diagnoses were risk factors for the development of the reported symptoms.
Type 1–type 2 interferon imbalance in dry eye disease

Purpose: Dry eye disease (DED) is characterized by altered ocular surface proinflammatory and antiinflammatory factors. Interferons (IFNs) are a class of pleiotropic cytokines well known for their antimicrobial, inflammatory, and immunomodulatory roles. Hence, this study investigates the ocular surface expression of different types of IFNs in patients with DED. Methods: The cross-sectional, observational study included patients with DED and normal subjects. Conjunctival impression cytology (CIC) samples were obtained from the study subjects (controls, n = 7; DED, n = 8). The mRNA expression levels of type 1 IFN (IFNα, IFNβ), type 2 IFN (IFNγ), and type 3 IFN (IFNλ1, IFNλ2, IFNλ3) were measured by quantitative PCR (polymerase chain reaction) in CIC samples. IFNα and IFNγ expression under hyperosmotic stress was also studied in human corneal epithelial cells (HCECs) in vitro. Results: The mRNA expression levels of IFNα and IFNβ were significantly lower and that of IFNγ was significantly higher in DED patients compared to healthy controls. The mRNA levels of IFNα, IFNβ, and IFNλ were significantly lower compared to IFNγ in DED patients. An inverse association between tonicity-responsive enhancer-binding protein (TonEBP; hyperosmotic stress maker) and IFNα or IFNβ expression and a positive association between TonEBP and IFNγ expression was observed in CIC samples. The expression of IFNα was lower than IFNγ in HCECs undergoing hyperosmotic stress compared to HCECs without the stress. Conclusion: The presence of an imbalance between type 1 and type 2 IFNs in DED patients suggests newer pathogenic processes in DED, plausible ocular surface infection susceptibility in DED patients, and potential therapeutic targets in the management of DED.
Whether induction of labor ahead in low-risk women improves pregnancy outcomes?: A retrospective cohort, observational study

The appropriate timing of delivery for pregnancies has always been a concern for medical staff, and the timing of elective labor induction at 41 weeks in low-risk pregnant women has always been controversial. We compared maternal and fetal outcomes between gestational age at 40 0/7 to 40 6/7 and 41 0/7 to 41 6/7 weeks. This retrospective cohort study was conducted at the obstetrics department of Jiangsu Province Hospital from January 1st to December 31st in 2020. Maternal medical records and neonatal delivery data were collected. One-way analysis of variance, Mann–Whitney U test, χ2 test, Fisher exact test and logistig regression analysis were performed. The study included 1569 pregnancies, with 1107 (70.6%) delivered at 40 0/7 to 40 6/7 weeks and 462 (29.4%) delivered at 41 0/7 to 41 6/7 weeks. Intrapartum cesarean section (8% vs 16%, P < .001), meconium-stained amniotic fluid (13% vs 19%, P = .004), episiotomy (41% vs 49%, P = .011), and macrosomia (13% vs 18%, P = .026) were significantly lower at 40 0/7 to 40 6/7 weeks. The premature rupture of membranes rate (22% vs 12%, P < .001), vaginal delivery rate of artificial rupture of membrane induction (83% vs 71%, P = .006) and balloon catheter combined with oxytocin induction (88% vs 79%, P = .049) were significantly higher at 40 0/7 to 40 6/7 weeks. Low-risk women who delivered at 40 0/7 to 40 6/7 weeks showed better outcomes in terms of the mother’s and baby’s health, such as decreased rates of intrapartum cesarean section, meconium-stained amniotic fluid, episiotomy, and macrosomia, compared with those who delivered at 41 0/7 to 41 6/7 weeks.
Monkeypox detection from skin lesion images using an amalgamation of CNN models aided with Beta function-based normalization scheme

We have recently been witnessing that our society is starting to heal from the impacts of COVID-19. The economic, social and cultural impacts of a pandemic cannot be ignored and we should be properly equipped to deal with similar situations in future. Recently, Monkeypox has been concerning the international health community with its lethal impacts for a probable pandemic. In such situations, having appropriate protocols and methodologies to deal with the outbreak efficiently is of paramount interest to the world. Early diagnosis and treatment stand as the only viable option to tackle such problems. To this end, in this paper, we propose an ensemble learning-based framework to detect the presence of the Monkeypox virus from skin lesion images. We first consider three pre-trained base learners, namely Inception V3, Xception and DenseNet169 to fine-tune on a target Monkeypox dataset. Further, we extract probabilities from these deep models to feed into the ensemble framework. To combine the outcomes, we propose a Beta function-based normalization scheme of probabilities to learn an efficient aggregation of complementary information obtained from the base learners followed by the sum rule-based ensemble. The framework is extensively evaluated on a publicly available Monkeypox skin lesion dataset using a five-fold cross-validation setup to evaluate its effectiveness. The model achieves an average of 93.39%, 88.91%, 96.78% and 92.35% accuracy, precision, recall and F1 scores, respectively. The supporting source codes are presented in https://github.com/BihanBanerjee/MonkeyPox.
Pre-Service Mathematics Teachers’ Problem Solving Processes with Geometer’s Sketchpad: Mirror Problem

Problem solving skill is the core of mathematics education and its importance cannot be denied. This study specifically examined 56 freshmen pre-service mathematics teachers’ problem solving processes on a specific problem with the help of Geometer’s Sketchpad (GSP). They were grouped into two-person teams to solve a problem called "the mirror problem". They were expected to solve it by means of GSP. According to their works on GSP and related reflections, there appeared two different solution methods for the problem. However, the results of the study revealed that pre-service teachers could not visualize the problem in their mind and apply it to GSP. More generally, they found the problem hard to solve. They experienced difficulty in transferring the static drawings into dynamic environment and in observing the manipulations on GSP.
Providing environmental enrichments can reduce subclinical spondylolisthesis prevalence without affecting performance in broiler chickens

Environmental enrichment can increase the occurrence of natural behavior and improve leg health and other animal welfare outcomes in broiler chickens. This study aimed to assess the effects of three environmental enrichments, specifically hay bales, step platforms, and laser lights, on subclinical spondylolisthesis prevalence, productivity, behavior, and gait of broiler chickens (Gallus gallus domesticus). Twenty-four hundred day-old male Ross® AP95 chicks from a commercial hatchery were used in a completely randomized design with four treatments and four replicate pens per treatment. Pens contained either a Control (C) treatment, an environment similar to a commercial broiler chicken system without environmental enrichments, or an environment with either additional hay bales (HB), additional step platforms (SP), or additional laser lights (LL). Performance, yield, behavior (frequencies), gait score, and subclinical spondylolisthesis prevalences were assessed. When raised with SP or LL access, fewer chickens had subclinical spondylolisthesis than chickens without enrichments (C) or with HB access. Chickens with access to SP exhibited higher wing yield and less abdominal fat than animals from the C group. Chickens from the LL and HB treatments explored more and rested less frequently than animals from the C and SP treatments. As chickens aged, they became less active, exploring less and increasing resting and comfort behaviors. Treatments did not affect gait. Gait was not associated with subclinical spondylolisthesis prevalence. Environmental enrichments benefitted chicken health (subclinical spondylolisthesis) and behavior (exploration) without negative consequences for performance and yield.
Assessing clinical and molecular outcomes of prophylactic thermal pulsation therapy on ocular surface health following refractive surgery

Purpose: To study ocular surface signs, symptoms, and tear film composition following prophylactic thermal pulsation therapy (TPT) prior to refractive surgery, and to compare these outcomes with those who underwent TPT after refractive surgery. Methods: Patients with mild-to-moderate evaporative dry eye disease (DED) and/or meibomian gland dysfunction (MGD) undergoing refractive surgery were included. Group 1 patients received TPT (LipiFlow) prior to laser-assisted in situ keratomileusis (LASIK; n = 32, 64 eyes), and Group 2 patients received TPT three months after LASIK (n = 27, 52 eyes). Ocular Surface Disease Index (OSDI) score, Schirmer's test (ST1, ST2), Tear Breakup Time (TBUT), meibography, and tear fluid were obtained preoperatively and at three months postoperatively in Groups 1 and 2. Additional postoperative evaluation was performed three months after TPT in Group 2. Tear soluble factor profile was measured by multiplex enzyme-linked immunosorbent assay (ELISA) using flow cytometry. Results: Postoperative OSDI score was significantly lower and TBUT was significantly higher when compared with matched preoperative values of Group 1 participants. On the other hand, the postoperative OSDI score was significantly higher and TBUT significantly lower when compared with matched preoperative values of Group 2 participants. TPT significantly reduced the postoperative elevation in OSDI and significantly reduced the postoperative reduction in TBUT in Group 2 participants. Tear Matrix metalloproteinase-9/ Tissue inhibitor matrix metalloproteinase 1 (MMP-9/TIMP1) ratio was significantly higher, postoperatively, when compared with matched preoperative levels in Group 2. However, MMP9/TIMP1 ratio remained unaltered in Group 1 participants. Conclusion: TPT prior to refractive surgery improved postsurgical ocular surface signs and symptoms and reduced tear inflammatory factors, thereby suggesting the plausibility of reduced post-refractive surgery DED in patients.
The GHB analogue HOCPCA improves deficits in cognition and sensorimotor function after MCAO via CaMKIIα

Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα) is a major contributor to physiological and pathological glutamate-mediated Ca2+ signals, and its involvement in various critical cellular pathways demands specific pharmacological strategies. We recently presented γ-hydroxybutyrate (GHB) ligands as the first small molecules selectively targeting and stabilizing the CaMKIIα hub domain. Here, we report that the cyclic GHB analogue 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA), improves sensorimotor function after experimental stroke in mice when administered at a clinically relevant time and in combination with alteplase. Further, we observed improved hippocampal neuronal activity and working memory after stroke. On the biochemical level, we observed that hub modulation by HOCPCA results in differential effects on distinct CaMKII pools, ultimately alleviating aberrant CaMKII signalling after cerebral ischemia. As such, HOCPCA normalised cytosolic Thr286 autophosphorylation after ischemia in mice and downregulated ischemia-specific expression of a constitutively active CaMKII kinase proteolytic fragment. Previous studies suggest holoenzyme stabilisation as a potential mechanism, yet a causal link to in vivo findings requires further studies. Similarly, HOCPCA’s effects on dampening inflammatory changes require further investigation as an underlying protective mechanism. HOCPCA’s selectivity and absence of effects on physiological CaMKII signalling highlight pharmacological modulation of the CaMKIIα hub domain as an attractive neuroprotective strategy.
Stability and Change in Substance Use Among Swedish Adolescents: A Latent Transition Analysis

Abstract Background: Research is needed on how substance use patterns develop over time in the general adolescent population. This knowledge is crucial in calibrating prevention and other interventions. Method: The study concerns use of cigarettes, alcohol, and cannabis in a nationally representative cohort of Swedish adolescents (n = 3999). Two waves (9th and 11th school grade) from the Futura01 study were analyzed using latent transition analysis (LTA) and multinomial regression analysis. Results: Four substance use patterns, were identified, ranging from Non-user, Alcohol experienced, Alcohol User to Co-user of cigarettes, alcohol, and cannabis. Statuses thus conveyed a continuum from no use to more advanced use. Half of the individuals remained in their original status between time-points, and half transitioned, most often one step on the continuum. Alcohol user was the most stable status over time (0.78), and the Non-user status the least (0.36). The probability of remaining in the Alcohol experienced status was 0.57, and 0.45 for the Co-user status. There was a low probability of transitioning from alcohol to cannabis use. Females were more likely to belong to Alcohol experienced and males to Co-user statuses, but these associations weakened over time. Conclusions: The study identified transitions across substance use statuses between time-points. These usually concerned different levels of alcohol use, and not into more advanced substance use that included the illegal substance cannabis. The study corroborates that young Swedes belong to a “sober” generation and usually do not transition from legal into illegal substance use during late adolescence, though with some gender differences.
Real Analytic Functions on Product Spaces and Separate Analyticity

Let f be a function on the product space V × W, where V and W are analytic manifolds, both either real or complex. The function f is said to be analytic (or bi-analytic) on V × W if it is analytic in the analytic structure induced on V × W by the corresponding structures on V and W. The function f is said to be separately analytic on V × W if, for each x in V, the function f(x, .) is analytic on W while, for each y in W, the function f (. ,y) is analytic on V. In the case of complex analytic manifolds, the classical theorem of Hartogs (3, chapter VII) states that the two notions of analyticity and separate analyticity are equivalent. For real analytic manifolds, it is known that such an equivalence does not hold, even if one adds the additional hypothesis that f is infinitely differentiate on V × W.