bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug–Drug Interactions With Cyclosporine in the Anti-Hepatitis C Viral PrOD Combination Regimen of Paritaprevir/Ritonavir–Ombitasvir and Dasabuvir in Organ Transplant Recipients With Severe Hepatic Fibrosis or Cirrhosis
Authors: Huang Ying-Yu , Huang Yu-Hsuan , Wu Tsai-Hung , Loong Che-Chuan , Hsu Chia-Chen , Chou Yueh-Ching , Chang Yuh-Lih 
Published: January 2022

Background:
The clinical guidelines suggest that the dosing of cyclosporine (CsA), during combination therapy with paritaprevir/ritonavir–ombitasvir and dasabuvir (PrOD), would be only one-fifth of the pre-PrOD total daily dose to be administered once daily. However, this dosing may not be applicable to all patients depending on their clinical condition. This study focuses on the pharmacokinetic dynamics of PrOD with CsA in Asian organ transplant recipients with severe liver fibrosis or cirrhosis who undergo concurrent treatment with PrOD treatment and CsA. The efficacy and safety of PrOD treatment was also evaluated.

Methods:
Data from 7 patients obtained between January 2017 and September 2017 were retrospectively analyzed. Determinations of the blood concentrations of CsA were made, whether used as a single treatment or in combination therapy with PrOD.

Results:
The combination regimen compared with CsA administered alone resulted in a 4.53-fold and 5.52-fold increase in the area under the concentration–time curve from time 0–12 hours (AUC0–12 h) of CsA on days 1 and 15, respectively. In addition, the maximal concentration, time to maximum concentration, and terminal phase elimination half-life (t1/2) of CsA were increased during the combined treatment of PrOD and CsA. The authors proposed reducing the CsA dosage during PrOD treatment to one-seventh of that of the pre-PrOD treatment of the total daily dose to maintain target CsA levels. All patients achieved sustained virologic responses at week 12. There were no episodes of serious adverse events or graft rejections observed.

Conclusions
Although the combination with PrOD significantly affects the pharmacokinetics of CsA, it is effective and safe with regular monitoring of the CsA blood concentrations and appropriate CsA dose adjustment.
Distinguishing Multisystem Inflammatory Syndrome in Children From COVID-19, Kawasaki Disease and Toxic Shock Syndrome
Authors: Godfred-Cato Shana , Abrams Joseph Y. , Balachandran Neha , Jaggi Preeti , Jones Kaitlin , Rostad Christina A. , Lu Austin T. , Fan Lucie , Jabbar Aysha , Anderson Evan J. , Kao Carol M. , Hunstad David A. , Rosenberg Robert B. , Zafferani Marc J. , Ede Kaleo C. , Ballan Wassim , Laham Federico R. , Beltran Yajira , Bryant Bobbi , Meng Lu , Hammett Teresa A. , Oster Matthew E. , Bamrah Morris Sapna , Belay Ermias D. 
Published: January 2022

Background:
Distinguishing multisystem inflammatory syndrome in children (MIS-C) from coronavirus disease 2019 (COVID-19), Kawasaki disease (KD), and toxic shock syndrome (TSS) can be challenging. Because clinical management of these conditions can vary, timely and accurate diagnosis is essential.

Methods:
Data were collected from patients <21 years of age hospitalized with MIS-C, COVID-19, KD, and TSS in 4 major health care institutions. Patient demographics and clinical and laboratory data were compared among the 4 conditions, and a diagnostic scoring tool was developed to assist in clinical diagnosis.

Results:
A total of 233 patients with MIS-C, 102 with COVID-19, 101 with KD, and 76 with TSS were included in the analysis. Patients with MIS-C had the highest prevalence of decreased cardiac function (38.6%), myocarditis (34.3%), pericardial effusion (38.2%), mitral regurgitation (31.8%) and pleural effusion (34.8%) compared with patients with the other conditions. Patients with MIS-C had increased peak levels of C-reactive protein and decreased platelets and lymphocyte nadir counts compared with patients with COVID-19 and KD and elevated levels of troponin, brain natriuretic peptide and pro-brain natriuretic peptide compared with COVID-19. Diagnostic scores utilizing clinical findings effectively distinguished MIS-C from COVID-19, KD, and TSS, with internal validation showing area under the curve ranging from 0.87 to 0.97.

Conclusions:
Compared with COVID-19, KD, and TSS, patients with MIS-C had significantly higher prevalence of cardiac complications, elevated markers of inflammation and cardiac damage, thrombocytopenia, and lymphopenia. Diagnostic scores can be a useful tool for distinguishing MIS-C from COVID-19, KD, and TSS.
Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network
Authors: Murad Yousif , Hung Te-Yu , Sadarangani Manish , Morris Shaun K. , Le Saux Nicole , Vanderkooi Otto G. , Kellner James D. , Tyrrell Gregory J. , Martin Irene , Demczuk Walter , Halperin Scott A. , Bettinger Julie A. ,   for the Members of IMPACT,   * Investigators participating in this IMPACT project included:, Bridger N. , Foo Cheryl , Halperin S.A. , Top K.A. , Thibeault R. , Moore D. , Papenburg J. , Lebel M. , Le Saux N. , Morris S. , Embree J. , Tan B. , McConnell Athena , Jadavji T. , Constantinescu C. , Vaudry W. , Scheifele D. , Sadarangani M. , Bettinger J. , Sauvé L. 
Published: January 2022

Background:
Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate.

Method:
This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0–16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada.

Results:
The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers.

Conclusion:
The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.
Association Between Real-time Polymerase Chain Reaction Cycle Threshold Value and Clinical Severity in Neonates and Infants Infected With Bordetella pertussis
Authors: Thuy Nga Do Thi , Thi Bich Thuy Phung , Ainai Akira , Takayama Ikuyo , Huong Do Thu , Saitoh Aya , Nakagawa Satoshi , Minh Dien Tran , Nakajima Noriko , Saitoh Akihiko 
Published: January 2022

Background:
Polymerase chain reaction (PCR) is highly sensitive and is thus the standard method for diagnosing pertussis. Real-time PCR is widely used because of its accuracy and the simplicity of the simultaneous cycle threshold (Ct) value, which represents the copy numbers of the target gene. Little is known of the association of Ct value with pertussis severity in neonates and infants.

Methods:
This study determined Ct values in neonates and infants diagnosed with pertussis by real-time PCR using nasopharyngeal samples at Vietnam National Children’s Hospital in Hanoi in 2017 and 2019. The association of disease severity and clinical parameters were analyzed using univariate and multivariate analyses.

Results:
We evaluated 108 patients with pertussis [median age: 63 days, interquartile range (IQR): 41–92 days]. Only 6/108 (6%) received at least 1 dose of a pertussis-containing vaccine. Among them, 24 (22.2%) had severe disease requiring care in a pediatric intensive care unit, 16 (13.8%) required mechanical ventilation, and 3 (2.6%) died. The median Ct value was lower in patients with severe disease (19.0, IQR: 16.5–22.0, n = 24) than in those without severe disease (25.5, IQR: 20.0–30.0, n = 84) (P = 0.002). Logistic regression analyses demonstrated that PCR Ct value [odds ratio (OR): 1.783, 95% confidence interval (CI): 1.013–3.138, P = 0.045], age (OR: 3.118, 95% CI: 1.643–5.920, P = 0.001), and white blood cell counts (OR: 0.446, 95% CI: 0.261–0.763, P = 0.003) remained significantly associated with severe disease.

Conclusions:
Real-time PCR Ct values for pertussis might be useful as a predictor of severe disease in neonates and infants.
NonTuberculous Mycobacteria Blood Stream Infection in Pediatric and Adult Patients
Authors: Dabaja-Younis Halima , Damouni-Shalabi Ranaa , Ganem-Zoubi Nesrin , Shachor-Meyouhas Yael , Hussein Khetam , Geffen Yuval , Kassis Imad 
Published: January 2022

Background:

Nontuberculous Mycobacteria (NTM) are rare causes of bloodstream infection (BSI). This study addresses the management and prognosis of NTM BSI and the differences between adult and pediatric patients.

Methods:
We retrospectively reviewed the medical charts of patients at any age with NTM BSI, from January 1, 2005, to June 30, 2020. Data on demographics, underlying conditions, clinical manifestations, NTM species, antibiotic treatments and outcomes were retrieved.

Results:
Positive blood cultures for NTM were detected in 43 patients, 30 children and 13 adults. Median age: 10.37 years (IQR 6.692–39.864). Thirty-seven (86%) patients had an active malignant disease. Fever was the chief sign in 23 (53.5%) patients and pulmonary manifestations in 14 (32.6%). Rapidly growing NTM comprised 39 (90.7%) of the isolates. Central venous catheter (CVC) was documented in 39 (90.7%) cases, 31 (79.5%) of which were removed as part of treatment. Antibiotic treatment directed against NTM was documented in 26 (60.5%) patients. CVC was removed in 7/17 patients who were not treated with antibiotics. Relapse occurred in 3 cases; no 30-days mortality was reported. Children and adults had similar clinical characteristics. However, children had a higher rate of CVC at the time of bacteremia and a higher chance to receive treatment.

Conclusion:
NTM BSI was seen mainly in oncologic patients with CVC. Children and adults had a similar disease course and outcome. Relapse was rare and NTM-related mortality was not reported.
Long-term Outcome After Acute Peripheral Facial Palsy
Authors: Ramsey David J. , Haas Laura P. , Tucker Susan M. 
Published: January 2022

Purpose:
To analyze long-term outcomes in a large cohort of patients with acute peripheral facial palsy (APFP).

Methods:
Hospital-based, cross-sectional study. Data were abstracted from the electronic medical record. Time to recovery was assessed with Kaplan-Meier survival analyses. Binary logistic regression analysis was used to identify factors associated with outcome.

Results:
Three hundred seventy-two patients with APFP seen at a tertiary hospital between February 2015 and March 2021 were analyzed. Seasonal variation of APFP peaked in the early fall (September 29) and had a peak-to-low ratio of 1.36 (R2 = 0.329, p < 0.001). Patients who tested positive for Lyme disease (10%) had an earlier peak (July 16) compared with those who were negative (October 15). Eighty-seven percent of patients had complete recovery (averaging 64 ± 61 days). Patients, with higher House-Brackmann (H-B) grades at presentation took longer to recover, were more likely to have aberrant regeneration and had lower final rates of recovery compared with those with lower H-B grades (χ2 = 12.03, p < 0.001). Of the patients with residual palsies, 70% had evidence of aberrant regeneration, and nearly half of those had hemifacial spasm.

Conclusions:
Most patients with APFP achieve complete recovery within 1 year, including those positive for Lyme. More severe palsy at presentation portends a worse outcome.
Orbital Exenteration for Advanced Periocular Adnexal Malignancies: Curative Versus Palliative Surgical Intent
Authors: Malik Mohsan , Vahdani Kaveh , Rose Geoffrey E. , Daniel Claire , Uddin J. M. , Verity D. H. , Collin J. R. O. 
Published: January 2022

Purpose:
To evaluate the survival benefit of orbital exenteration in periocular malignancy, taking account of preoperative intent.

Patients and methods:
Patients undergoing exenteration had retrospective chart review for demographics, clinical features, radiology, histology, and outcome. Based on systemic tumor status, the patient was either “Class I” (with absent or well-controlled systemic disease) or “Class II” (incurable active metastatic disease), and based on the extent of orbital disease and exenteration intent, was classed as either “Group A” (locally curative) or “Group B” (locally palliative).

Results:
One hundred thirty-three patients (78 females; 59%) underwent exenteration at an average age of 61 years (median 64; range 5–91) for sebaceous, squamous and basal cell carcinomas, or for melanoma (22%, 19%, 11%, and 28%, respectively). There were 20% systemically incurable patients (26/133; Class II), and incurable local disease (“Group B”) in 5% (5/107) of Class I and 15% (4/26) Class II patients. The overall survival (OS) was 88% at 12 months, 57% at 5 years, and 41% at 10 years, prognosis being worse with age more than 70 years (p = 0.005), prior local radiotherapy (p = 0.005) or positive resection margins (p = 0.002). The mean OS for Type IA exenteration (145 months; 95% CI 122–168) was significantly different to 50 months for Type IB (95% CI 22–79; p = 0.02); likewise, OS for Type IIA procedures (31 months; 95% CI 11–51) was different to Type IIB (19 months; 95% CI 2–36) (p = 0.001).

Conclusion:
Exenteration confers a significant survival with advanced periocular malignancies, even in patients with uncontrollable systemic disease, or where the local disease is deemed incurable.
Emotion Management for College Students: Effectiveness of a Mindfulness-Based Emotion Management Intervention on Emotional Regulation and Resilience of College Students
Authors: Jia-Yuan Zhang , Xiang-Zi Ji , Yi-Nan Fan , Yu-Xia Cui 
Published: January 2022

Abstract
The discovery of psychological healing methods that are easy to master and can be developed by the individual as a means of improving students' self-psychological adjustment ability is of great practical value. This study is a randomized control trial intended to investigate the effectiveness of mindfulness-based emotion management interventions and to test their effects on the mood state and resilience of college students. A total of 72 students were recruited and randomly divided into an intervention group and a control group. Thirty-six students in the intervention group received a modified mindfulness-based emotion management intervention once per week for 4 weeks, with each intervention having a duration of 80 minutes. Participants were assessed by questionnaires to measure mindfulness level, emotion, and resilience before and after intervention. There were significant interaction effects on mindfulness level (F = 97.76, p < 0.00), mood state (F = 353.52, p < 0.00), and resilience (F = 178.99, p < 0.00) scores. A modified 4-week mindfulness-based emotion management intervention can improve the mindfulness level and resilience of college students and is an innovative and feasible strategy for enhancing mental health in college students.
Uncertainty, Stress, and Resilience During the COVID-19 Pandemic in Greece
Authors: Nikopoulou Vasiliki A. , Gliatas Ioannis , Blekas Apostolos , Parlapani Eleni , Holeva Vasiliki , Tsipropoulou Virginia , Karamouzi Panayiota , Godosidis Athanasios , Diakogiannis Ioannis 
Published: January 2022

Abstract
The COVID-19 outbreak imposed stress worldwide, as daily routine changed almost overnight, with no time to prepare. A pandemic like this may trigger a chain reaction starting out as surprise, continuing to uncertainty and ending up either in adaptation or in symptoms of fear, anxiety, and/or depression. Resilience on the other hand could lessen anxiety and prove to be a prophylactic coping mechanism against distress. This study explored peritraumatic distress, intolerance of uncertainty (IU), and resilient coping in a sample of 2717 adults who voluntarily and anonymously participated in an online survey conducted in April 2020, in Greece.
Results indicated a moderate pandemic-related mental burden and medium resilient coping and designated IU as a significant positive predictor of peritraumatic distress; resilient coping proved to be a significant moderator that alters the strength of the association between IU and distress reactions.
Partner-Level and Sexual Networking Factors Are Associated With Vaccine-Type and Nonvaccine-Type Human Papillomavirus Infection After Vaccine Introduction in Young Women
Authors: Kahn Jessica , Washington Chalita , Ding Lili , Wyllie Tornia , Rosen Brittany , Gorbach Pamina 
Published: January 2022

Background
The aim of this study was to determine individual-level, partner-level, and sexual networking factors associated with vaccine- and non–vaccine-type human papillomavirus (HPV) in young women, by vaccination status.

Methods
Sexually experienced women 13 to 26 years old (n = 784) completed a survey and were tested for 36 HPV genotypes. We determined factors associated with 4-valent vaccine-type HPV (HPV-6, HPV-11, HPV-16, HPV-18) and non–vaccine-type HPV among vaccinated and unvaccinated women, using univariable and multivariable logistic regression models.

Results
Participants' mean age was 19.2 years, 77.7% had received ≥1 vaccine dose, and 7.7% were positive for vaccine-type HPV (HPV-6, HPV-11, HPV-16, and/or HPV-18). Factors associated with vaccine-type HPV in vaccinated women included gonorrhea history (adjusted odds ratio [AOR], 2.71), new female sex partner(s) (AOR, 4.79), age at vaccination (≥15 vs. <15 years; AOR, 2.47), and age discordance with most recent partner (don't know vs. discordant; AOR, 9.17). Factors associated with non–vaccine-type HPV in vaccinated women included history of sexually transmitted infection (AOR, 2.69), male most recent partner (AOR, 2.85), age of first sex (AOR, 1.15), and partner concurrency (don't know vs. 1 other partner; AOR, 2.03). Factors associated with vaccine-type HPV in unvaccinated women included new female sex partner(s) (AOR, 7.45) and partner concurrency (don't know vs. no; AOR, 2.95). Factors associated with non–vaccine-type HPV in unvaccinated women included race (White vs. multiracial; AOR, 4.10) and partner concurrency (don't know vs. 0; AOR, 4.65).

Conclusions
Novel findings of this study, including associations between female sex partners and HPV, and between not knowing about partner concurrency and HPV, have implications for sexual education, clinical counseling, and public health interventions.
Transcranial Magnetic Stimulation Therapy of Major Depressive Disorder Improves Heart Rate Variability
Authors: Onyilo Chukwuemeka V. , McCall William V. , Rosenquist Peter 
Published: January 2022

Abstract
Transcranial magnetic stimulation is typically administered daily for 6 to 9 weeks with gradual resolution of major depressive disorder. However, there is little evidence to guide clinicians when clinical improvement is not forthcoming as the course proceeds. We describe a patient whose depression score remained unchanged after 10 single daily intermittent thetaburst transcranial magnetic stimulation sessions targeting F3 in the dorsolateral prefrontal cortex and our efforts to modify the technique and monitor progress with heart rate variability (HRV) measures. The motor threshold position and intensity were verified to be unchanged from the baseline visit. Stimulation of F3 and treatment target 6 cm anterior to the mapped motor cortex site seemed to slow heart rate and increase HRV equally. We increased the number of daily intermittent thetaburst pulse trains for the remainder of the treatment course, targeting the 6-cm target. Our patient subsequently improved, and we observed concurrent changes in HRV suggestive of enhanced parasympathetic activity. These improvements were found to be durable at 10-week follow-up.
Distinct genetic determinants and mechanisms of SARS-CoV-2 resistance to remdesivir
Authors: Stevens Laura J. , Pruijssers Andrea J. , Lee Hery W. , Gordon Calvin J. , Tchesnokov Egor P. , Gribble Jennifer , George Amelia S. , Hughes Tia M. , Lu Xiaotao , Li Jiani , Perry Jason K. , Porter Danielle P. , Cihlar Tomas , Sheahan Timothy P. , Baric Ralph S. , Götte Matthias , Denison Mark R. 
Published: January 2022

AbstractThe nucleoside analog remdesivir (RDV) is an FDA-approved antiviral for the treatment of SARS- CoV-2 infections, and as such it is critical to understand potential genetic determinants and barriers to RDV resistance. In this study, SARS-CoV-2 was subjected to 13 passages in cell culture with increasing concentrations of GS-441524, the parent nucleoside of RDV. At passage 13 the RDV resistance of the lineages ranged from 2.7-to 10.4-fold increase in EC50. Sequence analysis of the three lineage populations identified non-synonymous mutations in the nonstructural protein 12 RNA-dependent RNA polymerase (nsp12-RdRp): V166A, N198S, S759A, V792I and C799F/R. Two of the three lineages encoded the S759A substitution at the RdRp Ser759-Asp-Asp active motif. In one lineage, the V792I substitution emerged first then combined with S759A. Introduction of the S759A and V792I substitutions at homologous nsp12 positions in viable isogenic clones of the betacoronavirus murine hepatitis virus (MHV) demonstrated their transferability across CoVs, up to 38-fold RDV resistance in combination, and a significant replication defect associated with their introduction. Biochemical analysis of SARS-CoV-2 RdRp encoding S759A demonstrated a ∼10- fold decreased preference for RDV-triphosphate (RDV-TP) as a substrate, while nsp12-V792I diminished the UTP concentration needed to overcome the template-dependent inhibition associated with RDV. The in vitro selected substitutions here identified were rare or not detected in the >6 million publicly available nsp12-RdRp consensus sequences in the absence of RDV selection. The results define genetic and biochemical pathways to RDV resistance and emphasize the need for additional studies to define the potential for emergence of these or other RDV resistance mutations in various clinical settings.One Sentence SummarySARS-CoV-2 develops in vitro resistance to remdesivir by distinct and complementary mutations and mechanisms in the viral polymerase