bluuebunny/crossref_metadata_2025 huggingface dataset:
Embedding patient safety in a scaffold of interprofessional education; a qualitative study with thematic analysis
Authors: Guraya Shaista Salman , Umair Akhtar Muhammad , Sulaiman Nabil , David Leena R. , Jirjees Feras Jassim , Awad Manal , AL Kawas Sausan , Hassan Taha Mohamed , Haider Mohamed , Maria Dias Jacqueline , Kodumayil Shada Aysha , Dash Nihar Ranjan , Al-Qallaf Amal , Hasswan Ahmed , Salmanpour Vida Abdolhamid , Guraya Salman Yousuf
Published: December 2023

Background

Regardless of a proliferation of interest in reducing unsafe practices in healthcare, threats to patient safety (PS) remain high. Moreover, little attention has been paid towards the role of interprofessional education (IPE) in enhancing PS. This qualitative study was conducted to unfold the insights of the senior medical, dental and health sciences students at the University of Sharjah (UoS) in the United Arab Emirates (UAE) about PS in an online IPE-based workshop.

Methods

This inductive thematic analysis study was conducted on senior medical and health students at the Colleges of Medicine, Dental Medicine, Health Sciences, and Pharmacy of UoS. During an online workshop, students discussed plausible solutions for four real practice-based clinical scenarios with elements of unsafe healthcare practices. During the breakout rooms, the students exhibited high level of articulation and proactively participated in discussions. The data from the online workshop were transcribed and then coding, categorizing, and labelling of recurrent themes were carried out. Multiple individual deliberations, consolidation, incorporation of the identified preliminary themes, and merging and reorganizing sub-themes led to a final thematic framework.

Results

This work delved into the perspectives of 248 students regarding teamwork, communication, problem-solving, and other aspects concerning PS in interprofessional settings in an online workshop. The iterative process of data transcription, curating and qualitative analysis surfaced 32 codes. Later, the inductive themaric analysis yielded five themes with distinct yet interconnected nested subthemes in the context of PS in IPE settings. These themes of information sharing and grounding (problem-solving, social skills), maintaining communication (clinical reasoning, shared mental model), executing interprofessional activities (collaborative practice, collaboration scripts), professional cognitive abilities (cognitive maturity, metacognition), and negotiating professional identities (systematic change, socio-economic scaffolding) emerged as fundamental pillars for enhancing PS in healthcare.

Conclusion

Our study demonstrated the outcome of an innovative and team-based workshop which embedded PS within a scaffold of IPE environment. This research calls for incorporation of the emerging areas of clinical reasoning, problem solving, collaborative practice, and shared mental model into medical curricula for structured IPE in improving PS domains in medical education. These findings underscore the need for multifaceted dimensions of IPE imperatives for cultivating collaborative competence.
Implementation and evaluation of a nurse-led intervention to augment an existing residential aged care facility outreach service with a visual telehealth consultation: stepped-wedge cluster randomised controlled trial
Authors: Sunner Carla , Giles Michelle , Ball Jean , Barker Roslyn , Hullick Carolyn , Oldmeadow Christopher , Foureur Maralyn
Published: December 2023

Background

Up to 75% of residents from residential aged care facilities (RACF) are transferred to emergency departments (ED) annually to access assessment and care for unplanned or acute health events. Emergency department presentations of RACF residents can be both expensive and risky, and many are unnecessary and preventable. Processes or triage systems to assess residents with a health event, prior to transfer, may reduce unnecessary ED transfer. The Aged Care Emergency (ACE) service is a nurse-led ED outreach service that provides telephone support to RACF nurses regarding residents’ health events. This service is available Monday to Friday, 8am to 4 pm (ED ACE hours). The primary objective of this study was to assess whether the augmentation of the phone-based ED ACE service with the addition of a visual telehealth consultation (VTC) would reduce RACF rate of ED presentations compared to usual care. The secondary objectives were to 1) monitor presentations to ED within 48 h post VTC to detect any adverse events and 2) measure RACF staff perceptions of VTC useability and acceptability.

Methods

This implementation study used a stepped wedge cluster randomised controlled trial design. Study settings were four public hospital EDs and 16 RACFs in two Local Health Districts. Each ED was linked to 4 RACFs with approximately 350 RACF beds, totalling 1435 beds across 16 participating RACFs. Facilities were randomised into eight clusters with each cluster comprising one ED and two RACFs.

Results

A negative binomial regression demonstrated a 29% post-implementation reduction in the rate of ED presentations (per 100 RACF beds), within ED ACE hours (IRR [95% CI]: 0.71 [0.46, 1. 09]; p = 0.122). A 29% reduction, whilst not statistically significant, is still clinically important and impactful for residents and EDs. A post-hoc logistic regression demonstrated a statistically significant 69% reduction in the probability that an episode of care resulted in an ED presentation within ED ACE hours post-implementation compared to pre-implementation (OR [95% CI]: 0.31 [0.11, 0.87]; p = 0.025).

Conclusion

Findings have shown the positive impact of augmenting ACE with a VTC. Any reduction of resident presentations to a busy ED is beneficial to healthcare overall, but more so to the individual older person who can recover safely and comfortably in their own RACF.

Trial registration

Australian New Zealand Clinical Trials Registry (ID ACTR N12619001692123) (02/12/2019) https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378629andisReview=true
Knowledge and attitudes of German and Swiss community pharmacists towards biologicals and biosimilars – a prospective survey before and after the COVID-19 pandemic
Authors: Messner Kirstin , Eickhoff Christiane , Schulz Martin , Allemann Samuel S. , Arnet Isabelle
Published: December 2023

Background

Knowledge, attitudes and substitution laws of biosimilars are not consistent across countries. Biosimilar acceptance among patients and healthcare professionals may be suffering from gaps in knowledge and understanding about biosimilars and their regulatory approval process. Pharmacists' roles and responsibilities changed considerably during the COVID-19 pandemic. Thus, they might have gained new skills and self-confidence in counseling and substitution of biosimilars.

Aims

To examine and compare the knowledge, perceptions and information needs of German and Swiss pharmacists regarding original biologicals and biosimilars in 2020 and 2022.

Methods

We conducted an online survey among Swiss and German community pharmacies in February 2020 (before) and August 2022 (after the COVID-19 pandemic). Descriptive statistics were calculated and the Chi-Square test was used for comparisons among categorical variables.

Results

A total of 764 pharmacists took part in the survey (390 in 2020 and 374 in 2022) with comparable demographics. The frequency of dispensing biologicals remained similar between German and Swiss pharmacists in 2020 and 2022, but the Swiss dispensation of biosimilars increased significantly in 2022 compared to 2020. Concerning the understanding of the term biosimilars, knowledge remained moderate in both countries in both years. Participants were equally familiar with the term and most felt sufficiently informed. In both countries, substitution with a biosimilar showed the least confidence of all attitudes. A third of the participants indicated correct substitution rules in their country. In both years, around 85% of the participants were highly interested in additional training on this topic.

Discussion/Conclusion

The results indicate that similarities and differences between Germany and Switzerland regarding knowledge and attitudes towards biologicals and biosimilars remained unchanged before and after the COVID-19 pandemic. An influence of the pandemic is unlikely. There is still a clear lack of knowledge among community pharmacists on biosimilars, especially regarding the substitution rules. Due to a rising market with many benefits but also big challenges to overcome, the topic of biosimilars should receive more attention in the future. This requires additional training for pharmacists.
MiR-146b-5p enriched bioinspired exosomes derived from fucoidan-directed induction mesenchymal stem cells protect chondrocytes in osteoarthritis by targeting TRAF6
Authors: Lou Chao , Jiang Hongyi , Lin Zhongnan , Xia Tian , Wang Weidan , Lin Chihao , Zhang Zhiguang , Fu Haonan , Iqbal Shoaib , Liu Haixiao , Lin Jian , Wang Jilong , Pan Xiaoyun , Xue Xinghe
Published: December 2023

Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.
Clinical value of station 4R node dissection in esophageal squamous cell carcinoma
Authors: Wang Xin-ye , Fu Xia-yu , Yang Hong , Wen Jing , Lin Peng , Fu Jian-hua
Published: December 2023

Background

Many controversies still exist concerning the optimal extent of lymphadenectomy during esophagectomy in esophageal squamous cell carcinoma (ESCC). The objective of this study was to explore the characteristics of 4R metastasis and evaluate the clinical value of 4R node dissection in ESCC.

Methods

A total of 736 ESCC patients who underwent radical esophagectomy between 2005 and 2013 were retrospectively collected, among which 393 ones underwent 4R dissection. Propensity score matching (PSM) method was applied to reduce the effects of confounding variables between the 4R dissection and non-dissection groups to analyze overall survival.

Results

Patients showed a low 4R metastasis rate of 5.1% (20/393) (5.2%, 5.8%, and 1.8% for upper, middle, and lower tumors, respectively). Correlation analyses identified that 4R metastasis was significantly associated with station 2R metastasis (p < 0.001) and pathologic tumor-node-metastasis (pTNM) stage (p < 0.001). All 4R metastases were observed in stages IIIB and IVA. Moreover, patients with station 4R dissection failed to achieve significantly improved overall survival compared with those without 4R dissection, regardless of tumor stage (overall: p = 0.696; stage 0-IIIA: p = 0.317; stage IIIB-IVA: p = 0.619).

Conclusion

4R metastasis is likely to be associated with more aggressive disease, and routine 4R node dissection might not be necessary for ESCC patients.
Targeting Src homology phosphatase 2 ameliorates mouse diabetic nephropathy by attenuating ERK/NF-κB pathway-mediated renal inflammation
Authors: Yu Che , Li Zhuo , Nie Cuili , Chang Lei , Jiang Tao
Published: December 2023

Renal inflammation is a pivotal mechanism underlying the pathophysiology of diabetic nephropathy (DN). The Src homology phosphatase 2 (SHP2) has been demonstrated to be linked to diabetes-induced inflammation, yet its roles and explicit molecular mechanisms in DN remain unexplored. Here, we report that SHP2 activity is upregulated in both DN patients and db/db mice. In addition, pharmacological inhibition of SHP2 with its specific inhibitor PHPS1 alleviates DN in db/db mice and attenuates renal inflammation. In vitro, PHPS1 administration prevents inflammatory responses in HK-2 cells stimulated by high glucose (HG). Mechanistically, PHPS1 represses HG-induced activation of the proinflammatory ERK/NF-κB signaling pathway, and these inhibitory effects are blocked in the presence of an ERK specific inhibitor, hence demonstrating that PHPS1 suppresses ERK/NF-κB pathway-mediated inflammation. Moreover, PHPS1 retards ERK/NF-κB pathway activation in db/db mice, and histologically, SHP2 activity is positively correlated with ERK/NF-κB activation in DN patients. Taken together, these findings identify SHP2 as a potential therapeutic target and show that its pharmacological inhibition might be a promising strategy to mitigate DN.
scNAT: a deep learning method for integrating paired single-cell RNA and T cell receptor sequencing profiles
Authors: Zhu Biqing , Wang Yuge , Ku Li-Ting , van Dijk David , Zhang Le , Hafler David A. , Zhao Hongyu
Published: December 2023

Many deep learning-based methods have been proposed to handle complex single-cell data. Deep learning approaches may also prove useful to jointly analyze single-cell RNA sequencing (scRNA-seq) and single-cell T cell receptor sequencing (scTCR-seq) data for novel discoveries. We developed scNAT, a deep learning method that integrates paired scRNA-seq and scTCR-seq data to represent data in a unified latent space for downstream analysis. We demonstrate that scNAT is capable of removing batch effects, and identifying cell clusters and a T cell migration trajectory from blood to cerebrospinal fluid in multiple sclerosis.
Performance evaluation of protocols for Taenia saginata and Ascaris suum egg recovery from the house fly’s gastrointestinal tract and exoskeleton
Authors: De Bock Sophie , Duchateau Luc , Levecke Bruno , Gabriël Sarah
Published: December 2023

Background

The synanthropic house fly (Musca domestica) can potentially contribute to the mechanical spread of eggs of Taenia and Ascaris spp. in the environment and between hosts. However, the absence of validated protocols to recover eggs hampers an in-depth analysis of the house fly's role in parasite egg transmission.

Methods

The gastrointestinal tract and exoskeleton of euthanized house flies were spiked with Taenia saginata eggs. The performance of several recovery protocols, in terms of both the recovery rate and ease-of-use, was (microscopically) evaluated and compared. These protocols employed steps such as washing, maceration, filtration, flotation and both passive and centrifugal sedimentation. The final validated protocols were subsequently evaluated for the recovery of Ascaris suum eggs.

Results

The final protocol validated for the recovery of T. saginata eggs from the house fly’s gastrointestinal tract involved homogenization in phosphate-buffered saline and centrifugation at 2000 g for 2 min, yielding a recovery rate of 79.7%. This protocol required 6.5 min to perform (which included 1.5 min of hands-on time) and removed large debris particles that could hinder the differentiation of eggs from debris. Similarly, the final protocol validated for the recovery of T. saginata eggs from the fly’s exoskeleton involved washing by vortexing for 2 min in Tween 80 (0.05%), 15 min of passive sedimentation and centrifugation at 2000 g for 2 min, yielding a recovery rate of 77.4%. This protocol required 20.5 min to perform (which included 3.5 min of hands-on time) and successfully removed debris. The same protocols yielded recovery rates of 74.2% and 91.5% for the recovery of A. suum eggs from the fly’s gastrointestinal tract and exoskeleton, respectively.

Conclusions

Effective, simple and easy-to-use protocols were developed and validated for the recovery of T. saginata and A. suum eggs from the house fly’s gastrointestinal tract and exoskeleton. These protocols can be applied to investigate the importance of flies as parasite egg transmitters in laboratory and field settings.

Graphical Abstract
Quantitative thresholds for variant enrichment in 13,845 cases: improving pathogenicity classification in genetic hearing loss
Authors: Liu Sihan , Zhong Mingjun , Huang Yu , Zhang Qian , Chen Ting , Xu Xiaofei , Peng Wan , Wang Xiaolu , Feng Xiaoshu , Kang Lu , Lu Yu , Cheng Jing , Bu Fengxiao , Yuan Huijun
Published: December 2023

Background

The American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) guidelines recommend using variant enrichment among cases as "strong" evidence for pathogenicity per the PS4 criterion. However, quantitative support for PS4 thresholds from real-world Mendelian case–control cohorts is lacking.

Methods

To address this gap, we evaluated and established PS4 thresholds using data from the Chinese Deafness Genetics Consortium. A total of 9,050 variants from 13,845 patients with hearing loss (HL) and 6,570 ancestry-matched controls were analyzed. Positive likelihood ratio and local positive likelihood ratio values were calculated to determine the thresholds corresponding to each strength of evidence across three variant subsets.

Results

In subset 1, consisting of variants present in both cases and controls with an allele frequency (AF) in cases ≥ 0.0005, an odds ratio (OR) ≥ 6 achieved strong evidence, while OR ≥ 3 represented moderate evidence. For subset 2, which encompassed variants present in both cases and controls with a case AF < 0.0005, and subset 3, comprising variants found only in cases and absent from controls, we defined the PS4_Supporting threshold (OR > 2.27 or allele count ≥ 3) and the PS4_Moderate threshold (allele count ≥ 6), respectively. Reanalysis applying the adjusted PS4 criteria changed the classification of 15 variants and enabled diagnosis of an additional four patients.

Conclusions

Our study quantified evidence strength thresholds for variant enrichment in genetic HL cases, highlighting the importance of defining disease/gene-specific thresholds to improve the precision and accuracy of clinical genetic testing.
Multimodal lifestyle engagement patterns support cognitive stability beyond neuropathological burden
Authors: Paolillo Emily W. , Saloner Rowan , VandeBunte Anna , Lee Shannon , Bennett David A. , Casaletto Kaitlin B.
Published: December 2023

Background

Modifiable lifestyle behaviors account for a large proportion of dementia risk. However, the combined contributions of multidomain lifestyle patterns to cognitive aging are poorly understood, as most studies have examined individual lifestyle behaviors in isolation and without neuropathological characterization. This study examined data-driven patterns of lifestyle behaviors across multiple domains among older adults and tested their associations with disease-specific neuropathological burden and cognitive decline.

Methods

Participants included 2059 older adults enrolled in the longitudinal Memory and Aging Project (MAP) at the Rush Alzheimer’s Disease Center; none of whom had dementia at baseline (73% no cognitive impairment (NCI), 27% mild cognitive impairment [MCI]). All participants completed cognitive testing annually. Lifestyle factors were measured during at least one visit and included (1) actigraphy-measured physical activity, as well as self-reported (2) sleep quality, (3) life space, (4) cognitive activities, (5) social activities, and (6) social network. A subset of participants (n = 791) had autopsy data for which burden of Alzheimer’s disease (AD), cerebrovascular disease (CVD), Lewy body disease, and hippocampal sclerosis/TDP-43 was measured. Latent profile analysis across all 2059 participants identified distinct subgroups (i.e., classes) of lifestyle patterns. Linear mixed-effects models examined relationships between lifestyle classes and global cognitive trajectories, with and without covarying for all neuropathologies. Classes were also compared on rates of incident MCI/dementia.

Results

Five classes were identified: Class 1Low Life Space (lowest lifestyle engagement), Class 2PA (high physical activity), Class 3Low Avg (low to average lifestyle engagement), Class 4Balanced (high average lifestyle engagement), and Class 5Social (large social network). Classes 4Balanced and 5Social had the lowest AD burden, and Class 2PA had the lowest CVD burden. Classes 2–5 had significantly less steep global cognitive decline compared to Class 1Low Life Space, with comparable effect sizes before and after covarying for neuropathological burden. Classes 4Balanced and 5Social exhibited the lowest rates of incident MCI/dementia.

Conclusions

Lifestyle behavior patterns among older adults account for differential rates of cognitive decline and clinical progression. Those with at least average engagement across all lifestyle domains exhibit greater cognitive stability after adjustment for neuropathology, highlighting the importance of engagement in multiple healthy lifestyle behaviors for later life cognitive health.
Uncertain of uncertainties? A comparison of uncertainty quantification metrics for chemical data sets
Authors: Rasmussen Maria H. , Duan Chenru , Kulik Heather J. , Jensen Jan H.
Published: December 2023

With the increasingly more important role of machine learning (ML) models in chemical research, the need for putting a level of confidence to the model predictions naturally arises. Several methods for obtaining uncertainty estimates have been proposed in recent years but consensus on the evaluation of these have yet to be established and different studies on uncertainties generally uses different metrics to evaluate them. We compare three of the most popular validation metrics (Spearman’s rank correlation coefficient, the negative log likelihood (NLL) and the miscalibration area) to the error-based calibration introduced by Levi et al. (Sensors2022, 22, 5540). Importantly, metrics such as the negative log likelihood (NLL) and Spearman’s rank correlation coefficient bear little information in themselves. We therefore introduce reference values obtained through errors simulated directly from the uncertainty distribution. The different metrics target different properties and we show how to interpret them, but we generally find the best overall validation to be done based on the error-based calibration plot introduced by Levi et al. Finally, we illustrate the sensitivity of ranking-based methods (e.g. Spearman’s rank correlation coefficient) towards test set design by using the same toy model ferent test sets and obtaining vastly different metrics (0.05 vs. 0.65).
Higher levels of circulating desphospho-uncarboxylated matrix Gla protein over time are associated with worse survival: the prospective Maastricht Intensive Care COVID cohort
Authors: Mulder Mark M. G. , Schellens Joep , Sels Jan-Willem E. M. , van Rosmalen Frank , Hulshof Anne-Marije , de Vries Femke , Segers Ruud , Mihl Casper , van Mook Walther N. K. A. , Bast Aalt , Spronk Henri M. H. , Henskens Yvonne M. C. , van der Horst Iwan C. C. , Cate Hugo ten , Schurgers Leon J. , Drent Marjolein , van Bussel Bas C. T.
Published: December 2023

Background

Extra-hepatic vitamin K-status, measured by dephosphorylated uncarboxylated matrix Gla protein (dp-ucMGP), maintains vascular health, with high levels reflecting poor vitamin K status. The occurrence of extra-hepatic vitamin K deficiency throughout the disease of COVID-19 and possible associations with pulmonary embolism (PE), and mortality in intensive care unit (ICU) patients has not been studied. The aim of this study was to investigated the association between dp-ucMGP, at endotracheal intubation (ETI) and both ICU and six months mortality. Furthermore, we studied the associations between serially measured dp-ucMGP and both PE and mortality.

Methods

We included 112 ICU patients with confirmed COVID-19. Over the course of 4 weeks after ETI, dp-ucMGP was measured serially. All patients underwent computed tomography pulmonary angiography (CTPA) to rule out PE. Results were adjusted for patient characteristics, disease severity scores, inflammation, renal function, history of coumarin use, and coronary artery calcification (CAC) scores.

Results

Per 100 pmol/L dp-ucMGP, at ETI, the odds ratio (OR) was 1.056 (95% CI: 0.977 to 1.141, p = 0.172) for ICU mortality and 1.059 (95% CI: 0.976 to 1.059, p = 0.170) for six months mortality. After adjustments for age, gender, and APACHE II score, the mean difference in plasma dp-ucMGP over time of ICU admission was 167 pmol/L (95% CI: 4 to 332, p = 0.047). After additional adjustments for c-reactive protein, creatinine, and history of coumarin use, the difference was 199 pmol/L (95% CI: 50 to 346, p = 0.010). After additional adjustment for CAC score the difference was 213 pmol/L (95% CI: 3 to 422, p = 0.051) higher in ICU non-survivors compared to the ICU survivors. The regression slope, indicating changes over time, did not differ. Moreover, dp-ucMGP was not associated with PE.

Conclusion

ICU mortality in COVID-19 patients was associated with higher dp-ucMGP levels over 4 weeks, independent of age, gender, and APACHE II score, and not explained by inflammation, renal function, history of coumarin use, and CAC score. No association with PE was observed. At ETI, higher levels of dp-ucMGP were associated with higher OR for both ICU and six month mortality in crude and adjusted modes, although not statistically significantly.
Report on the 21st International Symposium on Geo‑disaster reduction, 5–8 August 2023, Shanghai, China
Authors: Zheng Hu , Huang Yu , Li Bo , Wang Fawu
Published: December 2023

The joint event of 21st International Symposium on Geo-disaster Reduction (21st ISGdR) was held onsite and online during 5–8 August 2023 in Shanghai, China. This symposium focused on the theme of “A new era for safe and resilient coastal and marine systems”, providing a platform for academics, researchers and practitioners from different countries to discuss the research progress and exchange ideas on the reduction of disasters. The symposium consisted of keynote lecture, invited lectures and other presentations in parallel session.
COVID-19 and the financial resilience of Finland’s seaports
Authors: Leviäkangas Pekka , Ojala Lauri , Paik Seong Mok , Pekkala Veikko
Published: December 2023

This research quantifies the impacts that COVID-19 had on the financial performance of Finnish seaports. The data comprises annual financial statement information from 18 seaports. The ports are different in terms of ownership, size, and main lines of business. Most ports’ turnover dropped because of COVID-19, and their profitability declined. However, the ports were able to maintain their financial position quite well despite their declining turnovers. Statistically significant impacts of COVID-19 were observable regarding turnover growth, profitability, labor intensity and capital intensity. Surprisingly, ports with mainly import traffic had the least negative impacts on turnover growth.
Building quality primary health care development in the new era towards universal health coverage: a Beijing initiative
Authors: Ren Minghui , Zhang Tuohong , Xu Jin , Qiao Jie , Qiao Jianrong , Zhan Siyan , Qin Jiangmei , Song Daping , Fang Yanru , Lin Yifang , Jiang Xiaopeng , Guo Yan , Meng Qingyue , Qian Xu , Liu Yunguo , Chan Sophia Siu Chee , Zhao Feng , Yip Winnie , Wang Hong , Wang Minmin , Yin Hui , Liu Zuokun , Li Na , Song Xinyi , Liu Fangfang , Jin Yinzi , Liu Fangjing , Huang Yangmu
Published: December 2023

Primary health care (PHC) is the most effective way to improve people's health and well-being, and primary care services should act as the cornerstone of a resilient health system and the foundation of universal health coverage. To promote high quality development of PHC, an International Symposium on Quality Primary Health Care Development was held on December 4–5, 2023 in Beijing, China, and the participants have proposed and advocated the Beijing Initiative on Quality Primary Health Care Development. The Beijing Initiative calls on all countries to carry out and strengthen 11 actions: fulfill political commitment and accountability; achieve “health in all policies” through multisectoral coordination; establish sustainable financing; empower communities and individuals; provide community-based integrated care; promote the connection and integration of health services and social services through good governance; enhance training, allocation and motivation of health workforce, and medical education; expand application of traditional and alternative medicine for disease prevention and illness healing; empower PHC with digital technology; ensure access to medicinal products and appropriate technologies; and last, strengthen global partnership and international health cooperation. The Initiative will enrich the content of quality development of PHC, build consensus, and put forward policies for quality development of PHC in China in the new era, which are expected to make contributions in accelerating global actions.
Digital subtraction angiography findings of stroke in young adult population: a multi-center record-based study
Authors: Tini Kumara , Tedyanto Eric Hartono , Andaka Deddy , Pramana Nyoman Angga Krishna , Widyadharma I Putu Eka
Published: December 2023

Background

Stroke is one of the main causes of disability, in which nearly 2/3 of survivors experience disability and interferes with the patient’s daily functional activities. Hypertension, dyslipidemia, obesity, and smoking habits are the main causes of stroke in young adults. Vascular abnormalities are also risk factor for stroke in young adults. Advanced imaging examinations such as cerebral digital subtraction angiography (DSA) can provide a clear picture of the vasculature of the blood vessels of the human brain and provide a real-time picture of the hemodynamic status, blood flow and collateral circulation of the cerebral vessels.

Results

There were approximately 999 patients who had DSA cerebral examination during the study period. The total young adult population was 147 [92 males (62.4%) and 55 females (37.6%)]. There were 82 patients with ischemic stroke (60.7%). The main etiology of ischemic stroke in this study was intracranial atherosclerotic disease (ICAD) [44 (53.65%)]. The young adult population had 53 hemorrhagic stroke patients (39.3%). The main cause of hemorrhagic stroke is hypertensive vasculopathy (41.5%), followed by a ruptured cerebral arteriovenous malformation (CAVM) (37.7%). There were 12 patients with cerebral sinus venous thrombosis (CSVT). Headache is the main complaint of patients with venous stroke, followed by seizures and hemiparesis. The transverse sinus is the most common site for occlusion (66.7%).

Conclusion

This study describes the characteristics and prevalence of stroke in young adults based on the results of cerebral DSA examination. Stroke in young adults is not uncommon. Several traditional risk factors in old age are now found in young people. Lifestyle modification is needed to reduce the prevalence of stroke in young adults.
In vitro mitochondrial and myogenic gene expression is influenced by formoterol in human myotubes
Authors: Zumbro Emily L. , Duplanty Anthony A. , Gordon Ryan A. , Guerin Gena D. , Brisebois Matthew F. , Sokoloski Matthew L. , Rigby Brandon R.
Published: December 2023

Background

Exercise is an effective treatment for establishing and maintaining skeletal muscle health. The interconnected cascade of gene expression pathways related to myogenesis, mitochondrial homeostasis, and thyroid hormone metabolism are critical to skeletal muscle health. This in vitro study was conducted to investigate the effects of exercise mimetic (formoterol) stimulation on human skeletal muscle cell signaling during myogenesis, and to provide insight on potential targets for future studies exploring therapies for skeletal muscle atrophy. Human myoblasts were cultured and differentiated to evaluate the effects of exercise mimetic stimulation on gene expression during mid and late myogenesis.

Results

We characterized the expression of 24 genes related to myogenesis, mitochondrial biogenesis, thyroid hormone metabolism, and cellular homeostasis and found that 21 genes were altered in response to formoterol, thus affecting related skeletal muscle pathways. Additionally, formoterol stimulation resulted in a myogenic program that appears to favor prolonged myoblast proliferation and delayed myotube maturation. Robust, yet distinctive effects of exercise mimetic stimulation on gene expression during mid-myogenesis and at terminal differentiation occurred. For instance, MYF5 increased in D6 FORM compared to other groups (p < 0.001) while MYOD and MYOG both decreased expression in the FORM groups compared to CON (p < 0.01). Secondly, mitochondrial biogenesis genes were stimulated following formoterol administration, namely PGC-1α, PGC-1β, and TFAM (p < 0.05). Uniquely in our study, thyroid hormone metabolism related genes were differentially expressed. For instance, DIO2 and DIO3 were both stimulated following formoterol administration (p < 0.05).

Conclusions

The results of our study support the groundwork for establishing further experiments utilizing exercise signaling as a clinical treatment in models targeting dysfunctional skeletal muscle cell growth.
Biocontrol potential of entomopathogenic nematode, Heterorhabditis indica against pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae)
Authors: Thube Shivaji , Shinde Swati , Shah Vivek , Gokte-Narkhedkar Nandini , Ingole Dnyaneshwar , Nikoshe Akash , Tenguri Prabhulinga , Thavkar Snehal , Fand Babasaheb , Deshmukh Vrushali , Prasad Yenumula
Published: December 2023

Background

The emergence of pink bollworm (PBW), Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae), in cotton due to Bt resistance and concealed feeding habit has created a need for alternative, eco-friendly, and cost-effective control methods. This study aimed to evaluate the bio-efficacy and reproductive potential of two native strains of entomopathogenic nematodes (EPNs), Heterorhabditis indica, namely CICR-HI-CL and CICR-HI-MN, against PBW larvae and pupae under in-vitro conditions.

Results

The larval assay revealed that strain CICR-HI-CL exhibited higher potency than strain CICR-HI-MN against 2nd, 3rd, and 4th instar larvae, with median lethal dose (LD50) values of 5.45, 4.45, and 4.60 infective juveniles (IJs) per larva, respectively. In case of pupal bioassay, both EPN strains demonstrated greater virulence when applied directly (LD50 values: 29.65 and 73.88 IJs per pupa for strains CICR-HI-CL and CICR-HI-MN, respectively) compared to soil application (147.84 and 272.38 IJs per pupa). Both EPN strains successfully penetrated and reproduced on 4th instar larvae, resulting in maximum production of 19.28 and 20.85 lakh IJs per larva in the next generation when inoculated at 30 IJs per larva.

Conclusion

The present study has generated useful information on the virulence and reproductive potential of two strains of EPN H. indica (CICR-HI-CL and CICR-HI-MN) against PBW, a dreaded pest of cotton. Higher virulence and reproductive potential of EPN strains demonstrated their ability to multiply, sustain and perpetuate on larval and pupal stages of PBW. The knowledge generated will help formulate effective management strategies for PBW with the inclusion of EPN as a potential biological control candidate. The soil-dwelling life stages viz., last instar hibernating larvae and pupae of PBW can be the ideal weak links to make a successful use of H. indica for sustainable management of PBW in the cotton ecosystem. However, before taking these EPN strains to field for managing PBW, detailed studies investigating their biocontrol potential against PBW under field conditions are needed.
Evolution and ecology of Jeilongvirus among wild rodents and shrews in Singapore
Authors: Ch’ng Lena , Low Dolyce H.W. , Borthwick Sophie A. , Zhang Rong , Ong Zoe A. , Su Yvonne C.F. , Hitch Alan T. , Smith Gavin J.D. , Mendenhall Ian H.
Published: December 2023

Background

Jeilongvirus was proposed as a new genus within the Paramyxoviridae in 2018. The advancement in metagenomic approaches has encouraged multiple reports of Jeilongvirus detection following the initial species discovery, enriching species diversity and host range within the genus. However, Jeilongvirus remains understudied in Singapore, where interfaces between humans and small mammals are plentiful.

Methods

Here, we utilized metagenomic sequencing for the exploration of viral diversity in small mammal tissues. Upon discovery of Jeilongvirus, molecular screening and full genome sequencing was conducted, with the data used to conduct statistical modelling and phylogenetic analysis.

Results

We report the presence of Jeilongvirus in four species of Singapore wild small mammals, detected in their spleen and kidney. We show that full genomes of three Singapore Jeilongvirus encode for eight ORFs including the small hydrophobic and transmembrane proteins. All generated genomes cluster phylogenetically within the small mammal subclade, but share low genetic similarity with representative Jeilongvirus species. Statistical modelling showed no spatial or temporal patterns and differences among species, life history traits and habitat types.

Conclusions

This study serves as a basis for understanding dynamics between Jeilongvirus and small mammal hosts in Singapore by displaying the virus generalist nature. In addition, the initial detection can help to invoke improved routine surveillance and detection of circulating pathogens in synanthropic hosts.
Congenital absence of sternum with tetralogy of Fallot, right aortic arch, and bilateral superior vena cava
Authors: Chavan Santosh , Narkhede Nilima , Weling Rajaram
Published: December 2023

Background

Congenital complete absence of sternal bone or cleft sternum or absent sternum is a very rare and potentially life-threatening birth defect. An association of cleft sternum with tetralogy of Fallot, right aortic arch, and bilateral superior vena cava is extremely rare, and not many cases have been reported.

Case presentation

A 2-year-old child was brought for routine checkup. He was a known case of congenital heart disease and midline thoracic defect at age of 3 months. Further investigations revealed absent sternum with tetralogy of Fallot, large cono-ventricular defect with bidirectional shunt, severe infundibular pulmonary stenosis, superiorly located right aortic arch, and bilateral superior vena cava.

Conclusion

Congenital absence of the sternum with intracardiac defects like tetralogy of Fallot with right aortic arch and bilateral superior vena cava is extremely rare malformation. Early diagnosis and surgical correction give the infant the best chance of survival.
Misdiagnosed cystic pancreatic neuroendocrine tumor with bilobar hepatic metastasis managed with single-stage resection — a case report
Authors: Uddin Maham Nasir , Khan Muhammad Arsalan , Khan Abdaal Waseem
Published: December 2023

Background

Pancreatic neuroendocrine tumors (PNET) account for less than 2% of all pancreatic tumors, while cystic PNETs account for only 10–18% of all resected PNETs. The most common site for metastasis is the liver. Few detailed guidelines currently exist for management of stage 4 cystic PNETs. This is a unique case that was managed with complete surgical resection in one sitting.

Case presentation

Our report is on a young male patient who was initially misdiagnosed as having a pancreatic pseudocyst and treated accordingly. He was finally diagnosed with PNET but was reluctant to undergo surgery until he developed bilobar hepatic metastasis. We performed a pylorus-preserving pancreaticoduodenectomy with a Roux-en-Y hepaticojejunostomy and wedge resection of both hepatic metastatic deposits.

Conclusion

Cystic PNETs are rare and commonly misdiagnosed as pancreatic pseudocysts. Surgical resection is considered ideal, but sparse literature exists on the management due to a paucity of cases. We have reported this case as it was successfully managed with single-stage surgery for both the primary tumor as well as bilobar hepatic metastatic deposits, and no similar cases have been reported in literature. The follow-up scan revealed no residual disease.
Interaction of telmisartan and related sartans with the programmed cell death-ligand 1 (PD-L1) protein dimer: a molecular docking analysis
Authors: Vergoten Gérard , Bailly Christian
Published: December 2023

Background

Telmisartan (TLT) is a prototypic angiotensin receptor blocker largely used to treat hypertension worldwide. In addition to its cardioprotective effects, TLT presents pleiotropic activities and notably displays noticeable anti-inflammatory and antitumor effects. The repression of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint may be implicated antitumor action of TLT, as it is the case with many other compounds equipped with a biphenyl moiety. We have used molecular modeling to compare the interaction of TLT and derivatives with the PD-L1 dimer protein.

Results

Two molecules, TLT-dimer and TLT-acylglucuronide, were found to form more stable complexes with PD-L1 than TLT itself. In parallel, the docking analysis performed with a series of 12 sartans led to the identification of Olmesartan as a potential PD-L1 binder. The stacked biphenyl unit of Olmesartan positions the molecule along the groove delimited by the two protein monomers. The flanking tetrazole and imidazole moieties, on each side of the biphenyl unit of Olmesartan, contribute favorably to the protein interaction via specific hydrogen bonding interactions.

Conclusions

The computational analysis suggests a possible binding of Olmesartan to PD-L1 dimer and thus offers novel perspectives for the design of small molecules capable of interrupting the PD-1/PD-L1 immune checkpoint. Experimental studies are warranted to validate the hypothesis.

Graphical abstract
Chronic social defeat stress-induced depression reduces BCG efficacy by promoting regulatory T-cell levels in mice
Authors: Tyagi Rohit , Chen Xi , Dhar Atika , Yang Bing , Zhou Wei , Reheman Aikebaier , Lei Yingying , Cao Gang
Published: December 2023

Despite the initial successes of the Bacillus Calmette-Guerin (BCG) vaccine in children, its efficacy against tuberculosis is highly variable. There is a lack of understanding about how mental conditions influence BCG vaccination. Here, we used the chronic social defeat stress (CSDS) model to explore the effects of depression on BCG vaccination efficacy. We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice. Meanwhile, a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay (MGIA). Cytokine expression of IL-12p40, IL-1β, IL-17, TNF-α and IFN-γ was reduced, whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice. Moreover, the proportions of CD4+IFN-γ+, CD8+IFN-γ+ T lymphocytes and CD4+ effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice. Depression promotes CD4+ regulatory T cells (Treg) and myeloid-derived suppressor cell (MDSC) generation in depressed mice, contributing to the reduced pro-inflammatory immune response upon BCG vaccination. This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.
Low Perfusion and Missed Diagnosis of Hypoxemia by Pulse Oximetry in Darkly Pigmented Skin: A Prospective Study
Authors: Gudelunas M. Koa , Lipnick Michael , Hendrickson Carolyn , Vanderburg Sky , Okunlola Bunmi , Auchus Isabella , Feiner John R. , Bickler Philip E.
Published: December 2023

BACKGROUND:

Retrospective clinical trials of pulse oximeter accuracy report more frequent missed diagnoses of hypoxemia in hospitalized Black patients than White patients, differences that may contribute to racial disparities in health and health care. Retrospective studies have limitations including mistiming of blood samples and oximeter readings, inconsistent use of functional versus fractional saturation, and self-reported race used as a surrogate for skin color. Our objective was to prospectively measure the contributions of skin pigmentation, perfusion index (PI), sex, and age on pulse oximeter errors in a laboratory setting.

METHODS:

We enrolled 146 healthy subjects, including 25 with light skin (Fitzpatrick class I and II), 78 with medium (class III and IV), and 43 with dark (class V and VI) skin. We studied 2 pulse oximeters (Nellcor N-595 and Masimo Radical 7) in prevalent clinical use. We analyzed 9763 matched pulse oximeter readings (pulse oximeter measured functional saturation [Spo
2]) and arterial oxygen saturation (hemoximetry arterial functional oxygen saturation [Sao
2]) during stable hypoxemia (Sao
2 68%–100%). PI was measured as percent infrared light modulation by the pulse detected by the pulse oximeter probe, with low perfusion categorized as PI < 1%. The primary analysis was to assess the relationship between pulse oximeter bias (difference between Sao
2 and Spo
2) by skin pigment category in a multivariable mixed-effects model incorporating repeated-measures and different levels of Sao
2 and perfusion.

RESULTS:

Skin pigment, PI, and degree of hypoxemia significantly contributed to errors (bias) in both pulse oximeters. For PI values of 1.0% to 1.5%, 0.5% to 1.0%, and <0.5%, the P value of the relationship to mean bias or median absolute bias was <.00001. In lightly pigmented subjects, only PI was associated with positive bias, whereas in medium and dark subjects bias increased with both low perfusion and degree of hypoxemia. Sex and age was not related to pulse oximeter bias. The combined frequency of missed diagnosis of hypoxemia (pulse oximeter readings 92%–96% when arterial oxygen saturation was <88%) in low perfusion conditions was 1.1% for light, 8.2% for medium, and 21.1% for dark skin.

CONCLUSIONS:

Low peripheral perfusion combined with darker skin pigmentation leads to clinically significant high-reading pulse oximeter errors and missed diagnoses of hypoxemia. Darkly pigmented skin and low perfusion states are likely the cause of racial differences in pulse oximeter performance in retrospective studies.
Imperialism Ultimately Works for Us”
Authors: Allen Amy
Published: December 2023

Although Rosa Luxemburg is enjoying a well-deserved renaissance, much of the current discussion of her work fails to contend with her commitment to a rather orthodox reading of the Marxist theory of history. This article argues that all of the features that make Luxemburg's work so attractive to contemporary scholars—her revolutionary radicalism, her accounts of spontaneity and democracy, and her critique of imperialism—are undergirded by her commitment to that theory, along with its commitments to unilinearity, necessity, and progress. This theory provides the systematic backbone for Luxemburg's thought. In the wake of postcolonial, Indigenous, Black, and feminist critiques of the Marxist theory of history, this feature of Luxemburg's work considerably complicates her legacy for contemporary critical theory.