bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of epidemiological distribution and outcome of COVID-19 in patients with hereditary hemorrhagic telangiectasia: a nationwide retrospective multi-centre study during first wave in Italy
Authors: Suppressa Patrizia , Pagella Fabio , Lenato Gennaro Mariano , Gaetani Eleonora , Serio Ilaria , Masala Maristella Salvatora , Spinozzi Giuseppe , Lizzio Roberta , Matti Elina , De Silvestri Annalisa , Passali Giulio Cesare , Aguglia Maria , Crocione Claudia , Sabbà Carlo 
Published: September 2021

Abstract
Background
Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue.

Objectives
The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency.

Methods
The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period.

Results
The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population.

Conclusions
COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population.
Prevalence and genotype specific concordance of oro-genital and anal human papillomavirus infections among sexually active Nigerian women
Authors: Morhason-Bello Imran O. , Baisley Kathy , Pavon Miquel Angel , Adewole Isaac F. , Bakare Rasheed , de Sanjosé Silvia , Francis Suzanna C. , Watson-Jones Deborah 
Published: September 2021

Abstract
Background
Human papillomavirus (HPV) associated cancers are increasingly reported globally, including in sub-Saharan Africa (SSA). However, with the exception of cervical HPV infection, data from SSA on the epidemiology of oral and genital HPV infections are limited. This study assessed the prevalence and concordance of oro-genital and anal HPV genotype specific infections among women in the general population.

Methods
We conducted a cross-sectional study in sexually active women aged 18–45 years in Ibadan, Nigeria. After a face-to-face interview and clinical examination, oral, cervical, vulvar, and anal samples were collected from participants and tested by the Anyplex II 28 HPV assay. Descriptive and multivariable analyses were used to report prevalence and risk factors associated with HPV infections.

Results
The prevalence of any vulva, cervical, anal, and oral HPV infections was 68.0% (210/309), 59.7% (182/305), 56.8% (172/303), and 16.1% (14/286), respectively. There was an inverse relationship between age-group and HPV prevalence of HPV in all anatomic sites except for the oral HPV infections. HPV 35 was the most prevalent high-risk HPV genotype in the vulva, cervix and oral cavity. Associated risk factors for HPV infection in each of the anatomic sites were reported. Overall, 10.0% (31/310) women had concordance of any HPV type in the four anatomic sites.

Conclusion
There was a high prevalence of oro-genital and anal HPV infections among sexually active Nigerian women, with concordance of HPV types in the cervix, vulva, anus and oral cavity. We advocate large longitudinal studies that will involve sampling of multiple anatomic sites and inclusion of other women in the community for better understanding of HPV epidemiology in this region.
ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and cisplatin resistance in epithelial ovarian cancer
Authors: Nie Sipei , Zhang Lin , Liu Jinhui , Wan Yicong , Jiang Yi , Yang Jing , Sun Rui , Ma Xiaolling , Sun Guodong , Meng Huangyang , Xu Mengting , Cheng Wenjun 
Published: September 2021

Abstract
Background
Chemotherapy resistance remains a barrier to improving the prognosis of epithelial ovarian cancer (EOC). ALKBH5 has recently been shown to be one of the RNA N6-methyladenosine (m6A) demethyltransferases associated with various cancers, but its role in cancer therapeutic resistance remains unclear. This study aimed to investigate the role of AlkB homolog 5 (ALKBH5) in cisplatin-resistant EOC.

Methods
Functional assays were performed both in vitro and in vivo. RNA sequencing (RNA-seq), m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq), chromatin immunoprecipitation, RNA immunoprecipitation, and luciferase reporter and actinomycin-D assays were performed to investigate RNA/RNA interaction and m6A modification of the ALKBH5-HOXA10 loop.

Results
ALKBH5 was upregulated in cisplatin-resistant EOC and promoted cancer cell cisplatin resistance both in vivo and in vitro. Notably, HOXA10 formed a loop with ALKBH5 and was found to be the upstream transcription factor of ALKBH5. HOXA10 overexpression also facilitated EOC cell chemoresistance both in vivo and in vitro. Collective results of MeRIP-seq and RNA-seq showed that JAK2 is the m6A-modified gene targeted by ALKBH5. The JAK2/STAT3 signaling pathway was activated by overexpression of the ALKBH5-HOXA10 loop, resulting in EOC chemoresistance. Cell sensitivity to cisplatin was rescued by ALKBH5 and HOXA10 knockdown or inhibition of the JAK2/STAT3 signaling pathway in EOC cells overexpressing ALKBH5-HOXA10.

Conclusions
The ALKBH5-HOXA10 loop jointly activates the JAK2/STAT3 signaling pathway by mediating JAK2 m6A demethylation, promoting EOC resistance to cisplatin. Thus, inhibition of the expression of the ALKBH5-HOXA10 loop may be a potential strategy to overcome cisplatin resistance in EOC.
Beta-blockade is not associated with improved outcomes in isolated severe extracranial injury: an observational cohort study
Authors: Sadi Lin , Sjölin Gabriel , Ahl Hulme Rebecka 
Published: September 2021

Abstract
Background
There is evidence supporting the use of beta-blockade in patients with traumatic brain injury. The reduction in sympathetic drive is thought to underlie the relationship between beta-blockade and increased survival. There is little evidence for similar effects in extracranial injuries. This study aimed to assess the association between beta-blockade and survival in patients suffering isolated severe extracranial injuries.

Methods
Patients treated at an academic urban trauma centre during a 5-year period were retrospectively identified. Adults suffering isolated severe extracranial injury [Injury Severity Score (ISS) ≥ 16 with Abbreviated Injury Score of ≤ 2 for any intracranial injury] were included. Patient characteristics and outcomes were collected from the trauma registry and hospital medical records. Patients were subdivided into beta-blocker exposed and unexposed groups. Patients were matched using propensity score matching. Differences were assessed using McNemar’s or paired Student’s t test. The primary outcome of interest was 90-day mortality and secondary outcome was in-hospital complications.

Results
698 patients were included of whom 10.5% were on a beta-blocker. Most patients suffered blunt force trauma (88.5%) with a mean [standard deviation] ISS of 24.6 [10.6]. Unadjusted mortality was higher in patients receiving beta-blockers (34.2% vs. 9.1%, p < 0.001) as were cardiac complications (8.2% vs. 1.4%, p = 0.002). Patients on beta-blockers were significantly older (69.5 [14.1] vs. 43.2 [18.0] years) and of higher comorbidity. After matching, no statistically significant differences were seen in 90-day mortality (34.2% vs. 30.1%, p = 0.690) or in-hospital complications.

Conclusions
Beta-blocker therapy does not appear to be associated with improved survival in patients with isolated severe extracranial injuries.
Commentary: Pivoting during a pandemic: developing a new recruitment model for a randomised controlled trial in response to COVID-19
Authors: Milton Shakira , McIntosh Jennifer , Boyd Lucy , Karnchanachari Napin , Macrae Finlay , Emery Jon David 
Published: September 2021

Abstract
Background
Many non-COVID-19 trials were disrupted in 2020 and either struggled to recruit participants or stopped recruiting altogether. In December 2019, just before the pandemic, we were awarded a grant to conduct a randomised controlled trial, the Should I Take Aspirin? (SITA) trial, in Victoria, the Australian state most heavily affected by COVID-19 during 2020.

Main body
We originally modelled the SITA trial recruitment method on previous trials where participants were approached and recruited in general practice waiting rooms. COVID-19 changed the way general practices worked, with a significant increase in telehealth consultations and restrictions on in person waiting room attendance. This prompted us to adapt our recruitment methods to this new environment to reduce potential risk to participants and staff, whilst minimising any recruitment bias. We designed a novel teletrial model, which involved calling participants prior to their general practitioner appointments to check their eligibility. We delivered the trial both virtually and face-to-face with similar overall recruitment rates to our previous studies.

Conclusion
We developed an effective teletrial model which allowed us to complete recruitment at a high rate. The teletrial model is now being used in our other primary care trials as we continue to face the impacts of the COVID-19 pandemic.
Detection of Leishmania tarentolae in lizards, sand flies and dogs in southern Italy, where Leishmania infantum is endemic: hindrances and opportunities
Authors: Mendoza-Roldan Jairo Alfonso , Latrofa Maria Stefania , Iatta Roberta , R. S. Manoj Ranju , Panarese Rossella , Annoscia Giada , Pombi Marco , Zatelli Andrea , Beugnet Fred , Otranto Domenico 
Published: September 2021

Abstract
Background
Leishmania tarentolae is a protozoan isolated from geckoes (Tarentola annularis, Tarentola mauritanica), which is considered non-pathogenic and is transmitted by herpetophilic Sergentomyia spp. sand flies. This species occurs in sympatry with Leishmania infantum in areas where canine leishmaniasis is endemic. In the present study, we investigated the circulation of L. tarentolae and L. infantum in sand flies, dogs and lizards in a dog shelter in southern Italy, where canine leishmaniasis by L. infantum is endemic.

Methods
Sheltered dogs (n = 100) negative for Leishmania spp. (March 2020) were screened by immunofluorescence antibody test (IFAT) using promastigotes of both species at two time points (June 2020 and March 2021). Whole blood from dogs, tissues of Podarcis siculus lizards (n = 28) and sand flies (n = 2306) were also sampled and tested by a duplex real-time PCR (dqPCR). Host blood meal was assessed in sand flies by PCR.

Results
Overall, 16 dogs became positive for L. infantum and/or L. tarentolae by IFAT at one or both sampling periods. One canine blood sample was positive for L. infantum, whilst two for L. tarentolae by dqPCR. At the cytology of lizard blood, Leishmania spp. amastigote-like forms were detected in erythrocytes. Twenty-two tissue samples, mostly lung (21.4%), scored molecularly positive for L. tarentolae, corresponding to 10 lizards (i.e., 35.7%). Of the female Sergentomyia minuta sampled (n = 1252), 158 scored positive for L. tarentolae, four for L. infantum, and one co-infected. Two Phlebotomus perniciosus (out of 29 females) were positive for L. tarentolae. Engorged S. minuta (n = 10) fed on humans, and one P. perniciosus, positive for L. tarentolae, on lagomorphs.

Conclusions
Dogs and lacertid lizards (Podarcis siculus) were herein found for the first time infected by L. tarentolae. The detection of both L. tarentolae and L. infantum in S. minuta and P. perniciosus suggests their sympatric circulation, with a potential overlap in vertebrate hosts. The interactions between L. tarentolae and L. infantum should be further investigated in both vectors and vertebrate hosts to understand the potential implications for the diagnosis and control of canine leishmaniasis in endemic areas.

Graphical abstract
An effective processing pipeline for harmonizing DNA methylation data from Illumina’s 450K and EPIC platforms for epidemiological studies
Authors: Vanderlinden Lauren A. , Johnson Randi K. , Carry Patrick M. , Dong Fran , DeMeo Dawn L. , Yang Ivana V. , Norris Jill M. , Kechris Katerina 
Published: September 2021

AbstractObjectiveIllumina BeadChip arrays are commonly used to generate DNA methylation data for large epidemiological studies. Updates in technology over time create challenges for data harmonization within and between studies, many of which obtained data from the older 450K and newer EPIC platforms. The pre-processing pipeline for DNA methylation is not trivial, and influences the downstream analyses. Incorporating different platforms adds a new level of technical variability that has not yet been taken into account by recommended pipelines. Our study evaluated the performance of various tools on different versions of platform data harmonization at each step of pre-processing pipeline, including quality control (QC), normalization, batch effect adjustment, and genomic inflation. We illustrate our novel approach using 450K and EPIC data from the Diabetes Autoimmunity Study in the Young (DAISY) prospective cohort.ResultsWe found normalization and probe filtering had the biggest effect on data harmonization. Employing a meta-analysis was an effective and easily executable method for accounting for platform variability. Correcting for genomic inflation also helped with harmonization. We present guidelines for studies seeking to harmonize data from the 450K and EPIC platforms, which includes the use of technical replicates for evaluating numerous pre-processing steps, and employing a meta-analysis.
Toxic epidermal necrosis associated with phenobarbitone: a case report and brief review of the literatures
Authors: Ayele Biniyam A. , Ali Kemal , Mulatu Eliyas 
Published: September 2021

AbstractBackgroundToxic epidermal necrolysis (TEN)/Stevens–Johnson syndrome (SJS) is the spectrum of severe, acute, mucocutaneous, T-cell mediated delayed type IV hypersensitivity reaction and universally related to different drugs. Phenobarbitone is known to cause hypersensitivity reactions with benign pattern; ranging from a mild to moderate rashes but not life-threatening reactions such as TEN/SJS.Case reportWe report a 14-year-old asthmatic male patient admitted to a local hospital for an acute exacerbation of asthma, after he presented with shortness of breath, cough, and fever. He was treated with bronchodilator and antibiotics. On subsequent days, the patient developed new onset generalized tonic clonic seizure in the hospital for which he was started on phenobarbitone of 100 mg twice daily. Two weeks after initiation of phenobarbitone, the patient developed extensive blistering skin eruptions; which subsequently exfoliated unevenly. Associated with the hypersensitivity skin reaction, the patient reported low grade fever, sore throat, and dysphagia. The exfoliation also involved oral and conjunctival mucosa; with estimated 65% body surface area involvement. The laboratory investigations were relevant for mild leucocytosis, prolonged prothrombin time, and reduced albumin. Phenobarbitone was discontinued and replaced with clonazepam; and the patient was managed with fluids replacement, IV antibiotics, twice daily wound care, analgesics, and naso gastric tube feeding. On subsequent days the patients’ clinical condition started improving; the skin lesion also started to heal and exfoliate in most of the affected skin surface areas, and the patient was discharged improved after ten days of intensive care unit.ConclusionIn summary, the present case describes, a 14-years-old young child with history of asthma and seizure disorder; and developed toxic epidermal necrosis following exposure to Phenobarbitone. This case also highlighted the better prognosis observed in pediatric population with TEN.
Shift of musical hallucinations to visual hallucinations after correction of the hearing deficit in a patient with Lewy body dementia: a case report
Authors: Montalvo Alexandre , Azevedo Eryco , de Mendonça Alexandre 
Published: September 2021

Abstract
Background
Musical hallucinations are a particular type of auditory hallucination in which the patient perceives instrumental music, musical sounds, or songs. Musical hallucinations are associated with acquired hearing loss, particularly within the elderly. Under conditions of reduced auditory sensory input, perception-bearing circuits are disinhibited and perceptual traces released, implying an interaction between peripheral sensory deficits and central factors related to brain dysfunction.

Case presentation
A 71-year-old Caucasian man with hearing loss complained of memory difficulties and resting tremor of the right upper limb in the previous 2 years. He already had difficulties in instrumental activities of daily life. Neurological examination showed Parkinsonian signs and hypoacusia. Neuropsychological examination identified deficits in executive functions and memory tests. Brain computerized tomography and nuclear magnetic resonance scans showed mild cortical and subcortical atrophy. The clinical diagnosis of possible dementia with Lewy bodies was established. Five years later, the patient began complaining of musical hallucinations. There had been no previous change in medication. An otorhinolaryngologist diagnosed age-related hearing loss and prescribed bilateral hearing aids. After using the hearing aids, the patient did not hear the songs any longer, only some tinnitus, described as a whistle. However, at the same time, the patient started experiencing visual hallucinations he never had before.

Discussion
To our knowledge, the immediate shift of hallucinations from one sensory modality to another sensory modality when perception is improved has not been previously described. This report emphasizes the interaction between brain pathology and sensory deficits for the genesis of hallucinations, and reinforces the theory that attention and control networks must couple properly to the default mode network, as well as integrate and select adequately peripheral signals to the somatosensory cortices, in order to keep a clear state of mind.

Conclusion
The clinician should bear in mind and let the patient know that improving one sensory modality to ameliorate hallucinations may sometimes paradoxically lead to hallucinations in a different sensory modality.
2D SIFt: a matrix of ligand-receptor interactions
Authors: Mordalski Stefan , Wojtuch Agnieszka , Podolak Igor , Kurczab Rafał , Bojarski Andrzej J. 
Published: September 2021

AbstractDepicting a ligand-receptor complex via Interaction Fingerprints has been shown to be both a viable data visualization and an analysis tool. The spectrum of its applications ranges from simple visualization of the binding site through analysis of molecular dynamics runs, to the evaluation of the homology models and virtual screening. Here we present a novel tool derived from the Structural Interaction Fingerprints providing a detailed and unique insight into the interactions between receptor and specific regions of the ligand (grouped into pharmacophore features) in the form of a matrix, a 2D-SIFt descriptor. The provided implementation is easy to use and extends the python library, allowing the generation of interaction matrices and their manipulation (reading and writing as well as producing the average 2D-SIFt). The library for handling the interaction matrices is available via repository http://bitbucket.org/zchl/sift2d.
Loss of signal transducer and activator of transcription 3 impaired the osteogenesis of mesenchymal progenitor cells in vivo and in vitro
Authors: Huang Zijing , Feng Jingyi , Feng Xin , Chan Laiting , Lu Jiarui , Lei Lizhen , Huang Zhuwei , Zhang Xiaolei 
Published: September 2021

AbstractBackgroundSignal transducer and activator of transcription 3 (Stat3) is a cytoplasmic transcription factor that participates in various biologic processes. Loss of Stat3 causes hyperimmunoglobulin E syndrome, presenting with skeletal disorders including osteoporosis, recurrent fractures, scoliosis, and craniosynostosis. The objective of this study is to explore the effect and mechanism of Stat3 on osteogenesis of mesenchymal progenitors.MethodsStat3 was conditionally knockout (CKO) in mesenchymal progenitors by crossing the pair-related homeobox gene 1-cre (Prx1-Cre) with Stat3-floxed strain mice. Whole-mount-skeletal staining, histology, and micro-CT were used to assess the differences between Stat3 CKO and control mice. Further, in vitro experiments were conducted to evaluate the osteogenesis potential of primary isolated bone marrow mesenchymal stem cells (BMSCs) from both control and Stat3 CKO mice. After osteogenic induction for 14d, alizarin red staining was used to show the calcium deposit, while the western blotting was applied to detect the expression of osteogenic markers.ResultsCompared with the control, Stat3 CKO mice were present with shortened limbs, multiple fractures of long bone, and open calvarial fontanels. The abnormal growth plate structure and reduced collagen fiber were found in Stat3 CKO limbs. According to micro-CT analysis, the reduced cortical bone thickness and bone volume were found on Stat3 CKO mice. The in vitro osteogenic differentiation of BMSCs was inhibited in Stat3 CKO samples. After osteogenic induction for 14d, the significantly diminished calcium deposits were found in Stat3 CKO BMSCs. The decreased expression of osteogenic markers (OPN and COL1A1) was observed in Stat3 CKO BMSCs, compared with the control.ConclusionsStat3 played a critical role in bone development and osteogenesis. Loss of Stat3 impaired the osteogenesis of mesenchymal progenitors in vivo and in vitro.