bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning from implementation of a COVID case management desk guide and training: a pilot study in Sierra Leone
Authors: Witter Sophie , Zou Guanyang , Cheedella Kiran , Walley John , Wurie Haja 
Published: September 2023

Abstract
Background
When the COVID pandemic hit the world, there was need for applied guides and training materials to support frontline health care staff to manage patients effectively and safely and to educate themselves and communities. This article reports on the development and piloting of such a set of materials in Sierra Leone, which were based on international evidence but adapted to the local context. Reflecting on this experience, including community and health system barriers and enablers, is important to prepare for future regional shocks.

Methods
This study, in Bombali district in 2020, piloted user-friendly COVID guides for frontline health workers (the intervention), which was evaluated using facility checklists (pre and post training), routine data analysis and 32 key informant interviews.

Results
Key informants at district, hospital and community health centre levels identified gains from the training and desk guides, including improved diagnosis, triaging, infection prevention and management of patients. They also reported greater confidence to share messages on protection with colleagues and community members, which was needed to encourage continued use of essential services during the pandemic. However, important barriers were also revealed, including the lack of testing facilities, which reduced the sense of urgency, as few cases were identified. Actions based on the Ebola experience, such as setting up testing and isolation centres, which the community avoided, were not appropriate to COVID. Stigma and fear were important factors, although these were reduced with outreach activities. Supplies of essential medicines and personal protective equipment were also lacking.

Conclusion
This pilot study demonstrated the relevance and importance of guides adapted to the context, which were able to improve the confidence of health staff to manage their own and the community’s fears in the face of a new pandemic and improve their skills. Previous epidemics, particularly Ebola, complicated this by both creating structures that could be revitalised but also assumptions and behaviours that were not adapted to the new disease. Our study documents positive adaptations and resilience by health staff but also chronic system weaknesses (particularly for medicines, supplies and equipment) which must be urgently addressed before the next shock arrives.
Genome-wide identification and functional analysis of dysregulated alternative splicing profiles in sepsis
Authors: Tuerdimaimaiti Dilixiati , Abuduaini Buzukela , Kang Shaotao , Jiao Jinliang , Li Mengchen , Madeniyati Wolazihan , Tuerdi Baihetinisha , Aili Gulisitan , Tuerhong Reyila , Kulaxi Ajiguli 
Published: September 2023

Abstract
Background
An increasing body of evidence now shows that the long-term mortality of patients with sepsis are associated with various sepsis-related immune cell defects. Alternative splicing (AS), as a sepsis-related immune cell defect, is considered as a potential immunomodulatory therapy target to improve patient outcomes. However, our understanding of the role AS plays in sepsis is currently insufficient.

Aim
This study investigated possible associations between AS and the gene regulatory networks affecting immune cells. We also investigated apoptosis and AS functionality in sepsis pathophysiology.

Methods
In this study, we assessed publicly available mRNA-seq data that was obtained from the NCBI GEO dataset (GSE154918), which included a healthy group (HLTY), a mild infection group (INF1), asepsis group (Seps), and a septic shock group (Shock). A total of 79 samples (excluding significant outliers) were identified by a poly-A capture method to generate RNA-seq data. The variable splicing events and highly correlated RNA binding protein (RBP) genes in each group were then systematically analyzed.

Results
For the first time, we used systematic RNA-seq analysis of sepsis-related AS and identified 1505 variable AS events that differed significantly (p <= 0.01) across the four groups. In the sepsis group, the genes related to significant AS events, such as, SHISA5 and IFI27, were mostly enriched in the cell apoptosis pathway. Furthermore, we identified differential splicing patterns within each of the four groups. Significant differences in the expression of RNA Binding Protein(RBP) genes were observed between the control group and the sepsis group. RBP gene expression was highly correlated with variant splicing events in sepsis, as determined by co-expression analysis; The expression of DDX24, CBFA2T2, NOP, ILF3, DNMT1, FTO, PPRC1, NOLC1 RBPs were significant reduced in sepsis compared to the healthy group. Finally, we constructed an RBP-AS functional network.

Conclusion
Analysis indicated that the RBP-AS functional network serves as a critical post-transcriptional mechanism that regulates the development of sepsis. AS dysregulation is associated with alterations in the regulatory gene expression network that is involved in sepsis. Therefore, the RBP-AS expression network could be useful in refining biomarker predictions in the development of new therapeutic targets for the pathogenesis of sepsis.
Criterion validity of wrist accelerometry for assessing energy intake via the intake-balance technique
Authors: Hibbing Paul R. , Welk Gregory J. , Ries Daniel , Yeh Hung-Wen , Shook Robin P. 
Published: September 2023

AbstractBackgroundIntake-balance assessments measure energy intake (EI) by summing energy expenditure (EE) with concurrent change in energy storage (ΔES). Prior work has not examined the validity of such calculations when EE is estimated via open-source techniques for research-grade accelerometry devices. The purpose of this study was to test the criterion validity of accelerometry-based intake-balance methods for a wrist-worn ActiGraph device.MethodsHealthy adults (n = 24) completed two 14-day measurement periods while wearing an ActiGraph accelerometer on the non-dominant wrist. During each period, criterion values of EI were determined based on ΔES measured by dual X-ray absorptiometry and EE measured by doubly labeled water. A total of 11 prediction methods were tested, 8 derived from the accelerometer and 3 from non-accelerometry methods (e.g., diet recall; included for comparison). Group-level validity was assessed through mean bias, while individual-level validity was assessed through mean absolute error, mean absolute percentage error, and Bland–Altman analysis.ResultsMean bias for the three best accelerometry-based methods ranged from -167 to 124 kcal/day, versus -104 to 134 kcal/day for the non-accelerometry-based methods. The same three accelerometry-based methods had mean absolute error of 323–362 kcal/day and mean absolute percentage error of 18.1-19.3%, versus 353–464 kcal/day and 19.5-24.4% for the non-accelerometry-based methods. All 11 methods demonstrated systematic bias in the Bland–Altman analysis.ConclusionsAccelerometry-based intake-balance methods have promise for advancing EI assessment, but ongoing refinement is necessary. We provide an R package to facilitate implementation and refinement of accelerometry-based methods in future research (see paulhibbing.com/IntakeBalance).
Predictive ability of the Desire to Avoid Pregnancy scale
Authors: Hall Jennifer A. , Barrett Geraldine , Stephenson Judith , Rocca Corinne H. , Edelman Natalie 
Published: September 2023

Abstract
Background
A longstanding gap in the reproductive health field has been the availability of a screening instrument that can reliably predict a person’s likelihood of becoming pregnant. The Desire to Avoid Pregnancy Scale is a new measure; understanding its sensitivity and specificity as a screening tool for pregnancy as well as its predictive ability and how this varies by socio-demographic factors is important to inform its implementation.

Methods
This analysis was conducted on a cohort of 994 non-pregnant participants recruited in October 2018 and followed up for one year. The cohort was recruited using social media as well as advertisements in a university, school, abortion clinic and outreach sexual health service. Almost 90% of eligible participants completed follow-up at 12 months; those lost to follow-up were not significantly different on key socio-demographic factors. We used baseline DAP score and a binary variable of whether participants experienced pregnancy during the study to assess the sensitivity, specificity, area under the ROC curve (AUROC) and positive and negative predictive values (PPV and NPV) of the DAP at a range of cut-points. We also examined how the predictive ability of the DAP varied according to socio-demographic factors and by the time frame considered (e.g., pregnancy within 3, 6, 9 and 12 months).

Results
At a cut-point of 2 on the 0–4 range of the DAP scale, the DAP had a sensitivity of 0.78, a specificity of 0.81 and an excellent AUROC of 0.87. In this sample the cumulative incidence of pregnancy was 16% (95%CI 13%, 18%) making the PPV 43% and the NPV 95% at this cut-point. The DAP score was the factor most strongly associated with pregnancy, even after age and number of children were taken into account. The association between baseline DAP score and pregnancy did not differ across time frames.

Conclusions
This is the first study to assess the DAP scale as a screening tool and shows that its predictive ability is superior to the limited pre-existing pregnancy prediction tools. Based on our findings, the DAP could be used with a cut-point selected according to the purpose.
Supraclavicular nerve sparing versus sacrifice during open reduction internal fixation of acute midshaft clavicle fracture
Authors: Hu Ruei , Su Yu-Jung , Chien Chi-Sheng 
Published: September 2023

Abstract
Background
The branches of the supraclavicular nerve are often sacrificed during open reduction and internal fixation (ORIF) for clavicle fracture. No consensus exists on whether the supraclavicular nerve should be routinely identified and protected during ORIF.

Methods
We developed a simple method to make nerve sparing easier; Wide-Awake Local Anesthesia No Tourniquet (WALANT) solution is locally injected prior to the surgical incision being made. This retrospective study enrolled 340 patients and divided them into supraclavicular-nerve-sparing (n = 45) and supraclavicular-nerve-sacrifice (n = 295) groups. Surgical outcomes—including operative time, estimated blood loss, postoperative pain, union rate, time to union, functional score, paresthesia, complications, implant removal rate, and complication rate—were recorded.

Results
Incisional or anterior chest wall numbness and intraoperative blood loss were significantly less (p < 0.001) in the nerve-sparing group. The operative time was similar in the two groups. No significant differences were discovered in QuickDASH score, postoperative pain score, union rate, time to union, implant removal rate, complication rate, or revision rate.

Conclusions
Our study demonstrated that the outcomes of supraclavicular nerve sparing during ORIF with WALANT can reduce postoperative incisional and anterior chest wall numbness and intraoperative blood loss without increasing the operative time or complication rate.
Ginsenosides: changing the basic hallmarks of cancer cells to achieve the purpose of treating breast cancer
Authors: Jiang Rui-yuan , Fang Zi-ru , Zhang Huan-ping , Xu Jun-yao , Zhu Jia-yu , Chen Ke-yu , Wang Wei , Jiang Xiao , Wang Xiao-jia 
Published: September 2023

AbstractIn 2021, breast cancer accounted for a substantial proportion of cancer cases and represented the second leading cause of cancer deaths among women worldwide. Although tumor cells originate from normal cells in the human body, they possess distinct biological characteristics resulting from changes in gene structure and function of cancer cells in contrast with normal cells. These distinguishing features, known as hallmarks of cancer cells, differ from those of normal cells. The hallmarks primarily include high metabolic activity, mitochondrial dysfunction, and resistance to cell death. Current evidence suggests that the fundamental hallmarks of tumor cells affect the tissue structure, function, and metabolism of tumor cells and their internal and external environment. Therefore, these fundamental hallmarks of tumor cells enable tumor cells to proliferate, invade and avoid apoptosis. Modifying these hallmarks of tumor cells represents a new and potentially promising approach to tumor treatment. The key to breast cancer treatment lies in identifying the optimal therapeutic agent with minimal toxicity to normal cells, considering the specific types of tumor cells in patients. Some herbal medicines contain active ingredients which can precisely achieve this purpose. In this review, we introduce Ginsenoside's mechanism and research significance in achieving the therapeutic effect of breast cancer by changing the functional hallmarks of tumor cells, providing a new perspective for the potential application of Ginsenoside as a therapeutic drug for breast cancer.
Efficient targeting of HIF-1α mediated by YC-1 and PX-12 encapsulated niosomes: potential application in colon cancer therapy
Authors: Bakand Azar , Moghaddam Sevil Vaghefi , Naseroleslami Maryam , André Helder , Mousavi-Niri Neda , Alizadeh Effat 
Published: September 2023

AbstractA number of molecular biofactors have been documented in pathogenesis and poor prognosis of colorectal cancer (CRC). Among them, the Hypoxia-Inducible Factor (HIF-1a) is frequently reported to become over-expressed, and its targeting could restrict and control a variety of essential hallmarks of CRC. Niosomes are innovative drug delivery vehicles with the encapsulating capacity for co-loading both hydrophilic and hydrophobic drugs at the same time. Also, they can enhance the local accumulation while minimizing the dose and side effects of drugs. YC-1 and PX-12 are two inhibitors of HIF-1a. The purpose of this work was to synthesize dual-loaded YC-1 and PX-12 niosomes to efficiently target HIF-1α in CRC, HT-29 cells. The niosomes were prepared by the thin-film hydration method, then the niosomal formulation of YC-1 and PX-12 (NIO/PX-YC) was developed and optimized by the central composition method (CCD) using the Box-Behnken design in terms of size, polydispersity index (PDI), entrapment efficiency (EE). Also, they are characterized by DLS, FESEM, and TEM microscopy, as well as FTIR spectroscopy. Additionally, entrapment efficiency, in vitro drug release kinetics, and stability were assessed. Cytotoxicity, apoptosis, and cell cycle studies were performed after the treatment of HT-29 cells with NIO/PX-YC. The expression of HIF-1αat both mRNA and protein levels were studied after NIO/PX-YC treatment. The prepared NIO/PX-YC showed a mean particle size of 185 nm with a zeta potential of about-7.10 mv and a spherical morphology. Also, PX-12 and YC-1 represented the entrapment efficiency of about %78 and %91, respectively, with a sustainable and controllable release. The greater effect of NIO/PX-YC than the free state of PX-YC on the cell survival rate, cell apoptosis, and HIF-1α gene/protein expression were detected (p < 0.05). In conclusion, dual loading of niosomes with YC-1 and PX-12 enhanced the effect of drugs on HIF-1α inhibition, thus boosting their anticancer effects.
Graphical Abstract
Endoscopic ultrasonography-guided gastroenterostomy versus surgical gastrojejunostomy for palliation of malignant gastric outlet obstruction (ENDURO): study protocol for a randomized controlled trial
Authors: Kastelijn Janine B. , van de Pavert Yorick L. , Besselink Marc G. , Fockens Paul , Voermans Rogier P. , van Wanrooij Roy L. J. , de Wijkerslooth Thomas R. , Curvers Wouter L. , de Hingh Ignace H. J. T. , Bruno Marco J. , Koerkamp Bas Groot , Patijn Gijs A. , Poen Alexander C. , van Hooft Jeanin E. , Inderson Akin , Mieog J. Sven D. , Poley Jan-Werner , Bijlsma Alderina , Lips Daan J. , Venneman Niels G. , Verdonk Robert C. , van Dullemen Hendrik M. , Hoogwater Frederik J. H. , Frederix Geert W. J. , Molenaar I. Quintus , Welsing Paco M. J. , Moons Leon M. G. , van Santvoort Hjalmar C. , Vleggaar Frank P. ,   for the Dutch Pancreatic Cancer Group
Published: September 2023

Abstract
Background
Malignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs.

Methods
The ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs.

Discussion
The ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting.

Trial registration
International Clinical Trials Registry Platform (ICTRP): NL9592. Registered on 07 July 2021.
SND1 aggravates mitochondrial damage, apoptosis and extracellular matrix degradation in IL-1β-stimulated chondrocytes via PINK1/BECN1 pathway
Authors: Lin Shufeng , Guo Huiyang , You Xiaoxuan , Zhang Zefeng , Ye Hui 
Published: September 2023

AbstractRecently, evidence has suggested a regulatory role for SND1 in osteoarthritis progression. Interestingly, we found that SND1 protein expression was increased, mitochondria were shrunken and decreased in number, mitochondrial membrane potential was decreased, mitochondrial ROS production was increased, and ATP levels were decreased in IL-1β treated mouse chondrocytes, and SND1 silencing removed these changes. Furthermore, IL-1β treatment promoted inflammatory factor secretion in chondrocytes, promoted cell apoptosis, increased MMP13 protein and inhibited collagen II protein expression, and si-SND1 inhibited the IL-1β effects. We validated the association between SND1 and PINK1 and found that PINK1 reversed the inhibitory effects of SND1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation in mouse chondrocytes. Furthermore, we found that PINK1 upregulated BECN1 protein expression and that BECN reversed the inhibitory effects of PINK1 silencing on IL-1β-induced mitochondrial damage, inflammatory reaction, apoptosis and extracellular matrix degradation. Further mechanistic studies revealed that PINK1 inhibited the AMPK/mTOR signaling axis to aggravate IL-1β induced mouse chondrocytes injury by upregulating BECN1 protein expression. In vivo results showed that the damage to cartilage tissue was significantly alleviated in rats with osteoarthritis by knocking down SND1 expression.
Gender gap in STEM pathways: the role of secondary curricula in a highly differentiated school system—the case of Chile
Authors: Sevilla María Paola , Luengo-Aravena Daniela , Farías Mauricio 
Published: September 2023

AbstractBackgroundSTEM fields are instrumental in increasing the technological and innovative capacity of the economy. As women are underrepresented in the STEM workforce, diverse strategies have been implemented to boost their preparedness and interest in these fields, including early exposure to academic and vocational STEM courses. Using the case of Chile’s highly differentiated school system, this paper examines the role of secondary curricula on students’ enrollment and persistence in STEM programs offered by vocational postsecondary institutions and universities. In doing so, we seek to identify whether exposure to STEM courses within the academic or vocational tracks translates into fewer gender differences in STEM higher education.ResultsOur results reveal that upper-secondary tracks connected to STEM courses are positively associated with enrollment in STEM higher education and, to some degree, persistence. More specifically, exposure to STEM courses in the academic track is the most effective path to boost chances of enrolling in STEM university programs but has no connection to later persistence. In contrast, applied STEM courses within the vocational tracks perform better in the case of STEM programs in postsecondary vocational institutions both in enrollment and persistence. However, this STEM pipeline significantly amplifies gender gaps as males benefit more than women from early exposure to applied STEM courses. We also found that other indirect routes, such as enrolling in STEM university programs from the vocational track with applied STEM courses, boost female participation in these programs, helping reduce gender gaps.ConclusionsWhile secondary STEM courses attract more female students to STEM higher education, they alone are insufficient to achieve gender equality in STEM fields as gender gaps widen in the more effective routes. In highly differentiated school systems, policymakers and high school leaders should offer increased support to women interested in STEM studies and careers across all secondary tracks to boost female participation in STEM fields. At the same time, all high school students should be able to select both academic and applied STEM courses as a part of their non-mandatory curriculum.