bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intraventricular Tigecycline
Authors: Nnakwue Elizabeth C. , Charlier Jacques Christian , Jackson Toni M. , Chan Austin W. , Patel Manish 
Published: August 2024

Abstract
This case report discusses a novel therapeutic strategy in managing a severe intracranial infection caused by multidrug-resistant Stenotrophomonas maltophilia utilizing intraventricular tigecycline. The favorable clinical outcome observed suggests a potential promising role of intraventricular tigecycline in treating drug-resistant S. maltophilia meningitis, underscoring the necessity for further investigation and validation.
Navigating Complexities
Authors: Al Hennawi Hussam , Barney Kaitlyn , Qamar Zahra 
Published: August 2024

Abstract

Bartonella endocarditis is an exceedingly rare cause of culture-negative endocarditis in the United States and is associated with significant morbidity and mortality. Recent reports suggest growing prevalence in developing countries, emphasizing a high degree of suspicion. We present a case of a formerly homeless patient with Bartonella quintana native aortic and mitral valve endocarditis. This case highlights the importance of high clinical suspicion of Bartonella species among other infectious agents in culture-negative endocarditis in the right clinical settings and the importance of early diagnosis.
1, 6-dilauroyl-D-fructofuranose ameliorates lipopolysaccharide-induced septic acute kidney injury via inhibiting caspase 1 mediated pyroptosis formation in rat
Authors: Yu Ping-Hsun , Cheng Yu-Hsuan , Chung Shiu-Dong , Chien Chiang-Ting 
Published: August 2024

Background:
Sepsis is a systemic inflammatory state associated with acute kidney injury (AKI) and high mortality. However, sepsis-induced AKI cannot be effectively prevented or treated using current antimicrobial therapies and supportive measures. We explored the therapeutic effect of newly developed fructose esters on sepsis-induced AKI (S-AKI).

Methods:
We used the surface plasmon resonance technique and ultrasensitive chemiluminescence analyzer to characterize the lipopolysaccharide (LPS)/endotoxin binding activity and antioxidant capability of fructose esters. We assessed the extent of fructose ester gastrointestinal digestion using rat intestinal acetone powder. We examined the therapeutic effect of fructose esters on LPS-induced S-AKI by evaluating the blood and renal reactive oxygen species (ROS) amounts, caspase 1 mediated pyroptosis, inflammation, microcirculation, and renal dysfunction.

Results:
Our data showed that the fructose esters are not easily hydrolyzed by the rat intestinal acetone powder, suggesting their high stability in the gastrointestinal tract. 1,6-dilauroyl-D-fructofuranose (FDL) dose-dependently scavenged H2O2 and displayed a higher binding affinity to LPS compared to sialic acid and fructose did. LPS significantly enhanced caspase 1 mediated pyroptosis and increased leukocyte infiltration, blood and renal ROS amount, and blood urea nitrogen (BUN) and creatinine level, whereas FDL significantly depressed these LPS-enhanced parameters. In addition, the increased plasma inflammatory cytokines levels using LPS could be reduced by intravenous fructose ester FDL treatment.

Conclusion:
Our data suggest that FDL, with its antioxidant activity against H2O2, can neutralize LPS toxicity using a high binding affinity, and attenuate S-AKI by inhibiting caspase 1 mediated pyroptosis, thereby ameliorating renal oxidative stress and dysfunction.
Prevalence of integrase strand transfer inhibitor resistance in people living with HIV and virological failure
Authors: Tsai Hung-Chin , Chen I.-Tzu , Chang Hui-Min , Tseng Yu-Ting , Weng Ya-Wei , Chen Yao-Shen 
Published: August 2024

Background:
This study aims to delineate the resistance profiles of integrase strand transfer inhibitors (INSTIs) among patients in southern Taiwan who had experienced antiretroviral therapy (ART) failure. We focused on individuals previously treated with highly active ART (HAART) regimens, providing insights into the implications of INSTI resistance in a broader treatment-experienced population.

Methods:
Data were collected from patients failing an INSTI-containing regimen in a medical center in southern Taiwan between 2009 and 2022. Virological failure was defined as a plasma viral load >1000 copies/mL. Reverse transcriptase, protease, and integrase coding regions were sequenced at failure. Resistance-associated mutations included in the 2022 International Antiviral Society (IAS)-USA list were used. Drug resistance was analyzed using the HIV Stanford HIVDB 9.4 edition algorithm. Logistic regression analysis was used to analyze the risk factors associated with INSTI failure.

Results:
A total of 184 patients were enrolled for genotypic drug resistance testing due to virological failure, of whom 104 failed on nonnucleoside reverse transcriptase inhibitors, 58 on protease inhibitors (PIs), and 21 on INSTIs. Among 21 patients who failed INSTI therapy, 6 failed raltegravir-based treatment, 3 elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF), 2 bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), and 10 abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). Only 10 patients had INSTI drug resistance testing results available, and 40% (4/10) showed INSTI resistance at failure. Among the seven patients who failed on second-generation INSTIs with drug resistance reports available, one harbored E157Q and another with R263K mutations, respectively. Multivariable logistic regression analysis showed that patients with INSTI failure were less likely to have pol resistance (p = 0.007, adjusted odds ratio [OR], 0.176, 95% CI, 0.050-0.618), less previous exposure to NNRTI (p = 0.003, aOR, 0.063, 95% CI, 0.010-0.401), PIs (p = 0.002, aOR, 0.030, 95% CI, 0.003-0.272), and with long duration of HAART (p = 0.018, aOR, 1.02, 95% CI, 1.003-1.037).

Conclusion:
INSTI resistance was uncommon when used as the first-line single tablet regimen in Taiwan. The results confirmed the robustness of ABC/DTG/3TC and BIC/FTC/TAF regarding integrase resistance in cases of virological failure in routine clinical care.
Marriage and Fertility Desire and Associated Factors Among Unmarried People Living With HIV in Jinan, China: A Cross-Sectional Study
Authors: Yu Yong , Li Jiahong , Qin Keke , Xiao Fuqun , Cai Huiling 
Published: August 2024

Abstract
The desires for marriage and fertility among people living with HIV (PLWH) are increasing worldwide because of improved treatment and prognosis; yet they remain understudied in China, which has a family-oriented culture. This study aimed to investigate these desires for marriage and fertility among Chinese PLWH and explore their correlates. A cross-sectional study was conducted among 1,504 Chinese PLWH to assess their desires for marriage, fertility, and other variables through an online questionnaire. Logistic regression models were used to analyze factors associated with desires for marriage and fertility. Among the 1,504 participants, 53.9% aspired to marry at 34.76 ± 5.26 years old, whereas 62.0% desired parenthood at 36.43 ± 5.11 years old. Factors associated with these desires included age, gender, residence, education level, HIV transmission route, CD4+ T-cell count, time since HIV diagnosis, disclosure of HIV status, social support, and mental health indicators.
Optimizing kidney and cardiovascular protection in an era of multiple effective treatments
Authors: Taal Maarten W. 
Published: August 2024

Purpose of review
After decades of relying on the control of hypertension and treatment with renin angiotensin system inhibitors as the only evidence-based interventions to slow the progression of chronic kidney disease (CKD), we have entered an era when multiple effective treatment options are available. This review considers the mechanisms and benefits of these novel treatments as well as the challenges associated with achieving optimal combination therapy.

Recent findings
Over the past 5 years, large clinical trials have provided robust evidence that, when added to renin angiotensin system inhibitors, treatment with sodium glucose cotransporter 2 inhibitors reduces the rate of CKD progression and the risk of cardiovascular events in people with CKD with or without diabetes and with or without albuminuria; nonsteroidal mineralocorticoid antagonists and glucagon-like peptide-1 receptor agonists afford similar benefits in people with type 2 diabetes and CKD. The mechanisms of actions of these novel therapies suggest that combination therapy will produce additive benefits, though specific evidence is sparse.

Summary
Further trials are warranted to investigate the benefits of combination therapy with novel treatments in people with CKD. Clinical implementation of optimal combination therapy will require reorganization of services to ensure that patients receive adequate education, support and monitoring.
Griscelli syndrome: a diagnostic challenge of a rare disease: a case report
Authors: Abu Ghedda Sedra , Alkadamani Sedra , Sabouni Rami , Mahmoud Jaber 
Published: August 2024

Introduction:
Griscelli syndrome (GS) is a rare autosomal recessive genetic disorder that primarily manifests as hair and skin hypopigmentation, with three types differentiated by their specific genetic defects as well as by their clinical features. Clinically, GS type 1 is characterized by early neurological alterations, while GS type 2 is characterized by immunodeficiency and could present with neurological symptoms, and type 3 is characterized by a chromosomal anomaly without a specific clinical profile besides hypopigmentation. This article details the challenges faced in the diagnosis of a patient with GS who presents with neurological symptoms followed by immunological deficits.

Case presentation:
A 7-month-old female presented with complaints of developmental delay following an otitis media infection. Upon examination, she exhibited signs of psychomotor developmental regression and had pale bronze skin and silvery-gray hair, as well as hepatosplenomegaly. The examination of her hair shaft revealed a pattern consistent with GS. During her hospitalization, the patient developed an intermittent fever and signs of hemophagocytic lymphohistiocytosis (HLH). She subsequently developed recurrent seizures treated with phenytoin and Aciclovir. Shortly she succumbed to respiratory distress syndrome and multisystem failure.

Discussion:
The presence of HLH confirms the type of GS. However, in some cases, the HLH criteria could not be fulfilled, presenting a diagnostic challenge.

Conclusion:
The genetic examination is the only way to differentiate GS type 1 from type 2. However, when it is not available, the presence of specific symptoms and features may assist in the classification. Furthermore, treatments should be administered when GS type 2 is suspected since they have the potential to improve life quality through treating HLH, delaying and altering the neurological symptoms.
Lactation Support Services in Level III Neonatal Intensive Care Units in Canada
Authors: Pan Lingnong , Cooper Maeve Hay , Fucile Sandra 
Published: August 2024

Abstract

Introduction:
Lactation support services can improve exclusive breastfeeding rates among infants in the neonatal intensive care unit (NICU). There are limited data on how many NICUs offer these services.

Objective:
To assess prevalence and type of lactation services provided in level III Canadian NICUs.

Methods:
A nationwide comprehensive point-prevalence study was undertaken via a telephone survey of level III NICUs in Canada. Availability of lactation consultants, type of services offered, infrastructure such as centralized milk labs, private space for expressing milk, and refrigerators to store breast milk, and follow-up support programs were assessed.

Results:
There are 31 level III NICUs in Canada. Nineteen of the 31 NICUs participated in the survey, representing a 61% response rate. Of these, 79% (n = 15) offered lactation consultant services. Most (n = 13, 68%) noted they had International Board-Certified Lactation Consultants (IBCLCs). The types of lactation services offered were either a reactive care model, a proactive care model, or a combination of both. Seven (37%) units, both with and without LCs, offered alternate lactation assistance, such as helping mothers at the bedside with breastfeeds. Several units had available infrastructure (n = 10, 53%) and offered follow-up lactation support (n = 10, 53%).

Conclusion:
Most of the surveyed level III NICUs in Canada provided lactation support services; however, there was variation in type. More research is needed to identify barriers that NICUs face in offering lactation services for mothers of NICU babies.
Phase II Study Shows the Effect of Adenoviral Vascular Endothelial Growth Factor C and Lymph Node Transfer in Lymphedema
Authors: Rannikko Eeva H. , Pajula Susanna , Suominen Sinikka H. , Kiiski Juha , Mani Maria R. , Halle Martin , Kaartinen Ilkka S. , Lahdenperä Outi , Arnardottir Tinna H. , Kauhanen Susanna M. , Kavola Heli , Majava Marja , Niemi Tarja S. , Brück Nina M. , Mäki Maija T. , Seppänen Marko P. , Saarikko Anne M. , Hartiala Pauliina 
Published: August 2024

Background:
Breast cancer–related lymphedema is a common complication lacking medical treatment. Lymfactin is an adenovirus type 5–based gene therapy and prolymphangiogenic growth factor vector that induces vascular endothelial growth factor C expression. The authors’ aim was to evaluate the therapeutic effect of Lymfactin with vascularized lymph node transfer (VLNT).

Methods:
This phase II, double-blind, placebo-controlled, randomized, multicenter study evaluated the efficacy and safety of Lymfactin in combination with VLNT. The primary endpoints were edema volume, quality of life, and lymphoscintigraphy. All adverse events were recorded. A mixed model of repeated measures analysis of covariance was performed. This study was a continuation of a previous phase I Lymfactin study.

Results:
Thirty-nine patients with breast cancer–related lymphedema were recruited between June of 2018 and December of 2019 and randomized to receive either Lymfactin (n = 20) or placebo (n = 19). The primary endpoints showed a positive effect of VLNT in both groups compared with the baseline, but without statistical differences between groups at 12 months. In addition, greater improvements were observed in the tissue dielectric constant ratios measuring skin interstitial fluid levels in the Lymfactin group compared with the placebo group (P = 0.020). No differences in adverse events were detected between the groups.

Conclusions:
This study was one of the few studies to objectively show a positive effect of VLNT in a prospective, clinical, multicenter setting. It was also the first-ever randomized prospective clinical study showing a quantitatively positive effect of a medical therapy on the edema of lymphedema but failed to show differences between groups in primary outcome measures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.
A Novel Blood-Based Epigenetic Clock for Intrinsic Capacity Predicts Mortality and is Associated with Clinical, Immunological and Lifestyle Factors
Authors: Fuentealba Matías , Rouch Laure , Guyonnet Sophie , Lemaitre Jean-Marc , de Souto Barreto Philipe , Vellas Bruno , Andrieu Sandrine , Furman David 
Published: August 2024

AbstractAge-related decline in intrinsic capacity (IC), defined as the sum of an individual’s physical and mental capacities, is a cornerstone for promoting healthy aging and longevity, as it emphasizes maximizing function throughout the aging process instead of merely treating diseases. However, accurate assessments of IC are resource-intensive, and the molecular and cellular basis of its decline are poorly understood. Herein, we used the INSPIRE-T cohort, consisting of 1,014 individuals aged 20 to 102, to construct the IC clock, a DNA methylation (DNAm)-based predictor of IC trained on the clinical evaluation of cognition, locomotion, psychological well-being, sensory abilities, and vitality. In the Framingham Heart Study, age-adjusted DNAm IC correlates with first- and second-generation epigenetic clocks, predicts all-cause mortality, and is strongly associated with changes in molecular and cellular immune and inflammatory biomarkers, functional and clinical endpoints, health risk factors, and diet.
Simplified and Rapid Workflow Enhances Throughput ofDe NovoSequencing of COVID-19 Neutralizing Antibodies
Authors: Xiong Yueting , Xiao Jin , Jiang Wenbin , Wang Jingyi , Bu Qingfang , Chen Xiaoqing , Wu Yangtao , Yu Rongshan , Yuan Quan , Xia Ningshao 
Published: August 2024

ABSTRACTDuring the current COVID-19 pandemic, precise antibody sequencing is crucial for the rapid development of broad-spectrum or pan-β-coronavirus neutralizing antibodies (NAbs) to prevent new variants of the coronavirus and other highly pathogenic β-coronaviruses. However, mass spectrometry-basedde novosequencing remains challenging due to its high cost, low throughput, and unexpected missing of certain ion information. We developed an innovative approach using solely bottom-up to provide a rapid, robust, and refined solution for the currentde novosequencing challenges. The methodology, referred to as SP-MEGD for Single-Pot and Multi-Enzymatic Gradient Digestion, capitalizes on a five-protease gradient digestion by sampling every two hours for a total of 6 hours in an integrative reactor. The SP-MEGD method could engender numerous missed cleavage events and produce various peptide products of diverse lengths with overlapping stretches of residues, enabling efficient database-freede novosequencing. Antibody assembly for single or mixed COVID-19-NAbs with publicly available sequences and commercial antibodies with unknown sequences was efficiently deciphered using our previously proposed optimization method, Fusion assembler. Our innovative study represents the first successful simultaneous discrimination and achieving over 99% accurate sequence coverage of a mixture containing three humanized COVID-19-NAbs (S2P6LH, BD5514LH, and BD5840LH). Furthermore, we utilized SP-MEGD and Fusion to sequence commonly used anti-CD8 and anti-CD4, and successfully confirmed their impact on immune cell clearance through in vivo experiments. Overall, our developed workflow demonstrates promise in facilitating the discovery and development of vaccines and antibody therapeutics while providing deeper insights into monoclonal antibodies (mAbs).
A novel candidate neuromarker of central motor dysfunction in childhood apraxia of speech
Authors: Anastasopoulou Ioanna , Cheyne Douglas O. , van Lieshout Pascal , Wilson Peter H. , Ballard Kirrie J. , Johnson Blake W. 
Published: August 2024

AbstractChildhood apraxia of speech (CAS) is conceived as an impairment of the central motor system’s ability to program multiple speech movements, resulting in inaccurate transitions between and relative timing across speech sounds. However, the extant neuroimaging evidence base is scant and inconclusive and the neurophysiological origins of these motor planning problems remain highly underspecified. In the first magnetoencephalography study of this disorder, we measured brain activity from typically developing children (N = 19) and children with CAS (N=7) during performance of a speech task designed to interrogate function of the speech areas of primary sensorimotor cortex. Relative to their typically developing peers, our sample of CAS children showed abnormal speech-related responses within the mu-band motor rhythm, and beamformer source reconstruction analyses specify a brain origin of this speech rhythm in the left cerebral hemisphere, within or near pre-Rolandic motor areas crucial for the planning and control of speech and oromotor movements. These results provide a new and specific candidate mechanism for the core praxic features of CAS; point to a novel and robust neurophysiological marker of typical and atypical expressive speech development; and support an emerging neuroscientific consensus which assigns a central role for programming and coordination of speech movements to the motor cortices of the precentral gyrus.
Large Language Models Improve the Identification of Emergency Department Visits for Symptomatic Kidney Stones
Authors: Bejan Cosmin A. , Reed Amy M , Mikula Matthew , Zhang Siwei , Xu Yaomin , Fabbri Daniel , Embí Peter J. , Hsi Ryan S. 
Published: August 2024

AbstractBackgroundRecent advancements of large language models (LLMs) like Generative Pre-trained Transformer 4 (GPT-4) have generated significant interest among the scientific community. Yet, the potential of these models to be utilized in clinical settings remains largely unexplored. This study investigated the abilities of multiple LLMs and traditional machine learning models to analyze emergency department (ED) reports and determine if the corresponding visits were caused by symptomatic kidney stones.MethodsLeveraging a dataset of manually annotated ED reports, we developed strategies to enhance the performance of GPT-4, GPT-3.5, and Llama-2 including prompt optimization, zero- and few-shot prompting, fine-tuning, and prompt augmentation. Further, we implemented fairness assessment and bias mitigation methods to investigate the potential disparities by these LLMs with respect to race and gender. A clinical expert manually assessed the explanations generated by GPT-4 for its predictions to determine if they were sound, factually correct, unrelated to the input prompt, or potentially harmful. The evaluation includes a comparison between LLMs, traditional machine learning models (logistic regression, extreme gradient boosting, and light gradient boosting machine), and a baseline system utilizing International Classification of Diseases (ICD) codes for kidney stones.ResultsThe best results were achieved by GPT-4 (macro-F1=0.833, 95% confidence interval [CI]=0.826–0.841) and GPT-3.5 (macro-F1=0.796, 95% CI=0.796–0.796), both being statistically significantly better than the ICD-based baseline result (macro-F1=0.71). Ablation studies revealed that the initial pre-trained GPT-3.5 model benefits from fine-tuning when using the same parameter configuration. Adding demographic information and prior disease history to the prompts allows LLMs to make more accurate decisions. The evaluation of bias found that GPT-4 exhibited no racial or gender disparities, in contrast to GPT-3.5, which failed to effectively model racial diversity. The analysis of explanations provided by GPT-4 demonstrates advanced capabilities of this model in understanding clinical text and reasoning with medical knowledge.