bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocarditis Caused by Metapneumovirus with Klebsiella pneumoniae Infection: A Case Report
Authors: Wang Shih-Hung , Lee Mei-Hui , Lee Yuarn-Jang , Liu Yung-Ching
Published: June 2024

Background Human metapneumovirus (hMPV), classified in the Pneumoviridae family, primarily causes lower respiratory tract infections in children and immunocompromised individuals. However, rare cases have highlighted hMPV infections manifesting beyond the respiratory system, including cardiac impairment.
Case presentation We report the case of a 68-year-old man who presented at the emergency room with dyspnea and fever and who rapidly progressed to septic shock with increasing oxygen requirements, necessitating transfer to the medical intensive care unit (MICU). Diagnostic evaluations comprising cardiac echocardiography and coronary angiography were utilized to confirmmyocarditis while ruling out acute myocardial infarction. Despite the implementation of extracorporeal membrane oxygenation (ECMO) and intra-aortic balloon pump (IABP)therapy, the patient succumbed to the illness three days after admission to the MICU. Polymerase chain reaction (PCR) of a throat swab confirmed the diagnosis of Metapneumovirus infection, and Klebsiella pneumoniae was concurrently detected through sputum culture.
Conclusions Compared to previously reported cases of metapneumovirus-related myocarditis, this case is the first to demonstrate a notably adverse outcome associated with the concurrent presence of bacterial infection.
ADRB1 gene polymorphism regulated the positive inotropic effect of myocardial insufficiency with metabolic syndrome:a basic experimental research
Authors: Liu Ruining , Yang Feihong , Wang Pengcheng , Zhao Xia , Wu Wenfeng , Ma Haoli , Zhao Yan , Jiang Cheng
Published: June 2024

Background
The risk of cardiovascular disease (CVD) in metabolic syndrome (MS) patients is significantly higher than that in healthy people, and ADRB1 gene polymorphism is closely associated with CVD. Our previous study found that obesity can lead to the change of β-adrenergic receptor (β-AR) in myocardium, but the mechanism is not clear. The aim of the study was to investigate the effect of ADRB1 gene polymorphism on the β-AR and its downstream signaling molecules involved in a model of myocardial insufficiency with MS.
Materials and Methods
We constructed the β1AR-49M (HA-β1AR-S49G) and β1AR-389M (HA-β1AR-R389G) mutant plasmids for cell transfection. cAMP level was assessed by Fluorescence Resonance Energy Transfer (FRET). The Ca2+ flow detection was characterized by Fluo-4 indicator calcium concentration assay. H9C2 cardiomyocytes were treated with palmitic acid (PA) to construct the cell injury model. Wistar rats were subjected to normal chow diet (Control group) and high-fat diet (MS group) for 16 weeks. The cardiac function of rats was detected by echocardiography. The positive inotropic effect in vivo was observed by intravenous pumping of Isoproterenol (ISO), and in vitro, muscle force was determined by administering ISO using muscle force measurement system. The protein expression of β-AR and downstream molecular proteins in left ventricular tissue was detected by Western Blot.
Results
ADRB1 gene polymorphism did not affect the expression of β1-AR. Moreover, like wild type, carrying β1AR-389M was most sensitive to Bisoprolol, while β1AR-49M is most sensitive to Carvedilol. PA intervention resulted in up-regulation of β1-AR expression with no significant difference between the mutant groups. The inhibitory effect of Bisoprolol in those carrying β1AR-R389G mutant was stronger than that of carrying β1AR-S49G mutant. Echocardiographic results indicated that left ventricular systolic and diastolic functions were not impaired in MS group. The positive inotropic effect in MS rats was significantly weaker than that in Control group in vitro, without being impaired in vivo.
Conclusions
ADRB1 gene polymorphism can lead to the differences on the molecular mechanism and response to β1AR inhibitors, and especially, carrying the β1AR-R389G mutant is more conducive to the exertion of the pharmacological effects of Bisoprolol.
A dramatic case report: Achived remission in metamphetamine addiction after changing city, yet ended up in prison
Authors: Danışman Mustafa , Hasanlı Zehra Uçar , İspir Gamze Zengin , Katar Kübra Sezer
Published: June 2024

Background: Neuroscientific approaches to addiction as a brain disease often locate addiction within the individual's body or brain and describe it as a disordered or diseased state. However, such explanations ignore the importance of social contexts for addiction problems and how consumption patterns change over time and consider addiction as a process that is often independent of the environment for individuals who use substances. However, the impact of the environment is significant in the development and treatment of substance use disorders, which should be handled with a biopsychosocial model. Many studies prove that substance use behaviours change with changes in the environment. In addition, the fact that some people who use substances commit crimes and violate the law constitutes an important social aspect of substance addiction. While there may be many factors that lead individuals to commit crimes, drugs may be among the reasons that lead individuals to commit crimes by causing changes in their thoughts and behaviors.
Case Presentation: In this report, we present the story of a patient with methamphetamine use disorder who was placed on probation for theft offence during the period when he was using this substance. Although the patient was hospitalized and received treatment several times, he relapsed when he returned to his living environment. However, he entered the remission process after moving to a regular and developed area where he could receive family support. However, he was sentenced to prison for his previous offence during this period.
Conclusions: This is an essential example of the critical effect of the living environment on substance use behaviours, which was achieved through remission after moving from the socially disadvantaged area where the patient was living. Although it is sad for the patient's family and himself that his story ended in prison, the changes in his life during his stay with his sister and the fact that he did not continue substance use are promising for his treatment. In conclusion, it is essential to consider environmental factors and integrate these factors into treatment strategies for effective treatment in the fight against methamphetamine addiction.
Assessing the clinical utility of preoperative neutrophil-lymphocyte ratio as a predictor of clinicopathological parameters in patients being treated for primary breast cancer
Authors: Isik Burce , Davey Matthew G , Jaffer Alisha A. , Buckley Juliette , Baban Chwanrow , Merrigan Bridget Anne , Tormey Shona
Published: June 2024

Background
There is a paucity of data supporting the role of neutrophil-lymphocyte ratios (NLR) to determine clinicopathological parameters in patients being treated for primary breast cancer.
Aims
To evaluate the association between preoperative NLR and clinicopathological parameters in patients diagnosed with breast cancer.
Methods
A retrospective cohort study was performed. This included consecutive patients indicated to undergo surgery for primary breast cancer at University Hospital Limerick between January 2010 - June 2017. NLR was expressed as a continuous variable. Univariable and multivariable linear regression analyses were used to determine the correlation between NLR and clinicopathological data. Data analytics was performed using SPSS v29.0.
Results
673 patients met the inclusion criteria. Overall, the median preoperative NLR of 2.63 (standard deviation: 1.42). At univariable analysis, patient age (beta coefficient: 0.009, 95% confidence interval (CI): 0.001–0.017, P = 0.027), tumour size (beta coefficient: 0.013, 95% CI: 0.005–0.021, P = 0.001), and human epidermal growth factor receptor-2 status (beta coefficient: -0.370, 95% CI: -0.676 - -0.065, P = 0.017) were all predicted using NLR. However, at multivariable analysis, tumour size was the sole parameter predictable by NLR (beta coefficient: 0.011, 95% CI: 0.002–0.019, P = 0.013).
Conclusions
This study demonstrates that preoperative NLR may serve as an independent predictor of tumour size in patients being treated with primary breast cancer. Ratification of these preliminary findings is warranted before robustly adopted into clinical practice.
Podoplanin hetero-insufficiency demonstrates congenital protein-losing enteropathy by inflammation in the jejunum: NO synthase inhibitor may become a selective tool for pharmacological therapy
Authors: Ohhashi Toshio , Takasaka Mieko , Tsukiji Nagaharu , Watanabe-Asaka Tomomi , Hayashi Moyuru , Maejima Daisuke , Kaidoh Maki , Yokoyama Yumiko , Suzuki-Inoue Katsue , Kawai Yoshiko
Published: June 2024

We demonstrated that podoplanin was expressed in jejunal villi. Based on the finding, we aimed to clarify the pathogenesis of congenital protein-losing enteropathy (PLE) using podoplanin heterozygeous knock-out (Pdpn-het KO) mice and aspirin-mediated inflammation of the jejunum. Podoplanin was expressed with differential region of the jejunal villi in the Pdpn-het KO mice compared with wild-type one. Fluorescent intensity of intravenous administration of FITC-albumin in the jejunal villi of Pdpn-het KO mice was significantly greater than that of wild-type mice. In the wild-type mice, the blue-colored mesenteric lymph vessels and lymph nodes were observed around 6 min after intravenous injection of Evans blue dye. However, in the Pdpn-het KO mice, the blue-colored lymph vessel and lymph nodes were not observed until 15 min. In the Pdpn-het KO mice, aspirin-mediated jejunal inflammation leaked significantly the intravenous administration of FITC-albumin into the jejunal canal. To design pharmacological therapy for PLE, the effects of NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME) on permeant albumin in jejunal villi were investigated. Pretreatment with L-NAME significantly reduced the intravenous administration of FITC-albumin distribution in the jejunal villi of Pdpn-het KO mice. In conclusion, we proposed that Podoplanin hetero-insufficiency with jejunal inflammation causes the pathogenesis of congenital PLE. The NO synthase inhibitor may become pharmacological tool for the therapy of PLE.
Tensor-valued diffusion MRI detects brain microstructure changes in HIV infected individuals with cognitive impairment
Authors: Uddin Md Nasir , Singh Meera V. , Faiyaz Abrar , Szczepankiewicz Filip , Nilsson Markus , Boodoo Zachary D. , Sutton Karli R. , Tivarus Madalina E. , Zhong Jianhui , Wang Lu , Qiu Xing , Weber Miriam T. , Schifitto Giovanni
Published: June 2024

Despite advancements, the prevalence of HIV-associated neurocognitive impairment remains at approximately 40%, attributed to factors like pre-cART (combination antiretroviral therapy) irreversible brain injury. People with HIV (PWH) treated with cART do not show significant neurocognitive changes over relatively short follow-up periods. However, quantitative neuroimaging may be able to detect ongoing subtle microstructural changes. This study aimed to investigate the sensitivity of tensor-valued diffusion encoding in detecting such changes in brain microstructural integrity in cART-treated PWH. Additionally, it explored relationships between these metrics, neurocognitive scores, and plasma levels of neurofilament light (NFL) chain and glial fibrillary acidic protein (GFAP). Using MRI at 3T, 24 PWH and 31 healthy controls underwent cross-sectional examination. The results revealed significant variations in b-tensor encoding metrics across white matter regions, with associations observed between these metrics, cognitive performance, and blood markers of neuronal and glial injury (NFL and GFAP). Moreover, a significant interaction between HIV status and imaging metrics was observed, particularly impacting total cognitive scores in both gray and white matter. These findings suggest that b-tensor encoding metrics offer heightened sensitivity in detecting subtle changes associated with axonal injury in HIV infection, underscoring their potential clinical relevance in understanding neurocognitive impairment in PWH.
Production, Purification, Characterization, and Safety Evaluation of Constructed Recombinant D-Psicose 3-Epimerase
Authors: Watthanasakphuban Nisit , Sr Pimsiriya , Pinmanee Phitsanu , Punvittayagul Charatda , Petchyam Nopphon , Ninchan Boontiwa
Published: June 2024

Background D-psicose 3-epimerase (DPEase) is a potential catalytic enzyme for D-psicose production. D-psicose, also known as D-allulose is a low-calorie sweetener that has garnered considerable attention for healthy alternative sweetener due to its remarkable physicochemical properties. This research focused on an in-depth investigation of the expression of the constructed DPEase gene from Agrobacterium tumefaciens in Escherichia coli for D-psicose synthesis, with a strong emphasis on scalability. Experimentally, this research created the recombinant enzyme, explored the optimization of gene expression systems and protein purification strategies, and then investigated the enzymatic characterization to establish a robust and scalable process for D-psicose production. Additionally, the optimization of D-psicose production using the recombinant DPEase was also studied. Finally, the produced D-psicose syrup was underwent acute toxicity evaluation to provide scientific evidence supporting its safety.Results The optimization of DPEase expression involved the utilization of Mn2+ as a cofactor, fine-tuning isopropyl β-D-1-thiogalactopyranoside (IPTG) induction, and controlling induction temperature. The purification process was strategically designed to facilitate industrial-scale operations. A nickel column and an elution buffer containing 200 mM imidazole were employed, resulting in purified DPEase with a remarkable 21.03-fold increase in specific activity compared to the crude extract. The optimum D-psicose conversion conditions of purified DPEase were performed at pH 7.5 and 55°C under Mn2+ addition as the cofactor. Kinetic parameters of purified DPEase, Vmax and Km, were determined, demonstrating the high substrate affinity and efficiency of DPEase, which are crucial factors for achieving cost-effective for D-psicose production that was confirmed by binding site of fructose-DPEase-Mn2+ structure. Stability studies were conducted to ensure the enzyme's robustness during storage, which the glycerol supplementation and storage at -20°C were identified as effective strategies for maintaining its stability. D-psicose production using purified DPEase was investigated across a range of fructose concentrations, with a focus on optimizing yields for industrial applications. Moreover, the results from acute toxicity study showed no toxicity to rats, supporting the safety of mixed D-fructose-D-psicose syrup produced using recombinant DPEase.Conclusions These findings have direct and practical implications for the industrial-scale production of D-psicose, a valuable rare sugar with a broad range of applications in the food and pharmaceutical industries. Our research advances the understanding of DPEase biocatalysis and offers a roadmap for the successful scale-up production of rare sugars, opening new avenues for their utilization in various industrial processes.
Comprehensive Analysis of Immune Infiltration Identifies Predictors for Immunotherapy Efficacy in Hepatocellular Carcinoma
Authors: Liu Shaoru , Wu Zongfeng , Yuan Yichuan , Lin Zhu , Zuo Dinglan , Niu Yi , Li Binkui , Yuan Yunfei , Qiu Jiliang
Published: June 2024

Background
The aim of this study was to determine whether differences in the cellular composition of the immune infiltrate in HCC influence survival and identify predictors for immunotherapy efficacy in hepatocellular carcinoma.
Methods
A total of 362 patients from TCGA cohort and 204 patients from ICGC with HCC were included in the study. Two immune features were selected out of 24 immune features to construct immunotypes based on the Cox regression model. Hub genes of DEGs were identified by STRING and Cyto-scape. The role of hub genes on immunotherapy efficacy prediction was evaluated by Kaplan–Meier survival analysis in immunotherapy cohorts. The effects of LCK on HCC cell proliferation and migration were evaluated by CCK8, trans-well and wound healing assays.
Results
Eight immune cell subsets were associated with HCC prognosis. Two immune cells (MAIT and central-memory) were selected to construct 3 immunotypes which could predict overall survival in the TCGA cohort (X2 = 24.13, P < 0.0001) and ICGC cohort (validation cohort, X2 = 10.51, P = 0.005). GO and GSEA analysis showed up-regulated immune-related pathway in Cluster3, and Cluster3 showed significantly higher immune checkpoint molecules (PD-L1, PD-1, CTLA-4, PD-L2, LAG3 and TIM3) expression. Three hub genes (CCR5, CCR7 and LCK) were identified based on the differential expression genes between Cluster3 and Cluster1. CCR5, CCR7 and LCK were efficient predictors for immune infiltration, especially CTL, and immunotherapy efficacy. We also verified that LCK conferred proliferation and metastasis of HCC cells and immunotherapy resistance of HCC patients.
Conclusion
Immune cell abundance and immunotypes could effectively predict prognosis of HCC. Furthermore, CCR5, CCR7 and LCK were identified as predictors for immunotherapy efficacy in hepatocellular carcinoma.
Correlation analysis between ginsenoside content and rhizosphere soil microbial species in different forest types
Authors: Pang Fengyu , Ruan Xiaojia , Gao Yugang , Zhao Yan , Liu Qun
Published: June 2024

Inter-root microorganisms are major factors influencing the formation of high-quality herbs and promoting the accumulation of secondary metabolites, and this relationship has been well characterised in many supra-herbal medicinal herbs, but there is limited information on whether ginseng saponin accumulation is mediated by microorganisms in different forest types.Inter-root soil samples of ginseng and ginseng samples were collected from four different forest types (Theropencedrymion, Larch forest, Broad-leaved forest and Camphor pine forest) in the mountainous areas of Jingyu County, Jilin Province, China. The content of ginsenosides in the collected ginseng samples was determined by high performance liquid chromatography (HPLC). The results showed that the content of ginsenosides in Camphor pine forest was significantly higher than that in the other three forest types.The microorganisms in the soil samples were isolated and purified, and subsequently sequenced and analyzed by high-throughput sequencing methods, and a total of seven bacterial species were isolated and identified in the inter-root soil of ginseng from four different forest types. In broad-leaved forests (BF) and larch forests (LF), Bacillus megaterium is the most abundant microorganism. In the camphor pine forests (CPF) and theropencedrymion (TH), Luteibactor rhizovicinais the largest proportion of microorganisms. Relevant analysis shows that several identified strains from the four forest types, including Bacillus pseudomycoides, Bacillus subtilis, Pseudomonas alcaliphila, Luteibacter rhizovicinus and Pseudomonas alcaliphilacan promote the biosynthesis and accumulation of monomeric saponins Rc, Rb1, Rb2, Rb3, Rg2, Rb3, and Rh4. Our research findings emphasize the crucial role of different forest stand types in soil microbial community structure, and explore the accumulation mechanism of ginsenosides from a microbial perspective. In summary, this study provides more theoretical basis for the relationship between different forest types and the bioactive components of medicinal plants.
Impact of SARS-CoV-2 Infection During Various Pregnancy Trimesters on Maternal and Fetal Outcomes
Authors: Yin Mengyue , Peng Lingling , Zhang Chunling , Zhang Xueyan , Han Mei , Wang Yongmei , Hao Yafei , Guo Zhaolun , Li Hua , Zhang Lan
Published: June 2024

Background The specific impact and pathology of long COVID effects on mother and fetus post-infection have not been deeply investigated. Therefore, we explored the inflammatory response in fetal tissue from pregnant women infected at various stages.
Methods We collected villi, decidua, and placenta samples from 57 patients at Tai'an Central Hospital, who underwent either induced abortion or delivery between November 2022 and March 2023. HE staining was employed for histological examinations of these tissues. Furthermore, the concentrations of IL-6 in both umbilical cord blood and amniotic fluid were quantitatively analyzed using ELISA kits. Additionally, Western blot analysis was conducted to evaluate the expression levels of TNF-α and IL-1β in the placental tissues.
Results Among participants, 53 pregnant women were diagnosed with SARS-CoV-2 infection. No significant placental pathology differences were found between mid-term and late-term stages with the control group (P>0.05). However, Western blot analysis indicated that infected placental tissues showed higher TNF-α and IL-1β levels (P<0.05), with no notable variance in expression levels between mid-term and late-term pregnancies (P>0.05). IL-6 levels in amniotic fluid showed no significant difference, and detected no IL-6 expression in umbilical cord blood.
Conclusion Infection with SARS-CoV-2 during different periods of pregnancy can have different effects on the placenta and other tissues, emphasizing the importance of preventing and managing viral infection during pregnancy and providing clinical reference for formulating management strategies for SARS-CoV-2 infection.
Fourier-enhanced multi-modal 3D small object optical mark recognition and positioning method for percutaneous abdominal puncture surgical navigation
Authors: Guo Zezhao , Guo Yanzhong , Zhao Zhanfang
Published: June 2024

Navigation for thoracoabdominal puncture surgery is used to locate the needle entry point on the patient's body surface. The traditional reflective ball navigation method is difficult to position the needle entry point on the soft, irregular, smooth chest and abdomen. Due to the lack of clear characteristic points on the body surface using structured light technology, it is difficult to identify and locate arbitrary needle insertion points. Based on the high stability and high accuracy requirements of surgical navigation, this paper proposed a novel method, a muti-modal 3D small object medical marker detection method, which identifies the center of a small single ring as the needle insertion point. Moreover, this novel method leverages Fourier transform enhancement technology to augment the dataset, enrich image details, and enhance the network's capability. The method extracts the Region of Interest (ROI) of the feature image from both enhanced and original images, followed by generating a mask map. Subsequently, the point cloud of the ROI from the depth map is obtained through the registration of ROI point cloud contour fitting. In addition, this method employs Tukey loss for optimal precision. The experimental results show this novel method proposed in this paper not only achieves high-precision and high-stability positioning, but also enables the positioning of any needle insertion point.
The Effects of Different Breakfasts on Mood, Satiety, and Cognitive Function among White-collar Workers in China: A Randomized Cross-over Study
Authors: Bai Ruixue , Guo Jiaxin , Li Chihua , Zhang Yan , Hu Ping , Huang Wenjie , Xu Xianglong , Tang Zhenchuang , Zhao Yong , Sharma Manoj , Ma Guansheng
Published: June 2024

Background
Breakfast is considered of vital importance for health and working performance, however, previous studies reported that most people don’t eat breakfast every day. White-collar workers bear heavy mental work in their daily work, the breakfast is also important for them. To our knowledge, there are few or no studies on the relationship between breakfast intake and glucose level, mood, satiety, and cognitive function among white-collar workers, especially among the Chinese population. We therefore evaluate the impact of different-size breakfasts with differing types of food and quality on blood glucose, mood, satiety, and cognitive function among white-collar workers in Chongqing, China.
Methods
This was a field-based study using a randomized cross-over trial design. On every Monday for three successive weeks, 48 white-collar workers received different types of breakfast in a counterbalanced order. For all individuals, mood, and satiety were assessed using positive affect and negative affect scale visual analogue scales two hours after breakfast, respectively. Four cognitive function tests were applied to evaluate the capacity of short-term memory, learning and working memory, attention, and language logic. These cognitive function tests included the digit span test, digit-symbol substitution test, letter cancellation test, and grammatical transformation test.
Results
All participants who had breakfast (standard breakfast or light breakfast) presented a higher blood glucose level and a more satisfying feeling than those who had no breakfast (p < 0.05) across the experimental day. Based on the digit symbol test, women who had standard breakfast had a more powerful learning and working memory capacity than those who had light breakfast or skipped breakfast (p < 0.05).
Conclusion
Among white-collar workers, having breakfast is necessary and can exert a positive effect on people’s satiety. For women, having a standard breakfast is beneficial to maintain their learning and working memory function.
Investigation of short-term variability of ocular biometric measurements before cataract surgery: potential importance of preoperative dry eye
Authors: Ahn Sanghyuk , Eom Youngsub , Song Jong Suk , Kim Dong Hyun
Published: June 2024

This study aimed to investigate the short-term variability of ocular biometric measurements and to analyze the factors associated with high variability of biometric values in patients with cataract. This retrospective study included 60 eyes of patients who underwent ocular biometric measurements twice with the IOLMaster 700 before cataract surgery between March 2023 and November 2023. Ocular surface parameters included tear film break-up time (TBUT) and corneal and conjunctival staining scores (CSS and ConSS, respectively) before cataract surgery. Refractive surprise was defined as a mean absolute error exceeding 0.5 diopter (D). The participants comprised 22 men and 38 women, with a mean age of 70.6±8.4 years. Axial length and anterior chamber depth were remarkably consistent between the two measurements; however, the absolute difference of keratometric (K) values and astigmatism amount showed notable variability (mean K: 0.18±0.17D; astigmatism: 0.21±0.26D). A decreased TBUT and increased CSS were significantly associated with high variability (≥0.25D) of mean K (p=0.040 and p=0.008, respectively). The high K variability group (mean K variability≥0.25D) revealed a significantly higher incidence (p=0.037) of refractive surprise (45.4%) compared with the low K variability group (mean K variability<0.25D) (17.7%). Lower TBUT and higher CSS preoperatively influenced the variability of K values and the incidence of postoperative refractive surprise in cataract surgery.
Discovery of molecularly-informed therapeutic strategies for mature T-cell neoplasms
Authors: Koch Raphael , Schmidt Nicole , Kornrumpf Kevin , Ries Lena , Markus Katharina , Ksionsko Nora Anna Maria , Mazzeo Paolo , Lohrberg Melanie , Sitte Maren , Salinas Gabriela , Braun Till , Dechow Annika , Herling Marco , Ianevski Aleksandr , Aittokallio Tero , Höltermann Charlotte , Chapuy Björn , Bastians Holger , Wulf Gerald , Beißbarth Tim , Dönitz Jürgen
Published: June 2024

Mature T-cell lymphomas and leukemias (mTCL) comprise a clinically and genetically heterogeneous group of lymphoid malignancies. Most subtypes of peripheral T-cell lymphomas and leukemic T-cell malignancies show an aggressive clinical course and poor prognosis. Thus, these diseases urgently require novel therapeutic strategies. Taking advantage of recent progress deciphering the genetic basis of mTCL, we generated a comprehensive database of genetic alterations from >1 800 patients with mTCL and utilized bioinformatic methodology developed to support treatment decisions in molecular tumorboards to identify novel potential therapeutics. To assess the in vitro activity of potential therapeutics, broad drug screening was performed in molecularly characterized cell lines of mTCL. Notably, the cell cycle regulator WEE1 was identified as a novel therapeutic target in mTCL. Indeed, WEE1 kinase inhibitors potently induced replication stress, premature mitotic entry, accumulation of DNA damage and induction of apoptosis in mTCL cell lines. Exploring potential drug combination strategies through mechanistic studies, we identified strong synergistic effects of combined WEE1 and JAK inhibition in JAK/STAT driven preclinical models as well as in primary patient samples of T-cell prolymphocytic leukemia (T-PLL). In summary, our results identified combinatorial effects of WEE1 and JAK inhibition in genetically defined subtypes of mTCL.
Mindray CL900i CLIA HIV Ag/Ab Combo assay: a reliable solution for highly sensitive and specific HIV screening
Authors: Nasrallah Gheyath , Younes Nadin , Khalid Hadiya M. , Al-Emadi Jawaher A. , Younes Salma , Abouassali Mazen Najib , Elshaikh Manal Abdelmutaal , Karime Ibrahim Wisam , Ibrahim Mohammed Abdelfatah , Ali Mutaz Mohamed , Shaar Ibrahim Al , Liu Na , Ayoub Houssein , Yassine Hadi M , Abu-Raddad Laith J. , Ismail Ahmed
Published: June 2024

Background: Architect-HIV Ag/Ab combo chemiluminescence assay is globally recognized for its sensitivity but has a notable false-positive rate.
Aim:To evaluate the performance of a new cost-effective screening alternative, the chemiluminescence Ag/Ab combo assay (CL-900i-HIV) from Mindray, China.
Method: We selected 195 archived samples, classified based on the gold standard Inno-Lia HIVI/II-line immunoassay confirmatory assay. These samples included true positive (n=38; positive by Architect-HIV & Inno-Lia-HIV), true negative (n=101; negative by Architect-HIV & Inno-Lia-HIV), false positive (n=20; positive by Architect-HIV & negative by Inno-Lia-HIV), and indeterminate results (n=22; positive by Architect-HIV & indeterminate by Inno-Lia-HIV). We tested all samples using the Mindray CL-900i-HIV and all positive Architect-HIV samples (n=80) were confirmed by PCR.
Results: Compared to INNO-LIA™ HIVI/II line immunoassay confirmatory assay, Mindray CL-900i-HIV demonstrated a sensitivity of 100% (95% CI: 90.7-100), specificity of 100% (95% CI: 97.0-100), overall percent agreement (OPA) of 100% (95% CI: 97.7-100.0), and perfect agreement with the INNO-LIA confirmatory assay (𝜅= 1.00). Additionally, Mindray's CL-900i-HIV exhibited a significantly lower false-positive rate (8.75%) compared to Architect-HIV's (55%).
Conclusion: Mindray CL900i demonstrated high sensitivity and very low false-positive rate, thus, has the potential to serve as an excellent, cost-effective surrogate for HIV screening, overcoming the limitations of existing automated assays.
Analysis of Outcomes of Traumatic Colon and Rectal Injuries Managed With or Without Fecal Diversion
Authors: Mallick Taha , Hasan Mahera
Published: June 2024

Background:
Traumatic colorectal injuries can be managed by either fecal diversion or primary repair / resection and anastomosis. We aimed to study differences in outcomes in adult patients managed with or without fecal diversion at time of initial operation.
Methodology:
Using ICD-9 codes adult patients (18 years and older) in the National Trauma Databank with colonic and rectal injuries were identified for the years 2013-2015. The following datapoints were collected: age, gender, race, injury severity score (ISS), pulse rate, systolic blood pressure (SBP) and length of stay (LOS). Subjects with missing data or cardiac arrest at time of arrival were excluded.
Patients were divided into two groups based on whether or not fecal diversion was performed at time of initial operation. Incidence of the following morbidities was analyzed: acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), deep vein thrombosis (DVT), pulmonary embolism (PE), pneumonia, deep surgical site infection (SSI), severe sepsis, unplanned intubation and unplanned return to OR.
Statistical analysis was conducted using SPSS for windows. P-value < 0.05 was considered statistically significant.
Results
Of 2,598,467 patients, 8434 (0.32%) sustained a colonic or rectal injury. Mean age was 32.1 years. 87.8% were male. 665 patients (Group 1) underwent fecal diversion while 3866 (Group 2) underwent resection / anastomosis or primary repair.
Groups 1 and 2 were noted to be similar in terms of ISS (median of 14 in both groups), age (33.9 vs 33.1 years; p=0.15), percentage of male patients (87.1% vs 88.7%; p=0.23), SBP (125 vs 123 mmHg; p=0.051) and pulse rate (95.8 vs 97.3; p=0.46) respectively.
No statistically significant differences were found in the incidence of AKI (Odds ratio (OR): 1.29, 95% confidence interval (CI) 0.823-2.04), ARDS (OR: 1.42, 95% CI 0.732-2.75), DVT (OR: 1.38, 95% CI 0.827-2.30), pulmonary embolism (OR: 0.808, 95% CI 0.451-1.45), pneumonia (OR: 1.03, 95% CI 0.729-1.47), deep SSI (OR: 0.768, 95% CI 0.522-1.13), severe sepsis (OR: 1.37, 95% CI 0.862-2.17), unplanned intubation (OR: 1.15, 95% CI 0.650-2.02) or unplanned return to operating room (OR: 1.10, 95% CI 0.793-1.53).
LOS was 15.3 and 15.2 days for groups 1 and 2 respectively (p=0.92).
Conclusion
There does not appear to be a difference in outcomes between patients who undergo fecal diversion and those who do not. Therefore the decision to perform resection / anastomosis or primary repair should not be influenced by a concern for post-operative fecal leakage and subsequent morbidity but should be based on hemodynamic status and extent of injury.
Anti-tumor Effects of the eIF4A Inhibitor Didesmethylrocaglamide and Its Derivatives in Human and Canine Osteosarcomas
Authors: Oblinger Janet , Wang Jack , Wetherell Georgia , Agarwal Garima , Wilson Tyler , Benson Nicole , Fenger Joelle , Fuchs James , Kinghorn A Douglas , Chang Long
Published: June 2024

Inhibition of translation initiation using eIF4A inhibitors like (-)-didesmethylrocaglamide [(-)-DDR] and (-)-rocaglamide [(-)-Roc] is a potential cancer treatment strategy as they simultaneously diminish multiple oncogenic drivers. We showed that human and dog osteosarcoma cells expressed high levels of eIF4A1/2, particularly eIF4A2. Genetic depletion of eIF4A1 and/or 2 slowed osteosarcoma cell growth. To advance preclinical development of eIF4A inhibitors, we demonstrated the importance of (-)-chirality in DDR for growth-inhibitory activity. Bromination of DDR at carbon-5 abolished growth-inhibitory activity, while acetylating DDR at carbon-1 was tolerated. Like DDR and Roc, DDR-acetate increased the γH2A.X levels and induced G2/M arrest and apoptosis. Consistent with translation inhibition, these rocaglates decreased the levels of several mitogenic kinases, the STAT3 transcription factor, and the stress-activated protein kinase p38. However, phosphorylated p38 was greatly enhanced in treated cells, suggesting activation of stress response pathways. RNA sequencing identified RHOB as a top upregulated gene in both DDR- and Roc-treated osteosarcoma cells, but the Rho inhibitor Rhosin did not enhance the growth-inhibitory activity of (-)-DDR or (-)-Roc. Nonetheless, these rocaglates potently suppressed tumor growth in a canine osteosarcoma patient-derived xenograft model. These results suggest that these eIF4A inhibitors can be leveraged to treat both human and dog osteosarcomas.
Spatial and seasonal association study between P M2.5 and related risk factors in India
Authors: Sengupta Anwesha , Middya Asif Iqbal , Dutta Kunal , Roy Sarbani
Published: June 2024

Global environmental degradation and climate change causing persistent health issues due to increased exposure to pollution have become a serious matter of concern and studies. This human-generated environmental pollution is caused due to rapid industrialization, construction-related issues, different festive occasions, etc. Remarkable seasonal and spatial distributions have been observed in this context. Among all the existing pollutants, the fine airborne particles P M2.5(with aerodynamic equivalent diameter ≤ 2.5μm) and P M10 (with aerodynamic equivalent diameter ≤ 10μm) are associated with chronic pulmonary and cardiovascular diseases. This leads to carrying out the study regarding the varying relationship between P M2.5 and other related risk factors so that its concentration level might be under control. Existing literature has explored the geographical association between the pollutants with a few other important factors. To address this problem, the present study aims to explore the widespatiotemporal relationships between the particulate matter (P M2.5) with the other associated risk factors (e.g., socio-demographic, meteorological factors, and air pollutants). For this analysis, the geographically weighted regression (GWR)model with different kernels (viz. Gaussian and Bisquare kernels) and the ordinary least squares (OLS) model have been carried out to analyze the same from the perspective of the four major seasons (i.e., autumn, winter, summer, and monsoon) in different districts of India. It may be inferred from the results that the local model (i.e., GWR model with Bisquare kernel) captures the spatial heterogeneity in a better way with R2 values 0.994, 0.993, 0.992, 0.991, and 0.994respectively for four different seasons and for the corresponding 1-year cycle during October 2022-September 2023. The GWR model using the Bisquare kernel method performs better in terms of smaller corrected Akaike Information Criterion (AICc) (i.e., -896.883, -790.469, -618.686, -834.706, and -867.802 for four specific seasons and the corresponding 1-year cycle period respectively).
Deep Learning Based Signal Processing and Detection for Multiple Medical Devices OFDM Systems
Authors: Wang Haoyu , Yu Yaoping , Liu Xiaoguang , Wei Kun , Ye Youjie , Zhang Wangshu , Zhou Yulin
Published: June 2024

In general multiple medical devices orthogonal frequency-division multiplexing (OFDM) communication systems, all the interfering medical users are legitimate but will cause disturbance to the desired user. In this work, we evaluate three deep learning (DL) algorithms: fully connected deep neural networks, convolutional neural networks, and long short-term memory neural networks for signal processing and detection in uncoded multiple medical devices OFDM communications systems. The bit error rates (BER) of these DL methods are compared with the conventional linear minimum mean squared error (LMMSE) detector. Additionally, the relationships between the BER and signal-to-interference ratio, signal-to-noise ratio, the number of interferences, and modulation type are investigated. Numerical results show that DL methods outperform LMMSE under different multiple medical device interference situations and are robust when the wireless channel has high variability. Also, DL methods are proven to have strong anti-interference ability and are useful in multiple medical devices OFDM systems.
2-Brain Regulation to Achieve Improved Neuroprotection during Early Development (2-BRAINED): A translational hyperscanning research project
Authors: Billeci Lucia , Riva Valentina , Capelli Elena , Grumi Serena , Pili Miriam Paola , Cassa Maddalena , Siri Eleonora , Roberti Elisa , Provenzi Livio
Published: June 2024

Introduction. Very preterm (VPT) birth is a major risk condition for child development and parental well-being, mainly due to multiple sources of stress (e.g., separation and pain exposure) during the Neonatal Intensive Care Unit (NICU) stay. Early video-feedback (VF) interventions proved effective in promoting VOT infants’ development and parental well-being. Electroencephalography (EEG) hyperscanning allows the assessment of brain-to-brain co-regulation during live interaction between infants and parents and holds promises to highlight mechanisms behind the interactive benefits of early VF interventions. Goals. To compare indexes of brain-to-brain co-regulation between dyads of full-term (FT) and VPT infants interacting with their mothers. To investigate the effect of an early post-discharge VF intervention on the brain-to-brain co-regulation indexes of VPT dyads.
Methods and analysis. VPT and FT dyads will be enrolled at birth and the former will be randomly allocated to one of two arms: VF intervention or care as usual. Short-term effectiveness will be assessed through ratings of mother-infant interaction videotaped before and after the VF intervention or care as usual. Mothers of VPT and FT infants will report on their mental state, parenting stress and bonding, and infant temperament and sensory profile at 3 and 6 months (corrected age, CA). At 9 months CA, all dyads will participate in a lab-based EEG-hyperscanning paradigm to assess brain-to-brain co-regulation through phase-locking value (PLV) and other explorative indexes. Ethics and dissemination. This study is funded by the Italian Ministry of Health and received approval by the Ethics Committee of Pavia (Italy) and participating hospitals. Research findings will be reported in scientific publications, presented at international conferences, and disseminated to the general public.
Study registration number. GR-2021-12375213 (Italian Ministry of Health registry)
Start-up of anammox in an up-flow anaerobic sludge bed reactor: bacterial community composition and antibiotic resistance genes
Authors: Li Xin , Yao Junqin , Jia Yangyang , Liu Jiaqi , Chen Yinguang
Published: June 2024

Anaerobic ammonia oxidation (anammox) is considered a high-efficiency and low-consumption biological nitrogen removal process. In this study, synthetic wastewater was used to start an up-flow anaerobic sludge bed reactor with a starting temperature of 20–31℃, and subsequently, the activated sludge samples were used to analyze the changes in bacterial community and antibiotic resistance genes (ARGs) by metagenomic sequencing. The results showed that the reaction successfully started up after 132 days of cultivation, achieving NH4+-N and NO2−-N removal rates over 99.5%. Candidatus Kuenenia, an anammox bacterium, increased from 0.01 to 50.86%. The denitrifying bacteria Delftia, Acidovorax, Thauera and Alicycliphilus decreased from 18.70, 8.02, 4.94 and 4.59% to 7.01, 1.77, 3.06 and 3.96%, respectively. The ammonia-oxidizing bacterium Nitrosomonas decreased from 2.91 to 1.87%. After cultivation, the relative abundance of ARGs in sludge decreased from 90.23 to 64.29 ppm, with sulfonamide, macrolide-lincosamide-streptogramin, tetracycline, aminoglycoside and multidrug ARGs being the main types. Additionally, the ARG subtypes sul1, msrE and tetX decreased, while ermF, sul2 and floR increased. These results contribute to knowledge of the nitrogen removal performance, changes in bacterial community composition and ARGs in an anammox reactor, providing the guidance for the removal of ARGs by anammox.
Optimization of microwave parameters to enhance phytochemicals, antioxidants and metabolite profile of de-oiled rice bran
Authors: Chowdhury Alonkrita , Kumar Alla Yaswanth Naveen , Kumar Rajesh , Maurya Vivek Kumar , Mahesh M. S. , Singh Abhishek Kumar , Yadav Pavan Kumar , Ghosh Mayukh
Published: June 2024

The current study delves into the impact of microwave treatment with different wattage and durations on phytoconstituents, antioxidant status, anti-nutritional factors (ANFs), and metabolite profiles of de-oiled rice bran. The total phenolics and flavonoids exhibited both up- and down-regulation based on specific microwave parameters, while an overall up-regulation in flavonol content was observed across all treated groups compared to the control. The DPPH and ABTS free radical scavenging activity, total antioxidant capacity, FRAP, CUPRAC, metal chelating activity, and ascorbic acid content were enhanced in most of the microwaved samples; however, longer microwave exposure at higher wattage led to their diminution. A treatment-specific reduction was observed for ANFs, viz., condensed tannin, oxalate, and phytate. HR-MS-based untargeted metabolomics revealed diverse primary and secondary metabolites that clustered in a group-specific manner, indicating prominent group-wise metabolite variations. Analyses of discriminating metabolites revealed non-significant differences in the overall levels of phenolics, flavonoids, vitamins and cofactors, sugars, amino acids, terpenoids, fatty acids, and their derivatives among the various treated groups compared to the control; however, several individual metabolites within these metabolite classes differed significantly. The current findings suggest that optimized microwaving of de-oiled rice bran can enhance phytochemicals and antioxidants while improving the metabolite profile.
Beyond the Screen: Exploring Digital Health Experiences of Individuals Affected by Psoriasis – A Qualitative Interview Study
Authors: Erbas Mert Ege , Ziehfreund Stefanie , Biedermann Tilo , Zink Alexander
Published: June 2024

Background: Psoriasis, a chronic inflammatory skin disorder, imposes a high burden on those affected, often leading to stigma and increased depression risk. With the increasing importance of digital media in medical contexts, there is a notable prevalence of misinformation and low-quality content. This study aims to explore the experiences of individuals affected by psoriasis regarding their disease-related digital media use.
Methods: Semi-structured interviews with open-ended questions were conducted with psoriasis-affected people between August 2020 and January 2022 in Germany. The participants were recruited through digital media platforms, professional contacts, and in person at a university hospital department in southern Germany and were interviewed via video call. The recorded data was pseudonymized, transcribed verbatim, and analyzed using qualitative content analysis by Mayring which also allowed a quantitative evaluation of the category placements.
Results: Eight participants (50% female) with a median age of 40.5 years (range: 25 – 80 years) were included. Four main categories emerged: (1) strengths and (2) difficulties of digital media in the context of psoriasis, (3) digital media in the context of the physician-patient relationship, and (4) suggestions for improvement. Commonly mentioned strengths were the positive impact on one’s well-being and the access to alternative therapy options. Frequently named problems were qualitative shortcomings and commercial interests. Most participants reported that digital media was not addressed in the physician-patient communication. Nevertheless, instances where it was discussed revealed predominantly negative reactions from physicians. Participants desired an increased availability of online resources and enhanced cooperation between digital media platforms and physicians.
Conclusions: This study underscores the opportunities and challenges presented by digital media in managing psoriasis. Physicians should ensure that their patients access reliable platforms. Collaboration between physicians and affected individuals on digital media and adapting the traditional physician-patient relationship to an increasingly digitalized world are suggested to enhance patient care.