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Introduction: Convergence Insufficiency (CI) is the most prevalent oculomotor dysfunction of binocular vision that negatively impacts quality of life when performing visual near tasks. Decreased resting‐state functional connectivity (RSFC) is reported in the CI participants compared to binocularly normal control participants. Studies report that therapeutic interventions such as office‐based vergence and accommodative therapy (OBVAT) can improve CI participants' clinical signs, visual symptoms, and task‐related functional activity. However, longitudinal studies investigating the RSFC changes after such treatments in participants with CI have not been conducted. This study aimed to investigate the neural basis of OBVAT using RSFC in CI participants compared to the placebo treatment to understand how OBVAT improves visual function and symptoms. Methods: A total of 51 CI participants between 18 and 35 years of age were included in the study and randomly allocated to receive either 12 one‐hour sessions of OBVAT or placebo treatment for 6 to 8 weeks (1 to 2 sessions per week). Resting‐state functional magnetic resonance imaging and clinical assessments were evaluated at baseline and outcome for each treatment group. Region of interest (ROI) analysis was conducted in nine ROIs of the oculomotor vergence network, including the following: cerebellar vermis (CV), frontal eye fields (FEF), supplementary eye fields (SEF), parietal eye fields (PEF), and primary visual cortices (V1). Paired t‐tests assessed RSFC changes in each group. A linear regression analysis was conducted for significant ROI pairs in the group‐level analysis for correlations with clinical measures. Results: Paired t‐test results showed increased RSFC in 10 ROI pairs after the OBVAT but not placebo treatment (p < 0.05, false discovery rate corrected). These ROI pairs included the following: Left (L)‐SEF–Right (R)‐V1, L‐SEF–CV, R‐SEF–R‐PEF, R‐SEF–L‐V1, R‐SEF–R‐V1, R‐SEF–CV, R‐PEF–CV, L‐V1–CV, R‐V1–CV, and L‐V1–R‐V1. Significant correlations were observed between the RSFC strength of the R‐SEF–R‐PEF ROI pair and the following clinical visual function parameters: positive fusional vergence and near point of convergence (p < 0.05). Conclusion: OBVAT, but not placebo treatment, increased the RSFC in the ROIs of the oculomotor vergence network, which was correlated with the improvements in the clinical measures of the CI participants. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by progressive loss of dopamine‐producing neurons from the substantia nigra region of the brain. Mitochondrial dysfunction is one of the major causes of oxidative stress and neuronal cell death in PD. E3 ubiquitin ligases such as Parkin (PRKN) modulate mitochondrial quality control in PD; however, the role of other E3 ligases associated with mitochondria in the regulation of neuronal cell death in PD has not been explored. The current study investigated the role of TRIM32, RING E3 ligase, in sensitization to oxidative stress‐induced neuronal apoptosis. The expression of TRIM32 sensitizes SH‐SY5Y dopaminergic cells to rotenone and 6‐OHDA‐induced neuronal death, whereas the knockdown increased cell viability under PD stress conditions. The turnover of TRIM32 is enhanced under PD stress conditions and is mediated by autophagy. TRIM32 translocation to mitochondria is enhanced under PD stress conditions and localizes on the outer mitochondrial membrane. TRIM32 decreases complex‐I assembly and activity as well as mitochondrial reactive oxygen species (ROS) and ATP levels under PD stress. Deletion of the RING domain of TRIM32 enhanced complex I activity and rescued ROS levels and neuronal viability under PD stress conditions. TRIM32 decreases the level of XIAP, and co‐expression of XIAP with TRIM32 rescued the PD stress‐induced cell death and mitochondrial ROS level. In conclusion, turnover of TRIM32 increases during stress conditions and translocation to mitochondria is enhanced, regulating mitochondrial functions and neuronal apoptosis by modulating the level of XIAP in PD. [ABSTRACT FROM AUTHOR]

The growing cognizance of spectrum scarcity has become a more significant concern in wireless radio communications. Due to the exponential growth of data transmission in intelligent wireless sensor networks, energy spectrum detection has become a promising solution for resolving spectrum shortages. Primary user emulation attack (PUEA) has been identified as a significant attack vector in the cognitive radio (CR) domain's physical layer. In comparison, the CR is a promising method to increase spectrum efficiency by allowing unlicensed secondary users (SUs) to access licensed frequency bands without interfering with approved primary users (PUs). The study's primary findings are the methodology for preventing PUEA using authentication tags, which are unique sequences. This research blends SC‐FDMA with CR to protect CR networks from PUEA attacks, a Latin square (LS) matrix tag generation system is proposed to mitigate the PUEA effect. The technology is meant to provide effective authentication and protection against malicious users. In a secured environment, the LS tag technique is utilized to track and estimate the PU. For example, the BER of both techniques is virtually identical between 0 and 4 dB, while the BER performance of the suggested LS tag generation improves with increasing signal‐to‐noise ratio (SNR). As a result, the suggested LS tag generation is less susceptible to PUEA. To diminish the influence of PUEA in CR networks, an efficient enlightening approach for making the future Green Cognitive Radio Wireless networks structure is proposed. The simulation results also demonstrate the resilience of the proposed CR spectrum sensing techniques for energy‐efficient knowledge at varying degrees to reduce the adverse effects of environmental technologies. [ABSTRACT FROM AUTHOR]

Interest in cultivating valuable medicinal plants to collect bioactive components has risen extensively over the world to meet the demands of health care systems, pharmaceuticals, and food businesses. Farmers commonly use chemical fertilizers to attain maximal biomass and yield, which have negative effects on the growth, development, and bioactive constituents of such medicinally important plants. Because of its low cost, environmentally friendly behavior, and nondestructive impact on soil fertility, plant health, and human health, the use of beneficial rhizobial microbiota is an alternative strategy for increasing the production of useful medicinal plants under both standard and stressed conditions. Plant growth‐promoting rhizobacteria (PGPR) associated with medicinal plants belong to the genera Azotobacter, Acinetobacter, Bacillus, Brevibacterium, Burkholderia, Exiguobacterium, Pseudomonas, Pantoea, Mycobacterium, Methylobacterium, and Serratia. These microbes enhance plant growth parameters by producing secondary metabolites, including enzymes and antibiotics, which help in nutrient uptake, enhance soil fertility, improve plant growth, and protect against plant pathogens. The role of PGPR in the production of biomass and their effect on the quality of bioactive compounds (phytochemicals) is described in this review. Additionally, the mitigation of environmental stresses including drought stress, saline stress, alkaline stress, and flooding stress to herbal plants is illustrated. [ABSTRACT FROM AUTHOR]

EEG/MEG source localization requires a subject's brain MRI to compute the sourcemodel and headmodel. As part of this computation, co‐registration of the digitized head information and brain MRI scan is the essential step. However, in the absence of a brain MRI scan, an approximated sourcemodel and headmodel can be computed from the subject's digitized head information and brain MRI scans from other subjects. In the present work, we compared the fiducial (FID)‐ and iterative closet point (ICP)‐based co‐registration approaches for computing an approximated sourcemodel using single and multiple available brain MRI scans. We also evaluated the two different template MRI selection strategies: one is based on objective registration error, and another on sourcemodel approximation error. The outcome suggests that averaged approximated solutions using multiple template brain MRI scans showed better performance than single‐template MRI‐based solutions. The FID‐based approach performed better than the ICP‐based approach for co‐registration of the digitized head surface and brain MRI scan. While selecting template MRIs, the selection approach based on objective registration error showed better performance than a sourcemodel approximation error‐based criterion. Cross‐dataset performance analysis showed a higher model approximation error than within‐dataset analysis. In conclusion, the FID‐based co‐registration approach and objective registration error‐based MRI selection criteria provide a simple, fast and more accurate solution to compute averaged approximated models compared with the ICP‐based approach. The demography of brain MRI scans should be similar to that of the query subject whose brain MRI scan was unavailable. [ABSTRACT FROM AUTHOR]

Background and Aims: Binge drinking contributes to the immense public health burden associated with alcohol use, especially among younger drinkers. Little is known about the underlying neurobiology of changes in this behavior over time. This preliminary study aimed to identify neurobiological markers of binge drinking behavior change during emerging adulthood. Design Observational prospective investigation of neurobiological predictors of binge drinking behavior. Setting: Communities surrounding a large, public university in the northeastern United States. Participants: A total of 42 emerging adults (48% female), approximately half meeting criteria for an alcohol use disorder. Measurements Past month binge drinking, the dependent variable, was assessed at two time‐points (T1, T2) via self‐report. Ten indices of resting‐state functional connectivity within the central executive network (CEN), a brain network involved in executive function, were collected at T1 and specified as independent variables in cross‐sectional and prospective Poisson models. All models controlled for age, sex, and alcohol use disorder status. Findings The cross‐sectional model yielded five significant associations between CEN connectivity and binge drinking incidence. Connections anchored primarily in the anterior CEN exhibited negative associations with binge drinking incidence (P = 0.001, 0.004, 0.011), and connections stemming from the right posterior parietal cortex exhibited positive associations with binge drinking incidence (P = 0.041, 0.045). In prospective models, stronger frontoparietal connectivity between the right dorsolateral prefrontal cortex and left posterior parietal cortex predicted greater increases in binge drinking incidence over time (P = 0.003). Conclusions: There is an association between central executive network connectivity and heavy drinking, as well as evidence that functional pathways within the central executive network may contribute to changes in problematic drinking behaviors. [ABSTRACT FROM AUTHOR]

Water‐soluble electronics have become increasingly popular due to their potential applications in various fields such as biodegradable and wearable‐stretchable electronics. Flexible polymers such as polydimethylsiloxane are hydrophobic. Hence, water‐soluble polymers like polyvinyl alcohol (PVA) have been extensively utilized as substrates for water‐soluble electronics. However, the patterning of the PVA has never been achieved to enhance the sensing capabilities for such devices. Herein we report for the first time the micro‐pyramid patterning of PVA film embedded with MoS2 quantum dots (QDs) for improved pressure‐sensing capabilities. The fabricated sensor displayed superior sensitivity of 1.44 kPa−1 compared to the sensitivity of 0.51 kPa−1 unpatterned PVA films. This enhanced performance can be attributed to the easier transport of the charge carriers from QD‐PVA‐QD film and the decrement in the tunneling resistance between adjacent MoS2 QDs due to localized stress on the micropattern. Further, the fabricated sensor was tested for real‐time application as a touch sensor in both contact (pressure) and noncontact mode (humidity), which finds potential application in security and personal healthcare, and so forth. The fabricated film is subjected to ~1200 stimulus cycles to manifest good reproducibility of sensor responses. Moreover, the device dissolves in water within ~300 s exhibiting magnificent transient behavior. [ABSTRACT FROM AUTHOR]

The recent advancements of Internet of Things (IoT) embedded systems, wireless networks, and biosensors those have assisted in the rapid development of implanting wearable sensors are reviewed here. The applications of the internet of medical things (IoMT) that has gained major attention as an ecosystem of connected clinical systems, computing systems, and medical sensors geared towards improving the quality of healthcare services are also reviewed here. The 5G based AI technology can revolute the perception of healthcare and lifestyle. In light of the importance of IoT platforms and 5G networks, the purpose of this proposed research work is to identify threats that could undermine the integrity, privacy, and security of IoMT systems. Also, the novel blockchain‐based approaches that can help in improving the confidentiality of IoMT network. It has been discovered that IoMT is vulnerable to various types of attacks, including denial of service (DoS), malware, and eavesdropping attack. In addition, IoMT is exposed to various vulnerabilities, such as security, privacy, and confidentiality. Despite multiple security threats, there are novel cryptographic techniques, such as access control, identity authentication, and data encryption that can help in improving the security and reliability of IoMT devices. [ABSTRACT FROM AUTHOR]

We present a report of bilateral mandibular radiolucent lesions that were diagnosed as synchronous ameloblastoma and odontogenic keratocyst (OKC) in a 75‐year‐old female patient. To the best of our knowledge, the simultaneous occurrence of ameloblastoma and OKC of the jaws, as contralateral lesions, has not been previously reported. [ABSTRACT FROM AUTHOR]

The Masquelet induced‐membrane (IM) technique is indicated for large segmental bone defects. Attributes of the IM and local milieu that contribute to graft‐to‐bone union are unknown. Using a rat model, we compared global gene expression profiles in critically sized femoral osteotomies managed using a cement spacer as per Masquelet to those left empty. At the end of the experiment, IM and bone adjacent to the spacer were collected from the Masquelet side. Nonunion tissue in the defect and bone next to the empty defect were collected from the contralateral side. Tissues were subjected to RNA isolation, sequencing, and differential expression analysis. Cell type enrichment analysis suggested the IM and the bone next to the polymethylmethacrylate (PMMA) spacer were comparatively enriched for osteoblastic genes. The nonunion environment was comparatively enriched for innate and adaptive immune cell markers, but only macrophages were evident in the Masquelet context. iPathwayGuide was utilized to identify cell signaling pathways and protein interaction networks enriched in the Masquelet environment. For IM vs nonunion false‐discovery rate correction of P values rendered overall pathway differences nonsignificant, and so only protein interaction networks are presented. For the bone comparison, substantial enrichment of pathways and networks known to contribute to osteogenic mechanisms was revealed. Our results suggest that the PMMA spacer affects the cut bone ends that are in contact with it and at the same time induces the foreign body reaction and formation of the IM. B cells in the empty defect suggest a chronic inflammatory response to a large segmental osteotomy. [ABSTRACT FROM AUTHOR]

Resting state functional magnetic resonance imaging studies of psychosis have focused primarily on the amplitude of low‐frequency fluctuations in the blood oxygen level dependent (BOLD) signal ranging from.01 to 0.1 Hz. Few studies, however, have investigated the amplitude of frequency fluctuations within discrete frequency bands and higher than 0.1 Hz in patients with psychosis at different illness stages. We investigated BOLD signal within three frequency ranges including slow‐4 (.027–.073 Hz), slow‐3 (.074–0.198 Hz) and slow‐2 (0.199–0.25 Hz) in 89 patients with either first‐episode or chronic psychosis and 119 healthy volunteers. We investigated the amplitude of frequency fluctuations within three frequency bands using 47 regions‐of‐interest placed within 14 known resting state networks derived using group independent component analysis. There were significant group x frequency interactions for the visual and motor cortex networks, with the largest significant group differences (patients < healthy volunteers) evident in slow‐4 and slow‐3, respectively. Also, healthy volunteers had an overall higher amplitude of frequency fluctuations compared to patients across the three frequency ranges in the visual cortex, dorsal attention and motor cortex networks with the opposite effect (patients > healthy volunteers) evident within the salience and frontal gyrus networks. Subsequent analyses indicated that these effects were evident in both first‐episode and chronic patients. Our study provides new data regarding the importance of BOLD signal fluctuations within different frequency bands in the neurobiology of psychosis. [ABSTRACT FROM AUTHOR]

Abstract: Described here is an efficient stereoselective synthesis of vibegron enabled by an enzymatic dynamic kinetic reduction that proceeds in a high‐pH environment. To overcome enzyme performance limitations under these conditions, a ketoreductase was evolved by a computationally and structurally aided strategy to increase cofactor stability through tighter binding. [ABSTRACT FROM AUTHOR]

Abstract: Thermoreception is an important cutaneous sense, which plays a role in the maintenance of our body temperature and in the detection of potential noxious heat stimulation. In this study, we investigated event‐related fields (ERFs) and neural oscillatory activities, which were modulated by warmth stimulation. We developed a warmth stimulator that could elicit a warmth sensation, without pain or tactile sensation, by using a deep‐penetrating 980‐nm diode laser. The index finger of each participant (n = 24) was irradiated with the laser warmth stimulus, and the cortical responses were measured using magnetoencephalography (MEG). The ERFs and oscillatory responses had late latencies (∼1.3 s and 1.0–1.5 s for ERFs and oscillatory responses, respectively), which could be explained by a slow conduction velocity of warmth‐specific C‐fibers. Cortical sources of warmth‐related ERFs were seen in the bilateral primary and secondary somatosensory cortices (SI and SII), posterior part of the anterior cingulate cortex (pACC), ipsilateral primary motor, and premotor cortex. Thus, we suggested that SI, SII, and pACC play a role in processing the warmth sensation. Time–frequency analysis demonstrated the suppression of the alpha (8–13 Hz) and beta (18–23 Hz) band power in the bilateral sensorimotor cortex. We proposed that the suppressions in alpha and beta band power are involved in the automatic response to the input of warmth stimulation and sensorimotor interactions. The delta band power (1–4 Hz) increased in the frontal, temporal, and cingulate cortices. The power changes in delta band might be related with the attentional processes during the warmth stimulation. [ABSTRACT FROM AUTHOR]

This manuscript deals with the preparation of graphen oxide − metal oxide composite for the removal of heavy metal ions from water by adsoprtion. Composite of graphene oxide (GO) with zink oxide and titanium oxide has been prepared and analyzed structurally. Further, these composites has been used for the removal of heavy metals such as lead, chromium, mercury etc. from water. Metal oxide GO composites has been found efficient towards removal of heavy metal ions. [ABSTRACT FROM AUTHOR]

Fetal alcohol spectrum disorders (FASD) are characterized by impairment in cognitive function that may or may not be accompanied by craniofacial anomalies, microcephaly, and/or growth retardation. Resting-state functional MRI (rs-fMRI), which examines the low-frequency component of the blood oxygen level dependent (BOLD) signal in the absence of an explicit task, provides an efficient and powerful mechanism for studying functional brain networks even in low-functioning and young subjects. Studies using independent component analysis (ICA) have identified a set of resting-state networks (RSNs) that have been linked to distinct domains of cognitive and perceptual function, which are believed to reflect the intrinsic functional architecture of the brain. This study is the first to examine resting-state functional connectivity within these RSNs in FASD. Rs-fMRI scans were performed on 38 children with FASD (19 with either full fetal alcohol syndrome (FAS) or partial FAS (PFAS), 19 nonsyndromal heavily exposed (HE)), and 19 controls, mean age 11.3 ± 0.9 years, from the Cape Town Longitudinal Cohort. Nine resting-state networks were generated by ICA. Voxelwise group comparison between a combined FAS/PFAS group and controls revealed localized dose-dependent functional connectivity reductions in five regions in separate networks: anterior default mode, salience, ventral and dorsal attention, and R executive control. The former three also showed lower connectivity in the HE group. Gray matter connectivity deficits in four of the five networks appear to be related to deficits in white matter tracts that provide intra-RSN connections. Hum Brain Mapp 38:5217-5233, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The prevalence of mucormycosis is reportedly high in India, although the studies are mainly from north and south India only. We analysed the mucormycosis cases at tertiary care centres of West India. We retrieved the clinical details of all the patients with probable and proven mucormycosis diagnosed at Sterling Hospital and ID clinic at Ahmedabad, Gujarat over the period from 1 January 2013 through 30 April 2015. The data were analysed to determine demography, risk factors, underlying diseases, site of infection and outcome of these patients. A total of 27 patients with the median age of 50 (16-65) years were diagnosed with mucormycosis during the period. Rhino-orbital-cerebral mucormycosis was the most common (51.9%) presentation. Majority (55.6%) of the patients had uncontrolled diabetes with or without ketoacidosis; 25.9% patients had no underlying disease and most of them (85.7%) had cutaneous mucormycosis. In this group, the mortality was 25.9% and an equal percentage of patients were lost to follow up; 14 (51.9%) patients could complete 6 weeks of amphotericin B therapy. All patients who completed antifungal therapy survived except one. Like other parts of India, uncontrolled diabetes was the predominant risk factor for mucormycosis in our group. Patients completing 6 weeks of amphotericin B treatment were likely to survive. [ABSTRACT FROM AUTHOR]

Background and purpose The role of inheritance in ascertaining susceptibility to epilepsy is well established, although the pathogenetic mechanisms are still not very clear. Interviewing for a positive family history is a popular epidemiological tool in the understanding of this susceptibility. Our aim was to visualize and localize network abnormalities that could be associated with a positive family history in a group of patients with hot water epilepsy (HWE) using resting-state functional magnetic resonance imaging (rsfMRI). Methods Graph theory analysis of rsfMRI (clustering coefficient γ; path length λ; small worldness σ) in probands with a positive family history of epilepsy (FHE+, 25) were compared with probands without FHE (FHE−, 33). Whether a closer biological relationship was associated with a higher likelihood of network abnormalities was also ascertained. Results A positive family history of epilepsy had decreased γ, increased λ and decreased σ in bilateral temporofrontal regions compared to FHE− (false discovery rate corrected P ≤ 0.0062). These changes were more pronounced in probands having first degree relatives and siblings with epilepsy. Probands with multiple types of epilepsy in the family showed decreased σ in comparison to only HWE in the family. Conclusion Graph theory analysis of the rsfMRI can be used to understand the neurobiology of diseases like genetic susceptibility in HWE. Reduced small worldness, proportional to the degree of relationship, is consistent with the current understanding that disease severity is higher in closer biological relations. [ABSTRACT FROM AUTHOR]

Objective: We investigated the prevalence of xerostomia in dental patients and built a xerostomia risk prediction model by incorporating a wide range of risk factors.Materials and Methods: Socio-demographic data, past medical history, self-reported dry mouth and related symptoms were collected retrospectively from January 2010 to September 2013 for all new dental patients. A logistic regression framework was used to build a risk prediction model for xerostomia. External validation was performed using an independent data set to test the prediction power.Results: A total of 12 682 patients were included in this analysis (54.3%, females). Xerostomia was reported by 12.2% of patients. The proportion of people reporting xerostomia was higher among those who were taking more medications (OR = 1.11, 95% CI = 1.08-1.13) or recreational drug users (OR = 1.4, 95% CI = 1.1-1.9). Rheumatic diseases (OR = 2.17, 95% CI = 1.88-2.51), psychiatric diseases (OR = 2.34, 95% CI = 2.05-2.68), eating disorders (OR = 2.28, 95% CI = 1.55-3.36) and radiotherapy (OR = 2.00, 95% CI = 1.43-2.80) were good predictors of xerostomia. For the test model performance, the ROC-AUC was 0.816 and in the external validation sample, the ROC-AUC was 0.799.Conclusion: The xerostomia risk prediction model had high accuracy and discriminated between high- and low-risk individuals. Clinicians could use this model to identify the classes of medications and systemic diseases associated with xerostomia. [ABSTRACT FROM AUTHOR]

In current research scenario, an efficient synthesis has been developed for novel tetrazole scaffolds by single step multicomponent reaction. One of the most promising pathways is Ugi multi‐component process for the coupling of four different components in a single reaction step and isolate lead molecule which may serve better life to the society. The syntheses of tetrazoles were undertaken by the Ugi‐Multi Component approach with the condensation of aromatic aldehyde containing active pharmacophore, various aryl amines, isocyanide (cyclohexyl isocyanide) and TMS‐N3 under catalyst free reaction condition at room temperature. The structural conformation were carried out by most acceptable spectroscopic technique i.e. MS, IR, NMR and single crystal study (XRD) and potency of compounds (4a to 4h) were checked at NIH (National Institute of Health) use 60 different cell‐lines with respect to nine cancer panels among which compounds 4a and 4b have been found to be more potent against different cell lines. N‐((1‐Cyclohexyl‐1H‐tetrazol‐5‐yl)(3‐(cyclopropylmethoxy)‐4‐(difluoromethoxy) phenyl)methyl) aniline derivatives have been synthesized via tetrazole Ugi‐4CR reaction. Characterization was carried out by various spectroscopic techniques like IR, NMR and Mass spectrometry and it is further supported by single crystal XRD method. Synthesized products have been evaluated for their in vitro anticancer activity against NCI‐60 cancer cell lines. [ABSTRACT FROM AUTHOR]

Background and purpose Writer's cramp ( WC) is a focal task-specific dystonia of the hand which is increasingly being accepted as a network disorder. Non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (r TMS) has produced therapeutic benefits in some of these patients. This study aimed to visualize the motor network abnormalities in WC and also its rTMS induced modulations using resting state functional magnetic resonance imaging (rsf MRI). Methods Nineteen patients with right-sided WC and 20 matched healthy controls ( HCs) were prospectively evaluated. All patients underwent a single session of r TMS and rsf MRI was acquired before ( R1) and after ( R2) r TMS. Seed-based functional connectivity analysis of several regions in the motor network was performed for HCs, R1 and R2 using SPM8 software. Thresholded ( P < 0.05, false discovery rate corrected) group level mean correlation maps were used to derive significantly connected region of interest pairs. Results Writer's cramp showed a significant reduction in resting state functional connectivity in comparison with HCs involving the left cerebellum, thalamus, globus pallidus, putamen, bilateral supplementary motor area, right medial prefrontal lobe and right post central gyrus. After r TMS there was a significant increase in the contralateral resting state functional connectivity through the left thalamus−right globus pallidus−right thalamus−right prefrontal lobe network loop. Conclusions It is concluded that WC is a network disorder with widespread dysfunction much larger than clinically evident and changes induced by r TMS probably act through subcortical and trans-hemispheric unaffected connections. Longitudinal studies with therapeutic r TMS will be required to ascertain whether such information could be used to select patients prior to r TMS therapy. [ABSTRACT FROM AUTHOR]

This study evaluated the conventional jet cooking liquefaction process followed by simultaneous saccharification and fermentation (SSF) at 30% and 35% dry solids (DS) concentration of Indian sorghum feedstock for ethanol production, with addition of acid fungal protease or urea. To evaluate the efficacy of thermostable α-amylase in liquefaction at 30% and 35% DS concentration of Indian sorghum, liquefact solubility, higher dextrins, and fermentable sugars were analyzed at the end of the process. The liquefact was further subjected to SSF using yeast. In comparison with urea, addition of an acid fungal protease during SSF process was observed to accelerate yeast growth ( μ), substrate consumption ( Qs), ultimately ethanol yield based on substrate ( Yp/s) and ethanol productivity based on fermentation time ( Qp). The fermentation efficiency and ethanol recovery were determined for both concentrations of Indian sorghum and found to be increased with use of acid fungal protease in SSF process. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29: 329-336, 2013 [ABSTRACT FROM AUTHOR]

Atherosclerotic renal artery stenosis (ARAS) is an important cause of kidney disease, accelerated hypertension (HTN), and its treatment is controversial. Our aim was to evaluate the outcomes, safety, and efficacy of percutaneous transluminal angioplasty (PTA) for ARAS. Retrospective analysis of ARAS was performed among 470 angiographies during 1995-2010. Patients with nonatherosclerotic RAS and renal transplant were excluded. We assessed preintervention and postintervention mean arterial pressure (MAP), antihypertensive medications, and renal function to classify as deteriorated (>10% increase in MAP/increase in drugs/>20% reduced GFR), improved (>10% reduced MAP/reduced drugs/>20% increased eGFR), or stabilized (<10% change in MAP/same antihypertensive drugs/<20% change in eGFR) at last follow-up. A total of 220 subjects with mean age of 57.6 ± 10.4 years underwent PTA and/or stenting. The average follow-up was 23.07 ± 21.2 months. Accelerated HTN, HTN onset >50 years, unexplained renal failure, and unilateral small kidney were the most common presentations. In all, 255 significant stenotic lesions in 220 patients (119 unilateral, 66 single functioning kidney, and 35 bilateral) were observed. In total, 255 PTA were performed, including 177 stenting. Technical success was seen in 220/243 (90.5%) subjects. Combined MAP and antihypertensive drugs improved in 154/220 (70%) patients. Renal function improved/stabilized in 175/220 (79.5%). Angioplasty and stenting are relatively safe and feasible tools for control of blood pressure (BP) in ARAS. Angioplasty produced improvement/stabilization of BP in 70%, and the renal function in 79.5% subjects. [ABSTRACT FROM AUTHOR]

Background Clothing is considered the second skin of the human body. The aim of this study was to determine clothing-wearer interaction on skin physiology under mild cold conditions. Methods Skin physiological parameters, subjective sensory response, stress level, and physical properties of clothing fabric from two longitude parallel-designed wear trials were studied. The wear trials involved four kinds of pajamas made from cotton or polyester material that had hydrophilic or hydrophobic treatment, conducted for three weeks under mild cold conditions. Statistical tools, factor analysis, hierarchical linear regression, and logistic regression were applied to analyze the strong predictors of skin physiological parameters, stress level, and sensory response. Results A framework was established to illustrate clothing-wearer interactions with clothing fabric properties, skin physiology, stress level, and sensory response under mild cold conditions. Discussion Fabric has various effects on the human body under mild cold conditions. A fabric's properties influence skin physiology, sensation, and psychological response. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the sensitivity of mean absolute amplitudes of the thoracic and the abdominal signals as a prompt indicator of the occurrence of sleep apnoea events. BACKGROUND: To provide symptomatic management of sleep apnoea, a reliable method of detecting sleep apnoea is essential to ensure that the intervention can be applied only when needed. It is also crucial to identify the threshold for the trigger of an intervention using a deployed sensor. DESIGN: Twenty-six subjects aged between 18-65 years who were diagnosed with obstructive or central sleep apnoea underwent an overnight sleep study. METHOD: Signals of nasal and oral airflow, thoracic and abdominal efforts and pulse oximetry level were recorded using a polysomnography device. RESULTS: With a 95% CI, the overall area under the receiver operating characteristic of the thoracic signal, the abdominal signal and the combination of the thoracic and the abdominal signals were 84.56, 87.48 and 90.91%, respectively. Using -20, -25 and -30% as a cut-off point, the sensitivity values of thoracic signal, abdominal signal and combination of the thoracic and the abdominal signals ranged from 70.29-86.25% and the specificity values ranged from 74.82 to 90.09%. CONCLUSIONS: Using mean absolute amplitude analysis, the results of this study showed that combination of the thoracic and the abdominal signals achieved the best overall and individual performances compared with thoracic signal and abdominal signal. Overall, thoracic signal, abdominal signal and combination of the thoracic and the abdominal signals have a good performance with an receiver operating characteristic value higher than 80%. The thoracic and the abdominal signals were good parameters for the identification of the occurrence of sleep apnoea, being as quick as the nasal airflow signal. RELEVANCE TO CLINICAL PRACTICE: These results suggested that sleep apnoea events could be identified through constant monitoring of the patient's thoracic and abdominal signals. Knowledge of these signals could help nurses to manage sleep apnoea in patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to explore the effect of fabric material worn during nocturnal sleep on stratum corneum water content (SCWC) under mild cold conditions. Method: A controlled cross-over study has been designed to investigate systematically the effects of two kinds of pajama materials, cotton and polyester, on SCWC. Factors such as pajama fabric material, subjective perception and sleep quality were examined. Hierarchical linear regression was applied to assess the association between the factors and SCWC. Results: Fabric material and subjective perception of coldness significantly predicted SCWC in the wear trial. Polyester fabric had a negative effect on SCWC compared with cotton, and subjective perception of coldness also had a negative effect on SCWC. Conclusion: The mechanisms by which pajama fabrics affect the SCWC could be due to the different thermal/hygroscopicity properties of the polyester and cotton fabric and the integral involvement of physiological and neurophysiological processes. [ABSTRACT FROM AUTHOR]

Dictyostelium discoideum, a unicellular eukaryote, exhibits multicellularity upon nutrient starvation and is a good model system for developmental studies, and for the study of various signal transduction pathways. Reactive oxygen species at low doses act as signaling molecules; however, at high doses they are known to cause DNA damage that results in the activation of poly(ADP-ribose) polymerase (PARP). We have earlier reported the high resistance of the unicellular stage of D. discoideum to oxidative stress, and we now show the response of this organism to oxidative stress and the role of PARP during development. We used hydroxylamine (HA) to induce in situ generation of H2O2 and monitored the effect of benzamide, a PARP inhibitor, on oxidative stress-induced changes in D. discoideum development. Interestingly, oxidative stress resulted in PARP activation within 5 min that was inhibited by benzamide. Oxidative stress-induced delay in developmental pattern was also partially restored by benzamide. We studied the long-term effects of PARP inhibition under oxidative stress, and our results demonstrated that spores formed under HA stress exhibited significant delay in germination in comparison to benzamide-pretreated HA-stressed cells. However, second-generation cells showed normal development, signifying that PARP inhibition has no deleterious effect on D. discoideum development under oxidative stress. [ABSTRACT FROM AUTHOR]

To assess the incidence of ectopic adrenocortical tissue (EACT) in the groin in children, and examine the relationship between the incidence and the underlying diagnosis, age and sex.From computer records, all groin explorations between 1988 and 2002 in patients≤15 years old were identified. Cases of EACT were identified from computer histology records, and the incidence in different groups compared.Of 935 groin explorations, EACT was identified in 25 (2.7%); there were no cases in girls. The incidence was 0.7% at inguinal herniotomy (IH), 4.1% at ligation of the patent processus vaginalis for communicating hydrocele (P = 0.03 vs IH), and 3.3% at exploration for undescended testes (P = 0.02 vs IH). In boys with undescended testes the incidence of EACT was similar in different age groups (0–7 years, 3.3%; 8–15 years 3.2%,P= 0.96).The overall incidence of EACT at groin exploration was 2.7%, with none detected in girls. There was no evidence of involution of EACT with increasing age. The incidence of EACT varied with the underlying diagnosis, but the reason for this is unknown. [ABSTRACT FROM AUTHOR]

Although deep venous insufficiency is common and important, the anatomy of deep vein valves is poorly understood. The aim of this study was to investigate the location, number and consistency of venous valves in the femoral and popliteal veins in normal subjects. A detailed literature search of PubMed was performed. Abstracts and selected full text articles were scrutinised and relevant studies published between 1949 and 2010 reporting anatomical details of deep vein valves were included. From 7470 articles identified by the initial search strategy, nine studies with a total of 476 legs were included in this review. All studies were cadaveric and subjects ranged from stillborn fetuses to 103 years of age. Studies suggested that femoral veins contain between one and six valves, and popliteal veins contain between zero and four valves. Deep vein valves were consistently located in the common femoral vein (within 5 cm of the inguinal ligament), the femoral vein (within 3 cm of the deep femoral vein tributary) and in the popliteal vein near the adductor hiatus. Valves are consistently located at specific locations in the deep veins of the leg, although there is often significant variability between subjects. Further anatomical and functional studies using new imaging modalities available should target these areas to identify whether certain valves play a more important role in venous disease. This may guide us in the development of new treatment options for patients with deep venous disease. [ABSTRACT FROM AUTHOR]

In the era of minimally invasive surgery, esophagectomy remains a highly invasive procedure with a high rate of postoperative complications. Preoperative risk assessment is essential for planning esophagectomy in patients with esophageal cancer, and it is crucial to implement evidence‐based perioperative management to mitigate these risks. Perioperative support from multidisciplinary teams has recently been reported to improve the perioperative nutritional status and long‐term survival of patients undergoing esophagectomy. Intraoperative management of anesthesia and fluid therapy also significantly affects short‐term outcomes after esophagectomy. In this narrative review, we outline the recent updates in the perioperative management of esophagectomy, focusing on preoperative risk assessment, intraoperative management, and perioperative support by multidisciplinary teams to improve operative outcomes. [ABSTRACT FROM AUTHOR]

Microgrids (MGs) have emerged as a promising solution for providing reliable and sustainable electricity, particularly in underserved communities and remote areas. Integrating diverse renewable energy sources into the grid has further emphasized the need for effective management and sophisticated control strategies. This review explores the crucial role of control strategies in optimizing MG operations and ensuring efficient utilization of distributed energy resources, storage systems, networks, and loads. To maximize energy source utilization and overall system performance, various control strategies are implemented, including demand response, energy storage management, data management, and generation‐load management. Employing artificial intelligence (AI) and optimization techniques further enhances these strategies, leading to improved energy management and performance in MGs. The review delves into the control strategies and their architectures, and highlights the significant contributions of AI and emerging technologies in advancing MG energy management. [ABSTRACT FROM AUTHOR]

The genetic material within cells plays a pivotal role in shaping the structure and function of living organisms. Manipulating an organism's genome to correct inherited abnormalities or introduce new traits holds great promise. Genetic engineering techniques offers promising pathways for precisely altering cellular genetics. Among these methodologies, clustered regularly interspaced short palindromic repeat (CRISPR), honored with the 2020 Nobel Prize in Chemistry, has garnered significant attention for its precision in editing genomes. However, the CRISPR system faces challenges when applied in vivo, including low delivery efficiency, off‐target effects, and instability. To address these challenges, innovative technologies for targeted and precise delivery of CRISPR have emerged. Engineered carrier platforms represent a substantial advancement, improving stability, precision, and reducing the side effects associated with genome editing. These platforms facilitate efficient local and systemic genome engineering of various tissues and cells, including immune cells. This review explores recent advances, benefits, and challenges of CRISPR‐based genome editing delivery. It examines various carriers including nanocarriers (polymeric, lipid‐derived, metallic, and bionanoparticles), viral particles, virus‐like particles, and exosomes, providing insights into their clinical utility and future prospects. [ABSTRACT FROM AUTHOR]

Early‐stage disease detection, particularly in Point‐Of‐Care (POC) wearable formats, assumes pivotal role in advancing healthcare services and precision‐medicine. Public benefits of early detection extend beyond cost‐effectively promoting healthcare outcomes, to also include reducing the risk of comorbid diseases. Technological advancements enabling POC biomarker recognition empower discovery of new markers for various health conditions. Integration of POC wearables for biomarker detection with intelligent frameworks represents ground‐breaking innovations enabling automation of operations, conducting advanced large‐scale data analysis, generating predictive models, and facilitating remote and guided clinical decision‐making. These advancements substantially alleviate socioeconomic burdens, creating a paradigm shift in diagnostics, and revolutionizing medical assessments and technology development. This review explores critical topics and recent progress in development of 1) POC systems and wearable solutions for early disease detection and physiological monitoring, as well as 2) discussing current trends in adoption of smart technologies within clinical settings and in developing biological assays, and ultimately 3) exploring utilities of POC systems and smart platforms for biomarker discovery. Additionally, the review explores technology translation from research labs to broader applications. It also addresses associated risks, biases, and challenges of widespread Artificial Intelligence (AI) integration in diagnostics systems, while systematically outlining potential prospects, current challenges, and opportunities. [ABSTRACT FROM AUTHOR]

Extraction of graphene and graphene derivatives from non‐toxic, biocompatible, eco‐friendly, and biodegradable resources with a one‐step production process is a challenge. This work is the first attempt at the one‐step graphenization of Shellac, a biopolymer derived from natural resources, achieved using direct laser patterning. Interestingly, the process highlights substrate independence by producing reduced graphene oxide (rGO) from multiple substrates, such as glass slides, Copper (Cu) adhesive tape, and overhead projector (OHP) plastic films. The produced rGO is fully characterized, and it is found that the sheet resistance is as low as 5.4., 24.65, and 8.4 Ω Sq−1. on the glass slide, OHP plastic sheet, and Cu adhesive, respectively. Moreover, developing various logos on resin‐coated ceramic tiles demonstrated the possibility of patterning desired conductive rGO patterns. Furthermore, a recyclable flexible rGO/Shellac heater is fabricated to validate its electrothermal performance (117.3 °C at 9.5 V) with foldable stability. The proposed one‐step substrate independent two‐material fabrication will revolutionize the process, potentially replacing conventional toxic routes of graphene production. [ABSTRACT FROM AUTHOR]

Although white matter (WM) accounts for nearly half of adult brain, its wiring diagram is largely unknown. Here, an approach is developed to construct WM networks by estimating interregional morphological similarity based on structural magnetic resonance imaging. It is found that morphological WM networks showed nontrivial topology, presented good‐to‐excellent test‐retest reliability, accounted for phenotypic interindividual differences in cognition, and are under genetic control. Through integration with multimodal and multiscale data, it is further showed that morphological WM networks are able to predict the patterns of hamodynamic coherence, metabolic synchronization, gene co‐expression, and chemoarchitectonic covariance, and associated with structural connectivity. Moreover, the prediction followed WM functional connectomic hierarchy for the hamodynamic coherence, is related to genes enriched in the forebrain neuron development and differentiation for the gene co‐expression, and is associated with serotonergic system‐related receptors and transporters for the chemoarchitectonic covariance. Finally, applying this approach to multiple sclerosis and neuromyelitis optica spectrum disorders, it is found that both diseases exhibited morphological dysconnectivity, which are correlated with clinical variables of patients and are able to diagnose and differentiate the diseases. Altogether, these findings indicate that morphological WM networks provide a reliable and biologically meaningful means to explore WM architecture in health and disease. [ABSTRACT FROM AUTHOR]

There has been extensive evidence that aging affects human brain function. However, there is no complete picture of what brain functional changes are mostly related to normal aging and how aging affects brain function similarly and differently between males and females. Based on resting‐state brain functional connectivity (FC) of 25,582 healthy participants (13,373 females) aged 49–76 years from the UK Biobank project, we employ deep learning with explainable AI to discover primary FCs related to progressive aging and reveal similarity and difference between females and males in brain aging. Using a nested cross‐validation scheme, we conduct 4200 deep learning models to classify all paired age groups on the main data for females and males separately and then extract gender‐common and gender‐specific aging‐related FCs. Next, we validate those FCs using additional 21,000 classifiers on the independent data. Our results support that aging results in reduced brain functional interactions for both females and males, primarily relating to the positive connectivity within the same functional domain and the negative connectivity between different functional domains. Regions linked to cognitive control show the most significant age‐related changes in both genders. Unique aging effects in males and females mainly involve the interaction between cognitive control and the default mode, vision, auditory, and frontoparietal domains. Results also indicate females exhibit faster brain functional changes than males. Overall, our study provides new evidence about common and unique patterns of brain aging in females and males. [ABSTRACT FROM AUTHOR]

Background: Genomic sequencing technologies have made the possibility of population screening for whole panels of genetic disorders more feasible than ever before. As one of the most common single gene disorders affecting the UK population, hemophilia is an attractive candidate to include on such screening panels. However, very little is known about views toward genetic screening amongst people with hemophilia or their family members, despite the potential for a wide range of impacts on them. Methods: Twenty‐two in‐depth qualitative interviews were undertaken to explore the views of adults with hemophilia and their family members, recruited through the Haemophilia Society UK. These interviews were used to develop a survey, the Haemophilia Screening Survey (UK), which was distributed in paper and online format through the support group, receiving 327 returns between January and June 2018. Results: Fifty‐seven per cent of the sample supported preconception carrier screening of the population for hemophilia, and 59% supported prenatal carrier screening. Key reasons for support included a desire to reduce pregnancy terminations and increase awareness of hemophilia. Despite support for screening however, 90% of the sample disagreed with pregnancy terminations for hemophilia. Conclusions: Families and adults living with hemophilia are more supportive of screening for information and preparation purposes than to prevent boys with hemophilia from being born. A distinction was made between preventing the disease and preventing the lives of people with it, with support shown for the use of screening to achieve the former, but not at the expense of the latter. [ABSTRACT FROM AUTHOR]

Perovskite solar cells (PSCs) have gained tremendous research interest recently owing to several advantages, including low material cost, facile solution processability, bandgap tunability, and alluring device efficiency. The organic formamidinium (FA) cation‐based perovskites are mainly considered as one of the potential candidates for charge carrier generation due to their excellent properties, such as bandgap and thermal stability than traditional perovskites. However, the inevitable unfavorable polymorphism (i.e., α to δ) at room temperature still forms the basis for numerous research works to allow the fabrication of a high‐quality absorber and enhances the PSCs performance. The studies to resolve the polymorphism and several contemporary techniques (e.g., passivation strategy) with several recent novel fabrication methods presented in this review form the essence of the improvements in PSCs. The absorber morphology also influences the charge‐transfer behavior and the device's lifetime. Therefore, understanding these properties is essential to improve the absorber quality and avoid many defects. This review focuses on the structure and properties of pure and mixed FA perovskites with various halides, mainly the FA cation's role in the absorber composition. And a comprehensive overview of recent FA cation‐based double, triple, and quadrupole PSCs results with proper scientific explanations to understand the device physics. [ABSTRACT FROM AUTHOR]

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine‐related changes in large‐scale brain network dynamics and its implications in clinical features. We pooled data from two disease‐control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting‐state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single‐photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age‐ and sex‐matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age‐ and sex‐matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F‐DOPA‐positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F‐DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre‐processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k‐means clustering were conducted separately for each cohort to derive dFC states (reemerging intra‐ and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L‐dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large‐scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. Practitioner Points: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD‐specific changes in dynamic functional connectivity.Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state.Results only in the PPMI cohort suggest striatal dopamine availability influences large‐scale network dynamics that are relevant in motor control. [ABSTRACT FROM AUTHOR]

The uncertainty concerning the physiological effects of compression bandaging on the peripheral blood flow is a challenge for healthcare professionals. The main objective was to determine the haemodynamic impact on the distal posterior tibial artery after the application of a high‐compression leg multicomponent bandaging system using 4D flow magnetic resonance imaging. Leg dominance disparities of the posterior tibial artery before and after the application of the compressive bandage were also analysed. Twenty‐eight healthy female volunteers were recruited (mean: 25.71, standard deviation: 4.74 years old) through a non‐probability convenience sampling. The 4D flow magnetic resonance imaging of the distal tibial posterior artery was performed in all participants, first under standard resting conditions and after the application of a compression bandage in the leg. When the strong compressive bandage was applied, the area of the assessed artery decreased by 14.2%, whilst the average speed increased by 19.6% and the flow rate increased by 184.8%. There were differences between the haemodynamic parameters of both legs according to dominance, being statistically significantly lower in the dominant leg. The application of strong compressive bandaging significantly increases the arterial flow and mean velocity in the distal segment of the posterior tibial artery, in healthy volunteers by 4D flow magnetic resonance imaging. In this study, leg dominance influenced some of the haemodynamic parameters. According to the results, leg compression bandages cannot be contraindicated in vascular ulcers with arterial compromise. [ABSTRACT FROM AUTHOR]

More than 500 kinases are implicated in the control of most cellular process in mammals, and deregulation of their activity is linked to cancer and inflammatory disorders. 80 clinical kinase inhibitors (CKIs) have been approved for clinical use and hundreds are in various stages of development. However, CKIs inhibit other kinases in addition to the intended target(s), causing both enhanced clinical effects and undesired side effects that are only partially predictable based on in vitro selectivity profiling. Here, we report an integrative approach grounded on the use of chromatin modifications as unbiased, information-rich readouts of the functional effects of CKIs on macrophage activation. This approach exceeded the performance of transcriptome-based approaches and allowed us to identify similarities and differences among CKIs with identical intended targets, to recognize novel CKI specificities and to pinpoint CKIs that may be repurposed to control inflammation, thus supporting the utility of this strategy to improve selection and use of CKIs in clinical settings. Synopsis: Unbiased genome-wide analyses of epigenomic alterations induced by clinical kinase inhibitors (CKIs) in macrophages activated by inflammatory stimuli allow identifying insofar unknown similarities and differences among CKIs, improving their annotations and showing opportunities for repurposing. A genome-wide analysis was developed that exploits epigenetic changes as unbiased, high-content and information-rich read-outs of CKIs' effects. Effects of CKIs on epigenomic changes induced by macrophage activation can be explained by drug-specific combinations of on-target and off-target effects on different sets of signal-regulated transcription factors. CKIs with similar intended annotated target(s) show only partially overlapping epigenomic effects. Conversely, similarities among CKIs with distinct annotations indicate opportunities for drug repurposing. An epigenomic readout was shown to exceed transcription-based analyses in capturing functional effects of CKIs and similarities among them. Unbiased genome-wide analyses of epigenomic alterations induced by clinical kinase inhibitors (CKIs) in macrophages activated by inflammatory stimuli allow identifying insofar unknown similarities and differences among CKIs, improving their annotations and showing opportunities for repurposing. [ABSTRACT FROM AUTHOR]

Aims: Parkinson's disease (PD) patients experience improvement in motor symptoms after deep brain stimulation (DBS) and before initiating stimulation. This is called the microlesion effect. However, the mechanism remains unclear. The study aims to comprehensively explore the changes in functional connectivity (FC) patterns in movement‐related brain regions in PD patients during the microlesion phase through seed‐based FC analysis. Methods: The study collected the resting functional magnetic resonance imaging data of 49 PD patients before and after DBS surgery (off stimulation). The cortical and subcortical areas related to motor function were selected for seed‐based FC analysis. Meanwhile, their relationship with the motor scale was investigated. Results: The motor‐related brain regions were selected as the seed point, and we observed various FC declines within the motor network brain regions. These declines were primarily in the left middle temporal gyrus, bilateral middle frontal gyrus, right supplementary motor area, left precentral gyrus, left postcentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus after DBS. Conclusion: The movement‐related network was extensively reorganized during the microlesion period. The study provided new information on enhancing motor function from the network level post‐DBS. [ABSTRACT FROM AUTHOR]

Effective connectivity (EC) refers to directional or causal influences between interacting neuronal populations or brain regions and can be estimated from functional magnetic resonance imaging (fMRI) data via dynamic causal modeling (DCM). In contrast to functional connectivity, the impact of data processing varieties on DCM estimates of task‐evoked EC has hardly ever been addressed. We therefore investigated how task‐evoked EC is affected by choices made for data processing. In particular, we considered the impact of global signal regression (GSR), block/event‐related design of the general linear model (GLM) used for the first‐level task‐evoked fMRI analysis, type of activation contrast, and significance thresholding approach. Using DCM, we estimated individual and group‐averaged task‐evoked EC within a brain network related to spatial conflict processing for all the parameters considered and compared the differences in task‐evoked EC between any two data processing conditions via between‐group parametric empirical Bayes (PEB) analysis and Bayesian data comparison (BDC). We observed strongly varying patterns of the group‐averaged EC depending on the data processing choices. In particular, task‐evoked EC and parameter certainty were strongly impacted by GLM design and type of activation contrast as revealed by PEB and BDC, respectively, whereas they were little affected by GSR and the type of significance thresholding. The event‐related GLM design appears to be more sensitive to task‐evoked modulations of EC, but provides model parameters with lower certainty than the block‐based design, while the latter is more sensitive to the type of activation contrast than is the event‐related design. Our results demonstrate that applying different reasonable data processing choices can substantially alter task‐evoked EC as estimated by DCM. Such choices should be made with care and, whenever possible, varied across parallel analyses to evaluate their impact and identify potential convergence for robust outcomes. [ABSTRACT FROM AUTHOR]