Haematological setpoints are a stable and patient-specific deep phenotype.

The complete blood count (CBC) is an important screening tool for healthy adults and a common test at periodic exams. However, results are usually interpreted relative to one-size-fits-all reference intervals, undermining the precision medicine goal to tailor care for patients on the basis of their unique characteristics. Here we study thousands of diverse patients at an academic medical centre and show that routine CBC indices fluctuate around stable values or setpoints, and setpoints are patient-specific, with the typical healthy adult's nine CBC setpoints distinguishable as a group from those of 98% of other healthy adults, and setpoint differences persist for at least 20 years.

Reproductive factors and expression of stem cell markers in women with incident benign breast disease.

Reproductive factors are well-established risk factors for breast cancer. The prevailing hypothesis suggested that stem cell changes may be the key underlying mechanisms, but epidemiological evidence has been notably scarce. Herein we examined the relationship between reproductive risk factors and the expression of well-established stem cell markers CD44, CD24, and ALDH1A1 in benign breast biopsy non-cancerous samples.

Longitudinal timing of physical activity and associated cardiometabolic and behavioral health outcomes in young adults.

Background: This is the first study to examine longitudinal associations between self-selected timing of moderate-to-vigorous physical activity (MVPA) and health outcomes in young adults over 18 months.

Methods: Young adults (N = 434, Mage = 23.9, SDage = 4.

Serous-like breast carcinomas: immunophenotypic, genetic, and clinicopathologic characterization of a morphologically distinct group of tumours.

Aims: Unusual morphologic patterns of breast carcinomas can raise diagnostic consideration for metastasis or special breast cancer subtypes with management implications. We describe rare invasive breast cancers that mimic serous carcinoma of the gynaecologic tract (serous-like breast carcinomas, SLBC) and characterize their clinicopathologic, immunophenotypic, and genetic features.

Methods And Results: All patients were female (n = 15, median age 49 years) without a history of gynaecologic malignancy.

A framework for neural organoids, assembloids and transplantation studies.

As the field of neural organoids and assembloids rapidly expands, there is an emergent need for guidance and advice on designing, conducting and reporting experiments to increase the reproducibility and utility of these models. Here, our consortium- representing specialized laboratories from around the world- presents a framework for the experimental process that ranges from ensuring the quality and integrity of human pluripotent stem cells to characterizing and manipulating neural cells in vitro, and from transplantation techniques to considerations for modeling human development, evolution, and disease. As with all scientific endeavors, we advocate for rigorous experimental designs tailored to explicit scientific questions, and transparent methodologies and data sharing, to provide useful knowledge for both current research practices and for developing regulatory standards.

Risk of Incident Heart Failure and Heart Failure Subtypes in Patients With Rheumatoid Arthritis.

Objective: Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD) including heart failure (HF). However, little is known regarding the relative risks of HF subtypes such as HF with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF) in RA compared with non-RA.

Methods: We identified patients with RA and matched non-RA comparators among participants consenting to broad research from two large academic centers.

Revisiting ICD Therapy for Primary Prevention in Patients With Heart Failure and Reduced Ejection Fraction.

Implantable cardioverter-defibrillators (ICDs) are recommended to reduce the risk of sudden cardiac death (SCD) in patients with heart failure with reduced ejection fraction (HFrEF). The landmark studies leading to the current guideline recommendations preceded the 4 pillars of guideline-directed medical therapies (GDMTs). Therefore, some have questioned the role of ICDs for primary prevention in current clinical practice.

Primary medication adherence in Medicare beneficiaries prescribed sacubitril-valsartan or renin-angiotensin system blockers for heart failure with reduced ejection fraction.

Background: Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor (ARNI) that is now preferred over angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin-II-receptor blockers (ARBs) for treating heart failure with reduced ejection fraction (HFrEF). Primary medication adherence to a costly brand-name ARNI, compared to inexpensive generic ACE-Is or ARBs, is unknown.

Methods: This cohort study used a linked database of electronic health records and Medicare fee-for-service claims from a large integrated health care system in Boston to compare primary medication adherence among Medicare beneficiaries with HFrEF newly prescribed sacubitril-valsartan, those newly prescribed a generic ACE-I or ARB, and those switching from an ACE-I or ARB to sacubitril-valsartan.

The Emerging Role of Alarmin-Targeting Biologics in the Treatment of Patients With COPD.

Topic Importance: COPD is a complex, heterogeneous lung disease characterized by persistent airflow limitation secondary to airways and parenchymal abnormalities, and respiratory symptoms, including dyspnea, fatigue, chronic cough, and sputum production. Cigarette smoke exposure is a major contributor to COPD; however, inhalation of toxic particles and other environmental and host factors can contribute to its genesis. Over time, the clinical course is frequently punctuated by exacerbations that further accelerate lung function decline and increase exacerbation risk.

Per- and polyfluoroalkyl substances, apolipoproteins and the risk of coronary heart disease in US men and women.

Background: Existing evidence for associations of per- and polyfluoroalkyl substances (PFASs) with blood lipids, lipoproteins and apolipoproteins (apo), and coronary heart disease (CHD) risk is limited and inconsistent. This study aims to explore associations between plasma PFASs, blood lipoprotein subspecies defined by apolipoproteins, and CHD risk.

Methods: A case-control study of CHD was conducted in the Health Professionals Follow-Up Study (HPFS) and Nurses' Health Study (NHS).

Comparison of 3D facial photographs and clinical documentation in patients with craniofacial morphea.

Diagnosis of craniofacial morphea (CM) relies upon clinical examination of progressive craniofacial changes. We assess the utility of 3D stereophotogrammetry in documenting asymmetry of the face compared to clinical notetaking. This retrospective study of 3D images and clinical documentation included 32 patients (mean age 15.