bluuebunny/crossref_metadata_2025 huggingface dataset:
The roles of innate immune cells in atopic dermatitis
Authors: Pan Yuke , Wang Youyi , Xu Meinian , Zhong Meizhen , Peng Xiaoming , Zeng Kang , Huang Xiaowen
Published: July 2024

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by recurrent eczematous lesions and severe pruritus. The economic burden and time penalty caused by the relapse of AD reduce patients' life quality. AD has complex pathogenesis, including genetic disorders, epidermal barrier dysfunction, abnormal immune responses, microbial dysbiosis of skin, and environmental factors. Recently, the role of innate immune cells in AD has attracted considerable attention. This review highlighted recent findings on innate immune cells in the onset and progression of AD.
Nail Avulsion: Update with Technical Tips for Successful Outcomes
Authors: Jellinek Nathaniel J. , Baltz Julia O.
Published: July 2024

Background: Nail avulsion is a procedure with numerous nuanced iterations and uses within the management of nail diseases, that when performed with intention and skill can imbue the clinician with the ability to manage myriad nail conditions. Summary: This manuscript serves as a reference for the multiple techniques of nail avulsion as well as clinical indications in various disease states. Key Messages: Nail avulsion is an often over-simplified procedure with a multitude of uses and variations in technique. This manuscript should serve as an introduction to nail avulsion in the diagnosis and treatment of multiple nail conditions.
In vitro Generated Megakaryocytes for the Detection of Human Platelet Antigen-Specific Alloantibodies
Authors: Uzun Günalp , Lucic Josip , Marini Irene , Rigoni Flavianna , Lyshy Franziska , Haghighi Omid , Wolska Nina , Nowak-Harnau Stefanie , Althaus Karina , Sachs Ulrich J. , Bakchoul Tamam
Published: July 2024

Introduction: Serologic characterization of antihuman platelet antigen (HPA) alloantibodies is crucial in fetal neonatal alloimmune thrombocytopenia. The gold standard MAIPA assay requires fresh platelets from HPA-genotyped donors, which is challenging for some laboratories. Megakaryocytes express HPA epitopes and offer an alternative source for detecting anti-HPA antibodies. The objective of this study was to assess the efficacy of a novel assay called monoclonal antibody immobilization of megakaryocyte antigens (MAIMA) for detecting anti-HPA antibodies. Methods: CD34+ cells from buffy coats were differentiated into megakaryocytes in vitro. The performance of the MAIMA assay was evaluated using WHO reference reagents for HPA-1a, HPA-3a, and HPA-5b, along with sera samples from patients who had well-characterized anti-HPA antibodies. Results: The WHO anti-HPA-1a reference reagent showed similar binding to megakaryocytes and platelets in MAIMA and MAIPA, respectively. On the other hand, optical density (OD) values for the WHO anti-HPA-3a reference reagent were lower in MAIMA than in MAIPA. Anti-HPA-5b antibodies were not detectable in MAIMA. Patients’ sera containing anti-HPA-1a antibodies were successfully detected in MAIMA in all clinical samples. Moreover, OD values in MAIPA and MAIMA showed high correlation (r = 0.96, p < 0.001). MAIMA was reactive for samples with anti-HPA-3a as well as anti-HPA-3b; however, OD values were lower compared to MAIPA. Interestingly, all patient samples with anti-HPA-5b antibodies were tested negative in MAIMA. Conclusion: In vitro generated megakaryocytes can be used to detect anti-HPA-1a alloantibodies. However, despite this potential, they may be less suitable for the detection of alloantibodies against other HPAs such as HPA-5b.
Exploring the Association between Depression, Suicidality, and Serum Brain-Derived Neurotrophic Factor, FAM19A5, Total Antioxidant Status, Total Oxidant Status, Oxidative Stress Index, and Cytokine Levels: A Case-Control Study of Drug-Naive Adolescents with First-Episode Major Depressive Disorder
Authors: Uzun Çakir Aylin Deniz , Çakir Burak , Yalin Sapmaz Şermin , Bilaç Öznur , Taneli Fatma , Kandemir Hasan
Published: July 2024

Introduction: Considering the importance of neuroinflammation and neurodegeneration in the pathophysiology of major depressive disorder (MDD), peripheral blood biomarkers are promising for the prediction of diagnosis and treatment outcomes. We aimed to elucidate the neuroinflammatory pathophysiology of depression by evaluating serum levels of FAM19A5 as a new biomarker of inflammatory activation, proinflammatory cytokines, brain-derived neurotrophic factor (BDNF), and oxidative stress parameters. Methods: Adolescents diagnosed with first-episode drug-naive MDD (n = 35) were compared neurobiologically healthy control group (n = 33). Serum FAM19A5 levels, cytokine levels, BDNF and oxidative stress parameters were evaluated using the enzyme-linked immunoassay method. All participants were assessed with the Level-2 Depression Severity Scale, Sleep Disturbance Scale, Somatic Symptom Scale. Results: BDNF levels were significantly higher in the patient group compared to the control group. While BDNF showed a positive correlation with all scale scores; BDNF was significantly higher in the suicide risk groups than the control group. IL-1β levels displayed a negative correlation with the severity of sleep disturbances. Conclusions: In adolescents with MDD, inflammatory and oxidative stress markers were not raised in peripheral blood, unlike in adults. However, BDNF levels, which typically decrease in neurodegenerative conditions, were higher in those with MDD.
Effectiveness of Alternative Nostril Breathing on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Nam Tae Gwang , Jeong Hyein , Kim Kyeong Han , Jang Insoo
Published: July 2024

Introduction: Hypertension, a significant risk factor for cardiovascular disease, has a high prevalence rate globally. While drug use is the most common approach, lifestyle improvements are crucial. Recently, there has been a notable upsurge of interest in various breathing methods, including device-induced breathing techniques like Resperate. However, the reliance on a device for these techniques has prompted the popularity of alternative breathing methods that can be performed without any external devices. One such method that has gained significant attention is alternative nostril breathing, which serves as an alternative medical treatment known for its effectiveness in reducing blood pressure. Therefore, this study aimed to systematically investigate the therapeutic effects of alternate nostril breathing. Methods: We selected 16 articles published in English, Korean, and Chinese databases, of which 14 met the eligibility criteria, and a systematic literature review was conducted. A meta-analysis was conducted on six qualified studies. Meta and sensitivity analyses were conducted using a random effects model of six randomized clinical trials (RCTs). Results: Results of alternative nostril breathing (ANB) on 1,377 participants have been reported based on the effects of systolic and diastolic blood pressure (SBP and DBP). Both the lone ANB and combined yoga programs resulted in significant reductions in SBP and DBP. Meta-analysis of the 6 trials with 525 participants demonstrated that ANB was better in reducing SBP than that of the control group (nonintervention or placebo) (mean difference [MD]: −7.16, 95% confidence interval [CI]: −7.86 to −6.45, I2: 93%). Moreover, ANB was better in reducing DBP than that of the control group (nonintervention or placebo) (MD: −5.16, 95% CI: −5.89 to −4.44, I2: 87%). Conclusion: The results of the study are valid; however, attention is needed when interpreting the results because the heterogeneity exceeds 75%. A systematic review of 14 studies found that ANB can improve cardiovascular indicators, such as SBP and DBP, as well as non-cardiovascular factors, such as fatigue, intraocular pressure, and memory. However, the review noted that implementing double blinding in studies on yoga breathing intervention is difficult, and most studies were not double-blinded, suggesting the need for high-quality RCTs in the future.
The Role of Perceived Stress in the Relation between Childhood Maltreatment and Severity of Alcohol Use Disorder: A Mediation Analysis
Authors: Bougelet Emilie , Deffaa Mirjam , Türkmen Cagdas , Kiefer Falk , Vollstädt-Klein Sabine , Gerhardt Sarah
Published: July 2024

Introduction: Experiences of Childhood Maltreatment (CM) relate to relapse and lower treatment success in Alcohol Use Disorder (AUD), one of the most prevalent substance use disorders. However, the exact mechanisms of this relationship still remain unclear. This study examines perceived stress and “drinking to cope with negative affect” (coping) as possible mediators in this relationship. Moreover, it aims at uncovering the differential effects of the subtypes of CM. Methods: N = 96 individuals (42% women; mean age 41 ± 13 years) including healthy controls and individuals with varying severity of AUD and CM completed the Alcohol-Dependence Scale, Childhood Trauma Questionnaire, Perceived Stress Scale and German Inventory of Drinking Situations. Mediation analyses including perceived stress as a mediator between CM (and subtypes) and severity of AUD, as well as a serial mediation of the relationship between CM and AUD severity by perceived stress and coping were conducted. Results: Perceived stress significantly mediated the relation between CM and AUD severity and the serial mediation by perceived stress and coping turned out significant. Subtype-specific analyses did not yield significant results. Conclusion: This study reinforces perceived stress as a potential mechanism in the relation between CM and AUD severity. Moreover, coping further mediated the relationship between CM and AUD severity. Our results suggest including screening for CM (subtypes) in clinical routine in order to individually emphasize interventions focusing on stress regulation, as well as on developing healthy coping mechanisms, in patients with AUD. This might prevent heightened stress sensitivity, relapse and further maintenance of AUD.
Inflammatory Alterations to Renal Lymphatic Endothelial Cell Gene Expression in Mouse Models of Hypertension
Authors: McDermott Justin G. , Goodlett Bethany L. , Creed Heidi A. , Navaneethabalakrishnan Shobana , Rutkowski Joseph M. , Mitchell Brett M.
Published: July 2024

Introduction: Hypertension (HTN) is a major cardiovascular disease that can cause and be worsened by renal damage and inflammation. We previously reported that renal lymphatic endothelial cells (LECs) increase in response to HTN and that augmenting lymphangiogenesis in the kidneys reduces blood pressure and renal pro-inflammatory immune cells in mice with various forms of HTN. Our aim was to evaluate the specific changes that renal LECs undergo in HTN. Methods: We performed single-cell RNA sequencing. Using the angiotensin II-induced and salt-sensitive mouse models of HTN, we isolated renal CD31+ and podoplanin+ cells. Results: Sequencing of these cells revealed three distinct cell types with unique expression profiles, including LECs. The number and transcriptional diversity of LECs increased in samples from mice with HTN, as demonstrated by 597 differentially expressed genes (p<0.01), 274 significantly enriched pathways (p<0.01), and 331 regulons with specific enrichment in HTN LECs. These changes demonstrate a profound inflammatory response in renal LECs in HTN, leading to an increase in genes and pathways associated with inflammation-driven growth and immune checkpoint activity in LECs. Conclusion: These results reinforce and help to further explain the benefits of renal LECs and lymphangiogenesis in HTN.
Evaluation of the Management of Urachal Carcinoma: A Single-Center Experience over 13 Years
Authors: Chen Hengxin , Wu Menghai , Chen Minfeng
Published: July 2024

Introduction: Urachal carcinoma is characterized by high malignancy, poor prognosis, and late stage of diagnosis. There is a lack of unanimous clinical treatment guidelines. We summarize the characteristics, treatment, and outcomes of urachal carcinoma from our center, hoping to provide a reference for diagnosis and treatment. Methods: We retrospectively analyzed the clinical data of 21 patients with urachal carcinoma who were treated at our center from January 2010 to August 2022, and all patients were followed up. Results: The average survival time was 67.1 ± 9.1 (ranging from 49.3 to 84.9) months. The average relapse-free survival was 48.8 ± 9.9 (ranging from 29.5 to 68.2) months. Six patients received adjuvant therapy, mainly chemotherapy. Five patients died during follow-up. Conclusions: Early physical examination may be helpful for early detection of urachal carcinoma. Surgical treatment is still preferred for localized urachal carcinoma. Lymph node dissection may facilitate accurate staging, and positive margin usually results in a worse prognosis. Adjuvant therapy, mainly chemotherapy, may help improve the prognosis. The application of radiotherapy, targeted therapy, and immunotherapy still needs further exploration.
Impact of Post-Acute Sequelae of COVID-19 on Lives of Patients Post-Intensive Care Unit Discharge: A Cross-Sectional Study
Authors: Jasem Zainab A. , Manee Fahad , Alqattan Danah M. , Smith Theresa M.
Published: July 2024

Objectives: Post-acute sequelae of SARS-CoV-2 (PASC) are known for their prolonged and persistent effects on patients. This study aimed to investigate the impact of the PASC on the quality of life (QOL) of patients, their levels of activity participation, and satisfaction with these levels, in addition to exploring whether the duration of post-intensive care unit (ICU) discharge is associated with the effects of PASC. Subject and Methods: This cross-sectional study included 134 patients with COVID-19 discharged from an ICU in Kuwait. Data were collected using two validated questionnaires: the World Health Organization Quality of Life-Brief (WHOQOL-BREF) and Satisfaction with Daily Occupations. Additionally, demographic information was collected, and 11 categories of related symptoms were investigated. Results: Most patients reported health issues post-ICU discharge. Furthermore, most PASC-related symptoms decreased over time, whereas a few increased. Notably, we observed a negative association between post-discharge duration and overall improvement in level of participation in activities of daily living. However, patients discharged from the ICU for more than 6 months demonstrated higher satisfaction with functional performance and improved QOL. Additionally, patients who received rehabilitation, and were vaccinated were less likely to have poor QOL. No significant sex differences were observed in the WHOQOL-BREF score. Conclusion: PASC adversely affected the daily functioning of patients, especially in leisure, social, and religious aspects. However, these effects lessened over time, with corresponding improvement in QOL. Additionally, patient satisfaction with functional performance increased over time. These findings shed light on the rehabilitation needs of patients with COVID-19.
Effects of Simvastatin on Inflammatory Response and Biological Behaviour of Adamantinomatous Craniopharyngioma
Authors: Li Weizhao , Zhang Yunxiao , Zhuang Yishan , Chen Rongjun , Xiong Zhiwei , Li Kai , Liu Fang , Xu Haiyan , Li Danling , Peng Junxiang
Published: July 2024

Introduction: The aim of this study was to investigate the autoinflammatory effect and biological behaviour of simvastatin (SIM) on adamantinomatous craniopharyngioma (ACP) cells. Methods: Craniopharyngiomas imaging, intraoperative observations, and tumour histopathology were employed to investigate the correlation between esters and craniopharyngiomas. Filipin III fluorescent probe verified the validity of SIM on the alternations of synthesized cholesterol in craniopharyngioma cells. The cell counting kit-8 (CCK8) assay detected the impacts of SIM on cell proliferation and determined the IC50 value of tumour cells. Reverse transcription polymerase chain reaction (RT-PCR) measured the expression of inflammatory factors. Flow cytometry technique detected the cell cycle and apoptosis, and cell scratch assay judged the cell migration. Meanwhile, Western blot was adopted to determine the expression of proteins related to inflammation, proliferation, and apoptosis signalling pathways. Results: In the ACP tumour parenchyma, many cholesterol crystalline clefts were observed, and the deposition of esters was closely associated with craniopharyngioma inflammation. After SIM intervention, a reduction in cholesterol synthesis within ACP was noted. RT-PCR analysis revealed SIM inhibited the transcription of inflammatory factors in ACP cells. Western blot analysis demonstrated SIM inhibited nuclear factor-kappa B p65 activation expression while promoted the expressions of Cl-caspase-3 and P38 MAPK. CCK8 assay indicated a decrease in ACP cell activity upon SIM treatment. Scratch assay signified that SIM hindered ACP cell migration. Flow cytometry results suggested that the drug promoted ACP cell apoptosis. Conclusion: SIM suppressed the inflammatory response to craniopharyngiomas by inhibiting craniopharyngioma cholesterol synthesis, inhibited proliferation of ACP cells, and promoted their apoptosis.
Treatments for Onychomycosis: A Bibliometric Analysis
Authors: Gupta Aditya K. , Taylor Daniel , Polla Ravi Shruthi , Wang Tong , Talukder Mesbah
Published: July 2024

Introduction: Oral antifungals were the earliest treatments to receive approval for the management of onychomycosis and have a long-standing record to support their efficacy. Topical antifungals and device-based treatments have been explored and some implemented in more recent years as alternatives to traditional oral antifungals. The present bibliometric analysis summarizes trends in publication frequency for onychomycosis treatment modalities over time and characterizes their body of literature in terms of types of studies available and relative level of evidence. Methods: A comprehensive literature search was performed using Web of Science and SCOPUS databases. Results: Covering all publications from 1970 to present day, our search identified oral therapeutics n = 295 articles (n = 63 randomized control trials [RCTs]), topical therapeutics n = 358 articles (n = 72 RCTs), and device-based treatments n = 158 articles (n = 37 RCTs). Spikes in research activity surround FDA approval of therapeutics for each treatment modality. Research activity within the last decade has focused on topical and device-based treatments. Evidence for efficacy of device-based treatments is lacking from relatively few high-quality RCTs. Conclusion: With growing concern for non-dermatophyte mold onychomycosis and terbinafine resistance, researchers should validate the efficacy and safety of device-based treatments with high-quality studies.
The relationship between mentally active sedentary behavior and cognitive function across different educational levels
Authors: Hu Julinling , Deng Qian , Yong Chan , Peng Jie , Kong Chuiran , Li Nanyan , Li Xianlan , Ye Qin , Liu Qianqian , Wang Yufei , Zhou Junmin
Published: July 2024

Introduction: How education affects the relationship between sedentary behavior and cognitive function remains unclear. The aim of this study was to investigate the relationship between mentally active sedentary behavior and cognitive function in rural older Chinese across different levels of education.
Methods: Data from 517 participants aged 60 years and older in rural China at baseline, 4 weeks, 8 weeks, 6 months, 12 months, and 24 months were analyzed. Univariate analysis was carried out using descriptive statistical techniques and bivariate analysis was performed using Linear mixed effects models.
Results: Total mentally active sedentary behavior time and playing cards/mahjong time were significantly associated with global cognition (0.27 points (95% CI, 0.15 to 0.39), P＜0.001; 0.30 points (95% CI, 0.18 to 0.41), P＜0.001, respectively), the attention dimension (0.08 points (95% CI, 0.02 to 0.14), P = 0.005; 0.10 points (95% CI, 0.04 to 0.16), P = 0.001, respectively), and the memory dimension (0.18 points (95% CI, 0.05 to 0.31), P < 0.001; 0.19 points (95% CI, 0.13 to 0.25), P＜0.001, respectively). Such associations were more pronounced in illiterate participants.
Conclusion: Our study suggested a positive association between mentally active sedentary behavior and cognitive function, with the association being more pronounced among illiterate older adults compared to the relatively well-educated. Future cognitive interventions should focus more on mentally active behavior. In addition, education-specific intervention strategy may be considered in cognitive interventions.
High Risk of Non-Melanoma Skin Cancer in Actinic Keratosis Patients with Skin of Color: A Nationwide Register-Based Cohort Study
Authors: Park Hyoung Soo , Baek Du Jin , Kim You Chan , Choi Jee Woong
Published: July 2024

Introduction: Actinic keratoses (AKs) are rough, scaly patches from UV exposure, increasing the risk of non-melanoma skin cancer (NMSC). This study examines AK incidence in Korea and its role as a risk factor for NMSC. Methods: A retrospective nationwide register-based cohort study analyzed 2,917 AK patients and 14,585 controls from 2002 to 2019. Patients diagnosed with AK were followed until NMSC occurrence, death, emigration, or December 2019. Results: AK incidence reached 44.8 per 100,000 person-years in 2019. The adjusted hazard ratio for NMSC in AK patients was 8.91 (95% confidence interval, 5.72–13.90). Higher NMSC risk was observed in female AK patients, those under 60 years, and those with lower income levels. The 16-year cumulative incidence of NMSC was 4.19% in AK patients versus 0.44% in controls. Conclusion: AK significantly increases the risk of NMSC in Koreans, highlighting the need for tailored surveillance and treatment strategies.
Enhanced Survival of Chronic Myelomonocytic Leukemia-Dysplastic over Proliferative Subtype after Allogeneic Hematopoietic Cell Transplant: A Tertiary Center Experience and Literature Review
Authors: Niehus Hunter D. , Sabile Jean , Maziarz Richard T. , Meyers Gabrielle , Cook Rachel , Gandhi Arpita P. , Saultz Jennifer N. , Rakshe Shauna , Kaempf Andy , Braun Theodore , Migdady Yazan
Published: July 2024

Introduction: CMML is a rare neoplasm with overlapping myelodysplastic and myeloproliferative features whose only potential cure is allogeneic hematopoietic cell transplantation (allo-HCT). Methods: This retrospective study examined 27 CMML patients with high-risk clinical features who underwent first allo-HCT at our institution between 2004 and 2022. Results: Nineteen patients were diagnosed with the proliferative subtype (CMML-MPN) and 8 with the dysplastic subtype (CMML-MDS). Median OS was 15 months post-HCT (95% CI: 5–71); OS at 1, 3, and 5 years was 52%, 35%, and 35%, respectively. Compared to those with CMML-MPN, patients with CMML-MDS had longer OS (median, 8.6 vs. 0.9 years; p = 0.025), RFS (4.4 vs. 0.5 years; p = 0.021), and GVHD-free, relapse-free survival (GRFS, 9.4 vs. 3.4 months; p = 0.033) as well as lower 1-year NRM (13 vs. 47%; p = 0.043), with the statistical significance of this CMML subtype effect maintained in multivariable models. High-risk cytogenetics were associated with shorter GRFS in the univariable (median, 3.1 vs. 6.2 months; p = 0.013) and multivariable (HR = 4.88; p = 0.006) settings. Conclusions: Patients who underwent transplant for CMML-MDS experienced substantially better outcomes than those transplanted for CMML-MPN. Future studies are needed for transplantation optimization in CMML, especially CMML-MPN.
Chronic Myeloid Leukemia in Adolescents and Young Adults: Clinicopathological Variables and Outcomes
Authors: Abdulla Mohammad A.J. , Aldapt Mahmood B. , Chandra Prem , El Akiki Susanna , Alshurafa Awni , Nashwan Abdulqadir J. , Fernyhough Liam J. , Sardar Sundus , Chapra Ammar , Yassin Mohamed A.
Published: July 2024

Introduction: Adolescents and young adults (AYAs) diagnosed with chronic myeloid leukemia (CML) constitute a significant demographic group, particularly in regions with youthful populations like Qatar. Despite the global median age of CML diagnosis being 65 years, Qatar’s age distribution reflects a younger cohort. This study investigates whether AYAs with CML exhibit distinct clinicopathological characteristics or outcomes compared to older age groups. Methods: A total of 224 CML patients were enrolled, including 114 AYAs (defined as ages 15 through 39). Demographic and clinical parameters, including gender, BMI, BCR-ABL1 transcript type, white blood cell (WBC) count, hemoglobin level, platelet count, and spleen size, were compared between AYAs and older patients. Prognostic scoring systems (Sokal, Hasford, EUTOS, and ELTS) and molecular response rates (MMR and DMR) were also evaluated. Results: AYAs demonstrated higher WBC counts at diagnosis (median 142.3 vs. 120; p = 0.037) and lower hemoglobin levels (10.5 vs. 11.40; p = 0.004) compared to older patients. Spleen size was significantly larger in AYAs (18.8 vs. 15.5; p = 0.001). While AYAs showed better prognostic scores by Sokal and Hasford criteria, EUTOS and ELTS scores indicated comparable risk stratification. However, AYAs exhibited lower rates of MMR (56.7 vs. 73.4%; p = 0.016) and achieved MMR at a slower pace (median time 130 vs. 103 months; p = 0.064). Similarly, the percentage of DMR was lower in AYAs (37.1 vs. 46.8%; p = 0.175). Conclusion: Despite their younger age, AYAs with CML displayed poorer prognoses compared to older patients. These findings underscore the importance of tailored management strategies for AYAs with CML to optimize outcomes in this distinct patient population. Key Point: AYAs are underrepresented in CML studies and risk scores, so this is the focus of this study.
Effects of Nitrate and Nitrite on Plaque pH Decrease and Nitrite-Producing and -Degrading Activities of Plaque in vitro
Authors: Yamamoto Yuji , Washio Jumpei , Shimizu Koichi , Takahashi Nobuhiro
Published: July 2024

Introduction: The purpose of this study was to investigate the effects of nitrate and nitrite on the pH-lowering activity of human plaque, the nitrite-producing and -degrading activities of human plaque, and their correlation. Methods: Nitrate and nitrite were added to human plaque suspensions collected from the buccal aspect of maxillary molars of patients visiting a general dental clinic, and changes in pH were measured with and without glucose addition. Nitrite-producing and -degrading activities were evaluated by adding nitrate and nitrite to the plaque suspension and measuring the increase and decrease in nitrite with Griess reagent, respectively. Results: The addition of nitrate inhibited both endogenous and glucose-induced plaque pH-lowering. The addition of glucose enhanced the production of nitrite from nitrate by about 3.3-fold. The addition of nitrite also inhibited endogenous plaque pH-lowering, but the addition of glucose promoted nitrite degradation by only about 1.1-fold. Nitrite-producing activity was positively correlated with age, but not with nitrite-degrading activity. Conclusion: This study revealed that nitrite was produced from nitrate and inhibited the pH-lowering activity of human plaque, which may contribute to caries control. Both nitrite-producing and -degrading activities occurred in human plaque, but no correlation was found between them. Furthermore, nitrite production was enhanced by glucose metabolism, which may function as a self-regulatory mechanism (resilience) to prevent excessive acidification by glucose metabolism.
Towards a Biologically Coherent Account of the Brain and How It Develops
Authors: Marshall Peter J.
Published: July 2024

Different conceptualizations of brain function have different implications for understanding the relation of neuroscience to the study of human development. In one view, the brain is an isolated computational device that passively processes stimuli delivered from an external world and then mediates a response. An alternative view, which is more consistent with the evolutionary history of brains, moves away from simple causal linkages between stimulus and response and instead emphasizes the inherent, ongoing activity of the individual. Here the individual is not directly instructed by information from its environment but instead shapes its own sensory inputs through its goal-directed activity. Related conceptual confusions around instructions and information can be found in accounts of brain development that either fall back on a genetic blueprint or that elevate the role of extrinsic experience. A more coherent approach brings together aspects of developmental and evolutionary biology while drawing on developmental systems theory and particular themes in embodied cognitive science. Such an approach spans qualitatively different frames of explanation across a range of spatiotemporal scales, necessitating a reconsideration of disciplinary boundaries. Fully engaging in this effort can yield a more integrative science of brain, mind, and behavior and an enriched understanding of human development.
The Progression of Stargardt Disease (ProgStar) as determined by spectral-domain optical coherence tomography over a 24-month period (ProgStar Report No. 19)
Authors: Strauss Rupert Wolfgang , Lang Lang , Ho Alexander , Jha Anamika , Ip Michael , Bernstein Paul S. , Birch David G. , Cideciyan Artur V. , Michel Michaelides , Audo Isabelle , Sunness Janet S. , Traboulsi Elias I. , Zrenner Eberhart , Sadda SriniVas R. , Janeschitz-Kriegl Lucas , West Sheila , Kong Xiangrong , Scholl Hendrik P.N. ,   for the ProgStar Study Group
Published: July 2024

Introduction: To evaluate the progression of atrophy as determined by spectral-domain optical coherence tomography (SD-OCT) in patients with molecularly confirmed ABCA4-associated Stargardt disease type 1 (STGD1) over a 24-month period in a multicenter prospective cohort study.
Methods: SD-OCT images from 428 eyes of 236 patients were analyzed. Change of mean thickness (MT) and intact area were estimated after semi-automated segmentation for the following individual layers in the central subfield (CS), inner ring (IR) and outer ring (OR) of the ETDRS grid: retinal pigment epithelium (RPE), outer segments (OS), inner segments (IS), outer nuclear layer (ONL) inner retina (IR) and total retina (TR).
Results: Statistically significant decreases of all outer retinal layers (RPE, OS, IS, and ONL) could be observed over a 24-month period both in decline of mean retinal thickness and intact area (p<.0001, respectively); whereas the inner retina showed an increase of retinal thickness in the central subfield and inner ring and remained unchanged in the outer ring.
Conclusions: Significant loss could be detected in outer retinal layers by SD-OCT over a 24-month period in patients with STGD1. Loss of thickness and/or intact area of such layers may serve as potential endpoints for clinical trials that aim to slow down the disease progression of STGD1.
Development of a Patient-Centered Pathway of Care for Retinoblastoma Patients: A Mixed-Methods Pilot Study
Authors: Ristevski Ivana , Flegg Kaitlyn , Al-Hammadi Mawj , Livingstone Morgan , Dorna Taline , Low Leslie , Robert Jill , Ulster Alissa , Kletke Stephanie , Mallipatna Ashwin , Paton Katherine , Dimaras Helen ,   on behalf of the Canadian Retinoblastoma Research Advisory Board
Published: July 2024

Introduction: Retinoblastoma treatment and follow-up is complex and varies between patients. Pathways of care can enhance the quality of care, patient outcomes, safety, satisfaction, and resource optimization. Developing a pathway of care for retinoblastoma was identified as a top research priority by the retinoblastoma community. This study aimed to co-design and pilot a pathway of care called the “Retinoblastoma Journey Map” tailored for caregivers of newly diagnosed children with retinoblastoma. Methods: A working group of patients, health professionals and researchers used human-centered design to ideate, prototype and refine the Retinoblastoma Journey Map. Caregivers of affected children were recruited to use and evaluate the Map. Mixed-methods data was collected on feasibility, acceptability, usability and perceived impact on communication, self-efficacy, anxiety, depression, and the quality of physician-patient interaction. Results: The Retinoblastoma Journey Map consisted of an illustrated roadmap with 25 child-friendly stickers covering clinical treatment, medical education and milestones. Quantitative analysis revealed that the Map was feasible, acceptable, and useable; however, no significant effect on communication, self-efficacy, anxiety, depression or quality of physician-patient interaction was observed. Qualitative analysis identified 6 themes: Primary Use; Challenges; Impact; Limitations; Feasibility, Acceptability, and Usability; and Unmet Needs. Conclusion: A pathway of care for retinoblastoma, co-designed by researchers, health professionals, and patients, was useable, acceptable, and feasible by caregivers of children with retinoblastoma. While significant effects on communication and physician-patient interaction were not observed, “legacy building” – documentation of the pathway of care by families for later education of their child – emerged as an unanticipated yet important use of the Retinoblastoma Journey Map.
Effect of Water Bath versus Refrigerator Thaw on Cryoprecipitate Fibrinogen and Factor VIII Content Using a Pre-Pooled Plasma Experimental Approach
Authors: Swanson Jessie A. , Soland Michelle A. , Hammel Scott A. , Juskewitch Justin E.
Published: July 2024

Introduction: Originally developed as a form of factor VIII concentrate, cryoprecipitate’s primary clinical use has changed to treat fibrinogen deficiency as highlighted by recent approval of pathogen-reduced cryoprecipitated fibrinogen concentrates. The methodology by which frozen plasma is thawed during cryoprecipitate manufacturing is not standardized. This study compared plasma thawing techniques on cryoprecipitate fibrinogen and factor VIII levels. Methods: A matched pairwise experimental design was employed across three experiments to compare plasma thawing approaches (water bath or 24–48 h refrigerator). Each experiment involved the creation of 10 sets of ten homogenous frozen plasma pools which were then used to manufacture 10 pairs of cryoprecipitate pools differing only by assigned plasma thawing method. Total cryoprecipitate fibrinogen and factor VIII content between plasma thawing methods were compared using matched t-testing within each experiment. Results: Compared to water bath thawing, 24-h refrigerator thawing led to significantly higher cryoprecipitate fibrinogen content (2,554 mg vs. 1,824 mg; p < 0.001) and significantly lower cryoprecipitate factor VIII content (601 IU vs. 709 IU; p < 0.001). Longer refrigerator thaw times (36 and 48 h) led to significantly higher cryoprecipitate fibrinogen content than 24-h refrigerator thaw (3,180 mg vs. 2,956 mg and 2,893 mg vs. 2,483 mg, respectively; p = 0.01–0.03). Conclusion: Using homogenous frozen plasma units in a matched pairwise experimental design, refrigerator plasma thawing led to superior cryoprecipitate fibrinogen yields and inferior cryoprecipitate factor VIII yields. When maximizing cryoprecipitate fibrinogen yields, refrigerator plasma thawing, and in particular longer thawing times (36–48 h), should be considered.
Differences in Iron Kinetics during Cardiac Load between Patients with Atrial Fibrillation and Those with Sinus Rhythm
Authors: Kamihara Takahiro , Kawano Reo , Kinoshita Tomoyasu , Omura Takuya , Kaneko Shinji , Hirashiki Akihiro , Kokubo Manabu , Shimizu Atsuya
Published: July 2024

Introduction: The prevalence of atrial fibrillation (AF) increases with age. Although most AF cases are caused by irregular electrical impulses near the pulmonary vein, not all elderly individuals develop AF. Moreover, risk factors such as hypertension and diabetes do not always lead to AF, even in severe conditions such as pneumonia. We aimed to examine iron kinetics, including ferritin, in patients with AF and individuals in normal sinus rhythm (NSR) using peripheral blood samples. Methods: This case-control study included 178 patients who visited the outpatient clinic of a cardiovascular and arrhythmia specialist at the National Center for Geriatrics and Gerontology between August and October 2023. Patients with missing iron-related blood tests and those with pacemaker implantation were excluded. Iron parameters (ferritin, free iron, transferrin saturation) were compared between AF (n = 53) and NSR (n = 125) groups. Results: The AF group had higher log brain natriuretic peptide (BNP) levels, indicating increased cardiac load (AF 2.18 vs. NSR 1.53). However, there were no significant differences in iron parameters between the AF and NSR groups. After matching for age, sex, and coronary artery disease, the AF group showed an increasing trend in ferritin and a decreasing trend in free iron with BNP elevation, suggesting chronic inflammation. In contrast, the NSR group showed no significant changes in iron parameters with BNP elevation. Conclusion: Patients with AF are more likely to have elevated ferritin levels and decreased free iron levels during cardiac overload. Thus, they are more likely to present with chronic inflammation associated with cardiac overload in AF. Future studies should investigate the mechanisms underlying this phenomenon and its implications for AF treatment.
Homozygous Intragenic Deletion in WDR62 in Siblings with Primary Microcephaly
Authors: Singh Suzena M. , Maurya Rajesh K. , Moirangthem Amita
Published: July 2024

Introduction: Primary microcephaly is genetically heterogeneous. Despite the rapid evolution of scientific information and bioinformatic tools, etiology remains elusive in more than half of the affected population. A substantial fraction of these undiagnosed cases is anticipated to have large structural variations in one of the causative genes. This class of variations has been difficult to detect by exome sequencing. Case Presentation: We report a sibling pair with global developmental delay, microcephaly, and brain abnormalities who were recruited under the Indian Undiagnosed Disease Program (I-UDP) for further evaluation after an uninformative initial exome sequencing. Conclusion: Copy number analysis using whole genome sequencing data detected a large homozygous deletion of 9.78 kb encompassing exon 1 to exon 3 of WDR62 (OMIM*613583). These results were further validated by performing comparative quantification of the copy number of deleted exons in both siblings and parents.
Medical Cannabis Prescription Practices and Quality of Life in Thai Patients: A Nationwide Prospective Observational Cohort Study
Authors: Stienrut Pramote , Pongpirul Krit , Phutrakool Phanupong , Savigamin Chatuthanai , Sermsaksasithorn Pim , Chanhom Ornpapha , Jeamjumrus Panthakan , Pongchaichanon Pimlada , Nootim Preecha , Soisamrong Mala , Chuthaputti Anchalee , Wanaratna Kulthanit , Thaneerat Tewan
Published: July 2024

Introduction: The legalization of cannabis in Thailand has renewed interest in its traditional medical use. This study aimed to explore the prescribing patterns of traditional practitioners and assess the impact of cannabis oil on patients’ quality of life, with a specific focus on comparing outcomes between cancer and non-cancer patients. Methods: We conducted a prospective observational cohort study across 30 sites in 21 Thai provinces to analyze the use of “Ganja Oil,” a cannabis extract in 10% coconut oil, prescribed for symptoms like pain, anorexia, and insomnia across a diverse patient group, including cancer and migraines. Quality of life was assessed using the Edmonton Symptom Assessment Scale (ESAS) and EQ-5D-5L at baseline, 1, 2, and 3 months. The study included a predefined subgroup analysis to compare the effects on cancer versus non-cancer patients. Data management was facilitated through Research Electronic Data Capture (REDCap), with statistical analysis performed using Stata/MP. Results: Among 21,284 participants, the mean age was 54.10 ± 15.32 years, with 52.49% being male. The baseline EQ-5D-5L index was 0.85 ± 0.24. Significant differences in EQ-5D-5L indices were seen between cancer patients (0.79 ± 0.32) and non-cancer patients (0.85 ± 0.23; p < 0.001). ESAS scores also differed significantly between these groups for all symptoms, except anxiety. The most frequent prescription of Ganja Oil was oral administration at bedtime (88.26%), with the predominant dosage being three drops daily, approximately 0.204 mg of tetrahydrocannabinol in total. Posttreatment, significant improvements were noted: the EQ-5D-5L index increased by 0.11 points (95% CI: 0.11, 0.11; p < 0.001) overall, 0.13 points (95% CI: 0.12, 0.14; p < 0.001) for cancer patients, and 0.11 points (95% CI: 0.10, 0.11; p < 0.001) for non-cancer patients. ESAS pain scores improved by −2.66 points (95% CI: −2.71, −2.61; p < 0.001) overall, −2.01 points (95% CI: −2.16, −1.87; p < 0.001) for cancer patients, and −2.75 points (95% CI: −2.80, −2.70; p < 0.001) for non-cancer patients, with similar significant improvements in other symptoms. Conclusion: Our study indicates potential benefits of Ganja Oil for improving quality of life among Thai patients, as a complementary treatment. These findings must be viewed in light of the study’s design limitations. Further controlled studies are essential to ascertain its efficacy and inform dosing guidelines.
Quantifying Physical Resilience after Knee or Hip Surgery in Older Australian Women Based on Long-Term Physical Functioning Trajectories
Authors: Peeters Geeske , de Munck Isa , Tooth Leigh , Melis René
Published: July 2024

Introduction: To improve outcomes after knee or hip surgery, better insight is needed in long-term recovery patterns in the context of ageing-related decline. We examined long-term trajectories of physical functioning (PF) in older women with and without hip and knee surgery and described profiles of cases with higher and lower resilience after surgery. Methods: This observational study used data from 10,434 women (73–79 years) who completed survey 2 of the Australian Longitudinal Study on Women’s Health. Data were used from surveys 2 (1999) to 6 (2011). Covariable-adjusted linear mixed models were run to examine the surgery-by-time (−12 to +12 years) interaction in association with PF (SF-36 subscale). The differences between observed and expected PF were calculated, with positive/negative values reflecting higher/lower resilience, respectively. Results: Women with hip surgery (n = 982) had lower PF than those without surgery (n = 8,117) (p < 0.001). Among hip surgery patients, the decline was more rapid pre-surgery than post-surgery (Δslope = −0.7, p < 0.001). Women with knee surgery (n = 1,144) had lower PF than those without surgery (n = 7,971), but with a slower rate of decline (p = 0.01). Among knee surgery patients, the rate of decline was similar pre- and post-surgery (Δslope = −0.3, p = 0.25). Both in hip and knee patients, women with higher resilience had fewer comorbidities and symptoms and were more often physically active and independent in daily activities than those with lower resilience (all p < 0.05). Conclusion: Compared with women without surgery, PF was lower and declined more rapidly around the time of hip surgery, but not for knee surgery. Women with better long-term recovery after surgery had fewer health problems and were more independent around the time of surgery.
Lymphocyte-to-Monocyte Ratio Predicts Survival for Intraductal Papillary Mucinous Neoplasm with Associated Invasive Carcinoma of the Pancreas: Results from a High-Volume Center
Authors: Cui Ming , Hu Ya , Zheng Bang , Chen Tianqi , Dai Menghua , Guo Junchao , Zhang Taiping , Yu Jun , Liao Quan , Zhao Yupei
Published: July 2024

Introduction: Intraductal papillary mucinous neoplasm (IPMN) is an important precursor lesion of pancreatic cancer. Systemic inflammatory parameters are widely used in the prognosis prediction of cancer; however, their prognostic implications in IPMN with associated invasive carcinoma (IPMN-INV) are unclear. This study aims to explore the prognostic value of systemic inflammatory parameters in patients with IPMN-INV. Methods: From 2015 to 2021, patients with pathologically confirmed IPMN who underwent surgical resection at Peking Union Medical College Hospital were enrolled. The clinical, radiological, and pathological data of the enrolled patients were collected and analyzed. Preoperative systemic inflammatory parameters were calculated as previously reported. Results: Eighty-six patients with IPMN-INV met the inclusion criteria. The lymphocyte-to-monocyte ratio (LMR) was the only systemic inflammatory parameter independently associated with the cancer-specific survival (CSS). An LMR higher than 3.5 was significantly associated with a favorable CSS in univariate (hazard ratio [HR] 0.305, p = 0.003) and multivariate analyses (HR 0.221, p = 0.001). Other independently prognostic factors included the presence of clinical symptoms, cyst size, N stage, and tumor differentiation. Additionally, a model including LMR was established for the prognosis prediction of IPMN-INV and had a C-index of 0.809. Conclusions: Preoperative LMR could serve as a feasible prognostic biomarker for IPMN-INV. A decreased LMR (cutoff value of 3.5) was an independent predictor of poor survival for IPMN-INV.
Female Patients with Small Cell Lung Cancer Have Better Survival than Males with Extensive but Not Limited Disease
Authors: Tas Faruk , Ozturk Akin , Erturk Kayhan
Published: July 2024

Introduction: Several previous studies have explored whether sex has prognostic significance in patients with small cell lung cancer (SCLC). In this retrospective study, we aimed to show the clinical significance of sex in SCLC patients. Methods: A total of 378 SCLC patients were assessed retrospectively. Results: Sixty-one (16.1%) patients were women; 26 of 131 (19.9%) patients had limited disease (LD-SCLC); and 14.2% of patients (35 of 247 patients) had extended disease (ED-SCLC). In all SCLC patients, regardless of stage, female patients were more likely to be nonsmokers (7.7 vs. 1%, p = 0.04 for LD-SCLC; and 11.4 vs. 1.4%, p = 0.001 for ED-SCLC) and more often to be anemic (26.9 vs. 11.4%, p = 0.04 for LD-SCLC; and 45.7 vs. 28%, p = 0.03 for ED-SCLC). While women with LD-SCLC were diagnosed younger (<60) than men (65.4 vs. 37.1%, p = 0.009), they had larger (>5 cm) tumors (69.2 vs. 42.9%, p = 0.01). Moreover, obesity (77.1 vs. 56.4%, p = 0.02) and less weight loss (88.6 vs. 73.6%, p = 0.04) were more common in women with ED-SCLC than in men. However, there were no associations between sex and significant prognostic factors, such as performance status, metastasis site, serum LDH level, response to chemotherapy, and disease recurrence. Outcomes in LD-SCLC patients were found to be similar between sexes; median overall survivals in women compared to men was 18 versus 15 months, respectively (p = 0.8). On the other hand, female patients with ED-SCLC had better survivals; median survivals for women versus men were 10 versus 7 months, respectively (p = 0.008). This significance for female ED-SCLC patients was also maintained in the multivariate analysis (p = 0.001). Conclusion: While the survival rates of female patients, who constitute a small proportion of SCLC patients, are no different from men in LD-SCLC, they are better in ED-SCLC.