The priming of stimulus-elicited involuntary mental imagery.

Percepts, urges, and even high-level cognitions often enter the conscious field involuntarily. The Reflexive Imagery Task (RIT) was designed to investigate experimentally the nature of such entry into consciousness. In the most basic version of the task, participants are instructed not to subvocalize the names of visual objects. Involuntary subvocalizations arise on the majority of the trials. Can these effects be influenced by priming? In our experiment, participants were exposed to an auditory prime 300 ms before being presented with the RIT stimuli. For example, participants heard the word "FOOD" before seeing two RIT stimuli (e.g., line drawings of BANANA and CAT, with the former being the target of the prime). The short span between prime and target allowed us to assess whether the RIT effect is strategic or automatic. Before each trial, participants were instructed to disregard what they hear, and not to think of the name of any of the objects. On an average of 83% of the trials, the participants thought (involuntarily) of the name of the object associated with the prime. This is the first study to use a priming technique within the context of the RIT. The theoretical implications of these involuntary effects are discussed.

Risk Factors for Adjacent Segment Disease Following Anterior Cervical Discectomy and Fusion with Plate Fixation: A Systematic Review and Meta-Analysis.

BACKGROUND: Adjacent segment disease (ASD) following anterior cervical discectomy and fusion with plating (ACDF-P) may yield a poor prognosis or reoperation. This review aimed to summarize risk factors for radiographic ASD (RASD) and clinical ASD (CASD) after ACDF-P. METHODS: Six electronic databases were searched from inception to October 30, 2021. Four reviewers independently screened titles, abstracts, and full-text articles to identify relevant studies. Methodological quality of the included studies was evaluated. Meta-analyses for risk factors were conducted, if possible. RESULTS: Sixteen cohort and 3 case-control studies (3,563 participants) were included. These studies showed low (n = 2), moderate (n = 9), and high (n = 8) risk of bias. One risk factor for RASD was pooled for 2 meta-analyses based on the follow-up period. Four different risk factors for CASD at ≥4 years were pooled for meta-analyses. Limited evidence showed that multi-level fusion, greater asymmetry in total or functional cross-sectional area of the cervical paraspinal muscle, and preoperative degeneration in a greater number of segments were associated with a higher RASD incidence <4 years after ACDF-P. In contrast, no significant risk factors were identified for CASD <4 years after ACDF-P. At ≥4 years after ACDF-P, limited evidence supported that both cephalad and caudal plate-to-disc distances of <5 mm were associated with a higher RASD incidence, and very limited evidence supported that developmental canal stenosis, preoperative RASD, unfused C5-C6 or C6-C7 adjacent segments, use of autogenous bone graft, and spondylosis-related ACDF-P were associated with a higher CASD incidence. CONCLUSIONS: Although several risk factors for RASD and CASD development after ACDF-P were identified, the supporting evidence was very limited to limited. Future prospective studies should extend the existing knowledge by more robustly identifying risk factors for RASD and CASD after ACDF-P to inform clinical practice. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Treatment Options and Outcomes for Squamous Cell Carcinoma of the Nail Unit: A Systematic Review.

BACKGROUND: Nail squamous cell carcinoma (nSCC) is the most common nail unit malignancy. However, no studies to date have evaluated treatment options for nSCC based on recurrence data while controlling for invasion. OBJECTIVE: To identify temporal trends in nSCC treatment modalities and compare treatment outcomes based on invasion. METHODS AND MATERIALS: The authors performed a systematic review of articles published on PubMed, MEDLINE, and Scopus from inception to April 2020 reporting treatment of nSCC. The primary outcome was disease recurrence. RESULTS: Reports of nSCC treatments have increased in the past decade. Mohs micrographic surgery (MMS) is the most common treatment reported overall. The lowest recurrence rates for in situ nSCC were seen with wide surgical excision (WSE) and MMS. For invasive disease, the recurrence rates were lowest with amputation, MMS, and WSE. CONCLUSION: Complete surgical excision of nSCC with either WSE or MMS is associated with lower recurrence rates than limited excision and nonsurgical therapies, regardless of degree of invasion. The prognostic significance of in situ versus invasive disease remains unclear. Confirmation of complete excision may improve outcomes. Digital amputation is indicated for nSCC with bone invasion. Prospective studies and randomized controlled trials are needed to directly compare surgical modalities for nSCC.

Transcription factor networks in Drosophila melanogaster.

Specific cellular fates and functions depend on differential gene expression, which occurs primarily at the transcriptional level and is controlled by complex regulatory networks of transcription factors (TFs). TFs act through combinatorial interactions with other TFs, cofactors, and chromatin-remodeling proteins. Here, we define protein-protein interactions using a coaffinity purification/mass spectrometry method and study 459 Drosophila melanogaster transcription-related factors, representing approximately half of the established catalog of TFs. We probe this network in vivo, demonstrating functional interactions for many interacting proteins, and test the predictive value of our data set. Building on these analyses, we combine regulatory network inference models with physical interactions to define an integrated network that connects combinatorial TF protein interactions to the transcriptional regulatory network of the cell. We use this integrated network as a tool to connect the functional network of genetic modifiers related to mastermind, a transcriptional cofactor of the Notch pathway.

Patterns of skin metastases: a review of 25 years' experience at a single cancer center.

BACKGROUND: Skin metastases can be defined as the spread of a tumor from its site of primary origin to the skin. Skin metastasis may be the first sign of advanced cancer or an indicator of cancer recurrence. OBJECTIVES: To review patient data of 401 skin metastases available from our institution and compare this information to previously published studies. METHODS: Patient data from the Cancer Registry at RPCI database was reviewed for skin metastasis using vendor software. We included all cases of carcinoma, melanoma, sarcomas, and hematologic malignancies entered during a 25-year period from January 4, 1985, to March 1, 2010. Data identifying the relationship of tumor incidence, morphology, and skin metastasis was reviewed. A total of 401 patients who had skin metastases at the time of cancer diagnosis or had skin metastases as a recurrent site were included in this study. Extensive literature review was conducted using PubMed for articles relating to skin metastases and its clinical presentation and histological features. RESULTS: Breast cancer was the most common cancer to metastasize to the skin (32.7% of all skin metastases seen) followed by bronchus and lung (13.2%), skin (melanoma; 9.5%), lymph nodes (7.5%), oral cavity/pharynx/larynx (6.2%), blood and bone marrow (5.5%), and colorectal (4.2%). The most common histological types of tumors were identified as adenocarcinoma (infiltrating ductal carcinoma [22.7%]), lobular carcinoma (4.7%), and non-adenocarcinoma (squamous cell carcinoma [12.2%] and malignant melanoma [5.2%]). CONCLUSIONS: This is the largest review of skin metastases in the United States in the past 25 years. We found the primary cancers that metastasize to the skin have changed in frequency from previous studies. Our data are helpful in indicating which cancers have the strongest predilection for skin metastasis. Identification of these cancers can help both the clinician and patient detect early signs of metastases, which may allow for earlier diagnosis, implementation of therapy, and possible prolonged survival.

Santacruzamate A, a potent and selective histone deacetylase inhibitor from the Panamanian marine cyanobacterium cf. Symploca sp.

A dark brown tuft-forming cyanobacterium, morphologically resembling the genus Symploca, was collected during an expedition to the Coiba National Park, a UNESCO World Heritage Site on the Pacific coast of Panama. Phylogenetic analysis of its 16S rRNA gene sequence indicated that it is 4.5% divergent from the type strain for Symploca and thus is likely a new genus. Fractionation of the crude extract led to the isolation of a new cytotoxin, designated santacruzamate A (1), which has several structural features in common with suberoylanilide hydroxamic acid [(2), SAHA, trade name Vorinostat], a clinically approved histone deacetylase (HDAC) inhibitor used to treat refractory cutaneous T-cell lymphoma. Recognition of the structural similarly of 1 and SAHA led to the characterization of santacruzamate A as a picomolar level selective inhibitor of HDAC2, a Class I HDAC, with relatively little inhibition of HDAC4 or HDAC6, both Class II HDACs. As a result, chemical syntheses of santacruzamate A as well as a structurally intriguing hybrid molecule, which blends aspects of both agents (1 and 2), were achieved and evaluated for their HDAC activity and specificity.

Peroxiredoxin-1 from the human hookworm Ancylostoma ceylanicum forms a stable oxidized decamer and is covalently inhibited by conoidin A.

Hookworms are parasitic nematodes that have a devastating impact on global health, particularly in developing countries. We report a biochemical and structural analysis of a peroxiredoxin from the hookworm Ancylostoma ceylanicum, AcePrx-1. Peroxiredoxins provide antioxidant protection and act as signaling molecules and chaperones. AcePrx-1 is expressed in adult hookworms and can be inactivated by 2,3-bis(bromomethyl)quinoxaline-1,4-dioxide (conoidin A). Conoidin A inactivates AcePrx-1 by alkylating or crosslinking the catalytic cysteines, while maintaining the enzyme in the "locally unfolded" conformation. Irreversible oxidation of the resolving cysteine may contribute additional inhibitory activity. A crystal structure of oxidized AcePrx-1 reveals a disulfide-linked decamer. A helix macrodipole near the active site increases the reactivity of the catalytic cysteines to conoidin A. This work demonstrates the promise of conoidin compounds as probes to evaluate peroxiredoxins as drug targets in human parasites.