bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA sequencing reveals the immunoregulatory roles of PegIFN-α in patients with chronic hepatitis B
Authors: Jiang Penglei , Jia Hongyu , Qian Xinyue , Tang Tian , Han Yingli , Zhang Zhaoru , Jiang Lingli , Yu Zebin , Zheng Lin , Yu Guodong , Cai Huan , Zhang Shanyan , Zhang Xiaoli , Gu Jueqing , Ye Chanyuan , Yang Lisha , Lu Yingfeng , Liu Heng , Lu Xiaoqing , Jin Ciliang , Ren Yue , Lu Miaomiao , Xu Lingling , Yu Jiong , Jin Xi , Yang Yida , Qian Pengxu 
Published: June 2023

Background and Aims:
Chronic hepatitis B (CHB) is caused by HBV infection and affects the lives of millions of people worldwide by causing liver inflammation, cirrhosis, and liver cancer. Interferon-alpha (IFN-α) therapy is a conventional immunotherapy that has been widely used in CHB treatment and achieved promising therapeutic outcomes by activating viral sensors and interferon-stimulated genes (ISGs) suppressed by HBV. However, the longitudinal landscape of immune cells of CHB patients and the effect of IFN-α on the immune system are not fully understood.

Approach and Results:
Here, we applied single-cell RNA sequencing (scRNA-seq) to delineate the transcriptomic landscape of peripheral immune cells in CHB patients before and after PegIFN-α therapy. Notably, we identified three CHB-specific cell subsets, pro-inflammatory (Pro-infla) CD14+ monocytes, Pro-infla CD16+ monocytes and IFNG+ CX3CR1− NK cells, which highly expressed proinflammatory genes and positively correlated with HBsAg. Furthermore, PegIFN-α treatment attenuated percentages of hyperactivated monocytes, increased ratios of long-lived naive/memory T cells and enhanced effector T cell cytotoxicity. Finally, PegIFN-α treatment switched the transcriptional profiles of entire immune cells from TNF-driven to IFN-α-driven pattern and enhanced innate antiviral response, including virus sensing and antigen presentation.

Conclusions:
Collectively, our study expands the understanding of the pathological characteristics of CHB and the immunoregulatory roles of PegIFN-α, which provides a new powerful reference for the clinical diagnosis and treatment of CHB.
Healthcare-associated Infections Drive Antimicrobial Prescribing in Pediatric Departments at Three Academic Hospitals in South Africa
Authors: Chetty Terusha , Pillay Ashendri , Balakrishna Yusentha , Reddy Tarylee , Goga Ameena , Moore David P. , Karsas Maria , Cloete Jeané , Archary Moherndran , Kwawegen Alison van , Thomas Reenu , Nakwa Firdose Lambey , Waggie Zainab , Magrath Stephanie , Jeena Prakash 
Published: June 2023

Background:The prevalence of antimicrobial prescriptions for healthcare-associated infections (HAI) in South Africa is largely unknown. This study aimed to estimate the point prevalence of pediatric antibiotic and antifungal usage in 3 South African academic hospitals.Methods:This cross-sectional study included hospitalized neonates and children (0–15 years). We used the World Health Organization methodology for antimicrobial point prevalence studies, with weekly surveys to achieve a sample size of ~400 at each site.Results:Overall, 1,946 antimicrobials were prescribed to 1,191 patients. At least 1 antimicrobial was prescribed for 22.9% [95% confidence interval (CI): 15.5–32.5%] of patients. The prevalence of antimicrobial prescribing for HAI was 45.6%. In the multivariable analysis, relative to children 6–12 years, neonates [adjusted relative risk (aRR): 1.64; 95% CI: 1.06–2.53], infants (aRR: 1.57; 95% CI: 1.12–2.21) and adolescents (aRR: 2.18; 95% CI: 1.45–3.29) had significantly increased risk of prescriptions for HAI. Being preterm (aRR: 1.33; 95% CI: 1.04–1.70) and underweight (aRR: 1.25; 95% CI: 1.01–1.54) was predictive of antimicrobial usage for HAI. Having an indwelling device, surgery since admission, blood transfusions and classification as rapidly fatal on McCabe score also increased the risk of prescriptions for HAI.Conclusions:The high prevalence of antimicrobial prescribing for HAI to treat children with recognized risk factors in academic hospitals in South Africa is concerning. Concerted efforts need to be made to strengthen hospital-level infection prevention and control measures, with a critical review of antimicrobial usage through functional antibiotic stewardship programs to preserve the available antimicrobial armamentarium at the hospital level.
Chemotherapy for pain: reversing inflammatory and neuropathic pain with the anticancer agent mithramycin A
Authors: Xu Zheyun , Lee Man-Cheung , Sheehan Kayla , Fujii Keisuke , Rabl Katalin , Rader Gabriella , Varney Scarlett , Sharma Manohar , Eilers Helge , Kober Kord , Miaskowski Christine , Levine Jon D. , Schumacher Mark A. 
Published: June 2023

Abstract
The persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors. Here, we investigate the ability of MTM to reverse in vivo models of inflammatory and chemotherapy-induced peripheral neuropathy (CIPN) pain and explore MTM's underlying mechanisms. Mithramycin reversed inflammatory heat hyperalgesia induced by complete Freund adjuvant and cisplatin-induced heat and mechanical hypersensitivity. In addition, MTM reversed both short-term and long-term (1 month) oxaliplatin-induced mechanical and cold hypersensitivity, without the rescue of intraepidermal nerve fiber loss. Mithramycin reversed oxaliplatin-induced cold hypersensitivity and oxaliplatin-induced TRPM8 overexpression in dorsal root ganglion (DRG). Evidence across multiple transcriptomic profiling approaches suggest that MTM reverses inflammatory and neuropathic pain through broad transcriptional and alternative splicing regulatory actions. Mithramycin-dependent changes in gene expression following oxaliplatin treatment were largely opposite to and rarely overlapped with changes in gene expression induced by oxaliplatin alone. Notably, RNAseq analysis revealed MTM rescue of oxaliplatin-induced dysregulation of mitochondrial electron transport chain genes that correlated with in vivo reversal of excess reactive oxygen species in DRG neurons. This finding suggests that the mechanism(s) driving persistent pain states such as CIPN are not fixed but are sustained by ongoing modifiable transcription-dependent processes.
Age and Incidence of Cochlear Implantation in the Pediatric Population With Congenital Bilateral Profound Hearing Loss
Authors: Nassiri Ashley M. , Marinelli John P. , Lohse Christine M. , Carlson Matthew L. 
Published: June 2023

ObjectivesThe current study characterizes age and incidence of cochlear implantation among qualifying children with congenital bilateral profound hearing loss in the U.S.Study DesignDeidentified cochlear implantation data were acquired from prospectively collected patient registries from two cochlear implant (CI) manufacturers (Cochlear Americas and Advanced Bionics). Children <36 months old were assumed to have congenital bilateral profound sensorineural hearing loss.SettingU.S. CI centers.PatientsChildren <36 months old who received CIs.InterventionsCochlear implantation.Main Outcome MeasuresAge at implantation and incidence.ResultsA total of 4,236 children <36 months old underwent cochlear implantation from 2015 to 2019. The median age at implantation was 16 months (interquartile range, 12–24 mo) and did not change significantly during the 5-year study period (p= 0.09). Patients residing closer to CI centers (p= 0.03) and treated at higher-volume centers (p= 0.008) underwent implantation at a younger age. Bilateral simultaneous implantation increased from 38% to 53% of CI surgeries in 2015 and 2019, respectively. Children who received bilateral simultaneous CIs were younger compared with those receiving unilateral or bilateral sequential CIs (median, 14 versus 18 mo;p< 0.001). The incidence of cochlear implantation increased from 7,648 per 100,000 person-years in 2015 to 9,344 in 2019 (p< 0.001).ConclusionAlthough the incidence of pediatric CI recipients and the frequency of bilateral simultaneous implantation increased over the study period, age at implantation did not change significantly and far exceeded current Food and Drug Administration (9 mo) and American Academy of Otolaryngology and Head and Neck Surgery position statement (6–12 mo) guidelines.
Comparison of a Novel Binocular Refraction System to Standard Digital Phoropter Refraction
Authors: Bossie Timothy , Reilly Jennifer , Vera-Diaz Fuensanta A. 
Published: June 2023

ABSTRACT

SIGNIFICANCE
New refractive technologies are consistently emerging in the optometry market, necessitating validation against current clinical standards.

PURPOSE
To compare the refractive measurements between standard digital phoropter refraction and the Chronos binocular refraction system.

METHODS
Standardized subjective refraction was conducted on 70 adult participants using two separate refraction systems. The final subjective values from both devices were compared for M, J0, and J45. The time taken to complete refraction and patient’s comfort were also evaluated.

RESULTS
Good agreement was found between the standard and Chronos refraction, with narrow mean differences (including 95% confidence intervals), and no significant bias for M (0.03, -0.05 to 0.11 D), J0 (-0.02, -0.05 to -0.01 D) and J45 (-0.01, -0.03 to 0.01 D). The bounds of the limits of agreement (LoA) of M (lower bound -0.62, -0.76 to -0.49, and upper bound 0.68, 0.54 to 0.81), J0 (lower bound -0.24, -0.29 to -0.19) and upper bound (0.19, 0.15 to 0.24), and J45 (lower bound -0.18, -0.21 to -0.14) and upper bound (0.16, 0.12 to 0.19). No significant differences were noted between the two techniques for any of the refraction components (M standard: -3.03 ± 2.42 D, novel: -3.06 ± 2.37 D, Z = 0.07, P = .47, J0 standard: 0.12 ± 0.40 D, novel: 0.15 ± 0.41 D, Z = 1.32, P = .09, J45 standard: -0.04 ± 0.19 D, novel: -0.03 ± 0.19 D, Z = 0.50, P = .31). The Chronos was significantly faster than the standard technique, with an average difference of 19 seconds (standard: 190 ± 44 seconds, novel: 171 ± 38 seconds, Z = 4.91, P < .001).

CONCLUSIONS
The final subjective refraction endpoints of the standard technique and the Chronos were well aligned in this group of adult participants, and no statistically or clinically significant differences were noted in M, J0 or J45 components. The Chronos offered improved efficiency, meeting the demands of eye care.
Predictive Value of Serum Biomarkers for Response of Limited-Stage AIDS-Associated Kaposi Sarcoma to Antiretroviral Therapy With or Without Concomitant Chemotherapy in Resource-Limited Settings
Authors: Epeldegui Marta , Chang Di , Lee Jeannette , Magpantay Larry I. , Borok Margaret , Bukuru Aggrey , Busakhala Naftali , Godfrey Catherine , Hosseinipour Mina C. , Kang Minhee , Kanyama Cecilia , Langat Deborah , Mngqibisa Rosie , Mwelase Noluthando , Nyirenda Mulinda , Samaneka Wadzanai , Hoagland Brenda , Campbell Thomas B. , Martínez-Maza Otoniel , Krown Susan E. ,   for the A5264/AMC-067 team
Published: June 2023

Background:
Guidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking.

Setting:
We studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART.

Methods:
Serum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C–C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART.

Results:
Pretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammation-associated biomarkers and increasing levels post-treatment.

Conclusions:
Quantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.
Telemedicine and HIV Care Quality Measures During the COVID-19 Pandemic
Authors: Masters Mary Clare , Rivera Juan , Calamari Mia , Wright Katherine , Janulis Patrick , Rusie Laura , Bannon Jacqueline , Milne Patrick , Galvin Shannon R. , Molina Elena Gonzalez , Hirschhorn Lisa R. , Palella Frank J. , Kumar Rebecca , Brown Cory , Hawkins Claudia 
Published: June 2023

Background:
During the COVID-19 pandemic, telemedicine was adopted to ensure continuity of HIV care. We examined how introducing televisits affected technical quality of care for people with HIV (PWH) during this time.

Methods:
PWH receiving HIV care at Howard Brown Health Centers and Northwestern University in Chicago, Illinois were included. HIV care quality indicators were calculated using data extracted from electronic medical records during 4 timepoints every 6 months from March, March 1, 2020 to September 1, 2021. Generalized linear mixed models estimated differences in indicators across timepoints within each site while controlling for multiple observations of individuals. Generalized linear mixed models were also used to compare differences in outcomes among PWH who attended all versus a combination of in-person and televisits versus no televisits across the study time periods.

Results:
6447 PWH were included in the analysis. Compared with prepandemic levels, there were significant declines in care utilization and processes of care measures. Measures of HIV virologic suppression, blood pressure control, and HbA1C <7% (in both people with and without diabetes) were stable with no significant differences noted across the study timepoints. Similar trends were observed across all age, race, and sex subgroups. In multivariable models, televisits were not associated with decreased HIV viral suppression.

Conclusions:
During the COVID-19 pandemic and rapid implementation of televisits, indicators of care utilization and processes of care decreased compared with prepandemic levels. Among PWH who remained in care, televisits were not associated with worse virologic, blood pressure, and glycemic control in PWH.
Obsessive-Compulsive, Psychotic, and Autism Dimensions Overlap in Real World: A Case Report
Authors: Scala Mauro , Biondi Laura , Serretti Alessandro , Fabbri Chiara 
Published: June 2023

Background
Obsessions, compulsions, and stereotypes are common psychopathological manifestations of obsessive-compulsive, psychotic, and autism spectrum disorders (ASDs). These nosological entities may be present in comorbidity, with relevant clinical difficulties in the differential diagnosis process. Moreover, ASDs are a complex group of disorders, with a childhood onset, which also persist into adulthood and present heterogeneous symptom patterns that could be confused with psychotic disorders.

Methods and Results
We report a case of a 21-year-old man characterized by sexual and doubt obsessions; disorganized, bizarre, and stereotyped behaviors and compulsions; and social withdrawal, inadequate social skills, visual dispersions, and hypersensitivity to light stimuli. Obsessive and compulsive features were initially included within the differential diagnosis of psychotic and obsessive-compulsive spectrum disorders. However, aforementioned psychopathological elements did not improve when multiple antipsychotic drugs (olanzapine, haloperidol, and lurasidone) were administered in the hypothesis of schizophrenia and even worsened with clozapine therapy at a dose of 100 mg/d. Obsessions and compulsions progressively reduced during the fluvoxamine 14-week treatment paradigm at a dose of 200 mg/d. Considering the persistent deficits in social communication and interactions as well as the restricted interests pattern, a differential diagnostic hypothesis of ASD was formulated, and it was then confirmed at the final evaluation at a third-level health care center.

Conclusions
We discuss similarities and differences in the psychopathology of obsessions, compulsions, and stereotypes in the previously mentioned disorders, to underline factors that can help in the differential diagnosis of similar cases, and consequently in the appropriateness of treatment choice.
Multicenter Study of Perioperative Hepatic Angioembolization as an Adjunct for Management of Major Operative Hepatic Trauma
Authors: Deville Paige E , Marr Alan B , Cone Jennifer T , Hoefer Lea E , Mitchao Delbrynth P , Inaba Kenji , Kostka Ryan , Mooney Jennifer L , McNickle Allison G , Smith Alison A ,   for the MIT Liver Study Group
Published: June 2023

BACKGROUND:
The management of major liver trauma continues to evolve in trauma centers across the US with increasing use of minimally invasive techniques. Data on the outcomes of these procedures remain minimal. The objective of this study was to evaluate patient complications after perioperative hepatic angioembolization as an adjunct to management of major operative liver trauma.

STUDY DESIGN:
A retrospective multi-institutional study was performed at 13 level 1 and level 2 trauma centers from 2012 to 2021. Adult patients with major liver trauma (grade 3 and higher) requiring operative management were enrolled. Patients were divided into 2 groups: angioembolization (AE) and no angioembolization (NO AE). Univariate and multivariate analyses were performed.

RESULTS:
A total of 442 patients were included with AE performed in 20.4% (n = 90 of 442) of patients. The AE group was associated with higher rates of biloma formation (p = 0.0007), intra-abdominal abscess (p = 0.04), pneumonia (p = 0.006), deep vein thrombosis (p = 0.0004), acute renal failure (p = 0.004), and acute respiratory distress syndrome (p = 0.0003), and it had longer ICU and hospital length of stay (p < 0.0001). On multivariate analysis, the AE had a significantly higher amount intra-abdominal abscess formation (odds ratio 1.9, 95% CI 1.01 to 3.6, p = 0.05).

CONCLUSIONS:
This is one of the first multicenter studies comparing AE in specifically operative high-grade liver injuries and found that patients with liver injury that undergo AE in addition to surgery have higher rates of both intra- and extra-abdominal complications. This provides important information that can guide clinical management.
Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated Golden Syrian Hamsters
Authors: Diego Juan García-Bernalt , Singh Gagandeep , Jangra Sonia , Handrejk Kim , Laporte Manon , Chang Lauren A. , El Zahed Sara S. , Pache Lars , Chang Max W. , Warang Prajakta , Aslam Sadaf , Mena Ignacio , Webb Brett T. , Benner Christopher , García-Sastre Adolfo , Schotsaert Michael 
Published: June 2023

ABSTRACT
Hybrid immunity to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera. Transcriptomics post-infection reflects both vaccination status and disease course and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of high titers of neutralizing antibodies in the serum, correlates with recall of broadly reactive B and T-cell responses.
Observer-rated outcomes of Communication-Centered Treatment (CCT) for adults who stutter: A preliminary study
Authors: Byrd Courtney T. , Coalson Geoffrey A. , Werle Danielle 
Published: June 2023

AbstractPrevious studies have reported that adults who stutter demonstrate significant gains in communication competence, per self-ratings and clinician-ratings, upon completion of a communication-centered treatment, or CCT. The purpose of the present study was to determine whether gains in communication competence would also be reported by untrained observers. Eighty-one untrained observers completed an online survey that required each to view one of two videos depicting an adult who stutters during a mock interview recorded prior to CCT or after CCT. Participants were then asked to rate the communication competence of the interviewee on a 100-point visual analog scale and provide additional demographic information. Communication competence of the adult who stutters was rated significantly higher in their post-treatment video. Two observer-based factors were significantly associated with ratings of communication competence: years of education and years the respondent had known an adult who stutters. Upon controlling for these demographic factors, significantly higher ratings of communication competence for the post-treatment video were maintained. Although preliminary, findings suggest gains in communication competence demonstrated in previous studies through clinician and client observations are not limited to the sterile clinical environment, and further emphasizes the ecological validity of CCT. [ClinicalTrials.govNCT05908123;https://clinicaltrials.gov/show/NCT05908123]