bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Surveillance and Evolutionary Dynamics of Influenza A Virus in Sri Lanka
Authors: Jayadas Tibutius , Jeewandara Chandima , Senadheera Bhagya , Kuruppu Heshan , Wickramanayaje Rivindu , Bary Farha , Wijewickrama Ananda , Manilgama Suranga , Gamage Manouri , Perera Nilanka , Ogg Graham , MALAVIGE Gathsaurie
Published: October 2024

Background
Influenza A has been named as a priority pathogen by the WHO due to the potential to cause pandemics. Genomic sequencing of influenza strains is important to understand the evolution of the influenza strains and also to select the appropriate influenza vaccines to be used in the different influenza seasons in Sri Lanka. Therefore, we sought to understand the molecular epidemiology of the influenza viruses in the Western Province of Sri Lanka, including mutational analysis to investigate the evolutionary dynamics.
Methods
A total of 349 individuals presenting with fever and respiratory symptoms were enrolled in this study from November 2022 to May 2024. Nasopharyngeal and oropharyngeal specimens were collected and screened using quantitative PCR to detect Influenza A, Influenza B, and SARS-CoV-2. Subtyping and genomic sequencing was carried out on influenza A strains using Oxford Nanopore Technology.
Results
Influenza A was detected in 49 (14%) patients, influenza B in 20 (5.7%) and SARS-CoV-2 in 41 (11.7%). Co-infections were observed in five participants. The phylogenetic analysis assigned the H1N1 HA gene sequences within the 6B.1A.5a.2a clade. The HA gene of the H1N1 sequences in 2023 were assigned as belonging to the subclades C.1, C.1.2, and C.1.8, while the 2024 sequences were assigned to subclades C.1.8 and C.1.9. The H3N2 sequences from 2023 were assigned to the 3C.2a1b.2a.2a.1b clade and subclade G.1.1.2, while the 2024 sequences were assigned to the 3C.2a1b.2a.2a.3a.1 clade and subclade J.2. The K54Q, A186T, Q189E, E224A, R259K, K308R, I418V, and X215A amino acid substitutions were seen in the H1N1 in the 2023 and 2024 sequences. The 2024 H1N1 sequences additionally exhibited further substitutions, such as V47I, I96T, T120A, A139D, G339X, K156X, and T278S.
Conclusion
In this first study using genomic sequencing to characterize the influenza A strains in Sri Lanka, which showed different influenza A viruses circulating in an 18-month period. As the Sri Lankan strains also had certain mutations of unknown significance, it would be important to continue detailed surveillance of the influenza strains in Sri Lanka to choose the most suitable vaccines for the population and the timing of vaccine administration.
Six-Day Extreme Challenge: Can ECMO with Axillary Artery Cannulation Truly Reduce Cardiac Afterload? A Case Report A Case Report and minireview
Authors: Zhang Zhou-xing , Zeng Xiao-Kang , Qiu Chen-hui , Hu Wei , Zhu Ying , Yang Jing
Published: October 2024

Objective
The use of axillary artery cannulation in extracorporeal membrane oxygenation (ECMO) for patients with cardiogenic shock is gaining traction due to its potential to reduce cardiac afterload. However, clinical outcomes often diverge from theoretical expectations. This article presents a case study of a patient who experienced cardiac arrest and initiated veno-arterial ECMO (V-A ECMO) support 2 hours and 40 minutes after undergoing cardiopulmonary resuscitation (CPR). Despite ECMO intervention, the patient's aortic valve remained closed for up to six days. Transitioning from femoral to axillary artery cannulation did not yield a marked improvement in cardiac afterload. In the absence of abilities for atrial septostomy, conservative management was implemented, ultimately resulting in the normalization of aortic valve function and the patient's regained consciousness. This article seeks to examine the potential benefits and limitations of axillary artery cannulation in the context of ECMO for cardiogenic shock.
Methods
Following prolonged CPR, the patient experienced severe myocardial dysfunction and an impaired ability to open the aortic valve. The transition from femoral to axillary artery cannulation did not result in a significant reduction in cardiac afterload. However, through the optimization of ECMO parameters, intra-aortic balloon pump (IABP) support, improved fluid management, and tailored anticoagulation therapy, the patient’s cardiac function gradually recovered.
Results
After six days of therapeutic interventions, the patient's aortic valve function returned to normal, and consciousness was restored.
Whole genome transcriptional analysis of intestinal biopsies and blood cells indicate genes involved in antioxidant defense systems and antigen presentation in the pathogenesis of celiac disease
Authors: Naluai Åsa Torinsson , Sabbag Shafir , Abrahamsson Sanna , Gudjónsdóttir Audur H , Arnell Henrik , Agardh Daniel
Published: October 2024

Background: Celiac disease is closely linked to HLA-risk haplotypes, but non-HLA genes also play a significant role in disease susceptibility. In this study, we explore the molecular pathways involved in celiac disease by analyzing the differential expression of genes in both the gut and peripheral blood across various celiac disease phenotypes.
Methods: Whole genome RNA sequencing was performed on 298 samples from intestinal mucosa and peripheral blood from 81 children with celiac disease and 68 disease controls. Enrichr pathway analysis of top differentially expressed genes were performed.
Results: Overall, 7151 genes in intestinal biopsies and 532 genes in blood samples were differentially expressed between celiac cases and controls. Compared with controls, GBP1 (p=1.05×10-14) and TGM2 (p= 5.92×10-8), encoding for the protein tissue transglutaminase (TG2), the main autoantigen in celiac disease, were two of top up-regulated genes in intestinal biopsies from celiac cases. In contrast, PRKCD, encoding for the protein PKC-δ, also reported as an autoantigen in celiac disease, was down-regulated in intestinal biopsies of celiac cases compared with controls (p=4.61×10-5). The topmost differentially expressed genes in peripheral blood were HLA-DQB1 and HLA-DQB2. Among pathways identified as transcriptionally differentiated were antioxidant defense systems (e.g., Nrf2, glutathione, ergothioneine and caffeic acid metabolism), MHC class 1 antigen presentation, amino acid transport, mTORC1, bile secretion, liver homeostasis, the complement system and interferon signaling.
Conclusions: The differential expression of numerous genes across various molecular pathways suggests a complex molecular network related to liver metabolism and immunity, playing a role in the pathogenesis of celiac disease.
Pre-treatment prediction of response to neoadjuvant chemotherapy in breast cancer patients using a nomogram based on findings from cone-beam breast computed tomography
Authors: Zhang Yu-jiao , Liang Zhu-ming , Huang Xiang-yang , Yu Yan-jing , Mo Ya-nan , Luo Ning-bin , Ji Yi-nan
Published: October 2024

Background
Cone-beam breast computed tomography (CBBCT) can provide detailed information about breast tissue, but whether such information can help predict treatment response is unclear.
Purpose
To develop a nomogram based on findings from CBBCT as well as conventional clinical variables to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in patients with breast cancer.
Materials and Methods
Medical data were retrospectively analyzed for a consecutive series of women with breast cancer who underwent NAC followed within three months by resection surgery at our hospital between September 2019 and March 2022. Patients were randomized into a development cohort and validation cohort. A nomogram to predict pCR after chemotherapy was formulated based on uni- and multivariate logistic regression of pre-treatment data from the development cohort, and it was tested against data from the validation cohort. The performance of the nomogram was evaluated in terms of the area under receiver operating characteristic curves (AUC), calibration plots and decision curve analysis.
Results
Of the 215 breast cancer patients in this study, 69 (32.1%) achieved pCR after NAC. Multivariate logistic regression of the development cohort linked such response independently to absence of estrogen receptor (ER) expression, expression of human epidermal growth factor receptor 2 (HER-2), small tumor diameter and non-mass enhancement (NME) on CBBCT. The resulting nomogram predicted response with AUCs of 0.841 (95% CI: 0.78–0.90) in the development cohort (n = 150) and 0.836 (95% CI: 0.74–0.94) in the validation cohort (n = 65), and it was efficient against data from both cohorts based on calibration curves. Decision curve analysis suggested that the nomogram is clinically useful.
Conclusion
A nomogram incorporating molecular biomarkers and findings from CBBCT may help predict breast cancer patients more likely to respond to NAC.
The completeness, accuracy and impact on alerts, of wearable vital signs monitoring in hospitalised patients
Authors: Wilson Anthony Joseph , Parker Alexander J , Kitchen Gareth B , Martin Andrew , Hughes-Noehrer Lukas , Nirmalan Mahesh , Peek Niels , Martin Glen , Thistlethwaite Fiona
Published: October 2024

Background
Use of wearable vital signs sensors to monitor hospitalised patients is growing but uncertainty exists about completeness of data capture and accuracy of measurements. Implications for track and trigger systems are unclear.
Methods
In this observational study, adult inpatients with Covid-19 wore four wearable sensors recording heart rate/respiratory rate (HR/RR), oxygen saturation (SpO2), axillary temperature and blood pressure (BP). Wearable vitals were paired with traditional vitals recorded concurrently. The accuracy of the wearable vitals was assessed using traditional vitals as the reference. National early warning (NEWS2) scores were calculated using wearable and traditional vitals.
Results
48 patients were monitored for 204 days with the sensors. Median sensor wear was 3.9(IQR:1.7-5.9), 3.9(IQR:1.6-5.9) and 3.8(IQR:0.9-5.9) days for HR/RR, temperature and SpO2 respectively. The BP cuff was worn for median 1.9(IQR:0.9-3.8) days in 33 patients. Length of hospital stay was 8(IQR:6-13) days. Completeness of data capture was 84% for HR/RR, 98% for temperature, 72% for SpO2 and 36% for BP.
There were 1632 HR, 1613 RR, 1411 temperature, 1294 SpO2 and 51 BP wearable-traditional measurement pairs. 59.7% of HR pairs were within ±5bpm, 38.5% of RR pairs within ±3breaths/min, 24.4% of temperature pairs within ±0.3oC, 32.9% of SpO2 pairs within ±2% and 39.0% of BP pairs within ±10mmHg. Agreement between wearable and traditional RRs was poor at high RRs.
613 NEWS2 scores were calculated using wearable-traditional HR, RR, temperature and SpO2 pairs. The median NEWS2traditional was 1(IQR:1-2) and the median NEWS2wearable was 4(IQR:3-6). Using traditional NEWS2 alerts as a reference, 86% (225/262) of wearable NEWS2 5+ alerts and 89% (82/92) of wearable NEWS2 7+ alerts were false positives.
Conclusions
Agreement between vital signs recorded by wearable sensors and concurrent traditional vitals is poor. Data from wearable sensors should not be used in existing track and trigger systems.
Increased Left Ventricular Mass As A Marker Of Left Ventricular Hypertrophy In Normotensive Type2 DM Patients
Authors: Saad Moustafa Kamal Eldin Ibrahim Khalil , Gomaa Mohamed Saleh , Ewais Abdelrahman Ahmed , Alamir Maher Abobaker , Mahmoud Mohamed Shaban Hashem
Published: October 2024

BACKGROUND: Diabetes is one of the most important metabolic conditions responsible for left ventricular (LV) dysfunction including LV hypertrophy. Increased left ventricular mass (LVM) and left ventricular mass index (LVMI) are strong predictive factors of LV hypertrophy.
Aims: This study aims to illustrate the clinical significance of using echocardiography in detecting left ventricular hypertrophy in normotensive patients with type 2 Diabetes mellitus.
Materials and Methods: our study included one hundred participants who were distributed into two groups ;Group A which included normotensive patients with type 2 DM & Group B which included normotensive non-diabetic patients as a control group.
RESULTS: LVM values were significantly higher in diabetic cases than controls (187.11 ± 60.83 vs. 119.15 ± 41.87, p<0.001). As well as, LVMI values were significantly higher in diabetic cases than controls (96.64 ± 29.84 vs. 63.17 ± 20.38, p<0.001), Proportion of abnormal LVMI was higher in diabetic cases than controls (56% vs. 6%, p<0.001), There was a statistically significant positive correlation between LVM and several study parameters including mainly disease duration (r=0.369, p=0.008), FBS (r=0.478, p<0.001), 2HPP (0.400, p=0.004), HA1C (%) (r=0.589, p=0.003), LVEDD (r=0.790, p<0.001), LVESD (r=0.388, p=0.005), SWT (r=0.897, p<0.001), PWT (r=0.808, p<0.001), and LA (r=0.322, p=0.022).
CONCLUSION: Left ventricular mass is significantly higher in normotensive type 2 DM patients when compared to controls. LVM is a good marker of LVH among normotensive diabetics and is markedly correlated with DM control and duration.
Repeated monochromatic low-level red-light versus 0.01% atropine therapy for slowing myopia progression in children—a randomized controlled trial
Authors: Fu Aicun , Wang Weiqun , Zhong Mei , Shang Lili , Chang Minghang , Zheng Guangying , Jin Xuemin
Published: October 2024

Purpose
This research was designed to compare the effectiveness of repeated monochromatic low-level red-light (RMLRL) and 0.01% atropine in controlling myopia and axial elongation in myopic children.
Methods
We conducted a prospective, randomized, and single-blind controlled trial. A total of ninety-one children with myopia between the ages of 6 and 12 were selected for this study. These children had a cycloplegic spherical equivalent refraction (SER) ≥-5.00 D and ≤-0.75 D for each eye. The participants underwent random assignment in a 1:1 ratio between two experimental groups: the RMLRL group (n = 46, exposed to 650 nm red light passing through the pupil to the fundus, twice daily for 3 min with a minimum 4 h interval between each session) and 0.01% atropine group (n = 45, applied a single drop of 0.01% atropine bilaterally every night). The primary measured outcomes comprised alterations in SER and axial length (AL) after a duration of six months, while the secondary outcomes included changes in the subfoveal choroidal thickness(SFChT) and choroidal vessel volume (CVV).
Results
At the six-month follow-up, there were 45 children (97.8%) in the RMLRL group and 42 children (93.3%) in the 0.01% atropine group. The SER change was 0.24 ± 0.30 D compared to -0.29 ± 0.38 D (p < 0.001), and the change in AL was − 0.09 ± 0.14 mm compared to 0.15 ± 0.16 mm (p < 0.001) in the RMLRL and 0.01% atropine groups. The change in SFChT was 41.47 ± 34.27 um compared to 2.38 ± 16.69 µm (p < 0.001) in the RMLRL and 0.01% atropine groups. The CVV change was 0.01 ± 0.01 compared to 0.00 ± 0.01 (p < 0.001) in the corresponding two groups. No serious adverse events were reported in either the RMLRL or 0.01% atropine groups.
Conclusions
After six months of treatment, RMLRL had better effects than 0.01% atropine in preventing myopic progression and axial elongation among children with myopia in the central region of Mainland China.
Assessment the Contribution of the Major Quality Influencing Factors on the Measurements of TLS Scan
Authors: Mala Bakhtyar , Al-Shrafany Dleen Muhammed Salih
Published: October 2024

Surface qualities, range detectors, and measuring travel time are all major quality-influencing factors that affect the position accuracy of the measured point clouds by the terrestrial laser scanner (TLS). We conducted experimental tests using ScanStation2 TLS to investigate the accuracy of the scanned point clouds at various incident angles and ranges, and then examined the influence of different scanned surfaces on roughness and reflectivity. In this study, we selected four distinct surface properties from various materials (glass, steel, wood, ekoplast, and adhesive total station (TS) target), and painted three of these materials in five different colors to investigate the influence of colored surfaces on the reflected measured point clouds. During the experiment, approximately 250 scans were recorded, as the chosen materials were scanned at six scan angles (0, 15, 30, 45, 60, and 75) and ranges of 5m, 20m, 40m, and 60m. The experiment's findings show that, at various incident angles, smooth surfaces have a greater impact on the accuracy of the measured 3D points than do rough surfaces. Conversely, the total RMSEs of the red and black colors were greater than those of the blue, green, and white colors. At 0˚ incident angle, the TS target reflects approximately 20 cm closer to the TLS than the other materials; this difference decreases as the scan angle increases. In comparison to the other materials, the difference becomes about 2 mm at a 75˚ incidence angle. With the exception of the 30˚ scan angle of wood material, the maximum RMSE of rough materials is less than 1 cm, while the highest RMSE for smooth surfaces at 45˚ glass material is 4 cm. Moreover, the intensity of different materials varies significantly. For example, smooth materials like steel and glass have varying degrees of accuracy because of their respective properties. We have created a best-fit patch for all the scanned points to detect their deviation and characterize a suitable correction method. Due to the huge number of point clouds that resulted from those hundreds of scans at different conditions, it is very difficult and complex to directly apply a point position correction for all those complicated scanning conditions. Therefore, in this study, a comprehensive and intensive Python programming code was developed to correct a large number of point cloud positions within a standard processing time. This, in turn, contributes to the process's time and cost savings. Interestingly, this developed code is a novel procedure for correcting TLS point clouds at different measurement conditions, so it will be a good suggestion to add it to the Cyclone software.
Pseudocapsule Thickness is Positively Associated with Prognosis in Patients with Clear Cell Renal Cell Carcinoma
Authors: Xi Wei , Hou Yingyong , Hou Jun , Guo Jianming
Published: October 2024

Background
Tumour pseudocapsule shows plasticity, whose representative indicator- pseudocapsule thickness- was little studied in clear cell renal cell carcinoma (ccRCC).
Methods
We enrolled 1037 ccRCC patients who underwent surgery between 2006 and 2013 at our institution. The patients did not receive therapy before surgery and were confirmed to have a pathological pseudocapsule. The associations of pseudocapsule thickness with overall survival and progression-free survival were studied using multivariable Cox regression analyses. Patients were stratified using points of maximum separation. Influential factors were examined with logistic regression.
Results
The average thickness was 0.47 mm (median: 0.43, interquartile range: 0.28–0.6). The average follow-up was 92.1. In multivariable analyses, every 0.1-mm increase in thickness resulted in a decreased risk of death (hazard ratio (HR) 0.906, p = 0.011) but not progression (HR 0.948, p = 0.105). The estimated 10-year overall survival rates were 74.9%, 83.3%, 87.8%, 90.1% and 91.0%, respectively, and the 10-year progression-free survival rates were 69.6%, 76.6%, 80.8%, 83.1% and 84.1%, respectively, with the best cut-off value being approximately 0.37 mm. The results of logistic regression revealed that female sex (p < 0.001), age (p = 0.002), a higher neutrophil count (p = 0.011), large tumour size (p < 0.001) and necrosis (p = 0.011) were independently associated with a thin pseudocapsule (≤ 0.37 mm).
Conclusions
Pseudocapsule thickness is heterogeneous in clear cell renal cell carcinoma. Generally, increased thickness is associated with improvement in long-term survival. A pseudocapsule being 0.37mm or thinner is mostly influenced by both systematic and tumor-related parameters.
Phyllodes tumor of the distal end of ureter: A report of an extremely rare case
Authors: Xu LiXia , Song PengTao , Pin JinLiang
Published: October 2024

Background
The phyllodes tumor (PT) is a biphasic fibroepithelial lesion which most commonly found in breast tissue, whereas they are uncommon in ureter tissue. Only one case has been documented thus far. There are some similarities in histology and clinical characteristics between this type of tumor and PT of the female breast: the lesions can be surgically removed, but some recur locally and invade directly into the breast. This case of primary phyllodes tumor of the ureter is useful for pathologists and clinicians.
Clinical and laboratorial characterization of a cohort of patients with hereditary platelet disorders
Authors: Grassi Letícia Dalla Vecchia , Okazaki Erica , Rothschild Cynthia , Villaça Paula , Orsi Fernanda Andrade , Stefanello Bianca
Published: October 2024

Introduction: Inherited platelet disorders (IPDs) are rare conditions characterized by altered platelet function (IPFDs) and/or reduced platelet counts (IPNDs). Diagnosing IPDs is challenging which may results in delays, misdiagnosis and unappropriated treatment. In low and middle-income countries data on these disorders are scarce. Here, we describe a cohort of IPD patients at a reference center in Brazil. Methods: A descriptive analysis was conducted on patients with suspected or diagnosed IPDs at the Thrombosis and Hemostasis outpatient clinic of the Hospital das Clinicas, University of São Paulo, Brazil. From 857 patients identified between 1998 and 2023, 60 met the eligibility criteria for suspected or confirmed IPDs. Patients with acquired causes of platelet dysfunction were excluded. Results: The cohort comprised 60 patients, 65% with IPFDs and 35%, IPNDs. Women were 75%, with a median age of 48 years. IPDs were suspected based on clinical history, family history, and laboratory tests. In the IPND group, 62% had a family history of thrombocytopenia. In the IPFD group, family history was positive in 51% of cases. Previous misdiagnosis included ITP (immune thrombocytopenia) and von Willebrand disease. The bleeding phenotype, assessed using the ISTH BAT (Bleeding Assessment Tool) score, showed a median score of 6, with IPNDs scoring lower than IPFDs. Conclusions: Identifying IPDs is essential for proper treatment and follow-up. This study emphasizes the need for careful assessment of the familial history, bleeding risk, platelet count, morphology and function in diagnosing IPDs, particularly in low resource settings without access to advanced genetic testing.
Genetic analysis of a pedigree with hereditary coagulation factor XII deficiency
Authors: Fang Weiwei , Chen Bile , Zou Anqin , Xu Fei , Qin Langyi , Yang Lihong , Wang Mingshan , Zhou Xingxing
Published: October 2024

Objective: Analyze the clinical phenotype and gene mutations of a family with hereditary FXII deficiency, and preliminarily explore its molecular pathogenic mechanism.
Methods: The routine coagulation indicators and related coagulation factors were measured.. Thromboelastography and thrombin generation tests simulated coagulation and anticoagulation states in vitro and in vivo. PCR direct sequencing was utilized to analyze all exons and flanking sequences of the F12 gene in the proband, confirming suspected mutations through reverse sequencing, and identifying corresponding mutation sites in family members. Using ClustalX-2.1-win to analyze the conservation of the variant, and employing online software to predict the pathogenicity of mutations.
Results: The proband exhibited significantly prolonged APTT (169.1 seconds) and a pronounced decrease in FXII:C to 1.0%. Thromboelastography testing indicated a diminished function of the endogenous coagulation system, while thrombin generation testing revealed a normal ability for thrombin production in the proband. Gene sequencing revealed that the proband harbored a deletion mutation c.303_304delCA in exon 5 and a substitution mutation c.800+1G>A in intron 8. All three bioinformatics software indicated that the mutations were pathogenic and could lead to the production of a terminator, potentially altering the structure and function of the protein.
Conclusion: The deletion mutation c.303_304delCA and substitution mutation c.800+1G>A are associated with a decreased in FXII levels in this family, with the c.800+1G>A mutation being the first reported mutation worldwide.
In-depth Exploration of Cutaneous Anthrax: Clinical and Pathological Manifestations of a Case Report
Authors: Du Yongjun , Ma Jizhou , Liu Guozhen , Chai Zhi , Han Hang , Chen Tairen , Yang Lan , Jing Li , Xu Fangjing , Fan Yucheng
Published: October 2024

Anthrax is an acute infectious disease caused by Bacillus anthracis, which can infect various animals and humans. Cutaneous anthrax primarily presents as infiltrative, edematous erythema, surface vesicles, hemorrhagic vesicles, and necrotic eschar; some patients may also experience systemic symptoms such as fever and leukocytosis. With economic development and improvements in public health conditions, naturally occurring cases of cutaneous anthrax have significantly decreased, leading to limited reports on the pathological manifestations of this disease. This article reports a case of a patient with cutaneous anthrax diagnosed and treated in our hospital, aiming to explore the laboratory examinations, imaging, pathological features, and clinical treatment methods of the disease. The goal is to enhance understanding of anthrax and increase vigilance in clinical practice to avoid misdiagnosis and missed diagnosis.
Effects of the Japanese traditional medicine Goreisan on adverse events affecting mucosal edema in patients with subarachnoid hemorrhage treated with clazosentan
Authors: Akamatsu Yosuke , Chida Kohei , Miyoshi Kenya , Kojima Daigo , Yoshida Koji , Misaki Toshinari , Koji Takahiro , Fujiwara Shunrou , Kubo Yoshitaka , Kashimura Hiroshi , Ogasawara Kuniaki
Published: October 2024

Despite successful management of pulmonary complication with fluid restriction protocol in aneurysmal subarachnoid hemorrhage (aSAH) patients treated with clazosentan, management of symptoms related to mucosal edema, such as diarrhea, stuffy nose, and difficulty in breathing, remains challenging. Hence, we investigated the effect of Goreisan shown to be effective in the treatment of symptoms related with mucosal edema in aSAH patients treated with clazosentan. Patients with aSAH who received clazosentan for vasospasm after aneurysm obliteration were prospectively enrolled in the study. Fluid balance parameters and the incidence of vasospasm, pulmonary edema, mucosal edema-related symptom (such as diarrhea and swelling of the nasal mucosa) were compared between these patients treated with Goreisan (Group G) and without Goreisan (Group NG). As results, Groups NG and G comprised 29 and 40 consecutive patients, respectively. No significant differences in fluid intake, urine volume, frequency of furosemide injection, incidence of vasospasm, pulmonary edema, or discontinuation of clazosentan treatment between the two groups were found over the treatment course, although refractory hyponatremia occurred less frequently in Group G than in Group NG (0% and 10.3%, p = 0.039, respectively). The incidence of diarrhea and the relative mucosal thickness was also significantly lower in Group G than in Group NG (7.3% and 21.9%; p = 0.0004, 113.8% vs. 175.4%; p = 0.001). Clazosentan treatment combined with diuretics and Goreisan was effective in managing diarrhea and swelling of the nasal mucosa. Our treatment protocol may be reasonably applied to patients with aSAH who are treated with clazosentan.
Reduced taurine synthesis underlies morphine-promoted lung metastasis of triple-negative breast cancer
Authors: Chen Shih-Hong , Shih Chien-Hung , Ke Ting-Ling , Hsiung Chia-Ni , Chen Kuo-Chin , Huang Zi-Xuan , Chuang Tsung-Hsien , Chen Li-Kuei , Chen Linyi
Published: October 2024

Background
The mechanisms underlying the progression and metastasis of triple-negative breast cancer (TNBC) in the context of extended morphine exposure remain poorly understood. Morphine consumption has been a pressing issue in many countries. While the physiological impact of extended morphine use is multifaceted, cancer patients with a history of prolonged morphine usage often result in poor prognosis.
Methods
In this study, we investigated the impact of extended morphine treatment on the transcriptional profiles of TNBC. To this end, mice were administered morphine intraperitoneally for 14 days followed by the implantation of EO771 cells, which are triple negative breast cancer cells, into their mammary fat pad. After primary tumors were removed on 38th day, a subset of mice were continuously giving saline or morphine until the 68th day. Tumor size, organ metastasis, and tumor RNA expression were analyzed.
Results
Our findings showed that prolonged exposure to morphine led to an increase in lung metastasis in the mouse model of triple-negative breast cancer. We conducted RNA sequencing analysis on tumors to compare their transcriptional profiles with or without metastasis. Through pathway analysis, we specifically examined the novel impact of morphine on the downregulation of taurine/hypotaurine biosynthesis. Given that morphine, droperidol (a dopamine receptor antagonist), and naloxone (an opioid receptor antagonist) might act through either opioid receptors or dopamine receptors, we further demonstrated that taurine mitigated EO771 cell invasion induced by morphine, but not by droperidol or naloxone treatment. Additionally, morphine treatment markedly decreased the expression of GAD1, one of the enzymes essential for taurine biosynthesis, whereas droperidol and naloxone did not.
Conclusion
The findings of morphine-induced reduction in GAD1 level and the inhibition of invasion by taurine treatment suggest that taurine could serve as a potential supplement for triple-negative breast cancer patients who require morphine as part of their treatment regimen or due to their circumstances.
A Human-Centred Approach to Designing a Social Media-Based Digital Health Intervention to Foster HIV Awareness and Peer Learning Among Adolescents and Young People in a Resource-Limited Setting: A Protocol Paper
Authors: MACHARIA Paul , MUGO Cyrus , SEREMBE James , WANJIHIA Violet , BUKUSI David , IKAMARI Lawrence , NDUATI Ruth , NGARUIYA Christine
Published: October 2024

Background: Despite progress in HIV awareness among adolescents, gaps persist in knowledge, treatment adherence, and mental health support. While current social media apps show promise for information dissemination, privacy and confidentiality concerns remain a barrier. In 2020, WHO, UNICEF, UNFPA, and UNESCO published an inter-agency framework to guide the development of youth-centered digital health interventions (DHIs). This participatory approach, designed to incorporate adolescent aspirations and expectations, is crucial for DHI efficacy. This study explores the potential of applying the DHI inter-agency framework to co-design an adolescent-led web-based social media forum, potentially addressing adolescents’ information gaps while maintaining privacy and confidentiality.
Objective: we aimed to co-design an interactive and engaging social media app that fosters interaction and awareness among adolescents and young people on HIV, intimate partner violence, substance use, mental health, sexual health, and nutrition. The study would investigate the potential of a web-based social media forum to empower adolescent-led interaction and engagement.
Methodology: This proof-of-concept (PoC) study would employ a Design Science (DS) research design, guided by a Human-Centered Design (HCD) a multi-phased approach in the development of interventions. In phases 1 and 2 of the HCD process, focus group discussions (FGDs) would utilize an FGD guide to identify the health information needs of participants. In phase 3, a prospective cohort study at the co-design stage, would evaluate the usability and user experience of the developed web-based social media app.
Utility:The app aims to promote awareness and interaction around HIV, mental health, sexual health, nutrition, and intimate partner violence. The study would evaluate the effectiveness of this web-based platform in fostering adolescent-led engagement and communication on these topics.
Active Surveillance Follow-Up for Prostate Cancer: From Guidelines to Real-World Clinical Practice
Authors: Chiarelli Giuseppe , Stephens Alex , Finati Marco , Cirulli Giuseppe Ottone , Tinsley Shane , Wang Yuzhi , Kolanukuduru Kaushik , Sood Akshay , Carrieri Giuseppe , Briganti Alberto , Montorsi Francesco , Lughezzani Giovanni , Buffi Nicolò , Rogers Craig , Abdollah Firas
Published: October 2024

Purpose
To assess active surveillance (AS) adherence for prostate cancer (PCa) in a “real-world” clinical practice.
Materials and Methods
We utilized our institutional database which was built by interrogating electronic medical records for all men who got diagnosed with PCa from 1995 to 2022. Our cohort included all patients aged < 76 years, with PCa Gleason Grade (GG) 1 or 2, ≤ cT2c, PSA ≤ 20 ng/ml at diagnosis, enrolled on AS, and with at least one biopsy after diagnosis. Patients were separated into two groups based on the monitoring intensity.Patients with at least 1 PSA/year and at least 1 biopsy every 4 years were categorized as adherent to guidelines. Univariable and Multivariable logistic regression analyses were used to examine the impact of covariates on non-adherence to guidelines. Competing risks cumulative incidence was used to depict PCSM.
Results
A total of 546 men met the inclusion criteria. Overall, 63 (11%) patients were adherent to guidelines (Group 1), while 483 (89%) were not (Group 2). Median PSAs/year and median biopsies/year were 2.3 (2.0-2.7) and 0.4 (0.3-0.6) for Group 1, and 1.2 (0.7-1.8) and 0.2 (0.1-0.2) for Group 2, respectively (both p<0.0001). At multivariable analysis, Black men had a 2.20-fold higher risk of being in Group 2 than White men (p<0.05). Patients with cT2 (OR:0.24, CI:0.11-0.52) and those with CCI ³2(OR:0.40, CCI:0.19-0.82) were less likely to be in Group 2, when compared to cT1 stage and CCI=0, respectively (both p< 0.05). At 10 years, the cumulative incidence estimate of prostate cancer-specific mortality (PCSM) for the entire cohort was 2.1%.
Conclusion
We found substantial deviations from AS monitoring guidelines, particularly in biopsy frequency, which did not seem to compromise PCSM in patients with stable PSA. Notably, our findings suggest that strict adherence to guidelines, especially in patients with cT2 at diagnosis, remains crucial.
Amyotrophic Lateral Sclerosis developing in a patient with Chronic lymphocytic leukaemia and drug related a sarcoid-like reaction; teasing apart multiple diagnoses
Authors: Freiha Joumana , Grand Effie , Marshall Ben , Arunchalam Ramamurthy , Pinto Ashwin , Osman Chinar
Published: October 2024

Background
Sarcoid-like reaction is an autoinflammatory disease that can affect lymph nodes and organs but does not meet the diagnostic criteria for systemic sarcoidosis. Anti-CD20 auto-antibodies have been reported to be responsible for such reactions. There are several reported associations between Chronic lymphocytic leukaemia (CLL) , Amyotrophic lateral sclerosis (ALS) and Sarcoid-like reactions. We report a case of ALS developing in a patient with CLL and drug related sarcoid-like reaction.
Case presentation
A 60-year-old male presented with lower limb rash, left leg weakness followed by bulbar symptoms which progressed over 12-months. Workup demonstrated a CSF pleocytosis and inguinal lymphadenopathy. Skin and inguinal lymph node biopsies showed non-necrotising granulomata. Electromyography met diagnostic criteria for ALS. He was treated for presumed neurosarcoidosis presenting with ALS. Despite treatment, the clinical course progressed like a classical ALS.
Conclusion
ALS may occur on a background of pre-existing chronic haematological disorders. Additionally, there is an occasional association of ALS and sarcoidosis. More interestingly, Rituximab can induce a sarcoid-like reaction.
A phase II study of personalized ultrafractionated stereotactic adaptive radiotherapy for palliative head and neck cancer treatment (PULS-Pal): a single-arm clinical trial protocol
Authors: Courtney P. Travis , Santoso Milisuryani , Savjani Ricky R. , Reddy Vishruth , Chai-Ho Wanxing , Velez Maria A. Velez , Wong Deborah , Palodichuk Christy , Basehart T. Vincent , O’Connell Dylan , Cao Minsong , Telesca Donatello , Chin Robert K.
Published: October 2024

Background: Many patients with head and neck cancer will not be candidates for standard of care definitive treatments though often require palliative treatments given the frequent symptoms associated with head and neck cancer. While existing palliative radiotherapy regimens can provide adequate symptom control, they have limitations particularly with respect to local control which is becoming more important as advances in systemic therapy are improving survival. Personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR) is a novel radiotherapy regimen which leverages advances in radiotherapy treatment technology and extended interfraction intervals to enable adaptive radiotherapy and possible synergy with the immune system. Additionally, HyperArc© (Varian Medical Systems, Inc.) radiotherapy planning software allows for safe dose-escalation to head and neck tumors.
Methods: This single-arm phase II study will prospectively evaluate PULSAR with HyperArc software for palliative treatment of head and neck cancer. Patients with de novo or recurrent, localized or metastatic, head and neck cancer who are ineligible for or decline standard of care definitive treatments are eligible for enrollment. Forty-three patients will receive an 11 Gray fraction of radiation every two weeks for a total of five fractions and dose of 55 Gy. Adaptive radiotherapy planning is permitted. A safety and feasibility evaluation will be performed after enrollment of the first fifteen patients whereby the trial will continue if less than five patients experience a CTCAEv5.0 grade 3 or higher toxicity definitely attributable to PULSAR during or within thirty days after its completion. The primary endpoint is one-year local head and neck tumor control. Secondary endpoints include safety, disease progression-free and overall survival, symptomatic impact, frequency of re-simulation and/or adaptive planning, and radiation dosimetry of PULSAR. Additionally, enrolled patients are permitted to receive immunotherapy during PULSAR, which may allow for the analysis of the safety and efficacy of this combination.
Discussion: The PULS-Pal trial is the first prospective study of PULSAR with HyperArc software for head and neck cancer. We hypothesize that this radiotherapy regimen will lead to improved local tumor control compared with historical controls in patients undergoing palliative radiotherapy for head and neck cancer.
Trial Registration: Clinicaltrials.gov identifier: NCT06572423. Date of registration: August 28th, 2024. https://clinicaltrials.gov/study/NCT06572423.
Unexpected Hypereosinophilia after Sinopharm Vaccination: A Case Report
Authors: Dalfardi Behnam , Rad Niloofar Khoshnam , Alizade Tayebe Mohammad , Edalatifard Maryam , Asadi Sanaz , Rahimi Besharat
Published: October 2024

COVID-19 vaccines have been associated with various adverse events, though their safety profile is generally favorable.
We present a case of a 66-year-old male who developed hypereosinophilia (Absolute eosinophil count: 4063 cells/µL) and lymphadenopathy following the third dose of the Sinopharm COVID-19 vaccine. Despite extensive investigations, an underlying cause for these findings was not identified. While a causal relationship cannot be definitively established, the temporal association between the vaccine and symptom onset is intriguing. This case highlights the importance of continued surveillance for rare adverse events following vaccination and emphasizes the need for further research to understand the potential mechanisms linking COVID-19 vaccines to eosinophilic disorders.
The status of insecticide resistance of Anopheles coluzzii on the islands of São Tomé and Príncipe, after 20 years of malaria vector control
Authors: Correa Maria , Lopes Janete , Sousa Carla A. , Rocha Gustavo , Oriango Robin , Cardetas Andreia , Viegas Joao , Cornel Anthony J. , Lanzaro Gregory C. , Pinto João
Published: October 2024

Background
Insecticide based malaria vector control has been implemented on the islands of São Tomé and Príncipe (STP) for more than 20 years. During this period malaria incidence was significantly reduced to pre-elimination levels. While cases remained low through 2015, there has been a steady increase in cases since that time, challenging the country’s commitment of achieving malaria elimination by 2025. To better understand the reasons for increasing malaria cases, we characterized levels and underlying mechanisms of insecticide resistance in local Anopheles coluzzii populations.
Methods
Mosquito larval collections were performed in the rainy and dry seasons, between 2022 and 2024, in two localities in São Tomé and one in Príncipe. Susceptibility to permethrin, α-cypermethrin, pirimiphos-methyl and DDT was assessed using WHO bioassays and protocols. Intensity of resistance and reversal by PBO pre-exposure were determined for pyrethroid insecticides. The kdr locus was genotyped by PCR assays in subsamples of the mosquitoes tested.
Results
Anopheles coluzzii populations were fully susceptible to pirimiphos-methyl but high levels of resistance to pyrethroids and DDT were detected, particularly in São Tomé rainy season collections. Increasing the pyrethroid and DDT dosages to 5\(\:\times\:\) and 10\(\:\times\:\) did not restore full susceptibility in all populations. Pre-exposure to PBO resulted in partial reversal of the resistance phenotype suggesting the presence of cytochrome P450 oxidase-mediated metabolic resistance. The L1014F knockdown resistance mutation was present in An. coluzzii on both islands but at much higher frequency in São Tomé where it was associated with the resistant phenotype.
Conclusions
Future vector control interventions should consider the use of non-pyrethroid insecticides or combination with synergists to overcome the high levels of pyrethroid resistance. Alternative control methods not dependent on the use of insecticides should be additionally implemented to achieve malaria elimination in STP.
A Load Forecasting Model for Smart Grid Based on RF-BiLSTM and Federated Learning
Authors: Li Wenhui , Jiang Huilin , Zhang Lei
Published: October 2024

Accurate load forecasting is essential for improving the efficiency and reliability of smart grids. Traditional forecasting models face challenges in integrating high-dimensional data and protecting privacy. To address these issues, a novel load forecasting model is presented in this paper. The proposed approach combines a random forest (RF) and a bi-directional long short-term memory (BiLSTM) network based on a federated learning framework. To effectively process high-dimensional heterogeneous data in smart grids, the proposed model exploits the feature extraction capability of radio frequency. In addition, the sequential data processing capability of BiLSTM provides a means of processing time-varying load data in smart grids. The federated learning method protects user privacy and achieves the goal of global model training adopting distributed data. Experimental results demonstrate that the proposed model is superior to traditional models in accuracy and efficiency.
Recurrence Pattern and Mapping of Lymph Node Metastases from Rectal Neuroendocrine Tumors
Authors: Takaoka Ayumi , Tsukamoto Shunsuke , Takamizawa Yasuyuki , Moritani Konosuke , Imaizumi Jun , Kinugasa Yusuke , Kanemitsu Yukihide
Published: October 2024

Purpose
There are as yet no data on the long-term clinical outcomes or the frequency of lymph node metastasis after surgical resection in patients with rectal neuroendocrine tumors (NETs). Our study investigated the long-term clinical outcomes and the frequency of lymph node metastasis in patients with rectal NETs treated by surgical resection.
Methods
Fifty-one patients with rectal NETs who underwent rectal resection with total mesorectal excision between January 2000 and July 2020 at our hospital were enrolled. Twenty-eight patients had undergone preoperative endoscopic mucosal resection or endoscopic submucosal dissection before surgical resection. The indication for surgery was determined based on the Japan Neuroendocrine Tumor Society guidelines. Patients diagnosed with neuroendocrine carcinoma were excluded. Main Outcome Measures is frequency of pathological diagnosis of lymph node metastasis, site of lymph node metastasis, and the long-term prognosis after surgical resection.
Results
Lymph node metastasis was observed in 20 patients (39.2%) with lateral lymph node metastasis occurring in 4 patients (7.8%). There was no significant association between lymph node metastasis and 5-year relapse-free survival (90% for metastasis-negative patients vs 58.1% for metastasis-positive patients, p = 0.094).
Conclusions
The rate of lymph node metastasis in patients with rectal NETs treated by surgical resection with total mesorectal excision was found to be high. However, a good prognosis was achieved by surgical resection even in patients with lymph node metastasis.
Growing functional artificial cytoskeletons in the viscoelastic confinement of DNA synthetic cells
Authors: Walther Andreas , Chen Weixiang , Song Siyu , Samanta Avik , Sethi Soumya , Drees Christoph , Kappl Michael , Butt Hans-Jürgen
Published: October 2024

Intracellular structures, like the cytoskeletons, form within a crowded cytoplasm with defined viscoelastic properties. While crowding effects on self-assembly are well studied, the role of viscoelasticity in regulating structure formation remains elusive. Here, we engineer crowded all-DNA synthetic cells (SCs) with tunable viscoelastic interiors to investigate this phenomenon. We introduce a facile approach to integrate multiple DNA barcodes with adjustable concentrations into SCs, enabling selective enrichment of DNA tiles to form artificial cytoskeletons coupled to the viscoelastic SC interior. Distinct mechanistic differences in assembly occur compared to solution or simple crowding. Additionally, we develop light, molecular, and metabolic controls to direct structure formation and create self-sorted SC populations with distinct artificial cytoskeletons. These cytoskeletons enhance the mechanical stability of SCs and support stable contacts with mammalian cells. Our SC system serves as a versatile molecular engineering platform to study self-assembly under viscoelastic constraints and leverage sub-SC structures for challenging applications.