bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Diterpene Ginkgolides Meglumine Injection to Regulate Plasma Levels of PAI-1 and t-PA in Patients With Acute Atherosclerotic Cerebral Infarction
Authors: Chen Rui , Yan Luxia , Xie Peng , Tian Jisha , Zhao Ying , Liu Yue , Xu Jie , Wang Yuqian , Zhao Liandong 
Published: December 2021

Background:
To: (i) explore the effect of diterpene ginkgolides meglumine injection (DGMI) on neurological deficit symptoms in acute atherosclerotic cerebral infarction (AACI) patients; (ii) measure the level of plasma plasminogen activator inhibitor (PAI)-1 and tissue plasminogen activator (t-PA).

Methods:
Eighty AACI patients were divided equally and randomly into the DGMI group and control group. In addition to basic treatment, the DGMI group was treated with DGMI (25 mg/d) for 14 days. The control group had basic treatment without DGMI. Before and after treatment, the degree of neurological deficit was assessed, thromboelastography undertaken, and plasma levels of PAI-1 and t-PA measured.

Results:
The National Institutes of Health Stroke Scale score of patients in the DGMI group after treatment was lower than that in the control group, and the Barthel Index was higher than that in the control group (P<0.05). Thromboelastography revealed that, in the DGMI group, the R value and K value after treatment were higher than before treatment, the angle and maximum amplitude value were lower than before treatment, and both were significant (P<0.05). Compared with the control group, the plasma PAI-1 level of patients in the DGMI group was lower than that in the control group, and the t-PA level was higher than that in the control group (P<0.05) after 14 days of treatment.

Conclusions:
DGMI may affect the activity of the blood coagulation and fibrinolysis system by regulating the plasma level of PAI-1 and t-PA, and improving neurological deficit symptoms. DGMI is important for improving the prognosis of patients with AACI.
Association of Changed Serum Brain Biomarkers With Perihematomal Edema and Early Clinical Outcome in Primary ICH Patients
Authors: Simani Leila , Ramezani Mahtab , Mohammadi Ehsan , Abbaszadeh Fatemeh , Karimialavijeh Ehsan , Pakdaman Hossein 
Published: December 2021

Background:
Perihematomal edema (PHE) following primary intracranial hemorrhages (ICHs) affects the patient outcome. Also, serum biomarkers such as S100 calcium-binding protein B (S100B) and glial fibrillary acidic protein (GFAP) have been associated with ICHs outcome. We aimed to investigate the association between these biomarkers and PHE in ICH patients.

Methods:
In this cross-sectional study, patients with primary ICH between January 2020 and August 2020 were evaluated. All participants underwent spiral brain computed tomography scans upon admission, and 48 to 72 hours later and quantification of initial hematoma volume was performed. Serum level of matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), GFAP, and S100B on admission were measured by enzyme-linked immunosorbent assays. Acute clinical outcome was assessed by the modified-Rankin scale, National Institute of Health Stroke Scale (NIHSS), and ICH score.

Results:
Thirty-seven ICH patients (21 patients with a favorable outcome and 16 unfavorable) were studied. Compared with survival patients, nonsurvivor patients showed a higher serum level of MMP-9, VEGF, GFAP, and S100B (P<0.05). Scores of absolute PHE, edema expansion distance, and PHE growth rate in the nonsurvivor group were higher than the survivors (P<0.001). The regression model revealed that MMP-9, VEGF, ICH score, and hematoma volume were associated with the PHE growth rate. S100B and ICH score were associated with edema expansion distance.

Conclusions:
Our data showed that the serum level of molecular biomarkers was associated with higher PHE volume and PHE scores were higher in nonsurvival patients, suggesting it may have a pathogenic role in developing PHE after ICH.
Concurrent Cerebral, Splenic, and Renal Infarction in a Patient With COVID-19 Infection
Authors: Rigual Ricardo , Ruiz-Ares Gerardo , Rodriguez-Pardo Jorge , Fernández-Prieto Andrés , Navia Pedro , Novo Joan R. , Alonso de Leciñana María , Alonso-Singer Pablo , Fuentes Blanca , Díez-Tejedor Exuperio 
Published: December 2021

Introduction:
Thrombotic events are potentially devastating complications of coronavirus disease 2019 (COVID-19) infection. Although less common than venous thromboembolism, arterial thrombosis has been reported in COVID-19 cohorts in almost 3% of patients. We describe a patient with COVID-19 infection and concurrent cerebral and noncerebral infarction.

Case Report:
A 53-year-old man with history of COVID-19 pneumonia was admitted to a primary stroke center for speech disturbances and left hemiplegia. Urgent laboratory tests showed a great increase of inflammatory and coagulation parameters as D-dimer, ferritin, interleukin-6 and C-reactive protein. Neuroimaging found occlusion of the M1 segment of the right middle cerebral artery with early signs of ischemic stroke. He received intravenous thrombolysis and mechanical thrombectomy. Abdominal computed tomography discovered a splenic infarction with hemorrhagic transformation and bilateral renal infarction. Urgent angiography showed an associated splenic pseudoaneurysm, which was embolized without complications. He was treated with intermediate-dose anticoagulation (1 mg subcutaneous enoxaparin/kg/24 h), acetylsalicylic acid 100 mg and 5 days of intravenous corticosteroids. In the following days, inflammatory markers decreased so anticoagulant treatment was stopped and acetylsalicylic acid 300 mg was prescribed. His condition improved and he was discharged to a rehabilitation facility on hospital day 30.

Conclusion:
In this case, a patient with multiple thrombotic events in the acute phase of COVID-19 infection, the delimitation of the inflammatory state through analytical markers as D-dimer helped to individualize the antithrombotic treatment (full anticoagulation or anticoagulation at intermediate doses plus antiplatelet treatment as used in our patient) and its duration. However, more data are needed to better understand the mechanisms and treatment of stroke in patients with COVID-19 infection.
Pharmacokinetics and Safety of the Abacavir/Lamivudine/Lopinavir/Ritonavir Fixed-Dose Granule Formulation (4-in-1) in Neonates: PETITE Study
Authors: Bekker Adrie , Rabie Helena , Salvadori Nicolas , du Toit Samantha , Than-in-at Kanchana , Groenewald Marisa , Andrieux-Meyer Isabelle , Kumar Mukesh , Cressey Ratchada , Nielsen James , Capparelli Edmund , Lallemant Marc , Cotton Mark F. , Cressey Tim R. ,   for the PETITE Study Team
Published: December 2021

Background:
Antiretroviral options for neonates (younger than 28 days) should be expanded. We evaluated the pharmacokinetics, safety, and acceptability of the "4-in-1" fixed-dose pediatric granule formulation of abacavir/lamivudine/lopinavir/ritonavir (30/15/40/10 mg) in neonates.

Methods:
The PETITE study is an ongoing phase I/II, open-label, single-arm, 2-stage trial conducted in South Africa. In stage 1, term neonates exposed to HIV on standard antiretroviral prophylaxis (nevirapine ± zidovudine) received single dose(s) of the 4-in-1 formulation, followed by intensive pharmacokinetic sampling and safety assessments. At each PK visit, blood was drawn after an observed dose at 1, 2, 4, 8, and 12 hours postdose. In this study, we have reported the planned interim pharmacokinetic and safety analysis after completion of the single-dose administration.

Results:
Sixteen neonates, with a median (range) birth weight of 3130 g (2790–3590 g), completed 24 pharmacokinetic visits. The 4-in-1 formulation imposed relatively high doses of abacavir [8.6 mg/kg (6.6–11.4)] and lamivudine [4.3 mg/kg (3.3–5.7)] but lower doses of lopinavir [11.5 mg/kg (8.8–15.2)]. The geometric means (GM, 90% CI) AUC0–12 of abacavir, lamivudine, and lopinavir were 29.87 (26.29–33.93), 12.61 (10.72–14.83), and 3.49 (2.13–5.72) µg.h/mL, respectively. Lopinavir GM AUC0–12 was below the predefined target (20–100 µg.h/mL), and ritonavir concentrations were only detectable in 4 of the 120 (3%) samples. No adverse events were related to study drugs. No neonate had difficulty swallowing the 4-in-1 formulation.

Conclusions:
The high doses of abacavir and lamivudine (in mg/kg) and AUCs were safe, and the formulation was well tolerated; however, lopinavir/ritonavir exposures were extremely low, preventing its use in neonates use in neonates. Alternative pediatric solid antiretroviral formulations must be studied in neonates.
HIV and Herpes Simplex Virus Type 2 Incidence Among Adolescent Mothers in South Africa: A Longitudinal Analysis of HIV Prevention Trials Network 068 Data
Authors: Groves Allison K. , Bhushan Nivedita L. , Stoner Marie C. D. , Gómez-Olivé Francesc X. , Kahn Kathleen , Pettifor Audrey E. 
Published: December 2021

Background:
Adolescent motherhood is common in South Africa and occurs against a backdrop of high HIV risk. While childbearing during adolescence may result in social and economic strain that may negatively impact health, there has been limited study of whether adolescent motherhood increases the risk of HIV or herpes simplex virus type 2 (HSV-2) acquisition or engagement in high-risk sexual partnerships.

Setting:
Data are from HIV Prevention Trials Network 068, a longitudinal conditional cash transfer study of adolescent girls and young women (age, 13–23) in rural South Africa.

Methods:
We used survival analysis to estimate hazard ratios to determine if adolescent motherhood (live birth before 20 years) predicted incident HIV and incident HSV-2 and generalized estimating equations for behavioral risk ratios to determine if adolescent motherhood was associated with transactional sex and age-disparate partnerships.

Results:
Of 2452 adolescent girls and young women who were HIV negative at baseline, 5% were adolescent mothers; 16% were adolescent mothers by the end of the study period. After controlling for covariates, adolescent motherhood predicted incident HSV-2 acquisition [ adjusted hazard ratios, 1.30; 95% confidence interval (CI): 1.01 to 1.95] but not HIV acquisition ( adjusted hazard ratios, 1.19; 95% CI, 0.76 to 1.86). Adolescent motherhood was also associated with being in an age-disparate partnership (adjusted risk ratio, 1.30; 95% CI: 1.07 to 1.58) but not transactional sex.

Conclusion:
Adolescent motherhood increased the risk of HSV-2 and engagement in age-disparate partnerships, both known risk factors for HIV infection. Sexually transmitted infection screening and/or tailored combination HIV prevention interventions that account for the context of adolescent motherhood are critical to maximize adolescent mothers' long-term health and to meet UNAIDS 95-95-95 targets by 2030.
Simultaneous Zygomatic Osteotomies With Reduction Mandibuloplasty – An Approach to Mid- and Lower-Facial Feminization in the Transfeminine Patient
Authors: Kotha Vikas S. , Kanuri Arjun , Mandelbaum Max , Lakhiani Chrisovalantis , Hung Rex W. , Wang Jing , Rashid Waleed , Chao Jerry W. 
Published: December 2021

Background:
Facial feminization surgery (FFS) is effective at treating gender dysphoria associated with anthropometrically masculine facial features. For many transgender women, FFS is a crucial component of the gender transition process. The purpose of this study is to report our experience with a pragmatic technique for simultaneous mid- and lower-face feminization by zygomatic osteotomy malarplasty and reduction mandibuloplasty.

Methods:
The technique to perform zygomatic osteotomy malarplasty and reduction mandibuloplasty is described, utilizing harvested bone from the mandible for bone grafting the zygomatic osteotomy gap. A retrospective chart review was performed for patients who underwent simultaneous middle and lower FFS using the described technique. Independent reviewers evaluated cropped preoperative and postoperative photographs of the mid and lower face and assigned each photograph a “femininity score.”

Results:
Seventeen transgender women underwent simultaneous zygomatic osteotomy malarplasty and reduction mandibuloplasty over the study period with adequate follow-up (average 11.1 months). Transient nerve weaknesses were the primary complications noted. A statistically significant improvement in femininity score was reported in postoperative photographs, compared to preoperative photographs (P < 0.01).

Conclusions:
The technique described in this study is an effective application of craniofacial approaches and techniques for feminizing the facial skeleton in transgender women by utilizing harvested mandibular bone for simultaneous malarplasty.
SARS-CoV-2 infection dynamics revealed by wastewater sequencing analysis and deconvolution
Authors: Schumann Vic-Fabienne , de Castro Cuadrat Rafael Ricardo , Wyler Emanuel , Wurmus Ricardo , Deter Aylina , Quedenau Claudia , Dohmen Jan , Faxel Miriam , Borodina Tatiana , Blume Alexander , Meixner Martin , Grau José Horacio , Liere Karsten , Hackenbeck Thomas , Zietzschmann Frederik , Gnirss Regina , Böckelmann Uta , Uyar Bora , Franke Vedran , Barke Niclas , Altmüller Janine , Rajewsky Nikolaus , Landthaler Markus , Akalin Altuna 
Published: December 2021

AbstractThe use of RNA sequencing from wastewater samples is a valuable way for estimating infection dynamics and circulating lineages of SARS-CoV-2. This approach is independent from testing individuals and can therefore become the key tool to monitor this and potentially other viruses. However, it is equally important to develop easily accessible and scalable tools which can highlight critical changes in infection rates and dynamics over time across different locations given sequencing data from wastewater. Here, we provide an analysis of lineage dynamics in Berlin and New York City using wastewater sequencing and present PiGx SARS-CoV-2, a highly reproducible computational analysis pipeline with comprehensive reports. This end-to-end pipeline includes all steps from raw data to shareable reports, additional taxonomic analysis, deconvolution and geospatial time series analyses. Using simulated datasets (in silico generated and spiked-in samples) we could demonstrate the accuracy of our pipeline calculating proportions of Variants of Concern (VOC) from environmental as well as pre-mixed samples (spiked-in). By applying our pipeline on a dataset of wastewater samples from Berlin between February 2021 and January 2022, we could reconstruct the emergence of B.1.1.7(alpha) in February/March 2021 and the replacement dynamics from B.1.617.2 (delta) to BA.1 and BA.2 (omicron) during the winter of 2021/2022. Using data from very-short-reads generated in an industrial scale setting, we could see even higher accuracy in our deconvolution. Lastly, using a targeted sequencing dataset from New York City (receptor-binding-domain (RBD) only), we could reproduce the results recovering the proportions of the so-called cryptic lineages shown in the original study. Overall our study provides an in-depth analysis reconstructing virus lineage dynamics from wastewater, and that our tool can be used to identify new mutations and to detect any emerging new lineages with different amplification and sequencing methods. Our approach can support efforts to establish continuous monitoring and early-warning projects for detecting SARS-CoV-2 or any other pathogen.
Estimating the increase in reproduction number associated with the Delta variant using local area dynamics in England
Authors: Abbott Sam ,   CMMID COVID-19 Working Group, Kucharski Adam J. , Funk Sebastian 
Published: December 2021

AbstractBackgroundLocal estimates of the time-varying effective reproduction number (Rt) of COVID-19 in England became increasingly heterogeneous during April and May 2021. This may have been attributable to the spread of the Delta SARS-CoV-2 variant. This paper documents real-time analysis that aimed to investigate the association between changes in the proportion of positive cases that were S-gene positive, an indicator of the Delta variant against a background of the previously predominant Alpha variant, and the estimated time-varying Rt at the level of upper-tier local authorities (UTLA).MethodWe explored the relationship between the proportion of samples that were S-gene positive and the Rt of test-positive cases over time from the 23 February 2021 to the 25 May 2021. Effective reproduction numbers were estimated using the EpiNow2 R package independently for each local authority using two different estimates of the generation time. We then fit a range of regression models to estimate a multiplicative relationship between S-gene positivity and weekly mean Rt estimate.ResultsWe found evidence of an association between increased mean Rt estimates and the proportion of S-gene positives across all models evaluated with the magnitude of the effect increasing as model flexibility was decreased. Models that adjusted for either national level or NHS region level time-varying residuals were found to fit the data better, suggesting potential unexplained confounding.ConclusionsOur results indicated that even after adjusting for time-varying residuals between NHS regions, S-gene positivity was associated with an increase in the effective reproduction number of COVID-19. These findings were robust across a range of models and generation time assumptions, though the specific effect size was variable depending on the assumptions used. The lower bound of the estimated effect indicated that the reproduction number of Delta was above 1 in almost all local authorities throughout the period of investigation.
Antimicrobial stewardship among Nigerian children: A pilot study of the knowledge, attitude, and practices of prescribers at two tertiary healthcare facilities in Bayelsa State
Authors: Orubu Ebiowei S.F , Robert Faith O. , Emuren Leonard , Ifie-Ombeh Boboye 
Published: December 2021

AbstractAntimicrobial stewardship (AMS), the evidence-based use of antimicrobials, is an effective strategy in controlling antimicrobial resistance (AMR) in humans by reducing the irrational use of antimicrobials. Stewardship in children is less studied. This study assessed the knowledge, attitude, and practice of physicians prescribing antibiotics to children in Bayelsa State, Nigeria to identify gaps in AMS and possible solutions. Following ethical approval, a semi-structured questionnaire was distributed among 40 paediatricians and gynaecologists at the two public tertiary healthcare facilities in Bayelsa State – the Niger Delta University Teaching Hospital and the Federal Medical Centre – for self-completion. Responses were expressed as percentages and analyzed using Bloom’s cutoffs. The Capability, Opportunity, Motivation, and Behaviour (COM-B) model was employed to identify gaps for intervention in prescribing behavior with gaps in each component identified by aggregate scores <80%. Perceived approaches to improve prescribing among 14 selected options were assessed using 5-point Likert scales and options with scores >90% rated the most acceptable. Questionnaires were administered from August to September 2021. The response rate was 68% (27/40). Participants were paediatricians (81%, 22/27) and gynaecologists (19%, 5/27). Antimicrobial Susceptibility Testing (AST) was not performed before antibiotic selection nine times out of 10 (89%, 24/27). In a third (37%, 10/27) of cases, 2-3 antibiotics were prescribed. The top three antibiotics, in rank order, were: cefuroxime or amoxicillin 41% (11/27); ciprofloxacin or amoxicillin 30% (8/27), and azithromycin (33%, 9/27). Aggregate COM-B scores were: capability, 74%; opportunity, 78%; and motivation, 87%. The most acceptable (100%, 27/27) options to improving antibiotic prescribing were: availability of resistance data, availability of guidelines, readily accessible microbiological data, and easy access to infectious disease physicians. There are gaps in knowledge of AMR and opportunity for rational prescribing. There is need for antimicrobial resistance data to promote pediatric AMS at the surveyed healthcare facilities.
Clinical Risk Factors for COVID-19 related Severe Outcome
Authors: Huang Chaorui C. 
Published: December 2021

AbstractBackgroundWe aimed to evaluate the risk factors for Coronavirus disease 2019 (COVID-19) related severe outcome in New York State (NYS) and proposed a method that could be used to inform future work to develop clinical algorithms and predict resource needs for COVID-19 patients.MethodsWe analyzed COVID-19 related hospital encounter and hospitalization in NYS from April 1st to November 17th, 2020, using Statewide Planning and Research Cooperative System (SPARCS) hospital discharge dataset. Logistic regression was performed to evaluate the risk factors for COVID-19 related in-hospital death using demographic variables, symptom, rapid clinical examination, and medical history of chronic co-morbid conditions. Receiver operating characteristic (ROC) curve was calculated, and cut-off points for predictors were selected to stage the risk of COVID-19 related fatal outcome.FindingsLogistic regression analysis showed age was the greatest risk factor for COVID-19 related fatal outcome, which by itself achieved the diagnostic accuracy of 0.78 represented by the area under the ROC curve. By adding other demographic variables, dyspnea or hypoxemia and multiple chronic co-morbid conditions, the diagnostic accuracy was improved to 0.85. We selected cut-off points for predictors and provided a general recommendation to categorize the levels of risk for COVID-19 related fatal outcome.InterpretationWe assessed risk factors associated with in-hospital COVID-19 mortality and identified cut-off points that might be used to categorize the level of risk. Further studies are warranted to evaluate laboratory tests and develop laboratory biomarkers to improve the diagnostic accuracy for early intervention.
Sexual risk among pregnant women at risk of HIV infection in Cape Town, South Africa: What does alcohol have to do with it?
Authors: Miller Amanda P. , Shoptaw Steven , Mvududu Rufaro , Mashele Nyiko , Coates Thomas J. , Bekker Linda-Gail , Essack Zaynab , Groenewald Candice , Peterson Zaino , Gorbach Pamina M. , Myer Landon , Joseph Davey Dvora L. 
Published: December 2021

AbstractThis study examines associations between alcohol use and HIV sexual risk among a cohort of HIV-uninfected pregnant women (n=1201) residing in a high HIV burden community in South Africa. Alcohol use was measured using a modified version of the Alcohol Use Disorder Identification Test (AUDIT). HIV sexual risk was measured through a composite variable of four risk factors: diagnosis with a STI, self-report of >1 recent sex partners, partner HIV serostatus (unknown or HIV+) and condomless sex at last sex. Any past year alcohol use prior to pregnancy was reported by half of participants (50%); 6.0% reported alcohol use during pregnancy. Alcohol use prior to pregnancy was associated with increased odds of being at high risk of HIV (aOR=1.33 for 2 risks and aOR=1.47 for 3 risks). In addition to reducing alcohol use, several other strategies to address HIV sexual risk in this population were identified.