bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment and validation of a multigene model to predict the risk of relapse in hormone receptor-positive early-stage Chinese breast cancer patients
Authors: Liu Jiaxiang , Zhao Shuangtao , Yang Chenxuan , Ma Li , Wu Qixi , Meng Xiangzhi , Zheng Bo , Guo Changyuan , Feng Kexin , Shang Qingyao , Liu Jiaqi , Wang Jie , Zhang Jingbo , Shan Guangyu , Xu Bing , Liu Yueping , Ying Jianming , Wang Xin , Wang Xiang 
Published: March 2023

Abstract

Background:
Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery.

Methods:
In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan–Meier analysis, receiver operating characteristic curve (ROC).

Results:
A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes (CKMT1B, SMR3B, and OR11M1P) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model.

Conclusions:
A multigene model was established from RNA-seq data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Low-Grade Hidradenocarcinoma of the Foot With Metastasis to a Lymph Node
Authors: Roman Jorge , Chung Catherine G. , Sangueza Martin , Plaza Jose A. 
Published: March 2023

Abstract:
Hidradenocarcinoma (HAC) is a rare adnexal tumor associated with the potential for locoregional recurrence and systemic metastasis. The clinical appearance of HAC is nonspecific, frequently presenting as a solitary firm subcutaneous nodule or plaque on the head and neck region or distal extremities. These tumors show histomorphologic heterogeneity, as they can be low and high grade. Distinguishing HAC from hidradenoma, especially the low-grade variant of HAC, can be challenging as both tumors can show histologic overlapping features. In this article, we describe a case of a 33-year-old patient presenting with a low-grade HAC of the plantar foot who was subsequently found to have lymph node metastasis.
A Quest for Better Strategy in Pediatric Intraosseous Placement Using Radiographic Measurements in Patients Younger Than 2 Years
Authors: Chung SunHee , Phelps Andrew , Chan Daniela K. I. 
Published: March 2023

Abstract
Intraosseous (IO) needles are used to obtain vascular access in pediatric patients during emergent situations. Recent literature has raised concern about high rates of IO malposition in younger children. Despite the widespread use of IO access in the pediatric population, there is scarce evidence regarding the ideal needle length or optimal access site. This study uses a radiographic approach to determine the appropriate IO needle length and access site to minimize the risk of malposition in children younger than 2 years. Radiographs of the lower extremities were obtained from the electronic database from a single tertiary care center. Using lateral views, anteroposterior measurements were obtained at 2 axial planes, located 1 cm superior to distal femur physis and 1 cm inferior to distal tibia physis. Based on the measurements, we calculated the probable needle tip positions if the needle was placed to the hub at the skin level using the EZ-IO (Teleflex Ltd, Wayne, PA) preset needle sizes. For subjects younger than 6 months, the 25-mm needle minimized malposition in the femur site with a 45.7% appropriate position rate, and the 15-mm needle minimized malposition in the tibia site with a 57.1% appropriate position rate. For the older age groups, we did not find a standard needle that would consistently minimize malposition in the femur site. For the tibia site, the 25-mm needle minimized malposition risk, with appropriate position rates of 81.0%, 87.5%, and 91.1% in the 6- to 12-month, 13- to 18-month, and 19- to 24-month groups, respectively.
Optimizing Prepectoral Implant Placement and Concomitant Fat Grafting After Tissue Expansion
Authors: Girard Alisa O. , Lopez Christopher D. , Ambrosino Christina M. , Broderick Kristen P. 
Published: March 2023

BackgroundPrepectoral implant-based breast reconstruction is often supplemented by autologous fat grafting to optimize aesthetic outcomes. This usually entails several rounds of modest fat transfer to minimize risk of necrosis; however, the limits of fat grafting at expander exchange are not known.MethodsA single-institution retrospective review from July 2016 to February 2022 was performed of all patients who underwent (1) mastectomy, (2) prepectoral tissue expander placement, (3) expander exchange for implant, and (4) at least one round of autologous fat transfer. Studentttest and χ2test were used.ResultsA total of 82 breasts underwent a single round of fat grafting during implant placement (group 1); 75 breasts underwent fat grafting that occurred in multiple rounds and/or in delay to implant placement (group 2). Group 1 received more fat at the time of implant placement (100 mL; interquartile range, 55–140 mL;P< 0.001) and underwent fewer planned operative procedures compared with group 2 (1.0 vs 2.2,P< 0.001). Total fat volume in group 2 did not significantly exceed that of group 1 until after 3 rounds of fat transfer (128.5 mL; interquartile range, 90–130 mL;P< 0.01). There was no difference in the rate of fat necrosis between groups after the first round (15.9% vs 9.3%,P= 0.2) and final round (15.9% vs 12.0%,P= 0.5) of fat grafting. Complication rates were similar between groups (3.7% vs 8.0%,P= 0.2).ConclusionsA 2-stage approach of prepectoral tissue expander placement with single round of larger volume fat transfer at expander exchange reduces overall number of operative procedures without increased risks.
A Pilot Study Comparing Sensation in Buried Versus Nonburied Deep Inferior Epigastric Perforator Flaps
Authors: Lu Wang Marcos , Qin Nancy , Chadab Tara M. , Chen Yunchan , Huang Hao , Ellison Angela , Otterburn David M. 
Published: March 2023

Background
Neurotized deep inferior epigastic perforator (DIEP) flaps have been shown to improve sensory recovery after mastectomy and reconstruction. With the recent trend toward nipple-sparing mastectomies, sensation likely originates within the buried DIEP flap and then innervates the breast skin. In contrast, for patients undergoing skin-sparing mastectomies, the DIEP flap skin is preserved, brought up to the surface, and directly innervated. In this study, we aim to evaluate inner breast region sensation between patients whose DIEP flap is buried and whose DIEP flap skin is brought to the surface.

Methods
Seventy patients who underwent mastectomy with immediate reconstruction using the DIEP flap were prospectively identified. Of these, 60 patients underwent nipple-sparing mastectomy with buried DIEP flap reconstruction while 10 patients underwent skin-sparing mastectomy with nonburied DIEP flap reconstruction. Patients in both cohorts received nerve grafting using the 70 × 1–2-mm Avance Nerve Graft in identical fashion. Sensitivity evaluation was performed in five inner breast regions (corresponding to the nonburied DIEP flap area).

Results
In the buried DIEP cohort, at 6 months postoperatively, there was a statistically significant difference in inner breast region sensitivity measurements compared with baseline levels (P < 0.001). In contrast, in the nonburied DIEP cohort, at 6 months postoperatively, sensation in the inner breast region was comparable with preoperative baseline levels (P = 0.236). At 24 months postoperatively, inner breast region sensitivity measurements in both cohorts were comparable with preoperative baseline measurements (P > 0.05).

Conclusions
Neurotized DIEP flap skin raised directly to the surface confers earlier sensory recovery than buried DIEP flaps. In patients who undergo skin-sparing mastectomies with nonburied DIEP flap reconstruction, they can expect significantly better sensation in the inner regions of the breast at 6 months postoperatively. In patients who undergo nipple-sparing mastectomies with buried DIEP flap reconstruction, they can expect sensation in the inner breast to return to preoperative baseline levels at a later time point—beginning as early as 24 months postoperatively.
Redefining Multimorbidity in Older Surgical Patients
Authors: Ramadan Omar I , Rosenbaum Paul R , Reiter Joseph G , Jain Siddharth , Hill Alexander S , Hashemi Sean , Kelz Rachel R , Fleisher Lee A , Silber Jeffrey H 
Published: March 2023

Background:
Multimorbidity in surgery is common and associated with worse postoperative outcomes. However, conventional multimorbidity definitions (≥2 comorbidities) label the vast majority of older patients as multimorbid, limiting clinical usefulness. We sought to develop and validate better surgical specialty-specific multimorbidity definitions based on distinct comorbidity combinations.

Study Design:
We used Medicare claims for patients aged 66-90 undergoing inpatient general, orthopaedic, or vascular surgery. Using 2016-2017 data, we identified all comorbidity combinations associated with at least 2-fold (general/orthopaedic) or 1.5-fold (vascular) greater risk of 30-day mortality compared to the overall population undergoing the same procedure; we called these Qualifying Comorbidity Sets. We applied these to 2018-2019 data (general=230,410 patients, orthopaedic=778,131, vascular=146,570) to obtain 30-day mortality estimates. For further validation, we tested whether multimorbidity status was associated with differential outcomes for patients at better-resourced (based on nursing skill-mix, surgical volume, teaching status) versus all other hospitals using multivariate matching.

Results:
Compared to conventional multimorbidity definitions, the new definitions labeled far fewer patients as multimorbid: general=85.0% (conventional) versus 55.9% (new) (p<0.0001); orthopaedic=66.6% versus 40.2% (p<0.0001); vascular=96.2% versus 52.7% (p<0.0001). Thirty-day mortality was higher by the new definitions: general=3.96% (conventional) versus 5.64% (new) (p<0.0001); orthopaedic=1.13% versus 1.68% (p<0.0001); vascular=4.43% versus 7.00% (p<0.0001). Better-resourced hospitals offered significantly larger mortality benefits than all other hospitals for multimorbid versus non-multimorbid general and orthopaedic, but not vascular, patients (general surgery difference-in-differences=-0.94% [-1.36%,-0.52%], p<0.0001; orthopaedic=-0.20% [-0.34%,-0.05%], p=0.0087; vascular=-0.12% [-0.69%,0.45%], p=0.6795).

Conclusion:
Our new multimorbidity definitions identified far more specific, higher-risk pools of patients than conventional definitions, potentially aiding clinical decision-making.
Admission Thromboelastography at the Intersection of Traumatic Coagulopathy and Inflammation: A Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) Study Sub-Analysis
Authors: Savage Stephanie A , Zarzaur Ben L , Fox Erin E , Wade Charles E , Carney Patrick R , Do Trieu V , Holcomb John B 
Published: March 2023

Background:
Acute traumatic coagulopathy (ATC) has many phenotypes and varying morbidity and mortality. The MA-R ratio, calculated from the admission thromboelastogram (TEG), serves as a biomarker to identify one phenotype of ATC and has previously been associated with significant derangements in the inflammatory response. This study evaluates outcomes related to abnormal MA-R ratios, including inflammatory responses, in a heterogeneous patient population.

Study Design:
Patients from the PROPPR dataset were included. The MA-R ratio was calculated from admission thromboelastography, with a CRITICAL ratio was defined as ≤11. Key inflammatory mediators were identified as a priori. Cytokine expression was assessed over 24 hours using multivariable logistic regression.

Results:
Significant elevations in the pro-inflammatory cytokines IL-1b, IL6, and IL 8, as well as in the chemokines eotaxin, IP-10, MCP-1 and MIP-1β persisted over the first 24 hours. CRITICAL patients had significantly lower survival at 1, 3, 6, 12 and 18 hours and demonstrated significantly increased Acute Respiratory Distress Syndrome (ARDS) (1.817 (95% CI 1.082,3.051), p=0.0239). CRITICAL patients had fewer ICU-free (CRITICAL 10 days (IQR 0, 25) v. NORMAL 22 days (4, 26), p <0.0001) and fewer ventilator-free days (CRITICAL 15 (IQR 0, 28) v. NORMAL 26 (9, 28), p < 0.0001). CRITICAL patients were protected against Systemic Inflammatory Response (0.521 (95% CI 0.322, 0.816), p=0.0044).

Conclusions:
The subtype of ATC identified by the low MA-R ratio is associated with significant elevations in multiple pro-inflammatory cytokines at admission. Early mortality remains elevated in the CRITICAL group, in part due to coagulopathy. The MA-R ratio at admission is associated with a particularly morbid type of coagulopathy, associated with significant alterations in the inflammatory response following severe injury in heterogeneous patient populations.
Differential expression of fibroblast activation protein-alpha and lysyl oxidase in subtypes of ameloblastoma
Authors: Vangansewinkel Tim , Driesen Ronald , Olubanwo Agbaje Jimoh , Gervois Pascal , Olumuyiwa Adisa Akinyele , Adenike Olusanya Adeola , Tunde Arotiba Juwon , Wolfs Esther , Lambrichts Ivo , Politis Constantinus 
Published: March 2023

AbstractAmeloblastomas are benign, mostly intra-osseous, tumours originating from ectodermal odontogenic epithelium and display extracellular matrix remodelling. We determined whether fibroblast activation protein-alpha (FAP-α), a collagenolytic enzyme and lysyl oxidase (LOX), a collagen cross-linker were differentially regulated in ameloblastoma subtypes. Masson’s trichrome staining and immunohistochemistry were performed on human samples from gross mandibular or maxillary ameloblastoma. Co-localization studies in tumorigenic tissue of follicular, plexiform and desmoplastic ameloblastoma showed absence of the mesenchymal cell marker vimentin but high epithelial cell adhesion molecule (EPCAM) expression, an epithelial marker. Strong FAP-α staining was also noted, however, the stellate reticulum of plexiform ameloblastoma contained a higher number of FAP-α positive cells than the follicular subtype. Weak LOX staining was demonstrated in tumorigenic tissue of the follicular subtype but profound reactivity was observed in stromal plexiform and tumorigenic desmoplastic tissue. The desmoplastic staining profile for FAP-α and LOX shared resemblance with the unicystic subtypes. Tumorigenic outgrowths in desmoplastic ameloblastoma were associated with vimentin positive and EPCAM negative cancer-associated fibroblasts suggesting a role in tumour invasion. In conclusion, FAP-α expression in ameloblastoma seems to be involved in tumour growth and invasion whereas LOX expression is differentially regulated in ameloblastoma subtypes offering a new perspective for understanding specific growth patterns of ameloblastoma subtypes.
“Whenever I tell her to wear slippers, she turns a deaf ear. She never listens”: a qualitative descriptive research on the barriers to basic lymphedema management and quality of life in lymphatic filariasis patients in a rural block of eastern India
Authors: Kumar Pragya , Ahmad Shamshad , Bhar Ditipriya , Roy Ria , Singh Bhavna 
Published: March 2023

AbstractBackgroundChronic lymphatic filariasis cases in Bihar, India, need management of lymphedema to live a life free of disability. For patients who have recurrent attacks of acute dermato-lymphangio-adenitis (ADLA), WHO has recommended simple home-based measures that include maintaining hygiene, skin care, and limb movement. But patients in rural areas are unable to adopt them, resulting in a vicious cycle of ADLA attacks. So there might be multiple realities from patients’ and healthcare workers’ perspectives that are unexplored. A qualitative research was deemed best suitable to identify the barriers to practising home-based lymphedema practices that are adversely affecting quality of life.MethodsThe qualitative descriptive study was conducted in two villages in the rural field practice area under a tertiary care hospital in Bihar. Researchers purposively selected ten participants, including patients affected by lymphedema, their caregivers, the grassroots healthcare workers, and the block health manager. In-depth interviews were conducted using a semi-structured interview guide. Data was entered into QDA Miner Lite, where researchers did attribute, in-vivo, process, descriptive, emotion, and holistic coding, followed by content analysis, where categories and themes emerged from the codes.ResultsThree themes emerged: the inherent nature of disease, patient related factors, and healthcare system related factors. Besides low awareness and adherence, low health-seeking behaviour and poor personal hygiene, categories like signs and symptoms, seasonal factors, hampered activities of daily living, hopelessness from not getting cured, psychosocial difficulty, lack of capacity building and receipt of incentives by healthcare workers, unavailability of lab diagnosis and management of complications at the facility, inconsistent drug supply, and no financial assistance were the identified barriers.ConclusionsAccessibility to WaSH, regular training of home-based care, increasing the capacity and motivation of grassroots workers, and the generation of in-depth awareness among the patients are required to achieve the elimination of filariasis, with MMDP as a key component of that strategy for endemic districts across the whole country.
Dynamic phosphatase-recruitment controls B-cell selection and oncogenic signaling
Authors: Lee Jaewoong , Robinson Mark E. , Sun Ruifeng , Kume Kohei , Ma Ning , Cosgun Kadriye Nehir , Chan Lai N. , Leveille Etienne , Geng Huimin , Vykunta Vivasvan S. , Shy Brian R. , Marson Alexander , Katz Samuel , Chen Jianjun , Paietta Elisabeth , Meffre Eric , Vaidehi Nagarajan , Müschen Markus 
Published: March 2023

Initiation of B-cell receptor (BCR)1signaling, and subsequent antigen-encounter in germinal centers2,3represent milestones of B-lymphocyte development that are both marked by sharp increases of CD25 surface-expression. Oncogenic signaling in B-cell leukemia (B-ALL)4and lymphoma5also induced CD25-surface expression. While CD25 is known as an IL2-receptor chain on T- and NK-cells6–9, the significance of its expression on B-cells was unclear. Our experiments based on genetic mouse models and engineered patient-derived xenografts revealed that, rather than functioning as an IL2-receptor chain, CD25 expressed on B-cells assembled an inhibitory complex including PKCδ and SHIP1 and SHP1 phosphatases for feedback control of BCR-signaling or its oncogenic mimics.Recapitulating phenotypes of genetic ablation of PKCδ10–12, SHIP113,14and SHP114, 15,16, conditional CD25-deletion decimated early B-cell subsets but expanded mature B-cell populations and induced autoimmunity. In B-cell malignancies arising from early (B-ALL) and late (lymphoma) stages of B-cell development, CD25-loss induced cell death in the former and accelerated proliferation in the latter. Clinical outcome annotations mirrored opposite effects of CD25-deletion: high CD25 expression levels predicted poor clinical outcomes for patients with B-ALL, in contrast to favorable outcomes for lymphoma-patients. Biochemical and interactome studies revealed a critical role of CD25 in BCR-feedback regulation: BCR-signaling induced PKCδ-mediated phosphorylation of CD25 on its cytoplasmic tail (S268). Genetic rescue experiments identified CD25-S268tail-phosphorylation as central structural requirement to recruit SHIP1 and SHP1 phosphatases to curb BCR-signaling. A single point mutation CD25S268Aabolished recruitment and activation of SHIP1 and SHP1 to limit duration and strength of BCR-signaling. Loss of phosphatase-function, autonomous BCR-signaling and Ca2+-oscillations induced anergy and negative selection during early B-cell development, as opposed to excessive proliferation and autoantibody production in mature B-cells. These findings highlight the previously unrecognized role of CD25 in assembling inhibitory phosphatases to control oncogenic signaling in B-cell malignancies and negative selection to prevent autoimmune disease.