bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary data on symptom burden and quality of life among elderly patients at risk of dying during unplanned admissions to an NHS hospital: a cohort study using EuroQoL and the integrated palliative care outcome scale
Authors: Johnston Bridget M. , Miller Mary , Normand Charles , Cardona Magnolia , May Peter , Lowney Aoife C.
Published: February 2024

Background

Older people account heavily for palliative care needs at the population level and are growing in number as the population ages. There is relatively little high-quality data on symptom burden and quality of life, since these data are not routinely collected, and this group are under-recruited in primary research. It is unclear which measurement tools are best suited to capture burdens and experience.

Methods

We recruited a cohort of 221 patients aged 75 + years with poor prognosis who had an unplanned admission via the emergency department in a large urban hospital in England between 2019 and 2020. Risk of dying was assessed using the CriSTAL tool. We collected primary data and combined these with routine health records. Baseline clinical data and patient reported quality of life outcomes were collected on admission and reassessed within the first 72 h of presentation using two established tools: EQ-5D-5 L, EQ-VAS and the Integrated Palliative Outcomes Scale (IPOS).

Results

Completion rate was 68% (n = 151) and 33.1% were known to have died during admission or within 6 months post-discharge. The vast majority (84.8%) reported severe difficulties with at least one dimension of EQ-5D-5 L at baseline and improvements in EQ-VAS observed at reassessment in 51.7%. The baseline IPOS revealed 78.2% of patients rating seven or more items as moderate, severe or overwhelming, but a significant reduction (-3.6, p < 0.001) in overall physical symptom severity and prevalence was also apparent. No significant differences were noted in emotional symptoms or changes in communication/practical issues. IPOS total score at follow up was positively associated with age, having comorbidities (Charlson index score > = 1) and negatively associated with baseline IPOS and CriSTAL scores.

Conclusion

Older people with poor prognosis admitted to hospital have very high symptom burden compared to population norms, though some improvement following assessment was observed on all measures. These data provide valuable descriptive information on quality of life among a priority population in practice and policy and can be used in future research to identify suitable interventions and model their effects.
Systematic review and meta-analysis of the etiology of heavy menstrual bleeding in 2,770 adolescent females
Authors: Hall Erin M. , Ravelo Ana E. , Aronoff Stephen C. , Del Vecchio Michael T.
Published: February 2024

Background

Adolescent heavy menstrual bleeding(HMB), menorrhagia or abnormal uterine bleeding commonly occur in adolescent women. The differential diagnosis can be challenging. The pneumonic: PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified), is commonly used but it does not stratify as to the likelihood of a disorder. We have sought to develop a probability-based differential diagnosis for Adolescent HMB, menorrhagia or abnormal uterine bleeding.

Methods

A comprehensive literature search was conducted using PubMed, EMBASE, and SCOPUS databases. Case series describing adolescents from 10–19 years of age with HMB, menorrhagia or abnormal uterine bleeding was acceptable if: more than 10 patients were included; editorials, case reports, and secondary sources such as review articles, or book chapters were excluded. No language filter was used, but an English abstract was required. The etiology of HMB, menorrhagia or abnormal uterine bleeding, and the country of origin was extracted from articles that met inclusion criteria. Cumulative rate estimates were determined by Bayesian probability modeling.

Results

Seventeen full text articles were reviewed in detail; 2,770 patients were included. The most frequent causes of HMB were Ovarian Uterine Disorders (23.7%; 95% CredI 22–25.5%), Coagulation Disorders (19.4%; 95% CredI 17.8—21.1%), and Platelet Disorders (6.23%; 95% CredI 5.27–7.27%) with 45.9% (95% CredI 43.8—47.%9) of the cases of indeterminate origin.

Conclusions

The leading causes of HMB in healthy adolescent females were varied. The sub-analysis identified distinct etiologies, suggesting that multiple factors must be considered in the evaluation of HMB. While PALM-COEIN (polyp, adenomyosis, leiomyoma, malignancy and hyperplasia, coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, and not yet classified) provides us with a comprehensive picture of the possible causes of HMB in females, this systematic review assigns probabilities to the etiologies of HMB in adolescent females, providing physicians with a more focused and efficient pathway to diagnosis.
Tumor mutational burden assessment and standardized bioinformatics approach using custom NGS panels in clinical routine
Authors: Dupain Célia , Gutman Tom , Girard Elodie , Kamoun Choumouss , Marret Grégoire , Castel-Ajgal Zahra , Sablin Marie-Paule , Neuzillet Cindy , Borcoman Edith , Hescot Ségolène , Callens Céline , Trabelsi-Grati Olfa , Melaabi Samia , Vibert Roseline , Antonio Samantha , Franck Coralie , Galut Michèle , Guillou Isabelle , Halladjian Maral , Allory Yves , Cyrta Joanna , Romejon Julien , Frouin Eleonore , Stoppa-Lyonnet Dominique , Wong Jennifer , Le Tourneau Christophe , Bièche Ivan , Servant Nicolas , Kamal Maud , Masliah-Planchon Julien
Published: February 2024

Background

High tumor mutational burden (TMB) was reported to predict the efficacy of immune checkpoint inhibitors (ICIs). Pembrolizumab, an anti-PD-1, received FDA-approval for the treatment of unresectable/metastatic tumors with high TMB as determined by the FoundationOne®CDx test. It remains to be determined how TMB can also be calculated using other tests.

Results

FFPE/frozen tumor samples from various origins were sequenced in the frame of the Institut Curie (IC) Molecular Tumor Board using an in-house next-generation sequencing (NGS) panel. A TMB calculation method was developed at IC (IC algorithm) and compared to the FoundationOne® (FO) algorithm.

Using IC algorithm, an optimal 10% variant allele frequency (VAF) cut-off was established for TMB evaluation on FFPE samples, compared to 5% on frozen samples. The median TMB score for MSS/POLE WT tumors was 8.8 mut/Mb versus 45 mut/Mb for MSI/POLE-mutated tumors. When focusing on MSS/POLE WT tumor samples, the highest median TMB scores were observed in lymphoma, lung, endometrial, and cervical cancers. After biological manual curation of these cases, 21% of them could be reclassified as MSI/POLE tumors and considered as “true TMB high.” Higher TMB values were obtained using FO algorithm on FFPE samples compared to IC algorithm (40 mut/Mb [10–3927] versus 8.2 mut/Mb [2.5–897], p < 0.001).

Conclusions

We herein propose a TMB calculation method and a bioinformatics tool that is customizable to different NGS panels and sample types. We were not able to retrieve TMB values from FO algorithm using our own algorithm and NGS panel.
The impact of ageing on the distribution of preformed anti-HLA and anti-MICA antibody specificities in recipients from eastern China prior to initial HSCT
Authors: Pan Qinqin , Ma Xiao , You Yajie , Yu Yuejiao , Fan Su , Wang Xiaoyan , Wang Mengyuan , Gao Ming , Gong Guangming , Miao Kourong , Shen Jie , Zhou Xiaoyu
Published: February 2024

Background

With the development of Hematopoietic Stem Cell Transplantation (HSCT) technology, increasing numbers of elderly patients were undergoing allogeneic HSCT and elderly patients with hematologic malignancies could benefit most from it. Preformed donor-specific human leukocyte antigen (HLA) antibodies (DSA) were associated with graft failure in HLA-mismatched allogeneic HSCT and the absence of DSA was the main criterion of selecting the donor. Except for sensitization events such as transfusion, pregnancy or previous transplantation, ageing affects the humoral immune response both quantitatively and qualitatively. To evaluate the prevalence and distribution of anti-HLA and antibodies of MHC class I chain related antigens A (MICA) specificities in different age groups before initial HSCT would provide HLA and MICA specific antibody profiles under the impact of ageing, which could provide meaningful information in the process of selecting suitable HLA-mismatched donors by avoiding preformed DSA.

Results

There were no significant differences in the distribution of anti-HLA class I, class II and anti-MICA antibodies among the three age groups in this study except that a significant lower negative ratio of anti-HLA class I, class II antibodies and higher positive rate of MICA antibodies with maximum mean fluorescent intensity (MFI) > 5000 in the elderly than in young age group. The distribution of antibody specificities against HLA -A, -B, -C, -DR, -DQ, -DP and MICA antigens in the three age groups were generally consistent. The anti-HLA class I antibody specificities with higher frequencies were A80,A68;B76,B45;Cw17, which were unlikely to become DSA in Chinese. Anti-HLA class II antibody specificities were more likely to become potential DSA than class I.DR7, DR9, DQ7, DQ8 and DQ9 were most likely to become potential DSA.

Conclusions

The prevalence of anti-HLA and anti-MICA antibodies increased slightly as age increased. While ageing had a small impact on the distribution of antibody specificity frequencies against HLA-A, -B, -C, -DR,-DQ, -DP and MICA antigens in recipients awaiting initial HSCT from East China. The risk of developing preformed DSA was basically consistent in the three age groups and the elderly group might be more favorable in HLA-mismatched HSCT due to higher positive rate of anti-MICA antibody.
Clinical characteristics and surgical management of facial infiltrating lipomatosis: a single center experience
Authors: Chen Hongrui , Sun Bin , Xia Wenwen , Qiu Yajing , Gao Wei , Hua Chen , Lin Xiaoxi
Published: February 2024

Background

Facial infiltrating lipomatosis (FIL) is a rare condition characterized by congenital facial enlargement. Beyond its impact on physical appearance, FIL can also impair essential facial functions such as swallowing, chewing, vision, and breathing, imposing a substantial physiological and psychological burden. Currently, fewer than 80 cases of FIL have been reported, and the characteristics and management strategies for FIL remain unclear.

Methods

We reviewed the clinical, surgical, and radiological records of 39 FIL patients who were treated at our center. Of these, genetic testing was performed for 21 patients.

Results

Aberrant overgrowth involves subcutaneous fat, bones, muscles, glands, tongue, lips, and teeth. Epidermal nevi could be observed in the dermatomes innervated by the three branches of the trigeminal nerve, with the highest frequency seen in the dermatome of the mandibular branch. Four patients exhibited concurrent hemimegalencephaly (HMEG), with one case presenting HMEG on the opposite side of the FIL. Nineteen patients were confirmed to harbor the PIK3CA mutation. Thirty-three patients underwent surgical procedures, with a post resection recurrence rate of approximately 25%.

Conclusions

A variety of maxillofacial structures may be involved in FIL. PIK3CA mutations are important pathogenic factors. Emerging targeted therapies could present an additional treatment avenue in the future. However, surgery currently remains the predominant treatment choice for FIL. The timing and modality of surgery should be individually customized, taking into account each patient's unique circumstances. Notably, there is a significant possibility of postoperative recurrence during childhood and adolescence, necessitating early strategic planning of disease management.
Totally endoscopic concomitant aortic and mitral valve surgery in junctional epidermolysis bullosa: a case report
Authors: Yoshida Kazufumi , Yoshida Soshi , Hori Yoshimasa , Tsubota Hideki , Mochizuki Ryosuke , Nagano Tohru , Koyama Tadaaki
Published: February 2024

Background

Junctional epidermolysis bullosa is a rare skin and mucosal disorder characterized by blister formation in response to minor trauma and extracutaneous manifestations. There have been no reports of cardiac surgery and prognostication in patients with epidermolysis bullosa due to skin and mucosal fragility.

Case presentation

A 55-year-old man presented with congenital junctional epidermolysis bullosa, hypertension, and vasospastic angina. He complained of dyspnea on exertion, and transthoracic echocardiography revealed severe aortic valve regurgitation, moderate aortic valve stenosis (tricuspid valve), and severe mitral valve regurgitation. Considering that the skin condition in the right chest wall was relatively healthy, the right thoracotomy approach was preferred and totally endoscopic concomitant mitral valve repair and aortic valve replacement were performed using a sutureless bioprosthetic valve (Perceval™ (Corcym, Group, Milan, Italy)). Polyurethane and silicon dressing foams were used to protect the skin at the site of contact with the bag valve mask, arterial pressure catheter, intravenous catheter, and the tracheal intubation tube. Vertical mattress sutures were used for the skin sutures. The postoperative course was uneventful, and the patient was discharged nine days after the operation. There was no indication for reoperation until three years follow-up period.

Conclusions

The totally endoscopic concomitant aortic and mitral valve surgery using Perceval™ prosthesis can be performed safely in patients with junctional epidermolysis bullosa by adequate protection of the skin and mucosa.
Presepsin is a more useful predictor of septic AKI and ARDS for very-old sepsis patients than for young sepsis patients in ICUs: a pilot study
Authors: Shimoyama Yuichiro , Kadono Noriko , Umegaki Osamu
Published: February 2024

Objective

Sepsis is a syndrome of life-threatening organ dysfunction. This study aimed to determine whether presepsin is a useful predictor of septic acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and shock in very-old sepsis patients aged 75 years in intensive care units (ICUs).

Results

A total of 83 adult patients diagnosed with sepsis were prospectively examined and divided into two groups: those aged 75 years and older (over 75 group) and those aged younger than 75 years (under 75 group). Presepsin values were measured after ICU admission. Inflammation-based prognostic scores were also examined. For category classification, total scores (“inflammation-presepsin scores [iPS]”) were calculated. Presepsin values, inflammation-based prognostic scores, and iPS were compared between patients with septic AKI, ARDS, DIC, or shock and those without these disorders in the over 75 and under 75 groups. Areas under the curve of presepsin for predicting septic AKI and ARDS in the over 75 group were both > 0.7, which were significantly higher than those in the under 75 group. In conclusion, presepsin is a more useful predictor of septic AKI and ARDS for very-old sepsis patients (over 75 years) than for younger sepsis patients (under 75 years).
A therapeutic challenge relating to the association of orthostatic hypotension and supine hypertension in a patient with cardiac autonomic neuropathy: a case report
Authors: Dounia Jama , Kamal Haless , Marouane Selmaoui , Meryem Haboub , Rachida Habbal , Abdenasser Drighil , Leila Azzouzi
Published: February 2024

Background

Cardiac autonomic neuropathy is a highly prevalent pathology in the diabetic population, and is the leading cause of death in this population. Orthostatic hypotension is the main clinical manifestation of the disease. In some patients, this orthostatic hypotension is associated with supine hypertension, posing a therapeutic challenge since treatment of one entity may aggravate the other. The challenge is to manage each of these two hemodynamic opposites without exposing the patient to a life-threatening risk of severe hypotension or hypertension.

Case presentation

We report a case of a 62-year-old ethnic Moroccan woman who has cardiovascular risk factors such as type 2 diabetes, arterial hypertension, and dyslipidemia. The patient’s symptoms included dizziness, tremors, morning sickness, palpitations, and intolerance to exertion. Given her symptomatology, the patient benefited from an exploration of the autonomic nervous system through cardiovascular reactivity tests (Ewing tests), which confirmed the diagnosis of cardiac autonomic neuropathy. In addition to orthostatic hypotension, our patient had supine arterial hypertension, complicating management. To treat orthostatic hypotension, we advised the patient to avoid the supine position during the day, to raise the head of the bed during the night, and to have a sufficient fluid intake, with a gradual transition from decubitus to orthostatism and venous restraint of the lower limbs. Supine hypertension was treated with transdermal nitrates placed at bedtime and removed 1 hour before getting up. One week after the introduction of treatment, the patient reported a clear regression of functional symptoms, with an improvement in her quality of life. Improvement in symptomatology was maintained during quarterly follow-up consultations.

Conclusions

Cardiac autonomic neuropathy is a very common pathology in diabetic patients. It is a serious condition with a life-threatening prognosis. Its management must be individualized according to the symptomatology and profile of each patient. The treatment of patients with orthostatic hypotension and supine hypertension requires special attention to ensure that each entity is treated without aggravating the other.
Acute compartment syndrome of the thigh after total knee arthroplasty: a case report
Authors: Schuster Marie , Kappenschneider Tobias , Meyer Matthias , Holzapfel Dominik Emanuel
Published: February 2024

Introduction

Acute compartment syndrome of the thigh after total knee arthroplasty is a rarely described complication. After the assessment of the diagnosis, immediate surgical intervention is necessary to prevent further tissue damage. Since only a few cases have been described and because of the high complication rate, early detection is essential for ensuring patient outcomes.

Case presentation

After total knee arthroplasty in a high-volume university hospital, a 57-year-old Caucasian female patient experienced strong, disproportional pain in the ventromedial thigh of the affected leg, which did not respond to an adequate adjustment in pain medication. Imaging revealed a distinct swelling of the vastus intermedius muscle. This resulted in acute compartment syndrome of the thigh, which was immediately surgically treated. Apart from receiving surgery distal from the affected compartment and continuous intake of acetylsalicylic acid, the patient had no risk factors for developing compartment syndrome. The patient’s recovery was uneventful, with timely wound closure and discharge to outpatient care without significant functional limitations.

Conclusion

Acute compartment syndrome of the thigh represents a rare, but severe complication that can occur after orthopedic surgery. In our case, no triggering factors for the development of acute compartment syndrome, such as the use of a tourniquet, were detected. Even in unusual locations, compartment syndrome should be considered as a differential diagnosis. With sufficient evidence, immediate fasciotomy should be indicated.
Fungal coexistence in the skin mycobiome: a study involving Malassezia, Candida, and Rhodotorula
Authors: Naik Bharati , Sasikumar Jayaprakash , B Vishal , Das Shankar Prasad
Published: February 2024

Evidence of fungal coexistence in humans points towards fungal adaptation to the host environment, like the skin. The human commensalMalasseziahas evolved, especially residing in sebum-rich areas of the mammalian body where it can get the necessary nutrition for its survival. This fungus is primarily responsible for skin diseases like Pityriasis versicolor (PV), characterized by hypo or hyperpigmented skin discoloration and erythematous macules. In this manuscript, we report a 19-year-old healthy female who presented with a one-year history of reddish, hypopigmented, asymptomatic lesions over the chest and a raised erythematous lesion over the face. Upon clinical observation, the patient displayed multiple erythematous macules and erythematous papules over the bilateral malar area of the face, along with multiple hypopigmented scaly macules present on the chest and back. Based on the above clinical findings, a diagnosis of PV and Acne vulgaris (AV) was made. Interestingly, the patient was immunocompetent and didn’t have any comorbidities. Upon isolation of skin scrapings and post-culturing, we found the existence of three fungal genera in the same region of the patient’s body. We further went on to confirm the identity of the particular species and found it to representMalassezia, Rhodotorula, andCandida. We report howMalassezia, the predominant microbial resident skin fungus, coexists with other fungal members of the skin mycobiome. This study on an applied aspect of microbiology also shows how important it is to identify the fungal organism associated with skin infections so that appropriate therapeutics can be advised to avoid cases of relapse.
Generalized integral Jensen inequality
Authors: Nazari Pasari Saeed , Barani Ali , Abbasi Naser
Published: February 2024

In this paper we introduce necessary and sufficient conditions for a real-valued function to be preinvex. Some properties of preinvex functions and new versions of Jensen’s integral type inequality in this setting are given. Several examples are also involved.
Prevalence of undiagnosed metabolic syndrome using three different definitions and identifying associated risk factors among apparently healthy adults in Karachi, Pakistan: a cross-sectional survey in the year 2022
Authors: Adil Syed Omair , Musa Kamarul Imran , Uddin Fareed , Khan Asima , Khan Irfanullah , Shakeel Areebah , Shafique Kashif , Islam Md Asiful
Published: February 2024

Objective

To determine the prevalence and associated risk factors of undiagnosed metabolic syndrome (MetS) using three different definitions among apparently healthy adults of Karachi, Pakistan.

Methods

This community-based cross-sectional survey was conducted in Karachi, Pakistan, from January 2022 to August 2022. A total of 1065 healthy individuals aged 25–80 years of any gender were consecutively included. MetS was assessed using the National Cholesterol Education Program for Adult Treatment Panel (NCEP-ATP) III guidelines, International Diabetes Federation (IDF), and modified NCEP-ATP III.

Results

The prevalence of MetS was highest with the modified NCEP-ATP III definition at 33.9% (95% CI: 31–36), followed by the IDF definition at 32.2% (95% CI: 29–35). In contrast, the prevalence was lower at 22.4% (95% CI: 19–25) when using the NCEP ATP III definition. The risk of MetS significantly increases with higher BMI, as defined by the IDF criteria (adjusted OR [ORadj] 1.13, 95% CI 1.09–2.43), NCEP-ATP III criteria (ORadj 1.15, 95% CI 1.11–1.19), and modified NCEP-ATP III criteria (ORadj 1.16, 95% CI 1.12–1.20). Current smokers had significantly higher odds of MetS according to the IDF (ORadj 2.72, 95% CI 1.84–4.03), NCEP-ATP III (ORadj 3.93, 95% CI 2.55–6.06), and modified NCEP-ATP III (ORadj 0.62, 95% CI 0.43–0.88). Areca nut use was associated with higher odds of MetS according to both IDF (ORadj 1.71, 95% CI 1.19–2.47) and modified NCEP-ATP III criteria (ORadj 1.58, 95% CI 1.10–2.72). Furthermore, low physical activity had significantly higher odds of MetS according to the NCEP-ATP III (ORadj 1.36, 95% CI 1.01–1.84) and modified NCEP-ATP III criteria (ORadj 1.56, 95% CI 1.08–2.26).

Conclusion

One-third of the healthy individuals were diagnosed with MetS based on IDF, NCEP-ATP III, and modified NCEP-ATP III criteria. A higher BMI, current smoking, areca nut use, and low physical activity were significant factors.
Emerging role of senescent microglia in brain aging-related neurodegenerative diseases
Authors: Rim Chan , You Min-Jung , Nahm Minyeop , Kwon Min-Soo
Published: February 2024

Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood. Cellular senescence is considered to contribute to cellular dysfunction and inflammaging. According to the threshold theory of senescent cell accumulation, the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain. Given the role of microglia in eliminating senescent cells, the accumulation of senescent microglia may lead to the acceleration of brain aging, contributing to inflammaging and increased vulnerability to neurodegenerative diseases. In this review, we propose the idea that the senescence of microglia, which is notably vulnerable to aging, could potentially serve as a central catalyst in the progression of neurodegenerative diseases. The senescent microglia are emerging as a promising target for mitigating neurodegenerative diseases.
Monitoring soil quality of different land use systems: a case study in Suha watershed, northwestern highlands of Ethiopia
Authors: Yeneneh Nigussie , Elias Eyasu , Feyisa Gudina Legese
Published: February 2024

The problem of soil quality degradation has been becoming more severe in the highlands of Ethiopia due to soil erosion; land use and land cover change, and poor land management. The level of soil quality degradation was not well known and documented in the study area and the results of this study could provide new information to improve soil conditions. The present study was conducted to evaluate soil quality in terms of its physical and chemical fertility under different land use types in the Suha watershed, northwestern highlands of Ethiopia. A total of 27 composite surface soil samples (0–30 cm) were collected from adjacently located land-uses in three replications from two elevation gradients. Standard procedures were followed to analyze selected soil physical and chemical quality indicators. The differences in the mean values of the parameters were tested using a two-way analysis of variance. In addition, Soil Quality Degradation Index was evaluated to see the direction and magnitude of change in soil quality indicators. The analysis of variance results revealed that soil quality indicators such as index of soil aggregate stability, organic carbon (OC), total nitrogen (TN), and C:N ratio were significantly decreased in the cultivated land use system compared to other land use systems. On the other hand, the content of available Phosphorus was significantly higher in the cultivated land. Soil quality deterioration index values were highly negative for SOC (− 71.3%) and TN (− 67.7%) in the cultivated land, followed by grazing land (SOM = − 35.5% and TN = − 27.7%). Aggregated Soil Quality Index values also indicated that the status of soil quality under cultivated fields is rated as low, grazing land as optimal, and forest land as high. Generally, results indicated that land use and cover changes had adverse effects on soil quality indicators. Hence, soil management strategies, mainly Integrated Soil Fertility Management which integrates soil and water conservation strategies, are required to alleviate the problem of soil quality deterioration and improve agricultural productivity.
Low-dose hypomethylating agents cooperate with ferroptosis inducers to enhance ferroptosis by regulating the DNA methylation-mediated MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway in acute myeloid leukemia
Authors: Feng Shuya , Yuan Yigang , Lin Zihan , Li Min , Ye Daijiao , Shi Liuzhi , Li Danyang , Zhao Min , Meng Chen , He Xiaofei , Wu Shanshan , Xiong Fang , Ye Siyu , Yang Junjun , Zhuang Haifeng , Hong Lili , Gao Shenmeng
Published: February 2024

Background

Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown.

Methods

Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo.

Results

We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models.

Conclusions

Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.
Changes and continuity in pottery production and use at Wujiafentou in the core zone of Youziling and Shijiahe cultures in central China
Authors: Xie Zichen , Hu Ying , Shan Siwei , Lü Qin-Qin , Yuan Feiyong , Li Tao
Published: February 2024

The Wujiafentou site is located at the heart of the Youziling (5900–5500 cal BP) and Shijiahe (4500–4200 cal BP) cultures in the Handong region, a core area to understand the relationship among economic networks, sociopolitical integration, and regional identity in the middle Yangtze River valley (MYRV) of central China during the Late Neolithic times. Its pottery assemblages are important clues to understanding the pottery production and use before and after the extensive walled town construction activities in the Neolithic MYRV. Wujiafentou is less than 5 km from the Shijiahe walled town, the largest city of its time in the MYRV. This paper applies microscopic examination and chemical and mineralogical analyses to a sample of 152 sherds of the Youziling-period and Shijiahe-period utilitarian vessels unearthed from the Wujiafentou site, revealing the changes and continuity in pottery production and use over time. We also probe into the socio-economic ties between Wujiafentou and the Shijiahe walled town mainly through hong tao bei (red clay cups), which were widely distributed and presumably highly symbolic items of the Shijiahe culture related to drinking, feasts, and rituals. We propose that the Wujiafentou inhabitants produced their red clay cups by mimicking those made within the Shijiahe walled town. Our study highlights an alternative interpretation of the formation of a regional identity during the Shijiahe period.
Detecting DeFi securities violations from token smart contract code
Authors: Trozze Arianna , Kleinberg Bennett , Davies Toby
Published: February 2024

Decentralized Finance (DeFi) is a system of financial products and services built and delivered through smart contracts on various blockchains. In recent years, DeFi has gained popularity and market capitalization. However, it has also been connected to crime, particularly various types of securities violations. The lack of Know Your Customer requirements in DeFi poses challenges for governments trying to mitigate potential offenses. This study aims to determine whether this problem is suited to a machine learning approach, namely, whether we can identify DeFi projects potentially engaging in securities violations based on their tokens’ smart contract code. We adapted prior works on detecting specific types of securities violations across Ethereum by building classifiers based on features extracted from DeFi projects’ tokens’ smart contract code (specifically, opcode-based features). Our final model was a random forest model that achieved an 80% F-1 score against a baseline of 50%. Notably, we further explored the code-based features that are the most important to our model’s performance in more detail by analyzing tokens’ Solidity code and conducting cosine similarity analyses. We found that one element of the code that our opcode-based features can capture is the implementation of the SafeMath library, although this does not account for the entirety of our features. Another contribution of our study is a new dataset, comprising (a) a verified ground truth dataset for tokens involved in securities violations and (b) a set of legitimate tokens from a reputable DeFi aggregator. This paper further discusses the potential use of a model like ours by prosecutors in enforcement efforts and connects it to a wider legal context.
Infant feeding practices and associated factors among HIV-positive mothers of infants aged 0–6 months at public health facilities in Addis Ababa, Ethiopia
Authors: Gebremariam Zewdu Minwuyelet , Getahun Genanew , Sahile Addisu , Kejela Yared , Getachew Yeworkwuha , Sisay Fasil
Published: February 2024

Background

In the era of HIV infection, exclusive breast-feeding highly recommended for infants aged less than 6 months. Avoidance of exclusive breast-feeding by HIV-infected mothers recommended when replacement feeding is acceptable, feasible, affordable, sustainable and safe. The prevalence of exclusive breast-feeding has remained very low worldwide. Despite this fact, there is limited information on infant feeding practices of HIV-positive mothers and factors that affect the practice in the current study area.

Objective

This study assessed the magnitude of infant feeding practice and associated factors among HIV-positive mothers of infants aged 0–6 months at public health facilities in Addis Ababa, Ethiopia.

Methods

A multicenter facility-based cross-sectional study design was employed among a total of 397 study participants. The study participants were selected using a simple random sampling technique. The completeness of the data was checked, coded, cleaned and entered into Epi-data version 4.6 software, and exported to SPSS version 24 for analysis. Descriptive statistics and Binary logistic regression model were employed for the analysis with adjusted odds ratio (AOR) with a 95% CI and a P value ≤ 0.05 to determine the strength of association between infant feeding practice and its independent factors.

Results

The overall magnitude of appropriate infant feeding practice among HIV-positive mothers was 82.6% (95% CI 80.9–88.2). Good knowledge of mother’s toward infant feeding (AOR: 1.26, 95%, CI 1.11–3.34), better household monthly income, ≥ 6001 Ethiopian birr (AOR: 1.62, 95% CI 1.33–5.14) and favorable attitude of mother’s toward infant feeding (AOR: 1.71, 95% CI 1.01–2.92) were statistically significant associated factors with the recommended way of infant feeding practice.

Conclusions and recommendations

Hence, the current study area is the capital city of the Ethiopia, where a relatively educated population lived in, there was an opportunity for better income, and appropriate infant feeding practice among HIV-positive mothers was found slightly higher than even the overall national target (70%) that was planned by 2020. Therefore, different stakeholders should develop strategic plan to excel females’ education coverage and thereby their knowledge and attitude toward infant feeding to fully eradicate mother-to-child transmission of diseases.
Dimensional accuracy and precision and surgeon perception of additively manufactured bone models: effect of manufacturing technology and part orientation
Authors: Benca Emir , Eckhart Barbara , Stoegner Alexander , Unger Ewald , Bittner-Frank Martin , Strassl Andreas , Gahleitner Claudia , Hirtler Lena , Windhager Reinhard , Hobusch Gerhard M. , Moscato Francesco
Published: February 2024

Background

Additively manufactured (AM) anatomical bone models are primarily utilized for training and preoperative planning purposes. As such, they must meet stringent requirements, with dimensional accuracy being of utmost importance. This study aimed to evaluate the precision and accuracy of anatomical bone models manufactured using three different AM technologies: digital light processing (DLP), fused deposition modeling (FDM), and PolyJetting (PJ), built in three different part orientations. Additionally, the study sought to assess surgeons’ perceptions of how well these models mimic real bones in simulated osteosynthesis.

Methods

Computer-aided design (CAD) models of six human radii were generated from computed tomography (CT) imaging data. Anatomical models were then manufactured using the three aforementioned technologies and in three different part orientations. The surfaces of all models were 3D-scanned and compared with the original CAD models. Furthermore, an anatomical model of a proximal femur including a metastatic lesion was manufactured using the three technologies, followed by (mock) osteosynthesis performed by six surgeons on each type of model. The surgeons’ perceptions of the quality and haptic properties of each model were assessed using a questionnaire.

Results

The mean dimensional deviations from the original CAD model ranged between 0.00 and 0.13 mm with maximal inaccuracies < 1 mm for all models. In surgical simulation, PJ models achieved the highest total score on a 5-point Likert scale ranging from 1 to 5 (with 1 and 5 representing the lowest and highest level of agreement, respectively), (3.74 ± 0.99) in the surgeons’ perception assessment, followed by DLP (3.41 ± 0.99) and FDM (2.43 ± 1.02). Notably, FDM was perceived as unsuitable for surgical simulation, as the material melted during drilling and sawing.

Conclusions

In conclusion, the choice of technology and part orientation significantly influenced the accuracy and precision of additively manufactured bone models. However, all anatomical models showed satisfying accuracies and precisions, independent of the AM technology or part orientation. The anatomical and functional performance of FDM models was rated by surgeons as poor.
Role of intravoxel incoherent motion MRI in diagnosis and assessment of invasiveness of urothelial bladder carcinoma
Authors: Badawy Mohamed Ali , Zaky Samia Mounir , Korkor Mona S. , Fattah Sherif Abdel
Published: February 2024

Background

Urinary bladder cancer is a common malignancy. Preoperative accurate judgment of the degree of tissue invasion is crucial to determine the plan of therapy. We aimed in the current study to evaluate the role of intravoxel incoherent motion (IVIM) MRI and apparent diffusion coefficient (ADC) map in differentiating muscle invasive from non-muscle invasive carcinomas.

Results

Values of IVIM-derived true diffusion coefficient (D), pseudo-diffusion coefficient (D*) and perfusion fraction (F) and ADC were lower in muscle invasive carcinomas than non-invasive masses with p values < 0.001 and 0.001, respectively. In MIBC, ADC was (0.9 × 10−3 mm2/s), D was (0.8 × 10−3 mm2/s), D* was (6.9 × 10−3 mm2/s) and F was (16.9%). In NMIBC, ADC was (1 × 10−3 mm2/s), D was (1.1 × 10−3 mm2/s), D* was (10.2 × 10−3 mm2/s) and F was (17.7%). Mass D cut off values, sensitivity and specificity and AUC were < 0.9, 83.93, 96.30 and 0.945, respectively. Mass ADC cut off values, sensitivity and specificity and AUC were < 1.09, 87.50, 51.85 and 0.721, respectively. The degree of agreement between IVIM parameters and the pathological staging was assessed by Kappa test. The best agreement was detected for mass D (K = 0.796), while the mass ADC and wall beside mass D showed moderate and fair agreement (k = 0.418 and 0.325, respectively).

Conclusions

IVIM MRI parameters and ADC map can be utilized to detect the degree of tissue invasion caused by bladder cancer.
Surface crack treatment of concrete via nano-modified microbial carbonate precipitation
Authors: Li Tao , Yang Hanqing , Yan Xiaohui , He Maolin , Gu Haojie , Yu Liming
Published: February 2024

As a new concrete crack patching technology, microbial self-healing slurries offer favourable characteristics including non-pollution, ecological sustainability and good compatibility with concrete. In this paper, a nano-sio2-modified microbial bacteria liquid, combined with sodium alginate and polyvinyl alcohol, was used to prepare a nano-modified microbial self-healing slurry. This slurry was used to coat concrete under negative pressure in order to verify its restoration effect, and the micromorphology of the resulting microbial mineralization products was observed. The results revealed that patching the concrete using the nano-modified microbial slurry significantly improved its permeability, and increased its carbonization resistance by three times in comparison with the control group. Through a combination of Scanning electron microscopy (SEM) and X-ray diffraction (XRD) observation, it was determined that the microbial mineralization reaction products were mainly calcite crystals, which, integrated with the nano-sio2, sodium alginate and polyvinyl alcohol at the microscopic level, filled the internal pores of concrete, thus improving its durability.
Investigating age-related COVID-19 digital health literacy and sense of coherence among adolescents and young adults in schools across Northern Ghana
Authors: Srem-Sai Medina , Ankomah Francis , Agormedah Edmond Kwesi , Quansah Frank , Hagan John Elvis , Okan Orkan , Dadaczynski Kevin , Schack Thomas
Published: February 2024

Introduction

The empirical link between digital health literacy (DHL) and sense of coherence (SoC) has been extensively discussed in the literature. Yet, there seems to be limited evidence regarding the roles of age and depression status in the link between DHL and SoC of adolescents and young adults (AYAs), especially during the COVID-19 crises. This study investigated the interplay between age, DHL, SoC and psychological distress. Particularly, the study examined the following: (1) relationship between DHL and SoC, (2) moderating role of age in the relationship between DHL and SoC as well as (3) moderating role of depression in the relationship between DHL and SoC.

Methods

The study used a cross-sectional survey to select 998 AYAs in secondary schools in Northern Ghana through questionnaire administration using a stratified sampling procedure.

Results

Findings reveal that age was positively and significantly related to DHL and SoC. However, age failed to moderate the relationship between DHL and SoC. With the same level of DHL, students who exhibited depressive symptoms compared to those without, had lower levels of SoC regardless of their age.

Conclusions

Although AYAs’ DHL are likely to differ across different age brackets, this gap does not affect their rates of SoC and depression. Nonetheless, there is a need to improve DHL through regular standard training on internet search using basic audio-visual materials like laptops, smart phones, tablets, and lab computers for adolescent and young adult students. Additionally, school authorities, in collaboration with other stakeholders should develop student-centred cognitive-behavioural strategies aimed at reducing depressive symptoms in secondary school students who are at risk of depression in Northern Ghana.
The Impact of Preoperative Spinal Injection Timing on Postoperative Complications of Lumbar Decompression Surgery
Authors: Khalid Syed I. , Mirpuri Pranav , Massaad Elie , Thomson Kyle B. , Kiapour Ali , Shin John H. , Adogwa Owoicho
Published: February 2024

BACKGROUND AND OBJECTIVES:

Epidural steroid injections (ESIs) are commonly used for lower back pain management. The effect of these injections on lumbar decompression surgery outcomes is hitherto underexplored. The study objective was to determine the impact of ESIs on postoperative rates of medical and surgical complications and to define the appropriate interval before lumbar decompression surgery.

METHODS:

This retrospective all-payer database analysis identified 587 651 adult patients undergoing one- to three-level laminectomies from January 2010 to October 2021. A 2:1 propensity score match accounting for comorbidities, levels of surgery, and demographics was performed to create two cohorts: (1) 43 674 patients who had received an ESI in the 90 days before laminectomy and (2) 87 348 patients who had not received an ESI. The primary outcome was the rates of medical and surgical complications between groups at 30 days postoperatively. Patients were divided into five cohorts based on injection time before surgery: 1 to 30 days, 31 to 45 days, 46 to 60 days, 61 to 75 days, and 76 to 90 days. Logistic regression was performed between groups to identify temporal associations of complication rates. Confidence intervals of 95% are provided when appropriate. P values < .01 were considered significant.

RESULTS:

Rates of medical complications within 30 days of surgery were significantly higher in those with ESI compared with control (4.83% vs 3.9%, P < .001). Cerebrospinal fluid (CSF) leak rates were increased in the ESI group at 0.28% vs 0.1% (P < .001), but surgical site infection rates were not significantly different between groups (1.31% vs 1.42% P = .11). ESI performed within 30 days was associated with increased odds of CSF leak (OR: 5.32, 95% CI: 3.96-7.15).

CONCLUSION:

Preoperative ESI increases the risk of CSF leak and medical complications after lumbar decompression. Because these complications were significantly associated with ESIs given 1 to 30 days before surgery, avoiding ESIs at least 30 days before surgery may be advisable.