Impact of Artificial Intelligence (AI) Technology in Healthcare Sector: A Critical Evaluation of Both Sides of the Coin.

The influence of artificial intelligence (AI) has drastically risen in recent years, especially in the field of medicine. Its influence has spread so greatly that it is determined to become a pillar in the future medical world. A comprehensive literature search related to AI in healthcare was performed in the PubMed database and retrieved the relevant information from suitable ones. AI excels in aspects such as rapid adaptation, high diagnostic accuracy, and data management that can help improve workforce productivity. With this potential in sight, the FDA has continuously approved more machine learning (ML) software to be used by medical workers and scientists. However, there are few controversies such as increased chances of data breaches, concern for clinical implementation, and potential healthcare dilemmas. In this article, the positive and negative aspects of AI implementation in healthcare are discussed, as well as recommended some potential solutions to the potential issues at hand.

Improvement in Hypertension Control Among Adults Seen in Federally Qualified Health Center Clinics in the Stroke Belt: Implementing a Program with a Dashboard and Process Metrics.

Objective: Attain 75% hypertension (HTN) control and improve racial equity in control with the American Medical Association Measure accurately, Act rapidly, Partner with patients blood pressure (AMA MAP BP™) quality improvement program, including a monthly dashboard and practice facilitation. Methods: Eight federally qualified health center clinics from the HopeHealth network in South Carolina participated. Clinic staff received monthly practice facilitation guided by a dashboard with process metrics (measure [repeat BP when initial systolic ≥140 or diastolic ≥90 mmHg; Act [number antihypertensive medication classes prescribed at standard dose or greater to adults with uncontrolled BP]; Partner [follow-up within 30 days of uncontrolled BP; systolic BP fall after medication added]) and outcome metric (BP <140/<90). Electronic health record data were obtained on adults ≥18 years at baseline and monthly during MAP BP. Patients with diagnosed HTN, ≥1 encounter at baseline, and ≥2 encounters during 6 months of MAP BP were included in this evaluation. Results: Among 45,498 adults with encounters during the 1-year baseline, 20,963 (46.1%) had diagnosed HTN; 12,370 (59%) met the inclusion criteria (67% black, 29% white; mean (standard deviation) age 59.5 (12.8) years; 16.3% uninsured. HTN control improved (63.6% vs. 75.1%, p<0.0001), reflecting positive changes in Measure, Act, and Partner metrics (all p<0.001), although control remained lower in non-Hispanic black than in non-Hispanic white adults (73.8% vs. 78.4%, p<0.001). Conclusions: With MAP BP, the HTN control goal was attained among adults eligible for analysis. Ongoing efforts aim to improve program access and racial equity in control.

Design, Synthesis, and Characterization of I-BET567, a Pan-Bromodomain and Extra Terminal (BET) Bromodomain Oral Candidate.

Through regulation of the epigenome, the bromodomain and extra terminal (BET) family of proteins represent important therapeutic targets for the treatment of human disease. Through mimicking the endogenous N-acetyl-lysine group and disrupting the protein-protein interaction between histone tails and the bromodomain, several small molecule pan-BET inhibitors have progressed to oncology clinical trials. This work describes the medicinal chemistry strategy and execution to deliver an orally bioavailable tetrahydroquinoline (THQ) pan-BET candidate. Critical to the success of this endeavor was a potency agnostic analysis of a data set of 1999 THQ BET inhibitors within the GSK collection which enabled identification of appropriate lipophilicity space to deliver compounds with a higher probability of desired oral candidate quality properties. SAR knowledge was leveraged via Free-Wilson analysis within this design space to identify a small group of targets which ultimately delivered I-BET567 (27), a pan-BET candidate inhibitor that demonstrated efficacy in mouse models of oncology and inflammation.

Optimization of a Series of 2,3-Dihydrobenzofurans as Highly Potent, Second Bromodomain (BD2)-Selective, Bromo and Extra-Terminal Domain (BET) Inhibitors.

Herein, a series of 2,3-dihydrobenzofurans have been developed as highly potent bromo and extra-terminal domain (BET) inhibitors with 1000-fold selectivity for the second bromodomain (BD2) over the first bromodomain (BD1). Investment in the development of two orthogonal synthetic routes delivered inhibitors that were potent and selective but had raised in vitro clearance and suboptimal solubility. Insertion of a quaternary center into the 2,3-dihydrobenzofuran core blocked a key site of metabolism and improved the solubility. This led to the development of inhibitor 71 (GSK852): a potent, 1000-fold-selective, highly soluble compound with good in vivo rat and dog pharmacokinetics.

Cultural mosaics, social structure, and identity: The Acheulean threshold in Europe.

The period between 600 and 400 ka is a critical phase for human evolution in Europe. The south and northwest saw a dramatic increase in sites, the spread of handaxe technology alongside bone and wooden tool manufacture, efficient hunting techniques, and the use of fire. Lithic assemblages show considerable variation, including the presence/absence of handaxes and tool morphology. To explain this variation, we propose the Cultural Mosaic Model, which suggests that there is a range of expressions of the Acheulean, with local resources being instrumental in creating distinct material cultures with or without handaxes. We argue that if typologically and technologically distinct assemblage types are regionally distributed, chronologically separated, and persistent over time, then they are unlikely to be caused purely by raw material constraints or functional variation but rather reflect populations with different material cultures. We initially assess the model using British data. Britain was a northwestern peninsula of Europe, and oscillations in climate led to episodic occupation. The terraces of the pre-MIS 12 Bytham River provide a framework for dating occupation to MIS 13 and 15, while during MIS 11, archaeological sites with rich environmental records can be dated to substage level. We suggest there are six chronologically and typologically distinct assemblage types that reflect a series of population incursions into Britain. We review the broader European lithic record, which is consistent with the Cultural Mosaic Model. In developing the model, we suggest that during stable climate, localized cultures developed, while climatic change led to shifts in population, with increased knowledge exchange and gene flow. We suggest that group expression through material culture was an important stage in social development by promoting group cohesion, larger group size, better cooperation, improved knowledge transfer, and enabling populations to survive in larger foraging territories in northern Europe.

GSK789: A Selective Inhibitor of the First Bromodomains (BD1) of the Bromo and Extra Terminal Domain (BET) Proteins.

Pan-bromodomain and extra terminal (BET) inhibitors interact equipotently with all eight bromodomains of the BET family of proteins. They have shown profound efficacy in vitro and in vivo in oncology and immunomodulatory models, and a number of them are currently in clinical trials where significant safety signals have been reported. It is therefore important to understand the functional contribution of each bromodomain to assess the opportunity to tease apart efficacy and toxicity. This article discloses the in vitro and cellular activity profiles of GSK789, a potent, cell-permeable, and highly selective inhibitor of the first bromodomains of the BET family.

Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease.

The discovery and lead optimisation of a novel series of SYK inhibitors is described. These were optimised for SYK potency and selectivity against Aurora B. Compounds were profiled in a human skin penetration study to identify a suitable candidate molecule for pre-clinical development. Compound 44 (GSK2646264) was selected for progression and is currently in Phase I clinical trials.

Intra-peritoneal mature benign cystic teratoma deposits: an unusual complication from previous surgical resection of an ovarian mature benign cystic teratoma.

In this case, we describe multiple unusual intra-peritoneal lesions containing fat, soft tissue and calcification. These were found radiologically and histologically to be in keeping with mature benign cystic teratoma intra-peritoneal deposits, also described as dermoid cysts. These were presumed to be due to seeding from surgical resection of ovarian mature benign cystic teratoma 5 years previously. This surgical complication has not been well documented thus far in the literature.

Optimisation of a novel series of potent and orally bioavailable azanaphthyridine SYK inhibitors.

The optimisation of the azanaphthyridine series of Spleen Tyrosine Kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over hERG activity. A good pharmacokinetic profile was achieved by modification of the pKa. Morpholine compound 32 is a potent SYK inhibitor showing moderate selectivity, good oral bioavailability and good efficacy in the rat Arthus model but demonstrated a genotoxic potential in the Ames assay.

Visual processing at goal and effector locations is dynamically enhanced during motor preparation.

Previous theoretical and experimental works has shown that preparing to act causes enhanced perceptual processing at movement-relevant locations. Up until now, this has focused almost exclusively on the goal of an action, neglecting the role of the effector. We addressed this by measuring changes in visual processing across time during motor preparation at both goal and effector locations. We compared event related potentials (ERPs) elicited by task-irrelevant visual probe stimuli at both goal and effector locations during motor preparation. Participants were instructed to place their hands on two starting positions (effector locations) and an auditory tone instructed them to immediately move to one of two target buttons (goal locations). Probe stimuli were presented in the interval between the offset of the cue and the execution of the movement at either a goal or an effector location. Probes were presented randomly at either 100ms, 200ms or 300ms after the auditory cue. Analysis of the visual N1 ERP showed enhanced visual processing at moving vs. not-moving goal locations across all three SOAs. At effector locations, enhanced processing for the moving vs. not-moving effector was only observed during the middle (200ms) SOA. These results demonstrate, for the first time, simultaneous perceptual enhancement of goal and effector locations during motor preparation. We interpret these results as reflecting a temporally and spatially specific dynamic attentional map of the environment that adapts to maximise efficiency of movement by selectively weighting processing of multiple functional components of action in parallel.

Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.

PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation for, to our knowledge, the first time. The therapeutic potential of PAD4 inhibitors can now be explored.

Effectiveness of cold water immersion in the treatment of exertional heat stroke at the Falmouth Road Race.

PURPOSE: This study aimed to investigate the effectiveness (speed of cooling and survival rates) of cold water immersion (CWI) in the treatment of patients with exertional heat stroke (EHS). Secondly, this study aimed to compare cooling rates on the basis of gender, age, and initial rectal temperature (Tr). METHODS: Eighteen years of finish line medical tent patient records were obtained from the exertional heat illness treatment area at the Falmouth Road Race. Study participants included patients with EHS who were treated with CWI in the medical tent. The number of EHS cases was recorded for each year, and incidence was established on the basis of the number of finishers. Overall cooling rate and differences between initial Tr, age, and sex were evaluated. RESULTS: A total of 274 cases of EHS was observed over the 18 yr of collected data. A mean of 15.2 ± 13.0 EHS cases per year was recorded, with an overall incidence of 2.13 ± 1.62 EHS cases per 1000 finishers. The average initial Tr was 41.44°C ± 0.63°C, and the average cooling rate for patients with EHS was 0.22°C·min ± 0.11°C·min. CWI resulted in a 100% survival rate for all patients with EHS. No significant interactions between cooling rate and initial Tr (P = 0.778), sex (P = 0.89), or age (P = 0.70) were observed. CONCLUSIONS: CWI was found to effectively treat all cases of EHS observed in this study. CWI provided similar treatment outcomes in all patients, with no significant differences noted on the basis of initial Tr, age, or sex. On the basis of the 100% survival rate from EHS in this large cohort, it is recommended that immediate (on site) CWI be implemented for the treatment of EHS.

Environmental conditions and the occurrence of exertional heat illnesses and exertional heat stroke at the Falmouth Road Race.

CONTEXT: The Falmouth Road Race is unique because of the environmental conditions and relatively short distance, which allow runners to maintain a high intensity for the duration of the event. Therefore, the occurrence of exertional heat illnesses (EHIs), especially exertional heat stroke (EHS), is 10 times higher than in other races. OBJECTIVE: To summarize the occurrence and relationship of EHI and environmental conditions at the Falmouth Road Race. DESIGN: Descriptive epidemiologic study. SETTING: An 11.3-km (7-mile) road race in Falmouth, Massachusetts. PATIENTS OR OTHER PARTICIPANTS: Runners who sustained an EHI while participating in the Falmouth Road Race. MAIN OUTCOME MEASURE(S): We obtained 18 years of medical records and environmental conditions from the Falmouth Road Race and documented the incidence of EHI, specifically EHS, as related to ambient temperature (Tamb), relative humidity, and heat index (HI). RESULTS: Average Tamb, relative humidity, and HI were 23.3 ± 2.5°C, 70 ± 16%, and 24 ± 3.5°C, respectively. Of the 393 total EHI cases observed, EHS accounted for 274 (70%). An average of 15.2 ± 13.0 EHS cases occurred each year; the incidence was 2.13 ± 1.62 cases per 1000 runners. Regression analysis revealed a relationship between the occurrence of both EHI and EHS and Tamb (R(2) = 0.71, P = .001, and R(2) = 0.65, P = .001, respectively) and HI (R(2) = 0.76, P < .001, and R(2) = 0.74, P < .001, respectively). Occurrences of EHS (24.2 ± 15.5 cases versus 9.3 ± 4.3 cases) and EHI (32.3 ± 16.3 versus 13.0 ± 4.9 cases) were higher when Tamb and HI were high compared with when Tamb and HI were low. CONCLUSIONS: Because of the environmental conditions and race duration, the Falmouth Road Race provides a unique setting for a high incidence of EHS. A clear relationship exists between environmental stress, especially as measured by Tamb and HI, and the occurrence of EHS or other EHI. Proper prevention and treatment strategies should be used during periods of high environmental temperatures as the likelihood of runners experiencing EHS is exacerbated in these harsh conditions.

The electrophysiological time course of somatosensory spatial remapping: vision of the hands modulates effects of posture on somatosensory evoked potentials.

We investigated the electrophysiological correlates of somatosensory processing under different arm postures by recording event-related potentials at frontal, central and centroparietal sites during tactile stimulation of the hands. Short series of 200 ms vibrotactile stimuli were presented to the palms of the participants' hands, one hand at a time, in either uncrossed- or crossed-hands postures. The manipulation of posture allowed us to investigate the electrophysiological processes underlying the spatial remapping of somatosensory stimuli from anatomical into external frames of reference. To examine somatosensory spatial remapping independently of its effects on attentional processes, the stimuli were presented unpredictably in terms of location, and in temporal onset. We also examined how vision of the limbs affects the process of remapping. When participants had sight of their hands (Experiment 1) the effect of posture was observed over regions contralateral to the stimulated hand from 128 ms, whereas when their limbs were covered (Experiment 2) effects of posture influenced the ipsilateral regions from 150 ms. These findings add to an increasing body of evidence which indicates that sight of the hand modulates the way in which information in other modalities is processed. We argue that in this case, sight of the hand biases spatial encoding of touch towards an anatomical frame of reference.

The effects of autism and alexithymia on physiological and verbal responsiveness to music.

It has been suggested that individuals with autism will be less responsive to the emotional content of music than typical individuals. With the aim of testing this hypothesis, a group of high-functioning adults on the autism spectrum was compared with a group of matched controls on two measures of emotional responsiveness to music, comprising physiological and verbal measures. Impairment in participants ability to verbalize their emotions (type-II alexithymia) was also assessed. The groups did not differ significantly on physiological responsiveness, but the autism group was significantly lower on the verbal measure. However, inclusion of the alexithymia score as a mediator variable nullified this group difference, suggesting that the difference was due not to absence of underlying emotional responsiveness to music in autism, but to a reduced ability to articulate it.

Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor.

The lead optimisation of the diaminopyrimidine carboxamide series of spleen tyrosine kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over liability kinases and hERG activity. GSK143 is a potent and highly selective SYK inhibitor showing good efficacy in the rat Arthus model.

The "Haunt" project: an attempt to build a "haunted" room by manipulating complex electromagnetic fields and infrasound.

Recent research has suggested that a number of environmental factors may be associated with a tendency for susceptible individuals to report mildly anomalous sensations typically associated with "haunted" locations, including a sense of presence, feeling dizzy, inexplicable smells, and so on. Factors that may be associated with such sensations include fluctuations in the electromagnetic field (EMF) and the presence of infrasound. A review of such work is presented, followed by the results of the "Haunt" project in which an attempt was made to construct an artificial "haunted" room by systematically varying such environmental factors. Participants (N=79) were required to spend 50 min in a specially constructed chamber, within which they were exposed to infrasound, complex EMFs, both or neither. They were informed in advance that during this period they might experience anomalous sensations and asked to record on a floor plan their location at the time of occurrence of any such sensations, along with a note of the time of occurrence and a brief description of the sensation. Upon completing the session in the experimental chamber, they were asked to complete three questionnaires. The first was an EXIT scale asking respondents to indicate whether or not they had experienced particular anomalous sensations. The second was the Australian Sheep-Goat Scale, a widely used measure of belief in and experience of the paranormal. The third was Persinger's Personal Philosophy Inventory, although only the items that constitute the Temporal Lobe Signs (TLS) Inventory sub-scale were scored. These items deal with psychological experiences typically associated with temporal lobe epilepsy but normally distributed throughout the general population. Although many participants reported anomalous sensations of various kinds, the number reported was unrelated to experimental condition but was related to TLS scores. The most parsimonious explanation for our findings is in terms of suggestibility.