bluuebunny/crossref_metadata_2025 huggingface dataset:
Spike 1 trimer, a nanoparticle vaccine against porcine epidemic diarrhea virus induces protective immunity challenge in piglets
Authors: Li Linjie , Yin Shuanghui , Zhou Jingjing , Zhang Liping , Teng Zhidong , Qiao Lu , Wang Yunhang , Yu Jiaxi , Zang Haoyue , Ding Yaozhong , Liu Xinsheng , Sun Shiqi , Guo Huichen
Published: April 2024

Porcine epidemic diarrhea virus (PEDV) is considered the cause for porcine epidemic diarrhea (PED) outbreaks and hefty losses in pig farming. However, no effective commercial vaccines against PEDV mutant strains are available nowadays. Here, we constructed three native-like trimeric candidate nanovaccines, i.e., spike 1 trimer (S1-Trimer), collagenase equivalent domain trimer (COE-Trimer), and receptor-binding domain trimer (RBD-Trimer) for PEDV based on Trimer-Tag technology. And evaluated its physical properties and immune efficacy. The result showed that the candidate nanovaccines were safe for mice and pregnant sows, and no animal death or miscarriage occurred in our study. S1-Trimer showed stable physical properties, high cell uptake rate and receptor affinity. In the mouse, sow and piglet models, immunization of S1-Trimer induced high-level of humoral immunity containing PEDV-specific IgG and IgA. S1-Trimer-driven mucosal IgA responses and systemic IgG responses exhibited high titers of virus neutralizing antibodies (NAbs) in vitro. S1-Trimer induced Th1-biased cellular immune responses in mice. Moreover, the piglets from the S1-Trimer and inactivated vaccine groups displayed significantly fewer microscopic lesions in the intestinal tissue, with only one and two piglets showing mild diarrhea. The viral load in feces and intestines from the S1-Trimer and inactivated vaccine groups were significantly lower than those of the PBS group. For the first time, our data demonstrated the protective efficacy of Trimer-Tag-based nanovaccines used for PEDV. The S1-Trimer developed in this study was a competitive vaccine candidate, and Trimer-Tag may be an important platform for the rapid production of safe and effective subunit vaccines in the future.
Plant and soil responses to tillage practices change arbuscular mycorrhizal fungi populations during crop growth
Authors: Li Jing , Jia Lijuan , Struik Paul C. , An Zhengfeng , Wang Zhen , Xu Zhuwen , Ji Lei , Yao Yuqing , Lv Junjie , Zhou Tao , Jin Ke
Published: April 2024

Background

Tillage practices can substantially affect soil properties depending on crop stage. The interaction between tillage and crop growth on arbuscular mycorrhizal fungi (AMF) communities remains unclear. We investigated the interactions between four tillage treatments (CT: conventional tillage, RT: reduced tillage, NT: no tillage with mulch, and SS: subsoiling with mulch), maintained for 25 years, and two wheat growth stages (elongation stage and grain filling stage) on AMF diversity and community composition.

Results

The AMF community composition strongly changed during wheat growth, mainly because of changes in the relative abundance of dominant genera Claroideoglomus, Funneliformi, Rhizophagu, Entrophospora, and Glomus. Co-occurrence network analysis revealed that the grain filling stage had a more complex network than the elongation stage. Redundancy analysis results showed that keystone genera respond mainly to changes in soil organic carbon during elongation stage, whereas the total nitrogen content affected the keystone genera during grain filling. Compared with CT, the treatments with mulch, i.e., NT and SS, significantly changed the AMF community composition. The change of AMF communities under different tillage practices depended on wheat biomass and soil nutrients. NT significantly increased the relative abundances of Glomus and Septoglomus, while RT significantly increased the relative abundance of Claroideoglomus.

Conclusion

Our findings indicate that the relative abundance of dominant genera changed during wheat growth stages. Proper tillage practices (e.g., NT and SS) benefit the long-term sustainable development of the Loess Plateau cropping systems.
Uncorking the limitation—improving dual tasking using transcranial electrical stimulation and task training in the elderly: a systematic review
Authors: Jiang Yong , Ramasawmy Perianen , Antal Andrea
Published: April 2024

Introduction

With aging, dual task (DT) ability declines and is more cognitively demanding than single tasks. Rapidly declining DT performance is regarded as a predictor of neurodegenerative disease. Task training and non-invasive transcranial electrical stimulation (tES) are methods applied to optimize the DT ability of the elderly.

Methods

A systematic search was carried out in the PUBMED, TDCS (transcranial direct current stimulation) databases, as well as Web of Science, and a qualitative analysis was conducted in 56 included studies. Aiming to summarize the results of studies that implemented tES, task training, or the combination for improving DT ability and related performance changes in healthy elderly and geriatric patients. For different approaches, the training procedures, parameters, as well as outcomes were discussed.

Results

Task training, particularly cognitive-motor DT training, has more notable effects on improving DT performance in the elderly when compared to the neuromodulation method.

Discussion

Anodal transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (L-DLPFC), or its combination with task training could be promising tools. However, additional evidence is required from aged healthy people and patients, as well as further exploration of electrode montage.
Case report: Association between PTEN-gene variant and an aggressive case of multiple dAVFs
Authors: Jong-A-Liem Glaucia Suzanna , Sarti Talita Helena Martins , dos Santos Mariusi Glasenapp , Giacon Luciano Marcus Tirotti , Wuo-Silva Raphael , Baeta Alex Machado , de Campos Filho José Maria , Chaddad-Neto Feres
Published: April 2024

Introduction

Mutations of the phosphatase and tensin homolog (PTEN) gene have been associated with a spectrum of disorders called PTEN hamartoma tumor syndrome, which predisposes the individual to develop various types of tumors and vascular anomalies. Its phenotypic spectrum includes Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome (BRRS), Proteus syndrome, autism spectrum disorders (ASD), some sporadic cancers, Lhermitte–Duclos disease (LDD), and various types of associated vascular anomalies.

Clinical presentation

A previously healthy 27-year-old woman was experiencing visual scintillating scotomas and mild chronic headaches for the past 2 years. The initial computed tomographic (CT) and magnetic resonance imaging (MRI) scans did not reveal any abnormalities, but the possibility of pseudotumor cerebri was considered. Furthermore, a cerebral angiogram showed a posterior fossa dural arteriovenous fistula (dAVF), which was initially treated through embolization. However, in spite of proper treatment, this patient experienced multiple recurrent dAVFs in different locations, requiring multiple embolizations and surgeries. Despite exhibiting altered cerebral perfusion and hemodynamics, the patient did not display any significant symptoms until she experienced a sudden stroke resulting from deep venous thrombosis, which was not associated with any medical procedures or medication use. A comprehensive analysis was performed due to the aggressive nature of the dAVFs. Surprisingly, exome sequencing of a blood sample revealed a PTEN gene variant in chromosome 10, indicative of Cowden syndrome. However, no tumors or other vascular lesions were detected in other systems that would constitute Cowden syndrome.

Conclusion

The rapid formation of multiple and complex dAVFs, coupled with not meeting the criteria for any other PTEN-related syndrome, unequivocally leads to the presentation of a novel phenotype of the PTEN germline variant.
Primary CNS vasculitis: insights into clinical, neuropathological, and neuroradiological characteristics
Authors: Sheikh Tahani Saker , Rozenberg Ayal , Merhav Goni , Shifrin Alla , Stein Polina , Shelly Shahar
Published: April 2024

Background and objectives

Primary CNS vasculitis (PCNSV) is a rare inflammatory disorder that affects the blood vessels of the central nervous system (CNS). We aimed to analyze the neurological presentations, clinical follow-up, and long-term outcomes of patients with primary central nervous system vasculitis.

Methods

We conducted a retrospective analysis of medical records to assess the neurological presentation, rate of remission, and functional status at the last follow-up in patients with primary central nervous system vasculitis seen in our center in the last 13 years (2010–2023).

Results

We identified five patients, whose median age at symptom onset was 31 years (range: 15–41 years), including four male individuals (80%) from Muslim Arab (n = 4) and Ashkenazi Jewish (n = 1) backgrounds. Symptoms persisted for a median of 36 weeks (range: 3 weeks to 4 years) before diagnosis, with one case exceeding 3 years. Follow-up lasted a median of 56 months (range: 20–161 months). Clinical symptoms varied, presenting unilateral weaknesses (n = 2), cognitive and gait abnormality (n = 1), headaches (n = 1), and epileptic seizures (n = 1). MRI scans revealed abnormalities in the basal ganglia, corona radiata, parietal, and frontal lobes, showing hemorrhage, vasogenic edema, restricted diffusion, and enhancement post-gadolinium. All patients reported progressive holocephalic headaches and cognitive changes with overall progressive symptoms. Initial neurological examinations revealed abnormalities in all patients and included one or more of the following: cognitive or visual impairment (n = 2), seizures (n = 1), and unilateral UMN signs (n = 2) at the initial neurological examination, all but one patient required walking aids including (cane 2, wheelchair, bedridden 1). Patients were stable (n = 2), deteriorated (n = 1), or improved (n = 2). Following treatment, two patients still required ambulatory aids, with one using a cane and the other using a wheelchair, while the remaining three did not require any ambulatory aids.

Discussion

The study on PCNSV highlights varied symptoms and diagnostic challenges, including delayed diagnosis and a spectrum of neurological issues from cognitive impairments to seizures. Brain biopsies showed lymphocytic infiltration, thrombi, and necrosis. Immunotherapy significantly improved clinical and radiological outcomes. Over 56 months of follow-up, outcomes varied from stability and deterioration to improvement.
Hemorrhagic cerebral venous infarction after vein injury during intraoperative lesion resection: incidence, hemorrhagic stages, risk factors and prognosis
Authors: Wu Yingxi , Tian Qilong , Wang Shoujie , Li Kailu , Feng Dayun , Cai Qing
Published: April 2024

Objective

Cerebral venous infarction (CVI) after vein injury during intraoperative lesion resection is associated with intracranial hemorrhage. We conducted this study to identify the incidence, clinical and imaging features, and prognosis of hemorrhage CVI.

Methods

We performed a retrospective analysis of patients with confirmed CVI after vein injury who underwent craniotomy in our hospital. Postoperative clinical symptoms were observed, and imaging features were compared between patients with and without intracranial hemorrhages through CT examination. Variables were analyzed using univariate and multivariate regression analyses.

Results

Among 2,767 patients who underwent craniotomy, 93 cases of injured veins were identified intraoperatively. Hemorrhagic CVI was found in 38% (35/93). Multivariate analysis revealed that midline approach, meningioma, postoperative seizures, disorders of consciousness and interval in hours < 72 h were identified as predictors of hemorrhagic CVI. After 3 months of follow-up, the prognosis was poor in 15 cases (16%, 15/93), including death (two cases), vegetative survival (four cases), and severe disability (nine cases).

Conclusions

Hemorrhagic CVI, as a critical complication after venous injury, can have disastrous consequences. Do not injure known veins intraoperatively. In case of injury, requisite remedial measures should be adopted during and after surgery.
Neuromagnetic representation of musical roundness in chord progressions
Authors: Wöhrle Sophie D. , Reuter Christoph , Rupp André , Andermann Martin
Published: April 2024

Introduction

Musical roundness perception relies on consonance/dissonance within a rule-based harmonic context, but also on individual characteristics of the listener. The present work tackles these aspects in a combined psychoacoustic and neurophysiological study, taking into account participant’s musical aptitude.

Methods

Our paradigm employed cadence-like four-chord progressions, based on Western music theory. Chord progressions comprised naturalistic and artificial sounds; moreover, their single chords varied regarding consonance/dissonance and harmonic function. Thirty participants listened to the chord progressions while their cortical activity was measured with magnetoencephalography; afterwards, they rated the individual chord progressions with respect to their perceived roundness.

Results

Roundness ratings differed according to the degree of dissonance in the dominant chord at the progression’s third position; this effect was pronounced in listeners with high musical aptitude. Interestingly, a corresponding pattern occurred in the neuromagnetic N1m response to the fourth chord (i.e., at the progression’s resolution), again with somewhat stronger differentiation among musical listeners. The N1m magnitude seemed to increase during chord progressions that were considered particularly round, with the maximum difference after the final chord; here, however, the musical aptitude effect just missed significance.

Discussion

The roundness of chord progressions is reflected in participant’s psychoacoustic ratings and in their transient cortical activity, with stronger differentiation among listeners with high musical aptitude. The concept of roundness might help to reframe consonance/dissonance to a more holistic, gestalt-like understanding that covers chord relations in Western music.
Effectiveness of mangrove sword bean food bar addressed to older people of landslide disaster victims
Authors: Fatmah Fatmah
Published: April 2024

Background

Older people require extra attention due to their reduced ability to prepare for disasters, as they adequately possess distinct needs. These groups necessitate uncomplicated, readily consumable, and palatable food options that fulfill their micronutrient needs. The objective of this research was to assess the effects of a snack bar enriched with api-api mangrove (Avicennia marina) and sword bean (Canavalia ensiformis) on the body weight and Body Mass Index (BMI) of older people individuals afflicted by a landslide event.

Methods

A non-randomized pre-post-intervention study was undertaken, involving 31 senior participants. The intervention group consisted of 15 seniors who were provided with a mangrove sword bean snack bar, while the control group comprised 16 seniors who received a sword bean food bar during 15 days. All study participants received education on maintaining a balanced diet for older people individuals. The data analysis involved using univariate and bivariate analyses, explicitly applying the independent t-test and dependent t-test.

Results

In the hedonic evaluation, the mangrove sword bean food bar had superior average attributes in terms of scent, flavor, texture, and color compared to the sword bean food bar. The consumption of snack bars made from mangrove sword beans resulted in a significant rise in weight (0.2 kg), energy intake (240.8 kcal), protein content (5.8 g), carbohydrate content (40.06 g), and fat content (4.4 g). Carbohydrate can significantly increase weight in the treatment subjects. Furthermore, the provision of comprehensive nutrition education has the potential to enhance the post-study knowledge score, as seen by the observed increase of 40.6. A significant disparity was observed between the mean carbohydrate consumption and understanding of balanced nutrition among the intervention and control groups.

Conclusion

Api-api mangrove sword bean snack bars have been identified as a viable and efficient substitute for emergency food provisions, particularly in disaster-stricken communities. These food bars have demonstrated a significant capacity to contribute to the weight gain of individuals within such groups, thus addressing the nutritional needs of impacted populations in the aftermath of natural calamities. Subsequent investigations may include employing pregnant women as participants to explore the issue above.

Clinical Trial Registration

Clinicaltrials.gov, identifier: NCT05897892.
Anlotinib in Chinese patients aged ≥70 years with advanced non-squamous non-small cell lung cancer without prior chemotherapy: a multicenter, single-arm pilot trial
Authors: Zhao Da , Li Zhengguo , Hou Xinli , Yang Lei , Li Zeng , Yan Li , Li Hongling , Liu Hua , Liu Xiaoping , Song Feixue , Li Guixiang , Zhang Yu , Hou Xiaoming
Published: April 2024

Background

Based on pharmacoeconomics, drug availability and actual treatment, optimal treatment regimens for Chinese non-small-cell lung carcinoma (NSCLC) patients over 70 years old are needed.

Methods

This multicenter, single-arm pilot trial enrolled patients with advanced non-squamous NSCLC who refused systemic chemotherapy. Eligible patients received anlotinib (12 mg/day, d1-14, Q3W) until disease progression, intolerant toxicities, or withdrawal from the study. The primary endpoint was progression-free survival (PFS).

Results

Forty-nine patients were screened between January 2019 and September 2021, of whom 40 patients were eligible. The median age was 76 years. With a median follow-up period of 16.20 (95% CI: 8.77, 25.10) months, the median PFS was 5.45 months (95% CI: 3.52-9.23) and the median overall survival was 10.32 months (95% CI: 6.44-12.78). Three patients achieved a partial response and 34 had stable disease, with an objective response rate of 7.5% and a disease control rate of 92.5%. Thirty-three (82.5%; 33/40) patients reported treatment-related adverse events (TRAEs) of any grade, and the incidence rate of grade ≥3 TRAEs was 35% (14/40). The most common grade ≥3 TRAEs were hypertension (4/40; 10.0%), hand-foot syndrome (3/40; 7.5%), and proteinuria (2/40; 5.0%).

Conclusion

Anlotinib treatment was feasible and safe in Chinese elderly patients with advanced non-squamous NSCLC who did not receive any systemic chemotherapy.
Gastric mixed neuroendocrine non-neuroendocrine neoplasms
Authors: Liu Li , Li Qian , Liu Wenxuan , Qiu Zhendong , Wu Zhongkai , Yu Danli , Deng Wenhong
Published: April 2024

The uncommon tumour known as gastric mixed neuroendocrine-non-neuroendocrine neoplasms (G-MiNENs) is made up of parts of neuroendocrine carcinoma and adenocarcinoma. The biological and clinical features are different from those of gastric adenocarcinoma. Their pathophysiology, diagnostic standards, and clinical behaviour have all been the subject of lengthy debates, and their nomenclature has undergone multiple changes. Its emergence has created new challenges in the classification and diagnosis of gastric tumours. This review will update information on the topic, covering molecular aspects, diagnostic criteria, treatment, and prognostic factor discovery. It will also provide a historical context that will aid in understanding the evolution of the idea and nomenclature of mixed gastric tumours. Additionally, it will provide the reader a thorough understanding of this difficult topic of cancer that is applicable to real-world situations.
A novel nomogram model based on Ki-67 characteristic expression to predict prognosis in head and neck squamous cell carcinoma
Authors: Wang Tianyi , Xue Lili , Li Zhixin , Hong Zhicong , Hu Niting , Li Yi , Yan Bing
Published: April 2024

Objectives

This study aimed to examine Ki-67’s correlation with clinicopathological characteristics of head and neck squamous cell carcinoma (HNSCC), evaluate its prognostic significance, and develop a Ki-67 integrated prognostic model.

Methods

The retrospective study included 764 HNSCC patients hospitalized from 2012 to 2022. Data were sourced from medical records and immunohistochemical analysis of surgical specimens.

Results

Ki-67 expression was significantly associated with sex, pathological grade, clinical stage, and metastasis, but not with age or recurrence. Higher Ki-67 levels were linked to poorer prognosis, as indicated by Kaplan-Meier survival analysis. Utilizing a Cox proportional hazards model, four prognostic factors were identified: age, recurrence, metastasis, and Ki-67 expression. These factors were used to construct a prognostic model and a nomogram. The model’s predictive accuracy was confirmed by a high concordance index and a reliable calibration curve.

Conclusion

Ki-67 expression in HNSCC patients correlates with several clinicopathological features and serves as a negative prognostic marker. A prognostic model incorporating Ki-67 was successfully developed, offering a new tool for patient prognosis assessment in HNSCC.
Co-operation of MCL-1 and BCL-XL anti-apoptotic proteins in stromal protection of MM cells from carfilzomib mediated cytotoxicity
Authors: Galas-Filipowicz Daria , Chavda Selina J. , Gong Jia-Nan , Huang David C. S. , Khwaja Asim , Yong Kwee
Published: April 2024

Introduction

BCL-2 family proteins are important for tumour cell survival and drug resistance in multiple myeloma (MM). Although proteasome inhibitors are effective anti-myeloma drugs, some patients are resistant and almost all eventually relapse. We examined the function of BCL-2 family proteins in stromal-mediated resistance to carfilzomib-induced cytotoxicity in MM cells.

Methods

Co-cultures employing HS5 stromal cells were used to model the interaction with stroma. MM cells were exposed to CFZ in a 1-hour pulse method. The expression of BCL-2 family proteins was assessed by flow cytometry and WB. Pro-survival proteins: MCL-1, BCL-2 and BCL-XL were inhibited using S63845, ABT-199 and A-1331852 respectively. Changes in BIM binding partners were examined by immunoprecipitation and WB.

Results

CFZ induced dose-dependent cell death of MM cells, primarily mediated by apoptosis. Culture of MM cells on HS-5 stromal cells resulted in reduced cytotoxicity to CFZ in a cell contact-dependent manner, upregulated expression of MCL-1 and increased dependency on BCL-XL. Inhibiting BCL-XL or MCL-1 with BH-3 mimetics abrogated stromal-mediated protection only at high doses, which may not be achievable in vivo. However, combining BH-3 mimetics at sub-therapeutic doses, which alone were without effect, significantly enhanced CFZ-mediated cytotoxicity even in the presence of stroma. Furthermore, MCL-1 inhibition led to enhanced binding between BCL-XL and BIM, while blocking BCL-XL increased MCL-1/BIM complex formation, indicating the cooperative role of these proteins.

Conclusion

Stromal interactions alter the dependence on BCL-2 family members, providing a rationale for dual inhibition to abrogate the protective effect of stroma and restore sensitivity to CFZ.
Respiratory disease patterns in rural Western Uganda, 2019–2022
Authors: Weary Taylor E. , Tusiime Patrick , Tuhaise Shamilah , Mandujano Reyes Juan Francisco , Ross Elizabeth , Gern James E. , Goldberg Tony L.
Published: April 2024

Introduction

Respiratory disease is a major cause of morbidity and mortality in the developing world, but prospective studies of temporal patterns and risk factors are rare.

Methods

We studied people in rural Western Uganda, where respiratory disease is pervasive. We followed 30 adults (ages 22–51 years; 534 observations) and 234 children (ages 3–11 years; 1,513 observations) between May 2019 and July 2022 and collected monthly data on their respiratory symptoms, for a total of 2,047 case records. We examined associations between demographic and temporal factors and respiratory symptoms severity.

Results

The timing of our study (before, during, and after the emergence of COVID-19) allowed us to document the effects of public health measures instituted in the region. Incidence rates of respiratory symptoms before COVID-19 lockdown were 568.4 cases per 1,000 person-months in children and 254.2 cases per 1,000 person-months in adults. These rates were 2.6 times higher than the 2019 global average for children but comparable for adults. Younger children (ages 3–6 years) had the highest frequencies and severities of respiratory symptoms. Study participants were most likely to experience symptoms in February, which is a seasonal pattern not previously documented. Incidence and severity of symptoms in children decreased markedly during COVID-19 lockdown, illustrating the broad effects of public health measures on the incidence of respiratory disease.

Discussion

Our results demonstrate that patterns of respiratory disease in settings such as Western Uganda resemble patterns in developed economies in some ways (age-related factors) but not in others (increased incidence in children and seasonal pattern). Factors such as indoor air quality, health care access, timing of school trimesters, and seasonal effects (rainy/dry seasons) likely contribute to the differences observed.
Retroperitoneal neuroglial heterotopia: a case report and literature review
Authors: Zhong Jianhua , Yang Lijun , Lin Jinhui , Wu Ruifa , Liu Wenguang , Xu Qinfang , Ma Da , Qu Zhibo
Published: April 2024

Background

Neuroglial heterotopia is a rare lesion composed of differentiated neuroectodermal cells that manifest in extracranial locations, with the majority of cases predominantly occurring in the head and neck region. Retroperitoneal neuroglial heterotopia is exceptionally rare, with isolated cases published in the scientific literature.

Case report

Here, we present the case of a 3-year-old girl who was admitted without clinical signs but presented with a palpable abdominal mass. Ultrasonography and computed tomography scans revealed a sizable cystic lesion within the retroperitoneal space. Subsequently, laparoscopic resection was performed. Histological examination unveiled neuroglial cell-lined cysts encompassing fibrous connective tissue, ganglia, glial tissue, and nerve bundles. Notably, distinct areas and cell types exhibited expression of S100, glial fibrillary acidic protein, and neuron-specific enolase. Follow-up assessments revealed no relapses or late complications.

Conclusion

In cases of retroperitoneal neuroglial heterotopia, most children may remain asymptomatic without any congenital anomalies. Despite their detectability through imaging, accurate preoperative diagnosis is seldom achieved. Generally, a favorable prognosis follows complete surgical resection, although further cases are required to confirm its long-term efficacy, necessitating extended follow-up for verification.
Identification of hub genes and potential molecular mechanisms related to drug sensitivity in acute myeloid leukemia based on machine learning
Authors: Zhang Boyu , Liu Haiyan , Wu Fengxia , Ding Yuhong , Wu Jiarun , Lu Lu , Bajpai Akhilesh K. , Sang Mengmeng , Wang Xinfeng
Published: April 2024

Background: Acute myeloid leukemia (AML) is the most common form of leukemia among adults and is characterized by uncontrolled proliferation and clonal expansion of hematopoietic cells. There has been a significant improvement in the treatment of younger patients, however, prognosis in the elderly AML patients remains poor.

Methods: We used computational methods and machine learning (ML) techniques to identify and explore the differential high-risk genes (DHRGs) in AML. The DHRGs were explored through multiple in silico approaches including genomic and functional analysis, survival analysis, immune infiltration, miRNA co-expression and stemness features analyses to reveal their prognostic importance in AML. Furthermore, using different ML algorithms, prognostic models were constructed and validated using the DHRGs. At the end molecular docking studies were performed to identify potential drug candidates targeting the selected DHRGs.

Results: We identified a total of 80 DHRGs by comparing the differentially expressed genes derived between AML patients and normal controls and high-risk AML genes identified by Cox regression. Genetic and epigenetic alteration analyses of the DHRGs revealed a significant association of their copy number variations and methylation status with overall survival (OS) of AML patients. Out of the 137 models constructed using different ML algorithms, the combination of Ridge and plsRcox maintained the highest mean C-index and was used to build the final model. When AML patients were classified into low- and high-risk groups based on DHRGs, the low-risk group had significantly longer OS in the AML training and validation cohorts. Furthermore, immune infiltration, miRNA coexpression, stemness feature and hallmark pathway analyses revealed significant differences in the prognosis of the low- and high-risk AML groups. Drug sensitivity and molecular docking studies revealed top 5 drugs, including carboplatin and austocystin-D that may significantly affect the DHRGs in AML.

Conclusion: The findings from the current study identified a set of high-risk genes that may be used as prognostic and therapeutic markers for AML patients. In addition, significant use of the ML algorithms in constructing and validating the prognostic models in AML was demonstrated. Although our study used extensive bioinformatics and machine learning methods to identify the hub genes in AML, their experimental validations using knock-out/-in methods would strengthen our findings.
Progress of medicinal plants and their active metabolites in ischemia-reperfusion injury of stroke: a novel therapeutic strategy based on regulation of crosstalk between mitophagy and ferroptosis
Authors: Zhang Guozhen , Wang Qiang , Jiang Bing , Yao Lihe , Wu Wenjuan , Zhang Xiaoyan , Wan Dongjun , Gu Youquan
Published: April 2024

The death of cells can occur through various pathways, including apoptosis, necroptosis, mitophagy, pyroptosis, endoplasmic reticulum stress, oxidative stress, ferroptosis, cuproptosis, and disulfide-driven necrosis. Increasing evidence suggests that mitophagy and ferroptosis play crucial regulatory roles in the development of stroke. In recent years, the incidence of stroke has been gradually increasing, posing a significant threat to human health. Hemorrhagic stroke accounts for only 15% of all strokes, while ischemic stroke is the predominant type, representing 85% of all stroke cases. Ischemic stroke refers to a clinical syndrome characterized by local ischemic-hypoxic necrosis of brain tissue due to various cerebrovascular disorders, leading to rapid onset of corresponding neurological deficits. Currently, specific therapeutic approaches targeting the pathophysiological mechanisms of ischemic brain tissue injury mainly include intravenous thrombolysis and endovascular intervention. Despite some clinical efficacy, these approaches inevitably lead to ischemia-reperfusion injury. Therefore, exploration of treatment options for ischemic stroke remains a challenging task. In light of this background, advancements in targeted therapy for cerebrovascular diseases through mitophagy and ferroptosis offer a new direction for the treatment of such diseases. In this review, we summarize the progress of mitophagy and ferroptosis in regulating ischemia-reperfusion injury in stroke and emphasize their potential molecular mechanisms in the pathogenesis. Importantly, we systematically elucidate the role of medicinal plants and their active metabolites in targeting mitophagy and ferroptosis in ischemia-reperfusion injury in stroke, providing new insights and perspectives for the clinical development of therapeutic drugs for these diseases.
Research on the ditching resistance reduction of self-excited vibrations ditching device based on MBD-DEM coupling simulation
Authors: Zeng Ye , Li Jun , Li Hongcai , Zhang Qianqian , Li Can , Li Zhao , Jiang Runpeng , Mai Chaodong , Ma Zhe , He Hongwei
Published: April 2024

In plant horticulture, furrow fertilizing is a common method to promote plant nutrient absorption and to effectively avoid fertilizer waste. Considering the high resistance caused by soil compaction in southern orchards, an energy-saving ditching device was proposed. A standard ditching blade with self-excited vibration device was designed, and operated in sandy clay with a tillage depth of 30cm. To conduct self-excited vibration ditching experiments, a simulation model of the interaction between soil and the ditching mechanism was established by coupling the ADAMS and EDEM software. To begin with, the ditching device model was first set up, taking into account its motion and morphological characteristics. Then, the MBD-DEM coupling method was employed to investigate the interaction mechanism and the effect of ditching between the soil particles and the ditching blade. Afterwards, the time-domain and frequency-domain characteristics of vibration signals during the ditching process were analyzed using the fast fourier transform (FFT) method, and the energy distribution characteristics were extracted using power spectral density (PSD). The experimental results revealed that the vibrations ditching device has reciprocating displacement in the Dx direction and torsional displacements in the θy and θz directions during operation, verifying the correctness of the coupling simulation and the effectiveness of vibrations ditching resistance reduction. Also, a load vibrations ditching bench test was conducted, and the results demonstrated that the self-excited vibrations ditching device, compared with common ditching device, achieved a reduction in ditching resistance of up to 12.3%. The reasonable parameters of spring stiffness, spring damping, and spring quality in self-excited vibrations ditching device can achieve a satisfied ditching performance with relatively low torque consumption at an appropriate speed.
Reduction of Fusarium head blight and trichothecene contamination in transgenic wheat expressing Fusarium graminearum trichothecene 3-O-acetyltransferase
Authors: Yulfo-Soto Gabdiel , McCormick Susan , Chen Hui , Bai Guihua , Trick Harold N. , Hao Guixia
Published: April 2024

Fusarium graminearum, the causal agent of Fusarium head blight (FHB), produces various mycotoxins that contaminate wheat grains and cause profound health problems in humans and animals. Deoxynivalenol (DON) is the most common trichothecene found in contaminated grains. Our previous study showed that Arabidopsis-expressing F. graminearum trichothecene 3-O-acetyltransferase (FgTRI101) converted DON to 3-acetyldeoxynivalenol (3-ADON) and excreted it outside of Arabidopsis cells. To determine if wheat can convert and excrete 3-ADON and reduce FHB and DON contamination, FgTRI101 was cloned and introduced into wheat cv Bobwhite. Four independent transgenic lines containing FgTRI101 were identified. Gene expression studies showed that FgTRI101 was highly expressed in wheat leaf and spike tissues in the transgenic line FgTri101-1606. The seedlings of two FgTri101 transgenic wheat lines (FgTri101-1606 and 1651) grew significantly longer roots than the controls on media containing 5 µg/mL DON; however, the 3-ADON conversion and excretion was detected inconsistently in the seedlings of FgTri101-1606. Further analyses did not detect 3-ADON or other possible DON-related products in FgTri101-1606 seedlings after adding deuterium-labeled DON into the growth media. FgTri101-transgenic wheat plants showed significantly enhanced FHB resistance and lower DON content after they were infected with F. graminearum, but 3-ADON was not detected. Our study suggests that it is promising to utilize FgTRI101, a gene that the fungus uses for self-protection, for managing FHB and mycotoxin in wheat production.
Mental and social wellbeing trajectory during the pandemic for vulnerable populations
Authors: Joyce Andrew , Tran Thach , Stocker Ruby , Fisher Jane
Published: April 2024

Objectives

We investigated changes over time in mental and social wellbeing indicators for vulnerable population subgroups during the pandemic. These groups were younger people, people with disabilities, low-income groups, unemployed, culturally, and linguistically diverse communities (CaLD), and Aboriginal and Torres Strait Islander peoples.

Methods

A series of four repeated population representative surveys were conducted in June 2020, September 2020, January 2022, and June 2022. Questions included items on psychological distress, financial hardship, social connection, and life satisfaction.

Results

For most groups, social connection and life satisfaction improved in 2022 relative to 2020. Psychological distress and financial hardship showed the opposite pattern, with some groups having worse results in 2022 relative to 2020. People without any vulnerability had better mental health and social wellbeing outcomes at each time point relative to the vulnerable population subgroups.

Conclusion

Pandemic-related policies had differential effects over time and for different population groups. Future policies and research need to closely monitor how they impact population subgroups, and the overall results clearly demonstrate the inequity in mental health and social wellbeing outcomes for vulnerable population cohorts.
Impact of health investment on household income distribution: insights from China’s longitudinal survey data
Authors: Zheng Lili , Hou Wenhua , Huang Ming
Published: April 2024

This paper investigates the impact of health investment on household income distribution, drawing from data spanning over 10 years from the China Nutrition and Health Survey. The study aims to contribute to the literature by examining the nuanced pathways through which health investment influences income distribution. Utilizing a rich dataset, rigorous empirical methods including quantile regression and cross-sectional data modeling are employed to explore the relationship between health investment and income distribution. The analysis reveals a robust positive association between health investment and both absolute and relative income levels across various demographic and occupational groups. Additionally, the study elucidates the pathways through which health investment influences income, including its effects on illness duration, employment opportunities, effective working time, and educational attainment. The findings demonstrate the dynamic nature of the relationship, indicating that as income levels rise, the impact of health investment on income becomes more pronounced. Moreover, the analysis highlights the role of health investment in facilitating upward income mobility, particularly for low-income households. Overall, these findings provide valuable insights for policymakers, suggesting that strategic health investment initiatives can contribute to achieving more equitable income distribution.
Utilization of post-exposure prophylaxis potentially contributed to the changes of risk behaviors among men who have sex with men in China
Authors: Su Rong , Liu Yi , Li Peilong , Ge Lin , Liao Meizhen , Fu Yong , Song Xin , Tang Houlin , Li Dongmin
Published: April 2024

Background

The HIV infection status among men who have sex with men (MSM) in China is a cause for concern. Post-exposure prophylaxis (PEP) serves as a highly effective biomedical preventive measure against HIV infection. Substantial evidence has established an association between PEP utilization and risk behaviors among MSM, but whether the utilization of PEP has an impact on risk behaviors remains unknown. This study sought to elucidate the impact of PEP usage on risk behaviors among MSM and provide recommendations for developing targeted HIV prevention programs.

Methods

A cohort study was conducted in Qingdao, China, from April 2021 to January 2022. Participants were enlisted by volunteers from community-based organizations through a snowball sampling method. Face-to-face interviews were conducted to collect sociodemographic and behavioral information of participants. The study encompassed a retrospective investigation, baseline survey, and follow-up survey, representing periods before, during, and after PEP usage, respectively. Generalized estimating equations, fitting a Poisson regression model, were applied to scrutinize changes in risk behaviors of MSM during and after PEP usage, in comparison to before PEP usage.

Results

A total of 341 MSM were recruited in the cohort study, with 179 individuals completing the follow-up survey. In comparison to before PEP usage, there was a significant increase in the proportion of Rush Popper usage (17.6% vs. 23.8% vs. 29.6%) and commercial sexual partners (10.9% vs. 17.6% vs. 21.8%) among MSM during and after PEP usage. Before PEP usage, 88.7% of MSM reported having ≥3 temporary sexual partners in the last 6 months. This proportion exhibited no significant change during PEP usage (91.8%), but it significantly increased to 97.8% after PEP usage (P < 0.05). Notably, there was a significant decrease in group sex during and after PEP usage compared to before PEP usage (30.8% vs. 21.4% vs. 21.2%).

Conclusion

The utilization of PEP may impact risk behaviors among MSM, potentially leading to increased Rush Popper usage, temporary sexual partners, and commercial sexual partners after PEP usage, accompanied by a decrease in group sex. Further research is imperative to elucidate the impact of PEP utilization on MSM and develop targeted HIV prevention programs.
Analysis on time delay of tuberculosis among adolescents and young adults in Eastern China
Authors: Ge Rui , Zhu Guoying , Tian Min , Hou Zhigang , Pan Weizhe , Feng Hao , Liu Kui , Xiao Qinfeng , Chen Zhongwen
Published: April 2024

Background

Tuberculosis (TB) is recognized as a significant global public health concern. Still, there remains a dearth of comprehensive evaluation regarding the specific indicators and their influencing factors of delay for adolescents and young adults.

Methods

All notified pulmonary TB (PTB) patients in Jiaxing City were collected between 2005 and 2022 from China’s TB Information Management System. Logistic regression models were conducted to ascertain the factors that influenced patient and health system delays for PTB cases, respectively. Furthermore, the impact of the COVID-19 pandemic on local delays has been explored.

Results

From January 1, 2005 to December 31, 2022, a total of 5,282 PTB cases were notified in Jiaxing City, including 1,678 adolescents and 3,604 young adults. For patient delay, female (AOR: 1.18, 95%CI: 1.05–1.32), PTB complicated with extra-pulmonary TB (AOR: 1.70, 95% CI: 1.28–2.26), passive case finding (AOR: 1.46, 95% CI: 1.07–1.98) and retreatment (AOR: 1.52, 95% CI: 1.11–2.09) showed a higher risk of delay. For health system delay, minorities (AOR: 0.69, 95% CI: 0.53–0.90) and non-students (AOR: 0.83, 95% CI: 0.71–0.98) experienced a lower delay. Referral (AOR: 1.46, 95% CI: 1.29–1.65) had a higher health system delay compared with clinical consultation. Furthermore, county hospitals (AOR: 1.47, 95% CI: 1.32–1.65) and etiological positive results (AOR: 1.46, 95% CI: 1.30–1.63) were associated with comparatively high odds of patient delay. Contrarily, county hospitals (AOR: 0.88, 95% CI: 0.78–1.00) and etiological positive results (AOR: 0.67, 95% CI: 0.59–0.74) experienced a lower health system delay. Besides, the median of patient delay, health system delay, and total delay during the COVID-19 pandemic were significantly lower than that before.

Conclusion

In general, there has been a noteworthy decline in the notification rate of PTB among adolescents and young adults in Jiaxing City while the declining trend was not obvious in patient delay, health system delay, and total delay, respectively. It also found factors such as gender, case-finding method, and the hospital level might influence the times of seeking health care and diagnosis in health agencies. These findings will provide valuable insights for refining preventive and treatment strategies for TB among adolescents and young adults.
Targeting synthesis of the Chromosome Replication Initiator Protein DnaA by antisense PNA-peptide conjugates in Escherichia coli
Authors: Campion Christopher , Charbon Godefroid , Nielsen Peter E. , Løbner-Olesen Anders
Published: April 2024

Initiation of chromosome replication is an essential stage of the bacterial cell cycle that is controlled by the DnaA protein. With the aim of developing novel antimicrobials, we have targeted the initiation of DNA replication, using antisense peptide nucleic acids (PNAs), directed against DnaA translation. A series of anti-DnaA PNA conjugated to lysine-rich bacterial penetrating peptides (PNA-BPPs) were designed to block DnaA translation. These anti-DnaA PNA-BPPs inhibited growth of wild-type Escherichia coli cells at low micromolar concentrations, and cells exposed to anti-DnaA PNA-BPPs exhibited characteristic hallmarks of chromosome replication inhibition. These results present one of very few compounds successfully targeting initiation of chromosome replication, an essential step in the bacterial cell cycle.
An empirical assessment of the use of an algorithm factory for video delivery operations
Authors: Molnar Gabor , Ferreira Pires Luís , de Boer Oscar , Kovaleva Vera
Published: April 2024

Introduction

Video service providers are moving from focusing on Quality of Service (QoS) to Quality of Experience (QoE) in their video networks since the users’ demand for high-quality video content is continually growing. By focusing on QoE, video service providers can provide their subscribers with a more personalized and engaging experience, which can help increase viewer satisfaction and retention. This focus shift requires not only a more sophisticated approach to network management and new tools and technologies to measure and optimize QoE in their networks but also a novel approach to video delivery operations.

Methods

This paper describes the components, interactions, and relationships of an algorithm factory for video delivery operation that assures high QoE for video streaming services. The paper also showcases the results of gradually implementing an algorithm factory in the video industry. Using a dataset from 2016 to 2022, we present the case of a European PayTV service provider that achieved improved performance measured by both objective and subjective metrics.

Results

The use of an algorithm factory significantly improved the PayTV service provider’s performance. The study found a fivefold increase in the speed of critical incident resolution and a 59% reduction in the number of critical incidents, all while expanding the customer base and maintaining the same level of labor resources. The case also demonstrates a strong positive relation between the productivity measures of the PayTV operator and their survey-based quality ratings. These results underscore the importance of flawless QoS and operational excellence in delivering QoE to meet the evolving demands of viewers.

Discussion

The paper adds to the existing literature on relationships between operational efficiency, innovation, and subjective quality. The paper further offers empirical evidence from the PayTV industry. The insights provided are expected to benefit both traditional and over-the-top (OTT) video service providers in their quest to stay ahead in the rapidly evolving video industry. It may also translate to other service providers in similar industries committed to supporting high-quality service delivery.