Preimplantation genetic testing for structural rearrangements by genome-wide SNP genotyping and haplotype analysis: a prospective multicenter clinical study.

Background: Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) has been widely utilized to select euploid embryos in patients carrying balanced chromosomal rearrangements (BCRs) by chromosome copy number analysis. However, reliable and extensively validated PGT-SR methods for selecting embryos without BCRs in large-cohort studies are lacking.

Methods: In this prospective, multicenter, cohort study, carriers with BCRs undergoing PGT-SR were recruited across 12 academic fertility centers within China.

3D ultrasound localization microscopy of the nonhuman primate brain.

Background: Haemodynamic changes occur in stroke and neurodegenerative diseases. Developing imaging techniques allowing the in vivo visualisation and quantification of cerebral blood flow would help better understand the underlying mechanism of these cerebrovascular diseases.

Methods: 3D ultrasound localization microscopy (ULM) is a recently developed technology that can map the microvasculature of the brain at large depth and has been mainly used until now in rodents.

Hypothalamic volume is associated with age, sex and cognitive function across lifespan: a comparative analysis of two large population-based cohort studies.

Background: Emerging findings indicate that the hypothalamus, the body's principal homeostatic centre, plays a crucial role in modulating cognition, but comprehensive population-based studies are lacking.

Methods: We used cross-sectional data from the Rhineland Study (N = 5812, 55.2 ± 13.

Disentangling relationships between Alzheimer's disease plasma biomarkers and established biomarkers in patients of tertiary memory clinics.

Background: Several plasma biomarkers for Alzheimer's disease (AD) have demonstrated diagnostic and analytical robustness. Yet, contradictory results have been obtained regarding their association with standard diagnostic markers of AD. This study aims to investigate the specific relationship between the AD biomarkers currently used in clinical practice and the plasma biomarkers.

Expediting pathogen genomics adoption for enhanced foodborne disease surveillance in Africa.

The role of genomics in public health surveillance has been accentuated by its crucial contributions during the COVID-19 pandemic, demonstrating its potential in addressing global disease outbreaks. While Africa has made strides in expanding multi-pathogen genomic surveillance, the integration into foodborne disease (FBD) surveillance remains nascent. Here we highlight the critical components to strengthen and scale-up the integration of whole genome sequencing (WGS) in foodborne disease surveillance across the continent.

Untargeted metabolome atlas for sleep-related phenotypes in the Hispanic community health study/study of Latinos.

Background: Sleep is essential to maintaining health and wellbeing of individuals, influencing a variety of outcomes from mental health to cardiometabolic disease. This study aims to assess the relationships between various sleep-related phenotypes and blood metabolites.

Methods: Utilising data from the Hispanic Community Health Study/Study of Latinos, we performed association analyses between 40 sleep-related phenotypes, grouped in several domains (sleep disordered breathing (SDB), sleep duration, sleep timing, self-reported insomnia symptoms, excessive daytime sleepiness (EDS), and heart rate during sleep), and 768 metabolites measured via untargeted metabolomics profiling.

Feasibility and safety of autologous cord blood derived cell administration in extremely preterm infants: a single-centre, open-label, single-arm, phase I trial (CORD-SaFe study).

Background: Evidence from preclinical studies in small and large animal models has shown neuroprotective effects of intravenous administration of umbilical cord blood derived cells (UCBCs). This study aimed to evaluate the feasibility of umbilical cord blood (UCB) collection, extraction of UCBCs, and subsequent safety of intravenous autologous administration of UCBCs in extremely preterm infants (born <28 weeks gestation).

Methods: A single-centre, open-label, single-arm, safety and feasibility clinical intervention trial was conducted at Monash Medical Centre and Monash Children's Hospital, Melbourne, Australia.

Assessing the kinetics of oxygen-unloading from red cells using FlowScore, a flow-cytometric proxy of the functional quality of blood.

Background: Metrics evaluating the functional quality of red blood cells (RBCs) must consider their role in oxygen delivery. Whereas oxygen-carrying capacity is routinely reported using haemoglobin assays, the rate of oxygen exchange is not measured, yet also important for tissue oxygenation. Since oxygen-unloading depends on the diffusion pathlength inside RBCs, cell geometry offers a plausible surrogate.

OPG promotes lung metastasis by reducing CXCL10 production of monocyte-derived macrophages and decreasing NK cell recruitment.

Background: Lung metastasis is a critical and often fatal progression in cancer patients, with monocyte-derived macrophages (Mo-macs) playing multifaceted roles in this process. Despite the recognized importance of Mac-macs, most studies focus on these cells themselves, while the precise mechanisms through which tumor cells manipulate Mo-macs to promote metastasis remain poorly understood.

Methods: We developed an in vivo CRISPR screening system to identify genes involved in macrophage-dependent metastasis by depleting Mo-macs.

Safety and toxicity of Iopofosine I 131 (CLR 131) with external beam radiation therapy in recurrent or metastatic head and neck cancer: results of a phase 1 single-centre, open-label, single-arm, dose escalation and dose expansion study.

Background: Re-irradiation of recurrent head and neck cancer (HNC) is often limited by tumour adherence to critical structures and/or radiation tolerance of critical normal tissues. Iopofosine I 131 (CLR 131) is a targeted small molecular phospholipid ether (PLE) drug conjugate that delivers iodine-131 selectively to tumour cells. We conducted a phase 1, single-centre, open-label study to determine whether CLR 131 given with reduced dose of external beam radiation therapy (EBRT) would be tolerable and feasible.

Where, why, and how is bias learned in medical image analysis models? A study of bias encoding within convolutional networks using synthetic data.

Background: Understanding the mechanisms of algorithmic bias is highly challenging due to the complexity and uncertainty of how various unknown sources of bias impact deep learning models trained with medical images. This study aims to bridge this knowledge gap by studying where, why, and how biases from medical images are encoded in these models.

Methods: We systematically studied layer-wise bias encoding in a convolutional neural network for disease classification using synthetic brain magnetic resonance imaging data with known disease and bias effects.

An ultra-early, transient interferon-associated innate immune response associates with protection from SARS-CoV-2 infection despite exposure.

Background: A proportion of individuals exposed to respiratory viruses avoid contracting detectable infection. We tested the hypothesis that early innate immune responses associate with resistance to detectable infection in close contacts of COVID-19 cases.

Methods: 48 recently-exposed household contacts of symptomatic COVID-19 cases were recruited in London, UK between May 2020 and March 2021 through a prospective, longitudinal observational study.

Subunit protein CD40.SARS.CoV2 vaccine induces SARS-CoV-2-specific stem cell-like memory CD8 T cells.

Background: Ideally, vaccination should induce protective long-lived humoral and cellular immunity. Current licensed COVID-19 mRNA vaccines focused on the spike (S) region induce neutralizing antibodies that rapidly wane.

Methods: Herein, we show that a subunit vaccine (CD40.

Refinement of post-COVID condition core symptoms, subtypes, determinants, and health impacts: a cohort study integrating real-world data and patient-reported outcomes.

Background: Post-COVID-19 condition (PCC) affects millions of people, and is an essential component of the long-term impact of COVID-19 during the post-pandemic era. Yet, consensus on clinical case definition and core components of PCC remains lacking, affecting our ability to inform research and evidence-based management. Our study aims 1) to identify the most specific symptoms for PCC, and identify clinical subtypes; 2) to evaluate both virus- and host-related determinants of PCC, and 3) assess the impact of PCC on physical and mental health.

The Human Pathology Atlas for deciphering the prognostic features of human cancers.

Background: Cancer is one of the leading causes of mortality worldwide, highlighting the urgent need for a deeper molecular understanding and the development of personalized treatments. The present study aims to establish a solid association between gene expression and patient survival outcomes to enhance the utility of the Human Pathology Atlas for cancer research.

Methods: In this updated analysis, we examined the expression profiles of 6918 patients across 21 cancer types.

Accelerated biological aging increases the risk of short- and long-term stroke prognosis in patients with ischemic stroke or TIA.

Background: Biological age (BA), an integrated measure of physiological aging, has a clear link to stroke. There is a paucity of long-term longitudinal studies about the association between accelerated biological age and stroke prognosis in patients with previous strokes, and the differences in the predictive ability of various BA indicators calculated from clinical biochemistry biomarkers for future stroke outcomes are still unknown. To evaluate the role of three accelerated BA indicators for short- and long-term prognosis of patients with ischemic stroke or transient ischemic attack (TIA), and to identify the most appropriate predictor.

Histone lactylation in macrophage biology and disease: from plasticity regulation to therapeutic implications.

Epigenetic modifications have been identified as critical molecular determinants influencing macrophage plasticity and heterogeneity. Among these, histone lactylation is a recently discovered epigenetic modification. Research examining the effects of histone lactylation on macrophage activation and polarization has grown substantially in recent years.

Therapeutic interventions targeting enteropathy in severe acute malnutrition modulate systemic and vascular inflammation and epithelial regeneration.

Background: Severe acute malnutrition (SAM) is the most life-threatening form of undernutrition, and children hospitalised with complications have unacceptably high mortality. Complicated SAM is a multisystem disease characterised pathophysiologically by muscle wasting, systemic inflammation, metabolic dysfunction, and malnutrition enteropathy including epithelial barrier dysfunction. There is a clear need for novel interventions to address the underlying pathogenic perturbations of complicated SAM.