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Chronic pain commonly occurs in people living with HIV (PLWH). Many PLWH in the United States (U.S.) continue to obtain opioids for chronic pain management. In addition to the known risk of opioid misuse, evidence from non-HIV populations suggest that opioid use is associated with poor sleep and negative mood. Whether insomnia severity and depressive symptoms might be exacerbated by chronic pain and opioid use in PLWH remains to be determined. This study examined insomnia severity and depressive symptoms in 85 PLWH with chronic pain and 35 PLWH without chronic pain. Among PLWH with chronic pain, reported opioid use was examined in relation to severity of insomnia and depressive symptoms. PLWH with chronic pain reported significantly greater severity of insomnia symptoms (p = .033) and greater depressive symptoms (p = .025) than PLWH without chronic pain. Among PLWH with chronic pain who reported opioid use (n = 36), insomnia severity was greater compared to those who denied opioid use (n = 49), even after controlling for and pain severity and number of comorbidities (p = .026). Greater pain severity was significantly associated with greater insomnia severity (p < .001) and possibly greater depressive symptoms (p = .048) among PLWH with chronic pain who reported opioid use; however, these same associations were not significant among those PLWH with chronic pain who denied opioid use. Findings suggest that PLWH with chronic pain are likely to experience poor sleep (i.e., insomnia) and depressed mood. Furthermore, poor sleep was associated with opioid use among PLWH with chronic pain.

OBJECTIVE. Knee osteoarthritis (OA) is a leading source of pain and disability among older adults. Self-management (SM) strategies are recommended to manage OA symptoms. Sociodemographic and clinical characteristics, along with other factors, may influence SM utilization rate. This study sought to examine the prevalence and correlates of SM use for pain among non-Hispanic Black patients (NHB) and non-Hispanic White patients (NHW) older adults with or at risk for knee OA. METHODS. A secondary data analysis was conducted on the Understanding Pain and Limitations in Osteoarthritic Disease multisite observational study, which included NHB (n = 104) and NHW (n = 98) community-dwelling older adults with or at risk for knee OA. Participants completed measures of sociodemographics, pain SM use, coping, and clinical and experimental pain. RESULTS. Clinical and experimental pain were significantly greater among NHBs compared to NHWs. There were no significant differences in use of total SM by ethnicity/race. Interestingly, multiple linear regression revealed that clinical and experimental pain indices, as well as coping, number of pain sites, age, and sex were differentially associated with total SM use between NHBs and NHWs. There were significant ethnicity/race by type of pain management interaction effects for pain measures. CONCLUSION. SM is common among older adults with or at risk for knee OA pain, and the prevalence of SM does not differ by ethnicity/race, but many guideline-recommended interventions for OA are underutilized. Importantly, different factors were associated with the use of SM, highlighting distinct biopsychosocial mechanisms contributing to SM use in NHBs and NHWs.

Background and Purpose: How the Area Deprivation Index (ADI) performs compared to other measures of socioeconomic status (SES) is unknown. The study purpose is to compare the ADI and other measures of SES in their ability to predict pain severity/interference. Methods: Four measures of SES were compared—ADI, income, education, and subjective social status (SSS). Results: Pain severity/interference correlated positively with ADI (r = .396/r = .33), and negatively with income (r = –.507/r = –.428) and education (r = –.271/r = –.102). Criterion scores of the pain severity model suggest income performs best (AIC = 428.29/BIC = 436.22), followed by ADI (AIC = 437.24/BIC = 445.17), with education performing least well (AIC = 446.35/BIC = 454.29). Similar results were seen for the pain interference model. Conclusions: Neighborhood-level factors warrant consideration along with individual-level factors when attempting to understand the impact of SES on chronic low back pain.

Individuals with chronic low back pain (cLBP) frequently report sleep disturbances. Living in a neighborhood characterized by low-socioeconomic status (SES) is associated with a variety of negative health outcomes, including poor sleep. Whether low-neighborhood SES exacerbates sleep disturbances of people with cLBP, relative to pain-free individuals, has not previously been observed. This study compared associations between neighborhood-level SES, pain-status (cLBP vs. pain-free), and daily sleep metrics in 117 adults (cLBP = 82, pain-free = 35). Neighborhood-level SES was gathered from Neighborhood Atlas, which provides a composite measurement of overall neighborhood deprivation (e.g. area deprivation index). Individuals completed home sleep monitoring for 7-consecutive days/nights. Neighborhood SES and pain-status were tested as predictors of actigraphic sleep variables (e.g., sleep efficiency). Analyses revealed neighborhood-level SES and neighborhood-level SES*pain-status interaction significantly impacted objective sleep quality. These findings provide initial support for the negative impact of low neighborhood-level SES and chronic pain on sleep quality.

Background Biopsychosocial factors above and beyond pathoanatomical changes likely contribute to the severity of chronic low back pain. A pro-nociceptive endogenous pain modulatory balance (↓inhibition and ↑facilitation) may be an important contributor to chronic low back pain severity and physical function; however, additional research is needed to address this possibility. The objective of this study was to determine whether quantitative sensory tests of endogenous pain inhibition and facilitation prospectively predict movement-evoked pain and cLBP severity self-reported on a validated questionnaire. Methods One hundred thirty-four individuals with chronic low back pain were enrolled in this two-session study. During the first study session, temporal summation of mechanical pain and conditioned pain modulation were assessed at the lumbar spine to determine endogenous pain facilitation and inhibition, respectively. One week later, participants returned for a second study session whereby they reported their pain severity and pain interference using the Brief Pain Inventory-Short Form. Movement-evoked pain and physical function capacity were assessed upon completion of the balance, walking, and transition from sit to stand tests of the Short Physical Performance Battery. Results Temporal summation of mechanical pain, but not conditioned pain modulation, significantly and prospectively predicted greater movement-evoked pain and poorer physical function on the Short Physical Performance Battery. Neither temporal summation nor conditioned pain modulation were significantly related to self-reported pain severity or pain interference on the Brief Pain Inventory-Short Form. Conclusions Findings suggest that a pro-nociceptive pain modulatory balance characterized by enhanced pain facilitation may be an important driver of movement-evoked pain severity and poor physical function in individuals with chronic low back pain.

Background Pain is the hallmark symptom of knee osteoarthritis (OA), and varies widely across individuals. Previous research has demonstrated both fluctuating and stable pain trajectories in knee OA using various time periods. Changes in pain assessed quarterly (i.e. 3-month intervals) in knee OA are relatively unknown. The current study aimed to investigate temporal variations in pain over a one and a half year period (18 months) based on quarterly characteristic pain assessments, and to examine differences in pain patterns by sociodemographic and baseline pain characteristics. Methods The sample included a prospective cohort of 188 participants (mean age 58 years; 63% female; 52% non-Hispanic Black) with or at risk for knee OA from an ongoing multisite investigation of ethnic/race group differences. Knee pain intensity was self-reported at baseline and quarterly over an18-month period. Baseline pain assessment also included frequency, duration, and total number of pain sites. Group-based trajectory modeling was used to identify distinct pain trajectories. Multinomial logistic regression was used to examine associations between sociodemographic characteristics, risk factors, and pain trajectory groups. Results Pain trajectories were relatively stable among a sample of adults with knee pain. Four distinct pain trajectories emerged in the overall sample, with the largest proportion of participants (35.1%) classified in the moderate-high pain group. There were significant relationships between age, education, income, ethnicity/race and trajectory group; with younger, less educated, lower income, and non-Hispanic Black participants had a greater representation in the highest pain trajectory group. Conclusions Pain remained stable across a one and a half-year period in adults with or at risk for knee osteoarthritis, based on quarterly assessments. Certain sociodemographic variables (e.g. ethnicity/race, education, income, age) may contribute to an increased risk of experiencing greater pain.

Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. In a group of individuals with chronic MSK pain, we examined the relationships between a previously investigated resilience index, clinical pain and functioning measures, and pain-related brain structures, with consideration for sex and ethnicity/race. A cross-sectional analysis of 166 non-Hispanic Black and non-Hispanic White adults, 45–85 years of age with pain ≥ 1 body site (s) over the past 3 months was completed. Measures of clinical pain and functioning, biobehavioral and psychosocial resilience, and structural MRI were completed. Our findings indicate higher levels of resilience associate with lower levels of clinical pain and functional limitations. Significant associations between resilience, ethnicity/race, and/or sex, and pain-related brain gray matter structure were demonstrated in the right amygdaloid complex, bilateral thalamus, and postcentral gyrus. Our findings provide compelling evidence that in order to decipher the neurobiological code of chronic pain and related protective factors, it will be important to improve how chronic pain is phenotyped; to include an equal representation of females in studies including analyses stratifying by sex, and to consider other sociodemographic factors.

IgA vasculitis (IgAV) frequently occurs during or after a mucosal infection; it also rarely occurs in patients with cancer. We hypothesized that cancer could impact the baseline characteristics and/or outcome of vasculitis. We aimed to describe the presentation of IgAV in patients with cancer (IgAV ca+) compared to patients without cancer.We conducted a nationwide retrospective study of adult patients in France who presented with both IgAV and cancer. Baseline characteristics were described and compared with those of the 260 patients included in a nationwide French IgAV study.Thirty patients were included. The mean age was 69 ± 12 years; 80% were men. Compared to patients without underlying cancer, IgAV ca+ patients were older (69 ± 12 vs. 50 ± 18 years; p 0.0001) and they presented more frequently with necrotic purpura (53 vs. 26%; p 0.002) and intra-alveolar hemorrhage (10 vs. 0.5%; p 0.0001). IgAV ca+ patients frequently had elevated serum IgA levels (79 vs. 53%; p 0.034); most (n = 22, 73%) had adenocarcinoma or urothelial carcinoma involving the large intestines (n = 6), bladder (n = 5), and lung (n = 5). Most IgAV ca+ patients had progressive cancer (n = 21); a minority had metastatic disease (n = 2) at IgAV diagnosis. After a median follow-up of 3 months, 8 deaths were observed but none was related to IgAV.Compared to their noncancer counterpart, patients with IgAV related to cancer were older and more frequently presented with necrotizing purpura, intra-alveolar hemorrhage, and elevated serum IgA levels. Adult patients with IgAV and these latter characteristics should be carefully screened for cancer. Key Points • Clinical and biological characteristics of patients presenting with IgAV are distinct depending on the underlying cause of vasculitis related to cancer. • Patients with IgAV related to cancer are older, and compared to their counterparts without IgAV, they present more frequently with necrotic purpura, alveolar hemorrhage, and elevated serum IgA levels. • All adult patients with IgAV should be screened for cancer, and there should be a focus on elderly male patients presenting with necrotic purpura and/or alveolar hemorrhage.

Compelling evidence exists that non-Hispanic blacks (NHB) engage in pain catastrophizing (negatively evaluate one’s ability to cope with pain) more often than non-Hispanic whites (NHW). Functional neuroimaging studies revealed that individuals with high levels of trait pain catastrophizing show increased cerebral responses to pain in several pain-related brain regions (e.g., insula, primary somatosensory cortex [S1]), but associations between brain structure and catastrophizing remain largely unexplored. The current investigation was conducted at the University of Florida and the University of Alabama at Birmingham. Participants were 129 community-dwelling adults with or at risk of knee osteoarthritis (OA). Participants completed the pain catastrophizing subscale of the Coping Strategies Questionnaire-Revised and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain intensity subscale. Magnetic Resonance Imaging data were obtained. MANOVA and Chi-Square analyses assessed sociodemographic/clinical differences stratified by ethnicity/race. Multivariate regression analyses with insula and somatosensory cortical thickness entered as dependent variables with catastrophizing and the interaction between catastrophizing and ethnicity/race as the independent variables. Covariates include education, body mass index, study site, and WOMAC pain (ethnicity/race was an additional covariate in non-stratified analyses). There were significant interactions between ethnicity/race, pain catastrophizing, and brain structure. Higher pain catastrophizing was associated with thinner S1 bilaterally (ps < .05) in NHW, but not NHB participants with or at risk for knee OA. These results suggest that pain catastrophizing might have differing effects on pain-related central pathways and may contribute to ethnic/race group differences in individuals with or at risk for knee OA.

Pain intensity, pain interference, internalizing symptoms, and quality of life (HRQOL) were explored in three symptomatically similar gastrointestinal disorders: Recurrent Abdominal Pain, Eosinophi...

Aims Meningeal chondromas constitute a small fraction of central nervous system tumors, with only 61 cases reported in the literature. Somatic mutations of IDH1/2 genes have been described in enchondromas, and, in soft-tissue chondromas, rearrangements of the HMGA2 gene have been reported. The aim of our study was to perform molecular analyses of 3 additional cases and to do a complete review of the literature to better characterize this rare entity. Materials and methods Here, we report 3 cases of primitive meningeal chondromas in children and young adults. Immunohistochemical analyses for HMGA2 and IDH1R132H, molecular analyses of IDH1/2 mutations, and FISH analysis of the HMGA2 locus were performed. Results Immunohistochemical analyses of all cases were negative for IDH1R132H and HMGA2 proteins. Molecular analyses failed to reveal IDH1/2 mutations, and FISH analyses did not evidence any HMGA2 rearrangements. Similarly to what is reported in the literature, the 3 meningeal chondromas in this study were benign tumors with no recurrence after complete resection with a follow-up of 85, 46, and 89 months. Conclusion Meningeal chondroma is rare. It affects predominantly young adults and has a good outcome. No molecular alterations have currently been described in this entity.

Objective Chronological age is a risk factor in chronic pain; however, aging research supports the premise that physical and psychological health may better predict perceived age. Given the lack of evidence on perceived age in the context of chronic pain, the current study presents novel findings about the relationship between perceived age, chronic pain impact, and psychological function in adults with and without knee osteoarthritis. Methods This secondary analysis was part of an ongoing multisite observational cohort study to understand the progression of knee pain and disability. Community-dwelling adults (N=227) ages 45+ completed measures of trait resilience, trait positive and negative affect, pain catastrophizing, subjective perceptions of age, and the Graded Chronic Pain Scale. Results On average, participants reported feeling 10 years younger than their chronological age; however, this effect was attenuated in individuals reporting high-impact pain. Lower perceived age was associated with lower pain impact (low pain/low disability), while higher perceived age correlated with higher pain impact (high pain/high disability) and more adverse psychological effects. Using hierarchical linear regression, high-impact pain and positive affect emerged as statistically significant predictors of perceived age, whereas no differences were observed among trait resilience, negative affect, or pain catastrophizing. Discussion These findings highlight the importance of a biopsychosocial approach in understanding the intersection between psychological and physical factors associated with chronic pain. Addressing negative self-perceptions of aging, while simultaneously augmenting positive affect, through psychological therapies may mitigate pain and disability.

Purpose Research indicates pain-related disparities in the impact of knee osteoarthritis (OA) across both sex and ethnicity/race. While several factors likely contribute to these disparities, experiences of discrimination are associated with poor OA-related pain, disability, and functional performance. However, the mechanisms that mediate experiences of discrimination and OA-related outcomes are unclear. The current cross-sectional study examined the associations between everyday experiences of discrimination and clinical pain, disability and functional performance among non-Hispanic Black (NHB) and non-Hispanic White (NHW) persons with or at risk of knee OA and assessed the serial mediated model of perceived stress and pain catastrophizing on these relationships in women only. Patients and Methods Participants were 188 community-dwelling adults who presented with unilateral or bilateral knee pain and screened positive for clinical knee pain. Participants completed several measures including experiences of discrimination, Perceived Stress Scale, Coping Strategies Questionnaire-Revised (CSQ-R): Pain Catastrophizing subscale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Graded Chronic Pain Scale (GCPS), and Short Physical Performance Battery (SPPB). Results As compared to NHW participants, NHB individuals reported experiencing significantly higher levels of discrimination (F(1, 175)=26.660, p

ObjectiveFor most patients with chronic low back pain (cLBP), the cause is “nonspecific,” meaning there is no clear association between pain and identifiable pathology of the spine or associated tissues. Laypersons and providers alike are less inclined to help, feel less sympathy, dislike patients more, suspect deception, and attribute lower pain severity to patients whose pain does not have an objective basis in tissue pathology. Because of these stigmatizing responses from others, patients with cLBP may feel that their pain is particularly unjust and unfair. These pain-related injustice perceptions may subsequently contribute to greater cLBP severity. The purpose of this study was to examine whether perceived injustice helps explain the relationship between chronic pain stigma and movement-evoked pain severity among individuals with cLBP.MethodsParticipants included 105 patients with cLBP who completed questionnaires assessing chronic pain stigma and pain-related injustice perception, as well as a short physical performance battery for the assessment of movement-evoked pain and physical function.ResultsFindings revealed that perceived injustice significantly mediated the association between chronic pain stigma and cLBP severity (indirect effect = 6.64, 95% confidence interval [CI] = 2.041 to 14.913) and physical function (indirect effect = −0.401, 95% CI = −1.029 to −0.052). Greater chronic pain stigma was associated with greater perceived injustice (P = 0.001), which in turn was associated with greater movement-evoked pain severity (P = 0.003).ConclusionsThese results suggest that perceived injustice may be a means through which chronic pain stigma impacts nonspecific cLBP severity and physical function.

This article captures the webinar narrative on March 31, 2020 of four expert panelists addressing three questions on the current coronavirus disease 2019 (COVID-19) pandemic. Each panelist was selected for their unique personal expertise, ranging from front-line emergency physicians from multiple countries, an international media personality, former director of the US Strategic National Stockpile, and one of the foremost international experts in disaster medicine and public policy. The forum was moderated by one of the most widely recognized disaster medical experts in the world. The four panelists were asked three questions regarding the current pandemic as follows:1.What do you see as a particular issue of concern during the current pandemic?2.What do you see as a particular strength during the current pandemic?3.If you could change one thing about the way that the pandemic response is occurring, what would you change?

Inotersen, a 2'-O-methoxyethyl (2'-MOE) phosphorothioate antisense oligonucleotide, reduced disease progression and improved quality of life in patients with hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) in the NEURO-TTR and NEURO-TTR open-label extension (OLE) trials. However, 300 mg/week inotersen treatment was associated with platelet count reductions in several patients. Mean platelet counts in patients in the NEURO-TTR-inotersen group remained ≥140 × 10

Background Sex differences in pain sensitivity have been well documented, such that women often report greater sensitivity than men. However, clinical reports highlighting sex differences often equate gender and sex. This is a particularly critical oversight for those whose gender identity is different than their genetic sex. Methods This preliminary study sets to analyze differences in pain responses between cisgender and transgender individuals living with HIV and chronic pain. A total of 51 African-American participants (24 cisgender men, 20 cisgender women, 7 transgender women) with similar socioeconomic status were recruited. Genetic sex, gender identity, depression and anxiety, pain severity, pain interference and pain-related stigma were recorded. Participants also completed a quantitative sensory testing battery to assess pain in response to noxious heat and mechanical stimuli. Results Transgender women and cisgender women demonstrated a greater magnitude of temporal summation for heat pain stimuli or mechanical stimuli compared to cisgender men. Specifically, transgender women reported greater mechanical summation than either cisgender women or cisgender men. Transgender women and cisgender women similarly reported greater chronic pain severity compared to cisgender men. Conclusion These data support the notion that gender identity may play a more significant role in pain sensation than genetic sex. These results further maintain that not only gender identity and genetic sex are distinct variables but that treatment should be based on identity as opposed to genetic sex.

The relevance of circulating tumor DNA (ctDNA) analysis as a liquid biopsy and minimal residual disease tool in the management of classical Hodgkin lymphoma (cHL) patients was demonstrated in retrospective settings and remains to be confirmed in a prospective setting. We developed a targeted Next-Generation sequencing (NGS) panel for fast analysis (AmpliSeq® technology) of nine commonly mutated genes in biopies and ctDNA of cHL patients. We then conducted a prospective trial to assess ctDNA follow-up at diagnosis and after two cycles (C2) of chemotherapy. Sixty cHL patients treated by first line conventional chemotherapy (BEACOPPescalated [21.3%], ABVD/ABVD-like [73.5%] and other regimens [5.2%, for elderly patients]) were assessed in this noninterventional study. The median age of the patients was 33.5 years (range: 20-86). Variants were identified in 42 (70%) patients. Mutations of NFKBIE, TNFAIP3, STAT6, PTPN1, B2M, XPO1, ITPKB, GNA13 and SOCS1 were found in 13.3%, 31.7%, 23.3%, 5%, 33.3%, 10%, 23.3%, 13.3% and 50% of patients, respectively. ctDNA concentration and genotype were correlated with clinical characteristics and presentation. Regarding early therapeutic response, 45 patients (83%, not available [NA] =6) had a negative positron emission tomography (PET) after C2 (Deauville Score 1-3). The mean of DeltaSUVmax after C2 was -78.8%. ctDNA after C2 was analysed in 54 patients (90%). ctDNA became rapidly undetectable in all cases after C2. Variant detection in ctDNA is suitable to depict the genetic features of cHL at diagnosis and may help to assess early treatment response, in association with PET. Clinical Trial reference: NCT02815137.

Dispositional traits can be protective or contribute to increased vulnerability in individuals with chronic pain. This study aims to evaluate the association between two dispositional trait measures, affect balance style and multi-domain trait groups, with psychosocial measures, clinical pain, functional pain, and experimental pain at two years in individuals with chronic knee pain. The study is a prospective analysis of 168 community dwelling individuals aged 45-85 years old with knee pain with or at risk for knee osteoarthritis. At baseline, affect balance style and multi-domain trait groups were associated with psychosocial measures, clinical pain, and functional status. At the two-year time point, the multi-domain trait groups were associated with the clinical pain measures. Interestingly, individuals with previously demonstrated vulnerable traits showed more variability in dispositional trait status at the two-year time point compared to those with dispositional traits previously demonstrated as more protective. Findings reiterate that dispositional traits are predisposing but are not predetermining regarding pain-related experiences. Perspective Vulnerable and protective dispositional traits are positively and negatively associated with clinical pain and functional limitations respectively. Although considered relatively stable, a 30-50% shift in dispositional traits was indicated over a two-year period. Findings highlight that dispositional traits are modifiable and thus, predisposing but not predetermining for persisting chronic pain.

International audience; In the current context of global urbanization, interdisciplinary research is needed to identify planning and management practices in urban green spaces (UGS) that would enhance both biodiversity and visitors' well-being. The perception of landscape heterogeneity, a core ecological concept, has been demonstrated to have a positive impact on visitors' psychological restoration. In order to apply these findings within UGS to planning and management practices, we need to characterize visitors' perception of landscape heterogeneity. We gathered data on 390 visitors' perception of landscape heterogeneity. Our results highlighted that visitors perceive landscape heterogeneity through the mixing of different heights of three vegetation strata and flower areas. Planning and management practices should enhance this landscape aspect within UGS to simultaneously promote biodiversity and visitors' psychological well-being.

A human peripheral blood mononuclear cell (PBMC)-based assay was developed to identify antisense oligonucleotide (ASO) with the potential to activate a cellular innate immune response outside of an acceptable level. The development of this assay was initiated when ISIS 353512 targeting the mRNA for human C-reactive protein was tested in a phase I clinical trial in which healthy human volunteers unexpectedly experienced increases in interleukin-6 (IL-6) and C-reactive protein. This level of immune stimulation was not anticipated following rodent and non-human primate safety studies in which no evidence of exaggerated proinflammatory effects were observed. The IL-6 increase induced by ISIS 353512 was caused by activation of B-cells. The IL-6 induction was inhibited by chloroquine pretreatment of the PBMC and the nature of the ASOs suggested that the response is mediated by a toll like receptor, in all likelihood TLR9. While assessing the inter PBMC donor variability, two class of responders to ISIS 353512 were identified (discriminator and non-discriminators). The discriminator source of PBMC was shown to produce low level of IL-6 after 24 hours in culture in absence of ASO treatment. The PBMC assay using discriminator donors was shown to be reproducible allowing to assess reliably the immune potential of ASOs via comparison to known benchmark ASO controls that were previously shown to be either safe or inflammatory in clinical trials.

Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large.

International audience; No abstract available

Chronic pain is variably associated with brain structure. Phenotyping based on pain severity may address inconsistencies. Sociodemographic groups also differ in the experience of chronic pain severity. Whether differences by chronic pain severity and/or sociodemographic groups are indicated in pain-related areas of the brain is unknown. Relations between two measures of chronic pain severity and brain structure via T1-weighted MRI were investigated and sociodemographic group differences explored. The observational study included 142 community-dwelling (68 non-Hispanic Black [NHB] and 74 non-Hispanic White [NHW]) adults with/at risk for knee osteoarthritis. Relationships between chronic pain severity, sociodemographic groups, and a priori selected brain structures (postcentral gyrus, insula, medial orbitofrontal, anterior cingulate, rostral middle frontal gyrus, hippocampus, amygdala, thalamus) were explored. Chronic pain severity associated with cortical thickness. NHB participants reported lower sociodemographic protective factors and greater clinical pain compared to NHWs who reported higher sociodemographic protective factors and lower clinical pain.. Greater chronic pain severity was associated with smaller amygdala volumes in the NHB group and larger amygdala volumes in the NHW group. Brain structure by chronic pain stage differed between and within sociodemographic groups. Overall, chronic pain severity and sociodemographic factors are associated with pain-related brain structures. Our findings highlight the importance of further investigating social and environmental contributions in the experience of chronic pain to unravel the complex array of factors contributing to disparities. Perspective The study presents data demonstrating structural brain relationships with clinical pain severity, characteristic pain intensity and chronic pain stage, differ by sociodemographic groups. Findings yield insights into potential sources of previous inconsistent pain-brain relationships and highlights the need for future investigations to address social and environmental factors in chronic pain disparities research.

Imaging findings after thoracic surgery can be misleading. Knowledge of the normal post-operative anatomy helps the radiologist to recognise life-threatening complications and conversely not to wrongly evoke a complication in cases of trivial post-operative abnormalities. In this educational article, we reviewed the expected patterns after thoracic surgery including sublobar resection, lobectomy, pneumonectomy and related techniques. Imaging aspects of frequent and less common complications and their typical imaging features are then presented.

Within the context of a growing aquaculture production coupled with a plateau of the production in the main components of aquafeeds (fish oil and fishmeal), recent studies have typically focused on replacing these feedstuffs with terrestrial plant ingredients for cultured carnivorous aquatic species, such as rainbow trout (Oncorhynchus mykiss). Substitution rates without adverse effects have, however, reached their limit. One potential way forward would be to take advantage of the genetic variability that exists in the salmonid population. However, to date, little is known about the underlying molecular mechanisms responsible for this genetic variability. The aim of the present research was to understand why some genotypes are better able to utilize plant-based diets devoid of marine resources. In this regard, three isogenic lines of rainbow trout (R23h, AB1h, and A22h), with similar growth when fed marine resources-based diets and which differ greatly in their responses to a plant-based diet, were fed with either a complete plant-based diet (V diet) or a marine resources-based diet (M diet) since first-feeding. Fish traits and the hepatic transcriptome of these three genotypes were compared after 5 months of feeding. First, differences in the ability to grow with the V diet observed amongst genotypes was not due to higher feed intake, but instead due to differences in feed efficiency. The comparison of transcriptome profiles revealed 575 (R23h vs. AB1h), 1,770 (R23h vs. A22h), and 2,973 (AB1h vs. A22h) probes differentially expressed amongst the three genotypes when fed the V diet. Interestingly, R23h and AB1h fish, which were the least affected by the V diet, exhibited the highest growth. These results demonstrate that these fish were able to maintain a high level of energy production and protein synthesis. Moreover, these genotypes were also able to activate pathways linked to lipid and cholesterol metabolisms, such as the biosynthesis of long-chain polyunsaturated fatty acids. Finally, as previously, immunity seems to also play an important role in the ability of fish to use the V diet, and further studies are needed to understand the mechanisms by which immunity interacts with growth.

This was a monocentric prospective study testing the efficacy and safety of a first injection of BNT162b2 (Pfizer‐BioNTech) in 112 Allo‐HSCT patients. Antibody response to SARS‐CoV‐2 spike protein receptor‐binding domain was tested at the time of the second injection (Roche Elecsys). The study also included a non‐randomized control arm of 26 healthy controls. This study shows that a first dose of SARS‐CoV‐2 messenger RNA vaccine is safe and provides a 55% rate of seroconversion in allotransplanted patients compared to 100% for the controls (p

e21592 Background: While 10% of melanomas occur in a context suggesting hereditary predisposition, a clear molecular explanation has only been established for approximately 20% of families. In the course of clinical care, we identified a new CTNNA1 truncating germline mutation in a family affected by multiple early-onset melanomas. Methods: NGS and CGH-array were performed on the index case’s melanoma, followed by Sanger sequencing of the germline DNA of relatives. Immunochemistry (IHC) was employed to evaluate the level of αE-catenin (encoded by CTNNA1) in the family's samples. Stable CTNNA1 knockout human melanoma cell lines were generated to investigate the functional effects of CTNNA1 loss. Functional assays, including colony formation, 3-D tumor spheroid formation, wound healing, and transwell invasion were performed, as well as electron microscopy and RNAsequencing (RNAseq). CTNNA1 mutational status was determined in several databases and further sequencing of CTNNA1 in a DNA bank of families with multiple melanomas was done. Results: While the allele frequency in the index patient’s tumoral DNA was compatible with a germline mutation, the CTNNA1 F611fs*10 mutation was subsequently found cosegregating with individuals affected by melanoma in the family. CGH array on tumor DNA identified a segmental loss on chromosome 5, leading to a loss of heterozygosity of CTNNA1, resulting in a loss of αE-catenin observed by IHC. Clinically, the mean age of first melanoma diagnosis was 29,7 years (range: 18-56), 2 were metastatic, and the others were SSM (superficial spreading melanoma) in situ (n = 3) or Breslow index 0,56 mm (n = 1). Functional assays performed on CTNNA1 KO melanoma cell lines showed a loss of cell-to-cell adhesion phenotype, in accordance with the altered adherens junctions observed by electron microscopy, and the specific pathway enrichments observed by RNAseq. This specific phenotype could be rescued by transfection with a plasmid containing wild-type CTNNA1, as opposed to the CTNNA1 F611fs* plasmid. Germline CTNNA1 mutations are rare as none could be further identified in a DNA bank of 27 multiple melanoma families. In a database of 4743 melanomas somatically sequenced for CTNNA1, 131 of them had a CTNNA1 alteration (2,76%), with a median tumor mutational burden of 44 mut/MB of DNA (range from 0 to 451). Among them, 15 alterations were predicted to be inactivating, including 7 associated with a BRAF or NRAS activating mutation. Conclusions: Altogether, our results strongly support that CTNNA1 loss of function predisposes to melanoma formation characterized by a decreased cell adhesion. Since germline CTNNA1 alterations have already been implicated in lobular breast cancers and hereditary diffuse gastric cancers, CTNNA1 likely constitutes a tumor suppressor gene involved in familial melanoma, thus broadening the spectrum of syndromes associated with this gene.

ObjectiveTo characterize neuropathic-like pain among individuals with or at risk for knee osteoarthritis.SubjectsOne hundred eighty-four individuals who self-identified as non-Hispanic black or non-Hispanic white and presented with unilateral or bilateral knee pain.DesignNeuropathic-like pain was assessed using the painDETECT, and those with high vs low neuropathic-like pain were compared on clinical pain, psychological symptoms, physical function, and quantitative sensory testing. Analyses were unadjusted, partially and fully adjusted for relevant covariates.ResultsThirty-two (17.4%) participants reported experiencing neuropathic-like pain features above the painDETECT clinical cut-score. The neuropathic-like pain group reported significantly greater pain severity on all measures of clinical pain and higher levels of psychological symptoms when fully adjusted for covariates, but no differences emerged for disability and lower extremity function. The neuropathic-like pain group also reported greater overall heat pain ratings during the heat pain threshold and increased temporal summation of heat pain in the fully adjusted model. Additionally, those with neuropathic-like pain symptoms reported greater painful after-sensations following heat pain temporal summation in all analyses. No significant group differences in pressure pain threshold emerged at any of the testing sites. In contrast, temporal summation of mechanical pain was significantly greater at both the index knee and the ipsilateral hand for the neuropathic-like pain group in all analyses.ConclusionsParticipants with or at risk for knee osteoarthritis who reported high neuropathic-like pain experienced significantly greater clinical pain and increased heat and mechanical temporal summation at the index knee and other body sites tested, suggesting central sensitization.

Background Human immunology studies often rely on the isolation and quantification of cell populations from an input sample based on flow cytometry and related techniques. Such techniques classify cells into populations based on the detection of a pattern of markers. The description of the cell populations targeted in such experiments typically have two complementary components: the description of the cell type targeted (e.g. ‘T cells’), and the description of the marker pattern utilized (e.g. CD14−, CD3+). Results We here describe our attempts to use ontologies to cross-compare cell types and marker patterns (also referred to as gating definitions). We used a large set of such gating definitions and corresponding cell types submitted by different investigators into ImmPort, a central database for immunology studies, to examine the ability to parse gating definitions using terms from the Protein Ontology (PRO) and cell type descriptions, using the Cell Ontology (CL). We then used logical axioms from CL to detect discrepancies between the two. Conclusions We suggest adoption of our proposed format for describing gating and cell type definitions to make comparisons easier. We also suggest a number of new terms to describe gating definitions in flow cytometry that are not based on molecular markers captured in PRO, but on forward- and side-scatter of light during data acquisition, which is more appropriate to capture in the Ontology for Biomedical Investigations (OBI). Finally, our approach results in suggestions on what logical axioms and new cell types could be considered for addition to the Cell Ontology.

Objective Racial/ethnic disparities in pain are well-recognized, with non-Hispanic blacks (NHBs) experiencing greater pain severity and pain-related disability than non-Hispanic whites (NHWs). Although numerous risk factors are posited as contributors to these disparities, there is limited research addressing how resilience differentially influences pain and functioning across race/ethnicity. Therefore, this study examined associations between measures of psychosocial resilience, clinical pain, and functional performance among adults with knee osteoarthritis (OA), and assessed the moderating role of race/ethnicity on these relationships. Methods In a secondary analysis of the Understanding Pain and Limitations in Osteoarthritic Disease (UPLOAD-2) study, 201 individuals with knee OA (NHB = 105, NHW = 96) completed measures of resilience (ie, trait resilience, optimism, positive well-being, social support, positive affect) and clinical pain, as well as a performance-based measure assessing lower-extremity function and movement-evoked pain. Results Bivariate analyses showed that higher levels of psychosocial resilience were associated with lower clinical pain and disability and more optimal physical functioning. NHBs reported greater pain and disability, poorer lower-extremity function, and higher movement-evoked pain compared with NHWs; however, measures of psychosocial resilience were similar across race/ethnicity. In moderation analyses, higher optimism and positive well-being were protective against movement-evoked pain in NHBs, whereas higher levels of positive affect were associated with greater movement-evoked pain in NHWs. Conclusion Our findings underscore the importance of psychosocial resilience on OA-related pain and function and highlight the influence of race/ethnicity on the resilience-pain relationship. Treatments aimed at targeting resilience may help mitigate racial/ethnic disparities in pain.

African Americans disproportionately suffer more severe and debilitating morbidity from chronic pain than do non-Hispanic Whites. These differences may arise from differential exposure to psychosocial and environmental factors such as adverse childhood experiences, racial discrimination, low socioeconomic status, and depression, all of which have been associated with chronic stress and chronic pain. Race, as a social construct, makes it such that African Americans are more likely to experience different early life conditions, which may induce epigenetic changes that sustain racial differences in chronic pain. Epigenetics is one mechanism by which environmental factors such as childhood stress, racial discrimination, economic hardship, and depression can affect gene expression without altering the underlying genetic sequence. This article provides a narrative review of the literature on epigenetics as a mechanism by which differential environmental exposure could explain racial differences in chronic pain. Most studies of epigenetic changes in chronic pain examine DNA methylation. DNA methylation is altered in the glucocorticoid (stress response) receptor gene, NR3C1, which has been associated with depression, childhood stress, low socioeconomic status, and chronic pain. Similarly, DNA methylation patterns of immune cytokine genes have been associated with chronic stress states. Thus, DNA methylation changes may play an essential role in the epigenetic modulation of chronic pain in different races with a higher incidence of epigenetic alterations contributing to more severe and disabling chronic pain in African Americans.

Summary Introduction Based on the radiological responses obtained with a schedule of ten mg/kg every two weeks bevacizumab was approved by the FDA for recurrent glioblastomas. Due to the negative results concerning overall survival of patients receiving bevacizumab, the European application was rejected. Despite this, many centers apply an off-label prescription. Our aim was to evaluate the safety and efficacy of schedules of low doses of bevacizumab. Methods From September 2013 to August 2016, we recruited patients with progressive glioblastoma, whatever the previous treatments. We compared a routine control group (CG) of ten mg/kg, to a low dose group (LDG) composed of 5 subgroups: G5: five mg/kg, G4: four mg/kg, G3: three mg/kg, G2: two mg/kg, G1: one mg/kg; each patient was treated with the same dose every two weeks. Results Fifty-three patients were treated: 20 women and 33 men, 24 in the CG and 29 in the LDG. The median age at diagnosis was 62 years [35.0–77.0]. No statistical difference was found in overall survival either for the CG or the LDG (P = 0.086) or among groups (P = 0.251), with even a trend toward improvement for LDG: 62 weeks [20–145] versus 73 weeks [18–178]. The median progression free survival was comparable: 19.5 weeks [6.0–54.0] for the CG and 15.0 weeks [0.0–134.0] for the LDG (P = 0.221). Bevacizumab was stopped either due to progression (45.1%) or toxicity (52.9%), without significant differences between doses but maybe less toxicities in the LDG (16.7% for toxicity in G1). Discussion Use of bevacizumab at progression at lower than usual doses seems to give the same results as the standard dose without giving additional toxicity.

Chronic pain is a common comorbidity in people with HIV (PWH), with prevalence estimates of 25-85%. Research in this area is growing, but significant gaps remain. A Global Task Force of HIV experts was organized to brainstorm a scientific agenda and identify measurement domains critical to advancing research in this field. Experts were identified through literature searches and snowball sampling. Two online questionnaires were developed by Task Force members. Questionnaire 1 asked participants to identify knowledge gaps in the field of HIV and chronic pain and identify measurement domains in studies of chronic pain in PWH. Responses were ranked in order of importance in Questionnaire 2, which was followed by a group discussion. 29 experts completed Questionnaire 1, 25 completed Questionnaire 2, and 21 participated in the group. Many important clinical and research priorities emerged, including the need to examine etiologies of chronic pain in PWH. Pain-related measurement domains were discussed, with a primary focus on domains that could be assessed in a standardized manner across various cohorts that include PWH in different countries. We collaboratively identified clinical and research priorities, as well as gaps in standardization of measurement domains, that can be used to move the field forward.

Millions of patients with cancer pain are treated with prescription opioids each year. However, efforts to mitigate the ongoing opioid crisis result in unintended consequences with opioid pain management, including opioid stigma. Emerging research indicates that opioid stigma is problematic in patients with cancer, but few studies have examined contributors to and impacts of opioid stigma in this population. To guide future research in this area, we propose a conceptual framework-the opioid stigma framework (OSF)-with which to understand and improve opioid stigma in patients with cancer pain. Development of the OSF was guided by a literature review of stigma in health-related conditions, adaptation of the existing Health Stigma and Discrimination Framework, a topical review of challenges related to opioid cancer pain management, and author expertise in cancer, pain, and opioid prescribing. The proposed OSF highlights 5 domains: (1) contributors to opioid stigma, or factors that increase the likelihood that a patient will experience opioid stigma; (2) intersecting stigmas, or the convergence of multiple stigmatized identities within a patient; (3) stigma manifestations, or the ways opioid stigma is manifested in patients, clinicians, and the community; (4) proximal outcomes, or the immediate consequences of opioid stigma in patients; and (5) long-term impacts in patients. The OSF provides 2 main avenues to facilitate future research: (1) providing a framework to explore the mechanisms that underlie opioid stigma and its impact on cancer pain management and (2) supporting the development of targeted, tailored interventions to eliminate opioid stigma.

In the context of the Covid-19 pandemic, the consequences of misinformation are a matter of life and death. Correcting misconceptions and false beliefs are important for injecting reliable information about the outbreak. Fact-checking organisations produce content with the aim of reducing misinformation spread, but our knowledge of its impact on misinformation is limited. In this paper, we explore the relation between misinformation and fact-checking spread during the Covid-19 pandemic. We specifically follow misinformation and fact-checks emerging from December 2019 to early May 2020. Through a combination of spread variance analysis, impulse response modelling and causal analysis, we show similarities in how misinformation and fact-checking information spread and that fact-checking information has a positive impact in reducing misinformation. However, we observe that its efficacy can be reduced, due to the general amount of online misinformation and the short-term spread of fact-checking information compared to misinformation.

International audience; OBJECTIVES: To determine the frequency and prognosis of invasive pulmonary aspergillosis in critically ill patients with severe influenza pneumonia. DESIGN: Retrospective multicenter cohort study. SETTING: Five French ICUs. PATIENTS: Patients with influenza admitted to ICU between 2009 and 2018. MEASUREMENTS AND MAIN RESULTS: Of the 524 patients admitted for severe influenza diagnosed with a positive airway reverse-transcriptase polymerase chain reaction test, 450 (86%) required mechanical ventilation. A lower respiratory tract sample yielded with Aspergillus (Asp+) in 28 patients (5.3%). Ten patients (1.9%) were diagnosed with putative or proven invasive pulmonary aspergillosis, based on the validated AspICU algorithm. A multivariate model was built to identify independent risk factors for Aspergillus-positive pulmonary culture. Factors independently associated with Aspergillus-positive culture were liver cirrhosis (odds ratio = 6.7 [2.1-19.4]; p < 0.01), hematologic malignancy (odds ratio = 3.3 [1.2-8.5]; p = 0.02), Influenza A(H1N1)pdm09 subtype (odds ratio = 3.9 [1.6-9.1]; p < 0.01), and vasopressor requirement (odds ratio = 4.1 [1.6-12.7]; p < 0.01). In-hospital mortality of Asp+ patients was 36% versus 21% in patients without Aspergillus-positive pulmonary culture (p = 0.09). CONCLUSIONS: In this large retrospective multicenter cohort of critically ill patients, putative invasive pulmonary aspergillosis according to AspICU algorithm was a relatively rare complication of influenza. Patients at higher risk of Aspergillus pulmonary colonization included those with liver cirrhosis, hematologic malignancy, H1N1pdm09 influenza A virus, and requiring vasopressors. Our results provide additional data on the controversial association between severe influenza and invasive pulmonary aspergillosis. Reaching a consensual definition of invasive pulmonary aspergillosis becomes mandatory and confers further prospective research.

Importance Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown. Objective To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic. Design, setting, and participants In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included. Main outcomes and measures Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis. Results Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19. Conclusions and relevance Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy. Trial registration ClinicalTrials.gov Identifier: NCT04344119.

AimsAmyloidogenic transthyretin (ATTR) amyloidosis is a fatal disease characterized by progressive cardiomyopathy and/or polyneuropathy. AKCEA-TTR-LRx (ION-682884) is a ligand-conjugated antisense drug designed for receptor-mediated uptake by hepatocytes, the primary source of circulating transthyretin (TTR). Enhanced delivery of the antisense pharmacophore is expected to increase drug potency and support lower, less frequent dosing in treatment.Methods and resultsAKCEA-TTR-LRx demonstrated an approximate 50-fold and 30-fold increase in potency compared with the unconjugated antisense drug, inotersen, in human hepatocyte cell culture and mice expressing a mutated human genomic TTR sequence, respectively. This increase in potency was supported by a preferential distribution of AKCEA-TTR-LRx to liver hepatocytes in the transgenic hTTR mouse model. A randomized, placebo-controlled, phase 1 study was conducted to evaluate AKCEA-TTR-LRx in healthy volunteers (ClinicalTrials.gov: NCT03728634). Eligible participants were assigned to one of three multiple-dose cohorts (45, 60, and 90mg) or a single-dose cohort (120mg), and then randomized 10:2 (active:placebo) to receive a total of 4 SC doses (Day 1, 29, 57, and 85) in the multiple-dose cohorts or 1 SC dose in the single-dose cohort. The primary endpoint was safety and tolerability; pharmacokinetics and pharmacodynamics were secondary endpoints. All randomized participants completed treatment. No serious adverse events were reported. In the multiple-dose cohorts, AKCEA-TTR-LRx reduced TTR levels from baseline to 2weeks after the last dose of 45, 60, or 90mg by a mean (SD) of -85.7% (8.0), -90.5% (7.4), and -93.8% (3.4), compared with -5.9% (14.0) for pooled placebo (P&nbsp

Background: Non-Hispanic black (NHB) individuals have increased risk of Alzheimer’s disease (AD) relative to non-Hispanic whites (NHW). Ethnicity/race can serve as a proxy sociodemographic variable for a complex representation of sociocultural and environmental factors. Chronic pain is a form of stress with high prevalence and sociodemographic disparities. Chronic pain is linked to lower cognition and accelerated biological aging. Objective: The purpose of this study is to seek understanding of potential cognitive and temporal lobe structural brain AD vulnerabilities based on chronic pain stage and ethnicity/race. Methods: Participants included 147 community dwelling NHB and NHW adults without dementia between 45–85 years old who had or were at risk of knee osteoarthritis. All participants received an MRI (3T Philips), the Montreal Cognitive Assessment (MoCA), and assessment of clinical knee pain stage. Results: There were ethnic/race group differences in MoCA scores but no relationships with chronic knee pain stage. Ethnicity/race moderated the relationship between AD-related temporal lobe thickness and chronic pain stage with quadratic patterns suggesting thinner cortex in high chronic pain stage NHB adults. Conclusion: There appear to be complex relationships between chronic knee pain stage, temporal lobe cortex, and sociodemographic variables. Specifically, NHB participants without dementia but with high chronic knee pain stage appeared to have thinner temporal cortex in areas associated with AD. Understanding the effects of sociocultural and socioeconomic factors on health outcomes is the first step to challenging the disparities in healthcare that now appear to link disease conditions to neurodegenerative processes.

International audience; No abstract available

Background: Supervised classification methods have been used for many years for feature selection in metabolomics and other omics studies. We developed a novel primal-dual based classification method (PD-CR) that can perform classification with rejection and feature selection on high dimensional datasets. PD-CR projects data onto a low dimension space and performs classification by minimizing an appropriate quadratic cost. It simultaneously optimizes the selected features and the prediction accuracy with a new tailored, constrained primal-dual method. The primal-dual framework is general enough to encompass various robust losses and to allow for convergence analysis. Here, we compared PD-CR to two commonly used methods : Partial Least Squares Discriminant Analysis (PLS-DA) and Random Forests. We analyzed two metabolomics datasets: one urinary metabolomics dataset concerning lung cancer patients and healthy controls; and a metabolomics dataset obtained from frozen glial tumor samples with mutated isocitrate dehydrogenase (IDH) or wild-type IDH. Results: PD-CR was more accurate than PLS-DA and Random Forests for classification using the 2 metabolomics datasets. It also selected biologically relevant metabolites. PD-CR has the advantage of providing a confidence score for each prediction, which can be used to perform classification with rejection. This substantially reduces the False Discovery Rate. Conclusion: The confidence score provided with PD-CR adds considerable value to the prediction as it includes a metric that is implicitly used by every physician when they make a medical decision: the probability to make the wrong choice. So far, one of the main obstacles to the use of machine learning in medicine resides in the fact that it is harder to trust the decision of a machine learning method than that of a physician when it comes to health issues. We believe that providing a confidence score associated to the decision would make these new tools more convincing if used in routine clinical practice.

Correcting misconceptions and false beliefs are important for injecting reliable information about COVID-19 into public discourse, but what impact does this have on the continued proliferation of misinforming claims? Fact-checking organisations produce content with the aim of reducing misinformation spread, but our knowledge of its impact on misinformation for particular topics and demographics is limited. In this article, we explore the relation between misinformation and fact-checking spread during the COVID-19 pandemic for different topics, user demographics and attributes. We specifically follow misinformation and fact-checks emerging from December 2019 until the 4th of January 2021 on Twitter. Using a combination of spread variance analysis, impulse response modelling and causal analysis, we highlight the bidirectional, weak causation spread behaviour between misinformation and fact-checks. Although we observe that fact-checks about COVID-19 are appearing fairly quickly after misinformation is circulated, its ability to reduce overall misinformation spread appears to be limited. This is especially visible for misinformation about conspiracy theories and the causes of the virus.

Interpersonal violence (IPV) is highly prevalent in the United States and is a major public health problem. The emergence and/or worsening of chronic pain are known sequelae of IPV; however, not all those who experience IPV develop chronic pain. To mitigate its development, it is critical to identify the factors that are associated with increased risk of pain after IPV. This proof-of-concept study used machine-learning strategies to predict pain severity and interference in 47 young women, ages 18 to 30, who experienced an incident of IPV (i.e., physical and/or sexual assault) within three months of their baseline assessment. Young women are more likely than men to experience IPV and to subsequently develop posttraumatic stress disorder (PTSD) and chronic pain. Women completed a comprehensive assessment of theory-driven cognitive and neurobiological predictors of pain severity and pain-related interference (e.g., pain, coping, disability, psychiatric diagnosis/symptoms, PTSD/trauma, executive function, neuroendocrine, and physiological stress response). Gradient boosting machine models were used to predict symptoms of pain severity and pain-related interference across time (Baseline, 1-,3-,6- follow-up assessments). Models showed excellent predictive performance for pain severity and adequate predictive performance for pain-related interference. This proof-of-concept study suggests that machine-learning approaches are a useful tool for identifying predictors of pain development in survivors of recent IPV. Baseline measures of pain, family life impairment, neuropsychological function, and trauma history were of greatest importance in predicting pain and pain-related interference across a 6-month follow-up period. Present findings support the use of machine-learning techniques in larger studies of post-IPV pain development and highlight theory-driven predictors that could inform the development of targeted early intervention programs. However, these results should be replicated in a larger dataset with lower levels of missing data.

A Correction to this paper has been published: https://doi.org/10.1038/s42003-020-01502-2.