bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTORC1 inhibition uncouples lipolysis and thermogenesis in white adipose tissue to contribute to alcoholic liver disease
Authors: Song Qing , Chen Yingli , Ding Qinchao , Griffiths Alexandra , Liu Lifeng , Park Jooman , Liew Chong Wee , Nieto Natalia , Li Songtao , Dou Xiaobing , Jiang Yuwei , Song Zhenyuan 
Published: February 2023

Background:
Adipose tissue thermogenic activities use fatty acids from lipolysis for heat generation. Therefore, a tight coupling between lipolysis and thermogenesis is physiologically imperative in maintaining not only body temperature but also lipids homeostasis. Adipose tissue dysfunction contributes to alcoholic liver disease (ALD). Here, studies were conducted to examine how alcohol intake affects adipose tissue thermogenic activities and whether altered adipose tissue thermogenesis contributes to ALD.

Methods:
Both the Lieber-DeCarli and the NIAAA mouse models of ALD were used. Denervation surgery in epididymal fat pads was performed. CL316,243, a selective β3-adrenoceptor agonist, SR59230A, a selective β3 adrenoceptor (ADRB3) antagonist, and rapamycin, a selective mechanistic target of rapamycin complex 1 (mTORC1) inhibitor, were administrated through i.p. injection. Adipocyte-specific Prdm16 knockout mice were subjected to alcohol-containing diet chronically.

Results:
Chronic alcohol consumption, which enhances adipose tissue lipolysis, inhibits thermogenic activities of beige adipocytes in inguinal white adipose tissue (WAT), leading to an uncoupling status between lipolysis and thermogenesis in WAT at both basal and ADRB3 stimulation states. CL316,243 administration exacerbates liver pathologies of ALD. Alcohol intake inhibits mTORC1 activities in WAT. In mice, mTORC1 inhibition by rapamycin inhibits the thermogenesis of iWAT, whereas enhancing WAT lipolysis. Further investigations using adipocyte-specific Prdm16 knockout mice revealed that functional deficiency of beige adipocytes aggravates liver pathologies of ALD, suggesting that the inhibitory effect of alcohol on WAT browning/thermogenesis contributes to ALD pathogenesis.

Conclusion:
Chronic alcohol consumption induces an “uncoupling status” between lipolysis and browning/thermogenesis in WAT by inhibiting mTORC1 activation. Diminished WAT browning/thermogenesis, concomitant with enhanced lipolysis, contributes to ALD pathogenesis.
Diagnostic performance of Ga-68 FAPI 04 PET/CT in colorectal malignancies
Authors: Prashanth Arun , Kumar Ravichander Senthil , Eswaran Prasad , Kalyan Suman , Maheswari Babu Sridev 
Published: February 2023

Aim
To evaluate the role of Ga-68 fibroblast activation protein inhibitor 04 PET/computed tomography (FAPI) in colorectal cancers (CRCs) in terms of diagnostic accuracy and impact on clinical management. FAPI is compared with FDG PET/CT and conventional imaging in staging, restaging, recurrence detection, and response evaluation of CRC.

Methods
Twenty-nine consecutive patients of histopathologically confirmed primary or relapsed CRC were included in the study. Patients who underwent FAPI PET/CT along with either FDG PET/CT or conventional imaging were included. Primary lesions, recurrence sites, lymph nodes, and metastatic lesions were recorded on all the scans. Maximum standardized uptake value (SUVmax) was measured from both primary and metastatic lesions.

Results
The sensitivity of FAPI in primary and recurrence detection is 100% compared to 88% for FDG/conventional imaging. The overall sensitivity of FAPI stands at 98% with accuracy at 95% whereas for FDG/conventional imaging the sensitivity and accuracy are 78% and 77%, respectively, with P < 0.002. Significant difference was noted in the detection of peritoneal metastasis (96% vs. 66%).

Conclusion
FAPI PET/CT shows better sensitivity and accuracy in the evaluation of CRCs, especially in peritoneal disease compared to FDG PET/CT and conventional imaging. FAPI has the potential to replace FDG in CRCs.
Assessing Disease Activity in Pediatric Crohn’s Disease Using Ultrasound: The Pediatric Crohn Disease Intestinal Ultrasound Score
Authors: van Wassenaer Elsa A. , van Rijn Rick R. , de Voogd Floris A.E. , van Schuppen Joost , Kindermann Angelika , de Meij Tim G.J. , van Limbergen Johan E. , Gecse K.B. , D’Haens Geert R. , Benninga Marc A. , Koot Bart G.P. ,   on behalf of the RAINBOW group
Published: February 2023

Objectives:
Currently, there is no consensus on how to score Crohn disease (CD) activity assessed by intestinal ultrasound (IUS) in children. This study aimed to design an easy-to-use IUS score for disease activity in pediatric CD.

Methods:
Children undergoing ileo-colonoscopy for CD assessment underwent IUS the day before ileo-colonoscopy, assessed with simple endoscopic score for CD (SES-CD). IUS features were compared to the SES-CD on segmental level. Multiple regression analyses, separately for terminal ileum (TI) and colon, were done to assess predictors of disease activity and to develop a model.

Results:
In 74 CD patients (median 15 years, 48% female), 67 TI and 364 colon segments were assessed. Based on receiver operating characteristics curves, bowel wall thickness (BWT) was categorized into low [1 point: 2–3 mm (TI) and 1.6–2 mm (colon)], medium [2 points: 3.0–3.7 mm (TI) and 2.0–2.7 mm (colon)], and high [3 points: >3.7 mm (TI) and >2.7 mm (colon)]. In TI, only BWT was retained in the model [high BWT: odds ratio (OR) 11.50, P < 0.001]. In colon, BWT (high BWT: OR 8.63, P < 0.001) and mesenteric fat (1 point: OR 3.02, P < 0.001) were independent predictors. A pediatric Crohn disease IUS score (PCD-US) cut-off of 1 resulted in a sensitivity of 82% (95% confidence interval, CI: 65%–93%) and 85% (95% CI: 80%–89%) and a cut-off of 3 in a specificity of 88% (72%–97%) and 92% (87%–96%) for TI and colon, respectively. Inter-observer agreement was moderate for TI and colon (K: 0.42, K: 0.49, respectively).

Conclusions:
The PCD-US score is an easy-to-use and reliable score to detect or rule out CD activity on segmental level in children. External validation is needed before applying this score in clinical practice.
The Effectiveness and Safety of Methotrexate as the First-Line Immunomodulator of Maintenance Therapy in Pediatric Crohn Disease
Authors: Choi Young Min , Kim Jeong Min , Moon Jin Soo , Ko Jae Sung , Yang Hye Ran 
Published: February 2023

Objectives:Methotrexate (MTX) has been used as maintenance therapy for Crohn disease (CD) in adults and children. However, there are only a few studies on the MTX’s effectiveness in thiopurine-naïve CD adult patients and children. This study aimed to evaluate the MTX’s effectiveness and safety as first immunomodulator for maintenance therapy in pediatric CD.Methods:This retrospective cohort study recruited 64 pediatric CD patients treated with MTX as a first-line immunomodulator. Clinical remission (CR) was assessed at weeks 14, 26, and 52. Mucosal healing (MH) was assessed at weeks 26 and 52.Results:Of 64 patients who received MTX, CR was noted in 60.9% at week 14, 29.7% with MH in 68.0% at week 26, and 27.8% with MH in 81.8% at week 52. When comparing age subtypes according to the Paris classification, the CR rate was higher in A1a than in the other subtypes at week 26 (60.0% in A1a, 26.5% in A1b, 0% in A2;P= 0.038). There were no differences in disease location, behavior, or perianal involvement. Adverse effects were noted in 30 of 64 (46.9%) patients, including 1 patient who stopped MTX before 26 weeks owing to side effects; increased liver enzymes in 25 (39.0%) patients, leukopenia in 5 (7.8%), nausea in 5 (7.8%), skin erosion in 1 (1.6%), and headache in 1 (1.6%).Conclusion:MTX as a first-line immunomodulator may be an effective and safe maintenance therapy for pediatric CD patients.
Lateral Malleolar Bursitis in a Competitive In-Line Rollerblade Speed Skater – A Case Report
Authors: Koistinen Brendan , Herman Daniel C. 
Published: February 2023

AbstractA 10-year-old nationally-competitive female in-line rollerblade speed skater presented to a sports medicine clinic with bilateral lateral ankle pain and swelling over 2 months. Patient had tenderness to palpation and focal swelling at the lateral malleoli. Ultrasound examination confirmed a diagnosis of lateral adventitial malleolar bursitis, potentially due to repetitive shear forces across the lateral malleoli. Inspection of the patient's carbon-fiber boots revealed millimeters of discrepancy in fit around the patient's lateral malleoli. Following brief relative rest from sport, the patient had custom-molded boots made and was able to return to high-level competition and shortly thereafter was pain free. This case is the first known report of lateral malleolar bursitis in an athlete and highlights the role of equipment evaluation which may be necessary in these athletes.
Transmission of Bias in the Medical Record Among Physical Medicine and Rehabilitation Trainees
Authors: Qin Evelyn , Seeds Alicia , Wallingford Allison , Copley Michelle , Humbert Andrew , Junn Cherry , Starosta Amy 
Published: February 2023

ABSTRACT
Stigmatizing language can negatively influence providers’ attitudes and care toward patients, but this has not been studied among physiatrists. An online survey was created to assess whether stigmatizing language can impact physical medicine and rehabilitation (PM&R) trainees’ attitudes toward patients. We hypothesized stigmatizing language would negatively impact trainees’ attitudes. Participants were randomized to a stigmatizing or neutral language vignette describing the same hypothetical spinal cord injury patient. Questions were asked about attitudes and assumptions towards the patient, pain management based on the vignette, and general views regarding individuals with disabilities. Between August 2021 to January 2022, 75 U.S. PM&R residency trainees participated. Thirty-seven (49.3%) identified as women; 52 (69.3%) were white, and half (50.6%) received the stigmatized vignette. Participants exposed to stigmatizing language scored 4.8 points lower (p < 0.01) on the provider attitude toward patient scale compared to those exposed to neutral language. There were no significant differences in the disability attitude scores between the two groups (p = 0.81). These findings may indicate that stigmatizing language in the medical record may negatively affect PM&R trainees’ attitudes toward patients. Further exploration is needed to identify the best way to educate trainees and reduce the propagation of bias in the medical record.
Increased 68Ga-FAPI Activity in Benign Pulmonary Nodules
Authors: Su Dan , Li Zhuoyuan , Deng Jia , Qiu Chen , Chen Yue 
Published: February 2023

Abstract
A 68-year-old man who had recently been diagnosed with pulmonary nodules underwent both 18F-FDG and 68Ga-FAPI PET/CT. Both studies showed increased uptake in pulmonary nodules, which are suspected to be malignant. However, based on the histopathological findings after surgery, this is ultimately diagnosed as a benign pulmonary nodule. Our case suggests that pulmonary nodules with intense 68Ga-FAPI uptake may be benign as well.
Are We Approaching a Change in Paradigm in PET/CT Imaging of Solid Gastrointestinal (or Digestive) Tract Tumors With the Clinical Application of FAPI Imaging?
Authors: Delgado Bolton Roberto C. , Calapaquí Terán Adriana K. , Herrmann Ken , Fanti Stefano , Giammarile Francesco 
Published: February 2023

Abstract
Studies with [68Ga]Ga-labeled or [18F]F-labeled fibroblast activation protein inhibitor compounds have demonstrated favorable characteristics for PET/CT imaging, making them especially interesting for digestive tumors. In this review, the recent evidence in this field and its potential clinical applications are discussed.
Long-term Prolonged-release Tacrolimus-based Immunosuppression in De Novo Kidney Transplant Recipients: 5-Y Prospective Follow-up of Patients in the ADVANCE Study
Authors: Pernin Vincent , Glyda Maciej , Viklický Ondrej , Lõhmus Aleksander , Wennberg Lars , Witzke Oliver , von Zur-Mühlen Bengt , Anaokar Swapneel , Hurst Martin , Kazeem Gbenga , Undre Nasrullah , Kuypers Dirk R.J. 
Published: February 2023

Background.
Although prolonged-release tacrolimus (PR-T) is widely approved for posttransplantation immunosuppression in kidney recipients, large-scale studies are required to assess long-term outcomes. We present follow-up data from the Advagraf-based Immunosuppression Regimen Examining New Onset Diabetes Mellitus in Kidney Transplant Recipients (ADVANCE) trial, in which kidney transplant patients (KTPs) received corticosteroid minimization with PR-T.

Methods.
ADVANCE was a 24-wk, randomized, open-label, phase-4 study. De novo KTPs received PR-T with basiliximab and mycophenolate mofetil and were randomized to receive an intraoperative corticosteroid bolus plus tapered corticosteroids until day 10 (arm 1) or an intraoperative corticosteroid bolus (arm 2). In this 5-y, noninterventional follow-up, patients received maintenance immunosuppression according to standard practice. The primary endpoint was graft survival (Kaplan-Meier). Secondary endpoints included patient survival, biopsy-confirmed acute rejection-free survival, and estimated glomerular filtration rate (4-variable modification of diet in renal disease).

Results.
Follow-up study included 1125 patients. Overall graft survival at 1 and 5 y posttransplantation was 93.8% and 88.1%, respectively, and was similar between treatment arms. At 1 and 5 y, patient survival was 97.8% and 94.4%, respectively. Five-year graft and patient survival rates in KTPs who remained on PR-T were 91.5% and 98.2%, respectively. Cox proportional hazards analysis demonstrated similar risk of graft loss and death between treatment arms. Five-year biopsy-confirmed acute rejection-free survival was 84.1%. Mean ± standard deviation values of estimated glomerular filtration rate were 52.7 ± 19.5 and 51.1 ± 22.4 mL/min/1.73 m2 at 1 and 5 y, respectively. Fifty adverse drug reactions were recorded, probably tacrolimus-related in 12 patients (1.5%).

Conclusions.
Graft survival and patient survival (overall and for KTPs who remained on PR-T) were numerically high and similar between treatment arms at 5 y posttransplantation.
Performance of a Prospective Anticoagulation Stratification Algorithm After Liver Transplantation
Authors: Sanchez-Garcia Jorge , Lopez-Verdugo Fidel , LeCorchick Spencer , Tran Alexandria , Gilroy Richard K. , Fujita Shiro , Zendejas Ivan , Gagnon Andrew , Dow Sean , Krong Jake , Rodriguez-Davalos Manuel I. , Stevens Scott M. , Woller Scott C. , Alonso Diane 
Published: February 2023

Background.
Venous thromboembolism (VTE) occurs in 0.4% to 15.5% and bleeding occurs in 20% to 35% of patients after liver transplantation (LT). Balancing the risk of bleeding from therapeutic anticoagulation and risk of thrombosis in the postoperative period is challenging. Little evidence exists regarding the best treatment strategy for these patients. We hypothesized that a subset of LT patients who develop postoperative deep vein thromboses (DVTs) could be managed without therapeutic anticoagulation. We implemented a quality improvement (QI) initiative using a standardized Doppler ultrasound-based VTE risk stratification algorithm to guide parsimonious implementation of therapeutic anticoagulation with heparin drip.

Methods.
In a prospective management QI initiative for DVT management, we compared 87 LT historical patients (control group; January 2016–December 2017) to 182 LT patients (study group; January 2018–March 2021). We analyzed the rates of immediate therapeutic anticoagulation after DVT diagnosis within 14 d of LT, clinically significant bleeding, return to the operating room, readmission, pulmonary embolism, and death within 30 d of LT before and after the QI initiative.

Results.
Ten patients (11.5%) in the control group and 23 patients (12.6%; P = 0.9) in the study group developed DVTs after LT. Immediate therapeutic anticoagulation was used in 7 of 10 and 5 of 23 patients in the control and study groups, respectively (P = 0.024). The study group had lower odds of receiving immediate therapeutic anticoagulation after VTE (21.7% versus 70%; odds ratio = 0.12; 95% confidence interval, 0.019-0.587; P = 0.013) and a lower rate of postoperative bleeding (8.7% versus 40%; odds ratio = 0.14, 95% confidence interval, 0.02-0.91; P = 0.048). All other outcomes were similar.

Conclusions.
Implementing a risk-stratified VTE treatment algorithm for immediate post-LT patients appears to be safe and feasible. We observed a decrease in the use of therapeutic anticoagulation and a lower rate of postoperative bleeding without adverse impacts on early outcomes.
ChatGPT for Clinical Vignette Generation, Revision, and Evaluation
Authors: Benoit James R. A. 
Published: February 2023

AbstractObjectiveTo determine the capabilities of ChatGPT for rapidly generating, rewriting, and evaluating (via diagnostic and triage accuracy) sets of clinical vignettes.DesignWe explored the capabilities of ChatGPT for generating and rewriting vignettes. First, we gave it natural language prompts to generate 10 new sets of 10 vignettes, each set for a different common childhood illness. Next, we had it generate 10 sets of 10 vignettes given a set of symptoms from which to draw. We then had it rewrite 15 existing pediatric vignettes at different levels of health literacy. Fourth, we asked it to generate 10 vignettes written as a parent, and rewrite these vignettes as a physician, then at a grade 8 reading level, before rewriting them from the original parent’s perspective. Finally, we evaluated ChatGPT for diagnosis and triage for 45 clinical vignettes previously used for evaluating symptom checkers.Setting and participantsChatGPT, a publicly available, free chatbot.Main outcome measuresOur main outcomes for de novo vignette generation were whether ChatGPT followed vignette creation instructions consistently, correctly, and listed reasonable symptoms for the disease being described. For generating vignettes from pre-existing symptom sets, we examined whether the symptom sets were used without introducing extra symptoms. Our main outcome for rewriting existing standardized vignettes to match patient demographics, and rewriting vignettes between styles, was whether symptoms were dropped or added outside the original vignette. Finally, our main outcomes examining diagnostic and triage accuracy on 45 standardized patient vignettes were whether the correct diagnosis was listed first, and if the correct triage recommendation was made.ResultsChatGPT was able to quickly produce varied contexts and symptom profiles when writing vignettes based on an illness name, but overused some core disease symptoms. It was able to use given symptom lists as the basis for vignettes consistently, adding one additional (though appropriate) symptom from outside the list for one disease. Pediatric vignettes rewritten at different levels of health literacy showed more complex symptoms being dropped when writing at low health literacy in 87.5% of cases. While writing at high health literacy, it added a diagnosis to 80% of vignettes (91.7% correctly diagnosed). Symptoms were retained in 90% of cases when rewriting vignettes between viewpoints. When presented with 45 vignettes, ChatGPT identified illnesses with 75.6% (95% CI, 62.6% to 88.5%) first-pass diagnostic accuracy and 57.8% (95% CI, 42.9% to 72.7%) triage accuracy. Its use does require monitoring and has caveats, which we discuss.ConclusionsChatGPT was capable, with caveats and appropriate review, of generating, rewriting, and evaluating clinical vignettes.
Single cell transcriptomic analysis of renal allograft rejection reveals novel insights into intragraft TCR clonality
Authors: Shi Tiffany , Burg Ashley R. , Caldwell J. Timothy , Roskin Krishna , Castro-Rojas Cyd M. , Chukwuma P. Chukwunalu , Gray George I. , Foote Sara G. , Alonso Jesus , Cuda Carla M. , Allman David A. , Rush James S. , Regnier Catherine H. , Wieczorek Grazyna , Alloway Rita R. , Shields Adele R. , Baker Brian M. , Woodle E. Steve , Hildeman David A. 
Published: February 2023

AbstractBulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked cellular context critical to mechanistic understanding. We performed combined single cell RNA transcriptomic and TCRα/β sequencing on rBx from patients with ACR under differing immunosuppression (IS): tacrolimus, iscalimab, and belatacept. TCR analysis revealed a highly restricted CD8+T cell clonal expansion (CD8EXP), independent of HLA mismatch or IS type. Subcloning of TCRα/β cDNAs from CD8EXPinto Jurkat76 cells (TCR-/-) conferred alloreactivity by mixed lymphocyte reaction. scRNAseq analysis of CD8EXPrevealed effector, memory, and exhausted phenotypes that were influenced by IS type. Successful anti-rejection treatment decreased, but did not eliminate, CD8EXP, while CD8EXPwere maintained during treatment-refractory rejection. Finally, most rBx-derived CD8EXPwere also observed in matching urine samples. Overall, our data define the clonal CD8+T cell response to ACR, providing novel insights to improve detection, assessment, and treatment of rejection.
Insights intoTreponema pallidumgenomics from modern and ancient genomes using a novel mapping strategy
Authors: Pla-Díaz Marta , Akgül Gülfirde , Molak Martyna , du Plessis Louis , Panagiotopoulou Hanna , Doan Karolina , Bogdanowicz Wiesław , Dąbrowski Paweł , Oziębłowski Maciej , Kwiatkowska Barbara , Szczurowski Jacek , Grzelak Joanna , Arora Natasha , Majander Kerttu , González-Candelas Fernando , Schuenemann Verena J. 
Published: February 2023

ABSTRACTBackgroundTreponemal diseases pose significant global health risks, presenting severe challenges to public health due to their serious health impacts if left untreated. Despite numerous genomic studies onTreponema pallidumand the known possible biases introduced by the choice of the reference genome used for mapping, few investigations have addressed how these biases affect phylogenetic and evolutionary analysis of these bacteria. In this study, we assessed the impact of selecting an appropriate genomic reference on phylogenetic and evolutionary analyses ofT. pallidum.ResultsWe designed a multiple-reference-based (MRB) mapping strategy using four different reference genomes and compared it to traditional single-reference mapping. To conduct this comparison, we created a genomic dataset comprising 77 modern and ancient genomes from the three subspecies ofT. pallidum, including a newly sequenced 17th-century genome (35X coverage) of a syphilis-causing strain (designated as W86). Our findings show that recombination detection was consistent across different references, but the choice of reference significantly affected ancient genome reconstruction and phylogenetic inferences. The high-coverage W86 genome obtained here also provided a new calibration point for Bayesian molecular clock dating, improving the reconstruction of the evolutionary history of treponemal diseases. Additionally, we identified novel recombination events, positive selection targets, and refined dating estimates for key events in the species’ history.ConclusionsThis study highlights the importance of considering methodological implications and reference genome bias in High-Throughput Sequencing-based whole-genome analysis ofT. pallidum, especially of ancient or low-coverage samples, contributing to a deeper understanding of this pathogen and its subspecies.