bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing Azathioprine-Induced Myelosuppression and Alopecia Totalis: Lessons from a SLE Patient
Authors: Rupasinghe Saumya Dinithi , Abeysinghe Duminda 
Published: November 2024

Introduction Azathioprine (AZA), an immunosuppressant and mercaptopurine analog, is used to manage rheumatological and immunological conditions. Although effective, AZA can cause myelosuppression, sometimes necessitating dose adjustments or discontinuation. While severe pancytopenia or alopecia is rare, these issues can arise. This report describes a case of severe myelosuppression and alopecia totalis following AZA treatment in a patient with systemic lupus erythematosus (SLE). Case Report A 27-year-old healthy female presented with an 8-month history of fever, cough with pleuritic chest pain, and hemoptysis. Clinical and biochemical evaluations diagnosed her with SLE and secondary pulmonary vasculitis. She was initially treated with systemic steroids, followed by AZA. AZA was started at 25 mg daily (0.8 mg/kg) and increased to 75 mg daily (2 mg/kg) over three months. After dose escalation, she developed increased hair loss, feverishness, and lethargy, prompting her admission to a medical facility. Examination revealed significant non-scarring alopecia, (Figure 1) but no clinical signs of an SLE flare. Laboratory tests showed pancytopenia: hemoglobin 8.4 g/dL, white blood cells 880/[Formula: see text]L, platelets 130K/[Formula: see text]L, and absolute neutrophil count 38/[Formula: see text]L. Inflammatory markers, complement levels, and septic screening were normal. AZA was discontinued, and she was treated for neutropenic sepsis with high-dose steroids and GM-CSF. Despite these measures, blood parameters did not improve as expected. After 25 days of treatment, hair loss ceased, and cytopenias began to recover. Bone marrow analysis was not performed during the acute phase. Upon discharge, her blood counts were WBC 6,130/[Formula: see text]L, hemoglobin 10.9 g/dL, and platelets 85K/[Formula: see text]L. Given her SLE and lung pathology, she continued immunosuppressive therapy but was switched from AZA to IV Rituximab. Six weeks later, her blood counts had improved (WBC 10K/[Formula: see text]L, hemoglobin 10.9 g/dL, platelets 289K/[Formula: see text]L), and hair regrowth was observed. (Figure 2) Conclusion This case underscores the need for clinicians to be vigilant for early signs of severe myelosuppression, such as alopecia, in patients receiving azathioprine. Awareness of these uncommon side effects is crucial for effective management.
Health-Related Quality of Life in the Patients of Gout, A Multi-center, Cross-sectional Study
Authors: Towiwat Patapong , Louthrenoo Worawit , Chevaisrakul Parawee , Siripaitoon Boonjing , Jatuworaprek Kanon , Upakdee Nilawan , Buttham Bodin , Dilokthornsakul Piyameth 
Published: November 2024

Background: Although EuroQol 5-domain (EQ-5D) of the 5-level version (5L) instrument has been used to determine quality of life and health utility in gout, the health utility among patients with gout flare (GF) and non-gout flare (non-GF) is still limited. This study aimed to measure the utility values among GF and non-GF patients in Thailand. Methods: A multi-center cross-sectional survey study was performed. Patients with GF and non-GF were face-to-face interviewed by trained research staffs using the EQ-5D-5L (Thai version) and EQ-Visual Analog Scale (VAS) instrument. Those with GF were subdivided into those who received no treatment and those who received treatment less than 48 hours after GF. Results: Two hundred and sixteen patients (108 GF and 108 non-GF patients), male in 90.28%, were included. The disease duration was significantly longer in the non-GF than in the GF groups (median: 10 vs 5 years, p = 0.004). There was no difference in the tophi present between the two groups. When compared with non-GF group, the GF patients significantly had low health utility (0.34 ± 0.36 vs. 0.89 ± 0.15, p [Formula: see text] 0.001), and EQ-VAS score (54.73 ± 24.14 vs. 84.06 ± 13.38, p [Formula: see text] 0.001). In a subgroup analysis of the non-GF group, there was not significant health utility and EQ-VAS score between those with tophi and those without tophi (0.87 ± 0.14 vs. 0.90 ± 0.15, p = 0.351 and 83.37 ± 14.92 vs. 84.33 ± 12.84, p = 0.738, respectively). Conclusion: This study highlights the importance of assessing quality of life in managing gouty patients. Patients with GF had lower health utility and EQ-VAS status than the non-GF patients.
Willingness to Pay for Human Leukocyte Antigen Type-B* 58:01 Genetic Test to Prevent Allopurinol Hypersensitivity Syndrome in Gouty Patients: A Cross-sectional Survey in Thailand
Authors: Towiwat Patapong , Buttham Bodin , Banrungsawad Naruemon , Nakham Athagran , Upakdee Nilawan 
Published: November 2024

Background: Since Thailand have high prevalence of Human Leukocyte Antigen Type-B* 58:01 (HLA-B*58:01) genotype. This genetic has strongly associated with allopurinol hypersensitivity syndrome (AHS). The national health security guideline of Thailand has accepted the association of HLA-B*58:01 genotype with prevention of AHS. The present study aims to investigate willingness to pay (WTP) of gouty patients for HLA-B*58:01 testing prior to starting allopurinol and factors influencing their decision for the testing. Methods: This study is a cross-sectional survey. The contingent valuation by open-ended questionnaire interview on WTP of gouty patients for HLA-B*58:01. The descriptive statistics are used. Participants who are age [Formula: see text] 20 years, diagnosed based on the American College of Rheumatology/European League Against Rheumatism 2015 gout classification criteria at Naresuan university hospital (NUH), and three sub-district health promoting hospitals of NUH, Phitsanulok, Thailand are included. Results: Two hundred and fifty gouty patients are included. The majority of them are male, 214 patients (85.60%). The average age of the participants is 64.5 (± 12.8) years. Male patients are more WTP than female patients. The gouty patients with a monthly income between 10,001-30,000 Thai Baht (THB) (288.43-865.30 United states dollar (USD)) are the WTP patient group. The results show the majority of patients (64.2%) have WTP between 101-500 THB (2.88-14.42 USD) or average of median (IQR) is 500 (300, 800) THB or 14.37 8.62, 22.99) USD for the testing. The reason for decline the testing are the cost of the testing is too expensive. Other urate lowering agents, gouty patients have WTP for febuxostat, sulfinpyrazone and benzbromarone in 68%, 67.60% and 71.60%, respectively. Average WTP for febuxostat, sulfinpyrazone and benzbromarone 1,000 THB (28.74 USD), 1,000 THB (28.74 USD) and 285 THB (8.19 USD), respectively. Conclusion: The majority of gouty patients are willing to pay for the genetic testing even they have to pay for the testing cost themselves which is 1,000 THB (28.74 USD). They are willing to pay if they have to bear the cost of the testing themselves. For those un-WTP, the main reason is the cost of the genetic testing too expensive, followed by lack of income/low income. The maximum amount most participants are willing to pay for the testing is average of median (IQR) is 500 (300, 800) THB or 14.37 (8.62, 22.99) USD. This study may has affected to change a health policy for the genetic testing price or to switch from allopurinol to other urate lowering agents.
Advancements in B‐Cell Non‐Hodgkin’s Lymphoma: From Signaling Pathways to Targeted Therapies
Authors: Alfaifi Abdullah , Bahashwan Salem , Alsaadi Mohammed , Ageel Ali H. , Ahmed Hamzah H. , Fatima Kaneez , Malhan Hafiz , Qadri Ishtiaq , Almehdar Hussein 
Published: November 2024

Lymphoma is the sixth most prevalent cancer globally. Non‐Hodgkin’s lymphomas are the majority group of lymphomas, with B cells accounting for approximately 95% of these lymphomas. A key feature of B‐cell lymphoma is the functional perturbations of essential biological pathways caused by genetic aberrations. These lead to atypical gene expression, providing cells with a selective growth advantage. Molecular analysis reveals that each lymphoma subtype has unique molecular mutations, which pose challenges in disease management and treatment. Substantial efforts over the last decade have led to the integration of this information into clinical applications, resulting in crucial insights into clinical diagnosis and targeted therapies. However, with the growing need for more effective medication development, we anticipate a deeper understanding of signaling pathways and their interactions to emerge. This review aims to demonstrate how the BCR, specific signaling pathways like PI3K/AKT/mTOR, NF‐kB, and JAK/STAT are diverse in common types of B‐cell lymphoma. Furthermore, it offers a detailed examination of each pathway and a synopsis of the approved or in‐development targeted therapies. In conclusion, finding the activated signaling pathways is crucial for developing effective treatment plans to improve the prognosis of patients with relapsed or refractory lymphoma.Trial Registration: ClinicalTrials.gov identifier: NCT02180724, NCT02029443, NCT02477696, NCT03836261, NCT02343120, NCT04440059, NCT01882803, NCT01258998, NCT01742988, NCT02055820, NCT02285062, NCT01855750, NCT03422679, NCT01897571
What Is the Cost: Financial Toxicity and Screening Fatigue in Li–Fraumeni Syndrome
Authors: Underkofler Kaylee A. , Thomas Martha H. , Erickson Sarah H. , Panzer Alayna A. , Fitzgibbon Kara S. , Ring Kari L. 
Published: November 2024

Abstract
Patients with Li–Fraumeni syndrome (LFS) are recommended to follow a comprehensive surveillance protocol, but the demanding nature may limit adherence. We sought to identify barriers to adherence and to determine whether screening fatigue and financial hardship are contributors. A 39-item online survey was developed and distributed to patients presenting to a LFS clinic between 2017 and 2022. Of the 39 patients eligible, 20 responded to the survey (51%). Of the respondents, 75% reported they do not skip surveillance tests; however, this was not consistent when asked about specific tests, with only 65% and 40% up to date with colonoscopy and esophagogastroduodenoscopy, respectively. Hundred percent of those diagnosed within the last 5 years said they never skip tests, whereas only 50% of those diagnosed more than 5 years ago reported the same (P = 0.01). Barriers to adherence were reported by 85% and most commonly included finances (40%), time (25%), and difficulty scheduling (25%). Only 21% felt no financial stress, and 63% worried at least somewhat about their future financial situation because of LFS. Even with insurance, 65% felt their share of healthcare costs was too high. Adherence to rigorous cancer surveillance is imperfect and decreases over time among patients with LFS. Whereas number of tests was not a commonly cited barrier, time and difficulty scheduling were common and may contribute to screening fatigue. The degree of financial stress in the affluent population studied should raise even greater concern about financial strain in the LFS population in general.
Prevention Relevance: Li–Fraumeni syndrome (LFS) essentially guarantees a cancer diagnosis in an affected individual’s lifetime. Findings of this study reveal a difficulty for patients with LFS to adhere to recommended rigorous surveillance protocols and question how identified barriers can be broken down to reduce the morbidity and mortality of LFS.
Clinicopathologic Features of Oral Verrucous Carcinoma: A Systematic Review and Meta-Analysis
Authors: Duncan Steven , Finegersh Andrey , Orosco Ryan K. , Wu Nathaniel , Brumund Kevin T. , Califano Joseph A. , Coffey Charles S. , Moss William J. 
Published: November 2024

Objective: To further characterize the clinicopathologic features of oral verrucous carcinoma. Methods: In accordance with PRISMA guidelines, a systematic review of the Medline, Web of Science, Embase, and Cochrane databases was performed in search of articles evaluating clinicopathologic features of oral verrucous carcinoma. Primary outcomes of interest included tumor subsites, T-staging, rates of cervical lymph node metastases, rates of distant metastases, 5-year survival (overall, disease-free, or disease-specific), and recurrence rates. Meta-analysis was performed using a random effects model. Results: Nineteen articles with a total of 1458 subjects were ultimately included in the analysis. There were 17 studies with a total of 1353 patients reporting verrucous carcinoma subsites and the buccal mucosa (59.2%, 55.1%-63.3%) ( I2 = 98.1%) had the highest incidence of involvement. There were 10 papers with 277 patients reporting on rates of cervical lymph node metastases from surgical pathology yielding a pooled rate of 0% (0%-2.3%) ( I2 = 1%). There were 14 studies with a collective 712 patients commenting on rates of distant metastases and collectively, none were reported, yielding a pooled rate of 0% (0%-0%) ( I2 = 0%). Five year survival data was generally favorable relative to oral squamous cell carcinoma but was insufficient for meta-analysis. Conclusion: An international collection of evidence supports that pure oral verrucous carcinoma is a relatively indolent, non-metastasizing malignancy associated with areca nut consumption. A reliance on traditional squamous cell carcinoma staging and treatment algorithms for verrucous carcinoma patients can predispose to overtreatment.
Early-life exposure to political violence and domestic violence
Authors: Hussain Akseer , Mazumdar Sumit 
Published: November 2024

Globally, one in three women experiences domestic violence over their lifetimes. Yet, the factors that shape adult behavior toward domestic violence remain poorly understood. We examine the effect of exposure to political violence in early stages of life on likelihood of domestic violence in marital life. Combining household level survey with political violence datasets from 1988 to 2018, our findings show that it is the exposure of men to political violence that matters, but not the exposure of their wives. Furthermore, we show that the critical age bracket is between 4 and 6 years of age in which exposure to political violence seems to shape adult behavior toward domestic violence. This is true for physical and emotional violence. Moreover, exposure to political violence at almost any point in male individuals’ life increases their likelihood to perpetrate sexual violence on their wives. JEL classification: J12, J15, J16, O12
Total Contact Casting Remains an Effective Modality for Treatment of Diabetic Foot Ulcers
Authors: Zhang Jason , Sadek Mikel , Iannuzzi Lou , Rockman Caron , Garg Karan , Taffet Allison , Ratner Molly , Berland Todd , Maldonado Thomas , Jacobowitz Glenn , Ross Frank 
Published: November 2024

Objectives Total contact casting (TCC) is used to promote wound closure in diabetic foot ulcers (DFUs); however, this technique is underused today. This study aims to further evaluate the efficacy of TCC in a large cohort, including patients with peripheral artery disease (PAD). Methods This was a retrospective analysis of patients with DFUs who underwent TCC from 2017 to 2021. PAD was defined as absence of pedal pulse or ABI <0.9. Demographic data, DFU characteristics, and peripheral arterial intervention were evaluated. Outcomes included complete healing, healing time, and rate of major amputation. Subgroup analysis was performed on patients undergoing peripheral intervention. Results 152 patients underwent TCC. Mean age was 58.8 ± 12.1 years, 79.6% were male, and 26.3% had PAD. Mean DFU size was 8.27 ± 9.9 cm2, with mean depth 0.61 ± 0.49 cm. 112 patients had palpable pedal pulses on the affected extremity (73.7%). Average ABI was 1.12 ± 0.22 (n = 90). Complete healing was observed in 122 (80.3%) patients, with average healing time of 81.5 ± 57.1 days. Thirteen (8.6%) patients eventually required amputation (3 major). When compared to patients with healed DFUs, those without healing had higher rates of amputation (39.1% vs 3.1%, P < .001), intervention (43.4% vs 17.8%, P = .006), and noncompliance (39.1% vs 20.2%, P = .046). Thirty-three patients underwent revascularization, undergoing angioplasty (81.8%), atherectomy (63.6%), stent (15.2%), and/or bypass (9.1%). Interventions were performed in aortoiliac (3.0%), femoropopliteal (45.5%), and tibial (72.7%) segments. Twenty-two (66.7%) patients who underwent revascularization completely healed. Patients requiring revascularization were more likely to have previous intervention (57.6% vs 13.4%, P < .0001) and incompressible vessels (36.4% vs 7.6%, P < .00001), with lower ABIs (0.94 ± 0.25 vs 1.17 ± 0.18, P = .0008) compared to patients without intervention. Conclusions TCC remains an effective option for treatment of DFUs, as most were completely healed. Patients with PAD may benefit from TCC and revascularization, however, healing rates are lower in this cohort, necessitating the need for close observation.
Older adult immigrants’ experiences of being hospitalized: a qualitative study
Authors: Vestgarden Lisbeth Alnes , Dahlborg Elisabeth , Strunck Jeanne , Aasen Elin Margrethe 
Published: November 2024

Abstract
Background
Access to equal health services is a key issue in most European countries. In the coming years, immigrants will constitute an increasing proportion of older adults in Europe, and their need for healthcare services will likely increase. Healthcare services must prepare for such encounters to make them equitable. Older immigrants’ hospitalization experiences require elucidation. Their patient experiences can provide important knowledge when the healthcare system is working toward equal and equitable healthcare services.

Methods
This study employed an exploratory qualitative design. Data were collected through narrative interviews with a purposive sample of eight older adult immigrants, aged 61–79 years. Patient narratives were analyzed using thematic analysis with a reflexive approach, as outlined by Braun and Clarke.

Results
The analysis created three themes that shed light on older adult immigrants’ experiences as hospital patients. The themes conveyed experiences related to challenging involvement and interaction, notions of what an ideal patient should be like, and participants not feeling valued as a person.

Conclusion
The findings indicate that communication between healthcare professionals and older adult immigrant patients is deficient: older immigrants in this study did not make their voices heard nor were they invited to participate by healthcare professionals. This contributes to limited involvement in assessment, treatment, and care. The older immigrants felt that they were not valued nor met as unique individuals. The findings indicate that health policy goals regarding patient participation and person-centered care are not met when older immigrants are patients. Consequently, the experiences of older adult immigrants in this study indicate that equal health services are at risk.
OXPHOS mediators in acute myeloid leukemia patients: Prognostic biomarkers and therapeutic targets for personalized medicine
Authors: Abdel-Aziz Amal Kamal 
Published: November 2024

Abstract
Background
Despite significant advances in comprehending its tumorigenic role, the prognostic and therapeutic potential of targeting oxidative phosphorylation (OXPHOS) in acute myeloid leukemia (AML) remain obscure.

Methods
The prognostic value of ~ 200 mitochondrial/OXPHOS genes as candidate biomarkers was examined in AML patients over ~ 10 years follow-up using Kaplan–Meier and Cox regression analyses. Furthermore, the transcript levels of the assessed markers were inspected in healthy bone marrow tissues and the dependencies of AML cells on the assessed genes were examined.

Results
Elevated levels of NADH:ubiquinone oxidoreductase subunit A6 (NDUFA6), succinate dehydrogenase complex flavoprotein subunit A (SDHA), solute carrier family 25 member 12 (SLC25A12), electron transfer flavoprotein subunit beta (ETFB), carnitine palmitoyltransferase 1A (CPT1A) and glutathione peroxidase 4 (GPX4) were associated with poor overall survival of AML patients. SLC25A12, ETFB and CPT1A were overexpressed in AML compared to healthy tissues. Cytochrome B5 type A (CYB5A)high, SLC25A12high and GPX4high AML patients displayed higher levels of circulating and engrafted blasts compared to low-expressing cohorts. NPM1 and SRSF2 mutations were frequent in SDHAlow and CPT1Alow AML patients respectively. FLT3-ITD, NPM1 and IDH1 mutations were prevalent in CPT1Ahigh AML patients. FLT3-ITD AMLs were more dependent on OXPHOS.

Conclusions
This study identifies NDUFA6 and SDHA as novel companion prognostic biomarkers which might present a rational strategy for personalized therapy of AML patients.

Graphical Abstract
Thermo-amplifier circuit in probiotic E. coli for stringently temperature-controlled release of a novel antibiotic
Authors: Dey Sourik , Seyfert Carsten E. , Fink-Straube Claudia , Kany Andreas M. , Müller Rolf , Sankaran Shrikrishnan 
Published: November 2024

AbstractPeptide drugs have seen rapid advancement in biopharmaceutical development, with over 80 candidates approved globally. Despite their therapeutic potential, the clinical translation of peptide drugs is hampered by challenges in production yields and stability. Engineered bacterial therapeutics is a unique approach being explored to overcome these issues by using bacteria to produce and deliver therapeutic compounds at the body site of use. A key advantage of this technology is the possibility to control drug delivery within the body in real time using genetic switches. However, the performance of such genetic switches suffers when used to control drugs that require post-translational modifications or are toxic to the host. In this study, these challenges were experienced when attempting to establish a thermal switch for the production of a ribosomally synthesized and post-translationally modified peptide antibiotic, darobactin, in probiotic E. coli. These challenges were overcome by developing a thermo-amplifier circuit that combined the thermal switch with a T7 RNA Polymerase. Due to the orthogonality of the Polymerase, this strategy overcame limitations imposed by the host transcriptional machinery. This circuit enabled production of pathogen-inhibitory levels of darobactin at 40 °C while maintaining leakiness below the detection limit at 37 °C. Furthermore, the thermo-amplifier circuit sustained gene expression beyond the thermal induction duration such that with only 2 h of induction, the bacteria were able to produce pathogen-inhibitory levels of darobactin. This performance was maintained even in physiologically relevant simulated conditions of the intestines that include bile salts and low nutrient levels.
Graphical Abstract