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The universality of the strange metal phase in many quantum materials is often attributed to the presence of a quantum critical point (QCP), a zero-temperature phase transition ruled by quantum fluctuations. In cuprates, where superconductivity hinders direct QCP observation, indirect evidence comes from the identification of fluctuations compatible with the strange metal phase. Here we show that the recently discovered charge density fluctuations (CDF) possess the right properties to be associated to a quantum phase transition. Using resonant x-ray scattering, we studied the CDF in two families of cuprate superconductors across a wide doping range (up to p  = 0.22). At p * ≈ 0.19, the putative QCP, the CDF intensity peaks, and the characteristic energy Δ is minimum, marking a wedge-shaped region in the phase diagram indicative of a quantum critical behavior, albeit with anomalies. These findings strengthen the role of charge order in explaining strange metal phenomenology and provide insights into high-temperature superconductivity. It has been suggested that the strange metal phase in cuprates stems from a quantum critical point slightly above optimal doping. By resonant x-ray scattering in two cuprate families in a wide doping range, Arpaia et al. show that charge density fluctuations could be associated with this quantum critical point.

Monkeypox (MPX) has been regarded as a neglected tropic disease of Western and Central Africa since the early 70s. However, during May 2022, an unprecedent outbreak of MPX has involved most of European Countries, as well as North and South America. While the actual extent of this outbreak is being assessed by health authorities, we performed a pilot study on specific knowledge, attitudes, and practices (KAP) in a sample of Italian medical professionals (24–30 May 2022; 10,293 potential recipients), focusing on Occupational Physicians (OP), Public Health Professionals (PH), and General Practitioners (GP), i.e., medical professionals more likely involved in the early management of incident cases. More specifically, we inquired into their attitude on the use of variola vaccine in order to prevent MPX infection. From a total of 566 questionnaire (response rate of 5.5%), 163 participants were included in the final analyses. Knowledge status was quite unsatisfying, with substantial knowledge gaps on all aspect of MPX. In turn, analysis of risk perception suggested a substantial overlooking of MPX as a pathogen, particularly when compared to SARS-CoV-2, TB, HIV, and HBV. Overall, 58.6% of respondents were somehow favorable to implement variola vaccination in order to prevent MPX, and the main effectors of this attitude were identified in having been previously vaccinated against seasonal influenza (adjusted Odds Ratio [aOR] 6.443, 95% Confidence Interval [95%CI] 1.798–23.093), and being favorable to receive variola vaccine (aOR 21.416; 95%CI 7.290–62.914). In summary, the significant extent of knowledge gaps and the erratic risk perception, associated collectively stress the importance of appropriate information campaigns among first-line medical professionals.

In adoptive T cell therapy, the long term therapeutic benefits in patients treated with engineered tumor specific T cells are limited by the lack of long term persistence of the infused cellular products and by the immunosuppressive mechanisms active in the tumor microenvironment. Exhausted T cells infiltrating the tumor are characterized by loss of effector functions triggered by multiple inhibitory receptors (IRs). In patients, IR blockade reverts T cell exhaustion but has low selectivity, potentially unleashing autoreactive clones and resulting in clinical autoimmune side effects. Furthermore, loss of long term protective immunity in cell therapy has been ascribed to the effector memory phenotype of the infused cells. We simultaneously redirected T cell specificity towards the NY-ESO-1 antigen via TCR gene editing (TCR ) and permanently disrupted , or genes (IR ) via CRISPR/Cas9 in a protocol to expand early differentiated long-living memory stem T cells. The effector functions of the TCR -IR and IR competent (TCR -IR ) cells were tested in short-term co-culture assays and under a chronic stimulation setting . Finally, the therapeutic efficacy of the developed cellular products were evaluated in multiple myeloma xenograft models. We show that upon chronic stimulation, TCR -IR cells are superior to TCR -IR cells in resisting functional exhaustion through different mechanisms and efficiently eliminate cancer cells upon tumor re-challenge . Our data indicate that TIM-3 and 2B4-disruption preserve T-cell degranulation capacity, while LAG-3 disruption prevents the upregulation of additional inhibitory receptors in T cells. These results highlight that TIM-3, LAG-3, and 2B4 disruptions increase the therapeutic benefit of tumor specific cellular products and suggest distinct, non-redundant roles for IRs in anti-tumor responses.

Background and Objectives: Migraine is a debilitating disorder, whose incidence peak in the age group of 30–39 years overlaps with the peak of employment years, potentially representing a significant issue for occupational physicians (OP). The present study was performed in order to characterize their knowledge, attitudes and practices on migraine in the workplaces. Materials and Methods: A convenience sample of 242 Italian OP (mean age 47.8 ± 8.8 years, males 67.4%) participated in an internet-based survey by completing a structured questionnaire. Results: Adequate general knowledge of migraine was found in the majority of participants. Migraine was identified as a common and severe disorder by the majority of respondents (54.0% and 60.0%). Overall, 61.2% of participants acknowledged migraine as difficult to manage in the workplace, a status that made it more likely for OP understanding its potential frequency (Odds Ratio [OR] 3.672, 95% confidence interval [95%CI] 1.526–8.831), or reported previous managing of complicated cases requiring conditional fitness to work judgement (OR 4.761, 95%CI 1.781–2.726). Moreover, professionals with a qualification in occupational medicine (OR 20.326, 95%CI 2.642–156.358), acknowledging the difficult managing of migraine in the workplaces (OR 2.715, 95%CI 1.034–7.128) and having received any request of medical surveillance for migraine (OR 22.878, 95%CI 4.816–108.683), were more likely to recommend specific requirements for migraineur workers. Conclusions: Migraine was recognized as a common disorder, but also as a challenging clinical problem for OP. Participating OP exhibited a substantial understanding of migraine and its triggers, but residual false beliefs and common misunderstanding may impair the proper management of this disorder, requiring improved and specifically targeted interventions.

Engineered T cells expressing a tumor antigen specific T cell receptor (TCR) have shown promise for cancer immunotherapy. However, the introduced TCR chains can pair with the endogenous TCR chains in T cells, and in mice, these mismatched TCRs can cause a lethal autoimmune reaction. Provasi et al . now show that they can eliminate expression of the endogenous TCR chains using zinc finger nucleases and express only the desired exogenous TCR by lentiviral transduction. The resultant TCR-edited lymphocytes showed tumor specificity without the risk of off-target toxicity. The transfer of high-avidity T cell receptor (TCR) genes isolated from rare tumor-specific lymphocytes into polyclonal T cells is an attractive cancer immunotherapy strategy. However, TCR gene transfer results in competition for surface expression and inappropriate pairing between the exogenous and endogenous TCR chains, resulting in suboptimal activity and potentially harmful unpredicted antigen specificities of the resultant TCRs. We designed zinc-finger nucleases (ZFNs) that promoted the disruption of endogenous TCR β- and α-chain genes. Lymphocytes treated with ZFNs lacked surface expression of CD3-TCR and expanded with the addition of interleukin-7 (IL-7) and IL-15. After lentiviral transfer of a TCR specific for the Wilms tumor 1 (WT1) antigen, these TCR-edited cells expressed the new TCR at high levels, were easily expanded to near purity and were superior at specific antigen recognition compared to donor-matched, unedited TCR-transferred cells. In contrast to unedited TCR-transferred cells, the TCR-edited lymphocytes did not mediate off-target reactivity while maintaining their anti-tumor activity in vivo , thus showing that complete editing of T cell specificity generates tumor-specific lymphocytes with improved biosafety profiles.

Workers occupationally exposed to welding dusts and fumes have been suspected to be at increased risk of invasive pneumococcal disease (IPD). Since the 2010s, the United Kingdom Department of Health and the German Ständige Impfkommission (STIKO) actively recommend welders undergo immunization with the 23-valent polysaccharide (PPV23) pneumococcal vaccine, but this recommendation has not been extensively shared by international health authorities. The present meta-analysis was therefore designed to collect available evidence on the occurrence of pneumococcal infection and IPD among welders and workers exposed to welding fumes, in order to ascertain the effective base of evidence for this recommendation. PubMed, Embase and MedRxiv databases were searched without a timeframe restriction for the occurrence of pneumococcal infections and IPD among welders and workers exposed to metal dusts, and articles meeting the inclusion criteria were included in a random-effect meta-analysis model. From 854 entries, 14 articles (1.6%) underwent quantitative analysis, including eight retrospective studies (publication range: 1980–2010), and six reports of professional clusters in shipbuilding (range: 2017–2020). Welders had an increased likelihood of developing IPD compared with non-welders (odds ratio 2.59, 95% CI 2.00–3.35, I2 = 0%, p = 0.58), and an increased likelihood of dying from IPD (standardized mortality ratio (SMR) 2.42, 95% CI 1.96-2.99, I2 = 0%, p = 0.58). Serotype typing was available for 72 cases, 60.3% of which were represented by serotype 4, followed by 12F (19.2%) and serotype 8 (8.2%). Although the available data derive from a limited number of studies, available results suggest that pneumococcal vaccination should be recommended for workers exposed to welding fumes, and vaccination strategies should consider the delivery of recombinant formulates in order to combine the direct protection against serotypes of occupational interest with the mucosal immunization, reducing the circulation of the pathogen in occupational settings characterized by close interpersonal contact.

Healthcare workers (HCWs) are occupationally exposed to varicella zoster virus (VZV), and their inappropriate vaccination status could contribute to an outbreak involving both professionals and the patients they care for, with a potential impact on the general population. Therefore, since 2007, the Advisory Committee on Immunization Practices (ACIP) recommends that all HCWs have evidence of immunity against varicella. The present meta-analysis was therefore designed to collect the available evidence on the seronegative status of VZV among HCWs. PubMed, Scopus, and Embase databases were searched without backward limit for articles reporting on the seroprevalence of VZV among HCWs, and all articles meeting the inclusion criteria were included in a random-effect meta-analysis model. From 1744 initial entries, a total of 58 articles were included in the quantitative analysis (publication range: 1988 to 2024), for a pooled sample of 71,720 HCWs. Moreover, the included studies reported on seroprevalence data on measles (N = 36,043 HCWs) and rubella (N = 22,086 HCWs). Eventually, the pooled seronegative status for VZV was estimated to be 5.72% (95% confidence interval [95% CI] 4.59 to 7.10) compared to 6.91% (95% CI 4.79 to 9.87) for measles and 7.21% (5.36 to 9.64) for rubella, with a greater risk among subjects younger than 30 years at the time of the survey (risk ratio [RR] 1.434, 95% CI 1.172 to 1.756). Interestingly, medical history of either VZV infection/vaccination had low diagnostic performances (sensitivity 76.00%; specificity 60.12%; PPV of 96.12% but PNV of 18.64%). In summary, the available data suggest that newly hired HCWs are increasingly affected by low immunization rates for VZV but also for measles and rubella, stressing the importance of systematically testing test newly hired workers for all components of the measles–pertussis–rubella–varicella vaccine.