bluuebunny/crossref_metadata_2025 huggingface dataset:
No improvement in AUDIT-C screening and brief intervention rates among wait-list controls following support of Aboriginal Community Controlled Health Services: evidence from a cluster randomised trial
Authors: Conigrave James H. , Lee K. S. Kylie , Dobbins Timothy , Wilson Scott , Padarian José , Ivers Rowena , Morley Kirsten , Haber Paul S. , Vnuk Julia , Marshall Kushani , Conigrave Kate
Published: July 2024

Background

While Aboriginal and Torres Strait Islander Australians are less likely to drink any alcohol than other Australians, those who drink are more likely to experience adverse alcohol-related health consequences. In a previous study, providing Aboriginal Community Controlled Health Services (ACCHSs) with training and support increased the odds of clients receiving AUDIT-C alcohol screening. A follow-up study found that these results were maintained for at least two years, but there was large variability in the effectiveness of the intervention between services. In this study, we use services that previously received support as a comparison group to test whether training and support can improve alcohol screening and brief intervention rates among wait-list control ACCHSs.

Methods

Design: Cluster randomised trial using routinely collected health data. Setting: Australia. Cases: Twenty-two ACCHSs that see at least 1000 clients a year and use Communicare as their practice management software. Intervention and comparator: After initiating support, we compare changes in screening and brief intervention between wait-list control services and services that had previously received support. Measurement: Records of AUDIT-C screening and brief intervention activity in routinely collected data.

Results

During the reference period we observed 357,257 instances where one of 74,568 clients attended services at least once during a two-monthly data extraction period. Following the start of support, the odds of screening (OR = 0.94 [95% CI 0.67, 1.32], p = 0.74, $$B{F}_{10}$$$$\approx$$ 0.002) and brief intervention (OR = 1.43 [95% CI 0.69, 2.95], p = 0.34, $$B{F}_{10}$$$$\approx$$ 0.002) did not improve for the wait-list control group, relative to comparison services.

Conclusions

We did not replicate the finding that support and training improves AUDIT-C screening rates with wait-list control data. The benefits of support are likely context dependent. Coincidental policy changes may have sensitised services to the effects of support in the earlier phase of the study. Then the COVID-19 pandemic may have made services less open to change in this latest phase. Future efforts could include practice software prompts to alcohol screening and brief intervention, which are less reliant on individual staff time or resources.

Trial registration

Retrospectively registered on 2018-11-21: ACTRN12618001892202.
Assessing farmers’ willingness to pay for FMD vaccines and factors influencing payment: a contingent valuation study in central Oromia, Ethiopia
Authors: Layessa Misgana Lemi , Gebremedhin Endrias Zewdu , Sarba Edilu Jorga , Bune Wakuma Mitiku
Published: July 2024

Background

Foot and mouth disease is a contagious, transboundary, and economically devastating viral disease of cloven-hoofed animals. The disease can cause many consequences, including decreased productivity, limited market access, and elimination of flocks or herds. This study aimed to assess farmers’ willingness to pay (WTP) for foot and mouth disease (FMD) vaccines and identify factors influencing their WTP. A cross-sectional questionnaire survey was conducted on 396 randomly selected livestock-owning farmers from three districts in the central Oromia region (Ambo, Dendi, and Holeta districts. The study utilized the contingent valuation method, specifically employing dichotomous choice bids with double bounds, to evaluate the willingness to pay (WTP) for the FMD vaccine. Mean WTP was assessed using interval regression, and influential factors were identified.

Results

The study revealed that the farmer’s mean willingness to pay for a hypothetical foot and mouth disease vaccine was 37.5 Ethiopian Birr (ETB) [95% confidence interval [CI]: 34.5 40.58] in all data, while it was 23.84 (95% CI: 21.47–26.28) in the mixed farming system and 64.87 Ethiopian Birr (95% CI: 58.68 71.15) in the market-oriented farming system. We identified main livelihood, management system, sales income, breed, keeping animals for profit, and foot and mouth disease impact perception score as significant variables (p ≤ 0.05) determining the farmers’ WTP for the FMD vaccine.

Conclusion

Farmers demonstrated a high computed willingness to pay, which can be considered an advantage in the foot and mouth disease vaccination program in central Oromia. Therefore, it is necessary to ensure sufficient vaccine supply services to meet the high demand revealed.
Intracellular domain of epithelial cell adhesion molecule induces Wnt receptor transcription to promote colorectal cancer progression
Authors: Panda Sushree Shankar , Lee Chi-Chiu , Geevimaan Khamushavalli , Chen Kai-Chi , Yang Shung-Haur , Shen Chia-Ning , HuangFu Wei-Chun , Wu Han-Chung
Published: July 2024

Background

Epithelial cell adhesion molecule (EpCAM) has been widely studied as a tumor antigen due to its expression in varieties of solid tumors. Moreover, the glycoprotein contributes to critical cancer-associated cellular functionalities via its extracellular (EpEX) and intracellular (EpICD) domains. In colorectal cancer (CRC), EpCAM has been implicated in the Wnt signaling pathway, as EpICD and β-Catenin are coordinately translocated to the nucleus. Once in the nucleus, EpICD transcriptionally regulates EpCAM target genes that; however, remains unclear whether Wnt signaling is modulated by EpICD activity.

Methods

Patient-derived organoids (PDOs), patient-derived xenografts (PDXs), and various CRC cell lines were used to study the roles of EpCAM and EpICD in Wnt receptor expression. Fluorescence and confocal microscopy were used to analyze tumors isolated from PDX and other xenograft models as well as CRC cell lines. EpCAM signaling was intervened with our humanized form of EpCAM neutralizing antibody, hEpAb2-6. Wnt receptor promoters under luciferase reporters were constructed to examine the effects of EpICD. Luciferase reporter assays were performed to evaluate promoter, γ-secretase and Wnt activity. Functional assays including in vivo tumor formation, organoid formation, spheroid and colony formation experiments were performed to study Wnt related phenomena. The therapeutic potential of EpCAM suppression by hEpAb2-6 was evaluated in xenograft and orthotopic models of human CRC.

Results

EpICD interacted with the promoters of Wnt receptors (FZD6 and LRP5/6) thus upregulated their transcriptional activity inducing Wnt signaling. Furthermore, activation of Wnt-pathway-associated kinases in the β-Catenin destruction complex (GSK3β and CK1) induced γ-secretase activity to augment EpICD shedding, establishing a positive-feedback loop. Our hEpAb2-6 antibody blocked EpICD-mediated upregulation of Wnt receptor expressions and conferred therapeutic benefits in both PDX and orthotopic models of human CRC.

Conclusions

This study uncovers relevant functions of EpCAM where Wnt receptors are upregulated via the transcriptional co-factor activity of EpICD. The resultant enhancement of Wnt signaling induces γ-secretase activity further stimulating EpICD cleavage and its nuclear translocation. Our humanized anti-EpCAM antibody hEpAb2-6 blocks these mechanisms and may thereby provide therapeutic benefit in CRC.
Effect of noninvasive ventilation on mortality and clinical outcomes among patients with severe hypoxemic COVID-19 pneumonia after high-flow nasal oxygen failure: a multicenter retrospective French cohort with propensity score analysis
Authors: Goury Antoine , Houlla Zeyneb , Jozwiak Mathieu , Urbina Tomas , Turpin Matthieu , Lavalard Alexandra , Laghlam Driss , Voicu Sebastian , Rosman Jeremy , Coutureau Claire , Mourvillier Bruno
Published: July 2024

Background

We assessed the effect of noninvasive ventilation (NIV) on mortality and length of stay after high flow nasal oxygenation (HFNO) failure among patients with severe hypoxemic COVID-19 pneumonia.

Methods

In this multicenter, retrospective study, we enrolled COVID-19 patients admitted in intensive care unit (ICU) for severe COVID-19 pneumonia with a HFNO failure from December 2020 to January 2022. The primary outcome was to compare the 90-day mortality between patients who required a straight intubation after HFNO failure and patients who received NIV after HFNO failure. Secondary outcomes included ICU and hospital length of stay. A propensity score analysis was performed to control for confounding factors between groups. Exploratory outcomes included a subgroup analysis for 90-day mortality.

Results

We included 461 patients with HFNO failure in the analysis, 233 patients in the straight intubation group and 228 in the NIV group. The 90-day mortality did not significantly differ between groups, 58/228 (25.4%) int the NIV group compared with 59/233 (25.3%) in the straight intubation group, with an adjusted hazard ratio (HR) after propensity score weighting of 0.82 [95%CI, 0.50–1.35] (p = 0.434). ICU length of stay was significantly shorter in the NIV group compared to the straight intubation group, 10.0 days [IQR, 7.0-19.8] versus 18.0 days [IQR,11.0–31.0] with a propensity score weighted HR of 1.77 [95%CI, 1.29–2.43] (p < 0.001). A subgroup analysis showed a significant increase in mortality rate for intubated patients in the NIV group with 56/122 (45.9%), compared to 59/233 (25.3%) for patients in the straight intubation group (p < 0.001).

Conclusions

In severely hypoxemic COVID-19 patients, no significant differences were observed on 90-day mortality between patients receiving straight intubation and those receiving NIV after HFNO failure. NIV strategy was associated with a significant reduction in ICU length of stay, despite an increase in mortality in the subgroup of patients finally intubated.
The relationship and clinical significance of lactylation modification in digestive system tumors
Authors: Wang Gang , Zou Xiaosu , Chen Qicong , Nong Wenqian , Miao Weiwei , Luo Honglin , Qu Shenhong
Published: July 2024

Lactylation, an emerging post-translational modification, plays a pivotal role in the initiation and progression of digestive system tumors. This study presents a comprehensive review of lactylation in digestive system tumors, underscoring its critical involvement in tumor development and progression. By focusing on metabolic reprogramming, modulation of the tumor microenvironment, and the molecular mechanisms regulating tumor progression, the potential of targeting lactylation as a therapeutic strategy is highlighted. The research reveals that lactylation participates in gene expression regulation and cell signaling by affecting the post-translational states of histones and non-histone proteins, thereby influencing metabolic pathways and immune evasion mechanisms in tumor cells. Furthermore, this study assesses the feasibility of lactylation as a therapeutic target, providing insights for clinical treatment of gastrointestinal cancers. Future research should concentrate on elucidating the mechanisms of lactylation, developing efficient lactylation inhibitors, and validating their therapeutic efficacy in clinical trials, which could transform current cancer treatment and immunotherapy approaches. In summary, this review emphasizes the crucial role of lactylation in tumorigenesis and progression through a detailed analysis of its molecular mechanisms and clinical significance.
Lower energy intake associated with higher risk of cardiovascular mortality in chronic kidney disease patients on a low-protein diets
Authors: Liu Yao , Deng Fei , Zhou Ping , Peng Cong , Xie ChunPeng , Gao Wuyu , Yang Qianyu , Wu Tingyu , Xiao Xiang
Published: July 2024

Objective

An increasing number of studies shown that inadequate energy intake causes an increase in adverse incidents in chronic kidney disease (CKD) patients on low-protein diets (LPD). The study aimed to investigate the relationship between energy intake and cardiovascular mortality in CKD patients on a LPD.

Methods

This was a cross-sectional study, a total of 4264 CKD patients were enrolled from the NHANES database between 2009 and 2018. Restricted cubic spline plots and Cox regression analysis were used to analyze the association between energy intake and cardiovascular mortality in CKD patients on a LPD. Additionally, a nomogram was constructed to estimate cardiovascular survival in CKD patients on a LPD.

Results

Among CKD patients on a LPD in the United States, 90.05% had an energy intake of less than 25 kcal/kg/day, compared to 36.94% in CKD patients on a non-LPD. Energy intake and cardiovascular mortality showed a linear relationship in CKD patients on a LPD, while a ‘U-shaped’ relationship was observed in CKD patients on a non-LPD. Multifactorial Cox regression models revealed that for Per-standard deviation (Per-SD) decrement in energy intake, the risk of cardiovascular mortality increased by 41% (HR: 1.41, 95% CI: 1.12, 1.77; P = 0.004) in CKD patients on a LPD. The concordance index of the nomogram was 0.79 (95% CI, 0.75, 0.83).

Conclusion

CKD patients, especially those on a LPD, have significantly inadequate energy intake. Lower energy intake is associated with higher cardiovascular mortality in CKD patients on a LPD.
Unveiling the PDK4-centered rituximab-resistant mechanism in DLBCL: the potential of the “Smart” exosome nanoparticle therapy
Authors: Wu Xin , Ban Chunmei , Deng Woding , Bao Xuewei , Tang Ning , Wu Yupeng , Deng Zhixuan , Xiong Jianbin , Zhao Qiangqiang
Published: July 2024

Background

Diffuse large B-cell lymphoma (DLBCL) represents a prevalent malignant tumor, with approximately 40% of patients encountering treatment challenges or relapse attributed to rituximab resistance, primarily due to diminished or absent CD20 expression. Our prior research identified PDK4 as a key driver of rituximab resistance through its negative regulation of CD20 expression. Further investigation into PDK4’s resistance mechanism and the development of advanced exosome nanoparticle complexes may unveil novel resistance targets and pave the way for innovative, effective treatment modalities for DLBCL.

Methods

We utilized a DLBCL-resistant cell line with high PDK4 expression (SU-DHL-2/R). We infected it with short hairpin RNA (shRNA) lentivirus for RNA sequencing, aiming to identify significantly downregulated mRNA in resistant cells. Techniques including immunofluorescence, immunohistochemistry, and Western blotting were employed to determine PDK4’s localization and expression in resistant cells and its regulatory role in phosphorylation of Histone deacetylase 8 (HDAC8). Furthermore, we engineered advanced exosome nanoparticle complexes, aCD20@ExoCTX/siPDK4, through cellular, genetic, and chemical engineering methods. These nanoparticles underwent characterization via Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM), and their cellular uptake was assessed through flow cytometry. We evaluated the nanoparticles’ effects on apoptosis in DLBCL-resistant cells and immune cells using CCK-8 assays and flow cytometry. Additionally, their capacity to counteract resistance and exert anti-tumor effects was tested in a resistant DLBCL mouse model.

Results

We found that PDK4 initiates HDAC8 activation by phosphorylating the Ser-39 site, suppressing CD20 protein expression through deacetylation. The aCD20@ExoCTX/siPDK4 nanoparticles served as effective intracellular delivery mechanisms for gene therapy and monoclonal antibodies, simultaneously inducing apoptosis in resistant DLBCL cells and triggering immunogenic cell death in tumor cells. This dual action effectively reversed the immunosuppressive tumor microenvironment, showcasing a synergistic therapeutic effect in a subcutaneous mouse tumor resistance model.

Conclusions

This study demonstrates that PDK4 contributes to rituximab resistance in DLBCL by modulating CD20 expression via HDAC8 phosphorylation. The designed exosome nanoparticles effectively overcome this resistance by targeting the PDK4/HDAC8/CD20 pathway, representing a promising approach for drug delivery and treating patients with Rituximab-resistant DLBCL.
Moving from idea to reality: The barriers and enablers to implementing Child and Family Hubs policy into practice in NSW, Australia
Authors: Calik Anna , Liu Huei Ming , Montgomery Alicia , Honisett Suzy , Van Munster Kerri-Anne , Morris Tamara , Eapen Valsamma , Goldfeld Sharon , Hiscock Harriet , Eastwood John , Woolfenden Susan
Published: July 2024

Background

Adverse childhood experiences can impact physical and mental health throughout the lifespan. To support families experiencing adversity and improve child health and developmental equity, an integrated, multi-sector response is required. Child and Family Hubs (Hubs) are a feasible and acceptable approach to providing such a response. In the Australian context, a number of federal and New South Wales (NSW) state policies support an integrated, multi-sector response using Hubs to support families experiencing adversity. This study examined NSW policy stakeholder and health service manager perspectives on the barriers and enablers to translating policy into practice in the implementation of Child and Family Hubs.

Methods

Semi-structured interviews were conducted with 11 NSW government policy stakeholders and 13 community health service managers working in child and family policy and planning or child and family community-based services. Interviews were of 30–60 min duration and explored stakeholder knowledge, perspectives and experiences around childhood adversity, and barriers and enablers to operationalizing policies supporting Hubs. Analysis of barriers and facilitators to implementation of Hub models of care was undertaken using the Consolidated Framework for Implementation Research (CFIR).

Results

Key barriers that emerged included short-term and inconsistent funding, lack of resourcing for a Hub co-ordinator, limited support for evaluation and insufficient time to plan for Hub implementation. Key enablers included flexibility and adaptability of Hub models to meet local needs, formal change management processes, strong governance structures and engagement among Hub practitioners. Key insights included the importance of targeted strategies to support sustained individual practice change and the need for organization-wide commitment to enable the successful adoption and maintenance of the Hub model of care.

Conclusions

This study provides valuable insights and contributes evidence around what is needed to strengthen and support the operationalization and scalability of the Hub model of care. Key recommendations for Hub practitioners include the importance of formal change management processes and establishment of strong governance structures, while key recommendations for policymakers include the need for sustainable Hub funding and a standardized, evidence-based framework to support Hub implementation and evaluation.
Capturing the HIV-related social exclusion practices experienced by key populations through photovoice: an interpretative phenomenological study
Authors: Kamila Ami , Widyawati Widyawati , Hasanbasri Mubasysyir , Hakimi Mohammad
Published: July 2024

Background

Key populations are defined as groups that are susceptible to HIV, including Men Sex with Men (MSM), Transgender (TG), Persons who Inject Drug (PID), and Female Sex Worker (FSW). These key populations groups are among the fastest-growing populations in Indonesia. These vulnerable groups are ostracized by society and health services, which makes it difficult to get treatment. This project was carried out to investigate the different experiences and perspectives of these key populations in facing and addressing social and spiritual exclusion.

Methods

A qualitative phenomenological study using photovoice was carried out from July to December 2022. Key populations comprising MSM, TG, PID, and FSW were recruited from community-based peer groups in West Bandung Regency using snowball sampling. This was followed by the Photovoice stages, from workshops to focus group discussions and interviews with audio recordings. Furthermore, thematic data analysis was carried out by interpretative participant narratives and photographs supported by Atlas.ti software.

Result

Eighteen participants comprising four MSM, five TG, four PIDs, and five FSWs participated in this research. Among these eighteen participants, six were HIV-negative, including 3 PIDs and 3 FSWs, while the remaining were positive. The analysis of the collected data identified four main themes: 1) limited access like unequal treatment, disadvantage, and harassment, 2) social and spiritual impact, 3) coping mechanisms, and 4) self-reflection through photovoice. These results showed that social exclusion occurred in an environment where community values, beliefs, and norms dehumanised these key populations, and where removal of support and care was prominent. Despite these challenges, participant resilience was evidenced by using internal resources and peer support as coping mechanisms. The participants considered photovoice as a tool to foster self-confidence and self-awareness through a reflective process.

Conclusions

The findings of this study highlight the emphasis on participants' openness in sharing their experiences, which can build empathy and promote a more inclusive community in HIV prevention efforts. This research findings can be used to inform HIV policy and practice and inclusion of these key populations in the community. We advocate making the photovoice efforts accessible to a wider audience through exhibitions and various media.
The tumor-stroma ratio in giant cell tumor of bone: associations with the immune microenvironment and responsiveness to denosumab treatment
Authors: Wu Hai-Lin , Wang Xiao-Bin , Li Jing , Zheng Bo-Wen
Published: July 2024

Background

Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness.

Methods

We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness.

Results

Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS.

Conclusion

The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.
Pneumonectomy following penetrating trauma with ECMO as postoperative support: case report – (Lung trauma and ECMO)
Authors: Sánchez-Ortiz Álvaro Ignacio , Peña-González Diego , García Alberto F. , Bautista-Rincón Diego Fernando , García-González Carlos Alejandro , Moreno-Angarita Alejandro , Álvarez-Ortega Astrid Carolina , Torres-España Nicolas Felipe , Cadavid-Alvear Eduardo Alberto , Velásquez-Galvis Mauricio
Published: July 2024

Background

Penetrating thoracic injuries have a significant risk of morbi-mortality. Despite the advancements in damage control methods, a subset of patients with severe pulmonary vascular lesions and bronchial injuries persists. In some of these cases, post-traumatic pneumonectomy is required, and perioperative extracorporeal membrane oxygenation (ECMO) support may be required due to right ventricular failure and respiratory failure.

Case description

A male was brought to the emergency department (ED) with a penetrating thoracic injury, presenting with massive right hemothorax and active bleeding that required ligation of the right pulmonary hilum to control the bleeding. Subsequently, he developed right ventricular dysfunction and ARDS, necessitating a dynamic hybrid ECMO configuration to support his condition and facilitate recovery.

Conclusions

Penetrating thoracic injuries with severe pulmonary vascular lesions may need pneumonectomy to control bleeding. ECMO support reduces the associated mortality by decreasing the complications rate. A multidisciplinary team is essential to achieve good outcomes in severe compromised patients.
Deciphering the benefits and intensity levels of primary metabolites from Allium macrostemon Bunge and Allium chinense G. Don
Authors: Qin Zifei , Li Yuan , Liu Dongmei , Hua Yuzhuo , Lv Yuandong , Zhang Xiaojian , Fan Cailian , Yang Jing
Published: July 2024

Background

Allii Macrostemonis Bulbus is also named Xiebai in China. It is an edible vegetable, and also a famous herb for treating coronary heart disease. Allium chinense G. Don (ACGD) and Allium macrostemon Bunge (AMB) are it botanical sources. The aim of this study was to explore the cardioprotective effects, and decipher the visual spatial distribution and absolute content of primary metabolites derived from these two herbs.

Methods

H9c2 cells were used to perform the hypoxia-reoxygenation (H/R)-induced myocardial injury model. Their protective effects were evaluated by apoptosis levels. Furthermore, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry imaging approach (MALDI-TOF MSI) was carried out to present the spatial location of primary metabolites including fatty acids, amino acids, carotenoids, and vitamins in these two Allium herbs. Multiple analytical methods were applied to perform quantitative analysis of these primary metabolites in AMB and ACGD bulbs by liquid chromatography tandem mass spectrometry (LC–MS).

Results

First, AMB and ACGD extracts both could increase the cell viability in H9c2 cells, and attenuate H/R-induced injury. They markedly decreased apoptosis, accompanied by activating the BCL-2/BAX pathway. Further, MALDI-TOF MSI-based relative quantification results showed several amino acids, fatty acids, carotenoids, and vitamins were largely rich in the tunics and outside scales of fresh bulbs, while some primary metabolites were abundant in their developing flower buds. Absolute quantification results displayed total contents of amino acids in ACGD bulbs were higher than those in AMB, while total contents of fatty acids and vitamins provides opposite trends in these two Allium herbs. The total contents of carotenoids and trace elements showed no significant differences between AMB and ACGD samples.

Conclusions

This study would be helpful to understand the myocardial injury protection effects of these two Allium herbs, and the spatial accumulation and quantitative content levels of their main nutrients.

Graphical Abstract
A horizontal and perpendicular interlaminar approach for intrathecal nusinersen injection in patients with spinal muscular atrophy and scoliosis: an observational study
Authors: Huang Chanyan , Zhang Yuanjia , Diedrich Daniel A. , Li Jiawen , Luo Wei , Zhao Xu , Guo Yuting , Luo Yijun , Zhang Tao , Wang Xuan , Huang Wenqi , Xiao Ying
Published: July 2024

Background

Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture.

Methods

Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed.

Results

Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture.

Conclusions

The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.
Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial
Authors: Capion Tenna , Lilja-Cyron Alexander , Juhler Marianne , Møller Kirsten , Sorteberg Angelika , Rønning Pål André , Poulsen Frantz Rom , Wismann Joakim , Schack Anders Emil , Ravlo Celina , Isaksen Jørgen , Lindschou Jane , Gluud Christian , Mathiesen Tiit , Olsen Markus Harboe
Published: July 2024

Background

Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections.

Methods

DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts.

Conclusion

We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility.

Trial registration

ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.
Prenatal affective cognitive training to reduce the risk of postpartum depression (PACT): study protocol for a randomized controlled trial
Authors: Bjertrup Anne J. , Kofoed Jeanne , Egmose Ida , Wendelboe Katrine , Southgate Victoria , Væver Mette S. , Miskowiak Kamilla W.
Published: July 2024

Background

Postpartum depression (PPD) affects 30–50% of women with a history of previous depression or bipolar disorder and 8% of women with no history of depression. Negative cognitive biases in the perception of infant cues and difficulties with emotion regulation are replicated risk factors. Current interventions focus on detecting and treating rather than preventing PPD. The aim of this randomized controlled intervention trial is therefore to investigate the potential prophylactic effects of prenatal affective cognitive training for pregnant women at heightened risk of PPD.

Methods

The study will enrol a total of 292 pregnant women: 146 at high risk and 146 at low risk of PPD. Participants undergo comprehensive assessments of affective cognitive processing, clinical depressive symptoms, and complete questionnaires at baseline. Based on the responses, pregnant women will be categorized as either at high or low risk of PPD. High-risk participants will be randomized to either prenatal affective cognitive training (PACT) or care as usual (CAU) immediately after the baseline testing. The PACT intervention is based on emerging evidence for efficacy of affective cognitive training approaches in depression, including cognitive bias modification, attention bias modification, mindfulness-inspired emotion regulation exercises, and working memory training. Participants randomised to PACT will complete five individual computerised and virtual reality-based training sessions over 5 weeks. The primary outcome is the difference between intervention arms in the incidence of PPD, assessed with an interview 6 months after birth. We will also assess the severity of depressive symptoms, rated weekly online during the first 6 weeks postpartum.

Discussion

The results will have implications for future early prophylactic interventions for pregnant women at heightened risk of PPD. If the PACT intervention reduces the incidence of PPD, it can become a feasible, non-invasive prophylactic strategy during pregnancy, with positive mental health implications for these women and their children.

Trial registration

ClinicalTrials.gov NCT06046456 registered 21-09-2023, updated 08-07-2024.
The association between diet quality indices and oxidative stress biomarkers in male footballers and healthy active controls
Authors: Zare Mahsa , Shateri Zainab , Shakeri Mahboobeh , Nouri Mehran , Zare Sahar , Sarbakhsh Parvin , Eftekhari Mohammad Hassan , Gargari Bahram Pourghassem
Published: July 2024

Objective

The aim of the present study was the association between the relationship between Dietary Quality Index-International (DQI-I) and Healthy Eating Index (HEI) and the urinary levels of F2alpha-isoprostane (F2a-IP) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) was investigated as indicators of oxidative stress.

Results

Based on HEI (low, moderate, and good), the diet quality of both groups was classified as moderate. In all participants, HEI (β=-0.29; P = 0.04) and DQI-I (β=-0.46; P = 0.005) were inversely associated with 8-OHdG. Furthermore, a negative correlation was found between HEI (mean β=-3.53; P = 0.04) and DQI-I (mean β=-5.53; P = 0.004) with F2a-IP. The quality of the footballers’ diet was higher than that of the control group. Following a high-quality diet, which is rich in antioxidants, is likely to effectively reduce oxidative stress.
Sex-specific role of high-fat diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus
Authors: Shetty Sanutha , Duesman Samuel J. , Patel Sanil , Huynh Pacific , Toh Pamela , Shroff Sanjana , Das Anika , Chowhan Disha , Keller Benjamin , Alvarez Johana , Fisher-Foye Rachel , Sebra Robert , Beaumont Kristin , McAlpine Cameron S. , Rajbhandari Prashant , Rajbhandari Abha K.
Published: July 2024

Background

Scientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice.

Methods

To investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis.

Results

We observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress.

Conclusions

Overall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health.
Ualign: pushing the limit of template-free retrosynthesis prediction with unsupervised SMILES alignment
Authors: Zeng Kaipeng , Yang Bo , Zhao Xin , Zhang Yu , Nie Fan , Yang Xiaokang , Jin Yaohui , Xu Yanyan
Published: July 2024

Motivation

Retrosynthesis planning poses a formidable challenge in the organic chemical industry, particularly in pharmaceuticals. Single-step retrosynthesis prediction, a crucial step in the planning process, has witnessed a surge in interest in recent years due to advancements in AI for science. Various deep learning-based methods have been proposed for this task in recent years, incorporating diverse levels of additional chemical knowledge dependency.

Results

This paper introduces UAlign, a template-free graph-to-sequence pipeline for retrosynthesis prediction. By combining graph neural networks and Transformers, our method can more effectively leverage the inherent graph structure of molecules. Based on the fact that the majority of molecule structures remain unchanged during a chemical reaction, we propose a simple yet effective SMILES alignment technique to facilitate the reuse of unchanged structures for reactant generation. Extensive experiments show that our method substantially outperforms state-of-the-art template-free and semi-template-based approaches. Importantly, our template-free method achieves effectiveness comparable to, or even surpasses, established powerful template-based methods.

Scientific contribution

We present a novel graph-to-sequence template-free retrosynthesis prediction pipeline that overcomes the limitations of Transformer-based methods in molecular representation learning and insufficient utilization of chemical information. We propose an unsupervised learning mechanism for establishing product-atom correspondence with reactant SMILES tokens, achieving even better results than supervised SMILES alignment methods. Extensive experiments demonstrate that UAlign significantly outperforms state-of-the-art template-free methods and rivals or surpasses template-based approaches, with up to 5% (top-5) and 5.4% (top-10) increased accuracy over the strongest baseline.
Fish Iridoviridae: infection, vaccination and immune response
Authors: Leiva-Rebollo Rocío , Labella Alejandro M. , Gémez-Mata Juan , Castro Dolores , Borrego Juan J.
Published: July 2024

Each year, due to climate change, an increasing number of new pathogens are being discovered and studied, leading to an increase in the number of known diseases affecting various fish species in different regions of the world. Viruses from the family Iridoviridae, which consist of the genera Megalocytivirus, Lymphocystivirus, and Ranavirus, cause epizootic outbreaks in farmed and wild, marine, and freshwater fish species (including ornamental fish). Diseases caused by fish viruses of the family Iridoviridae have a significant economic impact, especially in the aquaculture sector. Consequently, vaccines have been developed in recent decades, and their administration methods have improved. To date, various types of vaccines are available to control and prevent Iridoviridae infections in fish populations. Notably, two vaccines, specifically targeting Red Sea bream iridoviral disease and iridoviruses (formalin-killed vaccine and AQUAVAC® IridoV, respectively), are commercially available. In addition to exploring these themes, this review examines the immune responses in fish following viral infections or vaccination procedures. In general, the evasion mechanisms observed in iridovirus infections are characterised by a systemic absence of inflammatory responses and a reduction in the expression of genes associated with the adaptive immune response. Finally, this review also explores prophylactic procedure trends in fish vaccination strategies, focusing on future advances in the field.
Generation of musculoskeletal cells from human urine epithelium-derived presomitic mesoderm cells
Authors: Gao Huiru , Huang Xingnan , Cai Zepo , Cai Baomei , Wang Kaipeng , Li Junyang , Kuang Junqi , Wang Bo , Zhai Ziwei , Ming Jin , Cao Shangtao , Qin Yue , Pei Duanqing
Published: July 2024

Background

Numerous studies have shown that somite development is a necessary stage of myogenesis chondrogenesis and osteogenesis. Our previous study has established a stable presomitic mesoderm progenitor cell line (UiPSM) in vitro. Naturally, we wanted to explore whether UiPSM cell can develop bone and myogenic differentiation.

Results

Selective culture conditions yielded PAX3 and PAX7 positive skeletal muscle precursors from UiPSM cells. The skeletal muscle precursors undergo in vitro maturation resulting in myotube formation. MYOD effectively promoted the maturity of the skeletal myocytes in a short time. We found that UiPSM and MYOD mediated UiPSM cell-derived skeletal myocytes were viable after transplantation into the tibialis anterior muscle of MITRG mice, as assessed by bioluminescence imaging and scRNA-seq. Lack of teratoma formation and evidence of long-term myocytes engraftment suggests considerable potential for future therapeutic applications. Moreover, UiPSM cells can differentiate into osteoblast and chondroblast cells in vitro.

Conclusions

UiPSM differentiation has potential as a developmental model for musculoskeletal development research and treatment of musculoskeletal disorders.
Efficacy of iron supplementation on physical capacity in non-anaemic iron-deficient individuals: protocol for an individual patient data meta-analysis
Authors: Dugan Cory , Peeling Peter , Burden Richard , Richards Toby
Published: July 2024

Background

A deficiency in iron stores is associated with various adverse health complications, which, if left untreated, can progress to states of anaemia, whereby there is significant detriment to an individual’s work capacity and quality of life due to compromised erythropoiesis. The most common methods employed to treat an iron deficiency include oral iron supplementation and, in persistent and/or unresponsive cases, intravenous iron therapy. The efficacy of these treatments, particularly in states of iron deficiency without anaemia, is equivocal. Indeed, both randomised control trials and aggregate data meta-analyses have produced conflicting evidence. Therefore, this study aims to assess the efficacy of both oral and intravenous iron supplementation on physical capacity, quality of life, and fatigue scores in iron-deficient non-anaemic individuals using individual patient data (IPD) meta-analysis techniques.

Methods

All potential studies, irrespective of design, will be sourced through systematic searches on the following databases: Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, Web of Science: Science Citation Index Expanded, Web of Science: Conference Proceedings Citation Index-Science, ClinicalTrials.gov, and World Health Organization (WHO) International Clinical Trials Registry Platform. Individual patient data from all available trials will be included and subsequently analysed in a two-stage approach. Predetermined subgroup and sensitivity analyses will be employed to further explain results.

Discussion

The significance of this IPD meta-analysis is one of consolidating a clear consensus to better inform iron-deficient individuals of the physiological response associated with iron supplementation. The IPD approach, to the best of our knowledge, is novel for this research topic. As such, the findings will significantly contribute to the current body of evidence.

Systematic review registration

PROSPERO CRD42020191739.