bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective validation study of an artificial neural network-based preoperative decision-support tool for noninvasive lymph node staging (NILS) in women with primary breast cancer (ISRCTN14341750)
Authors: Skarping Ida , Ellbrant Julia , Dihge Looket , Ohlsson Mattias , Huss Linnea , Bendahl Pär-Ola , Rydén Lisa
Published: January 2024

Background

Surgical sentinel lymph node biopsy (SLNB) is routinely used to reliably stage axillary lymph nodes in early breast cancer (BC). However, SLNB may be associated with postoperative arm morbidities. For most patients with BC undergoing SLNB, the findings are benign, and the procedure is currently questioned. A decision-support tool for the prediction of benign sentinel lymph nodes based on preoperatively available data has been developed using artificial neural network modelling.

Methods

This was a retrospective geographical and temporal validation study of the noninvasive lymph node staging (NILS) model, based on preoperatively available data from 586 women consecutively diagnosed with primary BC at two sites. Ten preoperative clinicopathological characteristics from each patient were entered into the web-based calculator, and the probability of benign lymph nodes was predicted. The performance of the NILS model was assessed in terms of discrimination with the area under the receiver operating characteristic curve (AUC) and calibration, that is, comparison of the observed and predicted event rates of benign axillary nodal status (N0) using calibration slope and intercept. The primary endpoint was axillary nodal status (discrimination, benign [N0] vs. metastatic axillary nodal status [N+]) determined by the NILS model compared to nodal status by definitive pathology.

Results

The mean age of the women in the cohort was 65 years, and most of them (93%) had luminal cancers. Approximately three-fourths of the patients had no metastases in SLNB (N0 74% and 73%, respectively). The AUC for the predicted probabilities for the whole cohort was 0.6741 (95% confidence interval: 0.6255–0.7227). More than one in four patients (n = 151, 26%) were identified as candidates for SLNB omission when applying the predefined cut-off for lymph node-negative status from the development cohort. The NILS model showed the best calibration in patients with a predicted high probability of healthy axilla.

Conclusion

The performance of the NILS model was satisfactory. In approximately every fourth patient, SLNB could potentially be omitted. Considering the shift from postoperatively to preoperatively available predictors in this validation study, we have demonstrated the robustness of the NILS model. The clinical usability of the web interface will be evaluated before its clinical implementation.

Trial registration

Registered in the ISRCTN registry with study ID ISRCTN14341750.

Date of registration 23/11/2018.
Psychosocial conditions during school-age as determinants of long-term labour market attachment: a study of the Northern Swedish Cohort from the 1980s to the 2020s
Authors: Virtanen Pekka , Nummi Tapio , Janlert Urban , Hammarström Anne
Published: January 2024

Background

This study, conducted on a Swedish population cohort, explores how internalized (depressive and functional somatic) and externalized (smoking, drinking, truancy, vandalism, delinquency) mental health symptoms, as well as close interpersonal relations (family climate and school connectedness) reported during adolescence, influence the work-life course up to late midlife.

Methods

We examined repeated measurements of labour market status from age 16 to 56 using sequence analyses. We identified five different labour market attachment (LMA16-56) trajectories, namely ‘strong,’ ‘early intermediate,’ ‘early weak,’ ‘late weak,’ and ‘constantly weak.’ Multinomial logistic regressions were employed to relate each of the nine determinants to the identified trajectories.

Results

When compared to the risk of ‘strong’ LMA16-56, adversity in all conditions, except for vandalism, entailed a higher risk of the ‘constantly weak’ trajectory. Moreover, all conditions, except for functional somatic symptoms, entailed a higher risk of the ‘late weak’ LMA16-56. The risk of the ‘early intermediate’ LMA16-56 was non-significant across all the conditions.

Conclusions

This study contributes to existing knowledge through its novel exploration of labour market attachment and the revelation of the significance of proximal interpersonal relationships in attachment outcomes. Additionally, the study reaffirms the importance of externalizing behaviour, while suggesting that internalized symptoms in adolescence might have a less influential, though not negligible, role. These results underscore the importance of addressing acting out behaviour and nurturing human relationships during compulsory basic education, when the entire age group is still within reach. This approach aims not only to reduce frictions in the school-to-work transition but also to prevent midlife labour market attachment problems that may arise with delayed intervention.
Enhancing understanding of healthy aging based on time-varying dependencies among multidimensional health, life satisfaction, and health behaviors of older adults aged 60 years and over
Authors: Zhang Jianghua , Zhang Yunbao , Wu Zhiyi , Fu Xuemei
Published: January 2024

Background

Healthy aging is a process of not only achieving good health but also increasing the life satisfaction of older adults aged 60 years and over, in which health behaviors play an important role. There is a lack of research on the time-varying dependencies between health, life satisfaction, and health behaviors, impeding a deeper understanding of healthy aging.

Purpose

To develop an integrated framework for modeling the interrelationships among the components of healthy aging between multiple time slices.

Methods

Based on the Chinese Longitudinal Healthy Living Survey (CLHLS) data in the three waves of 2011/2012, 2014, and 2017/2018, Bayesian network and dynamic Bayesian network are jointly employed to study the relationships among the components of healthy aging within one time slice, as well as to explore the time-varying dependencies among the components between time slices.

Results

The results of structure learning reveal the direction of effects between different dimensions of health, with mental health and social health affecting physical health and self-rated health affecting both physical and mental health. In addition, health behaviors are found to affect mental health and social health, while self-rated health can influence life satisfaction. The parameters learned from the data show the magnitude and direction of concurrent effects, one-period lagged effects and two-period lagged effects between the factors, which find that the time-varying dependencies vary but are generally positive, long-term, and accumulative over time. In addition, the results of autoregressive effects show the positive predictive effects of health and life satisfaction.

Conclusions

It confirms the influence pathway from health behaviors to multidimensional health to life satisfaction, and the time-varying dependencies among the components of healthy aging, which facilitates a deeper understanding of healthy aging. Combining the results of autoregressive effects and descriptive statistics, it further indicates that healthy aging is a comprehensive result arising from interactions of multiple factors. Policymakers should guide older adults aged 60 years and over to adopt healthier behaviors and ensure the long-term sustainability and continuity of policies.
Prophylactic use of vancomycin powder on postoperative infection after total joint arthroplasty
Authors: Gao Jian , Shu Li , Jiang Kan , Muheremu Aikeremujiang
Published: January 2024

Objective

By reviewing the literature analyzing vancomycin powder for preventive surgery, the effect of this method on reducing the infection rate after TJA was systematically evaluated to provide a basis for future clinical work.

Methods

Using PubMed, Medline, Elsevier, and CNKI, with the following mesh words: “vancomycin”, “local / intraoperative / topical / intrawound”, “TJA”, “TKA”, “THA”, “total joint arthroplasty”, “total knee arthroplasty”, “total hip arthroplasty”, “infection”, and “SSI”, to search for case-control research papers on the impact of prophylactic application of vancomycin powder on the incidence of postoperative infection, we compared the overall infection rate in the literature by using RevMan 5.3 meta-analysis software and analyzed the impact of vancomycin on the infection rate of different parts and types of TJA according to different subgroups.

Results

A total of 22 qualified studies were selected; twenty-five studies compared the effect of prophylactic use of vancomycin powder on infection rates after TJA. There were 23,363 cases in total, including 9545 cases in the vancomycin group and 13,818 cases in the control group. The results of the meta-analysis showed that the possibility of postoperative infection after prophylactic use of vancomycin powder was significantly lower than that without vancomycin risk ratio: 0.38 [0.23,0.59], P < 0.01). However, a meta-analysis of randomized controlled trials (RCTs) showed no significant effect of vancomycin on postoperative infection (P = 0.52).

Conclusion

Based on the retrospective studies, local prophylactic use of vancomycin powder in TJA can significantly reduce the incidence of postoperative infection. High-quality RCTs should be carried out to further evaluate these results.
Changes in mandibular radiomorphometric indices in osteoporosis patients treated with denosumab: a retrospective case-control study
Authors: Rupel Katia , Dal Broi Chiara , Ottaviani Giulia , Bellassai Laura , Bogdan Preda Theodora Magdalena , Di Lenarda Roberto , Biasotto Matteo
Published: January 2024

Background

Radiomorphometric indices measured on Dental Panoramic Radiography (DPR) can reflect Bone Mineral Density (BMD). The aim of our study is to evaluate changes in DPR radiographic markers in patients undergoing antiresorptive therapy with denosumab and correlate them to BMD and serum bone turnover markers (BTM).

Methods

We evaluated two radiomorphometric indices: Mandibular Cortical Width (MCW) and Panoramic Mandibular Index (PMI), in patients undergoing antiresorptive therapy with denosumab at T0 (before starting the therapy) and at T1 (after 12 months), comparing results with a control group of healthy patients who performed two DPRs at a one-year time distance. Correlation analysis was performed in the denosumab group, as well as ROC curves were obtained for both indices.

Results

The study included 18 patients and 21 controls according to specific inclusion and exclusion criteria, matched by gender and age. Both MCW and PMI were significantly lower at T0 in the denosumab group, consistently with lower BMD. MCW showed significant correlation with femoral and lumbar DEXA and was significantly lower in patients with osteoporosis compared to osteopenia. Only PMI index increased significantly in the denosumab group from T0 to T1. After one year (T1), there weren’t any differences between patients and controls for both indices. No significant correlations were found with BTMs. Sensitivity and specificity for MCW and PMI were also calculated.

Conclusions

Our results show how CMW shows sufficient sensitivity and specificity to be used as a radiographic marker to screen and intercept patients with osteoporosis. PMI seems to be able to reflect changes in response to antiresorptive therapy with denosumab. Further studies are needed to confirm our hypothesis.
Measuring palliative care integration in Malawi through service provision, access, and training indicators: the Waterloo Coalition Initiative
Authors: Kiyange Fatia , Atieno Mackuline , Luyirika Emmanuel B. K. , Ali Zipporah , Musau Helena , Thambo Lameck , Rhee John Y. , Namisango Eve , Rosa William E.
Published: January 2024

Background

Fewer than 1 in 20 people on the African continent in need of palliative care receive it. Malawi is a low-income country in sub-Saharan Africa that has yet to achieve advanced palliative care integration accompanied by unrestricted access to pain and symptom relieving palliative medicines. This paper studied the impact of Malawi’s Waterloo Coalition Initiative (WCI) – a local project promoting palliative care integration through service development, staff training, and increased service access.

Methods

Interdisciplinary health professionals at 13 hospitals in southern Malawi were provided robust palliative care training over a 10-month period. We used a cross-sectional evaluation to measure palliative care integration based on 11 consensus-based indicators over a one-year period.

Results

92% of hospitals made significant progress in all 11 indicators. Specifically, there was a 69% increase in the number of dedicated palliative care rooms/clinics, a total of 253 staff trained across all hospitals (a 220% increase in the region), substantive increases in the number of patients receiving or assessed for palliative care, and the number of hospitals that maintained access to morphine or other opioid analgesics while increasing the proportion of referrals to hospice or other palliative care programs.

Conclusion

Palliative care is a component of universal health coverage and Sustainable Development Goal 3. The WCI has made tremendous strides in establishing and integrating palliative care services in Malawi with notable progress across 11 project indicators, demonstrating that increased palliative care access is possible in severely resource-constrained settings through sustained models of partnership at the local level.
Reproductive outcomes among female health care workers
Authors: Izadi Nazanin , Aminian Omid , Ghafourian Kiana , Aghdaee AmirHossein , Samadanian Shadi
Published: January 2024

Objective

Occupational exposures may be associated with reproductive health and pregnancy outcomes. This study investigated the association between occupational exposures and reproductive health, pregnancy outcomes, and the lactation period among hospital staff.

Materials and methods

Seven hundred thirty-three female healthcare workers from hospitals affiliated with the Tehran University of Medical Sciences were invited to participate in this cross-sectional study. The measurement method for fertility consequences was self-report. Demographic characteristics, occupational data, medical history, and reproductive history were collected via data collection form. Finally, reproductive outcomes were evaluated in different occupational hazard categories.

Result

Chemical exposures (solvents) were a risk factor for stillbirth. Prolonged working hours were associated with spontaneous abortion and breastfeeding periods. Shift workers did not have a higher frequency of reproductive and pregnancy outcomes, but the breastfeeding period was significantly decreased in shift workers. Psychiatric disorders were associated with preterm labour, low birth weight, and stillbirth in sequence with nervousness, depression, and mood disturbance. Furthermore, depression affects the breastfeeding period. Moreover, we found a link between job titles and infertility. In addition, socioeconomic status was related to stillbirth and infertility.

Conclusion

The study revealed that chemical and ergonomic exposures have associations with some reproductive outcomes. We also conclude that shift work could adversely affect the breastfeeding period. So, implementing some organizational strategies to control adverse health effects of occupational hazards and modifying shift work and working hours for nursing mothers is recommended.
Raising awareness of anti-fat stigma in healthcare through lived experience education: a continuing professional development pilot study
Authors: Heidebrecht Christine , Fierheller Dianne , Martel Sara , Andrews Alex , Hollahan Amanda , Griffin Laura , Meerai Sonia , Lock Raeden , Nabavian Helia , D’Silva Chelsea , Friedman May , Zenlea Ian
Published: January 2024

Background

Anti-fat attitudes and weight-based discrimination are prevalent in healthcare settings and among healthcare practitioners and clinical trainees, and can result in immense harm to patients. There is increasing recognition that anti-fat bias in healthcare is a critical issue that must be addressed, but there is a dearth of evidence demonstrating sustained attitude and behavioural change among clinicians, illustrating a need for more innovative educational approaches and rigorous evaluation. We describe the co-design and delivery of a narrative-based continuing professional development curriculum aimed at raising awareness of weight-based bias and stigma.

Methods

Our research team of lived experience educators, clinicians and researchers collaboratively developed a series of seven podcast episodes comprised of narrative descriptions of lived experiences with and impacts of weight bias, stigma and discrimination in healthcare settings, as well as a post-podcast workshop to facilitate reflection and discussion between participants. The curriculum was piloted among 20 clinicians practicing at a large urban hospital in Mississauga, Canada. We explored feasibility, acceptability and learning impact by analyzing responses to questionnaires completed following each podcast episode and responses shared during the workshops and follow-up feedback sessions.

Results

We observed high acceptability and feasibility of the curriculum. Participants experienced the podcast as a practical and convenient learning format and the workshop as a valuable opportunity to collectively debrief and reflect. The learning impact of the curriculum was strong; participants described a range of emotions elicited by the podcasts, engaged in self-reflection, and expressed a desire to modify clinical approaches. Barriers to the application of learnings identified by participants include pervasiveness of the use of body mass index (BMI) as an indicator of risk and a criterion for referral; discomfort with difficult conversations; prevalent biomedical understandings about the association between weight and health; and clinicians’ defensiveness.

Conclusion

This pilot study yielded promising findings and demonstrated potential impact on weight bias and stigma among healthcare providers. Necessary next steps include conducting larger scale, rigorous evaluations of the curriculum among broader populations, both health professions trainees and current healthcare providers.
Teaching Scottish medical students about global health in partnership with LMIC institutions. Does it change their views on volunteering in LMIC settings?
Authors: Crichton Lesley , Daniels Katy , Merrylees Neil , Mukanyangezi Marie-Francoise , Sonkwe Hazel Mumphansha , Nduwayezu Richard , Thomson Emma
Published: January 2024

Context

An elective placement is a core part of most United Kingdom (UK) medical degrees, and a significant proportion of students choose to pursue their elective in low- and middle-income countries (LMIC). There is a risk that students are ill-prepared for some of the ethical challenges that they will face during these placements, and that they have little appreciation for some of the negative effects that their placement can have on the host healthcare system. This study sought to address some of these negative consequences by exploring the preparation of medical students for these experiences, and the effect of including the LMIC perspective in preparation materials.

Methods

This qualitative study used thematic analysis to explore the attitudes of final year medical students at a Scottish medical school to international volunteering, after completing a module on global health. This module was designed and delivered in partnership with academics from Malawi, Rwanda and Zambia, thus incorporating a strong LMIC perspective.

Findings

This study demonstrated the ability of a global health module with a strong LMIC perspective to influence the attitudes of final year medical students in the following ways: 1) Challenging assumptions around international volunteering and, in particular, around some of the negative effects of international volunteering that had not previously been considered. 2) Changing future practice around international volunteering.

Implications

This study provides good evidence that having a strong LMIC voice in preparation materials for medical students embarking on LMIC electives has the ability to increase awareness of some of the potential harms, and to positively influence how they plan to have discussions around and approach such experiences in the future.
Patients’ experience of accessing hepatitis C treatment through the Myanmar national hepatitis C treatment program: a qualitative evaluation
Authors: Draper Bridget , Yee Win Lei , Bowring Anna , Naing Win , Kyi Khin Pyone , Htay Hla , Howell Jessica , Hellard Margaret , Pedrana Alisa
Published: January 2024

Background

Globally, 56.8 million people are living with hepatitis C and over three-quarters of those reside in low and middle-income countries (LMICs). Barriers and enablers to hepatitis C care among people who inject drugs in high-income countries are well documented. However, there is scant literature describing the patient experience in LMICs. Understanding the barriers and enablers to care from the patient perspective is important to inform service refinements to improve accessibility and acceptability of hepatitis C care.

Methods

We conducted a qualitative evaluation of the patient experience of accessing the national hepatitis C program at eight hospital sites in Myanmar. Semi-structured interviews were conducted with four to five participants per site. Interview data were analysed thematically, with deductive codes from Levesque et al.’s (2013) Framework on patient-centred access to healthcare.

Results

Across the eight sites, 38 participants who had completed treatment were interviewed. Barriers to accessing care were mostly related to attending for care and included travel time and costs, multiple appointments, and wait times. Some participants described how they did not receive adequate information on hepatitis C, particularly its transmission routes, and on the level of cirrhosis of their liver and what they were required to do after treatment (i.e. reduce alcohol consumption, liver cirrhosis monitoring). Many participants commented that they had few or no opportunities to ask questions. Provision of treatment at no cost was essential to accessibility, and gratitude for free treatment led to high acceptability of care, even when accessing care was inconvenient.

Conclusions

These findings highlight the importance of streamlining and decentralising health services, adequate human resourcing and training, and affordable treatment in maximising the accessibility and acceptability of hepatitis C care in LMICs. Findings from this work will inform future service delivery refinements for national program and other decentralised programs to improve accessibility and acceptability of hepatitis C care in Myanmar.
Barriers and facilitators in developing patient versions of clinical practice guidelines - qualitative interviews on experiences of international guideline producers
Authors: Meyer Nora , Hauprich Julia , Breuing Jessica , Hellbrecht Irma , Wahlen Sarah , Könsgen Nadja , Bühn Stefanie , Becker Monika , Blödt Susanne , Carl Günther , Follmann Markus , Frenz Stefanie , Langer Thomas , Nothacker Monika , Schaefer Corinna , Pieper Dawid
Published: January 2024

Background

Several guideline organizations produce patient versions of clinical practice guidelines (PVGs) which translate recommendations into simple language. A former study of our working group revealed that few guideline organizations publish their methods used to develop PVGs. Clear definitions of PVGs do not prevail and their purposes often remain unclear. We aimed to explore experts’ perspectives on developing, disseminating and implementing PVGs to discuss and incorporate these experiences when consenting on methodological guidance and further improving PVGs.

Methods

We conducted 17 semi-structured telephone interviews with international experts working with PVGs from September 2021 through January 2022. We conducted the interviews in English or German, they were recorded and transcribed verbatim. We utilized Mayring’s qualitative content analysis with MAXQDA software to analyze the data.

Results

In two interviews two participants were interviewed at the same time. This resulted in a total of 19 participants from 16 different organizations and eight different countries participated. Most were female (16/19) and their experience in working with PVGs ranged from 1 to 20 years. All follow methodological standards when developing PVGs, but the extent of these standards and their public accessibility differs. Aims and target groups of PVGs vary between organizations. Facilitators for developing PVGs are working with a multidisciplinary team, financial resources, consultation processes and a high-quality underlying CPG. Facilitators for disseminating and implementing PVGs are using various strategies. Barriers, on the other hand, are the lack of these factors. All participants mentioned patient involvement as a key aspect in PVG development.

Conclusion

The steps in the PVG development process are largely similar across the countries. Focus is placed on the involvement of patients in the development process, although the extent of participation varies. The experts collectively attribute great importance to PVGs overall, but in order to constantly adapt to medical progress and changing conditions, the focus in the future may be more on formats like living guidelines. Although there are different views on the mandatory development of PVGs, there is a consistent call for more transparency regarding the methodology used for PVGs.
Construction of an ER stress-related prognostic signature for predicting prognosis and screening the effective anti-tumor drug in osteosarcoma
Authors: Chen Weidong , Liao Yan , Sun Pengxiao , Tu Jian , Zou Yutong , Fang Ji , Chen Ziyun , Li Hongbo , Chen Junkai , Peng Yuzhong , Wen Lili , Xie Xianbiao
Published: January 2024

Background

Osteosarcoma is the most common malignant primary bone tumor in infants and adolescents. The lack of understanding of the molecular mechanisms underlying osteosarcoma progression and metastasis has contributed to a plateau in the development of current therapies. Endoplasmic reticulum (ER) stress has emerged as a significant contributor to the malignant progression of tumors, but its potential regulatory mechanisms in osteosarcoma progression remain unknown.

Methods

In this study, we collected RNA sequencing and clinical data of osteosarcoma from The TCGA, GSE21257, and GSE33382 cohorts. Differentially expressed analysis and the least absolute shrinkage and selection operator regression analysis were conducted to identify prognostic genes and construct an ER stress-related prognostic signature (ERSRPS). Survival analysis and time dependent ROC analysis were performed to evaluate the predictive performance of the constructed prognostic signature. The “ESTIMATE” package and ssGSEA algorithm were utilized to evaluate the differences in immune cells infiltration between the groups. Cell-based assays, including CCK-8, colony formation, and transwell assays and co-culture system were performed to assess the effects of the target gene and small molecular drug in osteosarcoma. Animal models were employed to assess the anti-osteosarcoma effects of small molecular drug.

Results

Five genes (BLC2, MAGEA3, MAP3K5, STC2, TXNDC12) were identified to construct an ERSRPS. The ER stress-related gene Stanniocalcin 2 (STC2) was identified as a risk gene in this signature. Additionally, STC2 knockdown significantly inhibited osteosarcoma cell proliferation, migration, and invasion. Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Patients categorized by risk scores showed distinct immune status, and immunotherapy response. ISOX was subsequently identified and validated as an effective anti-osteosarcoma drug through a combination of CMap database screening and in vitro and in vivo experiments.

Conclusion

The ERSRPS may guide personalized treatment decisions for osteosarcoma, and ISOX holds promise for repurposing in osteosarcoma treatment.
On mental pain and suicide risk in modern psychiatry
Authors: Pompili Maurizio
Published: January 2024

Facing suicide risk is probably the most difficult task for clinicians when dealing with patients in crisis. It requires professional, intellectual, and emotional efforts. Suicide risk assessment can sometimes be distressing for clinicians, and such a state may favour the avoidance of an in-depth exploration of suicidal thoughts and behaviour. Patients often feel subjected to interpersonal assessments with little opportunity to explore their perspectives. The "One size fits all" approach tends to create distance and paradoxically contributes to an increase in the risk of suicide. Traditional clinical factors may be of limited value if a shared understanding of the patient’s suicide risk is missed. To understand the suicidal mind, it is necessary to take the point of view of the subject in crisis. In this essay, the “operational model of mental pain as a main ingredient of suicide” provided by Edwin Shneidman is overviewed with the aim of a better empathic understanding of patients’ sufferance. With a phenomenological approach, the suicidal crisis appears as a complex, pervasive state rather than as a symptom of a mental disorder, as the new paradigm also suggests. In this regard, the "mentalistic" aspects of suicide propose a broader insight into the suicidal scenario far beyond the diagnosis of psychiatric disorders. In this article, the perspective of individuals who deem their mental pain to be intolerable is described to make sense of their ambivalence between the wish to die and the wish to live that can prevail if relief is provided.
North Korea’s COVID-19 policy dilemma: epidemic prevention conflicting with trade
Authors: Park Byungjin , Cho Joonmo
Published: January 2024

Background

Amidst the COVID-19 pandemic, striking a delicate balance between sustaining economic activity and safeguarding public health has become a crucial concern. The border closures for COVID-19 prevention have further intensified concerns for North Korea, which conducts over 90% of its trade with China and Russia, countries sharing its borders.

Methods

This study aims to scrutinize North Korea’s response to these competing imperatives by examining the impact of border closures on the country’s trade dynamics with China and Russia. This study employed the difference-in-difference (DID) method to analyze transformations in North Korea’s economic activity before and after the border closures, utilizing trade data and nighttime satellite imagery captured in 2019 and 2020.

Results

The results reveal that North Korea actively reoriented its trade priorities towards Russia and accorded precedence to its epidemic prevention system over its economy during the pandemic. A noticeable increase in imports of food and pharmaceuticals was observed, indicating a significant rise in the inflow of these essential commodities.

Conclusion

The findings of this study suggest that during the early stages of the COVID-19 pandemic, North Korea placed significant policy emphasis on preserving public health. However, due to economic hardships and food shortages, if the pandemic persists in the long term, it indicates the possibility of partial or complete lifting of border closures to mitigate these challenges.
Quercetin inhibits caspase-1-dependent macrophage pyroptosis in experimental folic acid nephropathy
Authors: Gao Xianli , Guo Caiyun , Li Wenjun , Deng Yingdong , Ning Wenjun , Xie Jiaqi , Zhan Xiaoying , Fan Youling , Chen Hongtao , Huang Zengping , Zhou Jun
Published: January 2024

Background

The role of pyroptosis in kidney disease is limited and incomplete. Quercetin, a flavonoid compound present in a variety of fruits, vegetables, and plants, has shown antioxidant and anti-inflammatory properties. This study was designed to validate the importance of pyroptosis in an experimental model of folic acid nephropathy and to explore the effect of quercetin in protecting against pyroptosis.

Methods

Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were used to establish the correlation between pyroptosis and folic acid nephropathy. Immune cell infiltration, network pharmacology and single-cell RNA sequencing analysis were utilized to ascertain the specific target of quercetin in relation to pyroptosis. Finally, quercetin’s role was verified in vivo and in vitro.

Results

The GSEA analysis revealed a significant correlation between pyroptosis and folic acid nephropathy (NES = 1.764, P = 0.004). The hub genes identified through WGCNA were closely associated with inflammation. Molecular docking demonstrated a strong binding affinity between quercetin and caspase-1, a protein known to be involved in macrophage function, as confirmed by immune cell infiltration and single-cell analysis. Quercetin demonstrated a significant amelioration of kidney injury and reduction in macrophage infiltration in the animal model. Furthermore, quercetin exhibited a significant inhibition of caspase-1 expression, subsequently leading to the inhibition of pro-inflammatory cytokines expression, such as IL-1β, IL-18, TNF-α, and IL-6. The inhibitory effect of quercetin on macrophage pyroptosis was also confirmed in RAW264.7 cells.

Conclusion

This study contributes substantial evidence to support the significant role of pyroptosis in the development of folic acid nephropathy, and highlights the ability of quercetin to downregulate caspase-1 in macrophages as a protective mechanism against pyroptosis.
Imposter or knight in shining armor? Pelvic circumferential compression devices (PCCD) for severe pelvic injuries in patients with multiple trauma: a trauma-registry analysis
Authors: Trentzsch H. , Lefering R. , Schweigkofler U. ,   the TraumaRegister DGU
Published: January 2024

Background

Pelvic Circumferential Compression Devices (PCCD) are standard in hemorrhage-control of unstable pelvic ring fractures (UPF). Controversial data on their usefulness exists. Aim of the study was to investigate whether prehospital application of PCCD can reduce mortality and transfusion requirements in UPF.

Methods

Retrospective cohort study. From 2016 until 2021, 63,371 adult severely injured patients were included into TraumaRegister DGU® of the German Trauma Society (TR-DGU). We analyzed PCCD use over time and compared patients with multiple trauma patients and UPF, who received prehospital PCCD to those who did not (noPCCD). Groups were adjusted for risk of prehospital PCCD application by propensity score matching. Primary endpoints were hospital mortality, standardized mortality rate (SMR) and transfusion requirements.

Results

Overall UPF incidence was 9% (N = 5880) and PCCD use increased over time (7.5% to 20.4%). Of all cases with UPF, 40.2% received PCCD and of all cases with PCCD application, 61% had no pelvic injury at all. PCCD patients were more severely injured and had higher rates of shock or transfusion. 24-h.-mortality and hospital mortality were higher with PCCD (10.9% vs. 9.3%; p = 0.033; 17.9% vs. 16.1%, p = 0.070). Hospital mortality with PCCD was 1% lower than predicted. SMR was in favor of PCCD but failed statistical significance (0.95 vs. 1.04, p = 0.101). 1,860 propensity score matched pairs were analyzed: NoPCCD-patients received more often catecholamines (19.6% vs. 18.5%, p = 0.043) but required less surgical pelvic stabilization in the emergency room (28.6% vs. 36.8%, p < 0.001). There was no difference in mortality or transfusion requirements.

Conclusion

We observed PCCD overuse in general and underuse in UPF. Prehospital PCCD appears to be more a marker of injury severity and less triggered by presence of UPF. We found no salutary effect on survival or transfusion requirements. Inappropriate indication and technical flaw may have biased our results. TR-DGU does not contain data on these aspects. Further studies are necessary. Modular add-on questioners to the registry could offer one possible solution to overcome this limitation. We are concerned that PCCD use may be unfairly discredited by misinterpretation of the available evidence and strongly vote for a prospective trial.
Improved modeling of RNA-binding protein motifs in an interpretable neural model of RNA splicing
Authors: Gupta Kavi , Yang Chenxi , McCue Kayla , Bastani Osbert , Sharp Phillip A. , Burge Christopher B. , Solar-Lezama Armando
Published: January 2024

Sequence-specific RNA-binding proteins (RBPs) play central roles in splicing decisions. Here, we describe a modular splicing architecture that leverages in vitro-derived RNA affinity models for 79 human RBPs and the annotated human genome to produce improved models of RBP binding and activity. Binding and activity are modeled by separate Motif and Aggregator components that can be mixed and matched, enforcing sparsity to improve interpretability. Training a new Adjusted Motif (AM) architecture on the splicing task not only yields better splicing predictions but also improves prediction of RBP-binding sites in vivo and of splicing activity, assessed using independent data.
Strongyloides stercoralis genotyping in a human population in southwestern Iran
Authors: Beiromvand Molouk , Ashiri Alireza , de Ree Veroni , Harbecke Dorothee , Rödelsperger Christian , Streit Adrian , Rafiei Abdollah
Published: January 2024

Background

Strongyloidiasis is a neglected tropical disease (NTD) that is caused mainly by Strongyloides stercoralis, with an estimated 600 million people infected worldwide, and in fewer cases by Strongyloides fuelleborni fuelleborni and Strongyloides fuelleborni kellyi. A number of studies have been conducted on the genetic diversity of S. stercoralis in East and Southeast Asia; however, there is very limited corresponding information from West Asian countries, including Iran.

Methods

For Strongyloides worms collected from patients in southwestern Iran, the hypervariable regions I (HVR-I) and IV (HVR-IV) of the nuclear 18S ribosomal DNA (rDNA) locus (SSU) and a fragment of the subunit 1 mitochondrial cytochrome c oxidase gene (cox-1) were sequenced. For a subset of the worms, whole-genome sequencing data were generated.

Results

The cox-1 sequences of 136 worms isolated from 23 patients indicated that all isolates were S. stercoralis. Among the cox-1 sequences, 33 polymorphic sites and 13 haplotypes were found. The phylogenetic analysis demonstrated that some sequences clustered fairly closely with sequences from humans and dogs from other parts of the world, while others formed a separate, Iran-specific group. Among 64 S. stercoralis analyzed, we found three of the previously described SSU HVR-I haplotypes, with haplotype II being the most frequent haplotype. In contrast to Southeast Asia, where S. stercoralis heterozygous for different haplotypes at the HVR-I locus are rare, we found 20 worms to be heterozygous for two different HVR-I haplotypes, 18 of which fell into the Iran-specific cox-1 cluster. SSU-heterozygous worms also showed elevated heterozygosity at the whole-genome level.

Conclusions

We conclude that the S. stercoralis population from the Khuzestan province shares much of the genetic diversity with the population in Southeast Asia, but there is an indication of additional genetic input. There appears to be some population structure with different subpopulations, which however do interbreed at least occasionally.

Graphical Abstract
The causal relationship between immune cells and ankylosing spondylitis: a bidirectional Mendelian randomization study
Authors: Fei Yuchang , Yu Huan , Wu Yulun , Gong Shanshan
Published: January 2024

Background

Ankylosing spondylitis (AS) is one of several disorders known as seronegative spinal arthritis (SpA), the origin of which is unknown. Existing epidemiological data show that inflammatory and immunological factors are important in the development of AS. Previous research on the connection between immunological inflammation and AS, however, has shown inconclusive results.

Methods

To evaluate the causal association between immunological characteristics and AS, a bidirectional, two-sample Mendelian randomization (MR) approach was performed in this study. We investigated the causal connection between 731 immunological feature characteristic cells and AS risk using large, publically available genome-wide association studies.

Results

After FDR correction, two immunophenotypes were found to be significantly associated with AS risk: CD14 − CD16 + monocyte (OR, 0.669; 95% CI, 0.544 ~ 0.823; P = 1.46 × 10−4; PFDR = 0.043), CD33dim HLA DR + CD11b + (OR, 0.589; 95% CI = 0.446 ~ 0.780; P = 2.12 × 10−4; PFDR = 0.043). AS had statistically significant effects on six immune traits: CD8 on HLA DR + CD8 + T cell (OR, 1.029; 95% CI, 1.015 ~ 1.043; P = 4.46 × 10−5; PFDR = 0.014), IgD on IgD + CD24 + B cell (OR, 0.973; 95% CI, 0.960 ~ 0.987; P = 1.2 × 10−4; PFDR = 0.021), IgD on IgD + CD38 − unswitched memory B cell (OR, 0.962; 95% CI, 0.945 ~ 0.980; P = 3.02 × 10−5; PFDR = 0.014), CD8 + natural killer T %lymphocyte (OR, 0.973; 95% CI, 0.959 ~ 0.987; P = 1.92 × 10−4; PFDR = 0.021), CD8 + natural killer T %T cell (OR, 0.973; 95% CI, 0.959 ~ 0.987; P = 1.65 × 10−4; PFDR = 0.021).

Conclusion

Our findings extend genetic research into the intimate link between immune cells and AS, which can help guide future clinical and basic research.
Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation
Authors: Godfrey Laura K. , Forster Jan , Liffers Sven-Thorsten , Schröder Christopher , Köster Johannes , Henschel Leonie , Ludwig Kerstin U. , Lähnemann David , Trajkovic-Arsic Marija , Behrens Diana , Scarpa Aldo , Lawlor Rita T. , Witzke Kathrin E. , Sitek Barbara , Johnsen Steven A. , Rahmann Sven , Horsthemke Bernhard , Zeschnigk Michael , Siveke Jens T.
Published: January 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis. It is marked by extraordinary resistance to conventional therapies including chemotherapy and radiation, as well as to essentially all targeted therapies evaluated so far. More than 90% of PDAC cases harbor an activatingKRASmutation. As the most commonKRASvariants in PDAC remain undruggable so far, it seemed promising to inhibit a downstream target in the MAPK pathway such as MEK1/2, but up to now preclinical and clinical evaluation of MEK inhibitors (MEKi) failed due to inherent and acquired resistance mechanisms. To gain insights into molecular changes during the formation of resistance to oncogenic MAPK pathway inhibition, we utilized short-term passaged primary tumor cells from ten PDACs of genetically engineered mice. We followed gain and loss of resistance upon MEKiexposure and withdrawal by longitudinal integrative analysis of whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and mass spectrometry data.

Results

We found that resistant cell populations under increasing MEKitreatment evolved by the expansion of a single clone but were not a direct consequence of known resistance-conferring mutations. Rather, resistant cells showed adaptive DNA hypermethylation of 209 and hypomethylation of 8 genomic sites, most of which overlap with regulatory elements known to be active in murine PDAC cells. Both DNA methylation changes and MEKiresistance were transient and reversible upon drug withdrawal. Furthermore, MEKiresistance could be reversed by DNA methyltransferase inhibition with remarkable sensitivity exclusively in the resistant cells.

Conclusion

Overall, the concept of acquired therapy resistance as a result of the expansion of a single cell clone with epigenetic plasticity sheds light on genetic, epigenetic and phenotypic patterns during evolvement of treatment resistance in a tumor with high adaptive capabilities and provides potential for reversion through epigenetic targeting.
Innovative deep learning techniques for monitoring aggressive behavior in social media posts
Authors: Han Huimin , Asif Muhammad , Awwad Emad Mahrous , Sarhan Nadia , Ghadi Yazeed Yasid , Xu Bo
Published: January 2024

The study aims to evaluate and compare the performance of various machine learning (ML) classifiers in the context of detecting cyber-trolling behaviors. With the rising prevalence of online harassment, developing effective automated tools for aggression detection in digital communications has become imperative. This research assesses the efficacy of Random Forest, Light Gradient Boosting Machine (LightGBM), Logistic Regression, Support Vector Machine (SVM), and Naive Bayes classifiers in identifying cyber troll posts within a publicly available dataset. Each ML classifier was trained and tested on a dataset curated for the detection of cyber trolls. The performance of the classifiers was gauged using confusion matrices, which provide detailed counts of true positives, true negatives, false positives, and false negatives. These metrics were then utilized to calculate the accuracy, precision, recall, and F1 scores to better understand each model’s predictive capabilities. The Random Forest classifier outperformed other models, exhibiting the highest accuracy and balanced precision-recall trade-off, as indicated by the highest true positive and true negative rates, alongside the lowest false positive and false negative rates. LightGBM, while effective, showed a tendency towards higher false predictions. Logistic Regression, SVM, and Naive Bayes displayed identical confusion matrix results, an anomaly suggesting potential data handling or model application issues that warrant further investigation. The findings underscore the effectiveness of ensemble methods, with Random Forest leading in the cyber troll detection task. The study highlights the importance of selecting appropriate ML algorithms for text classification tasks in social media contexts and emphasizes the need for further scrutiny into the anomaly observed among the Logistic Regression, SVM, and Naive Bayes results. Future work will focus on exploring the reasons behind this occurrence and the potential of deep learning techniques in enhancing detection performance.