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Neutrino induced coherent charged pion production on nuclei, \\(\\overline{\\nu}_\\mu A\\to\\mu^\\pm\\pi^\\mp A\\), is a rare inelastic interaction in which the four-momentum squared transfered to the nucleus is nearly zero, leaving it intact. We identify such events in the scintillator of MINERvA by reconstructing |t| from the final state pion and muon momenta and by removing events with evidence of energetic nuclear recoil or production of other final state particles. We measure the total neutrino and antineutrino cross sections as a function of neutrino energy between 2 and 20 GeV and measure flux integrated differential cross sections as a function of \\(Q^2\\), \\(E_\\pi\\) and \\(\\theta_\\pi\\). The \\(Q^2\\) dependence and equality of the neutrino and anti-neutrino cross-sections at finite \\(Q^2\\) provide a confirmation of Adler's PCAC hypothesis.

Scattering of high energy particles from nucleons probes their structure, as was done in the experiments that established the non-zero size of the proton using electron beams 1 . The use of charged leptons as scattering probes enables measuring the distribution of electric charges, which is encoded in the vector form factors of the nucleon 2 . Scattering weakly interacting neutrinos gives the opportunity to measure both vector and axial vector form factors of the nucleon, providing an additional, complementary probe of their structure. The nucleon transition axial form factor, F A , can be measured from neutrino scattering from free nucleons, ν μ n  →  μ − p and ν ¯ μ p → μ + n , as a function of the negative four-momentum transfer squared ( Q 2 ). Up to now, F A ( Q 2 ) has been extracted from the bound nucleons in neutrino–deuterium scattering 3 – 9 , which requires uncertain nuclear corrections 10 . Here we report the first high-statistics measurement, to our knowledge, of the ν ¯ μ p → μ + n cross-section from the hydrogen atom, using the plastic scintillator target of the MINERvA 11 experiment, extracting F A from free proton targets and measuring the nucleon axial charge radius, r A , to be 0.73 ± 0.17 fm. The antineutrino–hydrogen scattering presented here can access the axial form factor without the need for nuclear theory corrections, and enables direct comparisons with the increasingly precise lattice quantum chromodynamics computations 12 – 15 . Finally, the tools developed for this analysis and the result presented are substantial advancements in our capabilities to understand the nucleon structure in the weak sector, and also help the current and future neutrino oscillation experiments 16 – 20 to better constrain neutrino interaction models. The authors measure the nucleon axial vector form factor, which encodes information on the distribution of the nucleon weak charge, through antineutrino–proton scattering.

Tumour cell plasticity is a major barrier to the efficacy of targeted cancer therapies but the mechanisms that mediate it are poorly understood. Here, we identify dysregulated RNA splicing as a key driver of tumour cell dedifferentiation in colorectal cancer (CRC). We find that Apc -deficient CRC cells have dysregulated RNA splicing machinery and exhibit global rewiring of RNA splicing. We show that the splicing factor SRSF1 controls the plasticity of tumour cells by controlling Kras splicing and is required for CRC invasion in a mouse model of carcinogenesis. SRSF1 expression maintains stemness in human CRC organoids and correlates with cancer stem cell marker expression in human tumours. Crucially, partial genetic downregulation of Srsf1 does not detrimentally affect normal tissue homeostasis, demonstrating that tumour cell plasticity can be differentially targeted. Thus, our findings link dysregulation of the RNA splicing machinery and control of tumour cell plasticity. The influence of mRNA splicing on colon cancer development and progression is unclear. In this study, the authors demonstrate that the SRSF1 splicing factor is essential to sustain the stem cell phenotype of WNT-activated colorectal cancers.

The slogan Undetectable equals Untransmittable (U = U) communicates that people living with HIV (PLHIV) who are on antiretroviral therapy (ART) will not transmit HIV to their sexual partners. We describe awareness of U = U among sexual and gender minorities (SGM) living in Brazil, Mexico, and Peru by self-reported HIV status (PLHIV, negative, unknown) during 2021 using an online survey. We estimated two models using Poisson regression for each population group: Model A including socio-demographic factors (country, gender, age, race, education, and income), and then Model B including taking ART (for PLHIV) or risk behavior, ever-taking PrEP, and HIV risk perception (for HIV-negative or of unknown HIV status). A total of 21,590 respondents were included (Brazil: 61%, Mexico: 30%, Peru: 9%). Among HIV-negative (74%) and unknown status (12%), 13% ever used PrEP. Among PLHIV (13%), 93% reported current use of ART. Awareness of U = U was 89% in both Brazil and Mexico, which was higher than in Peru 64%. Awareness of U = U was higher among PLHIV (96%) than HIV-negative (88%) and HIV-unknown (70%). In multivariate models, PLHIV with lower education were less aware of U = U, while those taking ART were more aware. Among HIV-negative, non-cisgender, lower income, and those with lower education had lower awareness of U = U, while individuals ever using PrEP had higher awareness. In conclusion, awareness of U = U varied by HIV status, socio-demographic characteristics, and HIV risk behavior. The concept of U = U should be disseminated through educational strategies and include a focus on SGM to combat HIV stigma.

Introduction The HIV epidemic continues to disproportionately impact Latin‐American transgender women (TGW). We assessed factors associated with long‐term pre‐exposure prophylaxis (PrEP) engagement and adherence among TGW enrolled in the Implementation of PrEP (ImPrEP) study, the largest PrEP demonstration study in Latin America. Methods HIV‐negative TGW aged ≥18 years reporting 1+eligibility criteria in the 6 months prior to enrolment (e.g. sex partner known to be living with HIV, condomless anal sex [CAS], transactional sex or having a sexually transmitted infection [STI]) who could safely take PrEP were enrolled. Follow‐up visits were conducted at 4 weeks and then quarterly. We conducted logistic regression to identify factors associated with long‐term PrEP engagement (3+ follow‐up visits in 52 weeks) and complete self‐reported adherence (no missed pills in the past 30 days) during follow‐up. For both outcomes, we constructed multivariable models controlling for country, socio‐demographics, sexual behaviour, substance use, STIs and self‐reported adherence at 4 weeks (long‐term engagement outcome only). Results From March 2018 to June 2021, ImPrEP screened 519 TGW, enrolled 494 (Brazil: 190, Mexico: 66 and Peru: 238) and followed them for 52 weeks. At baseline, 27.5% of TGW were aged 18–24 years, 67.8% were mixed‐race and 31.6% had >secondary education. Most, 89.9% reported CAS, 61.9% had >10 sex partners and 71.9% reported transactional sex. HIV incidence was 1.82 cases per 100 person‐years (95% confidence interval [CI]: 0.76–4.38). Almost half of TGW (48.6%) had long‐term PrEP engagement, which was positively associated with reporting complete adherence at week 4 (aOR:2.94 [95%CI:1.88–4.63]) and was inversely associated with reporting CAS with unknown‐HIV partner (aOR:0.52 [95%CI:0.34–0.81]), migration (aOR:0.54 [95%CI:0.34–0.84]), and being from Mexico (aOR:0.28 [95%CI:0.14–0.53]). Self‐reported adherence was associated with TGW aged >34 (aOR:1.61 [95%CI:1.10–2.34]) compared to those aged 25–34 and those with >secondary education (aOR:1.55 [95%CI:1.10–2.19]) and was lower among TGW from Peru (aOR:0.29 [95%CI:0.21–0.41]) or reporting PrEP‐related adverse effects (aOR:0.63 [95%CI:0.42–0.92]). Conclusions Although TGW were willing to enrol in ImPrEP, long‐term PrEP engagement and complete self‐reported adherence were limited, and HIV incidence remained relatively high. A successful HIV prevention agenda should include trans‐specific interventions supporting oral PrEP and exploring long‐acting PrEP strategies for TGW.

The COVID-19 pandemic has spread worldwide, and almost 396 million people have been infected around the globe. Latin American countries have been deeply affected, and there is a lack of data in this regard. This study aims to identify the clinical characteristics, in-hospital outcomes, and factors associated with ICU admission due to COVID-19. Furthermore, to describe the functional status of patients at hospital discharge after the acute episode of COVID-19. This was a prospective, multicenter, multinational observational cohort study of subjects admitted to 22 hospitals within Latin America. Data were collected prospectively. Descriptive statistics were used to characterize patients, and multivariate regression was carried out to identify factors associated with severe COVID-19. A total of 3008 patients were included in the study. A total of 64.3% of patients had severe COVID-19 and were admitted to the ICU. Patients admitted to the ICU had a higher mean (SD) 4C score (10 [3] vs. 7 [3)], p<0.001). The risk factors independently associated with progression to ICU admission were age, shortness of breath, and obesity. In-hospital mortality was 24.1%, whereas the ICU mortality rate was 35.1%. Most patients had equal self-care ability at discharge 43.8%; however, ICU patients had worse self-care ability at hospital discharge (25.7% [497/1934] vs. 3.7% [40/1074], p<0.001). This study confirms that patients with SARS CoV-2 in the Latin American population had a lower mortality rate than previously reported. Systemic complications are frequent in patients admitted to the ICU due to COVID-19, as previously described in high-income countries.

Introduction Syphilis remains a public health concern in Peru. Pre‐exposure prophylaxis (PrEP) implementation programmes in Latin America need to assess their impact on sexually transmitted infections (STIs), along with their feasibility. We assessed the relationship between PrEP adherence and syphilis incidence among men who have sex with men (MSM) and transgender women (TW) enrolled in ImPrEP, a multi‐country PrEP demonstration project; however, this analysis focuses on Peru. Methods Between April 2018 and June 2021, 2292 HIV‐negative MSM/TW attending Peruvian STI clinics were enrolled and followed in ImPrEP. Participants had to be aged ≥18 years and report recent condomless anal sex (CAS), sex with a partner living with HIV, STI history (diagnosis/symptoms) and/or transactional sex. Quarterly follow‐up visits included PrEP dispensing, behavioural assessment, HIV and syphilis screening (treponemal test and Rapid Plasma Reagin [RPR] if syphilis negative at enrolment; RPR only if reactive‐treponemal test at baseline). PrEP adherence was assessed using the medication possession ratio (MPR: #pills prescribed / #days between visits). Generalized estimating equation (GEE) Poisson regression models were used to evaluate factors related to syphilis incidence and also assessed syphilis incidence during two periods: pre‐COVID‐19 lockdown (up to 16 March 2020) and during COVID‐19‐lockdown (17 March 2020−June 2021). Results We enrolled 2039 cisgender‐MSM and 253 TW, with a median follow‐up time of 514 days; 205 incident syphilis cases were identified among 185 individuals. Overall syphilis incidence was 9.1 cases/100 person‐years (p.y.) (95% CI: 7.9−10.4), 14.7/100 p.y. (95% CI: 10.5−20.1) among TW and 8.3/100 p.y (95% CI: 7.1−10.0) among cisgender‐MSM. During the COVID‐19 pre‐lockdown period, syphilis incidence was 10.0/100 p.y. (95% CI: 8.3−12.1) and 8.1/100 p.y. (95% CI: 6.6−10.0) during‐lockdown. Multivariate GEE analysis showed higher syphilis incidence among PrEP‐adherent participants (MPR≥0.6) (adjusted incidence rate ratio [aIRR]: 1.46 [95% CI: 1.08−1.99]), those reporting receptive CAS (aIRR: 1.53 [95% CI: 1.11−2.11]) and TW (aIRR: 1.64 [95% CI: 1.08−2.51]). Syphilis incidence pre‐lockdown was higher for participants reporting receptive CAS (aIRR: 2.35 [95% CI: 1.43−3.86]); during‐lockdown, syphilis incidence was higher among those diagnosed with syphilis at enrolment (aIRR: 2.70 [95% CI: 1.67−4.36]). Conclusions Syphilis incidence is high among PrEP‐adherent MSM/TW, those reporting receptive‐CAS and among TW. Health systems implementing PrEP should strengthen existing STI prevention strategies and incorporate new ones, like Doxy‐PEP for PrEP‐adherent MSM, TW and individuals engaging in receptive‐CAS. MPR may be a tool to identify PrEP users at risk for syphilis.

There is limited long-term clinical outcome data supporting the use of cell-based therapy to treat heart failure. The HYPERION study (NCT03071835) followed long-term outcomes of patients with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NIDCM) who received mesenchymal stromal cells (MSC). We hypothesized that improved cardiac parameters predict longer event-free survival. We performed a Kaplan-Meier analysis to examine event-free survival as the primary outcome. Time-to-event information was captured from all eligible participants. Endpoint events were defined as death (all-cause), Left Ventricular Assist Device (LVAD) placement, or Heart Transplant. Subjects were categorized based on increase in Left Ventricular Ejection Fraction (LVEF) or decrease in Left Ventricular End Diastolic Volume (LVEDV) for comparisons within disease etiologies. There were 134 men and 21 women, with mean age 60.0 ± 11.0 years. There were 121 (78%) with ICM and 34 (22%) with NIDCM. By the end of long-term follow-up (~13 years), 38 (24.5%) subjects had deceased, 5 (3.2%) received LVAD, and 8 (5.2%) underwent heart transplantation. Post-therapy increase of ≥5% LVEF was associated with longer event-free survival in NIDCM (HR:0.31; 95%CI, 0.11,0.86; P = .025), but not ICM (HR:1.14; 95%CI, 0.47,2.72; P = .776). Conversely, reduction in left ventricular end-diastolic volume (LVEDV) was associated with longer event-free survival in ICM (HR:0.16; 95%CI, 0.05, 0.55; P = .008) but not NIDCM (HR:0.35; 95%CI, 0.1,1.2; P = .098). ICM improvers had LVEDV of 225.7 ± 95.9 mL at baseline and 209.0 ± 100.6 mL by year 5 (P = .046). NIDCM improvers had LVEF of 27.2 ± 8.9% at baseline and 36.1 ± 11.6% by year 5 (P = .018). In this long-term observational cohort analysis, improvement of LVEF and/or reduction in LVEDV was associated with survival benefits among subjects with NIDCM and ICM, respectively. In both etiologies the respective improvements are sustained for up to 5 years, providing evidence that cell-based therapy may be a promising and durable treatment option for patients with heart failure.

Background The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. Methods LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. Results Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some ‘lessons learnt’. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). Conclusion We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies.

Drosophila suzukii is a pest native to Southeast Asia that causes significant economic losses to soft fruit crops. Phytosanitary irradiation is a promising treatment for D. suzukii hosts; yet an internationally recognized irradiation protocol is lacking. To fulfil specific requirements for proposing an irradiation treatment for D. suzukii , naturally infested blueberries and cherries containing a total of 37,489 late pupae were irradiated with a maximum absorbed dose of 80 Gy. Infested hosts containing a total of 9578 late pupae were considered unirradiated controls. Prevention of egg laying by females that emerged from treated pupae was considered the treatment endpoint. The fecundity and egg viability of females that emerged from treated pupae mated with their siblings were evaluated using blueberries. While females from unirradiated pupae laid a total of 43,142 eggs, no egg was laid by females that emerged from irradiated pupae. In addition, 1-day-old adults were irradiated with nominal doses of 20 and 72 Gy to evaluate whether egg laying could be prevented in flies emerging before the irradiation treatment. Females irradiated with 72 Gy laid eggs that did not hatch. Our findings suggest the minimum absorbed dose of 80 Gy as a phytosanitary irradiation treatment against D. suzukii and may support its inclusion as a treatment option in the annex of the International Standard for Phytosanitary Measures 28 (ISPM 28).