bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Delirium in Patients With Neurological Diseases
Authors: Nisgaard Maja Gjerløv , Boesen Signe Vestergaard , Jensen Janet
Published: August 2024

BACKGROUND: Delirium is a common complication during hospitalization. Its consequences are severe, including reduced function, delayed rehabilitation, dementia, institutionalization, and death. Assessing delirium in neurological patients can be challenging due to the impact of neurological deficits. Therefore, the aim was to investigate the agreement between 2 delirium screening tools, factors associated with delirium, and assessing delirium in neurological patients. METHODS: This prospective observational study was conducted in 2 neurological units, using daily delirium screening. Intensive Care Delirium Screening Checklist and 2 versions of the Confusion Assessment Method were used to asses delirium in adult patients without baseline dementia, alcohol/drug detoxification, or palliative care. Descriptive analyses determined the number of delirium scores, and the analytical analyses were logistic regressions and a κ coefficient. RESULTS: The agreement between the screening tools was found to be substantial (κ = 0.71). Logistic regression analysis showed that the risk factors for a positive delirium screening were home care before admission (Confusion Assessment Method: odds ratio [OR], 4.21 [95% confidence interval (CI), 1.67–10.63]; Intensive Care Delirium Screening Checklist: OR, 6.14 [95% CI, 2.85–13.23]) and aphasia/dysarthria (Confusion Assessment Method: OR, 4.9 [95% CI, 1.32–6.81]; Intensive Care Delirium Screening Checklist: OR, 2.76 [95% CI, 1.3–5.87]). In total, 18.7% (n = 20/107) of the screening scores were positive. Specifically, the Confusion Assessment Method showed positive scores for 13.0% (n = 14/107) of participants, whereas the Intensive Care Delirium Screening Checklist showed positive scores for 16.8% (n = 18/107). CONCLUSION: The screening tools had a substantial degree of agreement. Therefore, nurses can use both screening tools to detect delirium in patients with neurological disorders. However, care should be taken in patients with aphasia to avoid misclassification with the Brief-Confusion Assessment Method. Moreover, special attention should be directed toward patients with language difficulties such as aphasia/dysarthria and those who received home care services before admission. These areas warrant further investigation in clinical practice and future studies.
Efficacy and safety of phototherapies for upper lip scars in cleft lip patients: a systematic review and meta-analysis
Authors: Wei Siqi , Zhang Guang , Wu Qian , Song Tao , Yin Ningbei , Wang Yongqian
Published: August 2024

Objective:

Cleft lip is a prevalent congenital developmental defect, and its surgical repair often results in scarring that adversely impacts facial esthetics, function, and mental health. Numerous studies have examined the efficacy and safety of phototherapy for scar treatment. However, definitive evidence is lacking. This study aims to evaluate the effectiveness and safety of phototherapies for treating upper lip scars in cleft lip patients.

Methods:

The authors searched PubMed, Cochrane Library, Embase, and Web of Science databases using specific search terms. The authors collected clinical trials on laser or other phototherapy treatments for upper lip scars after cleft lip surgery published up to the end of March 2024. Two researchers independently screened the literature, extracted data, and assessed quality based on inclusion and exclusion criteria. The data were analyzed by using RevMan 5.4 statistical software.

Results:

A total of nine studies were included. 1 Analysis of the clinical efficacy rate between the control group (routine care) and the intervention group (phototherapy) showed that laser or intense pulsed light (IPL) treatment significantly reduced total VSS scores (P<0.0001). 2 Analysis of the Pretest-Post-test cohort showed that total VSS scores were significantly reduced after phototherapy (P<0.00001). 3 Timing of phototherapy intervention analysis: early postoperative phototherapy intervention had a better effect. None of the literature reported permanent complications, nor were there any serious adverse events, only localized temporary erythema or blisters.

Conclusion:

Phototherapy can effectively improve the total VSS scores of upper lip scars after cleft lip surgery (including skin color, vascular distribution, softness, and thickness) with no apparent adverse reactions or serious complications. Early phototherapy intervention for upper lip scars has a better effect.
The safety and efficacy of neoadjuvant PD-1 inhibitor plus chemotherapy for patients with locally advanced gastric cancer: a systematic review and meta-analysis
Authors: Yu Zhiyuan , Liang Chen , Xu Qixuan , Yuan Zhen , Chen Miao , Li Rui , Zhou Sixin , Li Peiyu , Wei Bo , Zhao Xudong
Published: August 2024

Background:

The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitors for patients with locally advanced gastric cancer (LAGC).

Methods:

An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT.

Results:

After screening, six phase II/III randomized controlled trials (RCTs) and nine retrospective studies with 2953 patients were included. In meta-analysis, the NICT group demonstrated a significantly higher rate of pathological complete response (pCR) (P<0.001) and R0 resection (P=0.001), and a lower 2-year recurrence rate (P=0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) (P=0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization.

Conclusions:

The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.
Development and validation of a CT-based radiomics model to predict survival-graded fibrosis in pancreatic ductal adenocarcinoma
Authors: Shi Siya , Liu Ruihao , Zhou Jian , Liu Jiawei , Lin Hongxin , Mo Junyang , Zhang Jian , Diao Xianfen , Luo Yanji , Huang Bingsheng , Feng Shi-Ting
Published: August 2024

Background:

Tumor fibrosis plays an important role in chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC); however, there remains a contradiction in the prognostic value of fibrosis. The authors aimed to investigate the relationship between tumor fibrosis and survival in patients with PDAC, classify patients into high- and low-fibrosis groups, and develop and validate a CT-based radiomics model to non-invasively predict fibrosis before treatment.

Materials and methods:

This retrospective, bicentric study included 295 patients with PDAC without any treatments before surgery. Tumor fibrosis was assessed using the collagen fraction (CF). Cox regression analysis was used to evaluate the associations of CF with overall survival (OS) and disease-free survival (DFS). Receiver operating characteristic (ROC) analyses were used to determine the rounded threshold of CF. An integrated model (IM) was developed by incorporating selected radiomic features and clinical-radiological characteristics. The predictive performance was validated in the test cohort (Center 2).

Results:

The CFs were 38.22±6.89% and 38.44±8.66% in center 1 (131 patients, 83 males) and center 2 (164 patients, 100 males), respectively (P=0.814). Multivariable Cox regression revealed that CF was an independent risk factor in the OS and DFS analyses at both centers. ROCs revealed that 40% was the rounded cut-off value of CF. IM predicted CF with areas under the curves (AUCs) of 0.829 (95% CI: 0.753-0.889) and 0.751 (95% CI: 0.677-0.815) in the training and test cohorts, respectively. Decision curve analyses revealed that IM outperformed radiomics model and clinical-radiological model for CF prediction in both cohorts.

Conclusions:

Tumor fibrosis was an independent risk factor for survival of patients with PDAC, and a rounded cut-off value of 40% provided a good differentiation of patient prognosis. The model combining CT-based radiomics and clinical-radiological features can satisfactorily predict survival-grade fibrosis in patients with PDAC.
Hypothermic oxygenated machine perfusion influences the immunogenicity of donor livers in humans
Authors: Elgosbi Marwa , Kurt Ada Sera , Londoño Maria-Carlota , Caballero-Marcos Aranzazu , Lim Tiong Yeng , Lozano Juan J. , Dave Mona , Heaton Nigel , Sánchez-Fueyo Alberto , Cortes-Cerisuelo Miriam
Published: August 2024

Hypothermic oxygenated machine perfusion (HOPE) is an organ preservation strategy shown to reduce ischemia-reperfusion injury (IRI)-related complications following liver transplantation. In animal models, HOPE can also decrease alloimmune responses after transplantation, but this remains to be evaluated in humans. Our study, involving 27 patients undergoing liver transplantation enrolled in 2 randomized controlled trials comparing static cold storage with HOPE (14 HOPE-treated and 13 static cold storage–treated), delves into the impact of HOPE on the molecular profile of liver allografts and on the immune responses elicited after transplantation. Following HOPE treatment, fewer intrahepatic immune cells were observed in liver perfusates compared to static cold storage. Analysis of liver tissue transcriptome at reperfusion revealed an effect of HOPE on the reactive oxygen species pathway. Two weeks after transplantation, HOPE recipients exhibited increased circulating CD4+FOXP3+CD127lo regulatory T cells (p < 0.01), which corresponded to a higher frequency of donor-specific regulatory T cells (p < 0.01) and was followed by reduced alloreactivity index of CD8+ T cells 3 months after transplant. Our study provides novel mechanistic insight into the capacity of HOPE to influence liver ischemia-reperfusion injury and to modulate effector and regulatory donor-specific T-cell responses after transplantation. These findings, which confirm observations made in animal models, help explain the decreased rejection rates reported in patients receiving HOPE-treated allografts.
The emerging role of fat-inducing transcript 2 in endoplasmic reticulum proteostasis and lipoprotein biogenesis
Authors: Brodsky Jeffrey L. , Iyer Anuradha , Fortounas Konstantinos I. , Fisher Edward A.
Published: August 2024

Purpose of review

This review examines the evolving role of the fat-inducing transcript 2 (FIT2) protein in lipid droplet (LD) biology and its broader implications in cellular physiology and disease. With recent advancements in understanding FIT2 function across various model systems, this review provides a timely synthesis of its mechanisms and physiological significance.

Recent findings

FIT2, an endoplasmic reticulum (ER)-resident protein, has been established as a critical regulator of LD formation in diverse organisms, from yeast to mammals. It facilitates LD biogenesis by sequestering diacylglycerol (DAG) and potentially influencing ER membrane dynamics. Beyond its role in lipid metabolism, FIT2 intersects with the ER-associated degradation (ERAD), is critical for protein homeostasis, and is linked to the unfolded protein response (UPR). Dysregulation of FIT2 has also been linked to metabolic disorders such as insulin resistance and lipodystrophy, highlighting its clinical relevance.

Insights into FIT2 function underscore its pivotal role in LD formation and lipid homeostasis. Understanding its involvement in ER proteostasis and very low density lipoprotein biogenesis has broad implications for metabolic diseases and cancer. Therapeutic strategies targeting FIT2 may offer novel approaches to modulate lipid metabolism and mitigate associated pathologies. Further research is needed to elucidate the full spectrum of FIT2's interactions within cellular lipid and protein networks, potentially uncovering new therapeutic avenues for metabolic and ER stress-related disorders.
Where are we in 2024 in the development of materials for surgical treatment of pelvic organ prolapse and stress urinary incontinence?
Authors: Chapple Christopher R. , Bullock Anthony J. , MacNeil Sheila
Published: August 2024

Purpose of review

There is a long history of implantation of absorbable and nonabsorbable materials to treat stress urinary incontinence (SUI) and pelvic organ prolapse (POP). The focus of this review is to review the development of new materials for use in the surgical management of both pelvic conditions following an unacceptable level of severe complications in the use of polypropylene mesh (PPM). We discuss current concepts relating to the development of new materials with particular reference to our experience with polyurethane mesh.

Recent findings

Our review highlights the strategies that manufacturers and researchers are employing to improve PPM using collagen gels and stem cells, or to find alternatives. We conclude that current preclinical safety testing is inadequate, and the field requires better in vivo testing. Specifically, we highlight novel techniques demonstrating the degradation of polypropylene potentially elucidating the link between PPM degradation and induction of inflammation leading to adverse side effects.

This field badly needs innovation in developing new materials and in testing these to ensure materials will benefit patients. A collaboration between materials scientists and clinicians is needed to facilitate the translation of basic research and preclinical testing into patient benefit for the treatment of SUI and POP.
Factors Associated With Potentially Unnecessary Transfers for Children With Asthma
Authors: Peters Gregory A. , Cash Rebecca E. , Goldberg Scott A. , Gao Jingya , Escudero Taylor , Kolb Lily M. , Camargo Carlos A.
Published: August 2024

Objective

Our objective was to identify the hospital- and community-related factors associated with the hospital-level rate of potentially unnecessary interfacility transfers (IFTs) for pediatric patients with asthma exacerbations.

Methods

We analyzed California Emergency Department (ED) data from 2016 to 2019 to capture ED visits where a pediatric patient (age, 2–17 years) presented with an asthma exacerbation and was transferred to another ED or acute care hospital. The primary outcome was hospital-level rate of potentially unnecessary IFTs, defined as a visit where length of stay after transfer was <24 hours and no advanced services (eg, critical care) were used. Hospital- and community-related characteristics included urbanicity, teaching hospital status, availability of pediatric resources in the sending facility and patient's community, pediatric patient volume, and Social Vulnerability Index. We described and compared hospitals in the top quartile of potentially unnecessary IFT rate versus all others and used a multivariable modified Poisson model to identify factors associated with potentially unnecessary IFT.

Results

A total of 325 sending hospitals were included, with a median 573 pediatric asthma visits (interquartile range, 183–1309) per hospital annually. Nearly half of the hospitals (145/325, 45%) sent a potentially unnecessary IFT. Most (90%) hospitals were urban, 9% were teaching hospitals, 5% had >500 beds, and 22% had a pediatric ED on-site. Factors associated with higher adjusted prevalence of potentially unnecessary IFT included availability of pediatric telehealth (prevalence ratio [PR], 1.5; 95% confidence interval [CI], 1.2–2.0), increased pediatric volume (eg, <1800 vs ≥10,000 visits: PR, 2.6; 95% CI, 1.4–4.7), and higher community Social Vulnerability Index (PR, 1.5; 95% CI, 1.1–1.9).

Conclusions

Several hospital- and community-related factors were associated with potentially unnecessary IFTs among pediatric patients presenting to the ED with asthma exacerbations. These findings provide insight into disparities in potentially unnecessary IFT across communities and can guide the development of future interventions.
User experience of passive hip flexion device in people with multiple sclerosis: Exploring improvements and overcoming barriers
Authors: Liguori Sara , Panizzolo Fausto A. , Marcolin Giuseppe , Micaglio Giovanni , Mendicino Margherita , Semplicini Claudio , Baricich Alessio , Molteni Franco , Guanziroli Eleonora , Ciotti Silvia , Zampolini Mauro , Castelli Enrico , Gervasoni Fabrizio , Campagnoli Marcello M. , Quercio Marco , Gimigliano Francesca
Published: August 2024

Background:

Multiple sclerosis (MS) is a chronic disease that primarily affects young adults and causes disability by impairing the central nervous system. Gait impairments are common in people with MS (pwMS), and lower limb orthoses are often used to improve stability and mobility. However, compliance with orthotic devices can vary among individuals due to issues related to the appropriate prescription and lack of acceptability.

Objective:

In this observational, cross-sectional study, we aimed to explore the experience of wearing a passive hip flexion device in a cohort of pwMS.

Methods:

We included men and women >18 years old affected by MS (Expanded Disability Status Scale >4) who have been using a passive hip flexion device (ExoBand, Moveo srl) since 2020 for at least 15 days. The participants completed a phone survey that collected demographic, anthropometric, and clinical data, their perceptions of the device’s impact using the Psychosocial Impact of Assistive Devices (PIADS) questionnaire, and a qualitative part with an open-ended question.

Results:

A total of 41 patients completed the survey. The participants experienced improvements in all 3 areas of the PIADS questionnaire since using the ExoBand (P<0.001). The area of competence showed the highest improvement, particularly in terms of efficiency and usefulness. The majority of participants (85.4%) perceived an improvement from using the device, reporting better quality of movement and increased walking distance. Only a small percentage (26.8%) did not perceive any benefits, mainly due to discomfort and personal factors.

Conclusions:

This study highlighted the satisfaction among pwMS with the use of the ExoBand device and emphasized the importance of addressing individual needs during the orthotic prescription process. This study represents the first exploration of the perspective and perception of using a passive hip flexion device in pwMS. Our results support the need to assess user experience and the psychosocial impact of these devices on people’s lives to better understand the barriers and reasons behind their underutilization. Further research with a larger and heterogeneous population is recommended to gather more comprehensive data.
HIV Treatment Outcomes After 10 years on ART in the TREAT Asia Observational Database and Australian HIV Observational Database
Authors: Jiamsakul Awachana , Rupasinghe Dhanushi , Woolley Ian , Choi Jun Yong , Templeton David J. , Widhani Alvina , Petoumenos Kathy , Tanuma Junko ,   on behalf of the TREAT Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD) of IeDEA Asia-Pacific
Published: August 2024

Background:

Increasing numbers of people with HIV have received prolonged antiretroviral therapy (ART). We assessed long-term immunological and survival outcomes among people with HIV from Asia (TREAT Asia HIV Observational Database) and Australia (Australian HIV Observational Database).

Methods:

People with HIV receiving ART for ≥10 years were included. Factors associated with CD4 counts in years 11–15 of ART were analyzed using repeated measures linear regression. Survival after 10 years was analyzed using competing risk regression.

Results:

There were 7139 people included: 4867 (68%) from the TREAT Asia HIV Observational Database and 2272 (32%) from the Australian HIV Observational Database. Higher CD4 levels after 10 years were observed if the nadir CD4 in the first decade was higher (CD4 (cells/µL) 101–200: difference = 35, 95% CI: 18 to 51; >200: difference = 125, 95% CI: 107 to 142) compared with ≤50. The same patterns were observed in those who achieved CD4 ≥500 cells/µL, which subsequently decreased to <500 (difference = 225, 95% confidence interval [CI]: 213 to 236), or in those who achieved and maintained CD4 ≥500 cells/µL (difference = 402, 95% CI: 384 to 420), compared with always <500 in the previous decade. Previous protease inhibitor (PI)-based regimen (difference=−17, 95% CI −33 to −1) compared with no PI, and previous treatment interruptions (TI) of 14 days to 3 months and >6 months were associated with lower CD4 counts after 10 years (difference = −38, 95% CI −62 to −15 and difference=−44, 95% CI −61 to −27, respectively) compared with no TI. The mortality rate was 1.04 per 100 person-years. Virological failure was associated with subsequent mortality (subhazard ratio = 1.34, 95% CI: 1.04 to 1.71).

Conclusions:

Sustaining high CD4 levels and minimizing TI has far-reaching benefits well beyond the first decade of ART.
Abnormal Interhemispheric Functional Connectivity in Acute Pericoronitis: A Resting-State MRI Study
Authors: Li Xing , Qiu Luo-Yao , Shi Xue-Jiao , Zhu Yu-Ping , He Yu-Lin , Kuang Hong-Mei
Published: August 2024

Objective:

Acute pericoronitis (AP) is a prevalent cause of odontogenic toothache which can significantly impact brain function. Previous research has predominantly concentrated on localized brain activity. However, the synergistic changes between brain hemispheres induced by toothache and resulting abnormal functional connectivity across the brain have not been comprehensively studied.

Methods:

A total of 34 patients with AP and 34 healthy individuals, matched for age, sex, and education were recruited for this study. All participants underwent resting-state functional magnetic resonance imaging (rs-MRI) scans. The voxel mirror homotopic connectivity (VMHC) method was used to identify intergroup differences. Brain regions exhibiting statistically significant differences were selected as regions of interest for further functional connectivity analysis. The partial correlation method was utilized to assess the correlation between abnormal VMHC values in different regions and clinical parameters, with age and sex included as covariates.

Results:

Patients with AP exhibited reduced VMHC values in the thalamus and elevated VMHC values in the inferior frontal gyrus compared with healthy controls. Subsequent functional connectivity analyses revealed extensive changes in functional networks, predominantly affecting the default, frontoparietal, cerebellar, and pain networks.

Conclusion:

Changes in functional patterns across these brain networks offer novel insights into the neurophysiological mechanisms underlying pain information processing.
Efficacy of Self-Expandable Absorbable Stents during Liver Transplant to Minimize Early Biliary Complications
Authors: Lopez-Lopez Victor , Kuemmerli Christoph , Iniesta Maria , Hiciano-Guillermo Alberto , Cascales-Campos Pedro , Baroja-Mazo Alberto , Antonio-Pons Jose , Sánchez-Esquer Ignacio , Ferreras David , Sánchez-Bueno Francisco , Ramírez Pablo , Robles-Campos Ricardo
Published: August 2024

Objective:

We analyzed the use of a self-expandable absorbable biliary stent (SEABS) to reduce biliary complications in liver transplant (LT).

Background:

Complications related to biliary anastomosis are a still a challenge in LT with a high impact on the patient outcomes and hospital costs.

Methods:

This non-randomized prospective study was conducted between July 2019 and September 2023 in adult LT patients with duct-to-duct biliary anastomoses. The primary endpoint was to assess early biliary complications at 90 days in LT patients with intraoperative SEABS versus no SEABS. We also compared overall biliary complications, costs and SEABS- adverse effects related.

Results:

A total of 158 patients were included, 78 with SEABS and 80 no-SEABS (22 T-tube and 58 no-stent). There were no adverse effects related to SEABS. Early biliary complications (23.8 vs 2.6%, P <0.001) and hospital stay (19 vs 15 days, P= 0.001) were higher in no-SEABS. No-SEABS group required 63 ERCPs and 13 surgeries (including 2 LT) versus 35 ERCPs and 2 surgeries in SEABS group. After PSM between SEABS (n=58) vs no-SEABS (n=58), early biliary complications (40% vs 0%, P<.001) were higher in no-SEABS group. T-tube had more early biliary complications (22.7% vs 5%, P=0.23) compared SEABS high-risk biliary anastomosis. SEABS excess cost per patient was lower compared to T-Tube and no-stent (6.988€ vs 17.992€ vs 36.364€, P=0.036 and P=0.002, respectively).

Conclusions:

SEABS during biliary anastomosis in LT is feasible with no adverse effects and avoid the T-tube in high-risk biliary anastomoses. It use has been associated with less early biliary complications, hospital costs and reoperations or interventional treatments for biliary complications resolution.
Post-discharge Outcomes and Healthcare Utilization Among Hispanic/Latinx Injury Survivors
Authors: Valverde Madeline , Ilkhani Saba , Pinkes Nathaniel , Froehle Leah , Ortega Gezzer , Hwabejire John O. , Sanchez Sabrina E. , Haider Adil H. , Salim Ali , Anderson Geoffrey A. , Herrera-Escobar Juan P.
Published: August 2024

Objective:

We sought to compare post-discharge outcomes and healthcare utilization between English-speaking non-Hispanic White (NHW), English-speaking Hispanic/Latinx (ESHL), and Spanish-speaking Hispanic/Latinx (SSHL) survivors of traumatic injury.

Background:

While there is evidence of racial and ethnic disparities in healthcare utilization and post-discharge outcomes after injury, the role of English language proficiency in these disparities remains unclear.

Methods:

Moderate to severely injured adults from three level-1 trauma centers completed an interview in English or Spanish between 6-12 months post-injury to assess physical health-related quality of life (SF-12-PCS), return to work, and post-discharge healthcare utilization. The language used in the interview was used as a proxy for English-language proficiency, and participants were categorized as either NHW (reference), ESHL, or SSHL. Multivariable regression models estimated independent associations between language and race/ethnicity with SF-12-PCS, return to work, and post-discharge healthcare utilization outcomes.

Results:

3,304 injury survivors were followed: 2,977 (90%) NHW, 203 (6%) ESHL, and 124 (4%) SSHL. In adjusted analyses, no significant differences were observed between ESHL and NHW injury survivors for any outcomes at 6-12 months post-injury. However, SSHL injury survivors exhibited a lower mean SF-12-PCS (41.6 vs. 38.5), −3.07 (95% CI=−5.47, −0.66; P=0.012), decreased odds of returning to work (OR=0.47; CI=0.27 to 0.81; P=0.007), and were less likely to engage in non-injury related outpatient visits, such as primary care visits (OR=0.45; 95% CI 0.28, 0.73; P=0.001), compared to NHW patients.

Conclusion:

Hispanic/Latinx injury survivors have worse post-discharge outcomes and lower non-injury-related healthcare utilization than NHW if they have limited English-language proficiency. Addressing LEP-related barriers to care could help mitigate outcome and healthcare utilization disparities among Hispanic/Latinx injury survivors.
Evidence-informed decision-making in public health in Canada: a qualitative exploration
Authors: Romano Isabella , Clark Emily C. , Quiambao Janine , Horn Miranda , Dare Lynn , Rogers Kristin , Dobbins Maureen
Published: August 2024

Introduction:

Evidence-informed decision-making (EIDM) plays a vital role in public health practice. Canada has invested in support for evidence-informed approaches in public health. Despite growing expectations for EIDM, evidence integration has not been thoroughly evaluated.

Objective:

This study explores EIDM within Canadian public health organizations before the COVID-19 pandemic. A secondary objective is to explore how EIDM in public health was affected by the COVID-19 pandemic.

Methods:

Using a qualitative descriptive approach, data were collected and analyzed from interviews with public health professionals across Canada.

Results:

From interviews with 20 participants in four Canadian provinces and one territory, all participants noted that EIDM was valued, but there was considerable variation in implementation. Participants reported differences in consistency of evidence use, resources available at their public health organizations to support EIDM, and staff knowledge and skills in EIDM. Leadership emerged as a strong influencer of EIDM; however, leadership investment in EIDM varied. Changes in evidence use during the COVID-19 pandemic revealed an urgency for decision-making amidst an influx of evidence and reallocated staff roles.

Conclusions:

Despite gains in the recognized value of EIDM, gaps remain in the integration of evidence into decision-making and adequate resource investment to support EIDM. Time, resources, and skills to adapt processes and implement EIDM are needed for public health organizations in Canada to fully integrate EIDM into all aspects of public health decision-making.

Spanish abstract:

http://links.lww.com/IJEBH/A249
Polyploid cancer cells reveal signatures of chemotherapy resistance
Authors: Schmidt Michael J. , Naghdloo Amin , Prabakar Rishvanth K. , Kamal Mohamed , Cadaneanu Radu , Garraway Isla P. , Lewis Michael , Aparicio Ana , Zurita-Saavedra Amado , Corn Paul , Kuhn Peter , Pienta Kenneth J. , Amend Sarah R. , Hicks James
Published: August 2024

Therapeutic resistance in cancer significantly contributes to mortality, with many patients eventually experiencing recurrence after initial treatment responses. Recent studies have identified therapy-resistant large polyploid cancer cells in patient tissues, particularly in late-stage prostate cancer, linking them to advanced disease and relapse. Here, we analyzed bone marrow aspirates from 44 advanced prostate cancer patients and found the presence of circulating tumor cells with increased genomic content (CTC-IGC) was significantly associated with poorer progression- free survival. Single cell copy number profiling of CTC-IGC displayed clonal origins with typical CTCs, suggesting complete polyploidization. Induced polyploid cancer cells from PC3 and MDA-MB-231 cell lines treated with docetaxel or cisplatin were examined through single cell DNA sequencing, RNA sequencing, and protein immunofluorescence. Novel RNA and protein markers, including HOMER1, TNFRSF9, and LRP1, were identified as linked to chemotherapy resistance. These markers were also present in a subset of patient CTCs and associated with recurrence in public gene expression data. This study highlights the prognostic significance of large polyploid tumor cells, their role in chemotherapy resistance, and their expression of markers tied to cancer relapse, offering new potential avenues for therapeutic development.
Factors associated with pharmacologic serum concentration of Magnesium and corresponding obstetric outcomes among women with severe pre-eclampsia at Iringa Regional Referral Hospital
Authors: Kileo Joshua Stephen , matovelo Shubi , Kitinusa Gabriel
Published: August 2024

Introduction

Severe pre-eclampsia is managed by using Magnesium sulphate to prevent its progress into eclampsia with a success rate of more than 50%. This study aimed at establishing reliable data pertaining factors influencing pharmacologic serum concentration of Magnesium and their correlation to obstetric outcomes.

Methods

This study was carried out at Iringa regional referral hospital, spanning six months from November 2023 to April 2024. A convenient sampling technique was used to recruit 121 pre-eclamptic patients. Recruited women were tested serum Magnesium at admission, 4 and 12 hours post initial administration of MgSO4. IBM SPSS version 29 was used for analysis where, Continuous variables were analyzed by using median and interquartile range while categorical variables were analyzed using frequency and percentages. The associations between variables were determined using chi-square tests, univariate, and multivariate binary regression models. A p value<0.05 was considered statistically significant.

Results

The median age of participants were (29±10 IQR), the median serum Mg at admission was (0.8±0.29 IQR) Mmol/L majority with low 53(43.8%) levels. Proportion of subtherapeutic serum Mg was 38.8% with median of (1.9±1.02 IQR) Mmol/L. Multivariate regression showed that; low serum Mg at admission [p<0.001, OR= 9.17, 95% CI (3.07-27.37)], Creatinine level [p = 0.012, OR= 4.49, 95% CI (1.38-14.6)], Overweight [p= 0.002, OR= 5.52, 95% CI (1.83-16.68)] and proteinuria +++[p-value = 0.004, OR= 7.13, 95% CI (1.84-26.86)] were significantly associated with subtherapeutic level. After adjusting with other factors, it was found that subtherapeutic level [p<0.001, OR=25.44(5.73-112.90)], elevated creatinine [p=0.040, OR=3.59(1.66-12.15)], Reduced urine output [p=0.001, OR=6.69(2.15-20.90)] were significant predictors of adverse maternal outcomes.

Conclusion

Subtherapeutic serum Magnesium which significantly predict adverse obstetric outcomes, is influenced by factors which can be monitored and be useful in effective management of severe pre-eclampsia. This can help in administering tailored dose of MgSO4for better outcomes.
Advancing long-read nanopore genome assembly and accurate variant calling for rare disease detection
Authors: Negi Shloka , Stenton Sarah L. , Berger Seth I. , McNulty Brandy , Violich Ivo , Gardner Joshua , Hillaker Todd , O’Rourke Sara M , O’Leary Melanie C. , Carbonell Elizabeth , Austin-Tse Christina , Lemire Gabrielle , Serrano Jillian , Mangilog Brian , VanNoy Grace , Kolmogorov Mikhail , Vilain Eric , O’Donnell-Luria Anne , Délot Emmanuèle , Miga Karen H. , Monlong Jean , Paten Benedict
Published: August 2024

More than 50% of families with suspected rare monogenic diseases remain unsolved after whole genome analysis by short read sequencing (SRS). Long-read sequencing (LRS) could help bridge this diagnostic gap by capturing variants inaccessible to SRS, facilitating long-range mapping and phasing, and providing haplotype-resolved methylation profiling. To evaluate LRS’s additional diagnostic yield, we sequenced a rare disease cohort of 98 samples, including 41 probands and some family members, using nanopore sequencing, achieving per sample ∼36x average coverage and 32 kilobase (kb) read N50 from a single flow cell. Our Napu pipeline generated assemblies, phased variants, and methylation calls. LRS covered, on average, coding exons in ∼280 genes and ∼5 known Mendelian disease genes that were not covered by SRS. In comparison to SRS, LRS detected additional rare, functionally annotated variants, including SVs and tandem repeats, and completely phased 87% of protein-coding genes. LRS detected additionalde novovariants, and could be used to distinguish postzygotic mosaic variants from prezygoticde novos. Eleven probands were solved, with diverse underlying genetic causes includingde novoand compound heterozygous variants, large-scale SVs, and epigenetic modifications. Our study demonstrates LRS’s potential to enhance diagnostic yield for rare monogenic diseases, implying utility in future clinical genomics workflows.
Is Your Style Transfer Doing Anything Useful? An Investigation Into Hippocampus Segmentation and the Role of Preprocessing
Authors: Kalabizadeh Hoda , Griffanti Ludovica , Yeung Pak Hei , Voets Natalie , Gillis Grace , Mackay Clare E , Namburete Ana IL , Dinsdale Nicola K , Kamnitsas Konstantinos
Published: August 2024

Brain atrophy assessment in MRI, particularly of the hippocampus, is commonly used to support diagnosis and monitoring of dementia. Consequently, there is a demand for accurate automated hippocampus quantification. Most existing segmentation methods have been developed and validated on research datasets and, therefore, may not be appropriate for clinical MR images and populations, leading to potential gaps between dementia research and clinical practice. In this study, we investigated the performance of segmentation models trained on research data that were style-transferred to resemble clinical scans. Our results highlighted the importance of intensity normalisation methods in MRI segmentation, and their relation to domain shift and style-transfer. We found that whilst normalising intensity based on min and max values, commonly used in generative MR harmonisation methods, may create a need for style transfer, Z-score normalisation effectively maintains style consistency, and optimises performance. Moreover, we show for our datasets spatial augmentations are more beneficial than style harmonisation. Thus, emphasising robust normalisation techniques and spatial augmentation significantly improves MRI hippocampus segmentation.
Staphylococcus aureusTetracycline Resistance and Co-resistance in a Doxy-PEP-Eligible Population
Authors: Mittelstaedt Rachel , Kanjilal Sanjat , Helekal David , Robbins Gregory K. , Grad Yonatan H.
Published: August 2024

InStaphylococcus aureusinfections in men eligible for doxycycline post-exposure prophylaxis (doxy-PEP), tetracycline non-susceptibility is more prevalent than in the overall population and is associated with resistance to trimethoprim-sulfamethoxazole and clindamycin. Doxy-PEP may select forS. aureusmulti-drug resistance, underscoring the importance of surveillance.
Glaucoma classification through SSVEP derived ON- and OFF-pathway features
Authors: Scott Martin T.W. , Xu Hui , Yakovleva Alexandra , Tibshirani Robert , Goldberg Jeffrey L , Norcia Anthony M
Published: August 2024

Recent evidence from small animal models and human electrophysiology suggests that the OFF-pathway is more vulnerable to glaucomatous insult than the ON-pathway. Thus, OFF-pathway based measurements of visual function may be useful in the diagnosis of Glaucoma. The steady-state visually evoked potential (SSVEP) can be used to non-invasively make such functional measurements. Here, we examine whether OFF- and ON-pathway biasing SSVEP measurements differently predict glaucoma diagnosis using a large cohort of 98 glaucoma patients and 71 controls. Using both a logistic regression with k-fold cross-validation and a random forest classifier, we show that OFF-pathway biasing features produce a small improvement in predictive accuracy over ON-pathway biasing features. However, despite our inclusion of many more response features and the retention of both participants' eyes, our classifier did not perform as well as previous reports that used the isolated-check VEP. This is likely a result of the relatively small amount of data we collected for each participant, but may also be explained by the absence of any train-test splitting in preexisting work. Nevertheless, our results support further exploration of the diagnostic potential of OFF-pathway biasing functional biomarkers for glaucoma.
Genomic Epidemiology and Microevolution of the Zoonotic PathogenCorynebacterium ulcerans
Authors: Crestani Chiara , Passet Virginie , Rethoret-Pasty Martin , Criscuolo Alexis , Zidane Nora , Brémont Sylvie , Badell Edgar , Brisse Sylvain
Published: August 2024

Corynebacterium ulceransis an emerging zoonotic pathogen that belongs to theCorynebacterium diphtheriae(Cd) species complex (CdSC), and that causes diphtheria-like infections in humans. Our understanding of the transmission, phylogeography and evolution ofC. ulceransremains limited, in part due to the lack of a standardized genomic epidemiology toolkit.

The aim of this work was to develop a core genome multi-locus sequence typing (cgMLST) scheme for high-resolution genotyping and classification ofC. ulceransstrains, and to explore transmission, spatial spread and genomic evolution among 582C. ulceransisolates from sporadic clinical cases and reported case clusters.

The cgMLST scheme combines 1,628 loci with highly reproducible allele calls and shows high strain subtyping resolution. We demonstrate its utility for capturing population structure by defining sublineages (SL, maximum 940 allele differences) and clonal groups (CG, 194 allele differences, AD) and for epidemiological surveillance by defining genetic clusters, i.e., previously undetected chains of transmission (25 AD). Genetic clusters correspond to cryptic and case clusters that were associated with specific geographical regions within France. MajorC. ulceranssublineages (SL325, SL331, SL339) and clonal groups (CG325, CG331, CG583) showed strong associations with diphtheria toxin variants and tox-carrying prophages or other genetic elements. The evolutionary dynamics oftoxgene presence or absence varied sharply among clonal groups. The cgMLST scheme is publicly available (https://bigsdb.pasteur.fr/diphtheria) and provides a common framework for investigating the ecology, evolution and variations in virulence amongC. ulceransstrains. The implementation of a standardized high-resolution genotyping method will also facilitate the tracing ofC. ulceranstransmission and spread across hosts and from local to global spatial scales.
Multi-Layer Autocatalytic Feedback Enables Integral Control Amidst Resource Competition and Across Scales
Authors: Zand Armin M. , Anastassov Stanislav , Frei Timothy , Khammash Mustafa
Published: August 2024

Integral feedback control strategies have proven effective in regulating protein expression in unpredictable cellular environments. These strategies, grounded in model-based designs and control theory, have advanced synthetic biology applications. Autocatalytic integral feed-back controllers, utilizing positive autoregulation for integral action, are particularly promising due to their similarity to natural behaviors like self-replication and positive feedback seen across biological scales. However, their effectiveness is often hindered by resource competition and context-dependent couplings. This study addresses these challenges with a multi-layer feedback strategy, enabling population-level integral feedback and multicellular integrators. We provide a generalized mathematical framework for modeling resource competition in complex genetic networks, supporting the design of intracellular control circuits. Our controller motif demonstrated precise regulation in tasks ranging from gene expression control to population growth in multi-strain communities. We also explore a variant capable of ratiometric control, proving its effectiveness in managing gene ratios and co-culture compositions in engineered microbial ecosystems. These findings offer a versatile approach to achieving robust adaptation and homeostasis from subcellular to multicellular scales.
Endothelial MICU1 protects against vascular inflammation and atherosclerosis by inhibiting mitochondrial calcium uptake
Authors: Sun Lu , Leng Ruixue , He Qingze , Su Meiming , Zhang Zhidan , Liu Zhenghong , Wang Zhihua , Jiang Hui , Liu Monan , Wang Li , Huo Yuqing , Miller Clint L , Banach Maciej , Huang Yu , Evans Paul C , Pelisek Jaroslav , Camici Giovanni G , Berk Bradford C , Offermanns Stefan , Ge Junbo , Xu Suowen , Weng Jianping
Published: August 2024

Atherosclerosis is triggered by endothelial activation and vascular inflammation, which is closely related to mitochondrial dysfunction. Mitochondrial calcium uptake 1 (MICU1), as the gatekeeper of mitochondrial Ca2+ homeostasis, is a critical player in mitochondrial function and implicated in a plethora of pathophysiological conditions. However, the role of MICU1 in the pathogenesis of vascular inflammation and atherosclerosis is unknown. We ask whether endothelial MICU1 can prevent vascular inflammation and atherosclerosis by maintaining mitochondrial homeostasis. We observed that vascular inflammation in response to LPS was aggravated in EC-specific Micu1 knockout mice (Micu1ECKO) and reduced in EC-specific Micu1 transgenic mice (Micu1ECTg). Furthermore, hypercholesterolemic Micu1ECKO mice also showed accelerated formation of atherosclerotic plaques, while Micu1ECTg mice protected against atherosclerosis. Mechanistically, MICU1 regulated mitochondrial Ca2+ influx, thereby reducing the expression of the mitochondrial deacetylase SIRT3 and the ensuing deacetylation of SOD2, leading to the burst of mitochondrial reactive oxygen species (mROS). Of clinical relevance, we identified decreased MICU1 level in endothelial layer of human atherosclerotic plaques, as well as in primary human aortic endothelial cells (HAECs) exposed to serum from patients with coronary artery diseases. Two-sample Wald ratio Mendelian randomization further revealed that increased expression of MICU1 was associated with decreased risk of coronary artery bypass grafting (CABG). Our findings unravel a critical and unrecognized role of MICU1 in preventing vascular inflammation and atherosclerosis by maintaining mitochondrial Ca2+ homeostasis.
Opening and closing of a cryptic pocket in VP35 toggles it between two different RNA-binding modes
Authors: Mallimadugula Upasana L. , Cruz Matthew A. , Vithani Neha , Zimmerman Maxwell I. , Bowman Gregory R.
Published: August 2024

Cryptic pockets are of growing interest as potential drug targets, particularly to control protein-nucleic acid interactions that often occur via flat surfaces. However, it remains unclear whether cryptic pockets contribute to protein function or if they are merely happenstantial features that can easily be evolved away to achieve drug resistance. Here, we explore whether a cryptic pocket in the Interferon Inhibitory Domain (IID) of viral protein 35 (VP35) of Zaire ebolavirus aids its ability to bind double-stranded RNA (dsRNA). We use simulations and experiments to study the relationship between cryptic pocket opening and dsRNA binding of the IIDs of two other filoviruses, Reston and Marburg. These homologs have nearly identical structures but block different interferon pathways due to different affinities for blunt ends and backbone of the dsRNA. Simulations and thiol-labeling experiments demonstrate that the homologs have varying probabilities of pocket opening. Subsequent dsRNA-binding assays suggest that closed conformations preferentially bind dsRNA blunt ends while open conformations prefer binding the backbone. Point mutations that modulate pocket opening proteins further confirm this preference. These results demonstrate the open cryptic pocket has a function, suggesting cryptic pockets are under selective pressure and may be difficult to evolve away to achieve drug resistance.