bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudomyxoma Peritonei: Pathology, a Historical Overview, and Proposal for Unified Nomenclature and Updated Grading
Authors: Bradley Robert F. , Carr Norman J. 
Published: September 2023

Abstract
Pseudomyxoma peritonei (PMP) is a clinically distinctive form of malignancy that typically arises from the appendix and is characterized by bulky accumulation of mucinous tumor deposits in the peritoneal cavity. It has defied stable pathologic categorization ever since first being described in the late 19th century. Since the early 20th century, many accounts have emphasized the bland histology of those cases arising from appendiceal precursors that had been considered benign, in contrast to higher-grade cases with more conventionally malignant histology. Beginning in the late 20th century, this was exemplified by divided nomenclature, with “carcinoma” phraseology being reserved for cases with clear-cut high-grade morphology. Such a divided approach is rendered problematic by the spectrum of atypia in many cases, including a significant subset with “intermediate” features. More recently, unified nomenclature has been favored for PMP of appendiceal origin, with an emphasis on tiers of grading. The goal is a clinically relevant and objectively reproducible grading scheme for what appears to be the spectrum of one clinicopathological entity (except perhaps for cases purely composed of signet-ring cells). Currently proposed consensus criteria focus on the distinction of cases of PMP as low grade, high grade, or high grade with signet-ring cells.
Low Grade Mesothelial Tumors of the Peritoneum: Multicystic Mesothelioma, Well-Differentiated Papillary Mesothelioma, and Adenomatoid Tumor
Authors: Carr Norman John 
Published: September 2023

AbstractLow-grade neoplasms of the peritoneum are rare but include 2 entities that are more often encountered in the peritoneum than the pleura, namely, multicystic mesothelioma and well-differentiated papillary mesothelioma. Adenomatoid tumor is most common in the genital tract, but can occur in the peritoneum where it is sometimes found as a component of either multicystic mesothelioma or well-differentiated papillary mesothelioma. Indeed, all 3 tumors can occur in combination. The histological differential diagnosis of these neoplasms can include reactive mesothelial proliferations, malignant mesothelioma, and metastatic carcinoma. Cystic conditions such as lymphangioma can also enter the differential diagnosis. The question of whether cystic mesothelial lesions are neoplastic or reactive is controversial—multicystic lesions of the type that can recur after surgery and involve multiple sites are clinically neoplastic, and the presence of genetic abnormalities consistent with neoplasia has been described. However, the possibility that small, isolated mesothelial cysts are simple inclusions may be difficult to refute.
Gastric Polyposis Syndromes
Authors: Chiu Kenrry , Lee Lik Hang , Xiong Wei 
Published: September 2023

AbstractMost gastric polyps are fundic gland polyps and hyperplastic polyps. Adenomas, inflammatory fibroid polyps, and neuroendocrine tumors are other types of gastric polyps that occur less frequently. Rarely, a gastric polyp may be associated with a syndrome, including hereditary cancer syndromes. Some of these syndromes are also associated with an increased risk of gastric cancer. We present a case of a 50-year-old woman with known Cowden syndrome who presents with multiple gastric hamartomatous polyps. We then review the clinical, endoscopic, and pathologic features of various syndromes that are associated with gastric polyps. Fundic gland polyp–predominant syndromes include familial adenomatous polyposis, gastric adenocarcinoma and proximal polyposis of the stomach, andMUTYH-associated polyposis, all of which are hereditary cancer syndromes. Gastric hamartomatous polyps are found in patients with juvenile polyposis syndrome, Peutz-Jeghers syndrome,PTENhamartoma tumor syndrome including Cowden syndrome, and Cronkhite-Canada syndrome. Syndromic gastric polyps may be biopsied in patients with a previously established diagnosis of the underlying syndrome, such as surveillance endoscopies in familial adenomatous polyposis. On other occasions, the pathologic assessment of gastric polyps may prompt or contribute to a diagnostic workup of an underlying syndrome in conjunction with other clinical and endoscopic findings.
Pseudomyxoma Peritonei Arising From a Low-Grade Mucinous Neoplasm of the Urachus
Authors: Vora Chintan , Tzivanakis Alexios , Dayal Sanjeev , Carr Norman John 
Published: September 2023

AbstractUrachal mucinous tumors range from low-grade lesions traditionally called cystadenomas to frankly invasive mucinous adenocarcinomas. Occasionally, they can lead to the syndrome of pseudomyxoma peritonei (PMP). We report a patient who presented with abdominal distension and had raised tumor markers. A computed tomography scan revealed a calcified cystic lesion of the bladder dome together with features of PMP. These findings were confirmed at laparotomy, and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy was performed. Histologically, the urachal lesion was a low-grade urachal mucinous tumor (mucinous cystic tumor of low malignant potential). The peritoneal disease was associated with ovarian involvement and omental cake and was designated low-grade mucinous carcinoma peritonei on histology. The immunoprofile was typical for lesions of this type, featuring expression of CK20, CEA, and CDX2, but no expression of CK7. We review the literature of PMP arising from urachal primary neoplasms and identify 58 cases reported previously. Based on the limited data available, it appears that urachal lesions account for about 1 in 200 cases of PMP. Owing to the clinical and pathological similarities between urachal and appendiceal mucinous tumors, we recommend a simple classification based on the principles applied to appendiceal lesions and argue this is more appropriate than a classification based on ovarian nomenclature.
Marginal Zone Lymphoma, Immune Dysregulation, and High-Grade Transformation
Authors: Crane Genevieve M. , Chadburn Amy 
Published: September 2023

AbstractMarginal zone lymphoma (MZL) is a low-grade B-cell lymphoma, which includes mucosa-associated lymphoid tissue lymphoma, splenic MZL, and nodal MZL. Of these, mucosa-associated lymphoid tissue lymphoma is the most frequent. While all 3 subtypes are typically indolent, a subset undergoes transformation to an aggressive B-cell lymphoma resulting in treatment challenges and a worse prognosis. We present a patient with systemic lupus erythematosus and Sjögren disease who developed MZL while on cyclophosphamide and steroids for treatment of her autoimmune disease. Her MZL was associated with a relatively indolent initial course. Unfortunately, her systemic lupus erythematosus continued to progress, and she ultimately required a renal transplant for end-stage renal disease due to lupus nephritis. At transplant, her MZL was thought to be in remission, but shortly thereafter, she developed an enlarging neck mass. A biopsy demonstrated background MZL with focal transformation to diffuse large B-cell lymphoma. Evidence is emerging that the underlying biology of a subset of MZL based on mutational profile, gene expression, and/or cytogenetic factors may affect the risk of transformation. Immune status has not been linked to progression, but chronic inflammation and immune dysregulation in the setting of chronic infection or autoimmune disease may underlie MZL development. In addition, iatrogenic immunosuppression for solid organ transplant or acquired immunodeficiency in the setting of human immunodeficiency virus may also result in increased risk or unusual presentations of MZL. This article features a case-based approach to explore factors related to MZL progression in a patient with a complex history of autoimmunity and immune suppression.
Large B-Cell Lymphoma With IRF4 Rearrangement: From Theory to Practice
Authors: Vincent Gabriel , Richebourg Steven , Cloutier Stephanie , Fortin Melanie , Jacob Simon , Amin-Hashem Mohamed 
Published: September 2023

Abstract
Interferon regulatory factor 4 (IRF4) rearrangement is a common cytogenetic anomaly reported in various neoplastic lymphoproliferative disorders. IRF4 is a gene located on chromosome 6 that encodes for the IRF4 protein belonging to the IRF family of transcription factors. Large B-cell lymphoma with IRF4 rearrangement constitutes a novel provisional entity included in the classification of lymphoid tissue recently proposed by the World Health Organization in its fourth revised edition. This rare entity, with a specific clinical presentation, is defined by the presence of a rearrangement of the IRF4 gene. We report a rare case of a 19-year-old female patient presenting with a large B-cell lymphoma with IRF4 rearrangement located in the right tonsil, with characteristic histologic appearance and the phenotype of neoplastic cells. The presence of an IGH-IRF4 rearrangement was also confirmed, using a fluorescence in situ hybridization analysis with 2 successive hybridizations on the same slide. Patient was treated with 6 cycles of R-CHOP with no evidence of recurrence.
Gender-Affirming Mastectomy Trends and Surgical Outcomes in Adolescents
Authors: Tang Annie , Hojilla J. Carlo , Jackson Jordan E. , Rothenberg Kara A. , Gologorsky Rebecca C. , Stram Douglas A. , Mooney Colin M. , Hernandez Stephanie L. , Yokoo Karen M. 
Published: September 2023

Background
There are more than 150,000 transgender adolescents in the United States, yet research on outcomes after gender-affirming mastectomy in this age group is limited. We evaluated gender-affirming mastectomy incidence and postoperative complications, including regret, in adolescents within our integrated health care system.

Methods
Gender-affirming mastectomies performed from January 1, 2013, to July 31, 2020, in adolescents 12 to 17 years of age at the time of referral were identified. The incidence of gender-affirming mastectomy was calculated by dividing the number of patients undergoing these procedures by the number of adolescents assigned female at birth aged 12 to 17 years within our system at the beginning of each year and amount of follow-up time within that year. Demographic information, clinical characteristics (comorbidities, mental health history, testosterone use), surgical technique, and complications, including mention of regret, of patients who underwent surgery were summarized. Patients with and without complications were compared to evaluate for differences in demographic or clinical characteristics using χ2 tests.

Results
The incidence of gender-affirming mastectomy increased 13-fold (3.7–47.7 per 100,000 person-years) during the study period. Of the 209 patients who underwent surgery, the median age at referral was 16 years (range, 12–17 years) and the most common technique was double incision (85%). For patients with greater than 1-year follow-up (n = 137; 65.6%), at least one complication was found in 7.3% (n = 10), which included hematoma (3.6%), infection (2.9%), hypertrophic scars requiring steroid injection (2.9%), seroma (0.7%), and suture granuloma (0.7%); 10.9% underwent revision (n = 15). There were no statistically significant differences in patient demographics and clinical characteristics between those with and without complications (P > 0.05). Two patients (0.95%) had documented postoperative regret, but neither underwent reversal surgery at follow-up of 3 and 7 years postoperatively.

Conclusions
Between 2013 and 2020, we observed a marked increase in gender-affirming mastectomies in adolescents. The prevalence of surgical complications was low, and of more than 200 adolescents who underwent surgery, only 2 expressed regret, neither of which underwent a reversal operation. Our study provides useful and positive guidance for adolescent patients, their families, and providers regarding favorable outcomes with gender-affirming mastectomy.
Short Stay Management of Locally Advanced Breast Cancer Using Immediate Local Thoracoabdominal Advancement Flap and Enhanced Recovery After Surgery Protocol
Authors: Fahradyan Artur , Liu Alice , Taylor Lesley , Jones Veronica , Li Wai-Yee 
Published: September 2023

Background
Patients with locally advanced invasive breast cancer (LABC) are often considered inoperable, because of the anticipated chest wall defect and need for complex reconstruction. We present a series of patients who underwent mastectomy with extensive skin resection and immediate chest wall reconstruction using a local thoracoabdominal advancement flap (TAAF). All patients were managed after surgery with an ERAS (Enhanced Recovery After Surgery) protocol, to decrease length of stay in hospital. We also present 1 patient who subsequently had satisfactory bilateral delayed breast reconstruction with pedicled latissimus dorsi myocutaneous flaps with prepectoral silicone implants.

Methods
This is a single-surgeon, single-institution retrospective chart review of patients with LABC who underwent mastectomy with skin resection and local TAAF from May 2017 to October 2019, with minimum 3-month follow-up.

Results
Thirteen patients met inclusion criteria. Twelve of 13 patients presented with stage III or IV invasive breast cancer, with skin involvement. The mean chest wall defect measured 248.7 cm2 (140–336 cm2; SD, 63.2 cm2), and all were successfully reconstructed with immediate local TAAF. There were no intraoperative complications, but 1 patient developed a postop hematoma. The mean hospital stay was 1.3 nights, with 9 patients (69.2%) staying less than 23 hours and 4 patients (30.8%) staying 2 nights. Nine patients (69.2%) underwent adjuvant therapy, beginning on average 32 days (13–55 days; SD, 13.1 days) after surgery. The mean follow-up time was 13.8 months (4.5–31.6 months; SD, 9.2 months). One patient underwent successful delayed bilateral breast reconstruction with pedicled latissimus dorsi myocutaneous flaps and silicone implant placement.

Conclusions
Our study demonstrates that reconstruction with local TAAF is an outpatient procedure that reliably provides durable, immediate chest wall coverage, after mastectomy in patients with LABC. This technique has a short operative time, low blood loss, and low complication rate, allowing timely adjuvant therapy. Using an ERAS postop protocol we were able to reduce mean hospital stay to 1.3 days. Compared with other described techniques of reconstruction, the additional scars and donor site morbidity are minimal, allowing for delayed breast reconstruction. We also present survival outcomes data on these surgically managed patients.
Real-World Experience With Teprotumumab in Patients With Dysthyroid Optic Neuropathy
Authors: Tamhankar Madhura A. , Pradeep Tejus , Chen Yuanyuan , Briceño César A. 
Published: September 2023

Background:
Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improved proptosis, diplopia, inflammatory signs/symptoms, and quality of life in patients with active thyroid eye disease (TED) in clinical trials. The trials excluded patients with dysthyroid optic neuropathy (DON). Recently, many case reports and case series have reported the successful use of teprotumumab to treat DON. Here, we review the data from published cases and our clinical experience in treating patients having DON with teprotumumab.

Methods:
A literature search was conducted of patients with DON treated with teprotumumab from January 2020 through September 2022. Data from DON patients from the authors' (M.A.T. and C.A.B.) clinical practice were included. Primary outcome measure was mean (SD) improvements for visual acuity, color vision, and visual fields. Improvements in proptosis and clinical activity score (CAS) and diplopia were compared before and after teprotumumab administration.

Results:
Ten observational studies/case reports were identified along with 2 patients in our practice. In all, there were 24 active TED patients with DON (37 eyes) who were treated with teprotumumab. Mean (SD) age was 66.5 (13.6) years and 13 (54%) were females, disease duration ranged from 2 months to >15 years. 22/24 patients had none, minimal improvement or progression of visual loss with intravenous/oral corticosteroids, orbital decompression (n = 9), and orbital radiation (n = 2). There were 2 patients who received teprotumumab as the only therapy. Overall, 88% (21/24) reported improvement in visual acuity after teprotumumab and in 75% (18/24), improvement in vision was observed after just 2 infusions of teprotumumab. Three eyes had decompression surgery in close proximity to teprotumumab infusions and were excluded from analyses. Mean (SD) improvement in visual acuity was 3.73 lines (SD 3.74), range 2–15 lines in 33 eyes. The mean (SD) improvement in the mean deviation on visual field testing in 15 eyes was 5.6 db (3.0 db). Mean (SD) improvement in proptosis was 4.37 mm (SD: 2.11) (20 patients, 32 eyes); and clinical activity score: mean reduction of 5.1 (1.3) for 18 patients. Teprotumumab was well tolerated in all but one patient. Adverse events reported included fatigue, dysgeusia, hearing loss, nausea, hyperglycemia, and muscle spasms.

Conclusions:
Teprotumumab is an effective treatment for DON in our experience and in published cases in whom treatment with steroids, surgery, or orbital radiation was unsuccessful.
Transcriptome-based host epistasis and pathogen co-expression in barley-powdery mildew interactions
Authors: Velásquez-Zapata Valeria , Smith Schuyler , Surana Priyanka , Chapman Antony V.E. , Wise Roger P. 
Published: September 2023

ABSTRACTMildew locus a (Mla) from the Triticeae grain crop barley (Hordeum vulgareL.) encodes a multi-allelic series of nucleotide-binding leucine-rich repeat (NLR) immune receptors. These variable NLRs recognize complementary secreted effectors from the powdery mildew fungus,Blumeria hordei(Bh), to block disease progression. We used a dynamic time-course transcriptome of barley infected withBhto infer gene effects and epistatic relationships governed by theMla6NLR, two other host loci critical to the interaction,Blufensin1(Bln1) andRequired for Mla6 resistance3 (Rar3),and genes that interact with them.Bln1is anR-gene independent regulator of immunity and the resistantbln1mutant exhibits enhanced basal defense to compatibleBh.Rar3is required for MLA6-mediated generation of H2O2and the hypersensitive reaction; therar3mutant contains an in-frame Lys-Leu deletion in the SGT1-specific domain that compromises immunity by a subset ofMlaalleles. Interactions ofMla6andBln1resulted in symmetric, suppression and masked epistasis on theBh-induced barley transcriptome. Likewise, dominant or equal effects were caused byMla6andSgt1.Of a total of 468 barley NLRs, 366 were expressed in our dataset and 115 of those were grouped under different gene effect models, which localized to several chromosome hotspots. The correspondingBhinfection transcriptome was classified into nine co-expressed modules, linking differential expression with pathogen development. Expression of most of 517Bheffectors exhibited dependence on disease phenotype and was associated with appressorial or haustorial structures, suggesting that disease is regulated by a host-pathogen intercommunication network that diversifies the response.
Geranylgeranyl pyrophosphate (GGPP) is associated with hepatic lipid accumulation and insulin resistance in MAO by prenylating Perilipin4
Authors: Zhao Yue , Jiang Shan , Nie Hong-Yu , Zhao Meng-Fei , Sun Peng , Zhang Jing-Zi , Wang Xiao-Chen , Tang Yi-Ping , Yuan Xian-Wen , Sun Xi-Tai , Shan Xiao-Dong , He Jian , Liu Jiang-Huai , Bi Yan , Fang Lei , Han Xiao , Li Chao-Jun 
Published: September 2023

SUMMARYMetabolically Abnormal Obesity (MAO) is characterized by hepatic steatosis and type 2 diabetes (T2D), in contrast to Metabolically Healthy Obesity (MHO). In this study, we investigated the role of hepatic geranylgeranyl pyrophosphate (GGPP), a metabolite of the mevalonate (MVA) pathway, in regulating the differences in lipid metabolism between MAO and MHO. Our findings revealed that GGPP levels were significantly elevated in individuals with MAO, and deficiency of GGPP in the liver ameliorated the defects associated with MAO. Furthermore, we discovered that the prenylation of the lipid droplet-associated protein Perilipin 4 by GGPP enhances the formation of large lipid droplets, thereby exacerbating hepatic lipid accumulation and insulin resistance. Notably, the inhibitor DGBP, targeting the GGPP synthase Ggpps, effectively attenuated the traits of MAO, offering novel insights into the treatment of this condition.
Trial-to-trial similarity and distinctness of muscle synergy activation coefficients increases during learning and with a higher level of movement proficiency
Authors: Kaufmann Paul , Koller Willi , Wallnöfer Elias , Goncalves Basilio , Baca Arnold , Kainz Hans 
Published: September 2023

AbstractMuscle synergy analyses are used to increase our understanding of motor control. Spatially fixed synergy vectors coordinate multiple co-active muscles through activation commands, known as activation coefficients. To better understand motor learning, it is crucial to know how synergy recruitment varies during a learning task and different levels of movement proficiency. Within one session participants walked on a line, a beam, and learned to walk on a tightrope – tasks that represent different levels of proficiency. Muscle synergies were extracted over all conditions and the number of synergies was determined through the knee-point of the total variance accounted for (tVAF) curve. We found that the tVAF of one synergy decreased with task proficiency (line < beam < tightrope). Additionally, trial-to-trial similarity and distinctness of synergy activation coefficients increased with proficiency and after a learning process. We conclude that precise adjustment and refinement of synergy activation coefficients play a crucial role in motor learning.
HybridMimulusflowers attract a new pollinator
Authors: Peng Foen , Sun Xiaohe , van Vloten Claudia , Correll Jude , Langdon Marlena , Ngochanthra Weerin , Johnson Karl , Kane Suzanne Amador 
Published: September 2023

AbstractHybridization is common in flowering plants and is believed to be an important force driving adaptation and speciation. The hybrid flowers often have new trait combinations, which, theoretically, could attract new pollinators. In this study, we found that the hybrids between a hummingbird-pollinated speciesMimulus cardinalisand a self-pollinated speciesMimulus parishiiattract bumblebees (Bombus impatiens), a pollinator not attracted to either of the progenitor species. This novel attraction is explained by several floral traits in hybrids, including petal color, nectar concentration, and corolla size. We also found that theYUPlocus, previously shown to be important in bee attraction in otherMimulusspecies, also played an important role in this novel attraction. Hybrid plants’ attraction to new pollinators could be an underexplored avenue for pollinator shift and speciation.