bluuebunny/crossref_metadata_2025 huggingface dataset:
1236 Challenging Convention in Laparoscopic Pyeloplasty: A Prospective Analysis on the Successful Application of Knotless Continuous Barbed Suture
Authors: Gorman L O , Collins P , Hennessey D
Published: August 2024

Aim

Laparoscopic pyeloplasty (LP) is the standard treatment of pelviureteric junction obstruction (PUJO). One of the major technical challenges in this procedure is intracorporeal knot tying. The introduction of self-anchoring sutures offers a novel approach to tissue approximation. This report details our experience with a series of consecutive cases undergoing laparoscopic pyeloplasty using knotless barbed sutures.

Method

An analysis of a prospectively maintained LP database was performed. In LP, a 3-0 barbed suture was used. For open surgery a non-barbed suture was used. All patients had JJ stents for 6 weeks and had nuclear med renograms at 12 weeks post procedure for recurrence. Primary outcomes were suture technique used and PUJO recurrence. Secondary outcomes are conversion to open rates and complications.

Results

Twenty-two patients underwent LP and 3 patients LP with pyelolithotomy. Thirteen patents (52%) had left sided surgery. Three cases (12%) were converted to open surgery. The indication for conversion was inability to laparoscopically speculate the ureter in 2 cases and retro-peritoneal fibrosis in 1 case. Twenty-three (88%) patients had completed LP surgery with a knotless continuous barbed suture. The mean length of stay was 48hrs. No patient developed a PUJO recurrence. The complication rate for LP was 0%. One patient who had open pyeloplasty had an anastomotic leak. At 3 months post-surgery, all patients had improved drainage from their kidneys.

Conclusions

In this study, successful outcomes of the laparoscopic pyeloplasty using barbed suture were demonstrated. LP with barbed suture can potentially become the standard approach in near future.
157 Smoking Cessation - Are We Making the Most of the Opportunity to Modify the Long-Term Health of Surgical Inpatients?
Authors: Borumand M , Modasia T , Okunola R , Copley H C , Ajayi A , Pak H , Fazili A , Kuriakose J
Published: August 2024

Introduction

Smoking is the leading preventable cause of death and illness. NICE Guidelines (209) recommend documenting smoking history, providing smoking cessation advice at admission, offering nicotine replacement and behavioural therapy/referral to stop smoking services. A pilot study was undertaken at a district general hospital to establish compliance with the above guidelines.

Method

Medical and nursing notes were reviewed for patients (N=44) admitted on two surgical wards (Bedford Hospital) on a single date in October 2023 following snapshot audit methodology to establish smoking status documentation. Smokers were identified from the above two wards plus a further 5 wards using a transcript to establish the proportion of smokers who were offered smoking cessation advice, nicotine replacement offer, behavioural therapy, and smoking cessation services referral. Transcript results were cross-checked against case notes.

Results

11% (5/44) and 20% (9/44) had smoking status documented in their nursing/medical notes respectively. Seven current smokers were identified of which 57% (4/7) were given smoking cessation advice, 29% (2/7) offered nicotine replacement, 0% (0/7) were offered behavioural therapy and 57% (5/7) were offered referral to stop smoking services. Casenote review established the above were not documented.

Conclusions

Smoking cessation remains one of our greatest opportunities to modify long term health outcomes, compliance with NICE Guidelines is poor, and actions taken are not well documented. Further work is needed to establish the most effective strategies to improve our care of current smokers and achieve delivery of these key metrics.
Coalition and Multi-Positionality Research Teams: A Nuanced Approach for Anti-Oppressive Research
Authors: Chibaya Nyasha Hillary , Arora Manvi , Thibeault Charles-Antoine , Pullen Sansfaçon Annie
Published: August 2024

This article delves into the typically unexamined complexities of conducting research with vulnerable populations, specifically focusing on trans and gender-diverse children and youth. While ethical guidelines exist, there are persistent knowledge gaps in genuinely collaborative research practices with vulnerable populations. Using collaborative autoethnographic methodology, the study draws on the narratives and reflexive accounts of four researchers to explore the complexities of oppression. The article argues for the necessity of a coalition of knowledge and multi-positional perspectives to develop sensitive and rigorous intervention strategies and policymaking. We propose the adoption of two theoretical frameworks: intersectionality and queer reflexivity, to guide our reflections and enhance research outcomes. By acknowledging and integrating diverse positionalities, collaborative approaches can increase the sensitivity, relevance and impact of research. The article proposes that recognising the intersectionality and temporality of researchers’ and participants’ identities can help to effectively navigate complex ethical, methodological and empirical research terrain. This we argue, ultimately contributes to more robust knowledge production, inclusive and impactful research outcomes. In conclusion, the study highlights the significance of embracing coalition and multi-positionality in anti-oppressive research endeavours that can provide diversified perspectives and interventions to better address the complex and multifaceted nature of oppression.
Early detection of anal squamous cell carcinoma with the use of high-resolution anoscopy
Authors: Junejo Muhammad Hyder , Oyebanji Oluwatobiloba Ifeoluwa , Wang Baihan , Cappello Carmelina , Wait Brenton , Farrow Emily , Nathan Mayura , Bowring Julie , Cuming Tamzin
Published: August 2024

In the UK, few (12%) anal squamous cell carcinomas (aSCCs) are diagnosed early at stage 1 (T1N0M0). The Homerton Anogenital Neoplasia Service (HANS) is a highly specialized tertiary centre where high-resolution anoscopy (HRA) is performed to diagnose and treat anal intraepithelial neoplasia (AIN), a precursor to cancer. In some cases, aSCC (here defined as anal canal cancers and perianal cancers up to 5 cm from the anal verge) is found on referral for AIN; in others, aSCC may develop during management of AIN. We reviewed aSCC diagnoses at our specialist unit to establish whether HRA offers added value in the early detection of aSCC in a high-risk cohort. A cross-sectional analysis was performed of all primary aSCC diagnoses at HANS between January 2016 and June 2021. Patient records and histopathology and radiology reports were reviewed to define anal cancer stage per TNM classification (AJCC version 8). The results were compared with national anal cancer data published by the Office for National Statistics (AJCC version 8). Fifty-three aSCC diagnoses were made at HANS; 35 (66%) were stage 1 (14 prevalent, 21 incident), 11 (21%) stage 2 (9 prevalent, 2 incident) and 6 (11%) stage 3 (5 prevalent, 1 incident). None were stage 4, and one cancer was unstageable due to further management at another unit. By comparison, 5836 aSCCs were diagnosed in the UK between 2013 and 2017. Of these, 12.0% were stage 1, 22.8% stage 2, 33.0% stage 3 and 8.5% stage 4; 23.8% were unknown or unstageable. There was a statistically significant difference in the proportion of early (i.e. stage 1) HRA-detected cancers between HANS and national statistics (P < 0.001). Our results suggest that surveillance and examination within an HRA programme may lead to the detection of aSCC at an earlier stage, allowing for less morbid treatment and potentially lower mortality.
Deficiency in Epithelium RAD50 Aggravates UC via IL-6-Mediated JAK1/2-STAT3 Signaling and Promotes Development of Colitis-Associated Cancer in Mice
Authors: Zhang Jie , Mengli Yu , Zhang Tiantian , Song Xin , Ying Songmin , Shen Zhe , Yu Chaohui
Published: August 2024

Background

Ulcerative colitis (UC) is one of the most important risk factors for developing colitis-associated cancer (CAC). Persistent DNA damage increases CAC risk and has been observed in patients with UC. We aimed to identify the regulatory role of RAD50, a DNA double-strand breaks (DSBs) sensor, in UC progression to CAC.

Methods

DSBs and RAD50 expression in inflammatory bowel disease (IBD) and CAC cell and mouse models were assessed. Mice with intestinal epithelial RAD50 deletion (RAD50IEC-KO) were used to examine the role of RAD50 in colitis and CAC.

Results

Along with the increased γ-H2AX expression in colitis and CAC models, RAD50 expression was reduced in human IBD and CAC as well as in mouse models. Furthermore, RAD50IEC-KO sensitizes mice to dextran sulfate sodium (DSS)-induced acute and chronic experimental colitis. RNA-seq analyses revealed that RAD50IEC-KO activated the cytokine-cytokine receptor response, which was amplified through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. RAD50 directly interacts with STAT3 and subsequently inhibits its phosphorylation, which may disrupt the IL-6-JAK1/2-STAT3-IL-6 feed-forward loop. Pharmacological STAT3 inhibition relieves colitis in RAD50IEC-KO mice. Severe DSBs, increased cell proliferation, and extended inflammatory response were identified in RAD50-deficient cells, which promoted azoxymethane (AOM)-DSS-induced colon tumor development in RAD50IEC-KO mice.

Conclusions

RAD50 exerts anti-IL-6-related inflammatory effects in colitis and suppresses CAC. Increasing RAD50 level in colon tissues may be promising for treating patients with UC and CAC.
Microbial markets: socio-economic perspective in studying microbial communities
Authors: Mostafa Fariha , Krüger Aileen , Nies Tim , Frunzke Julia , Schipper Kerstin , Matuszyńska Anna
Published: August 2024

Studying microbial communities through a socio-economic lens, this paper draws parallels with human economic transactions and microbes’ race for resources. Extending the ‘Market Economy’ concept of social science to microbial ecosystems, the paper aims to contribute to comprehending the collaborative and competitive dynamics among microorganisms. Created by a multidisciplinary team of an economist, microbiologists, and mathematicians, the paper also highlights the risks involved in employing a socio-economic perspective to explain the complexities of natural ecosystems. Navigating through microbial markets offers insights into the implications of these interactions while emphasizing the need for cautious interpretation within the broader ecological context. We hope that this paper will be a fruitful source of inspiration for future studies on microbial communities.
Higher Striatal Dopamine is Related With Lower Physical Performance Fatigability in Community-Dwelling Older Adults
Authors: Rosano Caterina , Chahine Lana M , Gay Emma L , Coen Paul M , Bohnen Nico I , Studenski Stephanie A , LoPresti Brian , Rosso Andrea L , Huppert Theodore , Newman Anne B , Royse Sarah K , Kritchevsky Stephen B , Glynn Nancy W
Published: August 2024

Background

Fatigability in community-dwelling older adults is highly prevalent and disabling, but lacks a treatment. Greater nigrostriatal dopaminergic signaling can ameliorate performance fatigability in healthy young adults, but its role in community-dwelling older adults is not known. We hypothesized that higher nigrostriatal dopaminergic integrity would be associated with lower performance fatigability, independent of cardiopulmonary and musculoskeletal energetics and other health conditions.

Methods

In 125 older adults participating in the Study of Muscle, Mobility and Aging, performance fatigability was measured as performance deterioration during a fast 400 m walk (% slowing down from the 2nd to the 9th lap). Nigrostriatal DA integrity was measured using (+)-[11C] dihydrotetrabenazine (DTBZ) PET imaging. The binding signal was obtained separately for the subregions regulating sensorimotor (posterior putamen), reward (ventral striatum), and executive control processes (dorsal striatum). Multivariable linear regression models of performance fatigability (dependent variable) estimated the coefficients of dopamine integrity in striatal subregions, adjusted for demographics, comorbidities, and cognition. Models were further adjusted for skeletal muscle energetics (via biopsy) and cardiopulmonary fitness (via cardiopulmonary exercise testing).

Results

Higher [11C]-DTBZ binding in the posterior putamen was significantly associated with lower performance fatigability (demographic-adjusted standardized β = −1.08, 95% CI: −1.96, −0.20); results remained independent of adjustment for other covariates, including cardiopulmonary and musculoskeletal energetics. Associations with other striatal subregions were not significant.

Discussion

Dopaminergic integrity in the sensorimotor striatum may influence performance fatigability in older adults without clinically overt diseases, independent of other aging systems.
Fall Trajectories in Older Men: Trajectories of Change by Age and Predictors for Future Fall Risk
Authors: Guo Crystal , Ensrud Kristine E , Cauley Jane A , Orwoll Eric S , Cawthon Peggy M
Published: August 2024

Background

Very little is known about specific trajectories or patterns of falls over time. Using the well-characterized cohort of the Osteoporotic Fractures in Men Study (MrOS), we classified individuals by fall trajectories across age and identified predictors of group assignment based on characteristics at baseline.

Methods

Using an analysis sample of 5 976 MrOS participants and 15 years of follow-up data on incident falls, we used group-based trajectory models (PROC TRAJ in SAS) to identify trajectories of change. We assessed the association of baseline characteristics with group assignment using 1-way analysis of variance and chi-square tests. Multivariable logistic regression was used to analyze the outcome of the high-risk fall trajectory groups compared to the low-risk groups.

Results

Changes in rates of falls were relatively constant or increasing with 5 distinct groups identified. Mean posterior probabilities for all 5 trajectories were similar and consistently above 0.8 indicating a reasonable model fit. Among the 5 fall trajectory groups, 2 were deemed high risk, those with steeply increasing fall risk and persistently high fall risk. Factors associated with fall risk included body mass index, use of central nervous agents, prior history of diabetes and Parkinson’s disease, back pain, grip strength, and physical and mental health scores.

Conclusions

Two distinct groups of high fall risk individuals were identified among 5 trajectory groups, those with steeply increasing fall risk and persistently high fall risk. Statistically significant characteristics for group assignment suggest that future fall risk of older men may be predictable at baseline.
An integrated picture of chronic pancreatitis derived by mapping variants in multiple disease genes onto pathogenic pathways
Authors: Prasad Hari , Shah Idrees A , Kurien Reuben Thomas , Chowdhury Sudipta Dhar , Visweswariah Sandhya S
Published: August 2024

Chronic pancreatitis (CP) is an etiologically and genetically heterogeneous inflammatory syndrome characterised by progressive damage to the exocrine and endocrine components of the pancreas [ 1]. The multigenic paradigm of CP has sparked research in recent years [ 2]. We aimed to expand the current knowledge of genetic susceptibility of pancreatitis in patients of Indian origin. By employing whole-exome sequencing in an Indian hospital cohort, we dissect the genetic landscape associated with CP or recurrent acute pancreatitis (RAP). Notably, all patients had at least one genetic variant identified in a pancreatitis-risk gene, and most had a co-occurrence of a second variant in an additional risk gene. Based on the presence of both acinar and ductal gene variants in individual patients, we propose a two-hit hypothesis where variants in proteins expressed in both acinar and ductal cells are critical for RAP/CP development.
Outcomes of 576 patients with extracorporeal life support for the treatment of perioperative cardiogenic shock
Authors: Aboud Anas , Hüting Felix , Fujita Buntaro , Zittermann Armin , Al-Khalil Riad , Puehler Thomas , Ensminger Stephan , Gummert Jan
Published: August 2024

OBJECTIVES

This study aims to analyse the short- and long-term outcomes in patients who received extracorporeal life support for the treatment of perioperative low-output syndrome and identify risk factors for mortality.

METHODS

All consecutive patients who received extracorporeal life-support system during or after cardiac surgery at a high-volume German cardiac centre between 2008 and 2017 were identified retrospectively and followed up to December 2023. This cohort was characterized, and long-term survival (>10 years) was analysed. Univariate and multivariable regression analyses were performed to identify risk factors for mortality.

RESULTS

Five-hundred and seventy-six patients were included; 21.7% underwent isolated coronary bypass, 16.5% single valve surgery, 34.3% combined cardiac surgery and 13.2% heart transplantation. The system was implanted peripherally in 60.8% of patients. In-hospital and 1-year mortality for all patients was 66.0% and 77.7%, respectively. In the multivariable Cox adjustment, severe aortic valve stenosis, previous cardiac surgery and intra-aortic balloon pump were independent risk factors for in-hospital mortality (P < 0.05). Older age, severe mitral regurgitation and patients on insulin were predictors for long-term mortality (P < 0.05). However, peripheral cannulation significantly reduced mortality. There was no time-dependent interaction of perioperative stroke with mortality. For patients who were discharged alive, the estimated 10-year survival was 32.4%.

CONCLUSIONS

Treatment of perioperative low-output syndrome with extracorporeal life-support systems is associated with poor outcome and only 34% of patients could be discharged successfully. Peripheral cannulation is prognostically favourable. Special attention should be paid to these patients because age, insulin therapy and severe mitral regurgitation are strong predictors for mortality after 10 years.
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

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

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

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

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

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

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

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

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 < 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

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.
Clinical and laboratory analysis of a large imported typhoid fever outbreak in The Netherlands
Authors: Thelen Julinha M , van Lelyveld Steven F L , Slavenburg Serena , Lammers A J Jolanda , dos Santos Claudy Oliveira , Mascini Ellen M , de Vries Anne , Hassing Robert-Jan
Published: August 2024

Typhoid fever is a rarely encountered disease in the Western world. In our study, patients with imported typhoid fever were characterized by a febrile illness with a relative bradycardia, headache and abdominal pain. Only a few patients presented with diarrhoea. An elevated CRP and lactate dehydrogenase (LD) were the most common laboratory abnormalities. Complications like focal abscesses occurred quite frequently.
UK Collaborative Randomized Trial of Neonatal Extracorporeal Membrane Oxygenation
Authors: Liberio Brianna , Wright Clyde J.
Published: August 2024

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

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 (<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

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 < 0.001).
Promotion of Breastfeeding Intervention Trial. A Randomized Trial in the Republic of Belarus
Authors: Embleton Nicholas D.
Published: August 2024

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

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

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 <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 <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.
A Controlled Trial of Antepartum Glucocorticoid Treatment for Prevention of the Respiratory Distress Syndrome in Premature Infants
Authors: McDonald Sarah D.
Published: August 2024

This first randomized controlled trial of antenatal corticosteroids allocated 287 pregnant people between 24 to 36 weeks’ gestation to receive 2 doses, 24 hours apart, of either: 12 mg betamethasone or identical-appearing 6 mg cortisone acetate (<2% the potency) as the control. Five categories of pregnant patients were included, the majority being the preterm labor group (n = 213, 76%; with 226 infants), of whom approximately 23% delivered <24 hours after entry into the trial, and presumably did not receive the second dose. The primary outcome, respiratory distress syndrome was experienced by 12/143 (8.4%) in the betamethasone group and 31/120 (25.8%) in the control group; hence reported on in 263 infants among at least 295 infants in the trial (89%). Perinatal death occurred in 16/153 (10.4%) and 25/126 (19.8%) in the betamethasone and control groups, respectively. The authors noted their encouraging preliminary evidence warranted further study, including corticosteroid dose.
Prevention of Early-Onset Neonatal Group B Streptococcal Disease with Selective Intrapartum Chemoprophylaxis
Authors: Turner Megan J. , Wright Clyde J.
Published: August 2024

At the time of this trial, group B Streptococcus (GBS) was responsible for most newborn deaths from early-onset sepsis in the United States. However, mother-to-infant transmission was known to be preventable with maternal prophylaxis. This single-center study asked whether maternal and neonatal prophylaxis would prevent early-onset GBS disease when applied to the highest-risk population (GBS-colonized mothers with preterm labor or prolonged rupture of membranes). A total of 180 high-risk mothers were randomized to ampicillin during labor or no treatment. Neonatal colonization was present in 9% of treated infants versus 51% of control infants (p <0.001). There were no cases of bacteremia among treated infants at delivery, versus 6% among controls (p = 0.024).
Centers for Medicare and Medicaid Services Fraud and Abuse
Authors: George Alexander J. , Rothman Brian , Case Edward G.
Published: August 2024

False and fraudulent claims represent an important problem for healthcare payers. As the largest healthcare payer in the United States, the Centers for Medicare and Medicaid Services commit a significant number of resources to combat and litigate incidents of fraud. As such, healthcare providers should know how to recognize fraud and abuse; be familiar with major healthcare-related fraud and abuse laws, including the False Claims Act; understand his or her obligation in reporting fraudulent behavior and protections afforded to whistleblowers (qui tam or whistleblower lawsuits); and appreciate the importance of compliant practices. This chapter reviews these principles in a problem-based learning discussion format.
Assent and Consent in Pediatrics
Authors: Kennedy Kerri O. , Robins Berklee , Elster Nanette
Published: August 2024

Medical decision-making for children differs from decision-making in the adult population in several important ways. First, children should not be considered as simply “little adults” with respect to decision-making. They have unique needs and considerations which vary depending on the child’s age and developmental capacity. Additionally, rather than two parties (doctor and patient) constituting the therapeutic relationship, there are now three, perhaps even four if the parents are not in agreement with each other. In this triadic doctor-parent/guardian-child relationship, parents and physicians engage in shared decision-making about medical treatment for the child while seeking the child’s assent depending on their age, maturity level, the nature of the decision at hand, and the child’s desire to be involved. Finally, children’s capacity for understanding and involvement in the process may vary depending on developmental factors as well as lived experiences. This complexity has led to the development of several standards that may be applied in making decisions about the healthcare of children, which will be discussed in this chapter.
The Medical Ethics of the Placebo Effect
Authors: Rae Ali I. , Cetas Justin S.
Published: August 2024

The placebo effect is an important factor in both clinical medicine and biomedical research. This chapter explores the ethics surrounding the use of clinical placebos, which has recently been debated. Different strategies have been employed to circumvent the ethical quandaries surrounding the use of clinical placebo. While the use of placebo pills in clinical research has been generally accepted, the use of sham surgery in surgical placebo-controlled trials remains contested. This chapter explores the arguments surrounding sham-surgery controlled research. The authors also review the nocebo effect in order to discuss the inverse impact of negative expectation on treatment outcomes. Evidence suggests that each of these effects is modulated by a complex interaction of individual patient and larger sociocultural factors. These factors are briefly overviewed. A more nuanced understanding of the ethics of the placebo and nocebo effects and their functional utility in the enterprise of medicine is warranted.