bluuebunny/crossref_metadata_2025_split huggingface dataset:
DeepST: identifying spatial domains in spatial transcriptomics by deep learning
Authors: Xu Chang , Jin Xiyun , Wei Songren , Wang Pingping , Luo Meng , Xu Zhaochun , Yang Wenyi , Cai Yideng , Xiao Lixing , Lin Xiaoyu , Liu Hongxin , Cheng Rui , Pang Fenglan , Chen Rui , Su Xi , Hu Ying , Wang Guohua , Jiang Qinghua 
Published: October 2022

Abstract
Recent advances in spatial transcriptomics (ST) have brought unprecedented opportunities to understand tissue organization and function in spatial context. However, it is still challenging to precisely dissect spatial domains with similar gene expression and histology in situ. Here, we present DeepST, an accurate and universal deep learning framework to identify spatial domains, which performs better than the existing state-of-the-art methods on benchmarking datasets of the human dorsolateral prefrontal cortex. Further testing on a breast cancer ST dataset, we showed that DeepST can dissect spatial domains in cancer tissue at a finer scale. Moreover, DeepST can achieve not only effective batch integration of ST data generated from multiple batches or different technologies, but also expandable capabilities for processing other spatial omics data. Together, our results demonstrate that DeepST has the exceptional capacity for identifying spatial domains, making it a desirable tool to gain novel insights from ST studies.
The Cancer Epitope Database and Analysis Resource (CEDAR)
Authors: Koşaloğlu-Yalçın Zeynep , Blazeska Nina , Vita Randi , Carter Hannah , Nielsen Morten , Schoenberger Stephen , Sette Alessandro , Peters Bjoern 
Published: October 2022

Abstract
We established The Cancer Epitope Database and Analysis Resource (CEDAR) to catalog all epitope data in the context of cancer. The specific molecular targets of adaptive T cell and B cell immune responses are referred to as epitopes. Epitopes derived from cancer antigens are of high relevance as they are recognized by anti-cancer immune cells. Detailed knowledge of the molecular characteristic of cancer epitopes and associated metadata is relevant to understanding and planning prophylactic and therapeutic applications and accurately characterizing naturally occurring immune responses and cancer immunopathology. CEDAR provides a freely accessible, comprehensive collection of cancer epitope and receptor data curated from the literature and serves as a companion site to the Immune Epitope Database (IEDB), which is focused on infectious, autoimmune, and allergic diseases. CEDAR is freely accessible at https://cedar.iedb.org/.
The limits of molecular signatures for pancreatic ductal adenocarcinoma subtyping
Authors: Lautizi Manuela , Baumbach Jan , Weichert Wilko , Steiger Katja , List Markus , Pfarr Nicole , Kacprowski Tim 
Published: October 2022

Abstract
Molecular signatures have been suggested as biomarkers to classify pancreatic ductal adenocarcinoma (PDAC) into two, three, four or five subtypes. Since the robustness of existing signatures is controversial, we performed a systematic evaluation of four established signatures for PDAC stratification across nine publicly available datasets. Clustering revealed inconsistency of subtypes across independent datasets and in some cases a different number of PDAC subgroups than in the original study, casting doubt on the actual number of existing subtypes. Next, we built sixteen classification models to investigate the ability of the signatures for tumor subtype prediction. The overall classification performance ranged from ∼35% to ∼90% accuracy, suggesting instability of the signatures. Notably, permuted subtypes and random gene sets achieved very similar performance. Cellular decomposition and functional pathway enrichment analysis revealed strong tissue-specificity of the predicted classes. Our study highlights severe limitations and inconsistencies that can be attributed to technical biases in sample preparation and tumor purity, suggesting that PDAC molecular signatures do not generalize across datasets. How stromal heterogeneity and immune compartment interplay in the diverging development of PDAC is still unclear. Therefore, a more mechanistic or a cross-platform multi-omic approach seems necessary to extract more robust and clinically exploitable insights.
Investigation of a Prolonged and Large Outbreak of Healthcare-Associated Mucormycosis Cases in an Acute Care Hospital—Arkansas, June 2019–May 2021
Authors: Jordan Alexander , James Allison E , Gold Jeremy A W , Wu Karen , Glowicz Janet , Wolfe Frankie , Vyas Keyur , Litvintseva Anastasia , Gade Lalitha , Liverett Hazel , Alverson Mary , Burgess Mary , Wilson Amy , Li Ruoran , Benowitz Isaac , Gulley Trent , Patil Naveen , Chakravorty Rohan , Chu Winston , Kothari Atul , Jackson Brendan R , Garner Kelley , Toda Mitsuru 
Published: October 2022

Abstract

Background
Outbreaks of healthcare-associated mucormycosis (HCM), a life-threatening fungal infection, have been attributed to multiple sources, including contaminated healthcare linens. In 2020, staff at Hospital A in Arkansas alerted public health officials of a potential HCM outbreak.

Methods
We collected data on patients at Hospital A who had invasive mucormycosis during January 2017–June 2021 and calculated annual incidence of HCM (defined as mucormycosis diagnosed within ≥7 days after hospital admission). We performed targeted environmental assessments, including linen sampling at the hospital, to identify potential sources of infection.

Results
During the outbreak period (June 2019–June 2021), 16 patients had HCM; clinical features were similar between HCM patients and non-HCM patients. Hospital-wide HCM incidence (per 100 000 patient-days) increased from 0 in 2018 to 3 in 2019 and 6 in 2020. For the 16 HCM patients, the most common underlying medical conditions were hematologic malignancy (56%) and recent traumatic injury (38%); 38% of HCM patients died in-hospital. Healthcare-associated mucormycosis cases were not epidemiologically linked by common procedures, products, units, or rooms. At Hospital A and its contracted offsite laundry provider, suboptimal handling of laundered linens and inadequate environmental controls to prevent mucormycete contamination were observed. We detected Rhizopus on 9 (9%) of 98 linens sampled at the hospital, including on linens that had just arrived from the laundry facility.

Conclusions
We describe the largest, single-center, HCM outbreak reported to date. Our findings underscore the importance of hospital-based monitoring for HCM and increased attention to the safe handling of laundered linens.
A Multicenter Comparison of Prevalence and Predictors of Antimicrobial Resistance in Hospitalized Patients Before and During the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic
Authors: Bauer Karri A , Puzniak Laura A , Yu Kalvin C , Klinker Kenneth P , Watts Janet A , Moise Pamela A , Finelli Lyn , Ai ChinEn , Gupta Vikas 
Published: October 2022

Abstract

Background
Antibacterial therapy is frequently used in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without evidence of bacterial infection, prompting concerns about increased antimicrobial resistance (AMR). We evaluated trends in AMR before and during the SARS-CoV-2 pandemic.

Methods
This multicenter, retrospective cohort analysis included hospitalized adults aged ≥18 years with &gt;1-day inpatient admission and a record of discharge or death from 271 US facilities in the BD Insights Research Database. We evaluated rates of AMR events, defined as positive cultures for select gram-negative and gram-positive pathogens from any source, with nonsusceptibility reported by commercial panels before (1 July 2019–29 February 2020) and during (1 March 2020–30 October 2021) the SARS-CoV-2 pandemic.

Results
Of 5 518 666 admissions evaluated, AMR rates per 1000 admissions were 35.4 for the prepandemic period and 34.7 for the pandemic period (P ≤ .0001). In the pandemic period, AMR rates per 1000 admissions were 49.2 for SARS-CoV-2–positive admissions, 41.1 for SARS-CoV-2–negative admissions, and 25.7 for patients untested (P ≤ .0001). AMR rates per 1000 admissions among community-onset infections during the pandemic were lower versus prepandemic levels (26.1 vs 27.6; P &lt; .0001), whereas AMR rates for hospital-onset infections were higher (8.6 vs 7.7; P &lt; .0001), driven largely by SARS-CoV-2–positive admissions (21.8). AMR rates were associated with overall antimicrobial use, rates of positive cultures, and higher use of inadequate empiric therapy.

Conclusions
Although overall AMR rates did not substantially increase from prepandemic levels, patients tested for SARS-CoV-2 infection had a significantly higher rate of AMR and hospital-onset infections. Antimicrobial and diagnostic stewardship is key to identifying this high-risk AMR population.
Effect of Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Booster on Human Immunodeficiency Virus Reservoirs and Immune Markers
Authors: Rai M Ali , Shi Victoria , Kennedy Brooke D , Justement Jesse S , Gittens Kathleen , McCormack Genevieve , Blazkova Jana , Moir Susan , Chun Tae-Wook 
Published: October 2022

Abstract
We investigated effects of the severe acute respiratory syndrome coronavirus 2 (SARV-CoV-2) booster vaccination on human immunodeficiency virus (HIV) reservoir size, immune markers, and host immune responses in people with HIV receiving antiretroviral therapy. Our data suggest that the SARS-CoV-2 booster vaccine is not likely to replenish the persistent HIV reservoir nor provide an immunologic environment to facilitate active HIV expression/replication.
Auxin-Induced WUSCHEL-RELATED HOMEOBOX13 Mediates Asymmetric Activity of Callus Formation upon Cutting
Authors: Tanaka Hayato , Hashimoto Naoki , Kawai Satomi , Yumoto Emi , Shibata Kyomi , Tameshige Toshiaki , Yamamoto Yuma , Sugimoto Keiko , Asahina Masashi , Ikeuchi Momoko 
Published: October 2022

AbstractPlants have the regenerative ability to reconnect cut organs, which is physiologically important to survive severe tissue damage. The ability to reconnect organs is utilized as grafting to combine two different individuals. Callus formation at the graft junction facilitates organ attachment and vascular reconnection. While it is well documented that local wounding signals provoke callus formation, how callus formation is differentially regulated at each cut end remains elusive. Here, we report that callus formation activity is asymmetrical between the top and bottom cut ends and is regulated by differential auxin accumulation. Gene expression analyses revealed that cellular auxin response is preferentially upregulated in the top part of the graft. Disruption of polar auxin transport inhibited callus formation from the top, while external application of auxin was sufficient to induce callus formation from the bottom, suggesting that asymmetric auxin accumulation is responsible for active callus formation from the top end. We further found that the expression of a key regulator of callus formation, WUSCHEL-RELATED HOMEOBOX 13 (WOX13), is induced by auxin. The ectopic callus formation from the bottom end, which is triggered by locally supplemented auxin, requires WOX13 function, demonstrating that WOX13 plays a pivotal role in auxin-dependent callus formation. The asymmetric WOX13 expression is observed both in grafted petioles and incised inflorescence stems, underscoring the generality of our findings. We propose that efficient organ reconnection is achieved by a combination of local wounding stimuli and disrupted long-distance signaling.
Anti-transcription intermediary factor 1-gamma IgG2 isotype is associated with cancer in adult dermatomyositis: an ENMC multinational study
Authors: Cordel Nadège , Dechelotte Benoît , Jouen Fabienne , Lamb Janine A , Chinoy Hector , New Paul , Vencovsky Jiri , Mann Herman , Galindo-Feria Angeles S , Dani Lara , Selva-O’Callaghan Albert , Werth Victoria P , Ravishankar Adarsh , Landon-Cardinal Océane , Tressières Benoit , Boyer Olivier 
Published: October 2022

AbstractObjectiveTo assess the role of the anti-TIF1γ auto-antibody (aAb) IgG2 isotype as a biomarker of cancer in anti-TIF1γ aAb-positive adult DM.MethodsInternational multicentre retrospective study with the following inclusion criteria: (i) diagnosis of DM according to ENMC criteria; (ii) presence of anti-TIF1γ IgG aAb determined using an in-house addressable laser bead immunoassay (ALBIA) from cryopreserved serums sampled at time of DM diagnosis and (iii) available baseline characteristics and follow-up data until the occurrence of cancer and/or a minimum follow-up of 1 year for patients without known cancer at diagnosis. Detection and quantification of anti-TIF1γ IgG2 aAb was done using the in-house ALBIA. In addition, a recent ELISA commercial kit was used for anti-TIF1γ IgG aAb quantification.ResultsA total of 132 patients (mean age 55±15 years) of whom 72 (54.5%) had an associated cancer were analysed. The association between the presence of cancer and the presence of anti-TIF1γ IgG2 aAb was statistically significant (P = 0.026), with an OR of 2.26 (95% CI: 1.10, 4.76). Patients with cancer displayed significantly higher anti-TIF1γ IgG2 aAb ALBIA values with a median value of 1.15 AU/ml (IQR: 0.14–9.76) compared with 0.50 AU/ml (IQR: 0.14–1.46) for patients without cancer (P = 0.042). In addition, patients with cancer displayed significantly higher anti-TIF1γ IgG aAb ELISA values with a median value of 127.5 AU/ml (IQR: 81.5–139.6) compared with 93.0 AU/ml (IQR: 54.0–132.9) for patients without cancer (P = 0.004).ConclusionThese results suggest considering anti-TIF1γ IgG2 ALBIA and IgG ELISA values as biomarkers of cancer in anti-TIF1 γ aAb-positive adult DM.
Conifer water-use patterns across temporal and topographic gradients in the southern Sierra Nevada
Authors: Goodwin Marissa J , Kerhoulas Lucy P , Zald Harold S J , North Malcolm P , Hurteau Matthew D 
Published: October 2022

AbstractClimate change is increasing the severity and duration of drought events experienced by forest ecosystems. Because water is essential for tree physiological processes, the ability of trees to survive prolonged droughts will largely depend on whether they have access to reliable water sources. While many woody plant species exhibit the ability to shift water sources between different depths of soil and rock water in response to changes in climate and water availability, it is unclear if Sierra Nevada conifers exhibit this plasticity. Here we analysed the δ18O and δ13C values of annual tree rings to determine the water-use patterns of large Sierra Nevada conifers during the 2012–16 California drought and 4 years before this drought event (2004–07). We analysed four species (Pinus jeffreyi Grev. & Balf. (Jeffrey pine), Pinus lambertiana Dougl. (sugar pine), Abies concolor (Gord. & Glend.) Lindl. Ex Hilderbr (white fir) and Calocedrus decurrens (Torr.) Florin (incense-cedar)) across a range of topographic positions to investigate differences in water-use patterns by species and position on the landscape. We found no significant differences in δ18O and δ13C values for the pre-drought and drought periods. This stability in δ18O values suggests that trees did not shift their water-use patterns in response to the 2012–16 drought. We did find species-specific differences in water-use patterns, with incense-cedar exhibiting more depleted δ18O values than all other species. We also found trends that suggest the water source used by a tree may depend on topographic and growing environment attributes such as topographic wetness and the surrounding basal area. Overall, our results suggest that the water source used by trees varies by the species and topographic position, but that Sierra Nevada conifers do not switch their water-use patterns in response to the drought. This lack of plasticity could make Sierra Nevada conifers particularly vulnerable to drought mortality as their historically reliable water sources begin to dry out with climate change.
Legal Bans, Female Genital Cutting, and Education: Evidence from Senegal
Authors: García-Hombrados Jorge , Salgado Edgar 
Published: October 2022

Abstract
A law that banned the practice of female genital cutting (FGC) in Senegal in 1999 reduced its prevalence and increased educational investments in girls. These results are not driven by mechanisms like health, broader changes in empowerment, or child marriage. Suggestive evidence indicates that results could be driven by some parents of future brides reacting to the increase in the cost of FGC caused by the law by abandoning this practice and investing in their daughter’s education to compensate for smaller bride prices among uncut women.
Kif26b contributes to the progression of interstitial fibrosis via migration and myofibroblast differentiation in renal fibroblast
Authors: Yamamura Yuta , Iwata Yasunori , Furuichi Kengo , Kato Takahiro , Yamamoto Naoki , Horikoshi Keisuke , Ogura Hisayuki , Sato Koichi , Oshima Megumi , Nakagawa Shiori , Miyagawa Taro , Kitajima Shinji , Toyama Tadashi , Hara Akinori , Sakai Norihiko , Shimizu Miho , Horike Shinichi , Daikoku Takiko , Nishinakamura Ryuichi , Wada Takashi 
Published: October 2022

AbstractKinesin family member 26b (Kif26b) is essential for kidney development, and its deletion in mice leads to kidney agenesis. However, the roles of this gene in adult settings remain elusive. Thus, this study aims to investigate the role of Kif26b in the progression of renal fibrosis. A renal fibrosis model with adenine administration using Kif26b heterozygous mice and wild‐type mice was established. Renal fibrosis and the underlying mechanism were investigated. The underlying pathways and functions of Kif26b were evaluated in an in vitro model using primary renal fibroblasts. Kif26b heterozygous mice were protected from renal fibrosis with adenine administration. Renal expressions of connective tissue growth factor (CTGF) and myofibroblast accumulation were reduced in Kif26b heterozygous mice. The expression of nonmuscle myosin heavy chain II (NMHCII), which binds to the C‐terminus of Kif26b protein, was also suppressed in Kif26b heterozygous mice. The in vitro study revealed reduced expressions of CTGF, α‐smooth muscle actin, and myosin heavy chain 9 (Myh9) via transfection with siRNAs targeting Kif26b in renal fibroblasts (RFB). RFBs, which were transfected by the expression vector of Kif26b, demonstrated higher expressions of these genes than non‐transfected cells. Finally, Kif26b suppression and NMHCII blockage led to reduced abilities of migration and collagen gel contraction in renal fibroblasts. Taken together, Kif26b contributes to the progression of interstitial fibrosis via migration and myofibroblast differentiation through Myh9 in the renal fibrosis model. Blockage of this pathway at appropriate timing might be a therapeutic approach for renal fibrosis.
The “Kite-t-FAMMIF”: A Novel Technique for Reconstruction of Extensive Soft Palate Resection
Authors: Massarelli Olindo , Carnevale Claudio 
Published: October 2022

Summary:
Total soft palate reconstruction is a challenge for the head and neck surgeon. Velopharyngeal incompetence resulting from soft palate resection impairs both speech and swallowing and significantly affects the quality of life of the patients. Radial forearm free flap is the reconstructive technique most used worldwide, but it requires microsurgical skills, is associated with high donor site morbidity, and shrinks during the healing process, especially after adjuvant radiotherapy. We present a novel technique using a single “kite-shaped” tunnelized-facial artery myomucosal island flap (t-FAMMIF) and report very favorable functional outcomes. Three patients in whom a kite-shaped flap was used to reconstruct a total soft palate defect after squamous cell carcinoma resection were included. In two of them, the resection included both tonsils due to cancer spreading to the tonsillar fossae. The mucosal and muscular sides of a single t-FAMMIF flap were able to restore the oral and nasal lining of the palate, respectively, without the need to fold the flap. All patients were able to tolerate an oral soft diet 10 days after surgery. No complications were detected. A complete mucosalization on the nasal lining was observed by video-endoscopy 3 weeks after surgery. No case of shrinking of the flap was observed during the follow-up, and speech and swallowing functions were not impaired after complete wound healing. Kite-shaped t-FAMMIF represents an excellent and feasible reconstructive option for extensive postablative soft palate defects.
Trends in Fellowship Training across United States Plastic and Reconstructive Surgery Academic Faculty
Authors: Bovill John D. , Haffner Zoë K. , Huffman Samuel S. , Sayyed Adaah A. , Shan Holly D. , Abu El Hawa Areeg A. , Slamin Robert P. , Evans Karen K. , Song David H. 
Published: October 2022

Background:
Plastic and reconstructive surgery (PRS) academic positions are more coveted each year. We aim to determine the requirement of fellowship training before PRS academic appointments.

Methods:
PRS faculty at U.S. academic institutions associated with the American Society of Plastic Surgeons were identified. Outcomes studied included integrated versus independent training, fellowships, gender, academic title, years on faculty, and publications before current hire.

Results:
Of the 1052 PRS faculty identified, 646 were included across 41 states and the District of Columbia. Seventy-four percent were identified as men (n = 477), and 26.2% (n = 169) identified as women. Academic faculty were significantly more likely to have completed fellowship before hire than not (p<0.0001). An integrated route of training was associated with higher odds of fellowship completion before appointment (OR = 2.19, 95% CI: 1.49–3.22). Odds of fellowship completion was significantly greater among faculty who graduated 5–10 years ago (OR = 2.55, 95% CI: 1.48–4.41) and within the last 5 years (OR = 1.93, 95% CI: 1.18–3.17). Professors were less likely to have completed fellowship training before appointment compared with assistant professors (OR = 0.51, 95% CI: 0.33–0.80). Regarding gender, number of prior publications, or completion of another degree, no significant difference was found between fellowship- and non-fellowship-trained faculty.

Conclusions:
Although more plastic surgeons enter the field through a shortened integrated residency, the increasing demand for further subspecialization may cause significant challenges for upcoming graduates pursuing an academic appointment. Undergoing additional training considerably impacts social and financial decision-making early in surgical careers for newly graduated residents.