bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of angiogenic and lymphangiogenic genes in primary cutaneous melanoma: relationship with angiolymphatic invasion and disease-free survival
Authors: García-Pérez Omar , Melgar-Vilaplana Leticia , Sifaoui Ines , García-Bello Miguel-Ángel , Córdoba-Lanús Elizabeth , Fernández-de-Misa Ricardo 
Published: June 2023

Melanoma is one of the most common cancers in the world. The main routes of tumor progression are related to angiogenesis and lymphangiogenesis. These routes can occur by local invasion, which is called angiolymphatic invasion (ALI). In this study, we assess gene expression of relevant biomarkers of angiogenesis and lymphangiogenesis in 80 FFPE melanoma samples to determine a molecular profile that correlates with ALI, tumor progression, and disease-free survival. The results were enhanced by a posttranscriptional analysis by an immunofluorescence assay. Three SNPs in the VEGFR-2 gene were genotyped in 237 malignant melanoma (MM) blood DNA samples by qPCR.
A significant correlation was found for LYVE-1 and ALI, qualitative (P = 0.017) and quantitative (P = 0.005). An increased expression of protein LIVE-1 in ALI samples supported these results (P = 0.032).

VEGFR2 was lower in patients who showed disease progression (P = 0.005) and protein VEGFR2 posttranscriptional expression decreased (P = 0.016). DFS curves showed differences (P = 0.023) for VEGFR2 expression detected versus the absence of VEGFR2 expression.
No significant influence on DFS was detected for the remaining analyzed genes. Cox regression analysis suggested that VEGFR2 expression has a protective role (HR = 0.728; 95% CI = 0.552–0.962; P = 0.025) on disease progression. No significant association was found between any of the studied SNPs of VEGFR2 and DFS or progression rate.
Our main results suggest that LYVE-1 gene expression is closely related to ALI; the relationship with the development of metastases in MM deserves further studies. Low expression of VEGFR2 was associated with disease progression and the expression of VEGFR2 correlates with an increased DFS.
Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis
Authors: Agyemang Nana , Scarsi Kimberly K. , Baker Paxton , Smeaton Laura M. , Podany Anthony T. , Olefsky Maxine , Woolley Elizabeth , Barr Elizabeth , Pham Michelle , Mawlana Sajeeda , Supparatpinyo Khuanchai , Gatechompol Sivaporn , Jalil Emilia M. , Gadama Luis , Badal-Faesen Sharlaa , Van Schalkwyk Marije , Kayama Cecelia , Belaunzaran-Zamudio Pablo F. , Godfrey Catherine , Cohn Susan E. , Mngqibisa Rosie , Haas David W. ,   for the AIDS Clinical Trials Group A5375 Study Team
Published: June 2023

Objective
In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC0-8h). We characterized the pharmacogenetics of these interactions.

Methods
Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of CYP2B6 and NAT2 genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters.

Results
Of 118 evaluable participants, 17 received efavirenz/levonorgestrel 1.5 mg, 35 efavirenz/levonorgestrel 3 mg, 34 isoniazid-rifampin/levonorgestrel 3 mg, and 32 (control group) dolutegravir/levonorgestrel 1.5 mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz/levonorgestrel 3 mg group, CYP2B6 normal/intermediate metabolizers had levonorgestrel AUC0-8h values similar to controls, while CYP2B6 poor metabolizers had AUC0-8h values of 40% lower than controls. In the isoniazid-rifampin group, NAT2 rapid/intermediate acetylators had levonorgestrel AUC0-8h values similar to controls, while NAT2 slow acetylators had AUC0-8h values 36% higher than controls.

Conclusion

CYP2B6 poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. NAT2 slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.
Vitamin C in critical illness: end of the story or still a place?
Authors: Radke David I. , Homayr Anna Lulu , Stoppe Christian , Elke Gunnar 
Published: June 2023

Purpose of review
Critical illness is associated with decreased micronutrient levels, including vitamin C, an essential antioxidant for systemic inflammation. This review discusses the most recent evidence of high-dose vitamin C monotherapy in critically ill adults.

Recent findings
Three randomized-controlled trials (RCTs) were published in 2022. A pilot study including 40 patients with septic shock could not detect significant differences in outcome parameters after administering vitamin C. A multicenter study with 124 septic patients showed no significant difference in 28-day mortality, while vitamin C was associated with an increased risk of acute kidney dysfunction. The LOVIT trial, an international prospective RCT in 872 septic patients, revealed an increased risk of the composite endpoint persistent organ dysfunction plus death at day 28 in the high-dose vitamin C group. Six systematic reviews and meta-analyses (SRMA), including up to 4740 patients published before and 2 SRMA publications including these RCTs showed divergent results on clinical endpoints including mortality.

Summary
The use of high-dose intravenous vitamin C cannot be recommended for the septic critically ill in clinical practice since the LOVIT trial. Further research is needed to evaluate its potential role in other critically ill patients.
Insulin resistance in critical illness: consequences for nutrition therapy and glucose management
Authors: Gunst Jan , Verbruggen Sascha C. 
Published: June 2023

Purpose of review:
Critically ill patients usually develop insulin resistance and hyperglycemia, which is aggravated by early parenteral nutrition. In observational studies, the lowest mortality risk associates with glucose concentrations close to the antecedent average glucose level. This review summarizes the most recent evidence regarding glucose control in critical illness.

Recent findings:
Although pioneer randomized controlled trials showed morbidity and mortality benefit by normalizing blood glucose in intensive care, the largest multicenter randomized controlled trial found increased mortality. Differences in glucose targets, the accuracy of the glucose control protocol, and differences in feeding strategy may explain these differences.
Recent randomized controlled trials investigating the impact of individualized glucose control did not show benefits of targeting individualized or looser glucose values in critically ill patients with poorly controlled diabetes.

Summary:
It remains unclear whether tight glucose control in critical illness is beneficial or not in the absence of early parenteral nutrition, which is currently being studied in the multicenter TGC-fast randomized controlled trial. Without new evidence, it seems prudent to avoid severe hyperglycemia and hypoglycemia in all patients.
Lateropulsion in Right-Sided Stroke: Brain Anatomical Correlates of Severity and Duration
Authors: Salazar López Elvira , Krewer Carmen , Bergmann Jeannine , Möhwald Ken , Müller Friedemann , Jahn Klaus 
Published: June 2023

Background and Purpose:
Lateropulsion (LP) is a profound disorder of postural control that has a significant impact on neurorehabilitation. Knowledge of relevant brain areas could guide decisions on appropriate intervention methods. Although LP severity and duration are highly variable in individuals with LP, imaging studies on LP have not sufficiently considered these aspects. The aim of this study was to investigate the lesion location in individuals after stroke and the correlation with LP duration and severity.

Methods:
A retrospective case-control study using voxel lesion symptom mapping (VLSM) in 74 individuals with right-sided brain lesion (49 with and 25 without LP) was performed to analyze the correlation between lesion location and LP severity. Duration was investigated in a subsample of 22 individuals with LP. LP was diagnosed by means of the Scale for Contraversive Pushing.

Results:
Individuals with LP showed significantly larger lesion sizes compared with the individuals with no LP. VLSM analysis of LP severity did not reveal statistically significant results. VLSM analysis showed a statistically significant association with longer LP duration for the inferior frontal gyrus, the hippocampus, the inferior parietal gyrus, the supramarginal gyrus, the angular gyrus, the temporal cortex, the sagittal stratum, and the superior longitudinal fasciculus.

Discussion and Conclusion:
LP-relevant areas are located in the multisensory network. Areas of the frontoparietal network, which are related to spatial cognition, memory, and attention, were found to be relevant for duration and severity. The findings, especially those regarding duration involving the middle temporal cortex, could explain the better intervention outcomes for methods based more on implicit than on explicit knowledge of verticality.

Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A433).
Impact of Adjunct Corticosteroid Therapy on Quality of Life for Children With Suspected Pneumonia
Authors: Navanandan Nidhya , Florin Todd A. , Leonard Jan , Ramgopal Sriram , Cotter Jillian M. , Shah Samir S. , Ruddy Richard M. , Ambroggio Lilliam 
Published: June 2023

Objective
To determine the association between adjunct corticosteroid therapy and quality of life (QoL) outcomes in children with signs and symptoms of lower respiratory tract infection and clinical suspicion for community-acquired pneumonia (CAP) in the emergency department (ED).

Methods
Secondary analysis from a prospective cohort study of children aged 3 months to 18 years with signs and symptoms of LRTI and a chest radiograph for suspected CAP in the ED, excluding children with recent (within 14 days) systemic corticosteroid use. The primary exposure was receipt of corticosteroids during the ED visit. Outcomes were QoL measures and unplanned visits. Multivariable regression was used to evaluate the association between corticosteroid therapy and outcomes.

Results
Of 898 children, 162 (18%) received corticosteroids. Children who received corticosteroids were more frequently boys (62%), Black (45%), had history of asthma (58%), previous pneumonia (16%), presence of wheeze (74%), and more severe illness at presentation (6%). Ninety-six percent were treated for asthma as defined by report of asthma or receipt of ß-agonist in the ED. Receipt of corticosteroids was not associated with QoL measures: days of activity missed (adjusted incident rate ratio [aIRR], 0.84; 95% confidence interval [CI], 0.63–1.11) and days of work missed (aIRR, 0.88; 95% CI, 0.60–1.27). There was a statistically significant interaction between age (>2 years) and corticosteroids receipt; the patients had fewer days of activity missed (aIRR, 0.62; 95% CI, 0.46–0.83), with no effect on children 2 years or younger (aIRR, 0.83; 95% CI, 0.54–1.27). Corticosteroid treatment was not associated with unplanned visit (odds ratio, 1.37; 95% CI, 0.69–2.75).

Conclusions
In this cohort of children with suspected CAP, receipt of corticosteroids was associated with asthma history and was not associated with missed days of activity or work, except in a subset of children aged older than 2 years.
Creation of the Scaphocephalic Index: Measurement of Global and Regional Severity in Scaphocephaly
Authors: Bins Griffin P. , Zhou Larry Z. , Cull Deborah , Layton Ryan G. , Dunson Blake T. , Kogan Samuel , David Lisa R. , Runyan Christopher M. 
Published: June 2023

Background:
The recently described frontal bossing index (FBI) and occipital bullet index (OBI) allow for quantification of scaphocephaly. A similar index examining biparietal narrowing has not been described. Addition of such an index measuring width would allow for direct evaluation of the primary growth restriction in sagittal craniosynostosis and the formation of an optimized global width/length measure.

Methods:
Computed tomography scans and three-dimensional photographs were used to recreate scalp surface anatomy. Equidistant axial, sagittal, and coronal planes were overlaid, creating a Cartesian grid. Points of intersection were analyzed for population trends in biparietal width. Using the most descriptive point coupled with the sellion protrusion to control for head size, the vertex narrowing index is formed. By combining this index with the FBI and OBI, the scaphocephalic index (SCI) is created as a tailored width/length measure.

Results:
Using 221 controls and 360 individuals with sagittal craniosynostosis, the greatest difference occurred superiorly and posteriorly at a point 70% of the head’s height and 60% of the head’s length. This point had an area under the curve of 0.97 and sensitivity and specificity of 91.2% and 92.2%, respectively. The SCI has an area under the curve of 0.9997, sensitivity and specificity greater than 99%, and interrater reliability of 0.995. The correlation coefficient between computed tomography imaging and three-dimensional photography was 0.96.

Conclusions:
The vertex narrowing index, FBI, and OBI evaluate regional severity, while the SCI is able to describe global morphology in patients with sagittal craniosynostosis. These measures allow for superior diagnosis, surgical planning, and outcome assessment, independent of radiation.
Antivirals vs Antivirals and Steroids for Treatment of Herpes Zoster–Related Ophthalmoplegia: A Case Series and Systematic Review
Authors: Sverdlichenko Irina , Tayeb Safwan , Zaslavsky Kirill , Micieli Jonathan A. , Margolin Edward A. 
Published: June 2023

Background:
Up to 1/3 of patients with herpes zoster ophthalmicus (HZO) may develop ophthalmoplegia. Although zoster-related ophthalmoplegia (ZO) is typically treated with antiviral agents, there is controversy regarding the therapeutic role of systemic steroids.

Methods:
This was a retrospective case series and case report–based systematic review. For the case series, participants were recruited from tertiary neuro-ophthalmology clinics. Eligible participants were those who developed cranial nerve palsies (CNP) within 1 month of HZO diagnosis. In the systematic review, all adults with ZO in the literature who were treated with antivirals or steroids only, or combination therapy were included. Main outcomes were initial presentation, investigations, neuroimaging, treatment regimen, and final outcomes of ophthalmoplegia.

Results:
Eleven immunocompetent patients with ZO were included. The most common CNP was CN III (5/11), followed by CN VI (2/11) and CN IV (2/11). One patient had multiple CNPs. All patients were treated with antivirals, and 4 also treated with a short course of oral steroids. At 6-month follow-up, 75% of patients treated with combination therapy and 85.7% treated with antivirals alone had complete recovery of ZO. The systematic review identified 63 studies consisting of 76 cases of ZO. When comparing patients treated with antivirals with those treated with antivirals and steroids, patients on combination therapy had more severe ocular findings, including complete ophthalmoplegia (P < 0.001). Age was the only significant predictor of complete recovery of ophthalmoplegia on multivariable logistic regression (P = 0.037).

Conclusions:
The rate of complete recovery in immunocompetent patients with ZO was similar in patients treated with antivirals alone vs those treated with antivirals and oral steroids. The systematic literature review affirmed these findings. However, age may influence recovery of ophthalmoplegia.
Clinical Knowledge and Reasoning Abilities of AI Large Language Models in Pharmacy: A Comparative Study on the NAPLEX Exam
Authors: Angel Mirana , Patel Anuj , Alachkar Amal , Baldi Pierre 
Published: June 2023

AbstractObjectiveThis study aims to evaluate the capabilities and limitations of three large language models (LLMs) – GPT-3, GPT-4, and Bard, in the field of pharmaceutical sciences by assessing their pharmaceutical reasoning abilities on a sample North American Pharmacist Licensure Examination (NAPLEX). We also analyze the potential impacts of LLMs on pharmaceutical education and practice.MethodsA sample NAPLEX exam consisting of 137 multiple-choice questions was obtained from an online source. GPT-3, GPT-4, and Bard were used to answer the questions by inputting them into the LLMs’ user interface. The answers provided by the LLMs were then compared with the answer key.ResultsGPT-4 exhibited superior performance compared to GPT-3 and Bard, answering 78.8% of the questions correctly. This score was 11% higher than Bard and 27.7% higher than GPT-3. However, when considering questions that required multiple selections, the performance of each LLM decreased significantly. GPT-4, GPT-3, and Bard only correctly answered 53.6%, 13.9%, and 21.4% of these questions, respectively.ConclusionAmong the three LLMs evaluated, GPT-4 was the only model capable of passing the NAPLEX exam. Nevertheless, given the continuous evolution of LLMs, it is reasonable to anticipate that future models will effortlessly pass the exam. This highlights the significant potential of LLMs to impact the pharmaceutical field. Hence, we must evaluate both the positive and negative implications associated with the integration of LLMs in pharmaceutical education and practice.
High prevalence and risk factors of transmission of hepatitis delta virus in pregnant women in the Center Region of Cameroon
Authors: Ondigui Juliette-Laure Ndzie , Goumkwa Nadège Mafopa , Lobe Cindy , Wandji Brigitte , Awoumou Patrick , Djivida Prisca Voussou , Peyonga Puinta , Atah Solange Manju , Verbe Vivian , Simo Rachel Kamgaing , Moudourou Sylvie Agnès , Gutierrez Ana , Garcia Rosi , Fernandez Isabelle , Riwom Essama Sara Honorine , Mbu Robinson , Torimiro Judith 
Published: June 2023

ABSTRACTBackgroundHepatitis B virus (HBV) and hepatitis delta virus (HDV) co-infection has been described as the most severe form of viral hepatitis, and both can be co-transmitted from mother-to-child. A seroprevalence of 4.0% of HDV infection was reported in pregnant women in Yaoundé, and 11.9% in the general population in Cameroon. Our objective was to describe the rate of HDV infection in pregnant women and to determine risk factors associated with mother-to-child transmission of HDV.Materials and MethodsA cross-sectional, descriptive study was conducted from January 2019 to July 2022 among pregnant women attending antenatal contacts in seven health structures in the Centre Region of Cameroon. A consecutive sampling (non-probability sampling) was used to select only women of age over 21 years, who gave a written informed consent. Following an informed consent, an open-ended questionnaire was used for a Knowledge, Attitude and Practice (KAP) survey of these women, and their blood specimens collected and were screened for HBsAg, anti-HIV and anti-HCV antibodies by rapid tests and ELISA. HBsAg-positive samples were further screened for HBeAg, anti-HDV, anti-HBs, and anti HBc antibodies by ELISA, and plasma HDV RNA load measured by RT-qPCR.ResultsOf 1992 pregnant women, a rate of 6.7% of HBsAg (134/1992) with highest rate in the rural areas, and 3.9% of hepatitis vaccination rate were recorded. Of 134, 44 (32.3%) were anti-HDV antibody-positive, and 47.6% had detectable RNA viraemia. Two women of 44 anti-HDV-positive cases (4.5%) were co-infected with HBV and HCV, while 5 (11.4%) with HIV and HBV. Multiple deliveries, the presence of tattoos and/or scarifications were significantly statistically associated with the presence of anti-HDV antibodies. Of note, 80% of women with negative HBeAg and positive anti-HBe serological profile, had plasma HDV RNA load of more than log 3.25 (>10.000 copies/ml).ConclusionThese results show an intermediate rate of HDV infection among pregnant women with high level of HDV RNA viremia, which suggest an increased risk of vertical and horizontal co-transmission of HDV.
The impact of substance use on tuberculosis treatment adherence among tuberculosis patients in Limpopo Province, South Africa
Authors: Matakanye Hulisani , Tshitangano Takalani 
Published: June 2023

AbstractBackgroundSubstance use are associated with high discontinuation of tuberculosis treatment which is a barrier to tuberculosis control. Treatment discontinuation significantly increase the risk of poor treatment outcomes in both drug-susceptible and multidrug-resistant tuberculosis patients. This study aimed to explore the impact of substance use on tuberculosis treatment adherence among tuberculosis patients in Limpopo Province, South Africa.MethodThe study employed exploratory qualitative research design. Purposive sampling method was used to sample eight TB focal person and eight facility operational managers who were working in eight community health center within three selected districts in Limpopo province. Data were collected through key informant in-depth interviews and were analysed using Colaizzi’s method.ResultsThe study results show four individual major themes that emerged from data analysis: (1) Patients forget to take treatment, (2) Patients miss follow up visit and DOT support appointments (3) Patients refuse social support (4) Patients refuse to attend health education and counselling.ConclusionThe study highlighted serious impact of substance abuse on TB treatment adherence among TB patients. There is a need to integrate treatment for alcoholism and illicit drug users into primary health care to identify specific group of patients suffering from alcoholism and drug addiction on time, as a component of comprehensive TB treatment strategy.
Observation Of Laryngopharyngeal Reflux During Video-Laryngoscopy Was Common Per Our Single Observer Single Institution Experience
Authors: Suchocki Ewelina , Saasouh Wael , Gupta Deepak 
Published: June 2023

AbstractBackgroundVideo-laryngoscopy gives an opportunity to objectively document the peri-operative incidence of laryngopharyngeal reflux.Materials and MethodsTo quantify the local real-world incidence of laryngopharyngeal reflux, a single observer observed 100 adult patients undergoing elective video-laryngoscopy for their elective surgical procedures in the operating rooms at a single institution.ResultsLaryngopharynx in 4% of patients demonstrated visible active refluxing of gastroesophageal contents cranially into laryngopharynx during video-laryngoscopy but none of those underwent suctioning to remove the actively refluxing contents before successfully attempting tracheal intubation.ConclusionObserved laryngopharyngeal reflux during elective video-laryngoscopy was common among adult patients presenting for elective surgical procedures. The lack of suctioning prior to tracheal intubation warrants consensus discussion and statement regarding whether or not to perform suctioning of visible laryngopharyngeal reflux contents prior to intubation.