bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

IntroductionBCL-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.MethodsCo-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.ResultsCFZ 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.ConclusionStromal 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

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

BackgroundNeuroglial 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 reportHere, 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.ConclusionIn 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.
Mental and social wellbeing trajectory during the pandemic for vulnerable populations
Authors: Joyce Andrew , Tran Thach , Stocker Ruby , Fisher Jane 
Published: April 2024

ObjectivesWe 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.MethodsA 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.ResultsFor 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.ConclusionPandemic-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.
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

BackgroundThe 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.MethodsA 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.ResultsA 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 &lt; 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%).ConclusionThe 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

BackgroundTuberculosis (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.MethodsAll 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.ResultsFrom 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.ConclusionIn 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.
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

IntroductionVideo 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.MethodsThis 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.ResultsThe 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.DiscussionThe 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.
COVID-free surgical pathways for treating patients with acute calculous cholecystitis: a retrospective comparative study
Authors: Giacopelli Pietro , Cristaudi Alessandra , Majno Pietro , Roesel Raffaello , Iaquinandi Fabiano , Mongelli Francesco 
Published: April 2024

IntroductionDuring the Sars-Cov-2 crisis, some of the resources committed to emergency surgery services were transiently reallocated to the care of patients with severe COVID-19, preserving immediate treatment of mostly non-deferrable conditions. Moreover, the fear of contracting infections or hindering the treatment of critical COVID-19 patients has caused many individuals to defer seeking emergency care. This situation has then possibly modified the standard of care of some common surgical conditions and the relative outcomes. Our aims was to highlight any difference in surgical outcomes in patients treated for acute cholecystitis before and during the COVID-19 outbreak.MethodThis is a retrospective study on a prospectively collected database that included all consecutive patients treated for acute cholecystitis from March 2019 to February 2021 at the Lugano Regional Hospital, a COVID-free hospital for general surgery patients. Patients were divided into pre-and post-COVID-19 outbreak groups. We collected thorough clinical characteristics and intra-and postoperative outcomes.ResultsWe included 124 patients, of which 60 and 64 were operated on before and after the COVID-19 outbreak respectively. The two groups resulted similar in terms of patients' clinical characteristics (age, gender, body mass index, ASA score, and comorbidities). Patients in the post-outbreak period were admitted to the hospital 0.7 days later than patients in the pre-outbreak period (3.8 ± 6.0 days vs. 3.1 ± 4.1 days, p = 0.453). Operative time, recovery room time, complications, and reoperations resulted similar between groups. More patients in the post-outbreak period received postoperative antibiotic therapy (63.3% vs. 37.5%, p = 0.004) and for a longer time (6.9 ± 5.1 days vs. 4.5 ± 3.9 days, p = 0.020). No significant histopathological difference was found in operatory specimens.DiscussionDespite more frequent antibiotic therapy that suggests eventually worse inflammatory local status, our results showed similar outcomes for patients treated for acute cholecystitis before and during the COVID-19 pandemic. The local COVID management, reallocating resources, and keeping COVID-free hospitals was key to offering patients a high standard of treatment.
Pilot cadaveric study on the feasibility of cricothyroidotomy and the associated complications in 30 cats
Authors: Delle Cave Julia A. , Larcheveque Samuel R. , Martin Edouard , O’Toole Elizabeth 
Published: April 2024

ObjectivesThe study’s primary goal was to assess the feasibility of the cricothyroidotomy technique (CTT) in cats and evaluate its success rate (i.e., secure airway access). Secondary outcomes were the assessment of the subjective difficulty of airway access based on body score condition and weight. Further secondary outcomes consisted of procedural time and scoring of associated complications. The current study hypothesized that the CTT procedure would provide secure airway access with a reasonable success rate.Materials and methodsA prospective experimental study assessing the performance of CTT and associated complications was conducted on 30 feline cadavers. A procedural datasheet was completed to subjectively grade difficulty of landmark palpation, guide placement and tube placement and expected success of the procedure. A dissection was then performed post-procedure by a blinded observer to evaluate for any associated damages.ResultsCTT was successful in securing an airway in 100% of the cats. The time to completion of the CTT was rapid, with a median time of 49 s (ranging from 31 to 90 s) for securing an airway. Of importance, this procedure was judged to be overall easy (median “ease of procedure score” of 7/10; ranging from 3 to 10) by the experimenters. The post-procedural lesion rate was elevated (76.7%) in this population of cats, though based on the lesion scores, was deemed mild in 73.9% of the cases.Clinical significanceCTT warrants consideration as the primary option for emergency front-of-neck airway access for cats although further studies are necessary.
Peer Texting to Promote Quitline Use and Smoking Cessation Among Rural Participants in Vietnam: Randomized Clinical Trial
Authors: Sadasivam Rajani S. , Nagawa Catherine S. , Wijesundara Jessica G. , Flahive Julie , Nguyen Hoa L. , Larkin Celine , Faro Jamie M. , Balakrishnan Kavitha , Ha Duc Anh , Nguyen Cuong Kieu , Vuong Anh , Phan Phuong Thu , Pham Quyen Phi Li , Allison Jeroan J. , Houston Thomas Karr 
Published: April 2024

Objectives: We tested an adapted version of an effective U.S.-based peer-texting intervention to promote Quitline use and smoking cessation among rural participants in Vietnam.Methods: We conducted a two-arm randomized trial with participants recruited at four rural community centers. The intervention included peer messages sent for six months that promoted Quitline use and smoking cessation. Additionally, biweekly two-way text messages assessed participants’ interest in Quitline referral and current smoking status. Comparison participants received only the bi-weekly text message assessment of their current smoking status. At six months, we assessed Quitline use and smoking cessation. Smoking cessation was assessed using the 7-day point prevalence question and verified with a carbon monoxide breath monitor (&lt;=6 ppm).Results: Among 750 participants, the intervention had higher Quitline verified use (18%, 95% CI 0.14, 0.22) than comparison (1%, 95% CI .2, 2, p &lt; 0.0001). Carbon-monoxide-verified smoking cessation did not differ between the two groups. However, intervention (28.3%, 95% CI) and comparison (28.1%, 95% CI) participants had substantial rates of carbon monoxide cessation at 6 months (both 28%).Conclusion: Our study highlighted the promise of texting interventions to extend tobacco control efforts in Vietnam.