bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient, Parent, and Provider Perceptions of Barriers to Pediatric Inflammatory Bowel Disease Care
Authors: Dotson Jennifer L. , Bricker Josh , Chisolm Deena J. , Mackner Laura M. 
Published: November 2023

Objectives:
Children with inflammatory bowel disease (IBD) have a significant life-long burden as a result of disease, impacted by environmental and individual barriers. Successful health system interventions require a comprehensive approach, informed by various stakeholders. The main objective was to identify health system barriers and potential solutions from existing patients, families, and providers via focus groups.

Methods:
Participants for the focus groups were existing English-speaking patients (ages 9–18) with IBD, their caregiver(s), and providers including multiple professions (eg, physician, nurse, pediatrician, social worker, care coordinator, scheduler, and psychologist). Separate focus groups were led by experienced personnel for parents, children, and providers, using a standardized interview guide. Sessions were recorded, transcribed, and verified. Using content analysis, we systematically classified data through coding and identified themes.

Results:
Focus groups comprised (a) 3 patient groups (n = 20, 50% female, including 2 younger; mean age = 11.4 ± 1.5 years) and 1 older group (mean age = 15.6 ± 1.3 years), (b) 3 parent groups (n = 24, 83% female), and (c) 2 multidisciplinary provider groups (n = 19). Families shared several common concerns with providers (eg, school, care delay, psychosocial, and financial) but varied on specifics. Some barriers may be addressable through family or staff education, improved communication (eg, care delay/ access, transition), or training (eg, labs and diet), while others may require change at an institutional or policy level (eg, insurance).

Conclusions:
This qualitative analysis identified several barriers to IBD care, some shared, some unique to patients, parents, and providers, highlighting the importance of obtaining multiple stakeholder perspectives when exploring barriers to care.
Intrathecal production of anti-Epstein–Barr virus viral capsid antigen IgG is associated with neurocognition and tau proteins in people with HIV
Authors: Trunfio Mattia , Sacchi Alessandra , Vai Daniela , Pittaluga Fabrizia , Croce Michele , Cavallo Rossana , Imperiale Daniele , Bonora Stefano , Di Perri Giovanni , Letendre Scott Lee , Calcagno Andrea 
Published: November 2023

Objective:
HIV and Epstein–Barr virus (EBV) co-infection has been linked to increased immune activation and larger HIV reservoir. We assessed whether anti-EBV humoral responses are associated with increased cerebrospinal fluid (CSF) inflammation and with neurocognitive impairment (NCI) in people with HIV (PWH).

Design:
Cross-sectional analysis in 123 EBV-seropositive PWH either on antiretroviral therapy (n = 70) or not.

Methods:
Serum and CSF anti-EBV viral capsid antigen immunoglobulin G (anti-EVI) and CSF EBV DNA were measured by commercial immunoassay and RT-PCR. Seventy-eight participants without neurological confounding factors underwent neurocognitive assessment (Global Deficit Score, GDS). CSF total tau and 181-phosphorylated-tau (ptau) were measured by immunoassays together with biomarkers of blood–brain barrier (BBB) integrity, immune activation, astrocytosis, and intrathecal synthesis. Logistic and linear regressions and moderation analysis were used to investigate the relationships between CSF anti-EVI, GDS, and biomarkers.

Results:
Twenty-one (17.1%) and 22 participants (17.9%) had detectable CSF anti-EVI (10.5–416.0 U/ml) and CSF EBV DNA (25–971 copies/ml). After adjusting for BBB integrity, age, and clinical factors, the presence of CSF anti-EVI was only associated with serum levels of anti-EVI, and not with CSF EBV DNA. CSF anti-EVI, tau and ptau showed reciprocal interactions affecting their associations with GDS. After adjusting for demographics and clinical parameters, higher CSF anti-EVI levels were associated with worse GDS (aβ 0.45, P < 0.001), and CSF levels of tau and ptau had a moderation effect on the strength of this association (models’P < 0.001).

Conclusion:
Humoral immune responses against EBV within the central nervous system may contribute to NCI in PWH through mechanisms that involve neuronal injury.
Impact of coronavirus disease 2019-related clinic closures on HIV incidence in young adult MSM and transgender women in Kenya
Authors: Wahome Elizabeth , Otieno Fredrick O. , Kimani Joshua , Boyd Anders , Okall Duncan , Nzioka Joseph , Gichuru Evans , van der Elst Elise , Mehta Supriya D. , Bailey Robert C. , Graham Susan M. , Sanders Eduard J. ,   for the Tatu Pamoja (three-site) study group†
Published: November 2023

Introduction:
Little is known about the impact that the COVID-19 pandemic had on risk of HIV acquisition in sub-Saharan Africa. We assessed the impact of COVID-19-related clinic closures on HIV incidence in a cohort of gay, bisexual, and other men who have sex with men (MSM) and transgender women in Kenya.

Methods:
MSM and transgender women enrolled in a prospective, multicentre cohort study were followed quarterly for HIV testing, behaviour assessments, and risk. We estimated the HIV incidence rate and its 95% credible intervals (CrI) among participants who were HIV-negative before COVID-19-related clinic closure, comparing incidence rate and risk factors associated with HIV acquisition before vs. after clinic reopening, using a Bayesian Poisson model with weakly informative priors.

Results:
A total of 690 (87%) participants returned for follow-up after clinic reopening (total person-years 664.3 during clinic closure and 1013.3 after clinic reopening). HIV incidence rate declined from 2.05/100 person-years (95% CrI = 1.22–3.26, n = 14) during clinic closures to 0.96/100 person-years (95% CrI = 0.41–2.07, n = 10) after clinic reopening (IRR = 0.47, 95% CrI = 0.20–1.01). The proportion of participants reporting hazardous alcohol use and several sexual risk behaviours was higher during clinic closures than after clinic reopening. In multivariable analysis adjusting for study site and participant characteristics, HIV incidence was lower after clinic reopening (IRR 0.57, 95% CrI = 0.23–1.33). Independent risk factors for HIV acquisition included receptive anal intercourse (IRR 1.94, 95% CrI = 0.88–4.80) and perceived risk of HIV (IRR 3.03, 95% CRI = 1.40–6.24).

Conclusion:
HIV incidence during COVID-19-related clinic closures was moderately increased and reduced after COVID-19 restrictions were eased. Ensuring access to services for key populations is important during public health emergencies.
A study of the pharmacokinetics, safety, and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in virologically suppressed pregnant women with HIV
Authors: Zhang Haeyoung , Hindman Jason T. , Lin Ludwig , Davis Maggie , Shang Justin , Xiao Deqing , Avihingsanon Anchalee , Arora Priyanka , Palaparthy Ramesh , Girish Sandhya , Marathe Dhananjay D. 
Published: November 2023

Objective:
The objective of this study was to assess the pharmacokinetics, safety, and efficacy and confirm the dose of once-daily bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; B/F/TAF) during pregnancy.

Design:
An open-label, multicenter, single-arm, phase 1b study (NCT03960645) was conducted in 33 virologically suppressed pregnant women with HIV-1.

Methods:
Participants received B/F/TAF (50/200/25 mg) from the second or third trimester through ∼16 weeks postpartum. Steady-state maternal plasma pharmacokinetic samples were collected at the second and third trimesters and 6 and 12 weeks postpartum for BIC, FTC, and TAF. Neonates (n = 29) were followed from birth to 4–8 weeks with sparse washout pharmacokinetic sampling for BIC and TAF. The proportion of participants with HIV-1 RNA less than 50 copies/ml at delivery (missing = excluded) was evaluated.

Results:
Mean areas under the concentration–time curve over the dosing interval (AUCtau) for BIC, FTC, and TAF were lower during pregnancy versus postpartum but were closer to AUCtau values for nonpregnant adults with HIV reported in other studies. Geometric least-squares mean ratios for BIC, FTC, and TAF AUCtau during pregnancy versus postpartum ranged from 41 to 45%, 64 to 69% and 57 to 78%, respectively. Mean BIC trough concentrations during pregnancy were more than 6.5-fold greater than the protein-adjusted 95% effective concentration. In neonates, the median BIC half-life was 43 h. Virologic suppression was maintained in all adult participants throughout the study, with no virologic failure or treatment-emergent resistance to HIV-1, no discontinuations because of adverse events, and no perinatal transmission.

Conclusion:
Exposures to BIC, FTC, and TAF were lower during pregnancy than postpartum. However, mean BIC trough concentrations were maintained at levels indicative of efficacious exposure, and FTC/TAF data were concordant with published literature in this population. Pharmacokinetic and safety data, combined with maintenance of robust virologic suppression, suggest that once-daily B/F/TAF without dose adjustment is appropriate during pregnancy.
Elevated 68Ga-FAPI Activity in Klebsiella pneumoniae Invasion Syndrome
Authors: Xie Yang , Tang Wenxin , Ma Jiao , Wang Yudi , Chen Yue 
Published: November 2023

AbstractKlebsiella pneumoniaeinvasion syndrome is a rare disease associated with primary liver abscess and secondary extrahepatic infection. We report a case ofK. pneumoniaeinvasion syndrome with elevated68Ga-FAPI uptake, mimicking malignancy with multiple metastases. Our case illustrated thatK. pneumoniaeinvasion syndrome should be considered as a possible etiology when diagnosing multiple68Ga-FAPI–avid liver foci with metastatic lesions. Besides, PET/CT could be an integrated tool to search for systemic occult lesions inK. pneumoniaeinvasion syndrome.
Mandible Reconstruction in a Rural Population: Comparison of Radial Forearm and Free Fibula Flap Outcomes
Authors: Clegg Devin J. , Deek Andrew J. , Salomon Brett J. , Blackburn Caleb , Fahmy Mina D. , Heidel Robert E. , Stephenson Stacy M. , Herbig Kathleen S. , Chun Joseph T. , Carlson Eric R. , Boukovalas Stefanos 
Published: November 2023

Comparison of microsurgical reconstructive options after mandible resection is limited in the literature. Fibula free flaps (FFFs) can be costly and have timing limitations, but dental restoration can be performed, with varied reported rates of completion. The radial forearm free flap (RFFF) with mandible plating may be an alternative in select populations. The purpose of this study was to determine if the RFFF has similar outcomes to the FFF for mandible reconstruction in a rural population. A retrospective review of patients who underwent mandibulectomy from 2017 to 2021 at a single tertiary-care academic institution was performed. Those with FFF or RFFF reconstruction were included. Mandible defects were classified using the Jewer-Boyd H-C-L system. Sixty-eight patients were included with 53 undergoing FFF and 15 undergoing RFFF. Immediate reconstruction was significantly more common with RFFF than FFF (100% versus 64.2%; P=0.01). Lateral mandible defects were most common among both groups (52.9% FFF versus 73.3% RFFF; P=0.04). Osseous defect length was similar (9.5 cm FFF versus 7.7 cm RFFF; P=0.07), but soft tissue defect size was significantly larger in the RFFF group (28.6 cm2 versus 15.3 cm2; P=0.01). Complication rates (47.1% FFF versus 46.7% RFFF; P=0.98) and disease-free status at last follow-up (96.2% FFF versus 80.0% RFFF; P=0.06) were similar. Dental restoration occurred in 21.3% of patients undergoing FFF. Patients undergoing RFFF or FFF reconstruction after mandibulectomy had similar surgical and disease outcomes, with a low rate of completed dental restoration after FFF. Our findings suggest RFFF is a reasonable alternative to FFF for mandible reconstruction in select patients.
Surgical Apgar scores predict complications after emergency general surgery laparotomy
Authors: Tracy Brett M. , Srinivas Shruthi , Baselice Holly , Gelbard Rondi B. , Coleman Julia R. 
Published: November 2023

BACKGROUND
The Surgical Apgar Score (SAS) is a 10-point validated score comprised of three intraoperative variables (blood loss, lowest heart rate, and lowest mean arterial pressure). Lower scores are worse and predict major postoperative complications. The SAS has not been applied in emergency general surgery (EGS) but may help guide postoperative disposition. We hypothesize that SAS can predict complications in EGS patients undergoing a laparotomy.

METHODS
We performed a retrospective review of adult patients at a single, quaternary care center who underwent an exploratory laparotomy for EGS conditions within 6 hours of surgical consultation from 2015 to 2019. Patients were grouped by whether they experienced a postoperative complication (systemic, surgical, and/or death). Multivariable regression was performed to predict complications, accounting for SAS and other statistically significant variables between groups. Using this model, predicted probabilities of a complication were generated for each SAS.

RESULTS
The cohort comprised 482 patients: 32.8% (n = 158) experienced a complication, while 67.2% (n = 324) did not. Patients with complications were older, frailer, more often male, had worse SAS (6 vs. 7, p < 0.0001) and American Society of Anesthesiologists scores, and higher rates of perforated hollow viscus (p = 0.0003) and open abdomens (p < 0.0001). On multivariable regression, an increasing SAS independently predicted less complications (adjusted odds ratio, 0.85; 95% confidence interval, 0.75–0.96; p = 0.009). An SAS ≤4 was associated with a 49.2% predicted chance of complications, greater rates of septic shock (9.7% vs. 3%, p = 0.01), respiratory failure (20.5% vs. 10.8%, p = 0.02), and death (24.1% vs. 7.5%, p < 0.0001). An SAS ≤ 4 did not correlate with surgical complications (p = 0.1).

CONCLUSION
The SAS accurately predicts postoperative complications in EGS patients undergoing urgent laparotomy, with an SAS ≤ 4 identifying patients at risk for septic shock, respiratory failure, and mortality. This tool can aid in rapidly determining postoperative disposition and resource allocation.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV
Carer strain in post-stroke emotionalism: an initial evaluation
Authors: Broomfield Niall M , Walters Matthew , West Robert M 
Published: November 2023

ABSTRACTBackground and PurposePost-stroke emotionalism is a common, under-researched neurologic symptom of stroke, characterised by frequent crying episodes not under usual social control. Currently there are no data on carer strain in the context of emotionalism after stroke.AimsTo explore the degree of carer strain in carers of individuals with diagnosed PSE compared to carers of individuals with stroke but no PSE. To examine whether carer strain varies with particular characteristics of the cared for individual: patient age, sex, social deprivation, stroke type, functional status, mood status.Methods102 informants of people with stroke completed the Modified Carer Strain Index at 6-months as part of the TEARS longitudinal cohort study between October 1st2015 and September 30th2018. Stroke survivor diagnostic status was determined using Testing Emotionalism After Recent Stroke-Diagnostic Interview based on published, widely accepted diagnostic criteria of emotionalism.ResultsThere was little evidence of association between carer strain and sex, age, deprivation level or stroke type of the cared for individual. There was strong evidence that carer strain associated with both increased functional dependence post-stroke, and presence of post-stroke emotionalism.ConclusionsEven after accounting for increased functional dependence, our study data indicates that caring in a PSE context may significantly increase carer strain, comparable to a six-point reduction on Barthel Index.
The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses
Authors: Bigotti Maria Giulia , Klein Katja , Gan Esther S. , Anastasina Maria , Andersson Simon , Vapalahti Olli , Katajisto Pekka , Erdmann Maximilian , Davidson Andrew D. , Butcher Sarah J. , Collinson Ian , Ooi Eng Eong , Balistreri Giuseppe , Brancaccio Andrea , Yamauchi Yohei 
Published: November 2023

AbstractThe COVID-19 pandemic has shown the need to develop effective therapeutics in preparedness for further epidemics of virus infections that pose a significant threat to human health. As a natural compound antiviral candidate, we focused on α-dystroglycan, a highly glycosylated basement membrane protein that links the extracellular matrix to the intracellular cytoskeleton. Here we show that the N-terminal fragment of α-dystroglycan (α-DGN), as produced inE. coliin the absence of post-translational modifications, blocks infection of SARS-CoV-2 in cell culture, human primary gut organoids and the lungs of transgenic mice expressing the human receptor angiotensin I-converting enzyme 2 (hACE2). Prophylactic and therapeutic administration of α-DGN reduced SARS-CoV-2 lung titres and protected the mice from respiratory symptoms and death. Recombinant α-DGN also blocked infection of a wide range of enveloped viruses including the four Dengue virus serotypes, influenza A virus, respiratory syncytial virus, tick-borne encephalitis virus, but not human adenovirus, a non-enveloped virusin vitro. This study establishes soluble recombinant α-DGN as a broad-band, natural compound candidate therapeutic against enveloped viruses.
Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health
Authors: Smith Hannah M. , Moodie Joanna E. , Monterrubio-Gómez Karla , Gadd Danni A. , Hillary Robert F. , Chybowska Aleksandra D. , McCartney Daniel L. , Campbell Archie , Redmond Paul , Page Danielle , Taylor Adele , Corley Janie , Harris Sarah E. , Hernández Maria Valdés , Maniega Susana Muñoz , Bastin Mark E. , Wardlaw Joanna M. , Deary Ian J. , Boardman James P. , Mullin Donncha S. , Russ Tom C. , Cox Simon R. , Marioni Riccardo E. 
Published: November 2023

BackgroundBlood-based biomarkers of brain health could provide a cost-effective contribution to detecting individuals at risk of dementia. Epigenetic scores (EpiScores) for blood protein levels have previously associated with several disease outcomes and measures of brain health, however this has typically been limited to single EpiScore analyse.ResultsUsing 84 protein EpiScores as candidate biomarkers, associations with general cognitive function (both cross-sectionally and longitudinally) were tested in three independent cohorts: Generation Scotland (GS), and the Lothian Birth Cohorts of 1921 and 1936 (LBC1921 and LBC1936, respectively). A meta-analysis of general cognitive functioning results in all three cohorts identified 18 EpiScore associations (absolute meta-analytic standardised estimates ranged from 0.03 to 0.14, median of 0.04, FDR P<0.05). Several associations were also observed between EpiScores and global brain volumetric measures in the LBC1936. An EpiScore for the S100A9 protein (a known Alzheimer disease biomarker) was associated with general cognitive functioning (meta-analytic standardised beta: -0.06, P = 1.3 x 10-9), and with time-to-dementia in GS (Hazard ratio: 1.24, 95% confidence interval 1.08 – 1.44, P = 0.003), but not in LBC1936 (Hazard ratio: 1.11, P = 0.32).ConclusionsEpiScores might make a contribution to the risk profile of poor general cognitive function and global brain health, and risk of dementia, however these scores require replication in further studies.
Wrist Posture Unpredictably Affects the Perception of Transcutaneous Electrical Nerve Stimulation
Authors: Thomas Neha , Osborn Luke , Moran Courtney , Fifer Matthew , Christie Breanne 
Published: November 2023

AbstractObjectiveTargeted transcutaneous electrical nerve stimulation (TENS) is a non-invasive neural stimulation technique that involves activating sensory nerve fibers to elicit tactile sensations in a distal, or referred, location. Though TENS is a promising approach for delivering haptic feedback for those with somatosensory deficits, it was not known how the perception of TENS might be influenced by changing wrist position during sensorimotor tasks.ApproachWe worked with 12 able-bodied individuals and delivered TENS by placing electrodes on the wrist, thus targeting the ulnar and median nerves, and eliciting tactile sensations in the hand. We recorded perceptual data across three wrist postures: neutral, 45° extension, and 45° flexion. For each posture, the participants drew where they perceived the elicited percepts on a map of the hand. They verbally reported the quality of the percepts in their own words. We also varied the pulse amplitude and width of the stimulation to generate a strength-duration curve, from which we extracted the rheobase current and chronaxie time. Linear mixed models were run on the slope and intercept of the linear fit between pulse width and pulse amplitude to investigate effects of gender, posture, and electrode placement.Main resultsAs wrist posture changed, sensation quality was modulated for half of the participants, and percept location changed for 11/12 participants. There were no major changes in the surface area of the elicited percepts. The rheobase and chronaxie values were influenced by wrist posture, but the direction of these changes varied by participant and therefore the effect was not systematic. The statistical models indicated interactions between posture and electrode placement, as well as an effect of gender.SignificanceIf using TENS to convey haptic feedback in sensorimotor tasks, in which wrist posture will likely change, it may be important to characterize resulting perceptual changes for individual users.
Microsatellite Instability Detection in Clinical Cancer Samples: A Multiplex qPCR Approach without Matching Normal Samples
Authors: Chen Wei , Yan Yan Helen , Young Blake , Pinto Alessandro , Jiang Qi , Song Nanjia , Yao Weijie , Zhang David Yu , Zhang Jinny Xuemeng 
Published: November 2023

AbstractBackgroundMicrosatellite instability (MSI) indicates DNA mismatch repair deficiency in cancers like colorectal cancer. The current gold standard technique, PCR/capillary electrophoresis (CE), requires matching normal samples and specialized instrumentation. We developed VarTrace, a rapid and low-cost quantitative PCR (qPCR) assay, to evaluate MSI using solely the tumor sample DNA, obviating the requirement for matching normal samples.Methods101 formalin-fixed paraffin-embedded (FFPE) tumor samples were tested using VarTrace and compared to the Promega OncoMate assay utilizing PCR-CE. Tumor percentage limit of detection was evaluated on contrived samples derived from clinical MSI-H samples. Analytical sensitivity, specificity, limit of detection and input requirements were assessed using synthetic commercial reference standards.ResultsVarTrace demonstrated 100% test success rate, 100% sensitivity and 98% specificity compared to OncoMate across 101 clinical FFPE samples. It detected MSI-H with 97% accuracy down to 10% tumor percentage. Analytical studies using synthetic samples showed a limit of detection of 5% variant allele frequency and a limit of input of 0.5 ng.ConclusionsThis study validates VarTrace as a swift, accurate and economical assay for MSI detection in samples with low tumor percentages without the need for matching normal DNA. VarTrace’s capacity for highly sensitive MSI analysis holds potential for enhancing the efficiency of clinical workflows and broadening the availability of this crucial test.