Miracle-dz/UniFAR-FTUs huggingface dataset:
EMvelop stimulation: minimally invasive deep brain stimulation using temporally interfering electromagnetic waves

Objective. Recently, the temporal interference stimulation (TIS) technique for focal noninvasive deep brain stimulation (DBS) was reported. However, subsequent computational modeling studies on the human brain have shown that while TIS achieves higher focality of electric fields than state-of-the-art methods, further work is needed to improve the stimulation strength. Here, we investigate the idea of EMvelop stimulation, a minimally invasive DBS setup using temporally interfering gigahertz (GHz) electromagnetic (EM) waves. At GHz frequencies, we can create antenna arrays at the scale of a few centimeters or less that can be endocranially implanted to enable longitudinal stimulation and circumvent signal attenuation due to the scalp and skull. Furthermore, owing to the small wavelength of GHz EM waves, we can optimize both amplitudes and phases of the EM waves to achieve high intensity and focal stimulation at targeted regions within the safety limit for exposure to EM waves. Approach. We develop a simulation framework investigating the propagation of GHz EM waves generated by line current antenna elements and the corresponding heat generated in the brain tissue. We propose two optimization flows to identify antenna current amplitudes and phases for either maximal intensity or maximal focality transmission of the interfering electric fields with EM waves safety constraint. Main results. A representative result of our study is that with two endocranially implanted arrays of size 4.2 cm × 4.7 cm each, we can achieve an intensity of 12 V m−1 with a focality of 3.6 cm at a target deep in the brain tissue. Significance. In this proof-of-principle study, we show that the idea of EMvelop stimulation merits further investigation as it can be a minimally invasive way of stimulating deep brain targets and offers benefits not shared by prior methodologies of electrical or magnetic stimulation.
Predictors of sacubitril/valsartan high dose tolerability in a real world population with HFrEF

The angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all‐cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up‐titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up‐titration success.
Analysis of Pharmacological Activities and Mechanisms of Essential Oil in Leaves of C. grandis ‘Tomentosa’ by GC-MS/MS and Network Pharmacology

Background Citrus grandis ‘Tomentosa,’ a fruit epicarp of C. grandis ‘Tomentosa’ or C. grandis (L.) Osbeck is widely used in health food and medicine. Based on our survey results, there are also rich essential oils with bioactivities in leaves, but the chemical compounds in this part and relevant pharmacological activities have never been studied systematically. Therefore, this study was to preliminarily decipher the pharmacological activities and mechanisms of the essential oil in leaves of C. grandis ‘Tomentosa’ by an integrated network pharmacology approach. Methods Essential oil compositions from leaves of C. grandis ‘Tomentosa’ were identified using GC-MS/MS. And then, the targets of these oil compositions were predicted and screened from TCMSP, SwissTargetPrediction, STITCH and SEA databases. STRING database was used to construct the protein-protein interaction networks, and the eligible protein targets were input into WebGestalt 2019 to carry out GO enrichment and KEGG pathway enrichment analysis. Based on the potential targets, disease enrichment information was obtained by TTD databases. Cytoscape software was used to construct the component-target-disease network diagrams. Results Finally, 61 essential oil chemical components were identified by GC-MS/MS, which correspond to 679 potential targets. Biological function analysis showed 12, 19, and 12 GO entries related to biological processes, cell components and molecular functions, respectively. 43 KEGG pathways were identified, of which the most significant categories were terpenoid backbone biosynthesis, TNF signaling pathway and leishmaniasis. The component-target-disease network diagram revealed that the essential oil compositions in leaves of C. grandis ‘Tomentosa’ could treat tumors, immune diseases, neurodegenerative diseases and respiratory diseases, which were highly related to CHRM1, PTGS2, CASP3, MAP2K1 and CDC25B. Conclusion This study may provide new insight into C. grandis ‘Tomentosa’ or C. grandis (L.) Osbeck and may provide useful information for future utilization and development.
“We figured it out as we went along”: Staff perspectives of COVID‐19 response efforts at a large North American syringe services programme

Abstract Syringe services programmes face operational challenges to provide life‐sustaining services to people who use substances and those who have substance use disorders. COVID‐19 has disrupted operations at these programmes and is a threat to people with substance use disorder because of severe poverty, de‐prioritisation of COVID‐19 safety and high prevalence of comorbidities. This phenomenological qualitative study describes 16 in‐depth interviews with staff of one of the largest syringe services programme in North America—Prevention Point Philadelphia, located in the Kensington neighbourhood of Philadelphia, Pennsylvania. Interviews were conducted from December 2020 to February 2021, audio‐recorded, transcribed and coded to develop a thematic framework. Participants were mostly white (71.4%) and female (68.8%) with a median age of 31.5. Three main and four sub‐themes related to the impact of COVID‐19 on the syringe services programme were identified: (1) COVID‐19 altered services provision (sub‐theme: select service changes should be retained); (2) unclear or absent COVID‐19 response guidance which compromised mitigation (sub‐themes: COVID‐19 messaging was difficult to translate to practice, learn‐as‐we‐go); and (3) staff and clients experienced elevated mental anguish during the pandemic (sub‐theme: already limited resources were further strained). COVID‐19 presented complex challenges to an organisation normally strained in pre‐pandemic times. A staff culture of resourcefulness and resiliency aided the syringe services programme to balance client needs and staff safety. However, staff experienced a serious psychological impact, largely attributable to being unable to find reprieve from the stressors of COVID‐19 and the difficulties associated with navigating and acting‐on contradictory public health messaging. Staff also shared a belief that the relaxing of some pre‐pandemic barriers allowed staff to link clients more readily with services. Syringe services programmes should embrace the potential for lasting changes to health services delivery brought about by wide‐scale changes in service provisions because of COVID‐19.
Robotic vs Laparoscopic Ventral Hernia Repair with Intraperitoneal Mesh: 1-Year Exploratory Outcomes of the PROVE-IT Randomized Clinical Trial.

BACKGROUND Laparoscopic and robotic ventral hernia repair with intraperitoneal mesh have been demonstrated previously to have comparable 30-day outcomes in the PROVE-IT randomized clinical trial. Here we report our 1-year follow-up of enrolled patients to examine exploratory outcomes. STUDY DESIGN All patients enrolled in a previously published, registry-based, randomized trial investigating laparoscopic vs robotic ventral hernia repair with intraperitoneal mesh were reviewed. Several exploratory secondary outcomes were assessed: pain intensity (Patient-Reported Outcomes Measurement Information System [PROMIS 3a]), hernia-specific quality of life (Hernia-Specific Quality of Life Survey [HerQLes]), composite hernia recurrence, and reoperations. RESULTS A total of 95% (71 of 75) follow-up was achieved: 33 laparoscopic repairs and 38 robotic repairs. Median follow-up time was 12 months [interquartile range 10 to 12 months]. Following regression analysis adjusting for baseline scores, there was no difference in postoperative pain intensity at 1 year (p = 0.94). However, HerQLes scores increased by 12.0 more points following robotic repairs compared to laparoscopic counterparts (95% CI 1.3 to 22.7, p = 0.03). Composite hernia recurrence was 6% (2 of 33) for the laparoscopic cohort and 24% (9 of 38) for the robotic group (p = 0.04). There was no difference in rates of reoperation (p = 0.61). CONCLUSIONS Our exploratory analyses have identified potential differences in quality of life and recurrence, favoring the robotic and laparoscopic approaches, respectively. These findings warrant further study with larger patient cohorts to verify their potential significance.
Level of Suicidal Ideation Among Callers to the Danish Suicide Prevention Helpline

Abstract Objective The aim of this study was to: (1) determine the proportion of callers to a national helpline for suicide prevention who were evaluated to be at risk of suicide; (2) identify characteristics associated with being at risk; (3) determine the level of suicidal ideation among callers, as measured by a clinical scale, and compared to the general population. Method Data on all calls answered at the Danish helpline for suicide prevention during 2018–2019 were analyzed. These consisted of socio-demographic covariates and items related to suicidality, including the Suicidal Ideation Attribute Scale (SIDAS). Data on SIDAS for the general population derived from a survey. Being at risk of suicide, as evaluated by the counselors, was examined as outcome in adjusted logistic regressions. Results Among 42,393 answered calls, 24,933 (59%) related to personal concerns. Of these, 47% and 14% of callers, respectively, had suicidal thoughts and concrete suicidal plans, while 53% were evaluated to be at risk. Higher risks were found when issues related to self-harm, mental health problems, eating disorders, incest, physical health problems, substance abuse, or sexual assault were mentioned. In all 37% of callers who were administered the SIDAS scale were evaluated to be at high risk of suicide compared to 1.5% in the general population. Conclusions A substantial share of callers to a national helpline for suicide prevention were evaluated to be at risk of suicide, also when using a clinical scale. This emphasizes the potential for counselors to prevent suicidal behavior. Highlights More than half of callers reaching out to the helpline were evaluated to be at risk of suicide, and 37% were identified as being at high risk using SIDAS, a clinical scale. Being woman, of younger age, having a history of previous suicide attempt as well as experiencing problems related to self-harm, mental disorders, sexual assault, substance abuse, and physical health problems was associated with risk of suicide, as evaluated by counselors. This seemingly is the first study to compare clinical scores of helpline callers to those of the general population and significantly higher levels of suicidal ideation were found among helpline callers.
Monocyte Distribution Width in Children With Systemic Inflammatory Response: Retrospective Cohort Examining Association With Early Sepsis*

OBJECTIVES: To investigate the association between increased monocyte distribution width (MDW) and pediatric sepsis in the emergency department (ED). DESIGN: Retrospective cohort study. SETTING: A single academic hospital study. PATIENTS: Patients from birth to the age of 18 years who presented at the ED of an academic hospital with systemic inflammatory response syndrome (SIRS) were consecutively enrolled. Sepsis was diagnosed using the International Pediatric Surviving Sepsis Campaign criteria. INTERVENTIONS: Antibiotic treatment was administrated once infection was suspected. MEASUREMENTS and MAIN RESULTS: Routine complete blood cell count, neutrophil-to-lymphocyte ratio (NLR), and MDW, a new inflammatory biomarker, were evaluated in the ED. Logistic regression models were used to explore associations with early pediatric sepsis. We included 201 patients with sepsis and 1,050 without sepsis. In the multivariable model, MDW greater than 23 U (odds ratio [OR], 4.97; 95% CI, 3.42–7.22; p < 0.0001), NLR greater than 6 (OR, 2.06; 95% CI, 1.43–2.94; p = 0.0001), WBC greater than 11,000 cells/µL (OR, 6.52; 95% CI, 4.45–9.53; p < 0.0001), and the SIRS score (OR, 3.42; 95% CI, 2.57–4.55; p < 0.0001) were associated with pediatric sepsis. In subgroup analysis, MDW greater than 23 U remained significantly associated with sepsis for children 6–12 years old (OR, 6.76; 95% CI, 2.60–17.57; p = 0.0001) and 13–18 years (OR, 17.49; 95% CI, 7.69–39.76; p = 0.0001) with an area under the receiver operating curve of 0.8–0.9. CONCLUSIONS: MDW greater than 23 U at presentation is associated with the early diagnosis of sepsis in children greater than or equal to 6 years old. This parameter should be considered as a stratification variable in studies of pediatric sepsis.
Major Changes in Spatiotemporal Trends of US Rotavirus Laboratory Detections After Rotavirus Vaccine Introduction—2009–2021

For the 15 years before rotavirus vaccine introduction in 2006, annual rotavirus activity in the United States showed a distinct spatiotemporal pattern, peaking first in the Southwest and last in the Northeast. We modeled spatiotemporal trends in rotavirus laboratory detections from 2009 to 2021. Laboratories reporting to the National Respiratory and Enteric Virus Surveillance System were eligible for inclusion in a given surveillance year (July to June) if ≥1 polymerase chain reaction or enzyme immunoassay rotavirus test per week was reported during ≥26 weeks and totaling ≥100 annual tests. For each laboratory, the season peak was the week with the highest 7-week moving average of the number of rotavirus positive tests during the national season, defined as the period with a 3-week moving average of >10% rotavirus positivity lasting ≥2 consecutive weeks. We input peak week as a continuous variable and the geospatial coordinates of each laboratory into a spherical variogram model for Kriging spatial interpolation. We also created a state-level bivariate choropleth map using tertiles of the 2010–2019 average birth rates and rotavirus vaccine coverage. Following the established biennial trend, the 2010–2011, 2012–2013, 2014–2015, 2016–2017, and 2018–2019 surveillance years had >10% rotavirus positivity for ≥2 weeks and were included in the geospatial analysis. During all 5 seasons included in the geospatial analysis, the earliest peak week occurred in Oklahoma, Arkansas, and the western Gulf coast, a pattern markedly different from prevaccine seasons. These states also had the average lowest rotavirus vaccine coverage and highest birth rate, suggesting that more rapid accumulation of susceptible children drives annual rotavirus season activity. Increasing vaccine coverage remains a key tool in reducing rotavirus burden.
Violence against nurses by patients and visitors in the emergency department: A concept analysis

Abstract Aim This analysis investigates the concept of violence against nurses by patients and visitors in the emergency department. It aims to differentiate, clarify, and clearly identify this specific concept, which will facilitate more apt measurement and reporting, ultimately to contribute violence reduction measures. Background Due to contextual factors, occupational risk and patient characteristics, violence against nurses by patients and visitors in the emergency department varies from other types of violence against other health care staff. Methods This study employed Walker and Avant's concept analysis technique. Results The analysis found that violence against nurses by patients and visitors in the emergency department is primarily an occurrence of interpersonal violence based on the working relationship, whereby the patient and/or visitor becomes an assailant, and a nurse becomes a target in the absence of capable guardianship. There is also an intentional use of physical force or power, which results in or has a high chance of causing harm. Conclusion A clearer understanding of the antecedents, attributes, and consequences of violence against nurses by patients and visitors arising from this concept analysis provides a framework that will assist in the understanding, measurement, reporting, and prevention of violence and inform future research. Implications for Nursing Management Nursing managers are encouraged to adopt strategies that act on the factors related to attributes and antecedents that will serve to reduce the occurrence of intentional violent acts.
Dendritic Compartmentalization of Learning-Related Plasticity

Visual Abstract The dendrites of cortical pyramidal neurons receive synaptic inputs from different pathways that are organized according to their laminar target. This architectural scheme provides cortical neurons with a spatial mechanism to separate information, which may support neural flexibility required during learning. Here, we investigated layer-specific plasticity of sensory encoding following learning by recording from two different dendritic compartments, tuft and basal dendrites, of layer 2/3 (L2/3) pyramidal neurons in the auditory cortex of mice. Following auditory fear conditioning, auditory-evoked Ca2+ responses were enhanced in tuft, but not basal, dendrites leading to increased somatic action potential output. This is in direct contrast to the long held (and debated) hypothesis that, despite extensive dendritic arbors, neurons function as a simple one-compartment model. Two computational models of varying complexity based on the experimental data illustrated that this learning-related increase of auditory responses in tuft dendrites can account for the changes in somatic output. Taken together, we illustrate that neurons do not function as a single compartment, and dendritic compartmentalization of learning-related plasticity may act to increase the computational power of pyramidal neurons.
Champs aléatoires: autosimilarité, anisotropie et étude directionnelle

Nous etudions des champs aleatoires pouvant modeliser certains milieux poreux. Nous nous interessons a leurs statistiques au second ordre et en particulier a leur autosimilarite. Sous des hypotheses de stationnarite, une mesure spectrale caracterise le champ. L'homogeneite asymptotique directionnelle de la mesure determine l'autosimilarite asymptotique du champ; le plus petit coefficient d'homogeneite dans une echelle logarithmique en donne l'ordre. Pour determiner l'anisotropie on peut considerer une transformee de Radon du champ dont l'ordre d'autosimilarite depend de la direction. Ces resultats au second ordre sont adaptes a des modeles gaussiens, l'ordre d'autosimilarite s'estimant par les variations quadratiques. Nous considerons le probleme de l'injectivite des transformees de Radon. Enfin, nous etudions un modele poissonien obtenu par agregation de petites boules. Les proprietes d'autosimilarite sont analogues au second ordre mais atypiques pour la convergence en loi.
FOXM1‐mediated NUF2 expression confers temozolomide resistance to human glioma cells by regulating autophagy via the PI3K/AKT/mTOR signaling pathway

Glioma is the most common malignant tumor in the central nervous system and has a high mortality rate. Temozolomide (TMZ) is a widely used chemotherapeutic drug for glioma. NDC80 kinetochore complex (NUF2) is suggested to play a regulatory role in different cancers, but its specific function and mechanism in glioblastoma TMZ resistance remain unknown. NUF2, assessed by reverse transcription quantitative polymerase chain reaction (RT‐qPCR), was highly expressed in glioma cell lines. TMZ was used to treat cells to establish a TMZ‐resistant cell line. The potential functions of NUF2 in glioma were assessed using cell counting kit‐8 (CCK‐8) assays, colony formation assays, 5‐Ethynyl‐2'‐deoxyuridine (EdU) assays, flow cytometry, Western blotting, and a tumor xenograft model. The results showed that NUF2 knockdown attenuated malignant phenotypes of TMZ‐resistant cells and prevented tumor growth. Mechanistically, as luciferase reporter assays and chromatin immunoprecipitation (ChIP) as showed, Fox transcription factor M1 (FOXM1) had binding sites on the NUF2 promoter. Rescue assays demonstrated that FOXM1 upregulation counteracted the inhibitory effects of NUF2 depletion on the malignancies of TMZ‐resistant cells. This study demonstrates that FOXM1‐activated NUF2 promotes TMZ to human glioma cells by regulating proliferation, apoptosis, and autophagy.
Explorative Questionnaire Study About Education with Regard to the Health of Sexual Minorities at an Austrian Medical University

ABSTRACT Physicians can play a critical role in helping lesbian, gay, and bisexual-identified (LGB) individuals face minority stress. The current questionnaire study among 305 medical students (62.6% women/37.4% men; M age = 23.4, SD = 3.2) assessed whether medical students learn about LGB-specific concepts at an Austrian medical university. Students reported that their education contained little content about LGB-specific concepts. The majority of students did not hold negative attitudes toward homosexuality and they would like a larger range of courses concerning LGB-specific topics. The barrier most strongly associated with the intention to ask future patients about their sexual orientation was the belief that sexual orientation was irrelevant for clinical practice. Future education programs on LGB-specific topics may not need to focus on reducing negative attitudes toward sexual minorities, but should contain more facts on LGB individuals’ specific healthcare needs and explain to students why a patient’s sexual orientation is important to healthcare.
Improving colorectal cancer screening in rural primary care: Preliminary effectiveness and implementation of a collaborative mailed fecal immunochemical test pilot.

BACKGROUND Mailed fecal immunochemical test (FIT) outreach can improve colorectal cancer (CRC) screening rates. We piloted a collaborative mailed FIT program with health plans and rural clinics to evaluate preliminary effectiveness and refine implementation strategies. METHODS We conducted a single-arm study using a convergent, parallel mixed-methods design to evaluate the implementation of a collaborative mailed FIT program. Enrollees were identified using health plan claims and confirmed via clinic scrub. The intervention included a vendor-delivered automated phone call (auto-call) prompt, FIT mailing, and reminder auto-call; clinics were encouraged to make live reminder calls. Practice facilitation was the primary implementation strategy. At 12 months post mailing, we assessed the rates of: (1) mailed FIT return and (2) completion of any CRC screening. We took fieldnotes and conducted postintervention key informant interviews to assess implementation outcomes (eg, feasibility, acceptability, and adaptations). RESULTS One hundred and sixty-nine Medicaid or Medicare enrollees were mailed a FIT. Over the 12-month intervention, 62 participants (37%) completed screening of which 21% completed the mailed FIT (most were returned within 3 months), and 15% screened by other methods (FITs distributed in-clinic, colonoscopy). Enrollee demographics and the reminder call may encourage mailed FIT completion. Program feasibility and acceptability was high and supported by perceived positive benefit, alignment with existing workflows, adequate staffing, and practice facilitation. CONCLUSION Collaborative health plan-clinic mailed FIT programs are feasible and acceptable for implementation in rural clinics and support CRC screening completion. Studies that pragmatically test collaborative approaches to mailed FIT and patient navigation follow-up after abnormal FIT and support broad scale-up in rural settings are needed.