Miracle-dz/UniFAR-FTUs huggingface dataset:
Renin–angiotensin system in intestinal inflammation—Angiotensin inhibitors to treat inflammatory bowel diseases?

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract, which manifest in recurring gastrointestinal inflammation. The current treatment options of IBD are not curative and are lacking in aspects like prevention of fibrosis. New treatment options are needed to fulfil the unmet needs and provide alternatives to drugs with resistances and side effects. Drugs targeting the renin–angiotensin system (RAS), besides being antihypertensive, also possess anti‐inflammatory and antifibrotic properties and could offer an inexpensive alternative to control inflammation and fibrosis in the gut. RAS inhibitors have been effective in preventing and alleviating colitis in preclinical studies, but available human data are still sparse. This review outlines the pathophysiological functions of RAS in the gut and summarizes preclinical studies utilizing pharmacological RAS inhibitors in the treatment of experimental colitis. We discuss the alterations in intestinal RAS and the available evidence of the benefits of RAS inhibitors for IBD patients. Retrospective studies comparing IBD patients using ACE inhibitors or angiotensin II receptor blockers have provided optimistic results regarding a milder disease course and fewer hospitalizations and corticosteroid use in patients using RAS inhibitors. Prospective studies are needed to evaluate the effectiveness of these promising medications in the treatment of IBD.
Repurposing CRISPR-Cas Systems as Genetic Tools for the Enterobacteriales

Over the last decade, the study of CRISPR-Cas systems has progressed from a newly discovered bacterial defense mechanism to a diverse suite of genetic tools that have been applied across all domains of life. While the initial applications of CRISPR-Cas technology fulfilled a need to more precisely edit eukaryotic genomes, creative “repurposing” of this adaptive immune system has led to new approaches for genetic analysis of microorganisms, including improved gene editing, conditional gene regulation, plasmid curing and manipulation, and other novel uses. ABSTRACT Over the last decade, the study of CRISPR-Cas systems has progressed from a newly discovered bacterial defense mechanism to a diverse suite of genetic tools that have been applied across all domains of life. While the initial applications of CRISPR-Cas technology fulfilled a need to more precisely edit eukaryotic genomes, creative “repurposing” of this adaptive immune system has led to new approaches for genetic analysis of microorganisms, including improved gene editing, conditional gene regulation, plasmid curing and manipulation, and other novel uses. The main objective of this review is to describe the development and current state-of-the-art use of CRISPR-Cas techniques specifically as it is applied to members of the Enterobacteriales. While many of the applications covered have been initially developed in Escherichia coli, we also highlight the potential, along with the limitations, of this technology for expanding the availability of genetic tools in less-well-characterized non-model species, including bacterial pathogens.
Internet Interest in Colon Cancer Following the Death of Chadwick Boseman: Infoveillance Study

Background Compared with White Americans, Black Americans have higher colon cancer mortality rates but lower up-to-date screening rates. Chadwick Boseman was a prominent Black American actor who died of colon cancer on August 28, 2020. As announcements of celebrity diagnoses often result in increased awareness, Boseman’s death may have resulted in greater interest in colon cancer on the internet, particularly among Black Americans. Objective This study aims to quantify the impact of Chadwick Boseman’s death on web-based search interest in colon cancer and determine whether there was an increase in interest in regions of the United States with a greater proportion of Black Americans. Methods We conducted an infoveillance study using Google Trends (GT) and Wikipedia pageview analysis. Using an autoregressive integrated moving average algorithm, we forecasted the weekly relative search volume (RSV) for GT search topics and terms related to colon cancer that would have been expected had his death not occurred and compared it with observed RSV data. This analysis was also conducted for the number of page views on the Wikipedia page for colorectal cancer. We then delineated GT RSV data for the term colon cancer for states and metropolitan areas in the United States and determined how the RSV values for these regions correlated with the percentage of Black Americans in that region. Differences in these correlations before and after Boseman’s death were compared to determine whether there was a shift in the racial demographics of the individuals conducting the searches. Results The observed RSVs for the topics colorectal cancer and colon cancer screening increased by 598% and 707%, respectively, and were on average 121% (95% CI 72%-193%) and 256% (95% CI 35%-814%) greater than expected during the first 3 months following Boseman’s death. Daily Wikipedia page view volume during the 2 months following Boseman’s death was on average 1979% (95% CI 1375%-2894%) greater than expected, and it was estimated that this represented 547,354 (95% CI 497,708-585,167) excess Wikipedia page views. Before Boseman’s death, there were negative correlations between the percentage of Black Americans living in a state or metropolitan area and the RSV for colon cancer in that area (r=−0.18 and r=−0.05, respectively). However, in the 2 weeks following his death, there were positive correlations between the RSV for colon cancer and the percentage of Black Americans per state and per metropolitan area (r=0.73 and r=0.33, respectively). These changes persisted for 4 months and were all statistically significant (P<.001). Conclusions There was a significant increase in web-based activity related to colon cancer following Chadwick Boseman’s death, particularly in areas with a higher proportion of Black Americans. This reflects a heightened public awareness that can be leveraged to further educate the public.
Cyclic nucleotide‐dependent ionic currents in olfactory receptor neurons of the hawkmoth Manduca sexta suggest pull–push sensitivity modulation

Olfactory receptor neurons (ORNs) of the hawkmoth Manduca sexta sensitize via cAMP‐ and adapt via cGMP‐dependent mechanisms. Perforated patch clamp recordings distinguished 11 currents in these ORNs. Derivatives of cAMP and/or cGMP antagonistically affected three of five K+ currents and two non‐specific cation currents. The Ca2+‐dependent K+ current IK(Ca2+) and the sensitive pheromone‐dependent K+ current IK(cGMP−), which both express fast kinetics, were inhibited by 8bcGMP, while a slow K+ current, IK(cGMP+), was activated by 8bcGMP. Furthermore, application of 8bcAMP blocked slowly activating, zero mV‐reversing, non‐specific cation currents, ILL and Icat(PKC? ), which remained activated in the presence of 8bcGMP. Their activations pull the membrane potential towards their 0‐mV reversal potentials, in addition to increasing intracellular Ca2+ levels voltage‐ and ILL‐dependently. Twenty minutes after application, 8bcGMP blocked a TEA‐independent K+ current, IK(noTEA), and a fast cation current, Icat(nRP), which both shift the membrane potential to negative values. We conclude that conditions of sensitization are maintained at high levels of cAMP, via specific opening/closure of ion channels that allow for fast kinetics, hyperpolarized membrane potentials, and low intracellular Ca2+ levels. In contrast, adaptation is supported via cGMP, which antagonizes cAMP, opening Ca2+‐permeable channels with slow kinetics that stabilize depolarized resting potentials. The antagonistic modulation of peripheral sensory neurons by cAMP or cGMP is reminiscent of pull–push mechanisms of neuromodulation at central synapses underlying metaplasticity.
Participant Experiences of a Quit Smoking Attempt Through Either Nicotine Replacement Therapy (NRT) Methods or the Use of an E-cigarette

Objectives There is a lack of evidence exploring experiences of using e-cigarettes for smoking cessation. The study’s main aim was to explore participant experiences of e-cigarettes compared to nicotine replacement therapy (NRT) delivered through stop smoking services. Methods Semi-structured, face-to-face, and telephone interviews at 3-month post-quit follow-up in a randomized controlled trial comparing nicotine-containing e-cigarettes, nicotine-free e-cigarettes, and NRT for smoking cessation. N = 17 participants, 9 were male, mean age 44 years, 5 using nicotine-containing e-cigarettes, 7 nicotine-free e-cigarettes, and 5 NRT. Interviews were transcribed and analyzed using thematic analysis. Results Two global themes and 5 organizing themes were identified. Global themes included: (1) experiences of e-cigarette and NRT quit aids (e-cigarette positive impact and dilemmas, NRT perceptions and experiences), and (2) key mechanisms to support quit attempt (physical aids, advice and support, feedback and structure). E-cigarettes were viewed with caution, however, generally evaluated positively alongside NRT methods, finding e-cigarettes useful during a quit attempt due to their versatility in application. Nicotinecontaining e-cigarettes were favored due to their support with nicotine cravings. Participants were, however, wary of replacing smoking addiction with vaping habit. Conclusions Participant e-cigarette experience were generally positive; however, concerns over long-term application were noted. There was a noticeable preference for nicotine-containing e-cigarettes, but further research is required to better understand how nicotine is used in conjunction with e-cigarettes long-term as a quit aid alongside other NRT.
Schema therapy for violent PD offenders: a randomized clinical trial

Abstract Background Violent criminal offenders with personality disorders (PD's) can cause immense harm, but are often deemed untreatable. This study aimed to conduct a randomized clinical trial to test the effectiveness of long-term psychotherapy for rehabilitating offenders with PDs. Methods We compared schema therapy (ST), an evidence-based psychotherapy for PDs, to treatment-as-usual (TAU) at eight high-security forensic hospitals in the Netherlands. Patients in both conditions received multiple treatment modalities and differed only in the individual, study-specific therapy they received. One-hundred-three male offenders with antisocial, narcissistic, borderline, or paranoid PDs, or Cluster B PD-not-otherwise-specified, were assigned to 3 years of ST or TAU and assessed every 6 months. Primary outcomes were rehabilitation, involving gradual reintegration into the community, and PD symptoms. Results Patients in both conditions showed moderate to large improvements in outcomes. ST was superior to TAU on both primary outcomes – rehabilitation (i.e. attaining supervised and unsupervised leave) and PD symptoms – and six of nine secondary outcomes, with small to moderate advantages over TAU. ST patients moved more rapidly through rehabilitation (supervised leave, treatment*time: F(5308) = 9.40, p < 0.001; unsupervised leave, treatment*time: F(5472) = 3.45, p = 0.004), and showed faster improvements on PD scales (treatment*time: t(1387) = −2.85, p = 0.005). Conclusions These findings contradict pessimistic views on the treatability of violent offenders with PDs, and support the effectiveness of long-term psychotherapy for rehabilitating these patients, facilitating their re-entry into the community.
Operative Versus Nonoperative Treatment of Acute Displaced Distal Clavicle Fractures: A Multicenter Randomized Controlled Trial

Objectives: To evaluate the differences in patient outcomes after operative or nonoperative treatment of displaced, type II distal clavicle fractures. Design: Multicenter, prospective, randomized controlled trial. Setting: Level I trauma centers. Patients/Participants: Patients with completely displaced type II distal clavicle fractures were included. Fifty-seven patients were randomized: 27 to the operative group and 30 to the nonoperative group. Intervention: Patients randomized to nonoperative care received a standard shoulder sling, followed by pendulum or gentle range of motion shoulder exercises at any time as directed by the attending surgeon. Patients randomized to the operative group received plate fixation with a precontoured distal clavicular plate or a “hook” plate within 28 days from injury. Main Outcome Measure: Disabilities of the Arm, Shoulder and Hand scores at 1 year. Results: There were no between-group differences in Disabilities of the Arm, Shoulder and Hand or Constant scores at 1 year. More patients in the operative group went on to union (95% vs. 64%, P = 0.02) within 1 year. Twelve patients in the operative group underwent a second operation for implant removal (12/27, 44%). In the nonoperative group, 6 patients (6/30, 20%) subsequently underwent 8 operative procedures. Conclusion: Although this study failed to demonstrate a difference in functional outcomes between operative and nonoperative treatment of Neer type II distal clavicle fractures, nonoperative management led to more complications including a moderate rate of nonunion, which often required secondary surgery to correct, a higher rate of early dissatisfaction with shoulder appearance, and a delayed return to activities in the first 6 months. Operative management provided a safe and reliable treatment option with few complications, but often required secondary implant removal, especially with hook plate fixation. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
Organization of the central nervous system and innervation of cephalic sensory structures in the water bear Echiniscus testudo (Tardigrada: Heterotardigrada) revisited

The tardigrade brain has been the topic of several neuroanatomical studies, as it is key to understanding the evolution of the central nervous systems in Panarthropoda (Tardigrada + Onychophora + Arthropoda). The gross morphology of the brain seems to be well conserved across tardigrades despite often disparate morphologies of their heads and cephalic sensory structures. As such, the general shape of the brain and its major connections to the rest of the central nervous system have been mapped out already by early tardigradologists. Despite subsequent investigations primarily based on transmission electron microscopy or immunohistochemistry, characterization of the different regions of the tardigrade brain has progressed relatively slowly and open questions remain. In an attempt to improve our understanding of different brain regions, we reinvestigated the central nervous system of the heterotardigrade Echiniscus testudo using anti‐synapsin and anti‐acetylated α‐tubulin immunohistochemistry in order to visualize the number and position of tracts, commissures, and neuropils. Our data revealed five major synapsin‐immunoreactive domains along the body: a large unitary, horseshoe‐shaped neuropil in the head and four neuropils in the trunk ganglia, supporting the hypothesis that the dorsal brain is serially homologous with the ventral trunk ganglia. At the same time, the pattern of anti‐synapsin and anti‐tubulin immunoreactivity differs between the ganglia, adding to the existing evidence that each of the four trunk ganglia is unique in its morphology. Anti‐tubulin labeling further revealed two commissures within the central brain neuropil, one of which is forked, and additional sets of extracerebral cephalic commissures associated with the stomodeal nervous system and the ventral cell cluster. Furthermore, our results showing the innervation of each of the cephalic sensilla in E. testudo support the homology of subsets of these structures with the sensory fields of eutardigrades.
Characteristics and prognosis of patients with embolic stroke of undetermined source in China

Background and purpose We aimed to explore the frequencies, risk factors, and natural history of embolic stroke of undetermined source (ESUS) through a national prospective registry in China. Methods Between August 2015 and March 2018, the Third China National Stroke Registry recruited consecutive patients with ischemic stroke or transient ischemic attack in China. The baseline characteristics, risks of stroke, and prognosis in patients with embolic stroke of undetermined source were described and compared with that in patients with other causative subtypes. Results A total of 15,166 transient ischemic attack and ischemic stroke patients were enrolled in the Third China National Stroke Registry. Among 8528 ischemic stroke with standard diagnostic work-up, 2415 (28.3%) patients were diagnosed with embolic stroke of undetermined source. The mean age was 61 years and 70% of them were male. Compared to patients with cardioembolic strokes and small vessel disease, patients with embolic stroke of undetermined source had higher prevalence of nonstenosing large artery atherosclerosis (37.93% vs. 31.26%, P = 0.008 and 37.93% vs. 34.40%, P = 0.044 respectively). The cumulative probability of stroke recurrence in patients with embolic stroke of undetermined source at three months and one year was 5.59% and 8.74%. Compared with embolic stroke of undetermined source patients (0.70% and 1.99%), patients with the large artery atherosclerosis and cardioembolic strokes had higher cumulative probability of death at three months (1.94% and 3.22%) and one year (4.17% and 7.39%). Conclusions Embolic stroke of undetermined source is a common cause of ischemic stroke in Chinese population with a higher stroke recurrence than previously reported. It was more likely to have nonstenosing large artery atherosclerosis in patients with embolic stroke of undetermined source than with cardioembolic strokes and small vessel disease.
Social Support and Help-Seeking Among Suicide Bereaved: A Study With Italian Survivors

Background Research over how suicide survivors approach services is limited. Aims: This cross-sectional study explores the psychological state and perceived social support of Italian survivors, including those who have not sought for help, and investigates differences for gender or kinship with the departed. Methods: Rule-based system (RBS) analyses identified relationships between social support and reported formal/informal help-seeking behavior. One-hundred thirty-two (103F; 27M) suicide survivors (53 having never sought for support) answered an anonymous online survey. Life satisfaction, wellbeing, perceived social support, suicidal ideation and formal/informal help-seeking were investigated. Results: RBS analysis identified different help-seeking behaviors: survivors lacking social support may avoid reaching a psychologist and prefer GPs, look for advice in online forums and rely on people out of their narrower network such as co-workers. Conclusion: These unique study’s results offer insight to identify which specific areas would be fruitful to investigate while assessing social support in bereaved individuals.
Central sensitisation features are associated with neuropathic pain-like symptoms in patients with longstanding rheumatoid arthritis: a cross-sectional study using the central sensitisation inventory.

OBJECTIVES Several studies have indicated that arthralgia may be driven by central sensitisation. Central sensitivity syndrome (CSS) is a concept that unifies various symptoms due to central sensitisation. Recently, the central sensitisation inventory (CSI) was developed as a screening questionnaire to detect CSS. Using the CSI, we examined the prevalence, the clinical characteristics of CSS, and the association between CSS and neuropathic pain (NP)-like symptoms among rheumatoid arthritis (RA) patients. METHODS The CSI was administered to 240 RA outpatients. We evaluated their disease activity and several potentially relevant patient-reported outcomes. We compared the clinical parameters depending on the severity of CSS and examined the effect of the CSI score on NP-like symptoms among the relevant clinical parameters using multivariate analyses. RESULTS The mean disease duration was 9.58 ± 7.76 years. Eighteen (7.5 %) patients had CSS, which was associated with evaluator global assessment (EGA) (odds ratio (OR) 0.860); fibromyalgia symptom scale (OR 1.46); painDETECT questionnaire score (OR 1.24); hospital anxiety and depression scale-anxiety (OR 1.35); and physical (OR 0.898), mental (OR 0.828), and role-social (OR 0.946) component summary scores on the Short-Form 36-Item Health Survey. CSI score was the factor that contributed most to NP-like symptoms (p=0.000, β=0.266). CONCLUSIONS NP-like symptoms might be one of the symptoms of CSS in longstanding RA patients. In longstanding RA patients who have disproportionately greater NP-like symptoms and/or widespread pain compared with degree of inflammation, detecting CSS using CSI might help to understand the pathogenesis of patients.
Efficiency and Teamwork in Emergency Departments: Perception of Staff on Design Interventions

Objectives: The goal of this study is twofold: (1) identifying design strategies that enhance efficiency and support teamwork in emergency departments (EDs) and (2) identifying design features that contribute to the spread of COVID-19, based on staff perception. Background: Due to increasing ED visits annually, an efficient work environment has become one of the main concerns in designing EDs. According to the literature, an efficient work environment and teamwork improve healthcare outcomes and positively impact staff satisfaction. During the COVID-19 pandemic, EDs faced various changes such as workflow and space usage. Few studies explored staff perceptions about the influence of design features on efficiency, teamwork, and the COVID-19 spread. Method: An online survey with 14 open- and closed-ended questions was distributed among ED staff members to collect data about unit design features that impact efficiency, teamwork, and the COVID-19 spread. Results: The central nursing station was one of the preferred configurations that increased efficiency and teamwork in EDs. Decentralizing disposal rooms in small-size EDs and decentralizing the medication room in large-size EDs with more than 65 exam rooms can decrease staff walking steps. Flexibility to expand treatment spaces on demand, one-way track circulation path, and changing the air pressure in COVID-19 treatment areas were some of the staff suggestions for future EDs. Conclusion: The findings of this study contribute to the body of knowledge that EDs’ physical environments can impact efficiency and teamwork among staff and, consequently, healthcare outcomes. Compartmentalization of the ED layout can reduce the spread of COVID-19.