bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxicity of the methanol extracts and compounds of Brucea antidysenterica (Simaroubaceae) towards multifactorial drug-resistant human cancer cell lines
Authors: Youmbi Laetitia M. , Makong Yves S. D. , Mbaveng Armelle T. , Tankeo Simplice B. , Fotso Ghislain W. , Ndjakou Bruno L. , Wansi Jean D. , Beng Veronique P. , Sewald Norbert , Ngadjui Bonaventure T. , Efferth Thomas , Kuete Victor
Published: February 2023

Background

Cancer remains a global health concern and constitutes an important barrier to increasing life expectancy. Malignant cells rapidly develop drug resistance leading to many clinical therapeutic failures. The importance of medicinal plants as an alternative to classical drug discovery to fight cancer is well known. Brucea antidysenterica is an African medicinal plant traditionally used to treat cancer, dysentery, malaria, diarrhea, stomach aches, helminthic infections, fever, and asthma. The present work was designed to identify the cytotoxic constituents of Brucea antidysenterica on a broad range of cancer cell lines and to demonstrate the mode of induction of apoptosis of the most active samples.

Methods

Seven phytochemicals were isolated from the leaves (BAL) and stem (BAS) extract of Brucea antidysenterica by column chromatography and structurally elucidated using spectroscopic techniques. The antiproliferative effects of the crude extracts and compounds against 9 human cancer cell lines were evaluated by the resazurin reduction assay (RRA). The activity in cell lines was assessed by the Caspase-Glo assay. The cell cycle distribution, apoptosis via propidium iodide (PI) staining, mitochondrial membrane potential (MMP) through 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and the reactive oxygen species (ROS) via 2´,7´-dichlorodihydrofluoresceine diacetate (H2DCFH-DA) staining, were investigated by flow cytometry.

Results

Phytochemical studies of the botanicals (BAL and BAS) led to the isolation of seven compounds. BAL and its constituents 3, (3-(3-Methyl-1-oxo-2-butenyl))1H indole (1) and hydnocarpin (2), as well as the reference compound, doxorubicin, had antiproliferative activity against 9 cancer cell lines. The IC50 values varied from 17.42 µg/mL (against CCRF-CEM leukemia cells) to 38.70 µg/mL (against HCT116 p53−/− colon adenocarcinoma cells) for BAL, from 19.11 µM (against CCRF-CEM cells) to 47.50 µM (against MDA-MB-231-BCRP adenocarcinoma cells) for compound 1, and from 4.07 µM (against MDA-MB-231-pcDNA cells) to 11.44 µM (against HCT116 p53+/+ cells) for compound 2. Interestingly, hypersensitivity of resistant cancer cells to compound 2 was also observed. BAL and hydnocarpin induced apoptosis in CCRF-CEM cells mediated by caspase activation, the alteration of MMP, and increased ROS levels.

Conclusion

BAL and its constituents, mostly compound 2, are potential antiproliferative products from Brucea antidysenterica. Other studies will be necessary in the perspective of the discovery of new antiproliferative agents to fight against resistance to anticancer drugs.
The CASPER preparation program innovation: increasing self-perceived competence and confidence of underrepresented applicants on the novel CASPER Snapshot and CanMEDS roles
Authors: Mahmood Farhan , Oguntala Julianah O. , Henoud Claudine , Pierre-Louis Libny Lahelle , Fuad Asli , Okafor Ike
Published: February 2023

Background

Underrepresented Minorities in Medicine (URMMs) may face financial and social limitations when matriculating into medical schools. Performance on situational judgment tests such as Computer-based Assessment for Sampling Personal Characteristics (CASPER) can be enhanced by coaching and mentorship. The CASPER Preparation Program (CPP) coaches URMMs to prepare for the CASPER test. During the coronavirus 2019 pandemic (COVID-19), CPP implemented novel curricula on the CASPER Snapshot and CanMEDS roles.

Methods

Pre and post-program questionnaires were completed by the students, which assessed their: 1) confidence in understanding the CanMEDS roles, and 2) perceived confidence in performing well and their familiarity and preparedness with the CASPER Snapshot. With a second post-program questionnaire, participants’ scores on the CASPER test as well as medical school application outcome were also assessed.

Results

Participants reported a significant increase in the URMMs’ knowledge, self-perceived competency to complete the CASPER Snapshot, and their anxiety significantly decreased. The level of confidence in understanding CanMEDS roles for a career in healthcare increased as well. The majority (91%) agreed that the feedback received from tutors was adequate and the virtual component of the program was beneficial during COVID-19. 51% of students scored in the highest quartile on the CASPER test and 35% received an offer of admission from CASPER-requiring medical schools.

Conclusion

Pathway coaching programs have the potential to increase confidence and familiarity amongst URMMs for the CASPER tests and CanMEDS roles. Similar programs should be developed with the aim to increase the chances of URMMs matriculating into medical schools.
Key ethical issues encountered during COVID-19 research: a thematic analysis of perspectives from South African research ethics committees
Authors: Burgess Theresa , Rennie Stuart , Moodley Keymanthri
Published: February 2023

Background

The COVID-19 pandemic presents significant challenges to research ethics committees (RECs) in balancing urgency of review of COVID-19 research with careful consideration of risks and benefits. In the African context, RECs are further challenged by historical mistrust of research and potential impacts on COVID-19 related research participation, as well as the need to facilitate equitable access to effective treatments or vaccines for COVID-19. In South Africa, an absent National Health Research Ethics Council (NHREC) also left RECs without national guidance for a significant duration of the COVID-19 pandemic. We conducted a qualitative descriptive study that explored the perspectives and experiences of RECs regarding the ethical challenges of COVID-19 research in South Africa.

Methods

We conducted in-depth interviews with 21 REC chairpersons or members from seven RECs at large academic health institutions across South Africa that were actively involved in the review of COVID-19 related research from January to April 2021. In-depth interviews were conducted remotely via Zoom. Interviews (60–125 min) were conducted in English using an in-depth interview guide, until data saturation was achieved. Audio-recordings were transcribed verbatim and field notes were converted into data documents. Line-by-line coding of transcripts was performed, and data were organised into themes and sub-themes. An inductive approach to thematic analysis was used to analyse data.

Results

Five main themes were identified, namely: rapidly evolving research ethics landscape, extreme vulnerability of research participants, unique challenges to informed consent, challenges to community engagement during COVID-19, and overlapping research ethics and public health equity issues. Sub-themes were identified for each main theme.

Conclusions

Numerous, significant ethical complexities and challenges were identified by South African REC members in the review of COVID-19 related research. While RECs are resilient and adaptable, reviewer and REC member fatigue were major concerns. The numerous ethical issues identified also highlight the need for research ethics teaching and training, especially in informed consent, as well as the urgent requirement for the development of national guidelines for research ethics during public health emergencies. Further, comparative analysis between different countries is needed to develop the discourse around African RECs and COVID-19 research ethics issues.
Evaluating knowledge and attitudes scales for the care of older adults among nursing students in Ghana
Authors: Abudu-Birresborn Diana , Brennenstuhl Sarah , Puts Martine , McCleary Lynn , Yakong Vida , Chu Charlene H. , Cranley Lisa
Published: February 2023

Background

Understanding nursing students’ knowledge about and attitudes toward older adults’ using context-specific survey instruments can help to identify and design effective learning and teaching materials to improve the care for persons 60 years and above. However, there are no validated instruments to examine nursing students’ knowledge and attitudes toward the care for older adults in the African context. The study aimed to evaluate the items on the Knowledge about Older Patients Quiz and Kogan's Attitudes towards Old People Scale suitable for the African context.

Methods

A cross-sectional study was conducted using second-and third-year nursing students from two public Nursing Training Institutions in Ghana. Using Sahin’s rule of sample size estimate of at least 150 participants for unidimensional dichotomous scales, 170 nursing students were recruited to participate after an information session in their classrooms. Data were collected from December 2019—March 2020 using the Knowledge about Older Patients Quiz and Kogan’s Attitudes Towards Old People Scale. Item response theory was employed to evaluate the Knowledge about Older Patients Quiz difficulty level and discrimination indices. Corrected item-to-total correlation analysis was conducted for Kogan's Attitudes towards Old People Scale. The internal consistency for both scales was examined.

Results

Of the 170 participants, 169 returned completed surveys. The mean age of participants was 21 years (SD = 3.7), and (54%) were female. Of the 30-items of the Knowledge about Older Patients Quiz, seven items were very difficult for most students to choose the correct response, and one was easy, as most of the students chose the correct response. Although 22 items demonstrated appropriate difficulty level, discrimination indices were used to select the final 15- items that discriminated moderately between upper and lower 25% performing students. The Kuder-Richardson-20 reliability was. 0.30, which was low. Considering Kogan's Attitudes towards Old People scale, 10-items were removed following negative and low corrected item-to-total correlation and a high Alpha coefficient if items were deleted. The final 22-items had a Cronbach alpha coefficient of 0.65, which was moderately satisfactory.

Conclusion

Evaluation of the scales demonstrated essential content validity and moderate internal consistency for the context of our study. Further research should focus on ongoing context-specific refinement of the survey instruments to measure nursing students’ knowledge about and attitudes toward caring for older adults in the African context.
Experiences with telemedicine for HIV care in two federally qualified health centers in Los Angeles: a qualitative study
Authors: Walker Daisy , Moucheraud Corrina , Butler Derrick , de Vente Jerome , Tangonan Kevin , Shoptaw Steven , Currier Judith S. , Gladstein Jay , Hoffman Risa
Published: February 2023

Background

The SARS-CoV-2 pandemic has resulted in an increase in telemedicine utilization for routine HIV care. However, there is limited information on perceptions of and experiences with telemedicine from United States (U.S.) federally qualified health centers (FQHCs) offering HIV care. We sought to understand telemedicine experiences of stakeholders with various roles: people living with HIV (PLHIV), clinical (clinicians and case managers), programmatic (clinic administrators), and policy (policymakers).

Methods

Qualitative interviews about benefits and challenges of telemedicine (telephone and video) for HIV care were conducted with 31 PLHIV and 23 other stakeholders (clinicians, case managers, clinic administrators, and policymakers). Interviews were transcribed, translated to English if conducted in Spanish, coded, and analyzed for major themes.

Results

Almost all PLHIV felt capable of engaging in telephone visits, with some expressing interest in learning how to use video visits as well. Nearly all PLHIV wanted to continue telemedicine as part of their routine HIV care, and this was also endorsed by clinical, programmatic and policy stakeholders. Interviewees agreed that telemedicine for HIV care has benefits for PLHIV, especially savings of time and transportation costs, which also reduced stress. Clinical, programmatic, and policy stakeholders expressed concerns around patients’ technological literacy and resources, as well as their access to privacy, and some felt that PLHIV strongly preferred in-person visits. These stakeholders also commonly reported clinic-level implementation challenges, including integrating telephone and video telemedicine into workflows and difficulty with video visit platforms.

Conclusions

Telemedicine for HIV care, largely delivered via telephone (audio-only), was highly acceptable and feasible for both PLHIV, clinicians, and other stakeholders. Addressing barriers for stakeholders in incorporating video visits will be important for the successful implementation of telemedicine with video as part of routine HIV care at FQHCs.
Healthcare workers exposure risk assessment in the context of the COVID-19: a survey among frontline workers in Qazvin, Iran
Authors: Moosavi Saeideh , Namdar Peyman , Moghaddam Zeabadi Sakineh , Akbari Shahrestanaki Yousof , Ghalenoei Mehran , Amerzadeh Mohammad , Kalhor Rohollah
Published: February 2023

Background

Healthcare workers perform various clinical procedures for COVID-19 patients facing an elevated risk of exposure to SARS-COV-2.This study aimed to assess the healthcare workers’ exposure to COVID-19 in Qazvin, Iran in 2020.

Methods

We conducted this descriptive-analytical study among all healthcare workers on the frontline of exposure to COVID-19 in Qazvin province. We entered the participants into the study using a multi-stage stratified random sampling method. We utilized a questionnaire, "Health workers exposure risk assessment and management in the context of COVID-19 disease", designed by the World Health Organization (WHO) to collect data. We analyzed data using descriptive and analytical methods with SPSS software version 24.

Results

The results showed that all participants in the study had occupational exposure to the COVID-19 virus. So of 243 healthcare workers, 186 (76.5%) were at low risk and 57 (23.5%) at high risk of COVID-19 virus infection. Also, from the six domains mentioned in the questionnaire, health workers exposure risk assessment and management in the context of COVID-19 disease, the mean score of the domain of the type of healthcare worker interaction with a confirmed COVID-19 patient, the domain of health worker activities performed on a confirmed COVID-19 patient, the domain of the adherence to infection prevention and control (IPC) during health care interactions, and the domain of the adherence to IPC when performing aerosol-generating procedures in the high-risk group were more than the low-risk group.

Conclusion

Despite strict WHO guidelines, many healthcare workers are exposed at contracting COVID-19. Therefore, healthcare managers, planners, and policymakers can revise the policies, provide appropriate and timely personal protective equipment, and plan for ongoing training for staff on the principles of infection prevention and control.
Burnout, work engagement and work hours – how physicians’ decision to work less is associated with work-related factors
Authors: Jung FU , Bodendieck E , Bleckwenn M , Hussenoeder FS , Luppa M , Riedel-Heller SG
Published: February 2023

Background

According to new estimates, the health care sector will suffer a shortage of physicians in primary and specialty care. In this context, work engagement and burnout are two constructs that have gained attention recently. The aim of this study was to investigate how these constructs are related to work hour preference.

Method

The present study was based on the baseline survey of the long-term study of physicians with different specialties, in which 1,001 physicians took part (response rate: 33.4%). Burnout was measured using the Copenhagen Burnout Inventory adapted for health care professionals; work engagement was assessed using the Utrecht Work Engagement scale. Data analyses included regression and mediation models.

Results

Overall, 297 out of 725 physicians were planning to cut down work hours. Several reasons - such as burnout - are discussed. According to multiple regression analyses desire to work less hours was significantly linked to all three dimensions of burnout (p < 0.001), as well as work engagement (p = 0.001). In addition, work engagement significantly mediated the relationship between the burnout dimensions on work hour reduction (patient-related: b = − 0.135, p < 0.001; work-related: b = − 0.190, p < 0.001; personal: b = − 0.133, p < 0.001 ).

Discussion

Physicians tending to reduce work hours exhibited different levels of work engagement as well as burnout (personal, patient- and work-related). Moreover, work engagement influenced the relationship between burnout and work hour reduction. Therefore, interventions that increase work engagement may positively impact negative effects of burnout on work hour changes.
Prediction models of colorectal cancer prognosis incorporating perioperative longitudinal serum tumor markers: a retrospective longitudinal cohort study
Authors: Li Chunxia , Zhao Ke , Zhang Dafu , Pang Xiaolin , Pu Hongjiang , Lei Ming , Fan Bingbing , Lv Jiali , You Dingyun , Li Zhenhui , Zhang Tao
Published: February 2023

Background

Current prognostic prediction models of colorectal cancer (CRC) include only the preoperative measurement of tumor markers, with their available repeated postoperative measurements underutilized. CRC prognostic prediction models were constructed in this study to clarify whether and to what extent the inclusion of perioperative longitudinal measurements of CEA, CA19-9, and CA125 can improve the model performance, and perform a dynamic prediction.

Methods

The training and validating cohort included 1453 and 444 CRC patients who underwent curative resection, with preoperative measurement and two or more measurements within 12 months after surgery, respectively. Prediction models to predict CRC overall survival were constructed with demographic and clinicopathological variables, by incorporating preoperative CEA, CA19-9, and CA125, as well as their perioperative longitudinal measurements.

Results

In internal validation, the model with preoperative CEA, CA19-9, and CA125 outperformed the model including CEA only, with the better area under the receiver operating characteristic curves (AUCs: 0.774 vs 0.716), brier scores (BSs: 0.057 vs 0.058), and net reclassification improvement (NRI = 33.5%, 95% CI: 12.3 ~ 54.8%) at 36 months after surgery. Furthermore, the prediction models, by incorporating longitudinal measurements of CEA, CA19-9, and CA125 within 12 months after surgery, had improved prediction accuracy, with higher AUC (0.849) and lower BS (0.049). Compared with preoperative models, the model incorporating longitudinal measurements of the three markers had significant NRI (40.8%, 95% CI: 19.6 to 62.1%) at 36 months after surgery. External validation showed similar results to internal validation. The proposed longitudinal prediction model can provide a personalized dynamic prediction for a new patient, with estimated survival probability updated when a new measurement is collected during 12 months after surgery.

Conclusions

Prediction models including longitudinal measurements of CEA, CA19-9, and CA125 have improved accuracy in predicting the prognosis of CRC patients. We recommend repeated measurements of CEA, CA19-9, and CA125 in the surveillance of CRC prognosis.
Genetic susceptibility and lifestyle modify the association of long-term air pollution exposure on major depressive disorder: a prospective study in UK Biobank
Authors: Li Dankang , Xie Junqing , Wang Lulin , Sun Yu , Hu Yonghua , Tian Yaohua
Published: February 2023

Background

Evidence linking air pollution to major depressive disorder (MDD) remains sparse and results are heterogeneous. In addition, the evidence about the interaction and joint associations of genetic risk and lifestyle with air pollution on incident MDD risk remains unclear. We aimed to examine the association of various air pollutants with the risk of incident MDD and assessed whether genetic susceptibility and lifestyle influence the associations.

Methods

This population-based prospective cohort study analyzed data collected between March 2006 and October 2010 from 354,897 participants aged 37 to 73 years from the UK Biobank. Annual average concentrations of PM2.5, PM10, NO2, and NOx were estimated using a Land Use Regression model. A lifestyle score was determined based on a combination of smoking, alcohol drinking, physical activity, television viewing time, sleep duration, and diet. A polygenic risk score (PRS) was defined using 17 MDD-associated genetic loci.

Results

During a median follow-up of 9.7 years (3,427,084 person-years), 14,710 incident MDD events were ascertained. PM2.5 (HR: 1.16, 95% CI: 1.07–1.26; per 5 μg/m3) and NOx (HR: 1.02, 95% CI: 1.01–1.05; per 20 μg/m3) were associated with increased risk of MDD. There was a significant interaction between the genetic susceptibility and air pollution for MDD (P-interaction < 0.05). Compared with participants with low genetic risk and low air pollution, those with high genetic risk and high PM2.5 exposure had the highest risk of incident MDD (PM2.5: HR: 1.34, 95% CI: 1.23–1.46). We also observed an interaction between PM2.5 exposure and unhealthy lifestyle (P-interaction < 0.05). Participants with the least healthy lifestyle and high air pollution exposures had the highest MDD risk when compared to those with the most healthy lifestyle and low air pollution (PM2.5: HR: 2.22, 95% CI: 1.92–2.58; PM10: HR: 2.09, 95% CI: 1.78–2.45; NO2: HR: 2.11, 95% CI: 1.82–2.46; NOx: HR: 2.28, 95% CI: 1.97–2.64).

Conclusions

Long-term exposure to air pollution is associated with MDD risk. Identifying individuals with high genetic risk and developing healthy lifestyle for reducing the harm of air pollution to public mental health.
Echocardiographic parameters in French Bulldogs, Pugs and Boston Terriers with brachycephalic obstructive airways syndrome
Authors: Brložnik M. , Nemec Svete A. , Erjavec V. , Domanjko Petrič A.
Published: February 2023

Background

In this prospective study, we hypothesized that dogs with signs of brachycephalic obstructive airway syndrome (BOAS) would show differences in left and right heart echocardiographic parameters compared with brachycephalic dogs without signs of BOAS and non-brachycephalic dogs.

Results

We included 57 brachycephalic (30 French Bulldogs 15 Pugs, and 12 Boston Terriers) and 10 non-brachycephalic control dogs.

Brachycephalic dogs had significantly higher ratios of the left atrium to aorta and mitral early wave velocity to early diastolic septal annular velocity; smaller left ventricular (LV) diastolic internal diameter index; and lower tricuspid annular plane systolic excursion index, late diastolic annular velocity of the LV free wall, peak systolic septal annular velocity, late diastolic septal annular velocitiy, and right ventricular global strain than non-brachycephalic dogs.

French Bulldogs with signs of BOAS had a smaller diameter of the left atrium index and right ventricular systolic area index; higher caudal vena cava at inspiration index; and lower caudal vena cava collapsibility index, late diastolic annular velocity of the LV free wall, and peak systolic annular velocity of the interventricular septum than non-brachycephalic dogs.

Conclusions

The differences in echocardiographic parameters between brachycephalic and non-brachycephalic dogs, brachycephalic dogs with signs of BOAS and non-brachycephalic dogs, and brachycephalic dogs with and without signs of BOAS indicate higher right heart diastolic pressures affecting right heart function in brachycephalic dogs and those with signs of BOAS. Most changes in cardiac morphology and function can be attributed to anatomic changes in brachycephalic dogs alone and not to the symptomatic stage.
Sex differences and sex steroids influence on the presentation and severity of cardiovascular autonomic neuropathy of patients with type 1 diabetes
Authors: Nattero-Chávez Lía , Insenser María , Quintero Tobar Alejandra , Fernández-Durán Elena , Dorado Avendaño Beatriz , Fiers Tom , Kaufman Jean-Marc , Luque-Ramírez Manuel , Escobar-Morreale Héctor F.
Published: February 2023

Background

Sex differences characterize cardiovascular outcomes in patients with type 1 diabetes. Cardioautonomic neuropathy is a common complication of type 1 diabetes that associates increased morbi-mortality. Data regarding the interplay between sex and cardiovascular autonomic neuropathy are scarce and controversial in these patients. We aimed to address sex-related differences in the prevalence of seemingly asymptomatic cardioautonomic neuropathy in type 1 diabetes, and their associations with sex steroids.

Methods

We conducted a cross-sectional study including 322 consecutively recruited patients with type 1 diabetes. Cardioautonomic neuropathy was diagnosed using Ewing's score and power spectral heart rate data. We assessed sex hormones by liquid chromatography/tandem mass spectrometry.

Results

When considering all subjects as a whole, asymptomatic cardioautonomic neuropathy prevalence was not significantly different between women and men. When age was taken into account, the prevalence of cardioautonomic neuropathy was similar among young men and those > 50 years. However, in women > 50 years, the prevalence of cardioautonomic neuropathy doubled that of young women [45.8% (32.6; 59.7) vs. 20.4% (13.7; 29.2), respectively]. The OR of having cardioautonomic neuropathy was 3.3 higher in women > 50 years than in their younger counterparts. Furthermore, women presented more severe cardioautonomic neuropathy than men. These differences were even more marked when women were classified according their menopausal status instead of age. Peri- and menopausal women had an OR 3.5 (1.7; 7.2) of having CAN compared with their reproductive-aged counterparts [CAN prevalence: 51% (37; 65) vs. 23% (16; 32), respectively]. A binary logistic regression model (R2: 0.161; P = 0.001) displayed age > 50 years as a significant determinant of cardioautonomic neuropathy only in women. Androgens were positively associated with heart rate variability in men, and negatively in women. Accordingly, cardioautonomic neuropathy was associated with increased testosterone/estradiol ratio in women but to decreased testosterone concentrations in men.

Conclusions

Menopause in women with type 1 diabetes is accompanied by an increase in the prevalence of asymptomatic cardioautonomic neuropathy. This age-related excess risk of cardioautonomic neuropathy is not observed in men. Men and women with type 1 diabetes have opposite associations between circulating androgens and indexes of cardioautonomic function.

Trial registration ClinicalTrials.gov Identifier: NCT04950634.
Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment
Authors: Gao Zhifei , Bai Yifeng , Lin Anqi , Jiang Aimin , Zhou Chaozheng , Cheng Quan , Liu Zaoqu , Chen Xin , Zhang Jian , Luo Peng
Published: February 2023

As a nontraditional T-cell subgroup, γδT cells have gained popularity in the field of immunotherapy in recent years. They have extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious in tumor patients, have become pioneer drugs in the field of tumor immunotherapy since they were incorporated into clinical practice. In addition, γδT cells that have infiltrated into tumor tissues are found to be in a state of exhaustion or anergy, and there is upregulation of many immune checkpoints (ICs) on their surface, suggesting that γδT cells have a similar ability to respond to ICIs as traditional effector T cells. Studies have shown that targeting ICs can reverse the dysfunctional state of γδT cells in the tumor microenvironment (TME) and exert antitumor effects by improving γδT-cell proliferation and activation and enhancing cytotoxicity. Clarification of the functional state of γδT cells in the TME and the mechanisms underlying their interaction with ICs will solidify ICIs combined with γδT cells as a good treatment option.
SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities
Authors: Andrades Alvaro , Peinado Paola , Alvarez-Perez Juan Carlos , Sanjuan-Hidalgo Juan , García Daniel J. , Arenas Alberto M. , Matia-González Ana M. , Medina Pedro P.
Published: February 2023

Hematological malignancies are a highly heterogeneous group of diseases with varied molecular and phenotypical characteristics. SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complexes play significant roles in the regulation of gene expression, being essential for processes such as cell maintenance and differentiation in hematopoietic stem cells. Furthermore, alterations in SWI/SNF complex subunits, especially in ARID1A/1B/2, SMARCA2/4, and BCL7A, are highly recurrent across a wide variety of lymphoid and myeloid malignancies. Most genetic alterations cause a loss of function of the subunit, suggesting a tumor suppressor role. However, SWI/SNF subunits can also be required for tumor maintenance or even play an oncogenic role in certain disease contexts. The recurrent alterations of SWI/SNF subunits highlight not only the biological relevance of SWI/SNF complexes in hematological malignancies but also their clinical potential. In particular, increasing evidence has shown that mutations in SWI/SNF complex subunits confer resistance to several antineoplastic agents routinely used for the treatment of hematological malignancies. Furthermore, mutations in SWI/SNF subunits often create synthetic lethality relationships with other SWI/SNF or non-SWI/SNF proteins that could be exploited therapeutically. In conclusion, SWI/SNF complexes are recurrently altered in hematological malignancies and some SWI/SNF subunits may be essential for tumor maintenance. These alterations, as well as their synthetic lethal relationships with SWI/SNF and non-SWI/SNF proteins, may be pharmacologically exploited for the treatment of diverse hematological cancers.
Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application
Authors: Li Mingyang , Li Lei , Zheng Jianyi , Li Zeyu , Li Shijie , Wang Kefeng , Chen Xiaonan
Published: February 2023

Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and is one of the most common malignancies worldwide. The unremarkable symptoms of early stages, proneness to postoperative metastasis or recurrence, and low sensitivity to radiotherapy and chemotherapy pose a challenge for the diagnosis and treatment of RCC. Liquid biopsy is an emerging test that measures patient biomarkers, including circulating tumor cells, cell-free DNA/cell-free tumor DNA, cell-free RNA, exosomes, and tumor-derived metabolites and proteins. Owing to its non-invasiveness, liquid biopsy enables continuous and real-time collection of patient information for diagnosis, prognostic assessment, treatment monitoring, and response evaluation. Therefore, the selection of appropriate biomarkers for liquid biopsy is crucial for identifying high-risk patients, developing personalized therapeutic plans, and practicing precision medicine. In recent years, owing to the rapid development and iteration of extraction and analysis technologies, liquid biopsy has emerged as a low cost, high efficiency, and high accuracy clinical detection method. Here, we comprehensively review liquid biopsy components and their clinical applications over the past 5 years. Additionally, we discuss its limitations and predict its future prospects.
A randomized trial to evaluate the impact of Singapore’s forthcoming Nutri-grade front-of-pack beverage label on food and beverage purchases
Authors: Shin Soye , Puri Jyotika , Finkelstein Eric
Published: February 2023

Background

The epidemic of non-communicable diseases (NCDs) is a growing concern worldwide and Singapore is no exception to this global trend. As part of measures to address this concern, the Singapore government will implement a mandatory color-coded front-of-package (FOP) nutrition label for beverages, called Nutri-Grade (NG), which will complement the existing FOP label, Healthier Choice Symbol (HCS) logos, currently displayed on select food and beverage items. NG grades beverages on a four-point scale, A (healthiest) to D (least healthy), in terms of sugar and saturated fat levels. This study aimed to evaluate the effectiveness of the NG label on nutritional quality of pre-packaged beverages using a fully functional online grocery store.

Methods

We conducted a 2-arm crossover trial involving actual purchases with 138 participants randomly exposed to: 1) Control with HCS logos displayed on qualifying items; 2) Similar to Control except that all beverages displayed the NG label. The effects of the NG label were estimated using a linear mixed-effects model that addresses correlations between repeated measures and accommodates missing data.

Results

We found that the NG label encouraged consumers to choose beverages with higher ratings. This led to a reduction in sugar from beverages purchased by 1.51 g [95% CI: − 2.68, − 0.34] per serving but was not effective at reducing saturated fat purchased (− 0.009 g [95% CI: − 0.22, 0.20]) per serving or improvements in overall diet quality, measured by the weighted (by the number of servings) average Nutri-Score value ranging from 1 to 5 (− 0.024 [95% CI: − 0.13, 0.08]).

Conclusions

Results suggest that the Nutri-Grade label is likely to reduce sugar purchased from beverages. However, to improve overall diet quality in Singapore, additional measures will be needed.

Trial registration

This trial was registered on ClinicalTrials.gov under the identifier: NCT05018026 on 24th August 2021.
Emerging therapeutic strategies for unmet need in neovascular age-related macular degeneration
Authors: Khachigian Levon M. , Liew Gerald , Teo Kelvin Y. C. , Wong Tien Y. , Mitchell Paul
Published: February 2023

Neovascular age-related macular degeneration (nAMD) is a major cause of visual impairment and blindness. Anti-vascular endothelial growth factor (VEGF) agents, such as ranibizumab, bevacizumab, aflibercept, brolucizumab and faricimab have revolutionized the clinical management of nAMD. However, there remains an unmet clinical need for new and improved therapies for nAMD, since many patients do not respond optimally, may lose response over time or exhibit sub-optimal durability, impacting on real world effectiveness. Evidence is emerging that targeting VEGF-A alone, as most agents have done until recently, may be insufficient and agents that target multiple pathways (e.g., aflibercept, faricimab and others in development) may be more efficacious. This article reviews issues and limitations that have arisen from the use of existing anti-VEGF agents, and argues that the future may lie in multi-targeted therapies including alternative agents and modalities that target both the VEGF ligand/receptor system as well as other pathways.
Predicting later categories of upper limb activity from earlier clinical assessments following stroke: an exploratory analysis
Authors: Barth Jessica , Lohse Keith R. , Bland Marghuretta D. , Lang Catherine E.
Published: February 2023

Background

Accelerometers allow for direct measurement of upper limb (UL) activity. Recently, multi-dimensional categories of UL performance have been formed to provide a more complete measure of UL use in daily life. Prediction of motor outcomes after stroke have tremendous clinical utility and a next step is to explore what factors might predict someone’s subsequent UL performance category.

Purpose

To explore how different machine learning techniques can be used to understand how clinical measures and participant demographics captured early after stroke are associated with the subsequent UL performance categories.

Methods

This study analyzed data from two time points from a previous cohort (n = 54). Data used was participant characteristics and clinical measures from early after stroke and a previously established category of UL performance at a later post stroke time point. Different machine learning techniques (a single decision tree, bagged trees, and random forests) were used to build predictive models with different input variables. Model performance was quantified with the explanatory power (in-sample accuracy), predictive power (out-of-bag estimate of error), and variable importance.

Results

A total of seven models were built, including one single decision tree, three bagged trees, and three random forests. Measures of UL impairment and capacity were the most important predictors of the subsequent UL performance category, regardless of the machine learning algorithm used. Other non-motor clinical measures emerged as key predictors, while participant demographics predictors (with the exception of age) were generally less important across the models. Models built with the bagging algorithms outperformed the single decision tree for in-sample accuracy (26–30% better classification) but had only modest cross-validation accuracy (48–55% out of bag classification).

Conclusions

UL clinical measures were the most important predictors of the subsequent UL performance category in this exploratory analysis regardless of the machine learning algorithm used. Interestingly, cognitive and affective measures emerged as important predictors when the number of input variables was expanded. These results reinforce that UL performance, in vivo, is not a simple product of body functions nor the capacity for movement, instead being a complex phenomenon dependent on many physiological and psychological factors. Utilizing machine learning, this exploratory analysis is a productive step toward the prediction of UL performance.

Trial registration NA
The detectable anti-interferon-γ autoantibodies in COVID-19 patients may be associated with disease severity
Authors: Chen Po-Ku , Yeo Kai-Jieh , Chang Shih-Hsin , Liao Tsai-Ling , Chou Chia-Hui , Lan Joung-Liang , Chang Ching-Kun , Chen Der-Yuan
Published: February 2023

Background

Neutralizing anti-interferon (IFN)-γ autoantibodies are linked to adult-onset immunodeficiency and opportunistic infections.

Methods

To explore whether anti-IFN-γ autoantibodies are associated with disease severity of coronavirus disease 2019 (COVID-19), we examined the titers and functional neutralization of anti-IFN-γ autoantibodies in COVID-19 patients. In 127 COVID-19 patients and 22 healthy controls, serum titers of anti-IFN-γ autoantibodies were quantified using enzyme-linked immunosorbent assay, and the presence of autoantibodies was verified with immunoblotting assay. The neutralizing capacity against IFN-γ was evaluated with flow cytometry analysis and immunoblotting, and serum cytokines levels were determined using the MULTIPLEX platform.

Results

A higher proportion of severe/critical COVID-19 patients had positivity for anti-IFN-γ autoantibodies (18.0%) compared with non-severe patients (3.4%, p < 0.01) or healthy control (HC) (0.0%, p < 0.05). Severe/critical COVID-19 patients also had higher median titers of anti-IFN-γ autoantibodies (5.01) compared with non-severe patients (1.33) or HC (0.44). The immunoblotting assay could verify the detectable anti-IFN-γ autoantibodies and revealed more effective inhibition of signal transducer and activator of transcription (STAT1) phosphorylation on THP-1 cells treated with serum samples from anti-IFN-γ autoantibodies-positive patients compared with those from HC (2.21 ± 0.33 versus 4.47 ± 1.64, p < 0.05). In flow-cytometry analysis, sera from autoantibodies-positive patients could also significantly more effectively suppress the STAT1 phosphorylation (median,67.28%, interquartile range [IQR] 55.2–78.0%) compared with serum from HC (median,106.7%, IQR 100.0–117.8%, p < 0.05) or autoantibodies-negative patients (median,105.9%, IQR 85.5–116.3%, p < 0.05). Multivariate analysis revealed that the positivity and titers of anti-IFN-γ autoantibodies were significant predictors of severe/critical COVID-19. Compared with non-severe COVID-19 patients, we reveal that a significantly higher proportion of severe/critical COVID-19 patients are positive for anti-IFN-γ autoantibodies with neutralizing capacity.

Conclusion

Our results would add COVID-19 to the list of diseases with the presence of neutralizing anti-IFN-γ autoAbs. Anti-IFN-γ autoantibodies positivity is a potential predictor of severe/critical COVID-19.
Effect of a suitable treatment period on the genetic transformation efficiency of the plant leaf disc method
Authors: Xia Yufei , Cao Yuan , Ren Yongyu , Ling Aoyu , Du Kang , Li Yun , Yang Jun , Kang Xiangyang
Published: February 2023

Background

Agrobacterium tumefaciens-mediated leaf disc genetic transformation is an important way to achieve transgenics or gene editing. Ensuring stable and efficient genetic transformation is still an important problem in modern biology. It is assumed that the difference in the development status of genetic transformation cells of receptor materials is the main reason for the difference and instability of genetic transformation efficiency; the stable and efficient genetic transformation rate can be obtained by defining the appropriate treatment period of the receptor material and applying genetic transformation in a timely manner.

Results

Based on these assumptions, we studied and established an efficient and stable Agrobacterium-mediated plant transformation system with hybrid poplar (Populus alba × Populus glandulosa, 84 K) leaves, stem segments and tobacco leaves as the research objects. There were differences in the development process of leaf bud primordial cells from different explants, and the genetic transformation efficiency was significantly related to the cell development stage of the in vitro cultured materials. Among them, the genetic transformation rate of poplar and tobacco leaves was the highest on the 3rd and 2nd day of culture, reaching 86.6% and 57.3%, respectively. The genetic transformation rate of poplar stem segments was the highest on the 4th day of culture, reaching 77.8%. The best treatment period was from the development of leaf bud primordial cells to the S phase of the cell cycle. The number of cells detected using flow cytometry and 5-ethynyl-2ʹ-deoxyuridine (EdU) staining, the expression of cell cycle-related protein CDKB1; 2, CDKD1; 1, CYCA3; 4, CYCD1; 1, CYCD3; 2, CYCD6; 1, and CYCH; 1 of explants, and morphological changes of explants can be used as indicators to determine the appropriate treatment period for genetic transformation.

Conclusions

Our study provides a new and universal set of methods and characteristics to identify the S phase of the cell cycle and apply genetic transformation treatments at the appropriate time. Our results are of great significance for improving the efficiency and stability of plant leaf disc genetic transformation.
Characteristics of subsequent contralateral proximal femoral fracture: more convenient access is needed to treat osteoporosis
Authors: Jiang Yuxuan , Zhu Yangjun , Zhang Binfei , Feng Dongxu
Published: February 2023

Background

Patients with proximal femoral fracture (PFF) have high mortality and many complications. Osteoporosis increases the risk of subsequent fractures, leading to subsequent contralateral PFF. This study was performed to analyze the features of individuals with subsequent PFF following surgical therapy of first PFF and to ascertain whether such patients received an examination or treatment of osteoporosis. The reasons for lack of examination or treatment were also analyzed.

Methods

This retrospective study involved 181 patients with subsequent contralateral PFF who underwent surgical treatment in Xi'an Honghui hospital from September 2012 to October 2021. The patients’ sex, age, hospital day, mechanism of injury, surgical procedure, fracture interval, fracture type, fracture classification, and Singh index of the contralateral hip at the time of the initial and subsequent fractures were recorded. Whether the patients took calcium and vitamin D supplements, used anti-osteoporosis medication, or underwent a dual X-ray absorptiometry (DXA) scan was recorded, as was the start time of each. Patients who had never undergone a DXA scan or received anti-osteoporosis medication took part in a questionnaire.

Results

The 181 patients in this study comprised 60 (33.1%) men and 121 (66.9%) women. Patients with initial PFF and subsequent contralateral PFF had a median age of 80 years (range 49–96 years) and 82 years (range 52–96 years), respectively. The median fracture interval was 24 (7–36) months. Contralateral fractures occurred at the highest incidence between 3 months and 1 year (28.7%). The Singh index was not significantly different between the two fractures. In 130 (71.8%) patients, the fracture type was the same. No significant difference was found in the fracture type or fracture stability classification. A total of 144 (79.6%) patients had never received a DXA scan or anti-osteoporosis medication. The main reason for not treating osteoporosis further was concern about the safety of drug interactions (67.4%).

Conclusions

Patients with subsequent contralateral PFF were of advanced age, had a higher proportion of intertrochanteric femoral fractures, had more severe osteoporosis, and had longer hospital stays. The difficulty managing such patients requires multidisciplinary involvement. Most of these patients were not screened or formally treated for osteoporosis. Advanced-age patients with osteoporosis need reasonable treatment and management.
Tracheobronchial tooth and dental prosthesis aspirations: 15 cases
Authors: Eliçora Aykut , Sezer Hüseyin Fatih , Topçu Salih , Çardaközü Tülay
Published: February 2023

Background

Tracheobronchial foreign body is uncommon in adults. Among foreign body aspirations, tooth and dental prosthesis aspiration is a very rare condition. In the literature, dental aspiration is generally found as a case report and there is no single-center case series. In this study, we aimed to present our clinical experience in 15 cases with tooth and dental prosthesis aspiration.

Methods

Data from 693 patients who presented to our hospital for foreign body aspiration between the years 2006 and 2022 were analyzed retrospectively. Fifteen cases who aspirated tooth and dental prostheses as foreign bodies were included in our study.

Results

Foreign bodies were removed by rigid bronchoscopy in 12 (80%) cases and fiberoptic bronchoscopy in 2 (13.3%) cases. In one of our cases, foreign body was expected with cough.When evaluated in terms of foreign body, partial upper anterior tooth prosthesis in 5 (33.3%) cases, partial anterior lower tooth prosthesis in 2 (13.3%) cases, dental implant screw in 2 (13.3%) cases, lower molar crown in 1 (6.6%) case, lower jaw bridge prosthesis in 1(6.6%) case, upper jaw bridge prosthesis in 1(6.6%) case, broken tooth fragment in 1(6.6%) case, upper molar tooth crown coating in 1(6.6%) case and upper lateral incisor tooth in 1(6.6%) case were observed.

Conclusion

Dental aspirations can also occur in healthy adults. Anamnesis is the most important factor in diagnosis and diagnostic bronchoscopic procedures should be performed in cases where adequate anamnesis cannot be obtained.