bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pairs of Mutually Compensatory Frameshifting Mutations Contribute to Protein Evolution
Authors: Biba Dmitry , Klink Galya , Bazykin Georgii A 
Published: February 2022

Abstract
Insertions and deletions of lengths not divisible by 3 in protein-coding sequences cause frameshifts that usually induce premature stop codons and may carry a high fitness cost. However, this cost can be partially offset by a second compensatory indel restoring the reading frame. The role of such pairs of compensatory frameshifting mutations (pCFMs) in evolution has not been studied systematically. Here, we use whole-genome alignments of protein-coding genes of 100 vertebrate species, and of 122 insect species, studying the prevalence of pCFMs in their divergence. We detect a total of 624 candidate pCFM genes; six of them pass stringent quality filtering, including three human genes: RAB36, ARHGAP6, and NCR3LG1. In some instances, amino acid substitutions closely predating or following pCFMs restored the biochemical similarity of the frameshifted segment to the ancestral amino acid sequence, possibly reducing or negating the fitness cost of the pCFM. Typically, however, the biochemical similarity of the frameshifted sequence to the ancestral one was not higher than the similarity of a random sequence of a protein-coding gene to its frameshifted version, indicating that pCFMs can uncover radically novel regions of protein space. In total, pCFMs represent an appreciable and previously overlooked source of novel variation in amino acid sequences.
Dissecting Schizotypy and Its Association With Cognition and Polygenic Risk for Schizophrenia in a Nonclinical Sample
Authors: Tiego Jeggan , Thompson Kate , Arnatkeviciute Aurina , Hawi Ziarih , Finlay Amy , Sabaroedin Kristina , Johnson Beth , Bellgrove Mark A , Fornito Alex 
Published: February 2022

Abstract
Schizotypy is a multidimensional construct that captures a continuum of risk for developing schizophrenia-spectrum psychopathology. Existing 3-factor models of schizotypy, consisting of positive, negative, and disorganized dimensions have yielded mixed evidence of genetic continuity with schizophrenia using polygenic risk scores. Here, we propose an approach that involves splitting positive and negative schizotypy into more specific subdimensions that are phenotypically continuous with distinct positive symptoms and negative symptoms recognized in clinical schizophrenia. We used item response theory to derive high-precision estimates of psychometric schizotypy using 251 self-report items obtained from a non-clinical sample of 727 (424 females) adults. These subdimensions were organized hierarchically using structural equation modeling into 3 empirically independent higher-order dimensions enabling associations with polygenic risk for schizophrenia to be examined at different levels of phenotypic generality and specificity. Results revealed that polygenic risk for schizophrenia was associated with variance specific to delusional experiences (γ = 0.093, P = .001) and reduced social interest and engagement (γ = 0.076, P = .020), and these effects were not mediated via the higher-order general, positive, or negative schizotypy factors. We further fractionated general intellectual functioning into fluid and crystallized intelligence in 446 (246 females) participants that underwent onsite cognitive assessment. Polygenic risk scores explained 3.6% of the variance in crystallized intelligence. Our precision phenotyping approach could be used to enhance the etiologic signal in future genetic association studies and improve the detection and prevention of schizophrenia-spectrum psychopathology.
Patient Reported Outcomes in Metastatic Spine Disease: Concurrent Validity of PROMIS with the Spine Oncology Study Group Outcome Questionnaire
Authors: Richardson Michelle A. , Bernstein David N. , Kulp Andrea , Mesfin Addisu 
Published: February 2022

Study Design.
Cross-sectional prospective study.

Objective.
To evaluate the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), Pain Interference (PI), and Depression domains in comparison to the Spine Oncology Study Group-Outcomes Questionnaire (SOSG-OQ) in patients with metastatic spine disease.

Summary of Background Data.
While there remains a significant movement toward incorporating patient-reported outcome measures (PROMs) into clinical care, there are few validated PROMs for patients with metastatic spine disease. The SOSG-OQ was designed and validated for metastatic spine tumor patients. However, the use of general symptom-based PROMs, such as PROMIS domains, may reduce both patient and physician burden and improve interdisciplinary care if shown to be concurrently valid.

Methods.
Metastatic spine tumor patients from January 2017 to July 2021 at a single academic medical center were asked to complete PROMIS PF, PI, and Depression domains and the SOSG-OQ. Spearman correlation (p) coefficients were calculated.

Results.
A total of 103 unique visits, representing 79 patients met our inclusion criteria. A majority were men (59; 57%) and Caucasian (93; 90%), and the average age was 64-years-old (range: 34–87). There were 13 different types of histologies reported, with multiple myeloma, breast cancer, and prostate cancer representing 28 (27%), 26 (25%), and 13 (13%), respectively. Additional cancers included renal cell carcinoma, lung cancer, colon cancer, thyroid cancer, large B-cell lymphoma, nonHodgkin lymphoma, esophageal cancer, plasmacytoma, metastatic paraganglioma, and metastatic spindle cell sarcoma. SOSG-OQ was strongly correlated with PROMIS PI (ρ = 0.78) and PROMIS PF (ρ = 0.71), and moderately correlated with PROMIS Depression (ρ = 0.58).

Conclusion.
PROMIS PF, PI, and Depression appear to capture similar clinical insight as the SOSG-OQ. Spine surgeons can consider using these PROMIS domains in lieu of the SOSG-OQ in metastatic spine tumor patients.

Level of Evidence: NA
The Usefulness of Trabecular CT Attenuation Measurement at L4 Level to Predict Screw Loosening After Degenerative Lumbar Fusion Surgery
Authors: Shin Hee Kwon , Koo Hae-Won , Kim Kwang Hyeon , Yoon Sang Won , Sohn Moon-Jun , Lee Byung-Jou 
Published: February 2022

Study Design.
Retrospective study.

Objective.
To evaluate the absolute value of L4 trabecular region-of-interest (t-ROI) computed tomography (CT) attenuation, which can predict pedicle screw loosening, and determine the changes in value according to number of fused levels and sagittal balance in patients undergoing lumbar fusion surgery.

Summary of Background Data.
Although osteoporosis was not diagnosed in spinal dual x-ray absorptiometry preoperatively, we encountered several cases of screw loosening within 1 year of lumbar fusion surgery.

Methods.
We enrolled 478 patients and analyzed factors related to screw loosening. We evaluated the association between L4 t-ROI CT attenuation and screw loosening and determined the best cutoff value of t L4 t-ROI CT attenuation for predicting screw loosening.

Results.
The number of fused levels, postoperative C7-S1 sagittal vertical axis (SVA), and L4 t-ROI CT attenuation were independently correlated with screw loosening. According to number of fused level and postoperative C7-T1 SVA (≥36.9 mm or <36.9 mm), in patients with one-level fusion and C7-S1 SVA less than 36.9 mm, the optimal cutoff point of the L4 t-ROI CT attenuation predicting screw loosening was 106.5 Hounsfield unit (HU). L4 t-ROI attenuation did not change until two-level fusions. In patients with three-level fusions and C7-S1 SVA less than 36.9 mm, the optimal cutoff point of the L4 t-ROI CT attenuation predicting screw loosening was 159.0 HU. The optimal cutoff point of L4 t-ROI CT attenuation in patients with three-level fusions and C7-S1 SVA more than or equal to 36.9 mm was 191.0 HU.

Conclusion.
L4 t-ROI CT attenuation value considering number of fused levels and sagittal balance is an accurate measurement method to predict screw loosening. Spine surgeons should be aware of the L4 t-ROI attenuation before surgery to improve the fusion rate and reduce instrument-related complications of lumbar spine surgery in osteoporotic patients.

Level of Evidence.
3
Comparing Cardiac Output Measurements Using a Wearable, Wireless, Noninvasive Photoplethysmography-Based Device to Pulse Contour Cardiac Output in the General ICU: A Brief Report
Authors: Dvir Ayana , Goldstein Nir , Rapoport Avigal , Balmor Ronen Gingy , Nachman Dean , Merin Roei , Fons Meir , Ben Ishay Arik , Eisenkraft Arik 
Published: February 2022

OBJECTIVES:
Cardiac output (CO) measurements in the ICU are usually based on invasive techniques, which are technically complex and associated with clinical complications. This study aimed to compare CO measurements obtained from a noninvasive photoplethysmography-based device to a pulse contour cardiac output device in ICU patients.

DESIGN:
Observational, prospective, comparative clinical trial.

SETTING:
Single-center general ICU.

PATIENTS:
Patients admitted to the general ICU monitored using a pulse contour cardiac output device as per the decision of the attending physician.

INTERVENTIONS:
Parallel monitoring of CO using a photoplethysmography-based chest patch device and pulse contour cardiac output while the medical team was blinded to the values obtained by the noninvasive device.

MEASUREMENTS AND MAIN RESULTS:
Seven patients (69 measurements) were included in the final analysis. Mean CO were 7.3 ± 2.0 L/m and 7.0 ± 1.5 L/m for thermodilution and photoplethysmography, respectively. Bland-Altman showed that the photoplethysmography has a bias of 0.3 L/m with –1.6 and 2.2 L/m 95% limit of agreement (LOA) and a bias of 2.4% with 95% LOA between –25.7% and 30.5% when calculating the percentage of difference from thermodilution. The values obtained by thermodilution and photoplethysmography were highly correlated (r = 0.906).

CONCLUSIONS:
The tested chest patch device offers a high accuracy for CO compared to data obtained by the pulse contour cardiac output and the thermodilution method in ICU patients. Such devices could offer advanced monitoring capabilities in a variety of clinical settings, without the complications of invasive devices.
Inflammasome Activation in an In Vitro Sepsis Model Recapitulates Increased Monocyte Distribution Width Seen in Patients With Sepsis
Authors: Eisinger Gregory J. , Osman Wissam , Prather Evan R. , Julian Mark W. , Gavrilin Mikhail A. , Crouser Elliott D. , Wewers Mark D. 
Published: February 2022

OBJECTIVES:
Increased monocyte distribution width (MDW) has recently been shown to be a reliable indicator of early sepsis detection. This study therefore sought to determine if inflammasome activation can be linked to monocyte size changes in sepsis.

DESIGN:
An in vitro sepsis model using bacterial endotoxin (lipopolysaccharide [LPS]) to study the effect of inflammasome activation on monocyte cell size distribution by microscopy and MDW measurements using a standard clinical hematology analyzer.

SETTING:
University research laboratory.

SUBJECTS:
Healthy adult volunteers and cultured human monocyte cells in wild-type state and after clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 knockout of key inflammasome components (apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin-D).

INTERVENTIONS:
In vitro treatment of specimens with bacterial LPS.

MEASUREMENTS AND MAIN RESULTS:
Wild-type THP1 cells demonstrated a significant increase in cell area (207 μm2 [159–400 μm2] vs 160 μm2 [134–198 μm2]; p < 0.001) and distribution width (198 vs 55 μm2; p < 0.0001) by microscopy following treatment with LPS. Increased MDW correlated with inflammasome activation as demonstrated by release of interleukin (IL)-1β and with the presence of large distended pyroptotic cells by microscopy. All of these effects were blocked in the inflammasome knockout cells. Whole blood samples treated similarly also demonstrated IL-1β release and increased MDW (median 24.7 U [22.2–27.2 U] vs 16.3 U [15.1–17.6 U]; p = 0.008) as measured using the Beckman-Coulter Unicel DxH900 analyzer. When peripheral blood mononuclear cells were isolated prior to treatment with LPS, microscopy confirmed the presence of large pyroptotic cells correlating to IL-1β release in the human subject samples as well.

CONCLUSIONS:
The increased MDW seen in patients with sepsis can be reproduced in an in vitro sepsis model and blocked using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 technology to inactivate the inflammasome. These findings suggest that pyroptotic cellular swelling underlies changes in MDW in septic patients and connect MDW to early events in the inflammatory cascade of sepsis.
Cardiotoxicity in relation to treatment with aromatase inhibitors in breast cancer
Authors: Lund Marie , Ejlertsen Bent 
Published: February 2022

Summary
With the success of modern cancer therapy, breast cancer survival has steadily improved over the last decades. Treatment with aromatase inhibitors has become the preferred endocrine treatment in postmenopausal women with estrogen receptor-positive breast cancer. However, concerns have been raised over a possible cardiotoxic potential. The aim of the current paper is to review the evidence regarding cardiotoxicity with aromatase inhibitors in breast cancer.
Weighing benefits vs. risks, the improved effect of aromatase inhibitors vs. tamoxifen on breast cancer recurrence in most patients outweighs the potential risk of CV adverse events. At present it is advisable to ensure that standard measures of cardiovascular disease (CVD) management are applied to women with breast cancer, i.e., lifestyle intervention and if needed medical treatment of CVD and risk factors for CVD.
Supercharged Mechanical Stromal-cell Transfer (MEST)
Authors: Copcu H. Eray 
Published: February 2022

Summary:
PRP and fat-derived stromal-cell applications are the 2 most commonly used methods in regenerative medicine. PRP has a wide spectrum of indications. Mechanical methods have become very popular recently in fat-derived stromal-cell applications due to the advantages they provide. Combining these 2 methods has produced more successful results. To date, this combination has been in the form of combining 2 products obtained separately just before they are administered to the patient. In this study, fat tissue and blood samples obtained from eight volunteers were mixed with PPP as a new idea not previously reported in the literature, and stromal cells were obtained mechanically with sharp blades (adinizing). Later, the obtained PRP was added to the final product and became “supercharged.” The results were tested by the dual fluoroscopy method for cell number and viability, and the results obtained were analyzed statistically. By adding the plasma to the oil before stromal cells were obtained and cutting with sharp blades by mechanical separation, twice the volume and 4.7 times more cells were obtained compared with that obtained in the saline group (P < 0.001). We believe that the reason for this is the “binding” effect of the proteins in the plasma. This approach provided a higher cell count by using PPP, which is a “waste product,” and in addition, the potential efficiency was increased by adding PRP. However, the clinical results of this innovative method should be evaluated with advanced clinical studies.
Mandibular osteosarcoma: diagnosis and treatment
Authors: Ferri Andrea , Bianchi Bernardo , Ferrari Silvano 
Published: February 2022

Purpose of review
This article presents a review of the literature on mandibular osteosarcoma, focusing on the main aspects of its management, including diagnosis, histotype, and treatment. The literature published in the last 5 years was considered but because of the rarity of mandibular osteosarcoma, major publications from the past have also been included.

Recent findings
Management of mandibular osteosarcoma still lacks a clear standard of care, and treatment has not changed markedly over the past several years. The mainstay of treatment is surgical resection with free margins, but chemotherapy has recently begun to play a role in both adjuvant and neoadjuvant settings.

Summary
Mandibular osteosarcoma is a rare tumor and extensive randomized trials are not available in the international literature. Therefore, the standard of care is not defined, and diagnosis and treatment protocols have been extrapolated from analysis of multiple reports that are often discordant. This makes an interdisciplinary approach mandatory for the management of these patients, to provide the best care possible based on tumor size, site, and patient characteristics.
Prepectoral and Subpectoral Tissue Expander–Based Breast Reconstruction: A Propensity-Matched Analysis of 90-Day Clinical and Health-Related Quality-of-Life Outcomes
Authors: Nelson Jonas A. , Shamsunder Meghana G. , Vorstenbosch Joshua , Polanco Thais O. , Matros Evan , Coriddi Michelle R. , Mehrara Babak J. , Allen Robert J. , Dayan Joseph H. , Disa Joseph J. 
Published: February 2022

Background:
Prepectoral placement of tissue expanders for two-stage implant-based breast reconstruction potentially minimizes chest wall morbidity and postoperative pain. The authors explored 90-day clinical and health-related quality-of-life outcomes for prepectoral versus subpectoral tissue expander breast reconstruction.

Methods:
The authors conducted a propensity score-matching analysis (nearest neighbor, 1:1 matching without replacement) of patients who underwent immediate prepectoral or subpectoral tissue expander breast reconstruction between December of 2017 and January of 2019. Matched covariates included age, body mass index, race/ethnicity, smoking status, chemotherapy, radiotherapy, nipple-sparing mastectomy, and laterality of reconstruction. Outcomes of interest were perioperative analgesia use, 90-day postoperative patient-reported pain, complication rates, and BREAST-Q physical well-being of the chest scores.

Results:
Of the initial cohort of 921 patients, 238 were propensity-matched and included in the final analysis. The matched cohort had no differences in baseline characteristics. Postoperative ketorolac (p = 0.048) use was higher in the subpectoral group; there were no other significant differences in intraoperative and postoperative analgesia use. Prepectoral patients had lower pain on postoperative days 1 to 2 but no differences on days 3 to 10. BREAST-Q physical well-being of the chest scores did not differ. Prepectoral patients had higher rates of seroma than subpectoral patients (p < 0.001). Rates of tissue expander loss did not differ.

Conclusions:
This matched analysis of 90-day complications found lower early postoperative pain in prepectoral tissue expander patients but no longer-term patient-reported differences. Although prepectoral reconstruction patients experienced a higher rate of seroma, this did not translate to a difference in tissue expander loss. Long-term analysis of clinical and patient-reported outcomes is needed to understand the full profile of the prepectoral technique.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Immediate Breast Reconstruction Using the Goldilocks Procedure: A Balance between More Surgery and Patient Satisfaction
Authors: Manrique Oscar J. , Kuruoglu Doga , Yan Maria , Bustos Samyd S. , Boughey Judy C. , Harless Christin A. , Tran Nho V. , Martinez-Jorge Jorys , Forte Antonio J. , Nguyen Minh-Doan T. 
Published: February 2022

Background:
Since its first description in 2012, the Goldilocks procedure has become an option for immediate breast reconstruction, particularly for obese patients who are poor candidates for traditional implant or autologous reconstruction. In this work, the authors performed a longitudinal study of patients who underwent mastectomy with Goldilocks reconstruction to assess the incidence of additional surgical procedures, and to assess surgical outcomes and patient satisfaction.

Methods:
A retrospective review of patients who underwent mastectomy with the Goldilocks procedure only at Mayo Clinic Rochester between January of 2012 and September of 2019 was performed. Demographics, complications, additional breast procedures performed to attain the final results, and patient-reported outcomes using the BREAST-Q were recorded. Univariate and multivariable analyses were performed to identify statistical associations and risk factors.

Results:
Sixty-three patients (108 breasts) were included. Mean age was 57.8 years. Mean body mass index was 37.6 kg/m2. Median follow-up time after the mastectomy with the Goldilocks procedure was 15 months. The major complication rate within the first 30 days was 9.3 percent. Forty-four breasts (40.7 percent) underwent additional surgery. Dyslipidemia was significantly associated with an increased risk of additional surgery (adjusted hazard ratio, 2.00; p = 0.045). Scores in the four BREAST-Q domains were not statistically different between patients who had additional procedures and those who did not.

Conclusions:
Based on the results, the authors recommend a thorough preoperative discussion with patients who are candidates for the Goldilocks procedure to explore all options for reconstruction and their expectations, because it is crucial to reduce the necessity for additional operations in this high-risk population.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Risk, III.
The Impact of a Single Dual-Trained Surgeon in the Management of Mastectomy and Reconstruction
Authors: Piper Merisa L. , Nathan Shelby , Henderson Stacy , Lee Alfred , Broach Robyn B. , Kozak Geoffrey , Davis Harrison , Wu Liza C. 
Published: February 2022

Background:
Oncoplastic breast surgery is typically performed using a two-surgeon, two-team approach. The authors present their experience with patients undergoing mastectomy and immediate reconstruction performed by a single, dual-trained breast surgical oncologist and plastic and reconstructive microsurgeon.

Methods:
Patients who underwent mastectomy and/or immediate reconstruction performed by the senior author between 2015 and 2019 were divided into single-surgeon or dual-surgeon cohorts, and matched by age, body mass index, reconstruction type, and cancer stage.

Results:
The authors included 158 patients in their analysis (single-surgeon, n = 45; dual-surgeon, n = 113). Single-surgeon patients underwent surgery 13.2 days earlier than dual-surgeon patients (p < 0.01), and required significantly fewer preoperative (1.9 versus 3.4; p < 0.01) and postoperative visits (6.8 versus 10.7; p < 0.01). Operative duration was comparable (single-surgeon, 245 minutes; dual-surgeon, 245 minutes; p = 0.99). The authors found no significant difference in surgical-site infection, seroma, hematoma, abdominal donor-site healing, or flap and prosthesis loss between the groups. The authors did find that dual-surgeon patients had a significantly higher rate of mastectomy flap necrosis (20 percent versus 4 percent; p = 0.01), which held true on logistic regression when controlling for other variables. BREAST-Q data demonstrated that single-surgeon patients had significantly higher overall scores (p = 0.04), and were significantly more satisfied with their outcomes, surgeon, and the information provided (p = 0.03, p = 0.03, and p = 0.01, respectively).

Conclusions:
The single-surgeon approach has the potential to decrease patient burden by requiring fewer preoperative and postoperative visits without compromising surgical outcomes or oncologic safety. Further investigation is warranted into the financial implications and patient outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.