bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do Integrated Plastic Surgery Residency Program Websites and Instagram Accounts Address Diversity, Equity, and Inclusion?
Authors: Das Rishub K. , Drolet Brian C. 
Published: February 2023

Background:
An authentic, programmatic commitment to diversity, equity, and inclusion (DEI) in plastic surgery is necessary to attract and retain a diverse workforce. Plastic surgery residency program websites and social media accounts are important sources of information about program values and culture for applicants, especially with the shift to virtual recruitment. Therefore, we sought to evaluate whether integrated plastic surgery residency programs address DEI through content on their websites and Instagram accounts.

Methods:
Integrated plastic surgery residency programs were identified through the Accreditation Council for Graduate Medical Education in December 2021. We searched program websites and Instagram accounts for elements of DEI. We evaluated the impact of region, program director sex, and program director race on prevalence of DEI elements on websites using chi-squared tests.

Results:
A total of 82 integrated plastic surgery residency programs were identified. Overall, 40 (48%) program websites had at least one DEI element, and 10 (12.2%) were found to have 3 or more DEI elements. The number of DEI elements per program website did not vary by region, program director sex, and program director ethnicity. Among programs with Instagram accounts, 49 (65.3%) posted about women, 30 (40.0%) posted about racial/ethnic minority groups, and 25 (33.3%) posted about LGBTQ+ identities.

Conclusions:
Despite widely heralded DEI efforts in plastic surgery residency recruitment, relatively few programs address DEI online. Programs looking to recruit diverse applicants could benefit from increased DEI content on their websites and social media accounts.
Strengthening Association through Causal Inference
Authors: Lane Megan , Berlin Nicholas L. , Chung Kevin C. , Waljee Jennifer F. 
Published: February 2023

Summary
Understanding causal association and inference is critical to study health risks, treatment effectiveness, and the impact of healthcare interventions. Although defining causality has traditionally been limited to rigorous, experimental contexts, techniques to estimate causality from observational data are highly valuable for clinical questions in which randomization may not be feasible or appropriate. In this review, we highlight several methodological options to deduce causality from observational data, including regression discontinuity, interrupted time series, and difference-in-differences approaches. Understanding the potential applications, assumptions, and limitations of quasi-experimental methods for observational data can expand our interpretation of causal relationships for surgical conditions.
Making Headway in Surgical Education at Home and Abroad: Use of an Inexpensive, 3-D Learning Model to Improve Plastic Surgery Resident Confidence in Mohs Defect Assessment and Closure Planning.
Authors: Shaffrey Ellen C. , Grotting Ava G. , Michelotti Brett F. , Siebert John W. , Larson Jeffrey D. , Bentz Michael L. 
Published: February 2023

Background:
The development of simulation, particularly low-cost models, has become a focus of interest within plastic surgery education. Current simulators for Mohs reconstruction are either expensive or not reusable. 1–6 The authors hypothesize that using a Styrofoam head model during an interactive teaching session will positively impact plastic surgery trainee comfort in designing Mohs reconstructive options.

Methods:
A cohort of integrated plastic surgery residents at a single institution performed a pre-activity questionnaire to obtain baseline comfort in defect assessment and design for five Mohs defects. They subsequently underwent an interactive learning session and were instructed to design flaps on life-sized Styrofoam heads with feedback from the senior author. A post-activity questionnaire was completed to assess improvement in comfort in defect assessment and flap design. Three attending surgeons then compared trainee designs with the senior author’s design to assess accuracy. All surveys were based on a 5-point Likert scale.

Results:
When analyzing all defects, average post-activity scores increased by 0.63 (SD +/- 0.24) (p = 0.008). Junior residents (n=8) had a greater increase in average score responses (mean: 1.07, [0.5-1.75]) compared to senior residents (n=9) (mean: 0.27, [0-1]) (p<0.001). When assessed by senior level surgeons, senior residents had significantly greater accuracy in design for each defect (p<0.05), except cheek advancement flap (p=0.08).

Conclusions:
Participation in an interactive educational activity using a styrofoam head model demonstrated significant improvements in trainee assessment and design of reconstructive options for Mohs defects.
Computed Tomography–Based Radiomics Analysis for Prediction of Response to Neoadjuvant Chemotherapy in Breast Cancer Patients
Authors: Duan Yanli , Yang Guangjie , Miao Wenjie , Song Bingxue , Wang Yangyang , Yan Lei , Wu Fengyu , Zhang Ran , Mao Yan , Wang Zhenguang 
Published: February 2023

PurposePrevious studies have pointed out that magnetic resonance– and fluorodeoxyglucose positron emission tomography–based radiomics had a high predictive value for the response of the neoadjuvant chemotherapy (NAC) in breast cancer by respectively characterizing tumor heterogeneity of the relaxation time and the glucose metabolism. However, it is unclear whether computed tomography (CT)–based radiomics based on density heterogeneity can predict the response of NAC. This study aimed to develop and validate a CT-based radiomics nomogram to predict the response of NAC in breast cancer.MethodsA total of 162 breast cancer patients (110 in the training cohort and 52 in the validation cohort) who underwent CT scans before receiving NAC and had pathological response results were retrospectively enrolled. Grades 4 to 5 cases were classified as response to NAC. According to the Miller-Payne grading system, grades 1 to 3 cases were classified as nonresponse to NAC. Radiomics features were extracted, and the optimal radiomics features were obtained to construct a radiomics signature. Multivariate logistic regression was used to develop the clinical prediction model and the radiomics nomogram that incorporated clinical characteristics and radiomics score. We assessed the performance of different models, including calibration and clinical usefulness.ResultsEight optimal radiomics features were obtained. Human epidermal growth factor receptor 2 status and molecular subtype showed statistical differences between the response group and the nonresponse group. The radiomics nomogram had more favorable predictive efficacy than the clinical prediction model (areas under the curve, 0.82 vs 0.70 in the training cohort; 0.79 vs 0.71 in the validation cohort). The Delong test showed that there are statistical differences between the clinical prediction model and the radiomics nomogram (z= 2.811,P= 0.005 in the training cohort). The decision curve analysis showed that the radiomics nomogram had higher overall net benefit than the clinical prediction model.ConclusionThe radiomics nomogram based on CT radiomics signature and clinical characteristics has favorable predictive efficacy for the response of NAC in breast cancer.
Three-Dimensional Gradient-Echo–Based Amide Proton Transfer-Weighted Imaging of Brain Tumors: Comparison With Two-Dimensional Spin-Echo–Based Amide Proton Transfer-Weighted Imaging
Authors: Murayama Kazuhiro , Ohno Yoshiharu , Yui Masao , Yamamoto Kaori , Ikedo Masato , Ohba Shigeo , Hanamatsu Satomu , Iwase Akiyoshi , Ikeda Hirotaka , Hirose Yuichi , Toyama Hiroshi 
Published: February 2023

Objective
Although amide proton transfer–weighted (APTw) imaging is reported by 2-dimensional (2D) spin-echo–based sequencing, 3-dimensional (3D) APTw imaging can be obtained by gradient-echo–based sequencing. The purpose of this study was to compare the efficacy of APTw imaging between 2D and 3D imaging in patients with various brain tumors.

Methods
A total of 49 patients who had undergone 53 examinations [5 low-grade gliomas (LGG), 16 high-grade gliomas (HGG), 6 malignant lymphomas, 4 metastases, and 22 meningiomas] underwent APTw imaging using 2D and 3D sequences. The magnetization transfer ratio asymmetry (MTRasym) was assessed by means of region of interest measurements. Pearson correlation was performed to determine the relationship between MTRasym for the 2 methods, and Student's t test to compare MTRasym for LGG and HGG. The diagnostic accuracy to differentiate HGG from LGG of the 2 methods was compared by means of the McNemar test.

Results
Three-dimensional APTw imaging showed a significant correlation with 2D APTw imaging (r = 0.79, P < 0.0001). The limits of agreement between the 2 methods were −0.021 ± 1.42%. The MTRasym of HGG (2D: 1.97 ± 0.96, 3D: 2.11 ± 0.95) was significantly higher than those of LGG (2D: 0.46 ± 0.89%, P < 0.01; 3D: 0.15 ± 1.09%, P < 0.001). The diagnostic performance of the 2 methods to differentiate HGG from LGG was not significantly different (P = 1).

Conclusions
The potential capability of 3D APTw imaging is equal to or greater than that of 2D APTw imaging and is considered at least as valuable in patients with brain tumors.
Efficacy and Safety of Dl-3-n-Butylphthalide Combined With Human Urinary Kallidinogenase in the Treatment of Acute Ischemic Stroke
Authors: Zhang Yaqian , Zhou Feng , Li Huiqing , Lei Junjie , Mo Zhihuai , Li Guangrong , Wang Junfeng 
Published: February 2023

Objectives
Intravenous thrombolysis and mechanical endovascular thrombectomy are recommended for patients whose stroke onsets are within the first 6 hours; however, patients beyond this time window have very limited options. Dl-3-n-butylphthalide (NBP) and human urinary kallidinogenase (HUK) have shown potential clinical benefits in the treatment of acute ischemic stroke (AIS) patients. This research aims to investigate the efficacy and safety of NBP combined with HUK in the treatment of ischemic stroke patients.

Patients and Methods
We reviewed the 215 AIS patients registered in the database of the Fifth Affiliated Hospital of Sun Yat-sen University from April 2019 to October 2020. Among them, 65 patients received NBP sodium chloride injection treatment, 55 patients received HUK treatment, and 95 patients received NBP sodium chloride injection combined with HUK treatment. The recovery of neural function was evaluated by the National Institutes of Health Stroke Scale (NIHSS), and the recovery of daily function was evaluated by the modified Rankin Scale (mRS). The NIHSS and mRS scores after the 7-day treatment, 6-month independency rate (6-month mRS score ≤1), and related factors were compared among the 3 groups. The safety was monitored by recording adverse events.

Results
The NIHSS and mRS scores of 7-day and 6-month treatment in the NBP combined with HUK group were lower than the monotherapy (P < 0.05). In addition, the NBP combined with HUK treatment achieved an independency rate of 82.1%, whereas NBP and HUK treatments achieved only 53.8% and 63.6%, respectively (P < 0.001). Binary logistic regression showed that NBP combined with HUK therapy treatment could lead to a 5.28 times higher rate of patients' 6-month independency after AIS occurrence. No serious adverse events occurred in both the combined therapy and monotherapy.

Conclusions
Dl-3-n-butylphthalide combined with HUK is safe to treat AIS patients. It can significantly improve the neural function and the 6-month recovery of AIS patients.
Vascular endothelial growth factor-A is involved in intramuscular carrageenan-induced cutaneous mechanical hyperalgesia through the vascular endothelial growth factor-A receptor 1 and transient receptor potential vanilloid 1 pathways
Authors: Ueda Takashi , Watanabe Masaya , Miwa Youko , Shibata Yasuhiro , Kumamoto Natsuko , Ugawa Shinya 
Published: February 2023

Objectives
Vascular endothelial growth factor-A (VEGF-A) plays a leading role in angiogenesis and pain hypersensitivity in cancer and chronic pain. It is not only induced by ischemic conditions but is also highly correlated with proalgesic cytokines, both of which are prominent in inflammatory muscle pain. However, the molecular basis of the involvement of VEGF-A in muscle pain remains unknown.

Methods
In the present study, we performed behavioral and pharmacological analyses to determine the possible involvement of VEGF-A in the development of inflammatory muscle pain and the associated signal transduction pathway.

Results
Unilateral intramuscular injection of carrageenan, a classical model of inflammatory muscle pain, increased VEGF-A gene expression in the tissues surrounding the injection site. Intramuscular administration of recombinant VEGF-A165 on the same side induced cutaneous mechanical hyperalgesia during the acute and subacute phases. The application of a specific VEGFR1 antibody on the same side significantly reduced the mechanical hyperalgesia induced by carrageenan or VEGF-A165 injection, whereas both a VEGFR2-neutralizing antibody and a VEGFR2 antagonist showed limited effects. Local preinjection of capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist, also inhibited VEGF-A165-induced hyperalgesia. Finally, intramuscular VEGF-A165-induced mechanical hyperalgesia was not found in TRPV1 knockout mice during the subacute phase.

Conclusions
These findings suggest that inflammatory stimuli increase interstitial VEGF-A165, which in turn induces cutaneous mechanical pain via the VEGFR1-mediated TRPV1 nociceptive pathway during inflammatory muscle pain. VEGFR1 could be a novel therapeutic target for inflammation-induced muscle pain.
AMLs harboring DNMT3A-destabilizing variants show increased intratumor DNA methylation heterogeneity at bivalent chromatin domains
Authors: Lee Dohoon , Koo Bonil , Kim Seok-Hyun , Byun Jamin , Hong Junshik , Shin Dong-Yeop , Sun Choong-Hyun , Song Ji-Joon , Kim Jaesung , Jaiswal Siddhartha , Yoon Sung-Soo , Kim Sun , Koh Youngil 
Published: February 2023

ABSTRACTThe mechanistic link between the complex mutational landscape ofde novomethyltransferaseDNMT3Aand the pathology of acute myeloid leukemia (AML) has not been clearly elucidated so far. A recent discovery on the catalogue of DNMT3A-destabilizing mutations throughout theDNMT3Agene as well as the oligomerization-dependent catalytic property of DNMT3A prompted us to investigate the common effect of DNMT3A-destabilizing mutations (DNMT3AINS) on the genomewide methylation patterns of AML cells. In this study, we describe the characteristics ofDNMT3AINSAML methylomes through the comprehensive computational analyses on three independent AML cohorts. As a result, we show that methylomes ofDNMT3AINSAMLs are considerably different from those ofDNMT3AR882AMLs in that they exhibit both locally disordered DNA methylation states and increased across-cell DNA methylation heterogeneity in bivalent chromatin domains. This increased epigenetic heterogeneity was functionally associated with heterogeneous expression of membrane-associated factors shaping stem cell niche, implying the diversification of the modes of leukemic stem cell-niche interactions. We also present that the level of methylation disorder at bivalent domains predicts the response of AML cells to hypomethylating agents through cell line- and patient-level analyses, which supports that the survival of AML cells depends on stochastic DNA methylations at bivalent domains. Altogether, our work provides a novel mechanistic model suggesting the genomic origin of the aberrant epigenomic heterogeneity in disease conditions.
Pairtools: from sequencing data to chromosome contacts
Authors:   Open2C, Abdennur Nezar , Fudenberg Geoffrey , Flyamer Ilya M. , Galitsyna Aleksandra A. , Goloborodko Anton , Imakaev Maxim , Venev Sergey V. 
Published: February 2023

AbstractThe field of 3D genome organization produces large amounts of sequencing data from Hi-C and a rapidly-expanding set of other chromosome conformation protocols (3C+). Massive and heterogeneous 3C+ data require high-performance and flexible processing of sequenced reads into contact pairs. To meet these challenges, we presentpairtools– a flexible suite of tools for contact extraction from sequencing data.Pairtoolsprovides modular command-line interface (CLI) tools that can be flexibly chained into data processing pipelines.Pairtoolsprovides both crucial core tools as well as auxiliary tools for building feature-rich 3C+ pipelines, including contact pair manipulation, filtration, and quality control. Benchmarkingpairtoolsagainst popular 3C+ data pipelines shows advantages ofpairtoolsfor high-performance and flexible 3C+ analysis. Finally,pairtoolsprovides protocol-specific tools for multi-way contacts, haplotype-resolved contacts, and single-cell Hi-C. The combination of CLI tools and tight integration with Python data analysis libraries makespairtoolsa versatile foundation for a broad range of 3C+ pipelines.
Selection of a Promiscuous Minimalist cAMP Phosphodiesterase from a Library ofDe NovoDesigned Proteins
Authors: Schnettler J. David , Wang Michael S. , Gantz Maximilian , Karas Christina , Hollfelder Florian , Hecht Michael H. 
Published: February 2023

ABSTRACTThe ability of unevolved amino acid sequences to become biological catalysts was key to the emergence of life on Earth. However, billions of years of evolution separate complex modern enzymes from their simpler early ancestors. To study how unevolved sequences can develop new functions, we screened for enzymatic activity in a collection of > 1 million novel sequences based on ade novo4-helix bundle library of semi-random sequences. To mirror evolutionary selection for biological function, we screened the collection using ultrahigh-throughput droplet microfluidics to identify features that yield phosphoesterase activity. Characterization of active hits demonstrated that acquiring new function required a large jump in sequence space: screening enriched for truncations that removed > 40% of the protein chain and introduced a catalytically important cysteine. The truncated protein dimerized into a dynamic α-helical structure, consistent with the idea that gain of function was accompanied by an increase in structural dynamics relative to the parental 4-helix bundle. The purified protein catalyzes the hydrolysis of a range of phosphodiesters, with the greatest activity toward the biological second messenger cyclic AMP (cAMP). The novel cAMPase is a manganese-dependent metalloenzyme and catalyzes cAMP hydrolysis with a rate acceleration on the order of 109and catalytic proficiency on the order of 1014M−1, comparable to large enzymes shaped by billions of years of evolution. These findings suggest that fragmentation to modular primordial peptides can be a fertile avenue for introducing structural and functional diversity into proteins.GRAPHICAL ABSTRACT
Phyllotaxis as a dynamical system
Authors: Jean-Paul Walch 
Published: February 2023

AbstractOne of the major puzzles in phyllotaxis is the much higher frequency of Fibonacci spirals compared to other spiral arrangements such as Lucas spirals. We show that spirals are a form of symmetry, in the same way that axial symmetry is a form of symmetry, which explains why they can be the consequence of many different microscopic phenomena. We apply dynamical systems theory to the main types of phyllotaxis. We show that only Fibonacci spirals should exist and that the other spiral modes (including Lucas) are the consequence of developmental errors, such as the dislocation of a pseudo-orthostichy.
JUMP: replicability analysis of high-throughput experiments with applications to spatial transcriptomic studies
Authors: Lyu Pengfei , Li Yan , Wen Xiaoquan , Cao Hongyuan 
Published: February 2023

AbstractMotivationReplicability is the cornerstone of scientific research. The current statistical method for high-dimensional replicability analysis either cannot control the false discovery rate (FDR) or is too conservative.ResultsWe propose a statistical method, JUMP, for the high-dimensional replicability analysis of two studies. The input is a high dimensional paired sequence ofp-values from two studies and the test statistic is the maximum ofp-values of the pair. JUMP uses four states of thep-value pairs to indicate whether they are null or non-null. Conditional on the hidden states, JUMP computes the cumulative distribution function of the maximum ofp-values for each state to conservatively approximate the probability of rejection under the composite null of replicability. JUMP estimates unknown parameters and uses a step-up procedure to control FDR. By incorporating different states of composite null, JUMP achieves a substantial power gain over existing methods while controlling the FDR. Analyzing two pairs of spatially resolved transcriptomic datasets, JUMP makes biological discoveries that otherwise cannot be obtained by using existing methods.AvailabilityAn R package JUMP implementing the JUMP method is available on CRAN (https://CRAN.R-project.org/package=JUMP).
Methane production byMethanothrix thermoacetophilavia direct interspecies electron transfer withGeobacter metallireducens
Authors: Zhou Jinjie , Smith Jessica A. , Li Meng , Holmes Dawn E. 
Published: February 2023

AbstractMethanothrixis widely distributed in natural and artificial anoxic environments and plays a major role in global methane emissions. It is one of only two genera that can form methane from acetate dismutation and through participation in direct interspecies electron transfer (DIET) with exoelectrogens. AlthoughMethanothrixis a significant member of many methanogenic communities, little is known about its physiology. In this study, transcriptomics helped to identify potential routes of electron transfer during DIET betweenGeobacter metallireducensandMethanothrix thermoacetophila. Additions of magnetite to cultures significantly enhanced growth by acetoclastic methanogenesis and by DIET, while granular activated carbon (GAC) amendments impaired growth. Transcriptomics suggested that the OmaF-OmbF-OmcF porin complex and the octaheme outer membranec-type cytochrome, Gmet_0930, were important for electron transport across the outer membrane ofG. metallireducensduring DIET withMx. thermoacetophila. Clear differences in the metabolism ofMx. thermoacetophilawhen grown via DIET or acetate dismutation were not apparent. However, genes coding for proteins involved in carbon fixation and a surface associated quinoprotein, SqpA, were highly expressed in all conditions. Expression of gas vesicle genes was significantly lower in DIET-than acetate-grown cells, possibly to facilitate better contact between membrane associated redox proteins during DIET. These studies reveal potential electron transfer mechanisms utilized by bothGeobacterandMethanothrixduring DIET and provide important insights into the physiology ofMethanothrixin anoxic environments.ImportanceMethanothrixis a significant methane producer in a variety of methanogenic environments including soils and sediments as well as anaerobic digesters. Its abundance in these anoxic environments has mostly been attributed to its high affinity for acetate and its ability to grow by acetoclastic methanogenesis. However,Methanothrixspecies can also generate methane by directly accepting electrons from exoelectrogenic bacteria through direct interspecies electron transfer (DIET). Methane production through DIET is likely to further increase their contribution to methane production in natural and artificial environments. Therefore, acquiring a better understanding of DIET withMethanothrixwill help shedding light on ways to 1) minimize microbial methane production in natural terrestrial environments and 2) maximize biogas formation by anaerobic digesters treating waste.