bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occlusive Retinal Vasculitis Following Intravitreal Brolucizumab
Authors: Witkin Andre J. , Hahn Paul , Murray Timothy G. , Arevalo J. Fernando , Blinder Kevin J. , Choudhry Netan , Emerson Geoff G. , Goldberg Roger A. , Kim Stephen J. , Pearlman Joel , Schneider Eric W. , Tabandeh Homayoun , Wong Robert W. 
Published: July 2020

Purpose: To analyze a case series of retinal vasculitis reported to the American Society of Retina Specialists (ASRS) following Food and Drug Administration approval of brolucizumab for treatment of neovascular age-related macular degeneration. Methods: The ASRS Research and Safety in Therapeutics Committee analyzed clinical and imaging characteristics from submitted reports of retinal vasculitis after brolucizumab. Results: Retinal vasculitis was reported in 26 eyes of 25 patients (22 [88%] female) after treatment with brolucizumab. Imaging studies were available for 24 of 26 eyes. Most cases (92%) were associated with intraocular inflammation, which presented at a mean of 25 days (range, 3-63 days) after the most recent brolucizumab injection. Mean visual acuity (VA) was 20/52 (range, 20/25-4/200) before the adverse event, 20/151 (range, 20/25-hand motion) at presentation of the adverse event, and 20/243 (range, 20/30-light perception) at last follow-up. Twelve eyes (46%) had a greater than 3-line decrease in VA at final follow-up, and 12 eyes (46%) had a final VA of 20/200 or worse. Analysis of retinal imaging identified vasculopathy that involved retinal arteries (91%), retinal veins (79%), and choroidal vessels (48%). Occlusive disease was apparent on imaging in 83% of eyes. Treatment approaches were varied. Conclusions: Retinal vasculitis has been identified in a series of eyes following brolucizumab. Although a few eyes in this series were asymptomatic or minimally symptomatic, some eyes had significant vision loss. A careful examination for signs of active inflammation prior to brolucizumab injection is recommended. Once vasculopathy is suspected, angiographic imaging may help define the spectrum of involvement. Optimal treatment strategies remain unknown.
Extending cervicoplastic surgery: an alternative technique to overcome the limitation of office hysteroscopy
Authors: Calzolari Stefano , Comito Chiara , Pavone Dora , Sorbi Flavia , Castellacci Eleonora , Giarrè Giovanna , Andersson Karin Louise , Dubini Valeria , Petraglia Felice 
Published: July 2020

AbstractOur objective is to show a feasible approach to the hysteroscopic procedures when the cervical canal has a diameter smaller than the lesion. Our study is designed as a case series and illustration of the surgical hysteroscopic technique. A group of patients (n = 37) underwent office hysteroscopy in Regional Reference Center for Hysteroscopy Service at Palagi Hospital, Florence, Italy, to see and treat an endometrial polyp with unfavorable cervical conditions between January 2019 and December 2019. An office hysteroscopy in outpatient setting with vaginoscopic approach was performed in women with unfavorable cervical conditions. Fiber-based 3.5-mm hysteroscope, with 5F electrosurgery unit and 5F bipolar electrode, was used to perform the cervicoplasty in order to enlarge the cervical canal from internal to external os, following by the removal of the endometrial polyp with the excision of the base only without slicing. After 90 days, a follow-up hysteroscopy was performed. The procedure was performed successfully in 89.2% of patients.The surgical technique of cervicoplastic allows to perform an operative procedure without analgesia/sedation or anesthesia or blind cervical dilation, reducing the risk of complications and costs. Furthermore, cervicoplasty allowed the removal en bloc of the endocavitary lesion in all cases. At the follow-up hysteroscopy, the cervical passage was straight and smooth, without lesions repaired in all patients. Cervicoplasty is a technique which allows to perfume an ease and comfortable hysteroscopic procedure even in patients with unfavorable cervical canal. Due to the widening of the diameter of the cervical canal, intracavitary lesions are removed intact resulting in an optimal pathological evaluation.
Chromatin 3D structure reconstruction with consideration of adjacency relationship among genomic loci
Authors: Li Fang-Zhen , Liu Zhi-E , Li Xiu-Yuan , Bu Li-Mei , Bu Hong-Xia , Liu Hui , Zhang Cai-Ming 
Published: July 2020

Abstract
Background
Chromatin 3D conformation plays important roles in regulating gene or protein functions. High-throughout chromosome conformation capture (3C)-based technologies, such as Hi-C, have been exploited to acquire the contact frequencies among genomic loci at genome-scale. Various computational tools have been proposed to recover the underlying chromatin 3D structures from in situ Hi-C contact map data. As connected residuals in a polymer, neighboring genomic loci have intrinsic mutual dependencies in building a 3D conformation. However, current methods seldom take this feature into account.

Results
We present a method called ShNeigh, which combines the classical MDS technique with local dependence of neighboring loci modeled by a Gaussian formula, to infer the best 3D structure from noisy and incomplete contact frequency matrices. We validated ShNeigh by comparing it to two typical distance-based algorithms, ShRec3D and ChromSDE. The comparison results on simulated Hi-C dataset showed that, while keeping the high-speed nature of classical MDS, ShNeigh can recover the true structure better than ShRec3D and ChromSDE. Meanwhile, ShNeigh is more robust to data noise. On the publicly available human GM06990 Hi-C data, we demonstrated that the structures reconstructed by ShNeigh are more reproducible between different restriction enzymes than by ShRec3D and ChromSDE, especially at high resolutions manifested by sparse contact maps, which means ShNeigh is more robust to signal coverage.

Conclusions
Our method can recover stable structures in high noise and sparse signal settings. It can also reconstruct similar structures from Hi-C data obtained using different restriction enzymes. Therefore, our method provides a new direction for enhancing the reconstruction quality of chromatin 3D structures.
Identification of vital candidate microRNA/mRNA pairs regulating ovule development using high-throughput sequencing in hazel
Authors: Liu Jianfeng , Luo Qizheng , Zhang Xingzheng , Zhang Qiang , Cheng Yunqing 
Published: July 2020

Abstract
Background
Hazels (Corylus spp.) are economically important nut-producing species in which ovule development determines seed plumpness, one of the key parameters reflecting nut quality. microRNAs (miRNAs) play important roles in RNA silencing and the post-transcriptional regulation of gene expression. However, very little is currently known regarding the miRNAs involved in regulating ovule growth and development.

Results
In this study, we accordingly sought to determine the important miRNAs involved in ovule development and growth in hazel. We examined ovules at four developmental stages, namely, ovule formation (Ov1), early ovule growth (Ov2), rapid ovule growth (Ov3), and ovule maturity (Ov4). On the basis of small RNA and mRNA sequencing using the Illumina sequencing platform, we identified 970 miRNAs in hazel, of which 766 and 204 were known and novel miRNAs, respectively. In Ov1-vs-Ov2, Ov1-vs-Ov3, Ov1-vs-Ov4, Ov2-vs-Ov3, Ov2-vs-Ov4, and Ov3-vs-Ov4 paired comparisons, 471 differentially expressed microRNAs (DEmiRNAs) and their 3117 target differentially expressed messenger RNAs (DEmRNAs) formed 11,199 DEmiRNA/DEmRNA pairs, with each DEmiRNA changing the expression of an average of 6.62 target mRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of all DEmRNAs revealed 29 significantly enriched KEGG pathways in the six paired comparisons, including protein export (ko03060), fatty acid elongation (ko00062), starch and sucrose metabolism (ko00500), fatty acid biosynthesis (ko00061), and amino sugar and nucleotide sugar metabolism (ko00520). Our results indicate that DEmiRNA/DEmRNA pairs showing opposite change trends were related to stress tolerance, embryo and seed development, cell proliferation, auxin transduction, and the biosynthesis of proteins, starch, and fats may participate in ovule growth and development.

Conclusions
These findings contribute to a better understanding of ovule development at the level of post-transcriptional regulation, and lay the foundation for further functional analyses of hazelnut ovule growth and development.
Comparative RNA-Seq transcriptome analyses reveal dynamic time-dependent effects of 56Fe, 16O, and 28Si irradiation on the induction of murine hepatocellular carcinoma
Authors: Nia Anna M. , Khanipov Kamil , Barnette Brooke L. , Ullrich Robert L. , Golovko George , Emmett Mark R. 
Published: July 2020

Abstract
Background
One of the health risks posed to astronauts during deep space flights is exposure to high charge, high-energy (HZE) ions (Z > 13), which can lead to the induction of hepatocellular carcinoma (HCC). However, little is known on the molecular mechanisms of HZE irradiation-induced HCC.

Results
We performed comparative RNA-Seq transcriptomic analyses to assess the carcinogenic effects of 600 MeV/n 56Fe (0.2 Gy), 1 GeV/n 16O (0.2 Gy), and 350 MeV/n 28Si (0.2 Gy) ions in a mouse model for irradiation-induced HCC. C3H/HeNCrl mice were subjected to total body irradiation to simulate space environment HZE-irradiation, and liver tissues were extracted at five different time points post-irradiation to investigate the time-dependent carcinogenic response at the transcriptomic level. Our data demonstrated a clear difference in the biological effects of these HZE ions, particularly immunological, such as Acute Phase Response Signaling, B Cell Receptor Signaling, IL-8 Signaling, and ROS Production in Macrophages. Also seen in this study were novel unannotated transcripts that were significantly affected by HZE. To investigate the biological functions of these novel transcripts, we used a machine learning technique known as self-organizing maps (SOMs) to characterize the transcriptome expression profiles of 60 samples (45 HZE-irradiated, 15 non-irradiated control) from liver tissues. A handful of localized modules in the maps emerged as groups of co-regulated and co-expressed transcripts. The functional context of these modules was discovered using overrepresentation analysis. We found that these spots typically contained enriched populations of transcripts related to specific immunological molecular processes (e.g., Acute Phase Response Signaling, B Cell Receptor Signaling, IL-3 Signaling), and RNA Transcription/Expression.

Conclusions
A large number of transcripts were found differentially expressed post-HZE irradiation. These results provide valuable information for uncovering the differences in molecular mechanisms underlying HZE specific induced HCC carcinogenesis. Additionally, a handful of novel differentially expressed unannotated transcripts were discovered for each HZE ion. Taken together, these findings may provide a better understanding of biological mechanisms underlying risks for HCC after HZE irradiation and may also have important implications for the discovery of potential countermeasures against and identification of biomarkers for HZE-induced HCC.
Patient-reported and doctor-reported symptoms when faecal immunochemical tests are requested in primary care in the diagnosis of colorectal cancer and inflammatory bowel disease: a prospective study
Authors: Högberg Cecilia , Karling Pontus , Rutegård Jörgen , Lilja Mikael 
Published: July 2020

Abstract
Background
Rectal bleeding and a change in bowel habits are considered to be alarm symptoms for colorectal cancer and they are also common symptoms for inflammatory bowel disease. However, most patients with these symptoms do not have any of these diseases. Faecal immunochemical tests (FITs) for haemoglobin are used as triage tests in Sweden and other countries but little is known about the symptoms patients have when FITs are requested.

Objective
Firstly, to determine patients’ symptoms when FITs are used as triage tests in primary care and whether doctors record the symptoms that patients report, and secondly to evaluate the association between symptoms, FIT results and possible prediction of colorectal cancer or inflammatory bowel disease.

Methods and materials
This prospective study included 364 consecutive patients for whom primary care doctors requested a FIT. Questionnaires including gastrointestinal symptoms were completed by patients and doctors.

Results
Concordance between symptoms reported from patients and doctors was low. Rectal bleeding was recorded by 43.5% of patients versus 25.6% of doctors, FITs were negative in 58.3 and 52.7% of these cases respectively. The positive predictive value (PPV) of rectal bleeding recorded by patients for colorectal cancer or inflammatory bowel disease was 9.9% (95% confidence interval [CI] 5.2–14.7); for rectal bleeding combined with a FIT the PPV was 22.6% (95% CI 12.2–33.0) and the negative predictive value (NPV) was 98.9% (95% CI 96.7–100). For patient-recorded change in bowel habits the PPV was 6.1% (95% CI 2.4–9.8); for change in bowel habits combined with a FIT the PPV was 18.2% (95% CI 9.1–30.9) and the NPV 100% (95% CI 90.3–100).

Conclusions
Doctors should be aware that, during consultations, they do not record all symptoms experienced by patients. FITs requested in primary care, when found positive, may potentially be of help in prioritising referrals, also when patients present with rectal bleeding or change in bowel habits.
Treatment of urinary tract infections in Swiss primary care: quality and determinants of antibiotic prescribing
Authors: Plate Andreas , Kronenberg Andreas , Risch Martin , Mueller Yolanda , Di Gangi Stefania , Rosemann Thomas , Senn Oliver 
Published: July 2020

Abstract
Background
Urinary tract infections are one of the most common reasons for prescribing antibiotics in primary care. Current guidelines recommend fosfomycin, nitrofurantoin, or trimethoprim - sulfamethoxazol as empiric first line antimicrobial agents in uncomplicated infections. However, there is evidence that the use of fluoroquinolones, which are no longer recommended, is still inappropriate high. We determined antibiotic prescription patterns, quality and factors affecting antibiotic prescriptions in urinary tract infections in primary care in Switzerland.

Methods
From June 2017 to August 2018, we conducted a cross-sectional study in patients suffering from a urinary tract infection (UTI). Patient and general practitioners characteristics as well as antibiotic prescribing patterns were analysed.

Results
Antibiotic prescribing patterns in 1.352 consecutively recruited patients, treated in 163 practices could be analysed. In 950 (84.7%) patients with an uncomplicated UTI the prescriptions were according to current guidelines and therefore rated as appropriate. Fluoroquinolones were prescribed in 13.8% and therefore rated as inappropriate. In multivariable analysis, the age of the general practitioner was associated with increasing odds of prescribing a not guideline recommended antibiotic therapy.

Conclusions
We found a high degree of guideline conform antibiotic prescriptions in patients with an uncomplicated urinary tract infection in primary care in Switzerland. However, there is still a substantial use of fluoroquinolones in empiric therapy.
Mycobacterial antigens in pleural fluid mononuclear cells to diagnose pleural tuberculosis in HIV co-infected patients
Authors: Mustafa Tehmina , Wergeland Ida , Baba Kamaldeen , Pathak Sharad , Hoosen Anwar A. , Dyrhol-Riise Anne Margarita 
Published: July 2020

Abstract
Background
Extra pulmonary manifestation of tuberculosis (TB) accounts for approximately one-half of TB cases in HIV-infected individuals with pleural TB as the second most common location. Even though mycobacteria are cleared, mycobacterial antigens may persist in infected tissues, causing sustained inflammation and chronicity of the disease. The aim of this study was to explore various mycobacterial antigens in pleural effusions, the impact of HIV infection and CD4+ T-cell depletion on the presence of antigens, and the diagnostic potential of antigens for improved and rapid diagnosis of pleural TB.

Methods
Pleural fluid specimens were collected from patients presenting with clinically suspected pleural TB, and processed routinely for culture, cytology, and adenosine deaminase activity analysis. HIV status and CD4+ T-cell counts were recorded. Pleural fluid mononuclear cells (PFMC) were isolated, and cell smears were stained with acid-fast staining and immunocytochemistry for various mycobacterial antigens. Real-time and nested-PCR were performed. Patients were categorized as pleural TB or non-TB cases using a composite reference standard. Performance of the mycobacterial antigens as diagnostic test was assessed.

Results
A total of 41 patients were enrolled, of which 32 were classified as pleural TB and 9 as non-TB. Thirteen patients had culture confirmed pleural TB, 26 (81%) were HIV-TB co-infected, and 64% had < 100 CD4+ T-cells/microL. Both secreted and cell-wall mycobacterial antigens were detected in PFMC. Lipoarabinomannan (LAM) was the most frequently detected antigen. There was no direct correlation between positive culture and antigens. Cases with low CD4+ T-cell counts had higher bacterial and antigen burden. By combining detection of secreted antigen or LAM, the sensitivity and specificity to diagnose pleural TB was 56 and 78%, respectively, as compared to 41 and 100% for culture, 53 and 89% for nested PCR, and 6 and 100% for real-time PCR.

Conclusion
Mycobacterial antigens were detectable in PFMC from tuberculous pleural effusions, even in cases where viable mycobacteria or bacterial DNA were not always detected. Thus, a combination of secreted antigen and LAM detection by immunocytochemistry may be a complement to acid-fast staining and contribute to rapid and accurate diagnosis of pleural TB.
Incidence and predictors of virological failure among adult HIV patients on first-line antiretroviral therapy in Amhara regional referral hospitals; Ethiopia: a retrospective follow-up study
Authors: Agegnehu Chilot Desta , Merid Mehari Woldemariam , Yenit Melaku Kindie 
Published: July 2020

Abstract
Background
Although the United Nations program on HIV/AIDS 90–90-90-targets recommends achieving 90% of viral suppression for patients on first-line antiretroviral therapy by 2020, virological failure is still high and it remains a global public health problem. Therefore, assessing the incidence and predictors of virological failure among adult HIV patients on first-line ART in Amhara regional referral hospitals, Ethiopia is vital to design appropriate prevention strategies for treatment failure and preventing the unnecessary switching to second-line regimens.

Method
An institution-based retrospective follow-up study was conducted on 490 adult HIV patients. The simple random sampling technique was used, and data were entered into Epi data Version 4.2.0.0 and was exported to Stata version 14 for analysis. The proportional hazard assumption was checked, and the Weibull regression was fitted. Cox-Snell residual was used to test the goodness of fit, and the appropriate model was selected by AIC/BIC. Finally, an adjusted hazard ratio with a 95% CI was computed, and variables with P-value < 0.05 in the multivariable analysis were taken as significant predictors of virological failure.

Results
The overall incidence rate of virological failure was 4.9 events per 1000 person-month observations (95%CI: 3.86–6.38). Users of CPT (AHR = 0.55, 95%CI: 0.31–0.97), poor adherence (AHR = 5.46, 95%CI: 3.07–9.74), CD4 Count <=200 cells/mm3 (AHR = 3.9, 95%CI: 1.07–13.9) and 201–350 cells/mm3 (AHR 4.1, 95%CI: 1.12–15) respectively, and NVP based first line drug regimen (AHR = 3.53, 95%CI: 1.73–7.21) were significantly associated with virological failure.

Conclusion
The incidence rate of virological failure was high. CPT, poor adherence, low baseline CD4 count and NVP based first-line drug regimen were independent risk factors associated with virological failure. Therefore, strengthening HIV care intervention and addressing these significant predictors is highly recommended in the study setting.
A retrospective cohort investigation of seroprevalence of Marburg virus and ebolaviruses in two different ecological zones in Uganda
Authors: Nyakarahuka Luke , Schafer Ilana J. , Balinandi Stephen , Mulei Sophia , Tumusiime Alex , Kyondo Jackson , Knust Barbara , Lutwama Julius , Rollin Pierre , Nichol Stuart , Shoemaker Trevor 
Published: July 2020

Abstract
Background
Uganda has experienced seven Ebola Virus Disease (EVD) outbreaks and four Marburg Virus Disease (MVD) outbreaks between 2000 and 2019. We investigated the seroprevalence and risk factors for Marburg virus and ebolaviruses in gold mining communities around Kitaka gold mine in Western Uganda and compared them to non-mining communities in Central Uganda.

Methods
A questionnaire was administered and human blood samples were collected from three exposure groups in Western Uganda (gold miners, household members of miners, non-miners living within 50 km of Kitaka mine). The unexposed controls group sampled was community members in Central Uganda far away from any gold mining activity which we considered as low-risk for filovirus infection. ELISA serology was used to analyse samples, detecting IgG antibodies against Marburg virus and ebolaviruses (filoviruses). Data were analysed in STATA software using risk ratios and odds ratios.

Results
Miners in western Uganda were 5.4 times more likely to be filovirus seropositive compared to the control group in central Uganda (RR = 5.4; 95% CI 1.5–19.7) whereas people living in high-risk areas in Ibanda and Kamwenge districts were 3.6 more likely to be seropositive compared to control group in Luweeero district (RR = 3.6; 95% CI 1.1–12.2). Among all participants, filovirus seropositivity was 2.6% (19/724) of which 2.3% (17/724) were reactive to Sudan virus only and 0.1% (1/724) to Marburg virus. One individual seropositive for Sudan virus also had IgG antibodies reactive to Bundibugyo virus. The risk factors for filovirus seropositivity identified included mining (AOR = 3.4; 95% CI 1.3–8.5), male sex (AOR = 3.1; 95% CI 1.01–9.5), going inside mines (AOR = 3.1; 95% CI 1.2–8.2), cleaning corpses (AOR = 3.1; 95% CI 1.04–9.1) and contact with suspect filovirus cases (AOR = 3.9, 95% CI 1.04–14.5).

Conclusions
These findings indicate that filovirus outbreaks may go undetected in Uganda and people involved in artisan gold mining are more likely to be exposed to infection with either Marburg virus or ebolaviruses, likely due to increased risk of exposure to bats. This calls for active surveillance in known high-risk areas for early detection and response to prevent filovirus epidemics.