The financial impact of MD-PhD training compared with MD training for academic physicians.

To reduce debt burden and encourage the pursuit of research-focused careers, most MD-PhD programs provide medical school tuition remission and an annual stipend. However, prolonged training compared with MD physicians postpones the time until MD-PhD physicians earn a full salary. We compared lifetime earning potential for MD-PhD physicians in academia with their MD colleagues in the same clinical specialty.

More women than ever are entering MD-PhD programs. What lies ahead for them?

The earliest MD-PhD programs were small and enrolled mostly men. Here, we show that since 2014 there has been a steady increase in the number of women in MD-PhD programs, the number of women reaching parity with men in 2023. This change was due to an increase in female applicants, a decrease in male applicants, and an increase in the acceptance rate for women, which had previously been lower than that for men.

Husk Separation (Kubessa Method) Impacts the Aging Chemistry of Beer.

The removal of husks before the mashing process, also known as the Kubessa method, is an established brewing practice often positively associated with smoothness and better flavor-stability of beer. Empirical evidence on the effect of the Kubessa method on beer, however, has been lacking. Similarly, our study's comprehensive analysis of established brewing attributes revealed that traditional methods do not fully capture the impact of husk separation in beer brewing.

The National MD-PhD Program Outcomes Study: career paths followed by Black and Hispanic graduates.

Previous studies on attrition from MD-PhD programs have shown that students who self-identify as Black are more likely to withdraw before graduating than Hispanic students and students not from groups underrepresented in medicine (non-UIM). Here, we analyzed data collected for the National MD-PhD Program Outcomes Study, a national effort to track the careers of over 10,000 individuals who have graduated from MD-PhD programs over the past 60 years. On average, Black trainees took slightly longer to graduate, were less likely to choose careers in academia, and were more likely to enter nonacademic clinical practice; although, none of these differences were large.

Megakaryocyte-induced contraction of plasma clots: cellular mechanisms and structural mechanobiology.

Nonmuscle cell contractility is an essential feature underlying diverse cellular processes such as motility, morphogenesis, division and genome replication, intracellular transport, and secretion. Blood clot contraction is a well-studied process driven by contracting platelets. Megakaryocytes (MKs), which are the precursors to platelets, can be found in bone marrow and lungs.

A regulatory node involving Gα, PLCβ, and RGS proteins modulates platelet reactivity to critical agonists.

Background: Most platelet agonists work through G protein-coupled receptors, activating pathways that involve members of the G, G, and G/G families of heterotrimeric G proteins. G signaling has been shown to be critical for efficient platelet activation. Growing evidence suggests that regulatory mechanisms converge on G protein-coupled receptors and G to prevent overly robust platelet reactivity.

The Virtual Summer Research Program: supporting future physician-scientists from underrepresented backgrounds.

Introduction: Physician-scientist training programs expect applicants to have had extensive research experience prior to applying. Even at the best of times, this leaves individuals from underserved and underrepresented backgrounds at a competitive disadvantage, especially those remote from major academic centers. The COVID-19 pandemic exacerbated that disadvantage by closing research laboratories and suspending summer research opportunities.

Pearls of wisdom for aspiring physician-scientist residency applicants and program directors.

Postgraduate physician-scientist training programs (PSTPs) enhance the experiences of physician-scientist trainees following medical school graduation. PSTPs usually span residency and fellowship training, but this varies widely by institution. Applicant competitiveness for these programs would be enhanced, and unnecessary trainee anxiety relieved, by a clear understanding of what factors define a successful PSTP matriculant.

Gaps between college and starting an MD-PhD program are adding years to physician-scientist training time.

The average age when physician-scientists begin their career has been rising. Here, we focused on one contributor to this change: the increasingly common decision by candidates to postpone applying to MD-PhD programs until after college. This creates a time gap between college and medical school.

Thrombin spatial distribution determines protein C activation during hemostasis and thrombosis.

Rebalancing the hemostatic system by targeting endogenous anticoagulant pathways, like the protein C (PC) system, is being tested as a means of improving hemostasis in patients with hemophilia. Recent intravital studies of hemostasis demonstrated that, in some vascular contexts, thrombin activity is sequestered in the extravascular compartment. These findings raise important questions about the context-dependent contribution of activated PC (APC) to the hemostatic response, because PC activation occurs on the surface of endothelial cells.

The contribution of TFPIα to the hemostatic response to injury in mice.

Background: Tissue factor pathway inhibitor (TFPI) is an essential regulator of coagulation, limiting thrombin generation and preventing thrombosis. In humans and mice, TFPIα is the sole isoform present in platelets.

Objective: Here, we asked whether TFPIα, because of its release from platelets at sites of injury, has a unique role in limiting the hemostatic response.

A Human Vascular Injury-on-a-Chip Model of Hemostasis.

Hemostasis is an innate protective mechanism that plays a central role in maintaining the homeostasis of the vascular system during vascular injury. Studying this essential physiological process is often challenged by the difficulty of modeling and probing the complex dynamics of hemostatic responses in the native context of human blood vessels. To address this major challenge, this paper describes a microengineering approach for in vitro modeling of hemostasis.

Hemostasis vs. homeostasis: Platelets are essential for preserving vascular barrier function in the absence of injury or inflammation.

Platelets are best known for their vasoprotective responses to injury and inflammation. Here, we have asked whether they also support vascular integrity when neither injury nor inflammation is present. Changes in vascular barrier function in dermal and meningeal vessels were measured in real time in mouse models using the differential extravasation of fluorescent tracers as a biomarker.

RGS10 and RGS18 differentially limit platelet activation, promote platelet production, and prolong platelet survival.

G protein-coupled receptors are critical mediators of platelet activation whose signaling can be modulated by members of the regulator of G protein signaling (RGS) family. The 2 most abundant RGS proteins in human and mouse platelets are RGS10 and RGS18. While each has been studied individually, critical questions remain about the overall impact of this mode of regulation in platelets.

MD-PhD graduates remain underrepresented in orthopaedic surgery: National MD-PhD Program Outcome Survey update.

With the dramatic expansion of the biomedical knowledge base and increasing demands for evidence-based medicine, the role of the clinician-scientist is becoming increasingly important. In orthopaedic surgery, clinician-scientists are at the forefront of translational efforts to address the growing burden of musculoskeletal disease, yet MD-PhD trained investigators have historically been underrepresented in this field. Here, we examine the trend, over time, of MD-PhD graduates pursuing orthopaedic surgery, compared with other specialties.

GRK6 regulates the hemostatic response to injury through its rate-limiting effects on GPCR signaling in platelets.

G protein-coupled receptors (GPCRs) mediate the majority of platelet activation in response to agonists. However, questions remain regarding the mechanisms that provide negative feedback toward activated GPCRs to limit platelet activation and thrombus formation. Here we provide the first evidence that GPCR kinase 6 (GRK6) serves this role in platelets, using GRK6-/- mice generated by CRISPR-Cas9 genome editing to examine the consequences of GRK6 knockout on GPCR-dependent signaling.

The national MD-PhD program outcomes study: Relationships between medical specialty, training duration, research effort, and career paths.

MD-PhD programs were established in the 1950s as a new curriculum for training physician-scientists. Since then, the number of programs has grown considerably; however, concerns about the health of the US physician-scientist workforce have grown, as well. The largest attempt to date to assess whether MD-PhD programs are fulfilling their mission was the national MD-PhD program outcomes study, which was released as an American Association of Medical Colleges report in 2018.

The national MD-PhD program outcomes study: Outcomes variation by sex, race, and ethnicity.

In 2015, a nation-wide effort was launched to track the careers of over 10,000 MD-PhD program graduates. Data were obtained by surveys sent to alumni, inquiries sent to program directors, and searches in American Association of Medical Colleges (AAMC) databases. Here, we present an analysis of the data, focusing on the impact of sex, race, and ethnicity on career outcomes.

Correction: Increased Levels of Plasma Soluble Sema4D in Patients with Heart Failure.

[This corrects the article DOI: 10.1371/journal.pone.

Interrelationships between structure and function during the hemostatic response to injury.

Extensive studies have detailed the molecular regulation of individual components of the hemostatic system, including platelets, coagulation factors, and regulatory proteins. Questions remain, however, about how these elements are integrated at the systems level within a rapidly changing physical environment. To answer some of these questions, we developed a puncture injury model in mouse jugular veins that combines high-resolution, multimodal imaging with functional readouts in vivo.

Training the physician-scientist: views from program directors and aspiring young investigators.

There is growing concern that the physician-scientist is endangered due to a leaky training pipeline and prolonged time to scientific independence (1). The NIH Physician-Scientist Workforce Working Group has concluded that as many as 1,000 individuals will need to enter the pipeline each year to sustain the workforce (2). Moreover, surveys of postgraduate training programs document considerable variability in disposition and infrastructure (3).

RGS10 shapes the hemostatic response to injury through its differential effects on intracellular signaling by platelet agonists.

Platelets express ≥2 members of the regulators of G protein signaling (RGS) family. Here, we have focused on the most abundant, RGS10, examining its impact on the hemostatic response in vivo and the mechanisms involved. We have previously shown that the hemostatic thrombi formed in response to penetrating injuries consist of a core of fully activated densely packed platelets overlaid by a shell of less-activated platelets responding to adenosine 5'-diphosphate (ADP) and thromboxane A (TxA).