tbuckley/cabot-search huggingface dataset:
Multimodal Neuroimaging of Suicidal Thoughts and Behaviors in a U.S. Population-Based Sample of School-Age Children
Authors: Pablo Vidal-Ribas, Delfina Janiri, Gaelle E. Doucet, Narun Pornpattananangkul, Dylan M. Nielson, Sophia Frangou, Argyris Stringaris
Journal: American Journal of Psychiatry (2021)

Suicide deaths and suicidal thoughts and behaviors are considered a public health emergency, yet their underpinnings in the brain remain elusive. The authors examined the classification accuracy of individual, environmental, and clinical characteristics, as well as multimodal brain imaging correlates, of suicidal thoughts and behaviors in a U.S. population-based sample of school-age children.Children ages 9-10 years (N=7,994) from a population-based sample from the Adolescent Brain Cognitive Development study were assessed for lifetime suicidal thoughts and behaviors. After quality control procedures, structural MRI (N=6,238), resting-state functional MRI (N=4,134), and task-based functional MRI (range, N=4,075-4,608) were examined. Differences with Welch's t test and equivalence tests, with observed effect sizes (Cohen's d) and their 90% confidence intervals <|0.15|, were examined. Classification accuracy was examined with area under precision-recall curves (AUPRCs).Among the 7,994 unrelated children (females, N=3,757, 47.0%), those with lifetime suicidal thoughts and behaviors based on child (N=684, 8.6%), caregiver (N=654, 8.2%), and concordant (N=198, 2.5%) reports had higher levels of social adversity and psychopathology, among themselves and their caregivers, compared with never-suicidal children (N=6,854, 85.7%). Only one imaging test survived statistical correction: caregiver-reported suicidal thoughts and behaviors were associated with a thinner left bank of the superior temporal sulcus. On the basis of the prespecified bounds of |0.15|, approximately 48% of the group mean differences for child-reported suicidal thoughts and behaviors comparisons and approximately 22% for caregiver-reported suicidal thoughts and behaviors comparisons were considered equivalent. All observed effect sizes were relatively small (d≤|0.30|), and both non-imaging and imaging correlates had low classification accuracy (AUPRC ≤0.10).Commonly applied neuroimaging measures did not reveal a discrete brain signature related to suicidal thoughts and behaviors in youths. Improved approaches to the neurobiology of suicide are critically needed.
Functional Neuroimaging and the Law: Trends and Directions for Future Scholarship
Authors: Stacey A. Tovino
Journal: The American Journal of Bioethics (2007)

Under the umbrella of the burgeoning neurotransdisciplines, scholars are using the principles and research methodologies of their primary and secondary fields to examine developments in neuroimaging, neuromodulation and psychopharmacology. The path for advanced scholarship at the intersection of law and neuroscience may clear if work across the disciplines is collected and reviewed and outstanding and debated issues are identified and clarified. In this article, I organize, examine and refine a narrow class of the burgeoning neurotransdiscipline scholarship; that is, scholarship at the interface of law and functional magnetic resonance imaging (fMRI).
HP0021 Acupuncture in a rheumatology clinic
Authors: RE Alexander, AR White
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The first author was asked to set up an Acupuncture Clinic for a limited period, within a Rheumatology Department of Barnet and Chase Farm Hospital Trust. She had been practising acupuncture for fifteen years and had recently joined the department. An audit was taken as there are few published trials on Rheumatology Clinic patients.<sup>1</sup> <h3>Objectives</h3> To assess response of pain to acupuncture, alongside recording patients' analgesic intake. To assess whether the duration of pain or x-ray changes denoted a better result. <h3>Method</h3> A course of four to six sessions of traditional and myofascial acupuncture was offered, for a specified range of conditions, using electro-acupuncture after the first treatment. Average pain during the day and night was recorded weekly on a scale of 1 to 10, as well as the number and type of analgesics taken. An audit was analysed of the outcome for a series of 41 patients, who had a mean age of 57 years and pain for a mean duration of three years. <h3>Results</h3> The mean score for daytime pain fell from 6.8 (SD 1.2) to 4.9 (SD 2.5) points, which is highly significant (p &lt; 0.001). A total of 30 (73%) of the patients had a reduction in pain of at least 33% and 22 (54%) had a reduction in pain of at least 50%. Analgesic intake, (without distinguishing between different analgesic medication), was reduced from a mean of 17 (SD 15.3) tablets per week, to a mean of 6 (SD 7.9). Patients with normal x-rays had a much better response to acupuncture than those whose x-rays showed significant degenerative changes. <h3>Conclusions</h3> Over 65% of patients referred for acupuncture to a designated clinic showed a significant improvement after treatment and were able to reduce their intake of analgesic drugs. Patients with moderate or severe degenerative changes on x-ray did not respond as well as those with x-rays showing no abnormality. <h3>Reference</h3> Berman BM, Swyers JP, Ezzo J. The evidence for acupuncture as a treatment for rheumatologic conditions. Rheum Dis Clin North Am. 2000;26:103–15
METTL3 restrains papillary thyroid cancer progression via m6A/c-Rel/IL-8-mediated neutrophil infiltration
Authors: Jing He, Mingxia Zhou, Jie Yin, Junhu Wan, Jie Chu, Jinlin Jia, Jinxiu Sheng, Chang Wang, Huiqing Yin, Fucheng He
Journal: Molecular Therapy (2021)

Growing evidence indicates that N6-methyladenosine (m6A) is the most pervasive RNA modification in eukaryotic cells. However, the specific role of METTL3 in papillary thyroid carcinoma (PTC) initiation and development remains elusive. Here we found that downregulation of METTL3 was correlated with malignant progression and poor prognosis in PTC. A variety of gain- and loss-of-function studies clarified the effect of METTL3 on regulation of growth and metastasis of PTC cells in vitro and in vivo. By combining RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (meRIP-seq), our mechanistic studies pinpointed c-Rel and RelA as downstream m6A targets of METTL3. Disruption of METTL3 elicited secretion of interleukin-8 (IL-8), and elevated concentrations of IL-8 promoted recruitment of tumor-associated neutrophils (TANs) in chemotaxis assays and mouse models. Administration of the IL-8 antagonist SB225002 substantially retarded tumor growth and abolished TAN accumulation in immunodeficient mice. Our findings revealed that METTL3 played a pivotal tumor-suppressor role in PTC carcinogenesis through c-Rel and RelA inactivation of the nuclear factor κB (NF-κB) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth, which extends our understanding of the relationship between m6A modification and plasticity of the tumor microenvironment.
Ethical Allocation of Preexposure HIV Prophylaxis
Authors: Lawrence O. Gostin
Journal: JAMA (2011)

CIVIL SOCIETY–LED MOVEMENTS TRANSFORMED GLOBAL AIDS action from deep skepticism about extending antiretroviral (ARV) treatment in lowand middle-income countries to a historic scaling up of treatment toward universal access. During its first phase (2003-2008), the US President’s Emergency Plan for AIDS Relief (PEPFAR)—the largest national commitment to combat a single disease—supported treatment for more than 2 million people, care for more than 10 million people, and prevention of mother-to-child transmission in 16 million pregnancies. The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund), a unique international financing institution, has committed $19.3 billion in 144 countries to support large-scale prevention, treatment, and care, with most resources devoted to AIDS treatment. The AIDS movement, however, is at an inflection point due to the interplay of key health and economic determinants—the global financial downturn, tight foreign aid budgets, and intense resource competition. Even with historic global engagement, human immunodeficiency virus (HIV) treatment is insufficient in resource-poor settings. Although 5.2 million individuals currently receive treatment for HIV infection, 10 million more are in immediate need and 64% of those in need live in lowand middle-income countries. PEPFAR’s fiscal-year 2011 budget proposes only a 2% increase, which will result in future treatment enrollment freezes and a growing waiting list among 14 million treatment-eligible individuals. Similarly, Global Fund pledges reached only $11.7 billion for 2011-2013, failing to meet the fund’s lowest “austerity-level” target of $13 billion—the amount needed to sustain current treatment rates. A report by the Institute of Medicine concluded that because treatment can only reach a fraction of those in need, it is “not sustainable for the foreseeable future.” Policy makers will now have to consider implementing a new intervention, ie, preexposure prophylaxis (PrEP). Recent studies suggest that PrEP could mean a shift of ARVs from treatment to prevention. For instance, the iPrEx study found that men who have sex with men (MSM) taking tenofovir/emtricitabine were 44% less likely to become infected with HIV than those taking a placebo. The CAPRISA 004 trial (a proof-of-concept study) found that vaginal tenofovir disoproxil fumarate gel reduced the risk of contracting HIV by 39%, and the CDC 4323 study (an extended safety study) confirmed that oral tenofovir disoproxil fumarate was safe for use as PrEP in MSM. Although it will take several years to fully establish the clinical efficacy of PrEP in varying populations, these encouraging early results have accelerated global dialogue on its proof of deliverability.
Comparative Effectiveness and Safety of Sodium–Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults
Authors: Elisabetta Patorno, Ajinkya Pawar, Lily G. Bessette, Dae H. Kim, Chintan Dave, Robert J. Glynn, Medha N. Munshi, Sebastian Schneeweiss, Deborah J. Wexler, Seoyoung C. Kim
Journal: Diabetes Care (2021)

Both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in randomized controlled trials of patients with type 2 diabetes (T2D) generally <65 years old and mostly with cardiovascular disease. We aimed to evaluate the comparative effectiveness and safety of SGLT2i and GLP-1RA among real-world older adults.Using Medicare data (April 2013-December 2016), we identified 90,094 propensity score-matched (1:1) T2D patients ≥66 years old initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE) (i.e., myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections, fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections, and overall mortality. We estimated hazard ratios (HRs) and rate differences (RDs) per 1,000 person-years, controlling for 140 baseline covariates.Compared with GLP-1RA, SGLT2i initiators had similar MACE risk (HR 0.98 [95% CI 0.87, 1.10]; RD -0.38 [95% CI -2.48, 1.72]) and reduced HHF risk (HR 0.68 [95% CI 0.57, 0.80]; RD -3.23 [95% CI -4.68, -1.77]), over a median follow-up of ∼6 months. They also had 0.7 more DKA events (RD 0.72 [95% CI 0.02, 1.41]), 0.9 more LLA (RD 0.90 [95% CI 0.10, 1.70]), 57.1 more genital infections (RD 57.08 [95% CI 53.45, 60.70]), and 7.1 fewer AKI events (RD -7.05 [95% CI -10.27, -3.83]) per 1,000 person-years.Among older adults, those taking SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and genital infections versus those taking GLP-1RA.
Performance of a new integrated computer-assisted system (CADe/CADx) for detection and characterization of colorectal neoplasia
Authors: Jochen Weigt, Alessandro Repici, Giulio Antonelli, Ahmed Afifi, Leon Kliegis, Loredana Correale, Cesare Hassan, Helmut Neumann
Journal: Endoscopy (2021)

Abstract Background Use of artificial intelligence may increase detection of colorectal neoplasia at colonoscopy by improving lesion recognition (CADe) and reduce pathology costs by improving optical diagnosis (CADx). Methods A multicenter library of ≥ 200 000 images from 1572 polyps was used to train a combined CADe/CADx system. System testing was performed on two independent image sets (CADe: 446 with polyps, 234 without; CADx: 267) from 234 polyps, which were also evaluated by six endoscopists (three experts, three non-experts). Results CADe showed sensitivity, specificity, and accuracy of 92.9 %, 90.6 %, and 91.7 %, respectively. Experts showed significantly higher accuracy and specificity, and similar sensitivity, while non-experts + CADe showed comparable sensitivity but lower specificity and accuracy than CADe and experts. CADx showed sensitivity, specificity, and accuracy of 85.0 %, 79.4 %, and 83.6 %, respectively. Experts showed comparable performance, whereas non-experts + CADx showed comparable accuracy but lower specificity than CADx and experts. Conclusions The high accuracy shown by CADe and CADx was similar to that of experts, supporting further evaluation in a clinical setting. When using CAD, non-experts achieved a similar performance to experts, with suboptimal specificity.
AB0035 Platelet microparticles in patients with rheumatoid arthritis
Authors: EA Knijff-Dutmer, J Koerts, EM Kalsbeek-Batenburg, MA Van de Laar
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Platelet microparticles (PMP) contain pro-coagulant as well as pro-inflammatory substances like platelet activating factor (PAF) and P-selectin. Rheumatoid arthritis (RA) is associated with increased concentrations of both PAF and P-selectin, but the link with PMP has never been investigated. <h3>Objectives</h3> To test the hypothesis that patients with RA have elevated levels of PMPs and that these levels are associated with disease activity. <h3>Methods</h3> This was a descriptive study in patients with RA, using neither anticoagulants nor corticosteroids. The patients were divided in two groups, according to disease activity. Criteria for active RA were: ESR at least 28 mmh and/or CRP at least 28 mg/dl plus more than 8 painful and more than 5 swollen joints. Criteria for RA in remission were: ESR &lt;28 mmh and/or CRP &lt;28 mg/dl plus no painful and no swollen joints. PMPs were determined with flowcytometry (CD61/annexin-V). The values were compared with those from healthy volunteers, using nonparametric tests (Mann-Whitney). <h3>Results</h3> Ten patients with active RA and ten patients with RA in remission were included. There were 5 men and 15 women. The mean age was 61 years, the mean disease duration was 6 years and 75% was rheumatoid factor positive (comparable in both groups). The mean number of PMPs in RA patients was 3,173 × 106/L versus 451 × 106/L in healthy volunteers (p = 0.005). See Table 1 for further results: <h3>Conclusion</h3> This study confirms the hypothesis that patients with RA have higher numbers of PMPs; moreover, the presence of PMPs is associated with disease activity. This observation is most probably the missing link between the studies on the PMP content in general and the raised PAF- and P-selectin levels in sera from patients with RA. Moreover, one may speculate on the possible meaning of these elevated PMPs for the well-known high mortality due to cardiovascular disease in patients with RA. More research may clarify this.
Social care: Promise to propose reforms later this year is far from reassuring, says committee chair
Authors: Shaun Griffin
Journal: BMJ (2021)

The chair of an influential House of Lords committee has rebuked the government’s promise to bring forward proposals “later this year” about how to reform social care in England.

James Bethell, a health minister in England, was responding to a report from the Lords Economic Affairs Committee published in July 2019,1 which called for an extra £8bn (€9bn; $11bn) a year to tackle the “national scandal” of underfunding in the sector. The report said that 1.4 million people over 65 had unmet care needs in 2018, and it called for the government to fund free personal care for people with critical needs through general taxation.

Speaking on behalf of the government at a debate in the House of Lords on 28 January, Bethell said, “I acknowledge the frustration felt by many that there …
OP0065 Abnormalities in the pkc signalling system downstream to muscarinic receptors in an experimental model for sjÖgren’s syndrome (ss)
Authors: YT Konttinen, EK Tensing, M Hukkanen, HS Fox, J Ma, J Tornwall
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Postganglionic parasympathetic nerve fibers<sup>1</sup> release acetylcholine, which binds to acinar cell muscarinic receptors. Short-term stimulation leads to activation, but long-term stimulation leads to a negative feedback in form of proteolytic degradation. Salivary glands acinar cells in SS patients lack PKC beta II and are low in PKC alpha isoform<sup>2</sup> as if they had been consumed/proteolytically degraded. <h3>Objectives</h3> Our aim was to study, if also NOD mice have PKC involvement, which isoforms are involved and if this involvement is of the early activation type or like is seen as a result of a long-term, autoantibody-mediated stimulation in human disease. <h3>Methods</h3> Conventinal (alpha, beta, gamma), unusual (delta, epsilon, theta) and atypical (lambda, iota) PKC isoforms were studied using immunohistochemical staining and Western blotting. <h3>Results</h3> Control BALB/c mice had PKC alpha and beta like their human counterparts. They require calcium, DAG and phosphatidylserine for their activation. In contrast, NOD mice with sialadenitis had a strong expression of PKC alpha and beta. Transgenic NOD x IFN-gamma mice had an early involvement, but similar pattern to that of NOD mice. Acinar cells in NOD scid mice did not express any of the PKC isoforms studied. <h3>Conclusion</h3> Findings suggest that the calcium-dependent conventional PKC isoforms are involved also in NOD mice. In contrast to the human disease, mice with a short life span display upregulation and do not reach the stage with proteolytic degradation/loss of PKC. Interestingly, the altered PKC status modulates the susceptibility of cells to apoptosis. <h3>References</h3> Konttinen YT, Hukkanen M, Kemppinen P, <i>et al</i>. Arthritis Rheum. 1992;35:815–20 Törnwall J, Konttinen YT, Tuominen RK, Törnwall M. Lancet 1997;349:1814–15
Abstract 14869: Cardiac Magnetic Resonance Aids in Detection of Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Patients
Authors: Nazia Husain, Kae Watanabe, Haben Berhane, Arif Jivan, Daniel C Lee, Joshua D Robinson, Michael Markl, Cynthia K Rigsby
Journal: Circulation (2019)

Introduction: Coronary angiography (CA) is the gold standard for diagnosing cardiac allograft vasculopathy (CAV) for heart transplant surveillance. Cardiac magnetic resonance imaging (CMR) has emer...
Covid-19: India is at centre of global vaccine manufacturing, but opacity threatens public trust
Authors: Kamala Thiagarajan
Journal: BMJ (2021)

With the second largest population and one of the biggest pharmaceutical manufacturing capacities in the world, India has a central role in the covid-19 vaccination effort. But hurried approval of its own vaccine threatens to undermine domestic trust, writes <b>Kamala Thiagarajan</b>
Mental Health Act: doctors should not use video assessments to detain patients during pandemic, say judges
Authors: Clare Dyer
Journal: BMJ (2021)

Guidance from NHS England that doctors may lawfully use video assessments during the pandemic to decide whether patients should be detained in hospital under the Mental Health Act was wrong, two High Court judges have ruled.1

The act makes it a legal requirement that doctors must “personally examine” a patient before recommending detention. A code of practice requires “direct personal examination of the patient and their mental state.” But guidance from NHS England just after the start of the first lockdown last March said that “temporary departures from the code of practice may be justified in the interests of minimising risk to patients, staff, and the public.” Revised guidance in May 2020 included a section drafted jointly by …
SAT0098 Cox-2 specific inhibitors – is there any benefit of using these agents in patients on low dose aspirin (asa)?
Authors: G Singh, J Goldstein, N Agrawal, G Eisen, W Stenson, J Fort, A Bello, S Boots
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> COX-2 specific inhibitors have been shown to significantly reduce the risk of gastrointestinal complications compared to conventional NSAIDs, while providing equivalent efficacy. However, there is significant controversy regarding the UGI safety and tolerability benefits of COX-2 specific inhibitors, such as celecoxib, in patients on concomitant low-dose ASA ( &lt;325 mg/day) for cardiovascular protection. <h3>Objectives</h3> To evaluate the UGI tolerability and safety of celecoxib 200 or 400 mg per day and the commonly prescribed conventional NSAIDs (diclofenac or naproxen) in patients taking ASA in SUCCESS-1, a large multinational double-blind, randomised study. <h3>Methods</h3> SUCCESS-1 enrolled 13,274 patients from 1,142 centres in 39 countries in Europe and South Africa, Asia, Latin America, and the US and Canada. Patients were treated for 12 weeks using celecoxib (200 or 400 mg/d) and NSAIDs (naproxen 1000 mg/d in US and Canada and diclofenac 100 mg/d in all other countries). Adverse events were captured at week 6 and week 12 using standard adverse assessment ascertainment. In addition, all investigator-identified potentially clinically significant UGI events were referred to an independent Gastrointestinal Events Committee (GEC), which reviewed all data in a blinded fashion. Events were categorised as UGI ulcer complications (perforations, gastric outlet obstruction, bleeding), symptomatic UGI ulcerations or other GI events. <h3>Results</h3> Of the 13,194 patients randomised in the SUCCESS-1 trial, 4421 and 4429 patients received 200 or 400 mg per day of celecoxib respectively, 914 patients received 1000 mg per day of naproxen, and 3510 patients received 100 mg per day of diclofenac. Patients were mostly female (67%), and 42% were 65 years or older (mean age: 62 years). Patients in each group had comparable baseline aspirin use and past history of upper GI (UGI) bleeding. A total of 697 patients took celecoxib and ASA. In the NSAID arm, 348 patients took concomitant ASA. <h3>Conclusion</h3> Risk reduction with celecoxib and ASA is lower than risk reduction in patients not taking ASA. However, the magnitude of this risk reduction is clinically significant. Therefore, celecoxib continues to have a role in reducing risk of UGI complications even in patients on low dose ASA.