The Top 50 Articles and Authors of the New Millennium in Psychiatry: A Bibliometric Analysis.

The field of psychiatry faces significant challenges in the new millennium, marked by a surge in mental health diagnoses coupled with barriers to accessing adequate care. Despite obstacles, notable advancements have been achieved throughout the field, including the release of DSM-5, the introduction of esketamine, and the development of innovative assessment tools. This study aims to comprehensively analyze recent advances in psychiatry by examining the top 50 most cited articles and authors since 2000, addressing a gap in the literature left by previous subfield-focused bibliometric studies. Utilizing the Web of Science (WOS) database, this bibliometric analysis examined all publications in psychiatric journals from January 1, 2000, to September 18, 2022. The top 50 most cited articles and authors were identified and characterized based on various metrics, including times cited, article type, and institutional affiliations. WOS extracted 699,005 articles, with authors from the United States contributing the highest number of publications. The top 50 articles spanned a variety of formats, with cross-sectional studies, new measures, literature reviews, and randomized controlled trials being the most prevalent. The American Journal of Psychiatry emerged as the leading journal, hosting eight of the top 50 articles. Among the top 50 authors, female representation was limited, comprising 24% of first authors and 22% overall. Institutional affiliations revealed a majority of top authors worked at universities affiliated with the top 40 NIH-funded departments of psychiatry, with those affiliated with Harvard University leading in authorship contributions. This study sheds light on recent advancements in psychiatry, emphasizing the underrepresentation of female authors and the prevalence of top authors affiliated with major NIH-funded programs. This bibliometric analysis provides a comprehensive overview of recent advances and the top recent contributors in the field, fostering a deeper understanding of the evolving landscape of psychiatry in the new millennium.

Comparison of industry payments to psychiatrists and psychiatric advanced practice clinicians in the USA, 2021: a cross-sectional study.

OBJECTIVES: To compare industry payment patterns among US psychiatrists and psychiatric advanced practice clinicians (APCs) and determine how scope of practice laws has influenced these patterns. DESIGN: Cross-sectional study. SETTING: This study used the publicly available US Centers for Medicare and Medicaid Services Sunshine Act Open Payment database and the National Plan and Provider Enumeration System (NPPES) database for the year 2021. PARTICIPANTS: All psychiatrists and psychiatric APCs (subdivided into nurse practitioners (NPs) and clinical nurse specialists (CNSs)) included in either database. PRIMARY AND SECONDARY OUTCOME MEASURES: Number and percentage of clinicians receiving industry payments and value of payments received. Total payments and number of transactions by type of payment, payment source and clinician type were also evaluated. RESULTS: A total of 85 053 psychiatric clinicians (61 011 psychiatrists (71.7%), 21 895 NPs (25.7%), 2147 CNSs (2.5%)) were reviewed; 16 240 (26.6%) psychiatrists received non-research payment from industry, compared with 10 802 (49.3%) NPs and 231 (10.7%) CNSs (p<0.001) for pairwise comparisons). Psychiatric NPs were significantly more likely to receive industry payments compared with psychiatrists (incidence rate ratio (IRR), 1.85 (95% CI 1.81 to 1.88); p<0.001)). Compared with psychiatrists, NPs were more likely to receive payments of > United States Dollars (US) $) 100 (33.9% vs 14.6%; IRR, 2.14 (2.08 to 2.20); p<0.001) and > US$ 1000 (5.3% vs 4.1%; IRR, 1.29 (1.20 to 1.38); p<0.001) but less likely to receive > US$ 10 000 (0.4% vs 1.0%; IRR, 0.39 (0.31 to 0.49); p<0.001). NPs in states with 'reduced' or 'restricted' scope of practice received more frequent payments (reduced: IRR, 1.22 (1.18 to 1.26); restricted: IRR, 1.26 (1.22 to 1.30), both p<0.001). CONCLUSIONS: Psychiatric NPs were nearly two times as likely to receive industry payments as psychiatrists, while psychiatric CNSs were less than half as likely to receive payment. Stricter scope of practice laws increases the likelihood of psychiatric NPs receiving payment, the opposite of what was found in a recent specialty agnostic study.

Distribution of CARES Act Provider Relief Funding to Psychiatric Care Organizations.

More than $100 billion in Coronavirus Aid, Relief, and Economic Security (CARES) Act funding was intended to support financially stressed health care providers during the COVID-19 pandemic. The distribution of the CARES Act's Provider Relief Fund among psychiatrists is poorly understood. Analyzing funding received by 2,593 psychiatric care organizations (PCOs), the authors found that funding was more equally distributed across care organizations of different sizes in psychiatry versus other specialties. Substantially less relief funding was received by PCOs per provider relative to other specialties. This disparity in relief funding is surprising given that specific earmarks of the CARES Act were intended to improve U.S. mental health care capacity, meriting further attention.

Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays.

Genetic screening of the breast and ovarian cancer susceptibility gene BRCA1 has uncovered a large number of variants of uncertain clinical significance. Here, we use biochemical and cell-based transcriptional assays to assess the structural and functional defects associated with a large set of 117 distinct BRCA1 missense variants within the essential BRCT domain of the BRCA1 protein that have been documented in individuals with a family history of breast or ovarian cancer. In the first method, we used limited proteolysis to assess the protein folding stability of each of the mutants compared with the wild-type. In the second method, we used a phosphopeptide pull-down assay to assess the ability of each of the variants to specifically interact with a peptide containing a pSer-X-X-Phe motif, a known functional target of the BRCA1 BRCT domain. Finally, we used transcriptional assays to assess the ability of each BRCT variant to act as a transcriptional activation domain in human cells. Through a correlation of the assay results with available family history and clinical data, we define limits to predict the disease risk associated with each variant. Forty-two of the variants show little effect on function and are likely to represent variants with little or no clinical significance; 50 display a clear functional effect and are likely to represent pathogenic variants; and the remaining 25 variants display intermediate activities. The excellent agreement between the structure/function effects of these mutations and available clinical data supports the notion that functional and structure information can be useful in the development of models to assess cancer risk.

The BARD1 C-terminal domain structure and interactions with polyadenylation factor CstF-50.

The BARD1 N-terminal RING domain binds BRCA1 while the BARD1 C-terminal ankyrin and tandem BRCT repeat domains bind CstF-50 to modulate mRNA processing and RNAP II stability in response to DNA damage. Here we characterize the BARD1 structural biochemistry responsible for CstF-50 binding. The crystal structure of the BARD1 BRCT domain uncovers a degenerate phosphopeptide binding pocket lacking the key arginine required for phosphopeptide interactions in other BRCT proteins. Small angle X-ray scattering together with limited proteolysis results indicates that ankyrin and BRCT domains are linked by a flexible tether and do not adopt a fixed orientation relative to one another. Protein pull-down experiments utilizing a series of purified BARD1 deletion mutants indicate that interactions between the CstF-50 WD-40 domain and BARD1 involve the ankyrin-BRCT linker but do not require ankyrin or BRCT domains. The structural plasticity imparted by the ANK-BRCT linker helps to explain the regulated assembly of different protein BARD1 complexes with distinct functions in DNA damage signaling including BARD1-dependent induction of apoptosis plus p53 stabilization and interactions. BARD1 architecture and plasticity imparted by the ANK-BRCT linker are suitable to allow the BARD1 C-terminus to act as a hub with multiple binding sites to integrate diverse DNA damage signals directly to RNA polymerase.

Structural basis for phosphorylation-dependent signaling in the DNA-damage response.

The response of eukaryotic cells to DNA damage requires a multitude of protein-protein interactions that mediate the ordered repair of the damage and the arrest of the cell cycle until repair is complete. Two conserved protein modules, BRCT and forkhead-associated (FHA) domains, play key roles in the DNA-damage response as recognition elements for nuclear Ser/Thr phosphorylation induced by DNA-damage-responsive kinases. BRCT domains, first identified at the C-terminus of BRCA1, often occur as multiple tandem repeats of individual BRCT modules. Our recent structural and functional work has revealed how BRCT repeats recognize phosphoserine protein targets. It has also revealed a secondary binding pocket at the interface between tandem repeats, which recognizes the amino-acid 3 residues C-terminal to the phosphoserine. We have also studied the molecular function of the FHA domain of the DNA repair enzyme, polynucleotide kinase (PNK). This domain interacts with threonine-phosphorylated XRCC1 and XRCC4, proteins responsible for the recruitment of PNK to sites of DNA-strand-break repair. Our studies have revealed a flexible mode of recognition that allows PNK to interact with numerous negatively charged substrates.

Structure of the BRCT repeat domain of MDC1 and its specificity for the free COOH-terminal end of the gamma-H2AX histone tail.

MDC1 (mediator of DNA damage checkpoint protein 1) regulates the recognition and repair of DNA double strand breaks in mammalian cells through its interactions with nuclear foci containing the COOH-terminally phosphorylated form of the histone variant, H2AX. Here we demonstrate that the tandem BRCT repeats of MDC1 directly bind to the phosphorylated tail of H2AX-Ser(P)-Gln-Glu-Tyr, in a manner that is critically dependent on the free carboxylate group of the COOH-terminal Tyr residue. We have determined the x-ray crystal structure of the MDC1 BRCT repeats at 1.45 Angstroms resolution. By a comparison with the structure of the BRCA1 BRCT bound to a phosphopeptide, we suggest that two arginine residues in MDC1, Arg(1932) and Arg(1933) may recognize the COOH terminus of the peptide as well as the penultimate Glu of H2AX, while Gln(2013) may provide additional specificity for the COOH-terminal Tyr.

Interactions between BRCT repeats and phosphoproteins: tangled up in two.

The C-terminal region of the breast-cancer-associated protein BRCA1 contains a pair of tandem BRCA1 C-terminal (BRCT) repeats that are essential for the tumour suppressor function of the protein. Similar repeat sequences have been identified in many proteins that seem to mediate cellular mechanisms for dealing with DNA damage. The BRCT domain in BRCA1 has been recently shown to constitute a module for recognizing phosphorylated (phospho-) peptides, with a recognition groove that spans both BRCT repeats. The fact that many other BRCT-containing proteins have phospho-peptide binding activity suggests that BRCT repeats might mediate phosphorylation-dependent protein-protein interactions in processes that are central to cell-cycle checkpoint and DNA repair functions.

Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1.

The BRCT repeats in BRCA1 are essential for its tumor suppressor activity and interact with phosphorylated protein targets containing the sequence pSer-X-X-Phe, where X indicates any residue. The structure of the tandem BRCA1 BRCT repeats bound to an optimized phosphopeptide reveals that the N-terminal repeat harbors a conserved BRCT phosphoserine-binding pocket, while the interface between the repeats forms a hydrophobic groove that recognizes the phenylalanine. Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition. The diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations.

Evaluation of a mucoactive herbal drug, Radix Ophiopogonis, in a pathogenic quail model.

We investigated the effect of Radix Ophiopogonis on airway mucociliary clearance and mucus secretion in anesthetized quails. The oral administration of 10 g/kg of Radix Ophiopogonis significantly increased tracheal mucociliary transport velocity (MTV). Moreover, either 10 g/kg or 3 g/kg of Radix Ophiopogonis markedly attenuated the human neutrophil elastase (HNE)-induced decrease in MTV. Furthermore, we found that 10 g/kg of Radix Ophiopogonis significantly abolished the HNE-induced increases in fucose and protein contents of tracheal lavage, whereas Radix Ophiopogonis at the same dose only significantly decreased the protein content in the control group. These results suggest that Radix Ophiopogonis improves airway mucociliary clearance and that the improvement may, at least in part, be ascribed to the amelioration of airway mucus secretion.