bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galectin 9 Levels as a Potential Predictor of Intact HIV Reservoir Decay
Authors: Serrano-Villar Sergio , Gala Akshay , Bacchetti Peter , Hoh Rebecca , di Germanio Clara , Cohn Lillian B , Henrich Timothy J , Hunt Peter W , Laird Gregory M , Pillai Satish K , Deeks Steven G , Peluso Michael J 
Published: August 2024

Abstract

Background
During antiretroviral therapy (ART), the HIV reservoir shows variability, with cells carrying intact genomes decaying faster than those with defective genomes, particularly in the first years. The host factors influencing this decay remain unclear.

Methods
Observational study of 74 PWH on ART, 70 (94.6%) of whom were male. Intact proviruses were measured using the intact proviral DNA assay, and 32 inflammatory cytokines were quantified using Luminex immunoassay. Linear spline models assessed the impact of baseline cytokine levels and their trajectories on intact HIV kinetics over seven years.

Results
Baseline Gal-9 was the strongest predictor, with lower levels predicting faster decay. A 10-fold decrease in baseline Gal-9 correlated with a 45% (95% CI, 14%–84%) greater annual decay of intact HIV genomes. Higher baseline interferon-inducible T-cell α chemoattractant (ITAC), interleukin 17 (IL-17), and macrophage inflammatory protein 1α (MIP-1α) levels also predicted faster decay. Longitudinal increases in MIP-3α and decreases in IL-6 were linked to a 9.5% and 10% faster decay, respectively.

Conclusions
The association between lower baseline Gal-9 and faster intact HIV decay suggests targeting Gal-9 could enhance reservoir reduction. The involvement of MIP-3α and IL-6 highlights a broader cytokine regulatory network, suggesting potential multi-targeted interventions.
Impact of Human Leukocyte Antigen Allele–Killer Cell Immunoglobulin-like Receptor Partners on Sexually Transmitted Human Immunodeficiency Virus Type 1 Infection
Authors: Serrano-Rísquez Carmen , Omar Mohamed , Rallón Norma , Benito José Miguel , Gómez-Vidal Amparo , Márquez Francisco J , Alján Martina , Rivero-Juárez Antonio , Pérez-Valero Ignacio , Rivero Antonio , Sinangil Faruk , Saulle Irma , Biasin Mara , Clerici Mario , Forthal Donald , Saéz Maria Eugenia , Caruz Antonio 
Published: August 2024

Abstract
Human leukocyte antigen (HLA) class I/killer cell immunoglobulin-like receptor (KIR) genotypes influence human immunodeficiency virus type 1 (HIV-1) disease progression and viral load, but their role in primary infection is uncertain. Inconsistent results from previous studies suggest that the inoculum size and transmission route—parenteral versus sexual—may influence this association. We conducted a genome-wide association study in a population of people with HIV-1 and HIV-1–exposed seronegative individuals exposed to the virus through the sexual route. Our data do not support any role of the HLA/KIR system in susceptibility to sexually transmitted HIV-1 infection. The genetics basis of HIV-1 viral load and disease progression are distinct from the genetics of HIV resistance, a paradox worth exploring.
Population pharmacokinetics of oral fosfomycin calcium in healthy women
Authors: Isla Arantxa , Alarcia-Lacalle Ana , Solinís María Ángeles , del Pozo-Rodríguez Ana , Abajo Zuriñe , Cabero María , Canut-Blasco Andrés , Rodríguez-Gascón Alicia 
Published: August 2024

Abstract

Background
Fosfomycin is an antibiotic extensively used to treat uncomplicated urinary tract infections in women, and it is available in different salts and formulations. The European Medicines Agency (EMA) recommends further studies to characterize the pharmacokinetics of fosfomycin calcium for oral administration and to justify its dosage recommendation.

Objectives
A population pharmacokinetic model of fosfomycin calcium was developed after oral administration to healthy women.

Methods
A clinical trial (a randomized, open-label, bioavailability study of single and multiple doses of 1000 mg capsules, single dose of 500 mg capsule and single dose of 250 mg/5 mL suspension of oral fosfomycin calcium under fasted conditions in healthy women volunteers, Code: PD7522.22, EudraCT: 2020-001664-28) was carried out at the Clinical Trial Unit, Araba University Hospital (Vitoria-Gasteiz, Spain). Twenty-four healthy women were included in the study, and plasma samples were collected at different times over a period of 24 h. The concentration–time data of fosfomycin in plasma were modelled by a population approach using a nonlinear mixed-effects modelling implemented by NONMEM 7.4 (ICON Clinical Research LLC, North Wales, PA, USA).

Results
The pharmacokinetics of fosfomycin was best described by a two-compartment model. Creatinine clearance and body weight were identified as covariates for fosfomycin clearance and volume of distribution, respectively.

Conclusions
This study provides relevant information on the pharmacokinetic profile of fosfomycin in women after oral administration as calcium salt. This population model may be very useful for establishing dosage recommendations of fosfomycin calcium to treat urinary tract infections in women.
Sex and Population-Specific 99th Percentiles of Troponin for Myocardial Infarction in the Danish Population (DANSPOT)
Authors: Hasselbalch Rasmus Bo , Jørgensen Nicoline , Kristensen Jonas , Strandkjær Nina , Kock Thilde Olivia , Lange Theis , Ostrowski Sisse Rye , Nissen Janna , Larsen Margit Hørup , Pedersen Ole Birger Vesterager , Bor Mustafa Vakur , Afzal Shoaib , Kamstrup Pia Rørbæk , Dahl Morten , Hilsted Linda , Torp-Pedersen Christian , Bundgaard Henning , Iversen Kasper Karmark 
Published: August 2024

Abstract

Background
Sex- and population-specific 99th percentiles of high-sensitivity cardiac troponin (hs-cTn) are recommended in guidelines although the evidence for a clinical utility is sparse. The DANSPOT trial will investigate the clinical effect of sex- and population-specific 99th percentiles of cTn. We report the 99th percentiles derived from this trial and their dependency on kidney function.

Methods
We used samples from healthy Danish blood donors and measured hemoglobin A1c, N-terminal pro-brain natriuretic peptide and creatinine, and calculated an estimated glomerular filtration rate (eGFR). We compared 2 cutoffs for the eGFR of healthy participants (60 vs 90 mL/min/1.73 m2). The cTn assays investigated were Siemens Atellica and Dimension Vista hs-cTnI, Abbott hs-cTnI, and Roche hs-cTnT.

Results
A total of 2287 participants were sampled, of which 71 (3.1%) were excluded due to a history of heart disease (n = 4), insufficient material (n = 7), or a screening biomarker (n = 60). Of the remaining 2216 participants, 1325 (59.8%) had an eGFR ≥90 mL/min/1.73 m2. Compared to a cutoff of 60 mL/min/1.73 m2 for eGFR, using 90 mL/min/1.73 m2 resulted in lower 99th percentiles for females; Siemens Vista (46 vs 70 ng/L), Abbott (14 vs 18 ng/L), and Roche cTnT (10 vs 13 ng/L), and decreased the number of measurements above the manufacturers’ 99th percentiles for all assays.

Conclusions
We present reference values for 4 cTn assays for eGFR cutoffs of 60 and 90 mL/min/1.73 m2. These cutoffs differ based on the eGFR threshold for inclusion indicating that any chosen cutoff is also valuable with moderately reduced kidney function.
A review of reinforcement learning for natural language processing and applications in healthcare
Authors: Liu Ying , Wang Haozhu , Zhou Huixue , Li Mingchen , Hou Yu , Zhou Sicheng , Wang Fang , Hoetzlein Rama , Zhang Rui 
Published: August 2024

Abstract

Importance
Reinforcement learning (RL) represents a pivotal avenue within natural language processing (NLP), offering a potent mechanism for acquiring optimal strategies in task completion. This literature review studies various NLP applications where RL has demonstrated efficacy, with notable applications in healthcare settings.

Objectives
To systematically explore the applications of RL in NLP, focusing on its effectiveness in acquiring optimal strategies, particularly in healthcare settings, and provide a comprehensive understanding of RL’s potential in NLP tasks.

Materials and Methods
Adhering to the PRISMA guidelines, an exhaustive literature review was conducted to identify instances where RL has exhibited success in NLP applications, encompassing dialogue systems, machine translation, question-answering, text summarization, and information extraction. Our methodological approach involves closely examining the technical aspects of RL methodologies employed in these applications, analyzing algorithms, states, rewards, actions, datasets, and encoder-decoder architectures.

Results
The review of 93 papers yields insights into RL algorithms, prevalent techniques, emergent trends, and the fusion of RL methods in NLP healthcare applications. It clarifies the strategic approaches employed, datasets utilized, and the dynamic terrain of RL-NLP systems, thereby offering a roadmap for research and development in RL and machine learning techniques in healthcare. The review also addresses ethical concerns to ensure equity, transparency, and accountability in the evolution and application of RL-based NLP technologies, particularly within sensitive domains such as healthcare.

Discussion
The findings underscore the promising role of RL in advancing NLP applications, particularly in healthcare, where its potential to optimize decision-making and enhance patient outcomes is significant. However, the ethical challenges and technical complexities associated with RL demand careful consideration and ongoing research to ensure responsible and effective implementation.

Conclusions
By systematically exploring RL’s applications in NLP and providing insights into technical analysis, ethical implications, and potential advancements, this review contributes to a deeper understanding of RL’s role for language processing.
Relation extraction using large language models: a case study on acupuncture point locations
Authors: Li Yiming , Peng Xueqing , Li Jianfu , Zuo Xu , Peng Suyuan , Pei Donghong , Tao Cui , Xu Hua , Hong Na 
Published: August 2024

Abstract

Objective
In acupuncture therapy, the accurate location of acupoints is essential for its effectiveness. The advanced language understanding capabilities of large language models (LLMs) like Generative Pre-trained Transformers (GPTs) and Llama present a significant opportunity for extracting relations related to acupoint locations from textual knowledge sources. This study aims to explore the performance of LLMs in extracting acupoint-related location relations and assess the impact of fine-tuning on GPT’s performance.

Materials and Methods
We utilized the World Health Organization Standard Acupuncture Point Locations in the Western Pacific Region (WHO Standard) as our corpus, which consists of descriptions of 361 acupoints. Five types of relations (“direction_of”, “distance_of”, “part_of”, “near_acupoint”, and “located_near”) (n = 3174) between acupoints were annotated. Four models were compared: pre-trained GPT-3.5, fine-tuned GPT-3.5, pre-trained GPT-4, as well as pretrained Llama 3. Performance metrics included micro-average exact match precision, recall, and F1 scores.

Results
Our results demonstrate that fine-tuned GPT-3.5 consistently outperformed other models in F1 scores across all relation types. Overall, it achieved the highest micro-average F1 score of 0.92.

Discussion
The superior performance of the fine-tuned GPT-3.5 model, as shown by its F1 scores, underscores the importance of domain-specific fine-tuning in enhancing relation extraction capabilities for acupuncture-related tasks. In light of the findings from this study, it offers valuable insights into leveraging LLMs for developing clinical decision support and creating educational modules in acupuncture.

Conclusion
This study underscores the effectiveness of LLMs like GPT and Llama in extracting relations related to acupoint locations, with implications for accurately modeling acupuncture knowledge and promoting standard implementation in acupuncture training and practice. The findings also contribute to advancing informatics applications in traditional and complementary medicine, showcasing the potential of LLMs in natural language processing.
Forced Marriages in Times of Armed Conflict: An Implicit Paradox of Modern Slavery under International Humanitarian Law
Authors: Ali Nimra , Iqbal Zainab , Khadam Nadia 
Published: August 2024

Abstract
The idea of the world as a global village has brought about various transnational problems. One of these problems is the transition of forced marriages into the modern form of slavery. Forced marriage continues to be a violation of human rights specifically in the context of modern slavery, usually existing during armed conflicts. Such a violation is linked to modern slavery as it constitutes slavery-like practices, including abuse, sexual assault, rape, domestic violence, and so on. In literature and practice, forced marriages in times of armed conflicts are usually labelled as personal problems requiring personal solutions. Factors such as financial crisis, threats to honour, and family protection lead to forced marriages in conflict zones. Such factors have been overlooked, resulting in the absence of legislation across the globe to prohibit forced marriages during conflicts. Consequently, international laws need to be on the same page in the categorization of forced marriages as modern slavery by considering it a specified form of human rights violation. Inconsistent labelling in this regard has produced ambiguity in resolving the issue through practical mechanisms. Severe violations of human rights continue to occur due to the absence of an explicit prohibition of forced marriage in armed conflicts, as highlighted through multiple case studies in this research. A preventive solution is required to hinder the practice that is feasible through the codification of the prevention mechanisms under International Law (IL) and International Humanitarian Law (IHL).
Frequency of use and cost in Japan of first-line palliative chemotherapies for recurrent or metastatic squamous cell carcinoma of the head and neck
Authors: Yokoyama Kazuki , Wasano Koichiro , Sasaki Keita , Machida Ryunosuke , Nakahira Mitsuhiko , Kitamura Koji , Sakagami Tomofumi , Takeshita Naohiro , Ohkoshi Akira , Suzuki Motoyuki , Tateya Ichiro , Morishita Yohei , Sekimizu Mariko , Nakayama Masahiro , Koyama Taiji , Shibata Hirofumi , Miyamaru Satoru , Kiyota Naomi , Hanai Nobuhiro , Homma Akihiro 
Published: August 2024

Abstract

Background
Over the last decade, novel anticancer drugs have improved the prognosis for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). However, this has increased healthcare expenditures and placed a heavy burden on patients and society. This study investigated the frequency of use and costs of select palliative chemotherapy regimens in Japan.

Methods
From July 2021 to June 2022 in 54 healthcare facilities, we gathered data of patients diagnosed with RM-SCCHN and who had started first-line palliative chemotherapy with one of eight commonly used regimens. Patients with nasopharyngeal carcinomas were excluded. The number of patients receiving each regimen and the costs of each regimen for the first month and per year were tallied.

Results
The sample comprised 907 patients (674 were &lt; 75 years old, 233 were ≥ 75 years old). 330 (36.4%) received Pembrolizumab monotherapy, and 202 (22.3%) received Nivolumab monotherapy. Over 90% of patients were treated with immune checkpoint inhibitors as monotherapy or in combination with chemotherapy. Treatment regimens’ first-month costs were 612 851–849 241 Japanese yen (JPY). The cost of standard palliative chemotherapy until 2012 was about 20 000 JPY per month. The incremental cost over the past decade is approximately 600 000–800 000 JPY per month, a 30- to 40-fold increase in the cost of palliative chemotherapy for RM-SCCHN.

Conclusion
First-line palliative chemotherapy for RM-SCCHN exceeds 600 000 JPY monthly. Over the last decade, the prognosis for RM-SCCHN has improved, but the costs of palliative chemotherapy have surged, placing a heavy burden on patients and society.
Racial comparisons in treatment of rectal adenocarcinoma and survival in the military health system
Authors: Eaglehouse Yvonne L , Darmon Sarah , Gage Michele M , Shriver Craig D , Zhu Kangmin 
Published: August 2024

Abstract

Background
Racial disparities in treatment and outcomes of rectal cancer have been attributed to patients’ differential access to care. We aimed to study treatment and outcomes of rectal cancer in the equal access Military Health System (MHS) to better understand potential racial disparities.

Methods
We accessed the MilCanEpi database to study a cohort of patients aged 18 and older who were diagnosed with rectal adenocarcinoma between 1998 and 2014. Receipt of guideline recommended treatment per tumor stage, cancer recurrence, and all-cause death were compared between non-Hispanic White and Black patients using multivariable regression models with associations expressed as odds (AORs) or hazard ratios (AHRs) and their 95% confidence intervals (CIs).

Results
The study included 171 Black and 845 White patients with rectal adenocarcinoma. Overall, there were no differences in receipt of guideline concordant treatment (AOR = 0.76, 95% CI = 0.45 to 1.29), recurrence (AHR = 1.34, 95% CI = 0.85 to 2.12), or survival (AHR = 1.08, 95% CI = 0.77 to 1.54) for Black patients compared with White patients. However, Black patients younger than 50 years of age at diagnosis (AOR = 0.34, 95% CI = 0.13 to 0.90) or with stage III or IV tumors (AOR = 0.28, 95% CI = 0.12 to 0.64) were less likely to receive guideline recommended treatment than White patients in stratified analysis.

Conclusions
In the equal access MHS, although there were no overall racial disparities in rectal cancer treatment or clinical outcomes between Black and White patients, disparities among those with early-onset or late-stage rectal cancers were noted. This suggests that factors other than access to care may play a role in the observed disparities and warrants further research.
UK Collaborative Randomized Trial of Neonatal Extracorporeal Membrane Oxygenation
Authors: Liberio Brianna , Wright Clyde J. 
Published: August 2024

Abstract
Prior to this trial, evidence to support extracorporeal membrane oxygenation (ECMO) in newborns with severe respiratory failure was limited to small studies. ECMO was not quickly adopted due to concerns about cost-effectiveness and long-term disability in survivors. The UK Collaborative ECMO trial evaluated the policy of transfer for ECMO for neonates with severe respiratory failure on outcomes of death or severe disability at 1 year. The trial was stopped early due to advantage of ECMO, with subjects randomized to ECMO demonstrating decreased mortality or severe disability at 1 year compared with the conventional management group (33% versus 62%; relative risk 0.54, 95% confidence interval 0.36 to 0.80, p = 0.002).
Randomized Trial of Early Diet in Preterm Babies and Later Intelligence Quotient
Authors: Fernandes Michelle , Dorling Jon 
Published: August 2024

Abstract
The early brain critical growth spurt in preterm infants may be affected by early feeding composition. This trial evaluated the impact of nutrient-enriched preterm formula during the first 4 weeks of life on childhood developmental outcomes. This study was a parallel-group RCT, with randomization stratified by maternal preference for breast milk, and then further stratified by birth weight (&lt;1200 g, ≥1200 g). There was no difference in the primary outcome of overall intelligence quotient (IQ) scores at 7.5 to 8 years between children who had received preterm compared with standard formula, whether as their sole diet (2.2 point advantage; 95% CI –2.7 to 7.0) or as a supplement to mother’s milk (1.0; 95% CI –3.0 to 5.0). Some advantages were suggested for secondary outcomes and subgroup analyses, especially with respect to verbal IQ scores, male infants, and infants for whom preterm formula comprised ≥50% of early diet.
Vitamin A Supplementation for Extremely Low Birth Weight Infants
Authors: Franz Axel R. , Hay Susanne 
Published: August 2024

Abstract
Extremely low birth weight (ELBW) infants are born with low vitamin A stores, which are associated with higher risk for bronchopulmonary dysplasia (BPD). This trial randomized ELBW infants requiring mechanical ventilation or supplemental oxygen at 24 hours to either 12 intramuscular injections of 5000 IU vitamin A or sham procedures. Infants in the vitamin A group demonstrated a reduced the rate of death or BPD at 36 weeks’ postmenstrual age (55% versus 62%; adjusted relative risk [RR] 0.89, 95% confidence interval [CI] 0.80 to 0.99, p = 0.03). The reduction was mostly due to a reduced rate of BPD in survivors (47% versus 56%; RR 0.85, 95% CI 0.73 to 0.98, p = 0.03). The proportion of infants with serum retinol values below 20 μg/dL (0.70 μmol/L), indicating suboptimal levels, at 28 days was lower in the vitamin A group than in the control group (25% versus 54%; p &lt; 0.001).
Promotion of Breastfeeding Intervention Trial. A Randomized Trial in the Republic of Belarus
Authors: Embleton Nicholas D. 
Published: August 2024

Abstract
PROBIT assessed the impact of breastfeeding promotion on breastfeeding duration and exclusivity, infections, and eczema until 12 months (m). Thirty-one maternity hospitals and their associated clinics in the Republic of Belarus were randomly assigned to an experimental intervention (n = 16) modelled on the Baby-Friendly Hospital Initiative (BFHI) or control (n = 15). 17,046 mother–infant pairs of full-term singletons with birthweight of ≥2500 g were included, and 16,491 (96.7%) completed 12 m follow-up. Intervention site infants had higher rates of any breastfeeding at 3 m (73% versus 60%; adjusted odds ratio [aOR] 0.52, 95% CI 0.40 to 0.69) and lower rates of gastrointestinal infections (9.1% versus 13.2%; aOR 0.60, 95% CI 0.40 to 0.91). Other measures of breastfeeding (exclusive breastfeeding at 3 m and 6 m, and any breastfeeding at 12 m) were improved with the intervention, whereas lower rates of eczema were observed.
Dextrose Gel for Neonatal Hypoglycemia
Authors: Mohamed Adel , Shah Jyotsna , Shah Prakesh S. 
Published: August 2024

Abstract
Hypoglycemia is the most common metabolic disorder of newborns and has been associated with brain injury and adverse neurodevelopmental outcomes. The Sugar Babies trial investigated whether treatment with dextrose gel and feeding is more effective than placebo gel and feeding for reversal of hypoglycemia in at-risk babies. One hundred eighteen neonates were enrolled in the dextrose group and 119 in the placebo group. Dextrose gel reduced the frequency of treatment failure compared with placebo (14% versus 24%; relative risk 0.57, 95% confidence interval 0.33 to 0.98, p = 0.04). No adverse events associated with dextrose gel were noted. This treatment could be considered for first-line management of neonatal hypoglycemia.
A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants
Authors: Embleton Nicholas D. 
Published: August 2024

Abstract
In preclinical models, high-dose erythropoietin (EPO) demonstrated neuroprotective effects. Meta-analysis of 4 RCTs suggested potential benefit in preterm infants, but clinical efficacy remained uncertain. This multicenter RCT randomized 941 infants born 24 to &lt;28 weeks’ gestation to either EPO (intravenous then subcutaneous) or placebo from day 1 until 32 weeks’ postmenstrual age. Per-protocol efficacy analysis at 2 years included 741 infants. There was no difference in incidence of death or severe neurodevelopmental impairment (cerebral palsy or composite motor or cognitive scores &lt;70 on the Bayley Scales of Infant and Toddler Development, third edition [BSID III]), and no difference in key neonatal morbidities. Post hoc analysis showed infants in the EPO group received fewer blood transfusions.