bluuebunny/crossref_metadata_2025 huggingface dataset:
Heart surgery over two decades: what we have learned about results and changing risks
Authors: Tajdini Masih , Behnoush Amir Hossein , Pashang Mina , Jameie Mana , Khalaji Amirmohammad , Sadeghian Saeed , Vasheghani-Farahani Ali , Poorhosseini Hamidreza , Masoudkabir Farzad , Hosseini Kaveh , Davoodi Saeed , Sahebjam Mohammad , Barkhordari Khosro , Ashraf Haleh , Shafiei Akbar , Karimi Abbasali ,   T. H. C. Surgery Databank Collaborators, Ahmadi Tafti Seyed Hossein , Mansourian Soheil , Shirzad Mahmood , Bagheri Jamshid , Jalali Arash , Abbasi Kiomars , Zoroufian Arezou , Hosseinsabet Ali , Davarpasand Tahereh , Mohseni-Badalabadi Reza , Hali Reza , Mehrabanian Mohammadjavad , Dehghani Firoozabadi Mehdi , Nooralishahi Behrang , Mortazavi Seyedeh Hamideh , Lotfi-Tokaldany Masoumeh , Rostami Elham , Karimi Mahdieh
Published: April 2024

Objectives

Using the cardiac surgery database is of high importance in referral centers and can lead to a better quality of care for patients. Tehran Heart Center (THC) is a cardiovascular referral center that was inaugurated in 2001. In this report, we aimed to present the third report of trends in patients' cardiovascular risk factors and surgical procedures from 2002 to 2021 that have been gathered for all THC patients.

Methods

This serial cross-sectional study was conducted at Tehran Heart Center from 2002 to 2021. All patients undergoing cardiac surgeries were eligible to enter the study (N = 63,974). Those with miscellaneous types of surgeries were excluded (N = 9556). The distribution of cardiac surgeries (including isolated coronary artery bypass graft (CABG), isolated valve, and CABG + valve surgeries) and their respective in-hospital mortality were recorded. Furthermore, 20-year trends in the prevalence of various cardiovascular risk factors (CVRFs) among the following groups were evaluated: a) isolated CABG, b) aortic valve replacement/repair for aortic stenosis (AS/AVR/r), and c) isolated other valve surgeries (IVS).

Results

A total of 54,418 patients (male: 70.7%, age: 62.7 ± 10.8 years) comprised the final study population, with 84.5% prevalence of isolated CABG. Overall, the AS/AVR/r group was in between the CABG and IVS groups concerning CVRFs distribution. Excluding some exceptions for the AS/AVR/r group (in which the small sample size (N = 909) precluded observing a clear trend), all studied CVRFs demonstrated an overall rising trend from 2002 to 2021 in all three groups. Regarding in-hospital mortality, the highest rate was recorded as 4.0% in 2020, while the lowest rate was 2.0% in 2001.

Conclusions

Isolated CABG remained the most frequent procedure in THC. Notable, increasing trends in CVRFs were observed during this 20-year period and across various types of cardiac surgeries, which highlights the clinical and policy-making implications of our findings.

Graphical Abstract
HAPLN1 knockdown inhibits heart failure development via activating the PKA signaling pathway
Authors: Yan Tao , Song Shushuai , Sun Wendong , Ge Yiping
Published: April 2024

Background

Heart failure (HF) is a heterogeneous syndrome that affects millions worldwide, resulting in substantial health and economic burdens. However, the molecular mechanism of HF pathogenesis remains unclear.

Methods

HF-related key genes were screened by a bioinformatics approach.The impacts of HAPLN1 knockdown on Angiotensin II (Ang II)-induced AC16 cells were assessed through a series of cell function experiments. Enzyme-linked immunosorbent assay (ELISA) was used to measure levels of oxidative stress and apoptosis-related factors. The HF rat model was induced by subcutaneous injection isoprenaline and histopathologic changes in the cardiac tissue were assessed by hematoxylin and eosin (HE) staining and echocardiographic index. Downstream pathways regulated by HAPLN1 was predicted through bioinformatics and then confirmed in vivo and in vitro by western blot.

Results

Six hub genes were screened, of which HAPLN1, FMOD, NPPB, NPPA, and COMP were overexpressed, whereas NPPC was downregulated in HF. Further research found that silencing HAPLN1 promoted cell viability and reduced apoptosis in Ang II-induced AC16 cells. HAPLN1 knockdown promoted left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS), while decreasing left ventricular end-systolic volume (LVESV) in the HF rat model. HAPLN1 knockdown promoted the levels of GSH and suppressed the levels of MDA, LDH, TNF-α, and IL-6. Mechanistically, silencing HAPLN1 activated the PKA pathway, which were confirmed both in vivo and in vitro.

Conclusion

HAPLN1 knockdown inhibited the progression of HF by activating the PKA pathway, which may provide novel perspectives on the management of HF.
Barriers and facilitators of the reporting by family doctors of cases of domestic violence – a qualitative study across Portugal
Authors: Moreira Diana Nadine , Pinto da Costa Mariana
Published: April 2024

Background

Domestic violence (DV) is a serious and prevalent public health problem with devastating consequences for the victims and their families. Whilst the number of cases reported to the authorities has risen in recent years, many victims still chose not to present a complaint. In Portugal, to address this, DV became a public crime. As victims of DV present multiple health problems and frequently seek professional help, family doctors are in a privileged position to detect and report cases of DV to the authorities. However, little is known about what motivates these professionals to report or not the DV cases they encounter in their practice to the authorities.

Methods

We conducted semi-structured interviews with family doctors from all regional health administrations of continental Portugal. Interviews occurred between July 2020 and September 2022, were conducted in person or remotely, audio recorded, transcribed, and analysed using thematic analysis. Content analysis was conducted to assess the agreement or disagreement regarding mandatory reporting in each of the themes and subthemes.

Results

Fifty-four family doctors took part in this study (n = 39 women, n = 15 men). The main themes that arose from the analysis were: “Barriers related to the physician’s activity,” “Barriers related to the victim or aggressor,” “Facilitators related to the physician’s activity,” “Facilitators related to the victim or aggressor.” Although different barriers were described, most doctors agreed with the mandatory reporting of DV cases.

Conclusions

Family doctors encounter multiple barriers and facilitators when considering reporting a DV case to the authorities. The results of this study can help develop new interventions to address the barriers described by the doctors, increasing their compliance with mandatory reporting, the protection of victims and the just persecution of the aggressor.
Trajectories of depressive symptom and its association with air pollution: evidence from the Mr. OS and Ms. OS Hong Kong cohort study
Authors: Zhao Yinan , Liu Qingcai , Chen Yifei , Kwok Timothy C. Y. , Leung Jason C. S. , Feng Hui , Wong Samuel Yeung Shan
Published: April 2024

Background

Depression is a global health priority. Maintaining and delaying depressive symptoms in older adults is a key to healthy aging. This study aimed to identify depressive symptom trajectories, predictors and mortality, while also exploring the relationship between air quality and depressive symptoms in older adults in the Hong Kong community over 14 years.

Methods

This study is a longitudinal study in Hong Kong. The target population was community-dwelling older adults over age 65. Depressive symptoms were measured by the Geriatric Depression Scale (GDS-15). Group-based trajectory model was used to identify heterogeneity in longitudinal changes over 14 years and examine the associations between baseline variables and trajectories for different cohort members using multinomial logistic regression. The Kaplan–Meier method was employed to conduct survival analysis and explore the variations in survival probabilities over time among different trajectory group. Linear mixed model was used to explore the relationship between air quality and depressive symptoms.

Results

A total of 2828 older adults were included. Three different trajectories of depressive symptoms in older people were identified: relatively stable (15.4%), late increase (67.1%) and increase (17.5%). Female, more number of chronic diseases, poor cognitive function, and poor health-related quality of life (HRQOL) were significantly associated with other less favorable trajectories compared with participants with stable levels of depressive symptoms. The late increase group had a lower mortality rate than the relatively stable and increased groups. Lower baseline ambient air pollutant exposure to NO2 over 14 years was significantly associated with fewer depressive symptoms.

Conclusions

In this study, we found that a late increase in depressive symptoms was the predominant trend in older Chinese people in Hong Kong. Poorer HRQOL was predictive of less favorable trajectories of depressive symptoms. Ambient air pollution was associated with depressive symptoms. This novel observation strengthens the epidemiological evidence of longitudinal changes in depressive symptoms and associations with late-life exposure to air pollution.
Comparative safety of tramadol and other opioids following total hip and knee arthroplasty
Authors: Bosco Elliott , Riester Melissa R. , Beaudoin Francesca L. , Schoenfeld Andrew J. , Gravenstein Stefan , Mor Vincent , Zullo Andrew R.
Published: April 2024

Background

Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA.

Methods

This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models.

Results

The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons.

Conclusions

Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.
Fabry disease in W162C mutation: a case report of two patients and a review of literature
Authors: Furia Alessandro , Ditaranto Raffaello , Biagini Elena , Parisi Vanda , Incensi Alex , Parisini Sara , Liguori Rocco , Donadio Vincenzo
Published: April 2024

Background

Fabry disease is a multisystemic disorder characterized by deposition of globotriaosylceramide (Gb3) and its deacylated form in multiple organs, sometimes localized in specific systems such as the nervous or cardiovascular system. As disease-modifying therapies are now available, early diagnosis is paramount to improving life quality and clinical outcomes. Despite the widespread use of non-invasive techniques for assessing organ damage, such as cardiac magnetic resonance imaging (MRI) for patients with cardiac disease, organ biopsy remains the gold standard to assess organ involvement.

Case presentation

The cases of two patients, father and daughter with a W162C mutation, are described. The father presented with late-onset, cardiac Fabry disease, subsequently developing systolic dysfunction and heart failure. His daughter, while asymptomatic and with normal cardiac assessment (except for slightly reduced native T1 values by cardiac MRI), had already initial myocyte Gb3 deposits on the endomyocardial biopsy, allowing her to start therapy precociously and potentially modifying the course of her disease. A review of the literature concerning the W162C mutation is then provided, showing that it is usually associated to classic, multisystemic Fabry disease rather than the cardiac-restricted form as in these two cases.

Conclusions

Three main points can be concluded from this report. First, the W162C mutation can present with a more variegate phenotype than that predicted on a molecular basis. Second, endomyocardial biopsy was shown in this case to precede non-invasive investigation in determining organ involvement, justifying further studies on this potentially reliable technique, Third, difficulties can arise in the management of asymptomatic female carriers.
Impact of age on central lymph nodes involvement in papillary thyroid cancer
Authors: Awny Shadi , Abdallah Ahmed , Metwally Islam H , Abdelwahab Khaled , Zuhdy Mohammad , Hamdy Omar , Fareed Ahmed M , Atallah Khalid
Published: April 2024

Background

Total thyroidectomy is the main line of treatment for papillary thyroid cancer. Central lymph node dissection (CLND) is still debatable. In this study, we aimed to correlate the central lymph node status with the age of patients.

Methods

This is a retrospective study including patients with papillary thyroid cancer (PTC) who underwent total thyroidectomy and CLND at a tertiary cancer center during the period from January 2012 to September 2022. Patients were subdivided into 3groups: patients younger than 20 years old, patients between 20 and 40 years old, and patients older than 40 years old. Correlation between central lymph node status, lateral lymph node status, and harvest count with each other and between age groups was done.

Results

315 patients were included. The younger the age group the higher the possibility of harboring positive central nodes, however, the positivity of lateral nodes was similar. Neither central nodal harvest nor positive central node count significantly differed between groups. The lateral nodal harvest was significantly higher in the < 20 years group with no affection to the number of positive nodes retrieved. The younger the age group the longer the disease-free survival (DFS).

Conclusion

We can conclude that patients younger than twenty years had a higher probability of harboring malignancy in central nodes and higher lateral node harvest on dissection. In contrast, they do have a lower incidence of recurrence.
Cancer statistics in Yemen: incidence and mortality, in 2020
Authors: Ibrahim Amran , El Baldi Marwa , Mohammed Sawsan , El Rhazi Karima , Benazzouz Bouchra
Published: April 2024

Background

The current cancer epidemiological profile in Yemen suffers from a lack of locally representative data and resources, posing a challenge in determining the real incidence, prevalence, survival and mortality rates, particularly data extracted from national hospitals. This study aims to provide a comprehensive overview of the cancer burden and trends in Yemen for 2020, including incidence and mortality rates.

Methods

The current study provides cancer statistics and their trends in Yemen, including incidence and mortality, in 2020 by using descriptive statistics. The data was obtained using the Global Cancer Observatory (GCO) 2020 online database.

Results

According to the (GCP) database in 2020, the crude incidence rate (CIR) of all cancers in Yemen was 55.2 per 100.000. The age-standardized rate (ASR) was 97.0 per 100.000, and the cumulative risk (0–74) was 22.0 per 100.000. The age-standardized rate (ASR) was 76.5 per 100.000, and the cumulative risk (0–74) was 19.6 per 100.000. Furthermore, the crude mortality rate (CIR) of all cancers was 40.6 per 100.000. Breast cancer was most prevalent in Yemen across all age groups and genders (31.1%), followed by colorectal cancer (7.7%) and leukemia (5.7%). Breast cancer also ranked as the primary cause of mortality at an estimated percentage of 13.5%, followed by colorectal cancer (8.8%) and stomach cancer (7.1%).

Conclusion

Cancer has become a significant life-threatening illness in Yemen with an increase in the disease burden of breast cancer in women. Furthermore, leukemia in children and colorectal cancer in both sexes have experienced a more significant burden as well. Therefore, it is imperative for initiatives for cancer control and prevention to be prioritised at national and regional levels.
An immune-related adverse event of Behcet’s-like syndrome following pembrolizumab treatment
Authors: Chen Qiao , Li Deyu , Zhang Guifeng , Zhong Jiangming , Lin Li , Liu Zhenhua
Published: April 2024

Background

In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet’s-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China.

Case presentation

Here, we report a rare case of Behcet’s-like symptom following pembrolizumab treatment. A 43-year-old female was diagnosed as lymph node and bone metastasis of adenocarcinoma with unknown primary lesion, probably being of pulmonary origin. She was treated with pembrolizumab 200 mg every three weeks in combination with chemotherapy for 6 cycles, followed by pembrolizumab monotherapy maintenance. However, she developed Behcet’s-like syndrome with oral ulcer, genital uler, phlebitis, and vision loss after 9 cycles of pembrolizumab treatment. She was treated with prednisone 5 mg orally three times a day. Two weeks later, dose of glucocorticoid gaven to the patient gradually decreased with improved symptoms. After a treatment-free withdrawal period, the patient requested to continue pembrolizumab treatment. Unfortunately, the above symptoms recurred on the second day following pembrolizumab treatment, and glucocorticoid was taken once again. The symptoms improved and the condition was under control.

Conclusions

In view of the exponential growth of immunocheckpoint inhibitors (ICIs) in a variety of tumors, we should be alert to related adverse events, especially the rare rheumatic manifestations.
The metabolic reprogramming of γ-aminobutyrate in oral squamous cell carcinoma
Authors: Wu Shi-Lian , Zha Guang-Yu , Tian Ke-Bin , Xu Jun , Cao Ming-Guo
Published: April 2024

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy. The oncometabolites have been studied in OSCC, but the mechanism of metabolic reprogramming remains unclear. To identify the potential metabolic markers to distinguish malignant oral squamous cell carcinoma (OSCC) tissue from adjacent healthy tissue and study the mechanism of metabolic reprogramming in OSCC. We compared the metabolites between cancerous and paracancerous tissues of OSCC patients by 1HNMR analysis. We established OSCC derived cell lines and analyzed their difference of RNA expression by RNA sequencing. We investigated the metabolism of γ-aminobutyrate in OSCC derived cells by real time PCR and western blotting. Our data revealed that much more γ-aminobutyrate was produced in cancerous tissues of OSCC patients. The investigation based on OSCC derived cells showed that the increase of γ-aminobutyrate was promoted by the synthesis of glutamate beyond the mitochondria. In OSCC cancerous tissue derived cells, the glutamate was catalyzed to glutamine by glutamine synthetase (GLUL), and then the generated glutamine was metabolized to glutamate by glutaminase (GLS). Finally, the glutamate produced by glutamate-glutamine-glutamate cycle was converted to γ-aminobutyrate by glutamate decarboxylase 2 (GAD2). Our study is not only benefit for understanding the pathological mechanisms of OSCC, but also has application prospects for the diagnosis of OSCC.
“It is very hard to just accept this” – a qualitative study of palliative care teams’ ethical reasoning when patients do not want information
Authors: Björk Joar
Published: April 2024

Background

The aim of this study was to explore how palliative care staff reason about the autonomy challenge that arises when a patient who has first said he wants full information appears to change his mind and rejects being informed.

Methods

The study had a qualitative and exploratory design. Participants (physicians, registred nurses, social workers, physiotherapists and occupational therapists) were recruited from palliative care teams in southern Sweden. Six separate focus group interviews with a total number of 33 participants were conducted. The teams were asked to discuss a fictional case of a man who first wants, then rejects, information about his situation. The interviews were audiotaped and transcribed verbatim. Reflexive thematic analysis following Braun and Clarke was undertaken to analyse data.

Results

The analysis resulted in three themes: Patients have a right to reject information, Questioning whether this patient WANTS to reject information and There are other values at stake, too. Although participants endorsed a right to reject information, they were unsure whether this right was relevant in this situation, and furthermore felt that it should be balanced against counteracting factors. The effect of such balancing was that participants would aim to find a way to present relevant information to the patient, but in a probing and flexible way.

Conclusions

In their work with dying patients, palliative care staff meet many autonomy challenges. When faced with a choice to withhold information as per a patient’s wishes, or to provide information with the patient’s best interest in mind, staff find it hard to balance competing values. Staff also find it hard to balance their own interests against a purely professional stance. The overall strategy seems to be to look for caring ways to impart the information.
Protective effect of Ganoderma lucidum-fermented crop extracts against hydrogen peroxide- or β-amyloid-induced damage in human neuronal SH-SY5Y cells
Authors: Huang Chung-Hsiung , Liao Yu-Ting , Chen Chien-Li , Tsai Guo-Jane
Published: April 2024

Background

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of stacked β-amyloid peptides in the brain and associated with the generation of oxidative stress. So far, there is no cure for AD or a way to stop its progression. Although the neuroprotective effects of Ganoderma lucidum aqueous extract and G. lucidum-derived triterpenoids and polysaccharides have been reported, the influence of G. lucidum-fermented crops on AD still lacks clarity.

Methods

This study aimed to investigate the protective effect of G. lucidum-fermented crop extracts against hydrogen peroxide- or β-amyloid peptide (Aβ25-35)-induced damage in human neuroblastoma SH-SY5Y cells.

Results

Various extracts of G. lucidum-fermented crops, including extract A: 10% ethanol extraction using microwave, extract B: 70˚C water extraction, and extract C: 100˚C water extraction followed by ethanol precipitation, were prepared and analyzed. Extract B had the highest triterpenoid content. Extract C had the highest total glucan content, while extract A had the highest gamma-aminobutyric acid (GABA) content. The median inhibitory concentration (IC50, mg/g) for DPPH and ABTS scavenging activity of the fermented crop extracts was significantly lower than that of the unfermented extract. Pretreatment with these extracts significantly increased the cell viability of SH-SY5Y cells damaged by H2O2 or Aβ25-35, possibly by reducing cellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Moreover, extract B markedly alleviated the activity of acetylcholinesterase (AChE), which is crucial in the pathogenesis of AD.

Conclusion

These results clearly confirmed the effects of G. lucidum-fermented crop extracts on preventing against H2O2- or Aβ25-35-induced neuronal cell death and inhibiting AChE activity, revealing their potential in management of AD.
Mechanism of Smilax china L. in the treatment of intrauterine adhesions based on network pharmacology, molecular docking and experimental validation
Authors: Shi Tingting , Hou Chuqi , Duan Yongzhen , Li Yuliang , Liu Wenqin , Huang Peixian , Zhou Yuhua , Yu Shanshan , Song Luyao
Published: April 2024

Background

Smilax china L. (SCL) is a traditional herbal medicine for the potential treatment of intrauterine adhesion (IUA). However, the mechanisms of action have not yet been determined. In this study, we explored the effects and mechanisms of SCL in IUA by network pharmacology, molecular docking and molecular biology experiments.

Methods

Active ingredients and targets of SCL were acquired from TCMSP and SwissTargetPrediction. IUA-related targets were collected from the GeneCards, DisGeNET, OMIM and TTD databases. A protein‒protein interaction (PPI) network was constructed by Cytoscape 3.9.1 and analysed with CytoHubba and CytoNCA to identify the core targets. The DAVID tool was used for GO and KEGG enrichment analyses. Furthermore, molecular docking was employed to assess the interaction between the compounds and key targets. Finally, the mechanisms and targets of SCL in IUA were verified by cellular experiments and western blot.

Results

A total of 196 targets of SCL were identified, among which 93 were related to IUA. Topological and KEGG analyses results identified 15 core targets that were involved in multiple pathways, such as inflammation, apoptosis, and PI3K/AKT signalling pathways. Molecular docking results showed that the active compounds had good binding to the core targets. In vitro experiments showed that astilbin (AST), a major component of SCL, significantly reduced TGF-β-induced overexpression of fibronectin (FN), activation of the PI3K/AKT signalling pathway and the expression of downstream factors (NF-κB and BCL2) in human endometrial stromal cells, suggesting that AST ameliorates IUA by mediating the PI3K/AKT/NF-κB and BCL2 proteins.

Conclusions

AST, a major component of SCL, may be a potential therapeutic agent for IUA. Moreover, its mechanism is strongly associated with regulation of the PI3K/AKT signalling pathway and the downstream NF-κB and BCL2 proteins. This study will provide new strategies that utilize AST for the treatment of IUA.
A systematic review and meta-analysis on sodium tanshinone IIA sulfonate injection for the adjunctive therapy of pulmonary heart disease
Authors: Shao Huikai , Yu Fei , Xu Dongsheng , Fang Chunyan , Tong Rongsheng , Zhao Lingguo
Published: April 2024

Aims

Sodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study.

Methods

Randomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed.

Results

19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p < 0.001), partial pressure of oxygen (MD = 10.16; 95% CI, 5.07 to 15.24; p < 0.001), left ventricular ejection fraction (MD = 8.66; 95% CI, 6.14 to 11.18; p < 0.001) and stroke volume (MD = 13.10; 95% CI, 11.83 to 14.38; p < 0.001), meanwhile decreasing the low shear blood viscosity (MD = -1.16; 95% CI, -1.57 to -0.74; p < 0.001), high shear blood viscosity (MD = -0.64; 95% CI, -0.86 to -0.42; p < 0.001), plasma viscosity (MD = -0.23; 95% CI, -0.30 to -0.17; p < 0.001), hematokrit (MD = -8.52; 95% CI, -11.06 to -5.98; p < 0.001), fibrinogen (MD = -0.62; 95% CI, -0.87 to -0.37; p < 0.001) and partial pressure of carbon dioxide (MD = -8.56; 95% CI, -12.09 to -5.02; p < 0.001).

Conclusion

STS injection as adjunctive therapy seemed to be more effective than Western medicine alone for PHD. However, due to low quality of the included RCTs, more well-designed RCTs were necessary to verify the efficacy of STS injection.
The importance of creating the right conditions for group intervision sessions among medical residents– a qualitative study
Authors: Jorissen Anouk , van de Kant Kim , Ikiz Habibe , van den Eertwegh Valerie , van Mook Walther , de Rijk Angelique
Published: April 2024

Background

The burnout rates among residents urge for adequate interventions to improve resilience and prevent burnout. Peer reflection, also called group intervision sessions, is a potentially successful intervention to increase the resilience of young doctors. We aimed to gain insight into the perceived added value of intervision sessions and the prerequisite conditions to achieve this, according to residents and intervisors. Our insights might be of help to those who think of implementing intervision sessions in their institution.

Methods

An explorative, qualitative study was performed using focus groups and semi-structured interviews with both residents (n = 8) and intervisors (n = 6) who participated in intervision sessions in a university medical center in the Netherlands. The topic list included the perceived added value of intervision sessions and factors contributing to that. The interviews were transcribed verbatim and coded using NVivo. Thematic analysis was subsequently performed.

Results

According to residents and intervisors, intervision sessions contributed to personal and professional identity development; improving collegiality; and preventing burn-out. Whether these added values were experienced, depended on: (1) choices made during preparation (intervisor choice, organizational prerequisites, group composition, workload); (2) conditions of the intervision sessions (safety, depth, role of intervisor, group dynamics, pre-existent development); and (3) the hospital climate.

Conclusions

Intervision sessions are perceived to be of added value to the identity development of medical residents and to prevent becoming burned out. This article gives insight in conditions necessary to reach the added value of intervision sessions. Optimizing preparation, meeting prerequisite conditions, and establishing a stimulating hospital climate are regarded as key to achieve this.
Cancer immunometabolism: advent, challenges, and perspective
Authors: Dang Qin , Li Borui , Jin Bing , Ye Zeng , Lou Xin , Wang Ting , Wang Yan , Pan Xuan , Hu Qiangsheng , Li Zheng , Ji Shunrong , Zhou Chenjie , Yu Xianjun , Qin Yi , Xu Xiaowu
Published: April 2024

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.
Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy
Authors: Shen Wenqi , Li Yecheng , Yang Ziyi , Li Wenjing , Cao Yi , Liu Yilin , Wang Zheng , Pei Renjun , Xing Chungen
Published: April 2024

The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy.
Bi-directional neuro-immune dysfunction after chronic experimental brain injury
Authors: Ritzel Rodney M. , Li Yun , Jiao Yun , Doran Sarah J. , Khan Niaz , Henry Rebecca J. , Brunner Kavitha , Loane David J. , Faden Alan I. , Szeto Gregory L. , Wu Junfang
Published: April 2024

Background

It is well established that traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function and that systemic immune changes contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem/progenitor cells chronically and to what extent such changes may negatively impact innate immunity and neurological function has not been examined.

Methods

To further understand the role of BM cell derivatives on TBI outcome, we generated BM chimeric mice by transplanting BM from chronically injured or sham (i.e., 90 days post-surgery) congenic donor mice into otherwise healthy, age-matched, irradiated CD45.2 C57BL/6 (WT) hosts. Immune changes were evaluated by flow cytometry, multiplex ELISA, and NanoString technology. Moderate-to-severe TBI was induced by controlled cortical impact injury and neurological function was measured using a battery of behavioral tests.

Results

TBI induced chronic alterations in the transcriptome of BM lineage−c-Kit+Sca1+ (LSK+) cells in C57BL/6 mice, including modified epigenetic and senescence pathways. After 8 weeks of reconstitution, peripheral myeloid cells from TBI→WT mice showed significantly higher oxidative stress levels and reduced phagocytic activity. At eight months after reconstitution, TBI→WT chimeric mice were leukopenic, with continued alterations in phagocytosis and oxidative stress responses, as well as persistent neurological deficits. Gene expression analysis revealed BM-driven changes in neuroinflammation and neuropathology after 8 weeks and 8 months of reconstitution, respectively. Chimeric mice subjected to TBI at 8 weeks and 8 months post-reconstitution showed that longer reconstitution periods (i.e., time post-injury) were associated with increased microgliosis and leukocyte infiltration. Pre-treatment with a senolytic agent, ABT-263, significantly improved behavioral performance of aged C57BL/6 mice at baseline, although it did not attenuate neuroinflammation in the acutely injured brain.

Conclusions

TBI causes chronic activation and progressive dysfunction of the BM stem/progenitor cell pool, which drives long-term deficits in hematopoiesis, innate immunity, and neurological function, as well as altered sensitivity to subsequent brain injury.
The cell biology of HIV-1 latency and rebound
Authors: Mbonye Uri , Karn Jonathan
Published: April 2024

Transcriptionally latent forms of replication-competent proviruses, present primarily in a small subset of memory CD4+ T cells, pose the primary barrier to a cure for HIV-1 infection because they are the source of the viral rebound that almost inevitably follows the interruption of antiretroviral therapy. Over the last 30 years, many of the factors essential for initiating HIV-1 transcription have been identified in studies performed using transformed cell lines, such as the Jurkat T-cell model. However, as highlighted in this review, several poorly understood mechanisms still need to be elucidated, including the molecular basis for promoter-proximal pausing of the transcribing complex and the detailed mechanism of the delivery of P-TEFb from 7SK snRNP. Furthermore, the central paradox of HIV-1 transcription remains unsolved: how are the initial rounds of transcription achieved in the absence of Tat? A critical limitation of the transformed cell models is that they do not recapitulate the transitions between active effector cells and quiescent memory T cells. Therefore, investigation of the molecular mechanisms of HIV-1 latency reversal and LRA efficacy in a proper physiological context requires the utilization of primary cell models. Recent mechanistic studies of HIV-1 transcription using latently infected cells recovered from donors and ex vivo cellular models of viral latency have demonstrated that the primary blocks to HIV-1 transcription in memory CD4+ T cells are restrictive epigenetic features at the proviral promoter, the cytoplasmic sequestration of key transcription initiation factors such as NFAT and NF-κB, and the vanishingly low expression of the cellular transcription elongation factor P-TEFb. One of the foremost schemes to eliminate the residual reservoir is to deliberately reactivate latent HIV-1 proviruses to enable clearance of persisting latently infected cells—the “Shock and Kill” strategy. For “Shock and Kill” to become efficient, effective, non-toxic latency-reversing agents (LRAs) must be discovered. Since multiple restrictions limit viral reactivation in primary cells, understanding the T-cell signaling mechanisms that are essential for stimulating P-TEFb biogenesis, initiation factor activation, and reversing the proviral epigenetic restrictions have become a prerequisite for the development of more effective LRAs.
Brain–machine interface based on deep learning to control asynchronously a lower-limb robotic exoskeleton: a case-of-study
Authors: Ferrero Laura , Soriano-Segura Paula , Navarro Jacobo , Jones Oscar , Ortiz Mario , Iáñez Eduardo , Azorín José M. , Contreras-Vidal José L.
Published: April 2024

Background

This research focused on the development of a motor imagery (MI) based brain–machine interface (BMI) using deep learning algorithms to control a lower-limb robotic exoskeleton. The study aimed to overcome the limitations of traditional BMI approaches by leveraging the advantages of deep learning, such as automated feature extraction and transfer learning. The experimental protocol to evaluate the BMI was designed as asynchronous, allowing subjects to perform mental tasks at their own will.

Methods

A total of five healthy able-bodied subjects were enrolled in this study to participate in a series of experimental sessions. The brain signals from two of these sessions were used to develop a generic deep learning model through transfer learning. Subsequently, this model was fine-tuned during the remaining sessions and subjected to evaluation. Three distinct deep learning approaches were compared: one that did not undergo fine-tuning, another that fine-tuned all layers of the model, and a third one that fine-tuned only the last three layers. The evaluation phase involved the exclusive closed-loop control of the exoskeleton device by the participants’ neural activity using the second deep learning approach for the decoding.

Results

The three deep learning approaches were assessed in comparison to an approach based on spatial features that was trained for each subject and experimental session, demonstrating their superior performance. Interestingly, the deep learning approach without fine-tuning achieved comparable performance to the features-based approach, indicating that a generic model trained on data from different individuals and previous sessions can yield similar efficacy. Among the three deep learning approaches compared, fine-tuning all layer weights demonstrated the highest performance.

Conclusion

This research represents an initial stride toward future calibration-free methods. Despite the efforts to diminish calibration time by leveraging data from other subjects, complete elimination proved unattainable. The study’s discoveries hold notable significance for advancing calibration-free approaches, offering the promise of minimizing the need for training trials. Furthermore, the experimental evaluation protocol employed in this study aimed to replicate real-life scenarios, granting participants a higher degree of autonomy in decision-making regarding actions such as walking or stopping gait.
Space-efficient computation of k-mer dictionaries for large values of k
Authors: Díaz-Domínguez Diego , Leinonen Miika , Salmela Leena
Published: April 2024

Computing k-mer frequencies in a collection of reads is a common procedure in many genomic applications. Several state-of-the-art k-mer counters rely on hash tables to carry out this task but they are often optimised for small k as a hash table keeping keys explicitly (i.e., k-mer sequences) takes $$O(N\frac{k}{w})$$

O
(
N

k
w

)

computer words, N being the number of distinct k-mers and w the computer word size, which is impractical for long values of k. This space usage is an important limitation as analysis of long and accurate HiFi sequencing reads can require larger values of k. We propose , a space-efficient hash table for k-mers using $$O(N+u\frac{k}{w})$$

O
(
N
+
u

k
w

)

words of space, where u is the number of reads. Our framework exploits the fact that consecutive k-mers overlap by $$k-1$$

k
-
1

symbols. Thus, we only store the last symbol of a k-mer and a pointer within the hash table to a previous one, which we can use to recover the remaining $$k-1$$

k
-
1

symbols. We adapt to compute canonical k-mers as well. This variant also uses pointers within the hash table to save space but requires more work to decode the k-mers. Specifically, it takes $$O(\sigma ^{k})$$

O
(

σ
k

)

time in the worst case, $$\sigma$$
σ
being the DNA alphabet, but our experiments show this is hardly ever the case. The canonical variant does not improve our theoretical results but greatly reduces space usage in practice while keeping a competitive performance to get the k-mers and their frequencies. We compare canonical to a regular hash table storing canonical k-mers explicitly as keys and show that our method uses up to five times less space while being less than 1.5 times slower. We also show that canonical uses significantly less memory than state-of-the-art k-mer counters when they do not resort to disk to keep intermediate results.
Circ_0001786 facilitates gefitinib resistance and malignant progression in non-small cell lung cancer via miR-34b-5p/SRSF1
Authors: Ouyang Kaobin , Xie Dan , Liao Haojie , He Ying , Xiong Hailin
Published: April 2024

Background

Non-small cell lung cancer (NSCLC) is a widespread cancer and gefitinib is a primary therapy for NSCLC patients. Nevertheless, the underlying mechanisms for the progression of acquired drug resistance have not been clarified. The aim of this study was to investigate the role of circular RNA (circ_0001786) in gefitinib-resistant NSCLC.

Methods

Firstly, the expression of circ_0001786, miR-34b-5p and SRSF1 were assayed using qRT-PCR. Subsequently, CCK-8 test was utilized to measure the semi-inhibitory concentration (IC50) of cellular gefitinib. Apoptosis was identified by flow cytometry. At last, dual luciferase assay was applied to prove the binding association between miR-34b-5p, circ_0001786 or SRSF1.

Results

Our research disclosed that circ_0001786 was heightened in gefitinib-resistant NSCLC cells and tissues. Knockdown of circ_0001786 restrained IC50 values of gefitinib, attenuated the clonogenic ability and facilitated apoptosis in HCC827-GR and PC9-GR. In addition, circ_0001786 was a molecular sponge for miR-34b-5p. Silencing miR-34b-5p rescued the inhibitory impact of circ_0001786 knockdown on IC50 and cell cloning ability. Moreover, miR-34b-5p directly targeted SRSF1. Importantly, circ_0001786 enhanced gefitinib tolerance and malignant development in NSCLC through miR-34b-5p/SRSF1 pathway.

Conclusion

This research revealed a novel mechanism by which circ_0001786 enhanced NSCLC resistance to gefitinib by sponging miR-34b-5p and upregulating SRSF1. circ_0001786 was a potential target for improving the treatment of gefitinib-resistant NSCLC patients.
Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China
Authors: Jin Ye , Zhao Miao , Guo Qiuzhe , Zhao Wanyu , Lei Min , Zhang Yifei , zhang Yunhan , Shen Yan , Lin Keqin , Yang Zhaoqing , Chu Jiayou , Sun Hao , Luo Zhiling
Published: April 2024

Background

Atrial septal defect (ASD) is a common form of congenital heart disease. Although several genes related to ASD have been found, the genetic factors of ASD remain unclear. This study aimed to evaluate the correlation between 10 candidate single nucleotide polymorphisms (SNPs) and sporadic atrial septal defects.

Methods

Based on the results of 34 individual whole exome sequences, 10 candidate SNPs were selected. In total, 489 ASD samples and 420 normal samples were collected. The 10 SNPs in the case group and the control group were identified through Snapshot genotyping technology. The χ2-test and unconditional regression model were used to evaluate the relationship between ASD and each candidate SNP. Haploview software was used to perform linkage disequilibrium and haplotype analysis.

Results

The χ2 results showed that the FLT4 rs383985 (P = 0.003, OR = 1.115–1.773), HYDIN rs7198975 (P = 0.04621, OR = 1.003–1.461), and HYDIN rs1774266 (P = 0.04621, OR = 1.003–1.461) alleles were significantly different between the control group and the case group (P < 0.05). Only the association with the FLT4 polymorphism was statistically significant after adjustment for multiple comparisons.

Conclusion

These findings suggest that a possible molecular pathogenesis associated with sporadic ASD is worth exploring in future studies.