bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA/RNA helicase DHX36 is required for late stages of spermatogenesis
Authors: Zhang Kejia , Zhang Tianxin , Zhang Yujie , Yuan Jinyu , Tang Xinzhe , Zhang Chaobao , Yin Qianqian , Zhang Yonglian , Tong Ming-Han 
Published: December 2022

ABSTRACT
Spermatogenesis is a highly complex developmental process that typically consists of mitosis, meiosis, and spermiogenesis. DNA/RNA helicase DHX36, a unique guanine-quadruplex (G4) resolvase, plays crucial roles in a variety of biological processes. We previously showed that DHX36 is highly expressed in male germ cells with the highest level in zygotene spermatocytes. Here, we deleted Dhx36 in advanced germ cells with Stra8-GFPCre and found that a Dhx36 deficiency in the differentiated spermatogonia leads to meiotic defects and abnormal spermiogenesis. These defects in late stages of spermatogenesis arise from dysregulated transcription of G4-harboring genes, which are required for meiosis. Thus, this study reveals that Dhx36 plays crucial roles in late stages of spermatogenesis.
TEAD1 regulates cell proliferation through a pocket-independent transcription repression mechanism
Authors: Li Feng , Negi Vinny , Yang Ping , Lee Jeongkyung , Ma Ke , Moulik Mousumi , Yechoor Vijay K 
Published: December 2022

Abstract
The Hippo-TEAD pathway regulates cellular proliferation and function. The existing paradigm is that TEAD co-activators, YAP and TAZ, and co-repressor, VGLL4, bind to the pocket region of TEAD1 to enable transcriptional activation or repressive function. Here we demonstrate a pocket-independent transcription repression mechanism whereby TEAD1 controls cell proliferation in both non-malignant mature differentiated cells and in malignant cell models. TEAD1 overexpression can repress tumor cell proliferation in distinct cancer cell lines. In pancreatic β cells, conditional knockout of TEAD1 led to a cell-autonomous increase in proliferation. Genome-wide analysis of TEAD1 functional targets via transcriptomic profiling and cistromic analysis revealed distinct modes of target genes, with one class of targets directly repressed by TEAD1. We further demonstrate that TEAD1 controls target gene transcription in a motif-dependent and orientation-independent manner. Mechanistically, we show that TEAD1 has a pocket region-independent, direct repressive function via interfering with RNA polymerase II (POLII) binding to target promoters. Our study reveals that TEAD1 target genes constitute a mutually restricted regulatory loop to control cell proliferation and uncovers a novel direct repression mechanism involved in its transcriptional control that could be leveraged in future studies to modulate cell proliferation in tumors and potentially enhance the proliferation of normal mature cells.
Single-cell CRISPR immune screens reveal immunological roles of tumor intrinsic factors
Authors: Hou Jiakai , Liang Shaoheng , Xu Chunyu , Wei Yanjun , Wang Yunfei , Tan Yukun , Sahni Nidhi , McGrail Daniel J , Bernatchez Chantale , Davies Michael , Li Yumei , Chen Rui , Yi S Stephen , Chen Yiwen , Yee Cassian , Chen Ken , Peng Weiyi 
Published: December 2022

AbstractGenetic screens are widely exploited to develop novel therapeutic approaches for cancer treatment. With recent advances in single-cell technology, single-cell CRISPR screen (scCRISPR) platforms provide opportunities for target validation and mechanistic studies in a high-throughput manner. Here, we aim to establish scCRISPR platforms which are suitable for immune-related screens involving multiple cell types. We integrated two scCRISPR platforms, namely Perturb-seq and CROP-seq, with both in vitro and in vivo immune screens. By leveraging previously generated resources, we optimized experimental conditions and data analysis pipelines to achieve better consistency between results from high-throughput and individual validations. Furthermore, we evaluated the performance of scCRISPR immune screens in determining underlying mechanisms of tumor intrinsic immune regulation. Our results showed that scCRISPR platforms can simultaneously characterize gene expression profiles and perturbation effects present in individual cells in different immune screen conditions. Results from scCRISPR immune screens also predict transcriptional phenotype associated with clinical responses to cancer immunotherapy. More importantly, scCRISPR screen platforms reveal the interactive relationship between targeting tumor intrinsic factors and T cell-mediated antitumor immune response which cannot be easily assessed by bulk RNA-seq. Collectively, scCRISPR immune screens provide scalable and reliable platforms to elucidate molecular determinants of tumor immune resistance.
Clinical Implications and Treatment Strategies for ESR1 Fusions in Hormone Receptor-Positive Metastatic Breast Cancer: A Case Series
Authors: Brett Jamie O , Ritterhouse Lauren L , Newman Erik T , Irwin Kelly E , Dawson Megan , Ryan Lianne Y , Spring Laura M , Rivera Miguel N , Lennerz Jochen K , Dias-Santagata Dora , Ellisen Leif W , Bardia Aditya , Wander Seth A 
Published: December 2022

Abstract
In hormone receptor-positive metastatic breast cancer (HR+ MBC), endocrine resistance is commonly due to genetic alterations of ESR1, the gene encoding estrogen receptor alpha (ERα). While ESR1 point mutations (ESR1-MUT) cause acquired resistance to aromatase inhibition (AI) through constitutive activation, far less is known about the molecular functions and clinical consequences of ESR1 fusions (ESR1-FUS). This case series discusses 4 patients with HR+ MBC with ESR1-FUS in the context of the existing ESR1-FUS literature. We consider therapeutic strategies and raise the hypothesis that CDK4/6 inhibition (CDK4/6i) may be effective against ESR1-FUS with functional ligand-binding domain swaps. These cases highlight the importance of screening for ESR1-FUS in patients with HR+ MBC while continuing investigation of precision treatments for these genomic rearrangements.
Best practices in pain assessment and management for children
Authors: Trottier Evelyne D , Ali Samina , Doré-Bergeron Marie-Joëlle , Chauvin-Kimoff Laurel 
Published: December 2022

Abstract
Pain assessment and management are essential components of paediatric care. Developmentally appropriate pain assessment is an important first step in optimizing pain management. Self-reported pain should be prioritized. Alternatively, developmentally appropriate behavioural tools should be used. Acute pain management and prevention guidelines and strategies that combine physical, psychological, and pharmacological approaches should be accessible in all health care settings. Chronic pain is best managed using combined treatment modalities and counselling, with the primary goal of attaining functional improvement. The planning and implementation of pain management strategies for children should always be personalized and family-centred.
Les pratiques exemplaires pour l’évaluation et le traitement de la douleur chez les enfants
Authors: Trottier Evelyne D , Ali Samina , Doré-Bergeron Marie-Joëlle , Chauvin-Kimoff Laurel 
Published: December 2022

Résumé
L’évaluation et le traitement de la douleur sont des aspects essentiels des soins pédiatriques. L’évaluation de la douleur adaptée au développement représente une première étape importante pour en optimiser la prise en charge. L’autoévaluation de la douleur est à prioriser. Si c’est impossible, des outils appropriés d’évaluation du comportement, adaptés au développement, doivent être utilisés. Des directives et stratégies de prise en charge et de prévention de la douleur aiguë, qui combinent des approches physiques, psychologiques et pharmacologiques, doivent être accessibles dans tous les milieux de soins. Le meilleur traitement de la douleur chronique fait appel à une combinaison de modalités thérapeutiques et de counseling, dans l’objectif premier d’obtenir une amélioration fonctionnelle. La planification et la mise en œuvre de stratégies de prise en charge de la douleur chez les enfants doivent toujours être personnalisées et axées sur la famille.
Living with high potassium: Balance between nutrient acquisition and K-induced salt stress signaling
Authors: Pantha Pramod , Oh Dong-Ha , Longstreth David , Dassanayake Maheshi 
Published: December 2022

Abstract
High potassium (K) in the growth medium induces salinity stress in plants. However, the molecular mechanisms underlying plant responses to K-induced salt stress are virtually unknown. We examined Arabidopsis (Arabidopsis thaliana) and its extremophyte relative Schrenkiella parvula using a comparative multiomics approach to identify cellular processes affected by excess K and understand which deterministic regulatory pathways are active to avoid tissue damages while sustaining growth. Arabidopsis showed limited capacity to curb excess K accumulation and prevent nutrient depletion, contrasting to S. parvula which could limit excess K accumulation without restricting nutrient uptake. A targeted transcriptomic response in S. parvula promoted nitrogen uptake along with other key nutrients followed by uninterrupted N assimilation into primary metabolites during excess K-stress. This resulted in larger antioxidant and osmolyte pools and corresponded with sustained growth in S. parvula. Antithetically, Arabidopsis showed increased reactive oxygen species levels, reduced photosynthesis, and transcriptional responses indicative of a poor balance between stress signaling, subsequently leading to growth limitations. Our results indicate that the ability to regulate independent nutrient uptake and a coordinated transcriptomic response to avoid nonspecific stress signaling are two main deterministic steps toward building stress resilience to excess K+-induced salt stress.
A Single-Institution Cohort Study With Nevi of Special Site: Recurrence, Progression to Melanoma, and Patterns of Management
Authors: Elkeeb Dena M. , Hopkins Zachary H. , Bolender Caitlin M. , Moreno Christopher , Florell Scott R. , Bowen Anneli R. , Vitale Patricia , Zussman Jamie , Duffy Keith , Grossman Douglas , Secrest Aaron M. , Wada David A. 
Published: December 2022

Abstract:
Nevi of specialized sites (NOSS) occur on the scalp, ears, flexural, acral, and genital areas and display atypical clinical and histologic features. We assessed NOSS recurrence and progression to melanoma, management patterns, and associations between histologic features and treatment recommendations. We queried all histologic diagnoses of NOSS (n = 275) from 2012 to 2017 from a large U.S. academic medical center with reference dermatopathology laboratory and matched these to clinical records. A blinded panel of dermatopathologists re-evaluated lesions, catalogued histologic findings, and gave management recommendation. Associations with dermatopathologist decision and concordance between new and original recommendations were assessed. Of 117 cases with follow-up, 2 locally recurred (1.46%) and none eventuated in melanoma. Clinical features were not associated with original treatment recommendations. After histopathologic review, large melanocytes [odds ratio ratio (ORR) = 8.00, 95% CI, 1.35–47.4] and junctional mitotic figures (ORR = 65.0, 6.5–650) predicted excision recommendation. Likewise, accumulation of many (>9) high-risk features was associated with excision recommendation. Panel review changed treatment recommendation in 27% of cases. Fair concordance existed between original and panel recommendations (κ = 0.29, 0.15–0.44). The low rate of recurrence and lack of melanoma occurrence suggest that despite an atypical clinical and histopathologic appearance, these nevi have limited potential for malignant transformation. Histopathologic findings seem to be principal drivers behind the recommendation for excision in this analysis. Variability existed in treatment recommendations; the panel's consensus recommendation tended to downgrade treatment. This highlights the importance of further outcomes-based studies to identify true high-risk features and refine management guidelines.
Histiocytoid Sweet Syndrome Presenting in Two Sisters With Deficiency of Deaminase Type 2
Authors: Hui Ong Eugene Liat , Cooray Samantha , Brogan Paul , Calonje Eduardo 
Published: December 2022

Abstract:
Deficiency of adenosine deaminase type 2 (DADA2) is an autosomal recessive monogenic autoinflammatory syndrome that is classically characterised by polyarteritis nodosa, systemic vasculitis and stroke. The spectrum of disease manifestations has broadened to encompass a range of cutaneous, vascular and haematological manifestations. We report a novel association in two sisters with heterozygous p.R169G/p.M309l mutations in ADA2 with low serum ADA2 activity who both presented similarly with clinical and histological features consistent with histiocytoid Sweet syndrome.
A Case of a Rare Histologic Variant: Cavernous Hemangioma–Like Kaposi Sarcoma
Authors: Haller Courtney N. , Carrillo Brenda , Soldano Anthony C. , Keeling Brett H. 
Published: December 2022

Abstract:
Kaposi sarcoma (KS) is an endothelial tumor associated with human herpesvirus 8. Cutaneous lesions can present with pink or purple patches, plaques, and nodules which can be ulcerated. The main subtypes of KS generally have similar histologic appearances, with spindle cells and expression of human herpesvirus 8 being characteristic features. However, various histologic variants have been reported. We present the case of a 55-year-old man with cutaneous KS with cavernous hemangioma-like histological features. Cavernous hemangioma–like KS is a rare morphologic type of KS, with only a handful of cases reported in the literature.
Perieccrine Coil Elastosis: An Unusual and Previously Unrecognized Aging-Related Phenomenon
Authors: Monteagudo Carlos , Álvarez Esther 
Published: December 2022

Abstract:
Elastic fibers are present as a thin line around the normal secretory coil of eccrine and apocrine glands, although they are virtually imperceptible with hematoxylin-eosin staining. Skin aging is a consequence of intrinsic and extrinsic factors, and glycation and ultraviolet irradiation are involved in this process favoring elastosis. We report an unusual and prominent perieccrine elastosis on the left temple in the vicinity of a basal cell carcinoma in a 78-year old man with type 2 diabetes, dyslipidemia, and hypertension. Very thick multilamellar and tortuous elastic fibers surrounded the eccrine coils. This increased amount of elastic fibers was confirmed by orcein staining as well as amyloid-P and lysozyme immunostaining. Perieccrine coil elastosis is a very unusual phenomenon that to the best of our knowledge has not been reported. Similar to dermal actinic elastosis, the presence of perieccrine coil elastosis in a skin cancer microenvironment might hypothetically promote tumor growth because of the release of elastin-derived peptides.
Acquired Perforating Osteoma Cutis: A Rare Histopathological Diagnosis
Authors: Zipperer Kate , Munoz Ayezel , Kelly Erica , Goodwin Brandon 
Published: December 2022

Abstract:
Perforating osteoma cutis is a benign proliferation of mature bone within the dermis and subcutaneous tissue of the skin with transepidermal elimination. Transepidermal elimination of bone is the hallmark of perforating osteoma cutis and is defined by the breaching of bone through the epidermis. Perforating osteoma cutis is exceptionally rare because only 6 cases have been recorded in the literature at the time of preparation of this report. In this report, we present the case of a 65-year-old female patient with a medical history of nonmelanoma skin cancer, hypertension, hyperlipidemia, and type II diabetes mellitus presented for evaluation of a skin lesion of the posterior lower left leg, which had been present for 1 year. Clinical and histopathologic findings were consistent with the diagnosis of acquired perforating osteoma cutis. Treatment with surgical removal by tangential biopsy has thus far proven to be both diagnostic and therapeutic because no recurrence has been noted as of 6 months.
An Unusual Case of a Scrotal Porocarcinoma and Review of the Literature
Authors: Hartsough Emily Mae , Moran Jakob , Devins Kyle , Wszolek Matthew , Cornejo Kristine M. 
Published: December 2022

Abstract:
Porocarcinomas are rare tumors derived from the acrosyringium and eccrine ducts, which most commonly occur on the lower extremities or head and neck region in older adults. Microscopically, they invariably demonstrate continuity with the epithelium, showing downgrowth of broad anastomosing bands with more infiltrative intradermal cords and nests of pleomorphic tumor cells with ductal lumina; an associated poroma may also be seen. We report an unusual case of a porocarcinoma arising on the scrotum of a 55-year-old man. Because of the extraordinary location and the presence of keratinizing squamous differentiation, distinction from a squamous cell carcinoma was particularly challenging. Close examination revealed the presence of a co-existing poroma, and immunohistochemistry revealed loss of YAP1 with diffuse nuclear expression of NUT in both the porocarcinoma and poroma components. This finding is particularly suggestive of a YAP1::NUTM1 fusion which has been reported to be highly specific for poroid neoplasms. Distinction of porocarcinoma from its mimics is important due to the frequent aggressive behavior of this neoplasm.
Ponatinib-Associated Cutaneous Eruptions—A Case Series and Review of Clinicopathologic Findings
Authors: Weber Isaac , Gloss Catherine , Castillo Brianna , Smith Emily 
Published: December 2022

Abstract:
Ponatinib is a third-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia. Cutaneous toxicities are a commonly reported side effect of ponatinib treatment with “rash” being one of the most common. Specific subtypes are infrequently reported, but include hyperkeratotic, folliculocentric, ichthyosiform, and pityriasis rubra pilaris-like eruptions. Herein, we highlight the clinicopathologic features of 2 cases of ponatinib-induced pityriasis rubra pilaris-like eruptions. We also classify the clinical and histopathologic features of all previously reported ponatinib-associated eruptions in the literature and discuss treatment and potential diagnostic pitfalls.
The effect of subbranch for the quantification of local hemodynamic environment in the coronary artery: a computed tomography angiography–based computational fluid dynamic analysis
Authors: Shi Yibing , Zheng Jin , Yang Ning , Chen Yang , Sun Jingxi , Zhang Ying , Zhou Xuanxuan , Gao Yongguang , Li Suqing , Zhu Haijing , Acosta-Cabronero Julio , Xia Ping , Teng Zhongzhao 
Published: December 2022

Abstract

Background
Hemodynamic parameters derived from computed tomography angiography–based computational fluid dynamics (CFD) analysis have been widely used for clinical decision-making and researches to assess the vulnerability of atherosclerotic plaques and explain the initialization and development of atherosclerosis. Subbranches in the CFD model might affect the accuracy of hemodynamic parameters, but the effectiveness has been least quantified.

Methods
A coronary artery baseline model was generated with focal stenosis at the proximal left anterior descending artery. Nineteen comparing models were created by systematically removing various subbranches to examine the changes in hemodynamic parameters, including time-averaged pressure (TAP), time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and particle relative residence time (RRT). Changes in these parameters were assessed quantitatively around the stenosis and near the region where subbranches were removed.

Results
The removal of subbranches caused a significant change in outflow rate, and there was generally a decrease in all CFD parameters in the regions of interest with a decrease in outflow rate. The subbranch removal had a significant impact on the calculation of TAWSS, OSI, and RRT, whereas TAP was insensitive to the removal with approximately 0.25% variation in all 19 models. The local effect from removing branch segments generally became negligible after 5 diameters away from the cutting-off position, but the decrease could be affected by other factors, such as a large curvature.

Conclusion
The outflow rate is a dominant factor for the calculation of TAP, TAWSS, OSI, and RRT. Removal of subbranches has a minor effect on the TAP calculation, but its effect is considerable on the TAWSS, OSI, and RRT. The effect of subbranch removal is limited in a region with 5 local diameters.
The Influence of Iron and Ligand Type on Plutonium Uptake in Two Strains of Hydroponically Grown Corn (Zea Mays)
Authors: Phillips Stephanie Hoelbling , Donaher Sarah E. , Powell Brian A. , Tharayil Nishanth , Martinez Nicole E. 
Published: December 2022

Abstract
This work investigates the uptake and root-shoot transport of plutonium (Pu) and iron (Fe) in corn (Zea mays) to gain insight into the Pu uptake pathway. Plutonium has no known biological function in plants yet may feasibly enter plants through the uptake pathway used by Fe (an essential nutrient), as these two elements have similar chemical properties. A series of experiments was conducted in which two hydroponically grown corn strains (one normal and one deficient in the transporter protein for Fe) were exposed to varying concentrations of complexed Pu and Fe. Results suggest that while Fe did inhibit Pu uptake to a certain extent, Pu was able to use alternative uptake pathways. In a 10 ppb Pu:1 ppb Fe hydroponic solution, all shoots had detectable shoot Pu concentrations compared to only 22% of plants when the Fe concentration was raised to 10 ppb. While root Pu accumulation was reduced for the corn strain deficient in the Fe transporter protein at lower Pu media concentrations, there were no differences at higher Pu concentrations, signifying the existence of substitute transport routes. A comparison of citrate and deferoxamine B (DFOB) ligand influence found that Pu complexed with DFOB remained in the roots of the plant, while movement of Pu into the shoots of the plant was more prevalent with the Pu-citrate complex. This study advances understanding of the behavior and mobility of Pu in the terrestrial environment and specifically the interactions between Pu and an essential nutrient in a common crop species.
Intraoperative aberrometry: an update on applications and outcomes
Authors: Kaufman Aaron R. , Pineda Roberto 
Published: December 2022

Purpose of review
There is now a large body of experience with intraoperative aberrometry. This review aims to synthesize available data regarding intraoperative aberrometry applications and outcomes.

Recent findings
The Optiwave Refractive Analysis (ORA) System utilizes Talbot-moiré interferometry and is the only commercially available intraoperative aberrometry device. There are few studies that include all-comers undergoing intraoperative aberrometry-assisted cataract surgery, as most studies examine routine patients only or atypical eyes only. In non-post-refractive cases, studies have consistently shown a small but statistically significant benefit in spherical equivalent refractive outcome for intraoperative aberrometry versus preoperative calculations. In studies examining axial length extremes, most studies have shown intraoperative aberrometry to perform similarly to preoperative calculations. Amongst post-refractive cases, post-myopic ablation cases appear to benefit the most from intraoperative aberrometry. For toric intraocular lenses (IOLs), intraoperative aberrometry may be used for refining IOL power (toricity and spherical equivalent) and alignment, and most studies show intraoperative aberrometry to achieve low postoperative residual astigmatism.

Summary
Intraoperative aberrometry can be utilized as an adjunct to preoperative planning and surgeon's judgment to optimize cataract surgery refractive outcomes. Non-post-refractive cases, post-myopic ablation eyes, and toric intraocular lenses may have the greatest demonstrated benefit in intraoperative aberrometry studies to date, but other eyes may also benefit from intraoperative aberrometry use.