Miracle-dz/UniFAR-FTUs huggingface dataset:
Arabidopsis Raf‐like kinases act as positive regulators of subclass III SnRK2 in osmostress signaling

SUMMARY Given their sessile nature, land plants must use various mechanisms to manage dehydration under water‐deficit conditions. Osmostress‐induced activation of the SNF1‐related protein kinase 2 (SnRK2) family elicits physiological responses such as stomatal closure to protect plants during drought conditions. With the plant hormone ABA receptors [PYR (pyrabactin resistance)/PYL (pyrabactin resistance‐like)/RCAR (regulatory component of ABA receptors) proteins] and group A protein phosphatases, subclass III SnRK2 also constitutes a core signaling module for ABA, and osmostress triggers ABA accumulation. How SnRK2 is activated through ABA has been clarified, although its activation through osmostress remains unclear. Here, we show that Arabidopsis ABA and abiotic stress‐responsive Raf‐like kinases (AtARKs) of the B3 clade of the mitogen‐activated kinase kinase kinase (MAPKKK) family are crucial in SnRK2‐mediated osmostress responses. Disruption of AtARKs in Arabidopsis results in increased water loss from detached leaves because of impaired stomatal closure in response to osmostress. Our findings obtained in vitro and in planta have shown that AtARKs interact physically with SRK2E, a core factor for stomatal closure in response to drought. Furthermore, we show that AtARK phosphorylates S171 and S175 in the activation loop of SRK2E in vitro and that Atark mutants have defects in osmostress‐induced subclass III SnRK2 activity. Our findings identify a specific type of B3‐MAPKKKs as upstream kinases of subclass III SnRK2 in Arabidopsis. Taken together with earlier reports that ARK is an upstream kinase of SnRK2 in moss, an existing member of a basal land plant lineage, we propose that ARK/SnRK2 module is evolutionarily conserved across 400 million years of land plant evolution for conferring protection against drought.
Unexpected Caregiving in Later Life: Illuminating the Narratives of Resilience of Grandmothers and Relative Caregivers through Photovoice Methodology

ABSTRACT This research study implements photovoice methodology with unexpected caregivers to illuminate the lived experiences of female grandparents and relative caregivers who are raising young children in the later stages of their life. As they enter older adulthood, grandmothers are increasingly finding themselves taking care of their children’s children for various reasons, including, but not limited to, their adult child’s incarceration, mental health issues, drug and alcohol addiction, or child abuse or neglect. Informed by various feminist theoretical lenses, we use photovoice methodology to highlight the narratives of resilience and explore the ways in which grandmothers re-conceptualize their roles and identity as an unexpected caregiver and the sources of strength and resilience that inform the ways in which they navigate the various circumstances in their lives.
Stress Release Effect of Micro-hole Array for Flexible Electrode and Thin Film Transistor.

The effects of micro-hole arrays in thin metal film were studied as a method to release bending stress in flexible electrodes and flexible thin film transistors (TFTs). Interest in flexible electronics is increasing, and many approaches have been suggested to solve the issue of the electrical failure of electrodes or electrical components such as TFTs after repeated bending. Here, we demonstrate a micro-hole array structure as a common solution to release bending stress. Although micro-size cracks were generated and propagated from the hole edges, the cracks stopped within a certain range when enough stress was released. Moreover, since the crack sites were predictable and controllable, a fatal electrical breakdown in a conductive layer such as a metal electrode or the semiconducting junction of a TFT can be prevented by specifically arranging the hole arrays. Thin film layers fabricated without holes suffered electrical breakdown due to random crack propagation during bending tests. Aluminum (Al) thin film electrodes prepared with arrays of 3 μm diameter holes and 25 % hole area showed excellent durability after 300,000 bending cycles. The change in resistance was below 3 %. The electrical characteristics of an a-IGZO TFT with the micro-hole structure was almost equivalent to a standard a-IGZO TFT. After 10,000 bending cycles, ION and the ratio of ION/IOFF remained >107 A and ~107, respectively. Since the effective hole diameter is micrometer size, fabrication does not require additional process steps or expensive process equipment. Therefore, the approach can be an important way to enhance the reliability of various electrical devices in flexible and wearable applications.
Effects of Air Cavity in Dynamic Pressure Sensors: Experimental Validation

An air-backed diaphragm is the key structure of most dynamic pressure sensors and plays a critical role in determining the sensor performance. Our previous analytical model investigated the influence of air cavity length on the sensitivity and bandwidth. The model found that as the cavity length decreases, the static sensitivity monotonically decreases, and the fundamental natural frequency shows a three-stage trend: increasing in the long-cavity-length range, reaching a plateau value in the medium-cavity-length range, and decreasing in the short-cavity-length range, which cannot be captured by the widely used lumped model. In this study, we conducted the first experimental measurements to validate these findings. Pressure sensors with a circular polyimide diaphragm and a backing air cavity with an adjustable length were designed, fabricated, and characterized, from which the static sensitivities and fundamental natural frequencies were obtained as a function of the cavity length. A further parametric study was conducted by changing the in-plane tension in the diaphragm. A finite element model was developed in COMSOL to investigate the effects of thermoviscous damping and provide validation for the experimental study. Along with the analytical model, this study provides a new understanding and important design guidelines for dynamic pressure sensors with air-backed diaphragms.
Fractal biomarker of activity in patients with bipolar disorder

Abstract Background The output of many healthy physiological systems displays fractal fluctuations with self-similar temporal structures. Altered fractal patterns are associated with pathological conditions. There is evidence that patients with bipolar disorder have altered daily behaviors. Methods To test whether fractal patterns in motor activity are altered in patients with bipolar disorder, we analyzed 2-week actigraphy data collected from 106 patients with bipolar disorder type I in a euthymic state, 73 unaffected siblings of patients, and 76 controls. To examine the link between fractal patterns and symptoms, we analyzed 180-day actigraphy and mood symptom data that were simultaneously collected from 14 patients. Results Compared to controls, patients showed excessive regularity in motor activity fluctuations at small time scales (<1.5 h) as quantified by a larger scaling exponent (α1 > 1), indicating a more rigid motor control system. α1 values of siblings were between those of patients and controls. Further examinations revealed that the group differences in α1 were only significant in females. Sex also affected the group differences in fractal patterns at larger time scales (>2 h) as quantified by scaling exponent α2. Specifically, female patients and siblings had a smaller α2 compared to female controls, indicating more random activity fluctuations; while male patients had a larger α2 compared to male controls. Interestingly, a higher weekly depression score was associated with a lower α1 in the subsequent week. Conclusions Our results show sex- and scale-dependent alterations in fractal activity regulation in patients with bipolar disorder. The mechanisms underlying the alterations are yet to be determined.
Diet and the gut microbiome: from hype to hypothesis

Abstract Microbiome research in the last two decades has delivered as a key finding that the human intestine hosts a unique and complex ecosystem with many variables affecting the composition of the microbiota and in turn its function in metabolism and immune defence. Hundreds of external (environmental) factors have meanwhile been identified as significantly associated with bacterial biomass and diversity and, amongst these, diet is considered as a key determinant of microbial populations. However, dietary intervention studies, including those with fermentable substrates that have bulk effects on bowel functions, have revealed only very minor effects on overall microbiome composition and usually show only a very few species changing in population size. What that means in the context of hundreds of different species coexisting in competition or mutualism in the human colon is far from understood. This review addresses some of the current limits in research on diet effects by taking anatomical and physiological features of the intestine into consideration. It also provides some recommendations on future human studies needed to assess how the diet influences the microbiome and associated effects on metabolic health.
Predicting conversion to Alzheimer's disease among individual high‐risk patients using the Characterizing AD Risk Events index model

Both amnestic mild cognitive impairment (aMCI) and remitted late‐onset depression (rLOD) confer a high risk of developing Alzheimer's disease (AD). This study aims to determine whether the Characterizing AD Risk Events (CARE) index model can effectively predict conversion in individuals at high risk for AD development either in an independent aMCI population or in an rLOD population.
Coronavirus Disease 2019 and Children: What Pediatric Health Care Clinicians Need to Know.

Inconclusion,COVID-19isanemergingillnessthatisrapidlyspread-ing through the US and the world. Early data suggest that the ef-fectsonchildrenarelessseverethanthoseonadults,yetmanyques- tionsremain,especiallyregardingtheeffectsonchildrenwithspecial health care needs. Surveillance of COVID-19 in the pediatric popu-lation,includingseroprevalencestudies,isneededtobetterunder- standitsinfluenceonUSchildren.Cliniciansneedtoworkwithschool and community leaders to implement interventions that slow dis-easespreadandpreventsevereillnessanddeath,whileensuringthat unintended consequences of these interventions on children are minimized.
Third Place Award: Posttraumatic elbow arthrofibrosis incidence and risk factors a retrospective review

Background: Loss of elbow range of motion (ROM) can significantly decrease patient quality of life. Posttraumatic arthrofibrosis is a common cause of decreased elbow ROM, and it has been reported that loss of 50% of elbow motion can compromise 80% of extremity function. The aim of this study was to examine the incidence and risk factors of posttraumatic elbow arthrofibrosis. Methods: We performed a retrospective review of all patients with intraarticular elbow fracture treated with operative fixation over a 10-year period. Pearson’s Chi-squared, Student’s t-test, and a logistic multivariate regression model was used to predict arthrofibrosis risk factors. Results: A total of 390 consecutive patients with intra-articular elbow fractures were identified. A total of 105 (27%) patients developed arthrofibrosis with 72 surgical interventions performed to improve ROM. At final follow-up 88 (23%) patients had persistent arthrofibrosis. Using multivariate regression analysis, high-energy mechanism (odds ratio (OR) 3.61, 95% confidence interval (CI) 1.16-6.3, P<0.001), deep post operative infection (OR 2.3, 95% CI 1.26-4.37, P=0.038), elbow fracture-dislocations (OR 3.44, 95% CI 1.32-7.41, P=0.005), and distal humeral fractures (OR 1.9, 95% CI 1.1-3.19, P=0.027) were significantly associated with the development of arthrofibrosis. The effect of duration of immobilization was significant, with each extra day of immobilization increasing the odds of arthrofibrosis by 9% (OR 1.09, P=0.001). Conclusions: Duration of immobilization, fracture pattern, presence of deep postoperative infection, and energy of injury were all predictive factors for the development of elbow arthrofibrosis after operative treatment of intraarticular elbow fractures.
Constitutive deletion of astrocytic connexins aggravates kainate-induced epilepsy.

The astroglial gap junctional network formed by connexin (Cx) channels plays a central role in regulating neuronal activity and network synchronization. However, its involvement in the development and progression of epilepsy is not yet understood. Loss of interastrocytic gap junction (GJ) coupling has been observed in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy (MTLE) and in mouse models of MTLE, leading to the suggestion that it plays a causative role in the pathogenesis. To further elucidate this clinically relevant question, we investigated consequences of astrocyte disconnection on the time course and severity of kainate-induced MTLE with hippocampal sclerosis (HS) by comparing mice deficient for astrocytic Cx proteins with wild-type mice (WT). Continuous telemetric EEG recordings and video monitoring performed over a period of 4 weeks after epilepsy induction revealed substantially higher seizure and interictal spike activity during the chronic phase in Cx deficient versus WT mice, while the severity of status epilepticus was not different. Immunohistochemical analysis showed that, despite the elevated chronic seizure activity, astrocyte disconnection did not aggravate the severity of HS. Indeed, the extent of CA1 pyramidal cell loss was similar between the experimental groups, while astrogliosis, granule cell dispersion, angiogenesis, and microglia activation were even reduced in Cx deficient as compared to WT mice. Interestingly, seizure-induced neurogenesis in the adult dentate gyrus was also independent of astrocytic Cxs. Together, our data indicate that constitutive loss of GJ coupling between astrocytes promotes neuronal hyperexcitability and attenuates seizure-induced histopathological outcomes.
Cinnamaldehyde Ameliorates Vascular Dysfunction in Diabetic Mice by Activating Nrf2.

BACKGROUND Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear. METHODS Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group. RESULTS CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-β1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice. CONCLUSIONS A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice.
Patient factors associated with diabetes medication adherence at different health literacy levels: a cross-sectional study at a family medicine clinic

ABSTRACT Background Type 2 diabetes (T2D) incurs tremendous health costs associated with various complications due to poor diabetes control. Medication adherence, which is correlated with patients’ health literacy, should be consistently practiced achieving optimal diabetes control. A deeper understanding of the specific communication and psychosocial factors related to medication-taking behaviors across different levels of health literacy among people with T2D will guide the development of effective interventions and strategies to enhance medication adherence. Objectives This cross-sectional study aimed to identify salient patient factors associated with diabetes medication adherence across different levels of health literacy. Methods A questionnaire was administered via a face-to-face approach with 205 participants at a family medicine clinic. Study participants were all above 20 years of age with T2D, were prescribed at least one oral diabetes medication, and understood English. The questionnaire assessed participants’ health literacy, self-efficacy for medication use, beliefs in medicines, patient-provider communication, perceived barriers to medication adherence, and self-reported medication adherence. Separate analysis of covariance was used to compare the mean scores of patient factors related to medication adherence across people with different health literacy levels. Results The mean age of participants was 61 years old, and the majority of the participants were female (57%), White (75%), and college educated (62%). Thirty-three percent of the participants had adequate health literacy, but only 43% of them reported high adherence to their diabetes medications. Analysis of covariance showed that having stronger self-efficacy (P < 0.001), lower concern beliefs about medication (P = 0.047), and fewer perceived barriers to medication-taking (P < 0.001), are necessary for better medication adherence. Conclusion Findings suggest that practitioners should address concern beliefs among low-adherent patients with low health literacy, help improve self-efficacy, and address perceived barriers to medication adherence among all low-adherent patients to optimally support patients’ diabetes care.
Feasibility of markerless fluoroscopic real-time tumor detection for adaptive radiotherapy: development and end-to-end testing

Respiratory-gated radiotherapy treatments of lung tumors reduce the irradiated normal tissue volume and potentially lower the risk of side effects. However, in clinical routine, the gating signal is usually derived from external markers or other surrogate signals and may not always correlate well with the actual tumor position. This study uses the kV-imaging system of a LINAC in combination with a multiple template matching algorithm for markerless real-time detection of the tumor position in a dynamic anthropomorphic porcine lung phantom. The tumor was realized by a small container filled with polymer dosimetry gel, the so-called gel tumor. A full end-to-end test for a gated treatment was performed and the geometric and dosimetric accuracy was validated. The accuracy of the tumor detection algorithm in SI- direction was found to be 2.3±1.6 mm and the gel tumor was automatically detected in 98 out of 100 images. The measured 3D dose distribution showed a uniform coverage of the gel tumor and comparison with the treatment plan revealed a high 3D γ-passing rate of 86.7% ( 3%/3mm). The simulated treatment confirmed the employed margin sizes for residual motion within the gating window and serves as an end-to-end test for a gated treatment based on a markerless fluoroscopic real-time tumor detection.
Impact of genetic variants of ABCB1, APOB, CAV1, and NAMPT on susceptibility to pancreatic ductal adenocarcinoma in Chinese patients

Among the different types of cancer, pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is the most lethal malignancy, with poor early detection rates and prognosis. The aim of the present study was to investigate the potential genetic effects of the single‐nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs3789243, rs4148737), APOB (rs693, rs1042031), CAV1 (rs12672038, rs1997623, rs3807987, rs7804372), and NAMPT (rs9034, rs2505568, rs61330082) on PDAC.
Residual colonization by vaccine serotypes in rural South Africa four years following initiation of pneumococcal conjugate vaccine immunization

ABSTRACT Background We evaluated pneumococcal colonization in children and adults between the time of 7-valent pneumococcal conjugate vaccine (PCV) introduction in the immunization program in 2009 to two years after transitioning to PCV13 in 2011. Methods Community-based carriage surveillance was undertaken between May-November 2013 (Period-3), with similar surveys in 2009 (Period-1) and 2011 (Period-2). Households with children below two years had a similar probability of being sampled in all surveys. Nasopharyngeal swabs were processed using standard methods and serotyped by Quellung. Results In children>9-59 months old, overall pneumococcal colonization prevalence declined from 81.8% in Period-1 to 65.0% in Period-3 (p<0.001). Reductions of 70% (41.2% vs. 13.6%) in PCV7-serotypes colonization and 66% (15.3% vs. 4.4%) for the six additional PCV13-serotypes (PCV13-add6VT) were observed. There was, however, high residual colonization by PCV7-serotypes 19F (14.9% vs. 6.3%) and 23F (8.5% vs. 4.1%), despite reduction of 57% and 52%, respectively. Among individuals>12 years of age, there was 61% reduction in PCV7-serotype colonization (3.1% vs. 1.3%) and 75% decrease for PCV13-add6VT (2.1% vs. 0.6%) between Period-1 and Period-3. Conclusions The residual prevalence of serotypes 19F and 23F, four years after introducing PCV in the South Africa, suggests ongoing community transmission and transient vaccine effects.
Investigation of the quantification of hemoglobin and cytochrome-c-oxidase in the exposed cortex with near-infrared hyperspectral imaging: a simulation study

Abstract. Significance: We present a Monte Carlo (MC) computational framework that simulates near-infrared (NIR) hyperspectral imaging (HSI) aimed at assisting quantification of the in vivo hemodynamic and metabolic states of the exposed cerebral cortex in small animal experiments. This can be done by targeting the NIR spectral signatures of oxygenated (HbO2) and deoxygenated (HHb) hemoglobin for hemodynamics as well as the oxidative state of cytochrome-c-oxidase (oxCCO) for measuring tissue metabolism. Aim: The aim of this work is to investigate the performances of HSI for this specific application as well as to assess key factors for the future design and operation of a benchtop system. Approach: The MC framework, based on Mesh-based Monte Carlo (MMC), reproduces a section of the exposed cortex of a mouse from an in vivo image and replicates hyperspectral illumination and detection at multiple NIR wavelengths (up to 121). Results: The results demonstrate: (1) the fitness of the MC framework to correctly simulate hyperspectral data acquisition; (2) the capability of HSI to reconstruct spatial changes in the concentrations of HbO2, HHb, and oxCCO during a simulated hypoxic condition; (3) that eight optimally selected wavelengths between 780 and 900 nm provide minimal differences in the accuracy of the hyperspectral results, compared to the “gold standard” of 121 wavelengths; and (4) the possibility to mitigate partial pathlength effects in the reconstructed data and to enhance quantification of the hemodynamic and metabolic responses. Conclusions: The MC framework is proved to be a flexible and useful tool for simulating HSI also for different applications and targets.