bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination
Authors: Jeong Seo-Yeon , Hariharasudhan Gurusamy , Kim Min-Ji , Lim Ji-Yeon , Jung Sung Mi , Choi Eun-Ji , Chang In-Youb , Kee Younghoon , You Ho Jin , Lee Jung-Hee 
Published: September 2022

Abstract
Human CtIP maintains genomic integrity primarily by promoting 5′ DNA end resection, an initial step of the homologous recombination (HR). A few mechanisms have been suggested as to how CtIP recruitment to damage sites is controlled, but it is likely that we do not yet have full understanding of the process. Here, we provide evidence that CtIP recruitment and functioning are controlled by the SIAH2 E3 ubiquitin ligase. We found that SIAH2 interacts and ubiquitinates CtIP at its N-terminal lysine residues. Mutating the key CtIP lysine residues impaired CtIP recruitment to DSBs and stalled replication forks, DSB end resection, overall HR repair capacity of cells, and recovery of stalled replication forks, suggesting that the SIAH2-induced ubiquitination is important for relocating CtIP to sites of damage. Depleting SIAH2 consistently phenocopied these results. Overall, our work suggests that SIAH2 is a new regulator of CtIP and HR repair, and emphasizes that SIAH2-mediated recruitment of the CtIP is an important step for CtIP’s function during HR repair.
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

AbstractA 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

Abstract

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.
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.
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.
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.
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

Abstract
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

Abstract
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

Abstract
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.