bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary analysis of theLORELEIgene family in plants reveals regulatory subfunctionalization
Authors: Noble Jennifer A , Bielski Nicholas V , Liu Ming-Che James , DeFalco Thomas A , Stegmann Martin , Nelson Andrew D L , McNamara Kara , Sullivan Brooke , Dinh Khanhlinh K , Khuu Nicholas , Hancock Sarah , Shiu Shin-Han , Zipfel Cyril , Cheung Alice Y , Beilstein Mark A , Palanivelu Ravishankar
Published: September 2022

A signaling complex comprising members of the LORELEI (LRE)-LIKE GPI-anchored protein (LLG) and Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE (CrRLK1L) families perceive RAPID ALKALINIZATION FACTOR (RALF) peptides and regulate growth, reproduction, immunity, and stress responses in Arabidopsis (Arabidopsis thaliana). Genes encoding these proteins are members of multigene families in most angiosperms and could generate thousands of signaling complex variants. However, the links between expansion of these gene families and the functional diversification of this critical signaling complex as well as the evolutionary factors underlying the maintenance of gene duplicates remain unknown. Here, we investigated LLG gene family evolution by sampling land plant genomes and explored the function and expression of angiosperm LLGs. We found that LLG diversity within major land plant lineages is primarily due to lineage-specific duplication events, and that these duplications occurred both early in the history of these lineages and more recently. Our complementation and expression analyses showed that expression divergence (i.e. regulatory subfunctionalization), rather than functional divergence, explains the retention of LLG paralogs. Interestingly, all but one monocot and all eudicot species examined had an LLG copy with preferential expression in male reproductive tissues, while the other duplicate copies showed highest levels of expression in female or vegetative tissues. The single LLG copy in Amborella trichopoda is expressed vastly higher in male compared to in female reproductive or vegetative tissues. We propose that expression divergence plays an important role in retention of LLG duplicates in angiosperms.
Photographic grading for trachoma diagnosis within trachoma impact surveys in Amhara region, Ethiopia
Authors: Whitson Cassidy C , Nute Andrew W , Hailemariam Begashaw , Deathe Andrew R , Astale Tigist , Ayele Zebene , Gessese Demelash , Sata Eshetu , Zerihun Mulat , Melak Berhanu , Haile Mahteme , Zeru Taye , Getnet Banchalem , Wondimteka Bilen , Kabtu Endale , Getachew Habib , Shibiru Meskerem , Bayecha Social , Aragie Solomon , Wittberg Dionna M , Tadesse Zerihun , Callahan E Kelly , Keenan Jeremy D , Admassu Fisseha , Nash Scott D
Published: September 2022

Background

As countries reach the trachoma elimination threshold and cases of trachomatous inflammation follicular (TF) become rare, it becomes difficult to train survey graders to recognize clinical signs. We assess the use of photography as a grading tool, the efficiency of an in-country grading center and the comparability of field and photographic grading.

Methods

During January–February 2017 surveys in Amhara, Ethiopia, field graders assessed TF, trachomatous inflammation intense (TI) and trachomatous scarring (TS). Photographs were taken from each conjunctiva and later graded at the Gondar Grading Center (GGC) at the University of Gondar in Amhara. Two trained ophthalmology residents graded each set of photographs and a third grader provided an adjudicating grade when needed.

Results

A total of 4953 photographs of 2477 conjunctivae from 1241 participants in 10 communities were graded over 5 d at the GGC. Six examined participants were not photographed. Agreement between field and photographic grades were for TF: percent agreement (PA) 96.7%, κ=0.70 (95% confidence interval [CI] 0.64 to 0.77; for TI: PA 94.7%, κ=0.32 (95% CI 0.20 to 0.43); and for TS: PA 83.5%, κ=0.22 (95% CI 0.15 to 0.29).

Conclusions

Conjunctival photography may be a solution for programs near the elimination threshold where there are few available community cases for training field graders.
Management of Proximal Humeral Fractures in Adults: A Systematic Review and Meta-Analysis
Authors: Lapner Peter , Sheth Ujash , Nam Diane , Schemitsch Emil , Guy Pierre , Richards Robin ,   On behalf of the Canadian Shoulder and Elbow Society (CSES) and the Canadian Orthopedic Trauma Society (COTS)
Published: September 2022

Objectives:

Differences in function, pain, and reoperation rates were compared between the following treatment options: (1) operative vs. nonoperative treatment and (2) various surgical treatments including open reduction internal fixation, intramedullary nail, hemiarthroplasty (HA), and reverse shoulder arthroplasty (RSA).

Data Sources:

MEDLINE, Embase, and Cochrane were searched through February 1, 2022. All English-language randomized trials comparing operative and nonoperative treatment of proximal humeral fractures with a control group in patients 18 years or older were included.

Data Extraction:

Demographic data, functional and pain scores and re-operation rates were extracted. Study quality was determined with the Cochran risk of bias tool and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE). Heterogeneity was determined with the I-squared statistic.

Data Synthesis:

Meta-analysis of included studies using mean difference and odds ratios where appropriate.

Conclusions:

Surgical treatment with either locked plates or HA results in similar functional scores and pain outcomes as nonoperative treatment, although plates were associated with higher reoperation rates in 3-part and 4-part fractures. In 3-part and 4-part fractures, RSA results in higher function and pain scores compared with HA. Further high-quality trials should focus on RSA, and further study is required to better define the role of open reduction internal fixation in the younger patient population.

Level of Evidence:

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Efficacy of Cefazolin Versus Vancomycin Antibiotic Cement Spacers
Authors: Parry Joshua A. , Chavarria Joseph , Giddins Sara , Rojas David , Mauffrey Cyril , Baldini Todd , Lv Yang
Published: September 2022

Objective:

Cefazolin is a heat-labile antibiotic that is not usually added to polymethylmethacrylate (PMMA) cement spacers because it is believed to be inactivated by the high polymerization temperatures. The purpose of this study was to compare cefazolin versus vancomycin high-dose antibiotic cement spacers.

Methods:

High-dose antibiotic PMMA spacers with either cefazolin or vancomycin were fabricated. Setting time, compressive strength, and compression modulus of spacers were measured. Spacers were emerged in saline, and the eluent was tested on days 1, 2, 3, 7, 14, and 30 to determine the zone of inhibition of methicillin-sensitive Staphylococcus aureus and estimate the cumulative antibiotic released.

Results:

Cefazolin, compared with vancomycin-loaded spacers, had significantly shorter setting time [mean difference (MD) −1.8 minutes, 95% confidence interval (CI), −0.6 to −3.0], greater compressive strength (MD 20.1 megapascal, CI, 15.8 to 24.5), and compression modulus (MD 0.15 megapascal, CI, 0.06 to 0.23). The zone of inhibition of eluent from PMMA-C spacers was significantly greater than PMMA-V spacers at all time points, an average of 11.7 ± 0.8 mm greater across time points. The estimated cumulative antibiotic released from cefazolin spacers was significantly greater at all time points (P < 0.0001).

Conclusions:

Cefazolin was not inactivated by PMMA polymerization and resulted in spacers with superior antimicrobial and biomechanical properties than those made with vancomycin, suggesting that cefazolin could play a role in the treatment of infected bone defects with high-dose antibiotic PMMA spacers.
The Role of the Family Physician in Rural Maternity Care
Authors: QUINLAN JEFFREY D.
Published: September 2022

Of the 28 million rural women of reproductive age in the United States, ∼7 million of them live in areas of limited access to maternity care. While only 6.7% of Family Physicians currently provide maternity care, they are the only delivering physicians in 27% of rural hospitals. Of the 1.6% of Family Physicians performing cesarean deliveries as a primary surgeon, 57.3% do so in a rural county and 38.6% do so in a county without an obstetrician. Cultivation of the next generation of Family Physicians providing maternity care is essential to prevent further spread of existing maternity care deserts.
CLINICAL CHARACTERISTICS AND PROGNOSTIC FACTORS AFFECTING CLINICAL OUTCOMES IN CYTOMEGALOVIRUS RETINITIS WITH OR WITHOUT HIV INFECTION
Authors: Su Yu-Ting , Chen Yi-JUN , Lin Chang-Ping , Hsieh Yi-Ting , Yang Chung-May , Chiu-Ang Angelique , Yeh Po-Ting
Published: September 2022

Purpose:

To explore the clinical features and outcomes of cytomegalovirus retinitis (CMVR) in patients with HIV and non-HIV.

Methods:

This retrospective cohort study included all patients with CMVR in National Taiwan University Hospital from 2013 to 2018. Demographic data, clinical characteristics, CMVR recurrence, and overall survival were compared between the HIV and non-HIV groups. Generalized estimating equation models were implemented to analyze the risk factors of poor visual prognosis. The Kaplan–Meier survival analysis was performed to investigate recurrence and survival.

Results:

A total of 66 patients (95 eyes) with CMVR were enrolled, with no significant differences between the HIV (41 patients; 61 eyes) and non-HIV (25 patients; 34 eyes) groups in initial/final visual acuity, lesion area, or viral loads. Poor visual outcome was associated with poor initial visual acuity, retinal detachment, and a higher plasma cytomegalovirus titer. The HIV group had significantly longer survival rate (P = 0.033) and lower recurrence rate (P = 0.01) than the non-HIV group, and it also presented with better prognosis in recurrence-free survival analysis (P = 0.01).

Conclusion:

Patients with CMVR without HIV had higher mortality and recurrence rates than the HIV group. Risk factors of poor visual outcome included poor initial visual acuity, retinal detachment, and a high plasma cytomegalovirus titer.
Reproducibility and Reliability of Subbasal Corneal Nerve Parameters of the Inferior Whorl in the Neurotoxic and Healthy Cornea
Authors: Chiang Jeremy Chung Bo , Khou Vincent , Tavakoli Azadeh , Park Susanna B. , Goldstein David , Krishnan Arun V. , Markoulli Maria
Published: September 2022

Purpose:

The aim of this study was to investigate the reliability of subbasal corneal nerve plexus parameters of the inferior whorl compared with the central cornea with in vivo corneal confocal microscopy and to investigate the impact of inferior whorl pattern complexity on reproducibility.

Methods:

Subbasal corneal nerves of healthy controls (n = 10) and patients with chemotherapy-induced peripheral neuropathy (n = 10) were imaged with a laser scanning confocal microscope. Two masked, experienced observers and the original image taker were tasked with selecting representative images of the central cornea and inferior whorl for each participant. This was conducted on 2 occasions 1 week apart. Corneal nerve fiber length (CNFL) and fractal dimension (CNFrD) [central cornea: CNFL and CNFrD; inferior whorl region: inferior whorl length (IWL) and inferior whorl fractal dimension (IWFrD)] were analyzed. Intraclass correlation coefficient (ICC) was analyzed for interobserver and intraobserver reliability. Inferior whorl complexity was classified according to the ease of identification of the center point of convergence.

Results:

Interobserver ICC was 0.992 for CNFL, 0.994 for CNFrD, 0.980 for IWL, and 0.954 for IWFrD. When analyzed by inferior whorl complexity, the interobserver reliability was similar for simple (0.987 for IWL; 0.960 for IWFrD) and complex patterns (0.967 for IWL; 0.949 for IWFrD). However, intraobserver ICC were reduced for complex (IWL 0.841–0.970; IWFrD 0.830–0.955) compared with simple patterns (IWL 0.931–0.970; IWFrD 0.921–0.969).

Conclusions:

Although the overall interobserver reliability was excellent for the central corneal and inferior whorl parameters, there was lower intraobserver reliability for the inferior whorl parameters for complex morphological patterns. To improve reliability, more sophisticated wide-field imaging of the inferior whorl may be needed.
Characteristics of Pediatric Patients With Celiac Disease Identified Due to an Affected First‐Degree Family Member
Authors: Gould Michelle J. , Dowhaniuk Jenna , Arredondo Jorge , Azzopardi Paul , Hu Tina , Mileski Heather , Carpenter Andrea , Pai Nikhil , Brill Herbert
Published: September 2022

The incidence of celiac disease in first‐degree relatives of affected individuals is higher than in the general population, yet the clinical characteristics of this unique subset of patients has not been well described. Through a retrospective review of patients seen in a tertiary care pediatric celiac disease clinic, we identified 49 patients diagnosed with celiac disease following screening due to an affected first‐degree relative. Although 51% of patients screened due to an affected first‐degree relative were asymptomatic, their disease histology was as severe as those screened for symptoms suggestive of celiac disease. These findings support current recommendations to screen all first‐degree relatives of patients with celiac disease regardless of clinical symptoms.
Dexrazoxane Treatments Limits Subclinical Cardiac Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors Exposed to Doxorubicin Treatments
Authors: Lapointe Marc-Olivier , Caru Maxime , Curnier Daniel , Raboisson Marie-Josée , Andelfinger Gregor , Krajinovic Maja , Laverdière Caroline , Sinnett Daniel , Périé Delphine
Published: September 2022

Introduction:

Doxorubicin leads to dose dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. We investigated survivors’ heart health using echocardiography and evaluated doxorubicin and dexrazoxane treatments on cardiac function.

Methods:

A total of 196 childhood ALL survivors were stratified (standard risk [SR], high risk with and without dexrazoxane (HR+DEX and HR). We performed a complete transthoracic echocardiographic assessment with M-mode echocardiography, Doppler, and Tissue Doppler. We used 2-dimensional and 3-dimensional echocardiography to measure the left ventricular ejection fraction, whereas myocardial strain imaging was used to obtain global strain indices.

Results:

Although most cardiac and arterial dimension parameters were not different between groups, a difference was observed in posterior intima of the right carotid (P=0.017). Diastolic functions analyses reported that LV shortening fraction and left and right ventricular lateral S’ wave amplitudes were lower in HR than in SR and HR+DEX groups (P=0.028, P=0.048, and P=0.005, respectively). The LV lateral E’ in diastolic function was lower in the HR than in SR and HR+DEX groups (P=0.036). The LV end-systolic wall stress was higher in HR than in SR and HR+DEX groups (P=0.009). A decrease contractility was observed, while the effect was not group specific. Strain rate was not different between groups, as opposed to tissue Doppler measurements.

Conclusions:

This study showed that dexrazoxane treatments could limit subclinical cardiac dysfunction in childhood ALL survivors, whereas survivors in HR group who did not receive dexrazoxane had potential subclinical cardiac damage observable in heart failure patients. Echocardiographic screening for survivors must be part of the follow-up routine in cardio-oncology.
Glucose 6 Phosphate Isomerase Deficiency, a Rare Hemolytic Anemia Misdiagnosed as Hereditary Spherocytosis
Authors: Gruda Sussman Raizl , Yan Adam Paul , Baker Jillian M.
Published: September 2022

Hereditary hemolytic anemias are a heterogenous group of disorders that include membranopathies, enzymopathies, and hemoglobinopathies. Genetic testing is helpful in the diagnostic workup when the clinical and laboratory workup is not conclusive. Here, we present a case of a 21-month-old female who was initially diagnosed with hereditary spherocytosis based on the presence of a variant of unknown significance in the SPTB gene. Further genetic workup revealed a homozygous glucose 6 phosphate isomerase mutation and the patient was ultimately diagnosed with glucose 6 phosphate isomerase deficiency.
Intravenous Iron Therapy for Children With Iron Deficiency Anemia
Authors: Orhan Mehmet F. , Büyükavci Mustafa
Published: September 2022

Iron deficiency anemia in children is a public health problem. Although oral iron treatment is the first choice, common side effects and compliance problems can cause the treatment to be interrupted. This study retrospectively evaluated children treated with intravenous (IV) iron sucrose or ferric carboxymaltose (FCM) and compared the treatment processes and efficacy. The demographic characteristics and treatment details of the 44 children with iron deficiency anemia were retrospectively evaluated. Iron sucrose was administered to 25 patients and FCM was administered to 19 patients. The IV iron infusion was applied to 64% of the patients because of unresponsiveness to oral treatment, 25% of the patients because of compliance problems, and 11% of the patients because of severe anemia. IV iron therapy increased hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, red-cell distribution width, and serum ferritin levels and decreased platelet count. The mean number of infusions per patient in the FCM group was lower, and the total treatment time was shorter. In conclusion, IV iron sucrose or FCM can be used in children with nonadherence to oral therapy and severe anemia in addition to specific indications.
Gaucher Disease Type 2 Manifested as Hemophagocytic Lymphohistiocytosis in a Neonate in the COVID-19 Era
Authors: Kosmeri Chrysoula , Rallis Dimitrios , Baltogianni Maria , Bouza Helen , Lykopoulou Lilia , Lianou Loukia , Papadopoulou Eleni , Tzanoudaki Marianna , Farmaki Evangelia , Papadakis Vassilios , Giapros Vasileios , Makis Alexandros
Published: September 2022

Background:

A term neonate presented with persistent severe thrombocytopenia, elevated liver enzymes, conjugated hyperbilirubinemia, hepatosplenomegaly, and mild hypotonia.

Observations:

A thorough workup for infections, congenital thrombocytopenias, and neonatal malignancies was negative. Because of increased anti-SARS-CoV-2 IgG antibodies after maternal COVID-19, multisystem inflammatory syndrome of neonates was considered and intravenous immunoglobulin was administered. The clinical condition of the neonate deteriorated and due to laboratory evidence of hyperinflammation, hemophagocytic lymphohistiocytosis was suspected, and treatment with etoposide and dexamethasone was initiated with temporary stabilization. Gaucher disease type 2 was eventually diagnosed.

Conclusion:

Gaucher disease can rarely present in neonates as hemophagocytic lymphohistiocytosis.
Thromboprophylaxis Outcome in Childhood SARS-CoV-2 Infection: A Single-Center Experience
Authors: Karimi Mehran , Sanaei Dashti Anahita , Haghpanah Sezaneh , Mansoori Yasaman , Zarei Tahereh , Amanati Ali , Bordbar Mohammadreza
Published: September 2022

Background:

The SARS-CoV-2 infection has been associated with potentially endothelial damage and coagulation cascade activation that cause thrombosis. There is limited information on thrombosis and anticoagulant therapy in children with coronavirus disease 2019 (COVID-19).

Aims:

This study evaluates the outcome of thromboprophylaxis in children younger than 18-year old with COVID-19 infection.

Methods:

A retrospective study was conducted on 184 hospitalized pediatric patients with confirmed COVID-19 infection. A designed questionnaire was made to collect all demographic, clinical, and laboratory data. According to World Health Organization, the patients were classified as asymptomatic/mild, moderate, severe, and critically ill.

Results:

The mean age of the patients was 7.04±5.9 (1 wk to younger than 18 y). Overall, 33 patients received anticoagulant therapy. All patients who passed away (n=19) belonged to the critical group. One patient (1.28%) was complicated with deep vein thrombosis despite taking thromboprophylaxis, and 1 (1.28%) with pulmonary thromboembolism while the patient did not take an anticoagulant.

Conclusions:

Our data showed a lower rate of thrombosis (1.4%) than adult patients with COVID-19. It may underline the role of anticoagulants in moderate to severe/critically ill children with COVID-19 infection. Expert opinion and personal experience are necessary, while we have a significant knowledge gap in understanding COVID-19-associated coagulopathy and thrombotic risk in children.
Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells
Authors: Jin Fen-fen , Wang Chan-juan , Cui Lei , Liu Fei-fei , Wang Kai-ling , Li Wei-jing , Li Zhi-gang
Published: September 2022

Low expression levels of E2F3a and caspase 8-associated protein 2 (CASP8AP2) are associated with poor outcomes in children with acute lymphoblastic leukemia. Our previous study showed that a combined assessment of E2F3a and CASP8AP2 expression was more accurate in predicting relapse in children with acute lymphoblastic leukemia. However, the underlying mechanism remains unclear. In this study, the interaction between E2F3a and CASP8AP2 and its role in the regulation of histone expression, cell proliferation, the cell cycle, and chemosensitivity were investigated. Exogenous E2F3a-GST was coprecipitated with CASP8AP2-FLAG in HEK-293T cells. E2F3a was colocalized with CASP8AP2-GFP in the nucleus. The replication-dependent histones H2A and H2B were significantly upregulated when E2F3a or CASP8AP2 was overexpressed in HEK-293T or 697 cells and downregulated by E2F3a or CASP8AP2 knockdown. E2F3a and CASP8AP2 could collaboratively enhance the transcriptional activity of HIST1H2AG and HIST1H2BK. Both CASP8AP2 and E2F3a are involved in S phase progression. E2F3a and CASP8AP2 also affected the sensitivity of leukemic cells to daunorubicin. Therefore, CASP8AP2 and E2F3a collaboratively regulated replication-dependent histone expression, cell cycle progression, and chemosensitivity of leukemic cells.
Mitotic Checkpoints and the Role of WEE1 Inhibition in Head and Neck Squamous Cell Carcinoma
Authors: Khan Shihan N. , Swiecicki Paul L. , Doroshow Deborah B.
Published: September 2022

The WEE1 kinase family plays a crucial role in cell cycle regulation and DNA damage response pathways in malignant cells. Inhibition of WEE1 effectively overrides G2 cell cycle arrest and results in the accumulation of extensive DNA damage within dividing cells, potentiating mitotic catastrophe and cell death. As such, the development of WEE1 inhibitors as antineoplastic therapeutics has gained increasing interest in recent years. In particular, the role of WEE1 inhibitors for treatment of head and neck squamous cell carcinomas remains an area of active research with both preclinical and clinical studies investigating their use as both single-agent therapy and chemosensitizers when used in tandem with traditional chemotherapy, particularly in the context of TP53-mutant tumors. Here, we review the relevant available preclinical and clinical data on hand investigating the efficacy of WEE1 inhibitors for the treatment of head and neck cancers.
Aurora Kinases as Therapeutic Targets in Head and Neck Cancer
Authors: Nguyen Theodore T. , Silva Flaviane N. , Golemis Erica A.
Published: September 2022

The Aurora kinases (AURKA and AURKB) have attracted attention as therapeutic targets in head and neck squamous cell carcinomas. Aurora kinases were first defined as regulators of mitosis that localization to the centrosome (AURKA) and centromere (AURKB), governing formation of the mitotic spindle, chromatin condensation, activation of the core mitotic kinase CDK1, alignment of chromosomes at metaphase, and other processes. Subsequently, additional roles for Aurora kinases have been defined in other phases of cell cycle, including regulation of ciliary disassembly and DNA replication. In cancer, elevated expression and activity of Aurora kinases result in enhanced or neomorphic locations and functions that promote aggressive disease, including promotion of MYC expression, oncogenic signaling, stem cell identity, epithelial-mesenchymal transition, and drug resistance. Numerous Aurora-targeted inhibitors have been developed and are being assessed in preclinical and clinical trials, with the goal of improving head and neck squamous cell carcinoma treatment.
Targeting HRAS in Head and Neck Cancer
Authors: Desilets Antoine , Ho Alan L.
Published: September 2022

HRAS mutations define a unique biologic subset of head and neck squamous cell carcinoma. Oncogenic HRAS is uniquely dependent on posttranslational farnesylation for membrane localization and activation of downstream signaling. Tipifarnib, a farnesyltransferase inhibitor, demonstrated encouraging antitumor activity for HRAS mutant head and neck squamous cell carcinoma and modest activity for HRAS mutant salivary gland cancer. New combination strategies to circumvent intrinsic and acquired resistance to TFIs are being investigated.
Does Lower Extremity Nerve Decompression Surgery Improve Quality of Life?
Authors: Fakkel Tirzah M. , Rinkel Willem D. , Coert J. Henk
Published: September 2022

Background:

Entrapment neuropathies are more prevalent in patients with diabetes. The aim of this study was to assess the effects of lower extremity nerve decompression (LEND) surgery on quality of life (QOL), together with the determination of predictors of this surgical outcome and the incidence of surgical site problems.

Methods:

Patients who underwent LEND surgery between September 2017 and March 2019 were prospectively followed at the outpatient clinic of our hospital. The common, superficial and deep peroneal nerve, and tibial nerve at the tarsal tunnel and soleal sling were decompressed if an entrapment was diagnosed. The primary study outcome was QOL, measured with the Norfolk QOL-DN questionnaire. Secondary outcomes of interest were 1) change in Michigan Neuropathy Screening Instrument (MNSI) scores, 2) predictors of the Norfolk QOL-DN score at follow-up and 3) the occurrence of complications.

Results:

60 patients were operated (45 unilateral, 15 bilateral), with a median post-operative follow-up of 13.0 months (interquartile range (IQR): 7.3-18.0). QOL significantly improved in this period of observation (baseline: median 46.0 (34.0-62.0) vs. follow-up: median 37.0 (20.0-60.0), p=0.011), as were MNSI scores (7.0 (5.0-9.0) to 3.0 (0.0-6.5), p<0.01). Predictors of QOL were a higher baseline QOL score (beta: 0.59, p=0.001), a longer follow-up time (beta: 2.34, p<0.001) and hypertension (beta: 16.38, p=0.03). 26.7% of patients suffered from surgical site problems, including wound infections (18.3%).

Conclusions:

LEND surgery significantly improves QOL by reducing neuropathy symptoms in patients with lower extremity nerve compressions. However, attention should be given to lowering the risk of wound complications.
Negative pressure wound therapy improves take rate of skin graft in irregular, high-mobility areas compared to Tie-over Bolster Dressings: A Randomized Controlled Trial
Authors: Cao Xiaoling , Hu Zhicheng , Zhang Yi , Wang Peng , Huang Shaobin , Zhu Wenkai , Dong Yunxian , Xu Hailin , Tang Bing , Zhu Jiayuan
Published: September 2022

Background:

The clinical problem of tie-over bolster dressing (TBD) securing the skin graft is low graft take rates in irregular, high-mobility areas and suboptimal recipient wound beds. Negative pressure wound therapy (NPWT) has become a well-established method to securing the graft, and the graft take rate of this method were reported to 96.7%. However, comparative efficacies between the TBD and NPWT on irregular, high-mobility areas are yet to be determined.

Study Design:

Patients eligible for skin graft were randomly assigned to receive either NPWT or TBD between December 2014 and December 2015. The primary outcome was determined by the take rate of skin grafts between the fifth and seventh postoperative day. The secondary outcomes were dressing time and postoperative complications including hematoma, seroma, infection, displacement, and necrosis.

Results:

A total of 86 patients were enrolled to receive either NPWT (n=43) or TBD (n=43) for skin graft treatment. NPWT significantly improved the take rate of grafts as compared to TBD (97.2% vs. 90.2%; p = 0.005). The improvements came from the grafts in irregular, high-mobility areas in the respective groups (97.6% vs. 81.7%; p < 0.001). NPWT reduced the skin graft displacement in postoperative complications as compared with that in TBD (1 patient vs. 9 patients; p = 0.007). The dressing time of the NPWT was significantly shorter as compared with TBD (15. 2±4.2 min vs. 27.4±4.3 min; p = 0.001).

Conclusions:

NPWT could improve the take rate of skin grafts in irregular, high-mobility areas, and shorten the dressing time.
Fat Grafting as Regenerative Surgery: A Current Review
Authors: Firriolo Joseph M. , Condé-Green Alexandra , Pu Lee L.Q.
Published: September 2022

Autologous fat grafting has long been regarded an ideal filler, lauded for its ability to restore soft tissue contour. In recent times, fat grafting has exhibited regenerative capacity, largely secondary to the action of adipose-derived stem cells and preadipocytes in the stromal vascular fraction (SVF) of adipose tissue. This has birthed a new field of regenerative surgery with benefits germane to scarring, fibrosis, atrophy, burns, neuropathic pain, autoimmune disease and more. The broad clinical applications of regenerative fat grafting have the potential to improve quality of life through functional and aesthetic improvement. Fat grafting has the potential to serve as a regenerative option for difficult clinical problems that cannot be effectively treated at the present time. Fat grafting also exhibits angiogenic and immunomodulatory properties in the context of autoimmune disease. The broad clinical applications of regenerative fat grafting have the potential to improve quality of life both functionally and aesthetically. It may present a less invasive avenue for clinical issues that today necessitate conventional surgical techniques. However, regenerative fat grafting is still in its infancy; further research is required to ascertain evidence-based protocols for the various clinical indications and better understand the precise regenerative mechanisms after fat grafting.
Physician Loans: Understanding and Overcoming an Epidemic.”
Authors: Manisundaram Arvind D. , Nagai Michael Y. , Frey Jordan D.
Published: September 2022

Background:

Plastic surgeons face increasing financial pressure from debt, largely in two forms: education and practice loans. We aim to provide perspective and context when assessing their individual situations while providing straightforward and evidence-based guidance for plastic surgeons to effectively manage their physician loan burden.

Methods:

Data from the AAMC national Graduation Questionnaire was used and analyzed. Resources for physician loans (both public and private) were also explored to determine options available to physicians.

Results:

By graduation, the education debt for the average medical graduate is roughly $200,000. Medical school debt makes up the majority of education debt, with the four-year cost-of-attendance (COA) for the class of 2020 at over $275,000 for over half of all medical schools. Over the last decade, the median cost of attendance (COA) has grown at a faster rate than median debt levels at a rate double that of inflation.

Conclusion:

The two major forms of debt facing plastic surgeons are educational and practice debt. Through financial education and the enactment of sound financial strategies, these debts can be effectively managed, improving physician well-being and bringing the focus more squarely back on patient care.
Long-Term Effect of Group Support Psychotherapy on Depression and HIV Treatment Outcomes: Secondary Analysis of a Cluster Randomized Trial in Uganda
Authors: Nakimuli-Mpungu Etheldreda , Smith Colin M. , Wamala Kizito , Okello James , Birungi Josephine , Etukoit Micheal , Mojtabai Ramin , Nachega Jean B. , Harari Ofir , Musisi Seggane , Mills Edward J.
Published: September 2022

Objective

We aimed to determine the effect of group support psychotherapy (GSP) compared with group HIV education (GHE) on depression and HIV treatment outcomes 24 months after treatment. We further aimed to investigate the mediating role of depression and antiretroviral therapy (ART) adherence in the relationship between GSP and viral load suppression.

Methods

Thirty HIV clinics across three districts were randomly assigned to deliver either GSP or GHE for depression. Depression and optimal (≥95%) ART adherence was assessed at baseline and 6, 12, 18, and 24 months after treatment. Viral load was drawn from the medical charts at baseline and 12 and 24 months after treatment. Multilevel mixed-effects regression models and generalized structural equation modeling were used to estimate 24-month outcomes and mediation effects.

Results

Participants (N = 1140) were enrolled from HIV clinics offering either GSP (n = 578 [51%]) or GHE (n = 562 [49%]). Fewer GSP than GHE participants met the criteria for depression at 24 months after treatment (1% versus 25%; adjusted odds ratio [aOR] = 0.002, 95% confidence interval [CI] = 0.0002–0.018). More GSP than GHE participants reported optimal (≥95%) ART adherence (96% versus 88%; aOR = 20.88, 95% CI = 5.78–75.33) and improved viral suppression (96% versus 88%; aOR = 3.38, 95% CI = 1.02–11.02). The indirect effects of GSP through sequential reduction in depression and improvement in ART adherence at 12 months may partially explain the higher viral suppression rates at 24 months in GSP than GHE groups.

Conclusion

In settings where the HIV epidemic persists, depression treatment with GSP may be critical for optimal HIV treatment outcomes.

Trial Registration: The Pan African Clinical Trials Registry, number PACTR201608001738234.
Coronary Computed Tomography Angiography–derived Fractional Flow Reserve
Authors: Zhang Long Jiang , Tang Chunxiang , Xu Pengpeng , Guo Bangjun , Zhou Fan , Xue Yi , Zhang Jiayin , Zheng Minwen , Xu Lei , Hou Yang , Lu Bin , Guo Youmin , Cheng Jingliang , Liang Changhong , Song Bin , Zhang Huimao , Hong Nan , Wang Peijun , Chen Min , Xu Ke , Liu Shiyuan , Jin Zhengyu , Lu Guangming ,   on behalf of Chinese Society of Radiology
Published: September 2022

Invasive fractional flow reserve (FFR) measured by a pressure wire is a reference standard for evaluating functional stenosis in coronary artery disease. Coronary computed tomography angiography–derived fractional flow reserve (CT-FFR) uses advanced computational analysis methods to noninvasively obtain FFR results from a single conventional coronary computed tomography angiography data to evaluate the hemodynamic significance of coronary artery disease. More and more evidence has found good correlation between the results of noninvasive CT-FFR and invasive FFR. CT-FFR has proven its potential in optimizing patient management, improving risk stratification and prognosis, and reducing total health care costs. However, there is still a lack of standardized interpretation of CT-FFR technology in real-world clinical settings. This expert consensus introduces the principle, workflow, and interpretation of CT-FFR; summarizes the state-of-the-art application of CT-FFR; and provides suggestions and recommendations for the application of CT-FFR with the aim of promoting the standardized application of CT-FFR in clinical practice.
The Chinese Experience of Imaging in Cardiac Intervention
Authors: Liu Zinuan , Yang Junjie , Chen Yundai
Published: September 2022

Recent scientific and technological advances have greatly contributed to the development of medical imaging that could enable specific functions. It has become the primary focus of cardiac intervention in preoperative assessment, intraoperative guidance, and postoperative follow-up. This review provides a contemporary overview of the Chinese experience of imaging in cardiac intervention in recent years.
Venous thromboembolic screening in pediatric trauma: A prospective cohort study of risk-stratified ultrasonography
Authors: Tobias Joseph , Labuz Daniel F. , Cunningham Aaron , Dixon Alexandra , Selesner Leigh , Moss Lori , Dewey Elizabeth , Haley Kristina M. , Burns Erin , Schreiber Martin , Wilson Rachel , Hamilton Nicholas A. , Jafri Mubeen A.
Published: September 2022

BACKGROUND

This prospective observational cohort study evaluates risk-stratified venous thromboembolism (VTE) screening in injured children. While the reported incidence of VTE is 6% to 10% among critically injured children, there is no standard for screening. Venous thromboembolism may have long-term sequelae in children, including postthrombotic syndrome.

METHODS

Patients admitted to a level 1 pediatric trauma center were risk stratified for VTE using a validated prediction algorithm. Children at high risk (risk scores ≥523; i.e., ≥1% risk) received screening duplex ultrasonography. Children at moderate risk (risk scores 410–522; i.e., 0.3–0.99% risk) were screened as a comparison/control.

RESULTS

Three-hundred fifty-five children were consecutively risk stratified from October 2019 to May 2021. Forty-seven children received screening duplex ultrasounds: 21 from a high-risk cohort and 26 from a moderate-risk cohort. Four children were diagnosed with VTE in the high-risk cohort compared with seven in the moderate-risk cohort (p = 0.53). Total incidence of VTE among screened children was 23.4% (11 of 47). Asymptomatic VTE accounted for 81.8% of all events (9 of 11). Fifty-four percent (6 of 11) of VTE were central venous catheter associated. Venous thromboembolism in surviving children resolved by 3 to 6 months with no symptoms of postthrombotic syndrome after 1 year. No cases of VTE were identified in unscreened children, yielding an institutional VTE incidence of 3.1% (11 of 355).

DISCUSSION

Risk-stratified screening demonstrates a significant incidence of asymptomatic VTE in injured children. These results may guide reevaluation of prediction algorithms developed from symptomatic VTE risk and longitudinal study of the sequelae of asymptomatic VTE.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Resuscitative practices and the use of low-titer group O whole blood in pediatric trauma
Authors: Morgan Katrina M. , Leeper Christine M. , Yazer Mark H. , Spinella Philip C. , Gaines Barbara A.
Published: September 2022

Increasing rates of penetrating trauma in the United States makes rapid identification of hemorrhagic shock, coagulopathy, and early initiation of balanced resuscitation in injured children of critical importance. Hemorrhagic shock begins early after injury and can be challenging to identify in children, as hypotension is a late sign that a child is on the verge of circulatory collapse and should be aggressively resuscitated. Recent data support shifting away from crystalloid and toward early resuscitation with blood products because of worse coagulopathy and clinical outcomes in injured patients resuscitated with crystalloid. Multicenter studies have found improved survival in injured children who receive balanced resuscitation with higher fresh frozen plasma: red blood cell ratios. Whole blood is an efficient way to achieve balanced resuscitation in critically injured children with limited intravenous access and decreased exposure to multiple donors. Administration of cold-stored, low-titer O-negative whole blood (LTOWB) appears to be safe in adults and children and may be associated with improved survival in children with life-threatening hemorrhage. Many pediatric centers use RhD-negative LTOWB for all female children because of the risk of hemolytic disease of the fetus and newborn (0–6%); however. there is a scarcity of LTOWB compared with the demand. Low risks of hemolytic disease of the fetus and newborn affecting a future pregnancy must be weighed against high mortality rates in delayed blood product administration in children in hemorrhagic shock. Survey studies involving key stakeholder's opinions on pediatric blood transfusion practices are underway. Existing pediatric-specific literature on trauma resuscitation is often limited and underpowered; multicenter prospective studies are urgently needed to define optimal resuscitation products and practices in injured children in an era of increasing penetrating trauma.
The TH01 microsatellite and INS VNTR are strongly associated with type 2 diabetes and fasting insulin secretion
Authors: Berumen Jaime , Orozco Lorena , Gallardo-Rincón Héctor , Juárez-Torres Eligia , Barrera Elizabeth , Cruz-López Miguel , Benuto Rosa Elba , Ramos-Martinez Espiridión , Marin-Madina Melissa , Alvarado-Silva Anabel , Valladares-Salgado Adán , Peralta-Romero José de Jesús , García-Ortiz Humberto , Martinez-Juarez Luis Alberto , Montoya Alejandra , Alvarez-Hernández Diego-Abelardo , Alegre-Diaz Jesús , Kuri-Morales Pablo , Tapia-Conyer Roberto
Published: September 2022

Abstract

A variable number of tandem repeats (VNTR) located in the insulin gene (INS) control region may be involved in the development of type 2 diabetes (T2D). The TH01 microsatellite is located close to INS and has previously been suggested to be involved its regulation. Therefore, this observational study investigated whether the TH01 microsatellite and INS VNTR, as assessed via the surrogate marker single nucleotide polymorphism (SNP) rs689, are associated with T2D in the Mexican population. Logistic regression models were used to calculate the risk conferred by TH01 and INS VNTR loci for T2D development. TH01 alleles 6, 8, 9 and 9.3 and allele A of rs689 were independently associated with T2D; differences were found between age at T2D diagnosis and sex. Larger alleles of TH01 (≥8 repeats) conferred an increased risk for T2D in males when compared with smaller alleles (≤7 repeats) (odds ratio, ≥1.46; 95% confidence interval, 1.1–1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed at ≥46 years whereas they conferred protection when diagnosed at ≤45 years. Both TH01 and SNP rs689 were associated with T2D in the same groups; the association remained significant for both loci in multivariate models. The median fasting plasma insulin concentration was significantly higher in patients with T2D versus controls, and in those diagnosed at ≤45 versus ≥46 years. TH01 larger alleles or the A allele of rs689 may potentiate insulin synthesis in males, but not females, without T2D, a process that is disabled in those with T2D.
Relationship between gait parameters and cognitive indexes in elderly adults
Authors: Aznielle-Rodríguez Tania , Galán-García Lídice , Ontivero-Ortega Marlis , Aguilar-Mateu Karen , Castro-Laguardia Ana M. , Fernández-Nin Ana , García-Agustín Daysi , Valdés-Sosa Mitchell
Published: September 2022

Purposes

To select the summary cognitive index that is best predicted from spatio-temporal gait features (STGF) extracted from gait patterns.

Methods

125 participants were recruited, including 40 young and 85 elderly adults. Their performances in different cognitive domains were evaluated through 12 cognitive measures obtained from five neuropsychological tests. Four summary cognitive indexes were calculated in each case: 1) the z-score of Mini-Mental State Examination (MMSE) from a population norm (MMSE z-score); 2) the sum of the absolute z-scores of the patient’s neuropsychological measures from a population norm (ZSum); 3) the patient’s scores for the first principal component (PC) of the set of neuropsychological test scores (PCCog); and 4) the Mahalanobis distance of each patient’s score from a population norm (MDCog). The gait patterns were recorded while they executed four walking tasks (normal, fast, easy- and hard-dual tasks). Sixteen STGF were measured using a body-fixed Inertial Measurement Unit. Dual-task costs were computed. The proportion of variances (R2) that PCA-STGF scores accounted for the four summary cognitive indexes and for the 12 cognitive variables across individuals were measured in multiple linear regressions. The confidence intervals for each R2 were estimated by bootstrapping the regression 1000 times.

Results

The mean values of R2 for the summary cognitive indexes were: 0.0831 for MMSE z-score, 0.0624 for ZSum, 0.0614 for PCCog, and 0.4751 for MDCog. The mean values of R2 for the 12 cognitive values ranged between 0.0566 and 0.1211. The multivariate linear regression was only statistically significant for MDCog, with the highest value of the R2 estimation.

Conclusions

Individual cognitive variables and most of the summary cognitive indices showed a weak association with gait parameters. However, the MDCog index showed a stronger association, explaining about 50 % of the variance. This suggests that this index can be used to study the relationship between gait patterns and cognition.
Benchmarking Oxford Nanopore Read Alignment-Based Structural Variant Detection Tools in Crop Plant Genomes
Authors: Yildiz Gözde , Zanini Silvia F. , Afsharyan Nazanin P , Obermeier Christian , Snowdon Rod J , Golicz Agnieszka A.
Published: September 2022

Structural variations (SVs) are larger polymorphisms (>50 bp in length), which consist of insertions, deletions, inversions, duplications, and translocations. They can have a strong impact on agronomical traits and play an important role in environmental adaptation. The development of long-read sequencing technologies, including Oxford Nanopore, allows for comprehensive SV discovery and characterization even in complex polyploid crop genomes. However, many of the SV discovery pipeline benchmarks do not include complex plant genome datasets. In this study, we benchmarked popular long-read alignment-based SV detection tools for crop plant genomes. We used real and simulated Oxford Nanopore reads for two crops, allotetraploidBrassica napus(oilseed rape) and diploidSolanum lycopersicum(tomato), and evaluated several read aligners and SV callers across 5×, 10×, and 20× coverages typically used in re-sequencing studies. Our benchmarks provide a useful guide for designing Oxford Nanopore re-sequencing projects and SV discovery pipelines for crop plants.
Bio-Aurac – an open-source browser plugin to better navigate literature content
Authors: Etherington Nick E J , Evans Ashley J , Laing Mark P , Rollings Brad , Sweeton Michael J , Whitehorn Alex J , Southan C , Holliday Gemma L , Jimenez Rafael C , Dunlop Ian W
Published: September 2022

Bio-Aurac is an open-source web browser plugin designed to support the research community in drug discovery and life sciences. The tool has been designed to help researchers, scientists, and curators to better explore, navigate and understand content from literature accessing valuable integrated information from third party resources. It identifies, highlights, and provides additionally knowledge for names of biochemical entities like genes and proteins.

Availability and Implementation

Bio-Aurac has been implemented using a microservice architecture which is open-source and abstracted from non-technical users by utilizing Docker containers (Nüst, 2020). It can be run with minimal prerequisites on both Chrome and Firefox browsers.

The code for installing and running the web browser plugin can be found here:https://github.com/mdcatapult/bio-aurac(Along with detailed installation instructions). A comprehensive collection of all the code involved in building this open-source project can be found:https://github.com/mdcatapult/aurac-web-plugin,https://github.com/mdcatapult/PDF-Converter,https://github.com/mdcatapult/entity-recognition

Contact

SoftwareEngineering@md.catapult.org.uk,ian.dunlop@md.catapult.org.uk