Single-Cell Profiling of Sarcomas from Archival Tissue Reveals Programs Associated with Resistance to Immune Checkpoint Blockade.

Purpose: Sarcoma encompasses a diverse group of cancers that are typically resistant to current therapies, including immune checkpoint blockade (ICB), and underlying mechanisms are poorly understood. The contexture of sarcomas limits generation of high-quality data using cutting-edge molecular profiling methods, such as single-cell RNA-sequencing, thus hampering progress in understanding these understudied cancers.

Experimental Design: Here, we demonstrate feasibility of producing multimodal single-cell genomics and whole-genome sequencing data from frozen tissues, profiling 75,716 cell transcriptomes of five undifferentiated pleomorphic sarcoma and three intimal sarcoma samples, including paired specimens from two patients treated with ICB.

Exploring Temporomandibular Disorders (TMDs) and Occlusion Debate in Dentistry: Biting Into Controversy.

Some conditions known as temporomandibular disorders (TMDs) affect surrounding muscles and jaw joints. In dentistry, there has been discussion and research on the connection between TMDs and occlusion, which is how the upper and lower teeth meet. Although some dental experts have proposed a direct link between TMDs and occlusion, the specifics of this relationship are still unclear and have many facets.

Multidisciplinary Obstetric Simulation Training: Experience at KK Women's and Children's Hospital (KKH), Singapore, a Tertiary Referral Centre.

Background Multidisciplinary simulation training in the management of acute obstetric emergencies has the potential to reduce both maternal and perinatal morbidity. It is a valuable tool that can be adapted for targeted audiences of different specialities at all experience levels from medical students to senior consultants. Methods In this study, pre- and post-course questionnaires of learners with varying levels of clinical experience from Obstetrics and Gynaecology (O&G), Anaesthesia, Neonatology, Emergency Medicine, midwifery, and nursing who undertook two simulation courses (namely the Combined Obstetrics Resuscitation Training course, CORE, and the CORE Lite), which comprised lectures and simulation drills with manikins and standardized patients, between 2015 and 2023 were compared.

Retrospective Study Comparing Treatment Outcomes in Obstetric Patients With Iron Deficiency Anemia Treated With and Without Intravenous Ferric Carboxymaltose.

Introduction Iron deficiency anemia is associated with an increased risk of adverse maternal and perinatal outcomes. Intravenous iron preparation containing ferric carboxymaltose has been shown to be a safe and effective way of increasing hemoglobin (Hb) and mean corpuscular volume (MCV) levels and reducing the need for blood transfusion. In our center, it used to be given as an inpatient procedure because of the risks of potential drug reactions.

Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation.

Liver metastasis (LM) confers poor survival and therapy resistance across cancer types, but the mechanisms of liver-metastatic organotropism remain unknown. Here, through in vivo CRISPR-Cas9 screens, we found that Pip4k2c loss conferred LM but had no impact on lung metastasis or primary tumor growth. Pip4k2c-deficient cells were hypersensitized to insulin-mediated PI3K/AKT signaling and exploited the insulin-rich liver milieu for organ-specific metastasis.

Continuous Glucose Monitoring Feedback in the Subsequent Development of Gestational Diabetes: A Pilot, Randomized, Controlled Trial in Pregnant Women.

Objective: This study evaluated the effects of receiving glucose feedback from continuous glucose monitoring (CGM) by intermittent scanning (unblinded group), and CGM with masked feedback (blinded group) in the subsequent development of gestational diabetes mellitus (GDM).

Study Design: This was a prospective, single-center, pilot, randomized controlled trial including  = 206 pregnant women in the first trimester of pregnancy with no prior diagnosis of type 1 or type 2 diabetes. The participants were randomized into the unblinded group or blinded group and wore the CGM in the first trimester of pregnancy (9-13 weeks), the second trimester of pregnancy (18-23 weeks), and late-second to early-third trimester (24-31 weeks).

Electromyography: Processing, Muscles' Electric Signal Analysis, and Use in Myofunctional Orthodontics.

Electromyography, commonly known as EMG, utilizes superficial or needle electrodes to record and analyze the fundamental electrical characteristics of skeletal muscles, determining whether the muscles are contracting. The motor unit, which consists of a collection of group muscle fibers and the motor neurons that govern them, is the structural basis of EMG. Three types of electrode are used in EMG which are needle electrode, fine wire electrode, and surface electrode.

KLRG1 marks tumor-infiltrating CD4 T cell subsets associated with tumor progression and immunotherapy response.

Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature of antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel and performed high-throughput analyses in critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) and immune checkpoint blockade (ICB) response (MC38), respectively, and profiled multiple relevant tissues at and around key inflection points of immune surveillance and escape and/or ICB response.

Systematic Pan-cancer Functional Inference and Validation of Hyper, Hypo and Neomorphic Mutations.

While the functional effects of many recurrent cancer mutations have been characterized, the TCGA repository comprises more than 10M non-recurrent events, whose function is unknown. We propose that the context specific activity of transcription factor (TF) proteins-as measured by expression of their transcriptional targets-provides a sensitive and accurate reporter assay to assess the functional role of oncoprotein mutations. Analysis of differentially active TFs in samples harboring mutations of unknown significance-compared to established gain (GOF/hypermorph) or loss (LOF/hypomorph) of function-helped functionally characterize 577,866 individual mutational events across TCGA cohorts, including identification of mutations that are either neomorphic (gain of novel function) or phenocopy other mutations ( ).

Tranexamic acid, as an adjunct to oxytocin prophylaxis, in the prevention of postpartum haemorrhage in women undergoing elective caesarean section: A single-centre double-blind randomised controlled trial.

Objective: To evaluate the effectiveness of tranexamic acid (TXA) in reducing blood loss during elective caesarean sections in women with and without risk factors for postpartum haemorrhage (PPH).

Design: A double-blind, randomised placebo-controlled trial.

Setting: An academic tertiary referral centre in Singapore.

Multimodal single-cell and whole-genome sequencing of small, frozen clinical specimens.

Single-cell genomics enables dissection of tumor heterogeneity and molecular underpinnings of drug response at an unprecedented resolution. However, broad clinical application of these methods remains challenging, due to several practical and preanalytical challenges that are incompatible with typical clinical care workflows, namely the need for relatively large, fresh tissue inputs. In the present study, we show that multimodal, single-nucleus (sn)RNA/T cell receptor (TCR) sequencing, spatial transcriptomics and whole-genome sequencing (WGS) are feasible from small, frozen tissues that approximate routinely collected clinical specimens (for example, core needle biopsies).

tRNA methylation resolves codon usage bias at the limit of cell viability.

Codon usage of each genome is closely correlated with the abundance of tRNA isoacceptors. How codon usage bias is resolved by tRNA post-transcriptional modifications is largely unknown. Here we demonstrate that the N-methylation of guanosine at position 37 (mG37) on the 3'-side of the anticodon, while not directly responsible for reading of codons, is a neutralizer that resolves differential decoding of proline codons.

Dissecting the treatment-naive ecosystem of human melanoma brain metastasis.

Melanoma brain metastasis (MBM) frequently occurs in patients with advanced melanoma; yet, our understanding of the underlying salient biology is rudimentary. Here, we performed single-cell/nucleus RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spatial single-cell transcriptomics and T cell receptor (TCR)-seq. Cancer cells from MBM were more chromosomally unstable, adopted a neuronal-like cell state, and enriched for spatially variably expressed metabolic pathways.

Obstetric red cell transfusion in a high-volume tertiary hospital: a retrospective cohort study.

Introduction: Red cell transfusion is expensive and not without risks. Despite the availability of transfusion guidelines, studies report a wide interhospital variation in transfusion rates. This retrospective cohort study was conducted to define the incidence of red cell transfusion in a multi-ethnic obstetric population and to evaluate current transfusion practice with regard to indications and appropriateness.

A multi-organ chip with matured tissue niches linked by vascular flow.

Engineered tissues can be used to model human pathophysiology and test the efficacy and safety of drugs. Yet, to model whole-body physiology and systemic diseases, engineered tissues with preserved phenotypes need to physiologically communicate. Here we report the development and applicability of a tissue-chip system in which matured human heart, liver, bone and skin tissue niches are linked by recirculating vascular flow to allow for the recapitulation of interdependent organ functions.

Sleep quality and BMI in pregnancy- a prospective cohort study.

Background: Pregnancy associated sleep disturbances is a common pregnancy-related complication which can lead to significant maternal distress and adverse pregnancy outcomes. Sleep quality can be affected by multiple factors and obesity has been recognized as one of them. Various previous studies have demonstrated poorer sleep quality during pregnancy.

Perinatal Palliative Care Service: Developing a Comprehensive Care Package for Vulnerable Babies with Life Limiting Fetal Conditions.

Perinatal Palliative Care provides comprehensive and holistic care for expectant and new parents, who receive a diagnosis of life-limiting fetal condition and opt to continue pregnancy and care for their newborn infant. To develop a service providing individually tailored holistic care during pregnancy, birth, postnatal and bereavement period. Following a baseline survey of neonatologists and discussions with key stakeholders we launched the Perinatal Palliative service at the KK Women's and Children's hospital, Singapore in January 2017.

Dinoprostone vaginal insert (DVI) versus adjunctive sweeping of membranes and DVI for term induction of labor.

Aim: To compare the efficacy and safety of dinoprostone vaginal insert (DVI) alone versus DVI with adjunctive sweeping of membranes (ASM) for induction of labor (IOL).

Methods: Single-center, prospective, randomized controlled trial; women with singleton term pregnancies, cervical dilation ≥1 and <3 cm, intact membranes allocated to either DVI or DVI with ASM. The primary outcome was vaginal delivery within 24 h of insertion.

Multicentre randomised controlled trial comparing the safety in the first 12 h, efficacy and maternal satisfaction of a double balloon catheter and prostaglandin pessary for induction of labour.

Objective: To evaluate the safety in the first 12 h, efficacy and maternal satisfaction of a double balloon catheter (DBC) with vaginal prostaglandin (PGE) for induction of labour (IOL).

Methods: We conducted a multicentre randomised controlled study of 420 patients from 1st January 2016 to 31st December 2017 to evaluate the use of DBC in IOL in an Asian population looking at the adverse effects in the first 12 h after insertion. Women were assigned randomly to cervical ripening with either a DBC or a prostaglandin pessary.

A molecular single-cell lung atlas of lethal COVID-19.

Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection, but the host response at the lung tissue level is poorly understood. Here we performed single-nucleus RNA sequencing of about 116,000 nuclei from the lungs of nineteen individuals who died of COVID-19 and underwent rapid autopsy and seven control individuals. Integrated analyses identified substantial alterations in cellular composition, transcriptional cell states, and cell-to-cell interactions, thereby providing insight into the biology of lethal COVID-19.

A modular master regulator landscape controls cancer transcriptional identity.

Despite considerable efforts, the mechanisms linking genomic alterations to the transcriptional identity of cancer cells remain elusive. Integrative genomic analysis, using a network-based approach, identified 407 master regulator (MR) proteins responsible for canalizing the genetics of individual samples from 20 cohorts in The Cancer Genome Atlas (TCGA) into 112 transcriptionally distinct tumor subtypes. MR proteins could be further organized into 24 pan-cancer, master regulator block modules (MRBs), each regulating key cancer hallmarks and predictive of patient outcome in multiple cohorts.

Pregnancy Outcomes in COVID-19: A Prospective Cohort Study in Singapore.

Introduction: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore.

DORSCON Orange: An Approach to Challenges in a Busy Antenatal Diagnostic Centre in the Midst of a Global Pandemic.

The WHO declared the coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. Lessons from SARS epidemic led Singapore to develop stringent infection control protocols in preparation for future pandemics. However, unlike SARS, COVID-19 appears to be more transmissible and is predicted to continue for longer.