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ZF2001 contains a tandem-repeat dimeric receptor-binding domain of the SARS-CoV-2 spike protein with aluminum hydroxide adjuvant. In a phase 3 trial, 28,904 participants in five countries were randomly assigned to receive three doses of ZF2001 or placebo. After 6 months of follow-up, efficacy was 76% against infection, 87% against critical or severe disease, and 86% against death. Most side effects were local, low-grade, and transient.

[...]it might also be possible to specifically target individuals to address their patterns of risk-taking behaviour.183 Irrespective of the target population, information campaigns should employ a range of measures to raise awareness of key issues in prevention and care for TBI. Since awareness of child abuse has increased and family risk factors have been elucidated, local programmes have been developed in the USA and other countries to educate parents about the dangers and long-term effects of brain injury, and to provide caregiver relief and advice on coping skills for stress. The GCS42 is the most commonly used approach to quantify the clinical severity of TBI358 (figure 2), but this is relatively crude and does not reflect different pathoanatomical subsets of TBI. [...]the increasing use of prehospital sedation and tracheal intubation often confounds assessment with the GCS and has reduced its usefulness as a metric of injury severity.359 Existing International Classification of Diseases codes360 also do not adequately capture severity of TBI.361 Alternative TBI coding taxonomies-including the Abbreviated Injury Scale (AIS), which categorises severity of intracranial and extracranial injury,362 and the Marshall classification system, which is based on head CT findings363-are anatomically oriented and summarise the type, location, and severity of injuries. [...]current management strategies are based on guidelines that favour a one-size-fits-all approach, and the care of patients with TBI is therefore poorly individualised (section 5). [...]despite investment of many billions of dollars by pharmaceutical companies, no effective drugs exist for treatment in the acute setting-a failing due, in part, to insufficient targeting of therapies to patients in whom the relevant mechanism is active.

An outbreak of Psoroptes sp.-caused mange was detected in a llama herd of Larcas, Jujuy province, Argentina. Infested llamas showed alopecia, erythema, hyperpigmentation, hyperkeratosis, and inflammation of the ear pinnae, as well as crusts and serous, serosanguineous, or purulent drainage with unpleasant smell in the external ear canal. Microscopic evaluation of skin scrapings revealed 0.5- to 0.7-mm-long acari identified as Psoroptes sp. based on their morphology. Histology showed a typical allergic reaction with perivascular to periadnexal mixed inflammatory infiltrate. Phylogenetic tree analysis showed that the cytochrome c oxidase subunit I gene sequences analyzed from the sampled acari clustered into a single P. ovis clade including sequences isolated from rabbits and bighorn sheep, with P. natalensis as a sister taxon that infested bighorn sheep from the USA. Phylogenetic analysis of cytochrome b sequences showed three well-supported clades, one of which contained the sequences of the Larcas llamas and US bighorn sheep isolates. This is the first report on P. ovis infestation of llamas raised in their original location. Investigations on mange etiological agents acting on South American camelids and their distribution are necessary to implement control strategies to mitigate the negative impacts of these parasitic infections.

Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).

Obesity and type 2 diabetes are causally related, yet there is considerable heterogeneity in the consequences of both conditions and the mechanisms of action are poorly defined. Here we show a genetic-driven approach defining two obesity profiles that convey highly concordant and discordant diabetogenic effects. We annotate and then compare association signals for these profiles across clinical and molecular phenotypic layers. Key differences are identified in a wide range of traits, including cardiovascular mortality, fat distribution, liver metabolism, blood pressure, specific lipid fractions and blood levels of proteins involved in extracellular matrix remodelling. We find marginal differences in abundance of Bacteroidetes and Firmicutes bacteria in the gut. Instrumental analyses reveal prominent causal roles for waist-to-hip ratio, blood pressure and cholesterol content of high-density lipoprotein particles in the development of diabetes in obesity. We prioritize 17 genes from the discordant signature that convey protection against type 2 diabetes in obesity, which may represent logical targets for precision medicine approaches. Coral et al. characterize genetically determined discordance between obesity and type 2 diabetes, identifying discordant genes that may convey protection against type 2 diabetes in obesity.

Abstract A workshop titled “Beyond the Symptom: The Biology of Fatigue” was held virtually September 27–28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.

It is unclear whether performing surgery for most patients with an acute subdural hematoma (ASDH) and traumatic brain injury (TBI) is superior to conservative treatment. To compare the effectiveness of a strategy preferring acute surgical ASDH evacuation with one preferring initial conservative treatment. This comparative effectiveness study used data from February 1, 2014, to July 31, 2018, from the prospective observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study, conducted at 18 Level 1 trauma centers in the US. The study included patients with nonpenetrating TBI presenting to the emergency department and admitted within 24 hours after injury with ASDH detected on acute head computed tomography scan. Statistical analysis was performed from December 1, 2022, to December 20, 2024. Acute surgical hematoma evacuation vs initial conservative treatment, comparing outcomes between centers according to treatment preferences, measured by the case mix-adjusted probability of undergoing acute surgery (vs conservative treatment) per center. Functional disability at 6 months was assessed with the Glasgow Outcome Scale-Extended at 6 months, analyzed with ordinal logistic regression adjusted for prespecified confounders, quantified with a common odds ratio (OR). Variation in center preference was quantified with a median OR (MOR). Of 2697 included patients, 711 (mean [SD] age, 46.5 [19.4] years; 539 men [76%]) had an ASDH, of whom 148 (21%) underwent acute cranial surgery and 563 (79%) underwent initial conservative treatment. The acute surgery cohort had lower mean (SD) Glasgow Coma Scale scores (6.8 [4.4] vs 11.4 [4.6]), more pupil abnormalities (both pupils unreacting: 43 of 133 [32%] vs 41 of 477 [9%]), and fewer isolated ASDHs (eg, more with concurrent intracranial lesions; 92 of 133 [69%] vs 297 of 563 [53%%]) compared with the conservative treatment cohort. In the surgical cohort, 129 of 148 patients (87%) underwent decompressive craniectomy (DC), and 17 of 148 (11%) underwent craniotomy. In the conservative treatment cohort, 67 of 563 patients (12%) underwent delayed cranial surgery (DC or craniotomy). The proportion of patients undergoing acute surgery ranged from 0% to 86% (median, 17% [IQR, 5%-27%]) between centers, with up to a 3-fold higher probability of prognostically similar patients receiving acute surgery in one center compared with another random center (MOR, 2.95 [95% CI, 1.79-7.47]; P = .06). Center preference for acute surgery over initial conservative treatment was not associated with a better outcome (OR, 1.05 [95% CI, 0.88-1.26] per 22% [IQR, 5%-27%] increase in acute surgery at a given trauma center). In this comparative effectiveness study, similar patients with traumatic ASDH were treated differently due to center-specific treatment preferences. Outcomes were similar in centers preferring surgical evacuation and those preferring initial conservative treatment. This study suggests that, for a patient with ASDH for whom a neurosurgeon experiences clinical equipoise between acute surgery vs (initial) conservative treatment, conservative treatment may be considered.

GPR30 is a novel G protein-coupled estrogen receptor (ER) associated with metastases in breast cancer (BC) and poor survival in endometrial and ovarian tumors. The association of GPR30 expression with inflammatory breast cancer (IBC), an aggressive and commonly hormone-independent form of BC, has not been studied. GPR30, ER, progesterone receptor (PR), epidermal growth factor receptor (EGFR), and HER-2 expression were assessed by immunohistochemistry (and FISH for HER-2) in 88 primary IBCs. GPR30 expression was correlated with patient overall survival (OS), disease-free survival (DFS), pathologic variables, and other biomarkers. GPR30 expression was found in 69% of IBC cases. ER, PR, HER-2, and EGFR were found in 43, 35, 39, and 34% of IBC cases, respectively. GPR30 expression correlated inversely with ER expression (P = 0.02). Co-expression of ER and GPR30 was found in 24% of IBC samples; 19% expressed only ER and 46% expressed only GPR30. Univariate analysis showed no association between GPR30 expression and OS or DFS. However, co-expression of ER and GPR30 was associated with improved OS (P < 0.03) and marginally with DFS (P < 0.06); the absence of both ER and GPR30 was associated with worse OS and DFS (P = 0.03 for both). Multivariate analysis identified ER as an independent prognostic factor of OS (P = 0.008) and DFS (P = 0.02). The majority of IBC tumors are GPR30-positive, suggesting that estrogen signaling may be active in ER-negative IBC patients. These findings suggest potential new therapeutic targets for IBC such as novel endocrine agents or direct modulation of GPR30.

Capacity building using Earth observing (EO) systems and data (i.e., from orbital and nonorbital platforms) to enable societal applications includes the network of human, nonhuman, technical, nontechnical, hardware, and software dimensions that are necessary to successfully cross the valley [of death; see NRC (2001)] between science and research (port of departure) and societal application (port of arrival). In many parts of the world (especially where ground-based measurements are scarce or insufficient), applications of EO data still struggle for longevity or continuity for a variety of reasons, foremost among them being the lack of resilient capacity. An organization is said to have resilient capacity when it can retain and continue to build capacity in the face of unexpected shocks or stresses. Stresses can include intermittent power and limited Internet bandwidth, constant need for education on ever-increasing complexity of EO systems and data, communication challenges between the ports of departure and arrival (especially across time zones), and financial limitations and instability. Shocks may also include extreme events such as disasters and losing key staff with technical and institutional knowledge.