A Review of the Enablers and Barriers of Medical Student Participation in Research.

Unlabelled: Although research is an integral component in medicine, student participation in research remains limited. This is a systematic review conducted using rapid review methods conforming to the WHO and Cochrane guidelines to synthesise evidence on the enablers and barriers of medical student participation in research. PubMed, EMBASE, and PsycINFO were searched, yielding 27 final studies.

Kafka's beautiful eyes: Forensic intelligence utilisation of phenotypic information.

Franz Kafka had beautiful eyes. So striking, that many of the famous author's friends and peers commented on them - but quite variously ('dark', 'brown', 'grey' & 'blue'). Eye colour as perceived by an observer is subjective, being influenced by physiological, environmental, and even sociocultural factors.

Exploring the Role of Rehabilitation Medicine within an Inclusion Health Context: Examining a Population at Risk from Homelessness and Brain Injury in Edinburgh.

People experiencing homelessness are at risk from a number of comorbidities, including traumatic brain injury, mental health disorders, and various infections. Little is known about the rehabilitation needs of this population. This study took advantage of unique access to a specialist access GP practice for people experiencing homelessness and a local inclusion health initiative to explore the five-year period prevalence of these conditions in a population of people experiencing homelessness through electronic case record searches and to identify barriers and facilitators to healthcare provision for this population in the context of an interdisciplinary and multispecialist inclusion health team through semi-structured interviews with staff working in primary and secondary care who interact with this population.

Identification of Small Molecule Inhibitors and Ligand Directed Degraders of Calcium/Calmodulin Dependent Protein Kinase Kinase 1 and 2 (CaMKK1/2).

CaMKK2 signals through AMPK-dependent and AMPK-independent pathways to trigger cellular outputs including proliferation, differentiation, and migration, resulting in changes to metabolism, bone mass accrual, neuronal function, hematopoiesis, and immunity. CAMKK2 is upregulated in tumors including hepatocellular carcinoma, prostate, breast, and gastric cancer, and genetic deletion in myeloid cells results in increased antitumor immunity in several syngeneic models. Validation of the biological roles of CaMKK2 has relied on genetic deletion or small molecule inhibitors with activity against several biological targets.

Neither sulfoxaflor, Crithidia bombi, nor their combination impact bumble bee colony development or field bean pollination.

Many pollinators, including bumble bees, are in decline. Such declines are known to be driven by a number of interacting factors. Decreases in bee populations may also negatively impact the key ecosystem service, pollination, that they provide.

A review and meta-analysis: Cross-tissue telomere length correlations in healthy humans.

Background And Aim: Tissue source has been shown to exert a significant effect on the magnitude of associations between telomere length and various health outcomes and exposures. The purpose of the present qualitative review and meta-analysis is to describe and investigate the impact of study design and methodological features on the correlation between telomere lengths measured in different tissues from the same healthy individual.

Methods: This meta-analysis included studies published from 1988 to 2022.

Impact of prenatal tobacco smoking on infant telomere length trajectory and ADHD symptoms at 18 months: a longitudinal cohort study.

Background: Prenatal maternal tobacco smoking is a predictor of child attention-deficit/hyperactivity disorder (ADHD) and is associated with offspring telomere length (TL). In this study, we examine the relationship between maternal prenatal smoking, infant TL, and maternal report of early childhood symptoms of ADHD.

Methods: One-hundred and eighty-one mother-infant dyads were followed prospectively for the infant's first 18 months of life.

Dental Policy Lab 3: towards oral and dental health through partnership.

The third and last of the successful Alliance for a Cavity-Free Future (ACFF)/King's College London Dental Policy Lab series, held in 2019, focused on outlining how dental and oral health industries could benefit from enabling positive behaviour change in patients and the public, allowing progress towards caries reduction. During a two-day event, experts from across public health, dentists, global multi-national corporations and dental industry start-ups discussed the issue, collaboratively developing ideas around policy, technology, messaging and engagement for change. An analysis of the current trends in oral health laid out how the implications for industry and corporate social responsibility were identified as crucial.

Dental Policy Lab 2 - towards paying for health in dentistry.

The first Alliance for a Cavity-Free Future (ACFF)/King's College London Dental Policy Lab, held in 2017, identified the need for a review of dental payment systems in order to see progress towards achieving improvements in caries and cavities. The lack of incentivisation for preventive intervention and care has long been a barrier to progress. The second Dental Policy Lab, held in July 2018, focused on this issue with the overarching question: 'How can we create and implement acceptable prevention-based dental payment systems to achieve and maintain health outcomes?' Using a design approach and participatory research, 29 participants from five stakeholder categories developed a blueprint report that aims to serve as a framework to adapt or create remuneration systems that are compatible with evidence-based dentistry with a focus on preventive care.

Dental Policy Lab 1 - towards a cavity-free future.

Although many dental professionals argue that prevention of oral diseases, including dental caries, will benefit both the patient and public finances, a paradigm shift has yet to happen in most countries. The literature has demonstrated that caries prevention and control is possible, but authorities have yet to implement health systems that allow patients to stay in a good health state. 'Policy Labs' are an innovative policy-making initiative that allow a positive collaboration between the many stakeholders around a given policy issue.

Assembly and Analysis of Cell-Scale Membrane Envelopes.

The march toward exascale computing will enable routine molecular simulation of larger and more complex systems, for example, simulation of entire viral particles, on the scale of approximately billions of atoms─a simulation size commensurate with a small bacterial cell. Anticipating the future hardware capabilities that will enable this type of research and paralleling advances in experimental structural biology, efforts are currently underway to develop software tools, procedures, and workflows for constructing cell-scale structures. Herein, we describe our efforts in developing and implementing an efficient and robust workflow for construction of cell-scale membrane envelopes and embedding membrane proteins into them.

Making Cavities History: A Global Policy Consensus for Achieving a Dental Cavity-Free Future.

These global consensus recommendations on caries and cavities, as well as evidence that caries is the most prevalent noncommunicable disease (NCD) globally, should be shared throughout institutional, health care professional, industrial, civil society, and patient communities so that the recommendations can be incorporated into policies for achieving a dental cavity-free future. Appropriate inclusion within strategies and action plans globally and locally will accelerate progress toward Making Cavities History, as well as improving NCDs and wider health.

Defining the Energetic Basis for a Conformational Switch Mediating Ligand-Independent Activation of Mutant Estrogen Receptors in Breast Cancer.

Although most primary estrogen receptor (ER)-positive breast cancers respond well to endocrine therapies, many relapse later as metastatic disease due to endocrine therapy resistance. Over one third of these are associated with mutations in the ligand-binding domain (LBD) that activate the receptor independent of ligand. We have used an array of advanced computational techniques rooted in molecular dynamics simulations, in concert with and validated by experiments, to characterize the molecular mechanisms by which specific acquired somatic point mutations give rise to ER constitutive activation.

Ustekinumab dose escalation improves clinical responses in refractory Crohn's disease.

Background: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn's disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST.

Methods: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted.

A mutant form of ERα associated with estrogen insensitivity affects the coupling between ligand binding and coactivator recruitment.

A homozygous missense mutation in the gene encoding the estrogen receptor α (ERα) was previously identified in a female patient with estrogen insensitivity syndrome. We investigated the molecular features underlying the impaired transcriptional response of this mutant (ERα-Q375H) and four other missense mutations at this position designed to query alternative mechanisms. The identity of residue 375 greatly affected the sensitivity of the receptor to agonists without changing the ligand binding affinity.

2018 French dental contracts: On the road to achieving universal dental health coverage?

Following the failure of earlier negotiations, the new French Government decided not to go ahead with a unilateral decision to define fees in the dental contracts, and to reopen the negotiations. This in a bid to satisfy the providers' requests, as well as to negotiate Emmanuel Macron's presidential campaign promise of no out-of-pocket expenses on dental prosthetics. The three stakeholders, the National Health Insurance System, Dental Trade Unions and Complementary Health Insurers, started another round of negotiations which lead to an agreement.

Surface runoff alters cave microbial community structure and function.

Caves formed by sulfuric acid dissolution have been identified worldwide. These caves can host diverse microbial communities that are responsible for speleogenesis and speleothem formation. It is not well understood how microbial communities change in response to surface water entering caves.

Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex.

Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4 E3 ubiquitin ligase is a plausible major driver of thalidomide teratogenicity. The structure of the second zinc finger of SALL4 in complex with pomalidomide, cereblon and DDB1 reveals the molecular details of recruitment. Sequence differences and a shifted binding position relative to Ikaros offer a path to the rational design of cereblon-binding drugs with reduced teratogenic risk.

The Role of Micronutrients in Graft-VS.-Host Disease: Immunomodulatory Effects of Vitamins A and D.

Graft-vs.-host disease (GVHD) remains a major obstacle to the success of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD occurs because donor T cells in the allograft recognize the genetically disparate host as foreign and attack the transplant recipient's tissues.

The SERM/SERD bazedoxifene disrupts ESR1 helix 12 to overcome acquired hormone resistance in breast cancer cells.

Acquired resistance to endocrine therapy remains a significant clinical burden for breast cancer patients. Somatic mutations in the (estrogen receptor alpha (ERα)) gene ligand-binding domain (LBD) represent a recognized mechanism of acquired resistance. Antiestrogens with improved efficacy versus tamoxifen might overcome the resistant phenotype in ER +breast cancers.

Antagonists for Constitutively Active Mutant Estrogen Receptors: Insights into the Roles of Antiestrogen-Core and Side-Chain.

A major risk for patients having estrogen receptor α (ERα)-positive breast cancer is the recurrence of drug-resistant metastases after initial successful treatment with endocrine therapies. Recent studies have implicated a number of activating mutations in the ligand-binding domain of ERα that stabilize the agonist conformation as a prominent mechanism for this acquired resistance. There are several critical gaps in our knowledge regarding the specific pharmacophore requirements of an antagonist that could effectively inhibit all or most of the different mutant ERs.

Publisher Correction: Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance.

The originally published article contained an error in the legend of supplementary figure 1. A figure permission line was left off. The correct figure permission line has now been added to the HTML and PDF versions of the article, stating that "Data shown in (B) and (C) of this figure were originally published in Jeyakumar, M.

A model of TH17-associated ileal hyperplasia that requires both IL-17A and IFNγ to generate self-tolerance and prevent colitis.

Homeostasis in the ileum, which is commonly disrupted in patients with Crohn's disease, involves ongoing immune responses. To study how homeostatic processes of the ileum impact CD4T cell responses, we used TCR transgenic tools to breed mice that spontaneously produced CD4T cells reactive to an antigen expressed in the ileum. At an early age, the ilea of these mice exhibit crypt hyperplasia and accumulate increased numbers of T17 cells bearing non-transgenic clonotypes.

A "cross-stitched" peptide with improved helicity and proteolytic stability.

A new computational approach to obtain quantitative energy profiles for helix folding was used in the design of orthogonal hydrocarbon and lactam bicyclic peptides. The proteolytically stable, "cross-stitched" peptide SRC2-BCP1 shows nanomolar affinity for estrogen receptor α and X-ray crystallography confirms a helical binding pose.

Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance.

Oestrogen receptor-α (ERα), a key driver of breast cancer, normally requires oestrogen for activation. Mutations that constitutively activate ERα without the need for hormone binding are frequently found in endocrine-therapy-resistant breast cancer metastases and are associated with poor patient outcomes. The location of these mutations in the ER ligand-binding domain and their impact on receptor conformation suggest that they subvert distinct mechanisms that normally maintain the low basal state of wild-type ERα in the absence of hormone.