bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex difference in the relationship of the Atherogenic index of plasma with coronary artery lesions in diabetes: a cross-sectional study
Authors: Hu Yi , Wang Xuan , Luo Chaodi , Zheng Tingting , Tian Gang
Published: January 2023

Background

Coronary artery disease (CAD) tends to progress more rapidly in the type 2 diabetes mellitus (T2DM) population and may be associated with dyslipidemia. This study explored the relationship of the atherogenic index of plasma (AIP) to coronary artery lesions in the T2DM population of different sexes.

Methods

The research included 737 individuals who underwent coronary angiography from 2018 to 2019. The included clinical data and coronary angiographic findings were analyzed in the study.

Results

Among the included male patients, those with coronary artery disease had a higher adjusted AIP (aAIP). In correlation analysis, the Gensini score was positively and linearly correlated with the aAIP in male T2DM patients. An aAIP cutoff value of 1.17 was determined from the receiver operating characteristic (ROC) curve of aAIP versus CAD risk in the study population. After dividing the aAIP into two groups by the cutoff value of aAIP, the group with the lower value was used as the control for logistic regression analysis. The results showed that the risk of CAD and multivessel lesions was higher when the aAIP was higher in men with T2DM, and this positive association was not affected by HbA1c, age, or the presence of glucose-lowering therapy. The ROC curve suggested that the aAIP can predict CAD risk in male T2DM patients. However, no relationship was found in the included female patients.

Conclusion

In male T2DM patients, AIP may serve as a reliable marker for coronary artery lesions.
The relationship between NAFLD and retinol-binding protein 4 - an updated systematic review and meta-analysis
Authors: Hu Rui , Yang Xiaoyue , He Xiaoyu , Song Guangyao
Published: January 2023

Purpose

Retinol-binding protein 4 (RBP4) has been considered to be related to metabolic related diseases, such as hyperuricemia, obesity, and diabetes mellitus. However, whether nonalcoholic fatty liver disease (NAFLD) is related to RBP4 is unclear. Previous studies on the relationship between NAFLD and RBP4 levels have yielded inconsistent results. Hence, this meta-analysis was aimed to clarify whether circulating RBP4 levels are in relation to the risk of NAFLD.

Methods

A meta-analysis was performed by applying observational studies to evaluate circulating RBP4 levels and NAFLD. Eligible studies published up to September 23, 2022, were searched in Embase, PubMed, and Cochrane databases.

Results

In this study, 17 cross-sectional studies involving 8423 participants were included. Results from a random effects model showed that circulating RBP4 levels were higher in NAFLD patients than non-NAFLD (standardized mean difference (SMD) 0.28; 95% confidence intervals (CI): 0.11–0.46, I2: 89.8%). This association was confirmed in the Yellow race. However, no significant association was noted in the Caucasian race. After excluding the morbidly obese Population from the weight loss study (n = 2), the results of the comparison remained largely unchanged (SMD 0.28; 95% CI: 0.10–0.47, I2: 90.8%). Remarkable publication bias was not found. Although considerable heterogeneity was observed among the studies, no potential sources of heterogeneity were found in the subgroup analysis. Diagnostic methods for NAFLD were determined to be a potential source of statistical heterogeneity in meta-regression.

Conclusion

The findings provide evidence that NAFLD patients exhibit higher levels of circulating RBP4 compared with controls, but high heterogeneity was observed. Thus, a high RBP4 level is probably a potential risk factor for NAFLD. To confirm the causal link between NAFLD and RBP4 level of causality, further prospective cohort studies are needed.
Ups and downs of addiction harm reduction in Iran: key insights and implications for harm reduction policy and policing
Authors: Shafiee S. Ali , Vedadhir AbouAli , Razaghi Emran
Published: January 2023

Drug use is a critical behavioral disorder or a delinquency behavior (in the judiciary system's words) that comes with a burden at multiple levels: individual, community, public, and global. These social structures apply different interventions to reduce this burden in their field. Given the society as a whole, these structures must be harmonious and synergistic to optimize these endeavors in terms of cost–benefit. In practice, however, reducing the burden of addiction is followed by conflicting approaches by different organizations, in terms such as “eradicating drugs,” “eliminating drug users,” “obliterating addiction,” and ultimately, drug use harm reduction. In the harm reduction philosophy, drug use is recognized as an inescapable fact in human societies, and tries to control its personal and public consequences in different dimensions (health, economic, and social). Therefore, this approach includes broad measures such as: changing the pattern of consumption (from high-risk substances to less dangerous substances) through modification of the laws and law enforcement measures, distributing disposable syringes to prevent HIV transmission, providing basic life needs such as shelter for street-based drug users to reduce the social consequences like homelessness, prescribing substitute agonists to reduce the committing crime to obtain the needed drugs, and even the drug court program, which prevents the exacerbation of complications in a person with a chronic and relapsing disorder, due to the imposition of inappropriate sentences (like incarceration in unacceptable conditions). It is contrary to the approaches that aim to reduce the drug supply rate and drug use incidence and prevalence to zero. As a result of the conflict of interests, goals discrepancies, and differences in organizational culture, these approaches may contrast with each other. We see this in the harm reduction between the health system and law enforcement. Different factors affect the harmony or conflict between these two structures. This article addresses the impact of ideology, social conditions, and bureaucratic administration on the relationship between the health system and the police in drug use harm reduction in Iran.
Myeloid CCN3 protects against aortic valve calcification
Authors: Tu Peinan , Xu Qian , Zhou Xianming , Villa-Roel Nicolas , Kumar Sandeep , Dong Nianguo , Jo Hanjoong , Ou Caiwen , Lin Zhiyong
Published: January 2023

Background

Cellular communication network factor 3 (CCN3) has been implicated in the regulation of osteoblast differentiation. However, it is not known if CCN3 can regulate valvular calcification. While macrophages have been shown to regulate valvular calcification, the molecular and cellular mechanisms of this process remain poorly understood. In the present study, we investigated the role of macrophage-derived CCN3 in the progression of calcific aortic valve disease.

Methods

Myeloid-specific knockout of CCN3 (Mye-CCN3-KO) and control mice were subjected to a single tail intravenous injection of AAV encoding mutant mPCSK9 (rAAV8/D377Y-mPCSK9) to induce hyperlipidemia. AAV-injected mice were then fed a high fat diet for 40 weeks. At the conclusion of high fat diet feeding, tissues were harvested and subjected to histologic and pathologic analyses. In vitro, bone marrow-derived macrophages (BMDM) were obtained from Mye-CCN3-KO and control mice and the expression of bone morphogenic protein signaling related gene were verified via quantitative real-time PCR and Western blotting. The BMDM conditioned medium was cocultured with human valvular intersititial cells which was artificially induced calcification to test the effect of the conditioned medium via Western blotting and Alizarin red staining.

Results

Echocardiography revealed that both male and female Mye-CCN3-KO mice displayed compromised aortic valvular function accompanied by exacerbated valve thickness and cardiac dysfunction. Histologically, Alizarin-Red staining revealed a marked increase in aortic valve calcification in Mye-CCN3-KO mice when compared to the controls. In vitro, CCN3 deficiency augmented BMP2 production and secretion from bone marrow-derived macrophages. In addition, human valvular interstitial cells cultured with conditioned media from CCN3-deficient BMDMs resulted in exaggerated pro-calcifying gene expression and the consequent calcification.

Conclusion

Our data uncovered a novel role of myeloid CCN3 in the regulation of aortic valve calcification. Modulation of BMP2 production and secretion in macrophages might serve as a key mechanism for macrophage-derived CCN3’s anti-calcification function in the development of CAVD.
The epigenetic factor CHD4 contributes to metastasis by regulating the EZH2/β-catenin axis and acts as a therapeutic target in ovarian cancer
Authors: Wang Jieyu , Zhong Fangfang , Li Jun , Yue Huiran , Li Wenzhi , Lu Xin
Published: January 2023

Background

The overall survival rate of patients with advanced ovarian cancer (OC) has remained static for several decades. Advanced ovarian cancer is known for its poor prognosis due to extensive metastasis. Epigenetic alterations contribute to tumour progression and therefore are of interest for potential therapeutic strategies.

Methods

Following our previous study, we identified that CHD4, a chromatin remodelling factor, plays a strong role in ovarian cancer cell metastasis. We investigated the clinical significance of CHD4 through TCGA and GEO database analyses and explored the effect of CHD4 expression modulation and romidepsin treatment on the biological behaviour of ovarian cancer through CCK-8 and transwell assays. Bioluminescence imaging of tumours in xenografted mice was applied to determine the therapeutic effect of romidepsin. GSEA and western blotting were used to screen the regulatory mechanism of CHD4.

Results

In ovarian cancer patient specimens, high CHD4 expression was associated with a poor prognosis. Loss of function of CHD4 in ovarian cancer cells induced suppression of migration and invasion. Mechanistically, CHD4 knockdown suppressed the expression of EZH2 and the nuclear accumulation of β-catenin. CHD4 also suppressed the metastasis of ovarian cancer cells and prevented disease progression in a mouse model. To inhibit the functions of CHD4 that are mediated by histone deacetylase, we evaluated the effect of the HDAC1/2 selective inhibitor romidepsin. Our findings indicated that treatment with romidepsin suppressed the progression of metastases in vitro and in vivo.

Conclusions

Collectively, our results uncovered an oncogenic function of CHD4 in ovarian cancer and provide a rationale for clinical trials of romidepsin in ovarian cancer patients.
Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging
Authors: Wan Wei , Zhang Lieliang , Lin Yue , Rao Xiuqing , Wang Xifeng , Hua Fuzhou , Ying Jun
Published: January 2023

MOTS-c is a peptide encoded by the short open reading frame of the mitochondrial 12S rRNA gene. It is significantly expressed in response to stress or exercise and translocated to the nucleus, where it regulates the expression of stress adaptation-related genes with antioxidant response elements (ARE). MOTS-c mainly acts through the Folate-AICAR-AMPK pathway, thereby influencing energy metabolism, insulin resistance, inflammatory response, exercise, aging and aging-related pathologies. Because of the potential role of MOTS-c in maintaining energy and stress homeostasis to promote healthy aging, especially in view of the increasing aging of the global population, it is highly pertinent to summarize the relevant studies. This review summarizes the retrograde signaling of MOTS-c toward the nucleus, the regulation of energy metabolism, stress homeostasis, and aging-related pathological processes, as well as the underlying molecular mechanisms.
An iceberg I can’t handle: a qualitative inquiry on perceptions towards paediatric rheumatology among healthcare workers in Kenya
Authors: Migowa Angela , Bernatsky Sasha , Ngugi Anthony , Foster Helen E. , Muriuki Peter , Lusambili Adelaide , Luchters Stanley
Published: January 2023

Background

Delay in diagnosis and access to specialist care is a major problem for many children and young people with rheumatic disease in sub-Saharan Africa. Most children with symptoms of rheumatic disease present to non-specialists for care. There is an urgent need to understand and scale-up paediatric rheumatology knowledge and skills amongst non-specialist healthcare workers to promote early diagnosis, prompt referral, and management.

Purpose

We evaluated the knowledge, attitudes and practices towards diagnosis and care of paediatric rheumatology patients among health care workers in Kenya.

Methods

We conducted 12 focus group discussions with clinical officers (third-tier community health workers) nurses, general practitioners and paediatricians across 6 regions in Kenya. Interviews were conducted on zoom, audio-recorded, transcribed, and analysed using NVIVO software.

Results

A total of 68 individuals participated; 11 clinical officers, 12 nurses, 10 general practitioners, 27 paediatricians and 7 others. Most (n = 53) were female, and the median age was 36 years (range 31–40 years). Fifty per cent of the participants (34 of 68) worked in public health facilities. Our study revealed gaps in knowledge of paediatric rheumatology amongst healthcare workers which contributes to delayed diagnosis and poor management. Healthcare workers reported both positive and negative attitudes towards diagnosis and care of paediatric rheumatology patients. Perceived complexity and lack of knowledge in diagnosis, management and lack of health system clinical pathways made all cadres of healthcare workers feel helpless, frustrated, inadequate and incompetent to manage paediatric rheumatology patients. Positive attitudes arose from a perceived feeling that paediatric rheumatology patients pose unique challenges and learning opportunities.

Conclusion

There is an urgent need to educate healthcare workers and improve health systems to optimize clinical care for paediatric rheumatology patients.
Abcc8 (sulfonylurea receptor-1) knockout mice exhibit reduced axonal injury, cytotoxic edema and cognitive dysfunction vs. wild-type in a cecal ligation and puncture model of sepsis
Authors: Cummings Jessica , Wu Yijen L. , Dixon C. Edward , Henchir Jeremy , Simard J. Marc , Panigrahy Ashok , Kochanek Patrick M. , Jha Ruchira M. , Aneja Rajesh K.
Published: January 2023

Sepsis-associated brain injury (SABI) is characterized by an acute deterioration of mental status resulting in cognitive impairment and acquisition of new and persistent functional limitations in sepsis survivors. Previously, we reported that septic mice had evidence of axonal injury, robust microglial activation, and cytotoxic edema in the cerebral cortex, thalamus, and hippocampus in the absence of blood–brain barrier disruption. A key conceptual advance in the field was identification of sulfonylurea receptor 1 (SUR1), a member of the adenosine triphosphate (ATP)-binding cassette protein superfamily, that associates with the transient receptor potential melastatin 4 (TRPM4) cation channel to play a crucial role in cerebral edema development. Therefore, we hypothesized that knockout (KO) ofAbcc8(Sur1 gene) is associated with a decrease in microglial activation, cerebral edema, and improved neurobehavioral outcomes in a murine cecal ligation and puncture (CLP) model of sepsis. Sepsis was induced in 4–6-week-oldAbcc8KO and wild-type (WT) littermate control male mice by CLP. We used immunohistochemistry to define neuropathology and microglial activation along with parallel studies using magnetic resonance imaging, focusing on cerebral edema on days 1 and 4 after CLP.Abcc8KO mice exhibited a decrease in axonal injury and cytotoxic edema vs. WT on day 1.Abcc8KO mice also had decreased microglial activation in the cerebral cortex vs. WT. These findings were associated with improved spatial memory on days 7–8 after CLP. Our study challenges a key concept in sepsis and suggests that brain injury may not occur merely as an extension of systemic inflammation. We advance the field further and demonstrate that deletion of the SUR1 gene ameliorates CNS pathobiology in sepsis including edema, axonal injury, neuroinflammation, and behavioral deficits. Benefits conferred byAbcc8KO in the murine CLP model warrant studies of pharmacologicalAbcc8inhibition as a new potential therapeutic strategy for SABI.
Cost-effectiveness analysis of overground robotic training versus conventional locomotor training in people with spinal cord injury
Authors: Pinto Daniel , Heinemann Allen W. , Chang Shuo-Hsiu , Charlifue Susan , Field-Fote Edelle C. , Furbish Catherine L. , Jayaraman Arun , Tefertiller Candace , Taylor Heather B. , French Dustin D.
Published: January 2023

Background

Few, if any estimates of cost-effectiveness for locomotor training strategies following spinal cord injury (SCI) are available. The purpose of this study was to estimate the cost-effectiveness of locomotor training strategies following spinal cord injury (overground robotic locomotor training versus conventional locomotor training) by injury status (complete versus incomplete) using a practice-based cohort.

Methods

A probabilistic cost-effectiveness analysis was conducted using a prospective, practice-based cohort from four participating Spinal Cord Injury Model System sites. Conventional locomotor training strategies (conventional training) were compared to overground robotic locomotor training (overground robotic training). Conventional locomotor training included treadmill-based training with body weight support, overground training, and stationary robotic systems. The outcome measures included the calculation of quality adjusted life years (QALYs) using the EQ-5D and therapy costs. We estimate cost-effectiveness using the incremental cost utility ratio and present results on the cost-effectiveness plane and on cost-effectiveness acceptability curves.

Results

Participants in the prospective, practice-based cohort with complete EQ-5D data (n = 99) qualified for the analysis. Both conventional training and overground robotic training experienced an improvement in QALYs. Only people with incomplete SCI improved with conventional locomotor training, 0.045 (SD 0.28), and only people with complete SCI improved with overground robotic training, 0.097 (SD 0.20). Costs were lower for conventional training, $1758 (SD $1697) versus overground robotic training $3952 (SD $3989), and lower for those with incomplete versus complete injury. Conventional overground training was more effective and cost less than robotic therapy for people with incomplete SCI. Overground robotic training was more effective and cost more than conventional training for people with complete SCI. The incremental cost utility ratio for overground robotic training for people with complete spinal cord injury was $12,353/QALY.

Conclusions

The most cost-effective locomotor training strategy for people with SCI differed based on injury completeness. Conventional training was more cost-effective than overground robotic training for people with incomplete SCI. Overground robotic training was more cost-effective than conventional training for people with complete SCI. The effect estimates may be subject to limitations associated with small sample sizes and practice-based evidence methodology. These estimates provide a baseline for future research.
Differential proteomic profile of lumbar and ventricular cerebrospinal fluid
Authors: Rostgaard Nina , Olsen Markus Harboe , Ottenheijm Maud , Drici Lylia , Simonsen Anja Hviid , Plomgaard Peter , Gredal Hanne , Poulsen Helle Harding , Zetterberg Henrik , Blennow Kaj , Hasselbalch Steen Gregers , MacAulay Nanna , Juhler Marianne
Published: January 2023

Background

Pathological cerebral conditions may manifest in altered composition of the cerebrospinal fluid (CSF). Although diagnostic CSF analysis seeks to establish pathological disturbances in the brain proper, CSF is generally sampled from the lumbar compartment for reasons of technical ease and ethical considerations. We here aimed to compare the molecular composition of CSF obtained from the ventricular versus the lumbar CSF compartments to establish a relevance for employing lumbar CSF as a proxy for the CSF bathing the brain tissue.

Methods

CSF was collected from 46 patients with idiopathic normal pressure hydrocephalus (iNPH) patients during their diagnostic workup (lumbar samples) and in connection with their subsequent CSF diversion shunt surgery (ventricular samples). The mass-spectrometry-based proteomic profile was determined in these samples and in addition, selected biomarkers were quantified with ELISA (S100B, neurofilament light (NfL), amyloid-β (Aβ40, Aβ42), and total tau (T-tau) and phosphorylated tau (P-tau) forms). The latter analysis was extended to include paired porcine samples obtained from the lumbar compartment and the cerebromedullary cistern closely related to the ventricles.

Results

In total 1231 proteins were detected in the human CSF. Of these, 216 distributed equally in the two CSF compartments, whereas 22 were preferentially (or solely) present in the ventricular CSF and four in the lumbar CSF. The selected biomarkers of neurodegeneration and Alzheimer’s disease displayed differential distribution, some with higher (S100B, T-tau, and P-tau) and some with lower (NfL, Aβ40, Aβ42) levels in the ventricular compartment. In the porcine samples, all biomarkers were most abundant in the lumbar CSF.

Conclusions

The overall proteomic profile differs between the ventricular and the lumbar CSF compartments, and so does the distribution of clinically employed biomarkers. However, for a range of CSF proteins and biomarkers, one can reliably employ lumbar CSF as a proxy for ventricular CSF if or a lumbar/cranial index for the particular molecule has been established. It is therefore important to verify the compartmental preference of the proteins or biomarkers of interest prior to extrapolating from lumbar CSF to that of the ventricular fluid bordering the brain.
Qualitative description of outreach and engagement in perinatal substance treatment in Finland
Authors: Sorsa Minna , Hohenthal Maria , Pikulinsky Miia , Sellergren Hanna , Puura Kaija
Published: January 2023

Background

Women with perinatal substance problems experience a multitude of barriers to care. They have specific early intervention needs, they endure societal stigma, and both substances and mental health issues influence the way they navigate within support and treatment systems. Early interventions for women with perinatal substance problems are underresearched contexts. The aim of the study is to describe building relationships and engagement within an outreach and low threshold service encounter tailored for pregnant women with SUD (substance use disorder).

Methods

The data consist of online written narratives from 11 workers involved in the program and feedback from 504 families in the recovery process comprising 228 open-ended answers. The data were analyzed with a thematic analysis.

Results

The programs are characterized by flexibility and the implementation of inclusive ways to approach families. The themes for enhancing relationships and engagement within outreach and low threshold programs are Acceptance and attitude: a sensitive approach of approval; flexibility within strictness to allow for diversity and individuality; availability and space to ensure a trustful atmosphere; negotiating via doing to build connections; and everyday life changes: imagining recovery. The themes represent the need of being available, focusing on the worker’s attitudes and building connections by doing together, and visioning recovery together.

Conclusions

The study results can add to the understanding of SUD outreach and low threshold work during pregnancy. The elements described in this study need further theoretical development, research and critical assessment. Building relationships during pregnancy were characterized by connecting within everyday life situations and supporting the development of an attachment relationship between the baby and the parents. To promote recovery, a comprehensive approach in which substance-related issues and mental health conditions are interconnected can be favored. Engaging early on during pregnancy might enhance success during future rehabilitation.
Proposed prognostic subgroups and facilitated clinical decision-making for additional locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: a retrospective study based on recursive partitioning analysis
Authors: Yao Yuyi , Sun Xuesong , Huang Huageng , Wang Zhao , Fang Xiaojie , Chen Meiting , Chen Zegeng , Weng Huawei , Guo Chengcheng , Hong Huangming , Huang He , Lin Tongyu
Published: January 2023

Background

The high heterogeneity of de novo metastatic nasopharyngeal carcinoma (dmNPC) makes its prognosis and treatment challenging. We aimed to accurately stage dmNPC and assess the patterns of treatment strategies for different risk groups.

Methods

The study enrolled a total of 562 patients, 264 from 2007 to 2013 in the training cohort and 298 from 2014 to 2017 in the validation cohort. Univariate and multivariate Cox regression analyses were conducted to determine the independent variables for overall survival (OS). Recursive partitioning analysis (RPA) was applied to establish a novel risk-stratifying model based on these variables.

Results

After pairwise comparisons of OS, three risk groups were generated: low-risk (involved lesions ≤ 4 without liver involvement), intermediate-risk (involved lesions ≤ 4 with liver involvement or involved lesions > 4 with Epstein–Barr virus (EBV)-DNA < 62,000 copies/ml), and high-risk (involved lesions > 4 with EBV-DNA > 62,000 copies/ml). The 3-year OS rate differed significantly between groups (80.4%, 42.0%, and 20.4%, respectively, all P < 0.05). Adding locoregional intensity-modulated radiotherapy (LRRT) followed by palliative chemotherapy (PCT) resulted in a significant OS benefit over PCT alone for the low- and intermediate-risk groups (P = 0.0032 and P = 0.0014, respectively). However, it provided no survival benefits for the high-risk group (P = 0.6). Patients did not benefit from concurrent chemotherapy during LRRT among the three subgroups (P = 0.12, P = 0.13, and P = 0.3, respectively). These results were confirmed with the validation cohort.

Conclusions

The novel RPA model revealed superior survival performance in subgroup stratification and could facilitate more effective treatment strategies for dmNPC.
The lived experience of patients with conflict associated injuries whose wounds are affected by antimicrobial resistant organisms: a qualitative study from northwest Syria
Authors: Aldbis Ahmet , Naal Hady , Kishawi Tarik , Wazni Rim , Abbara Aula
Published: January 2023

Introduction

For those with severe conflict-associated wounds which are affected by antimicrobial resistant (AMR) organisms, health systems during protracted conflict are often ill-equipped to respond to their needs. In this study, our aim is to explore the experiences of those with conflict-associated wounds whose wounds have been infected with AMR bacteria and who reside in northwest Syria (NWS). This is with a view to understanding the challenges they face and how the health and humanitarian system can better respond to their needs.

Methods

A qualitative research methodology where in-depth interviews were conducted with patients who are known to have AMR organisms infecting conflict-associated wounds was used. Patients were recruited from Bab Al-Hawa hospital in NWS based on pre-set inclusion criteria. They were invited to participate in remote interviews due to the ongoing COVID-19 pandemic. Interviews were conducted during January and February 2021 and transcribed in Arabic before thematic analysis was undertaken to identify key themes and subthemes.

Results

14 in-depth interviews were conducted of which 12 were with men. The age range was 20–49 years. We categorised the findings into 6 themes: i. those related to the mechanism of injury, ii, the impact of the conflict on health system accessibility, iii. experiences of immediate inpatient management, iv. the experience of outpatient and home management, v. the current impact of the injury on participants, and vi. participant perspectives around improving healthcare access for those with conflict-related wounds affected by AMR organisms. Important findings relate to the quality and capacity for both immediate and longer-term care and the psychosocial and socioeconomic impacts of the injuries which many of the participants continue to grapple with.

Conclusion

This is the first exploration through qualitative research of the experiences of those with conflict-affected wounds which are infected with AMR organisms in NWS. Emerging themes as told by participants can help stakeholders, including policy makers, humanitarian organisations and those involved with health system planning in NWS consider gaps in current and future care needs (including livelihood opportunities) for this vulnerable group.
Novel CD19-specific γ/δ TCR-T cells in relapsed or refractory diffuse large B-cell lymphoma
Authors: Li Chenggong , Zhou Fen , Wang Jing , Chang Qi , Du Mengyi , Luo Wenjing , Zhang Yinqiang , Xu Jia , Tang Lu , Jiang Huiwen , Liu Lin , Kou Haiming , Lu Cong , Liao Danying , Wu Jianghua , Wei Qiuzhe , Ke Sha , Deng Jun , Liu Cheng , Mei Heng , Hu Yu
Published: January 2023

Background

T cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer.

Methods

We previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule. ET019003 cells were tested in preclinical studies followed by a phase 1 clinical trial.

Results

ET019003 cells produced less cytokines but retained comparable antitumor potency than ET190L1-CAR-T cells in vivo and in vitro. In the first-in-human trial, eight patients with relapsed or refractory DLBCL were treated. CRS of grade 1 was observed in three (37.5%) patients; ICANS of grade 3 was noted in one (12.5%) patient. Elevation of serum cytokines after ET019003 infusion was almost modest. With a median follow-up of 34 (range 6–38) months, seven (87.5%) patients attained clinical responses and six (75%) achieved complete responses (CR). OS, PFS and DOR at 3 years were 75.0%, 62.5%, and 71.4%, respectively. Notably, patient 1 with primary CNS lymphoma did not experience CRS or ICANS and got an ongoing CR for over 3 years after infusion, with detectable ET019003 cells in CSF. ET019003 showed striking in vivo expansion and persisted in 50% of patients at 12 months. Three patients received a second infusion, one for consolidation therapy after CR and two for salvage therapy after disease progression, but no response was observed. ET019003 expansion was striking in the first infusion, but poor in the second infusion.

Conclusions

CD19-specific γ/δ TCR-T cells, ET019003, had a good safety profile and could induce rapid responses and durable CR in patients with relapsed or refractory DLBCL, even primary CNS lymphoma, presenting a novel and potent therapeutic option for these patients.

Trial registration: NCT04014894.
High visceral fat-to-muscle ratio is an independent factor that predicts worse overall survival in patients with primary epithelial ovarian, fallopian tube, and peritoneal cancer
Authors: Ham Sooji , Choi Jin Hwa , Shin Soo Gui , Lee Eun-Ju
Published: January 2023

Background

The intra-abdominal cavity, surrounded by adipocytes, is the main metastatic site of epithelial ovarian, fallopian tube, and peritoneal cancer. Epidemiological and molecular studies have demonstrated a link between adipose tissue and ovarian cancer. However, the clinical significance of fatty tissue has not been elucidated. Thus, we investigated the clinical significance of body composition in patients with epithelial ovarian, fallopian tube, and peritoneal cancer.

Methods

Fat and skeletal muscle areas were measured using software based on pretreatment computed tomography scans at the third lumbar vertebra. Fat-to-muscle ratios were calculated using the total (visceral and subcutaneous) fat area or visceral fat area. High fat-to-muscle ratios were defined by values greater than the mean. Sarcopenia was defined as a skeletal muscle index < 38.7 cm2/m2. The clinicopathological parameters and survival of 153 patients were analyzed.

Results

High visceral fat-to-muscle ratios and sarcopenia at the time of diagnosis were observed in 43.8% and 33.3% of the patients, respectively. Multivariate analysis showed that high visceral fat-to-muscle ratio (p = 0.014), advanced Federation of Gynecology and Obstetrics stage (p = 0.008), and chemoresistance (p = 0.027) were independent factors for worse overall survival. Patients with high visceral fat-to-muscle ratios were older, had higher body mass indexes, and were more likely to have diabetes/hypertension, serous cancer subtypes, and implementation of neoadjuvant chemotherapy than those with low visceral fat-to-muscle ratios. The platelet count was significantly higher in the high visceral fat-to-muscle ratio group than in the low visceral fat-to-muscle ratio group (p = 0.011).

Conclusions

Pretreatment visceral fat area could be an independent predictive factor of overall survival in patients with epithelial ovarian, fallopian tube, and peritoneal cancer and may be significantly associated with thrombocytosis.
Relationship between nutrient intakes in the transition phase and postnatal growth of preterm infants: a systematic review
Authors: Wang Na , Zhang Jia , Wang Bo , Yu Zhangbin , Zhang Jun , Qu Linlin , Tang Bin
Published: January 2023

Nutrition practices for preterm infants include phases of parenteral nutrition, gradually interrupted parenteral nutrition (transition phase), and full enteral nutrition. However, nutrition management during the transition phase is frequently overlooked. This review examined the relationship between nutrient intake during the transition phase and preterm infant growth. PubMed, Embase, Web of Science, Cochrane, Chinese National Knowledge Infrastructure Database, Wanfang Database, and Chinese Science and Technique Journals Database were searched for studies examining the relationship between nutrient intake during the transition phase and postnatal growth of preterm infants from each database's earliest inception through February 28, 2022. The quality of the studies was assessed using the Newcastle–Ottawa scale. A total of three studies conducted in the USA, Italy and China met the inclusion criteria. The growth indicators were extrauterine growth restriction (weight < 10th percentile for post-menstrual age) or inadequate weight growth velocity (growth velocity < 15 g/kg/d) at discharge or the end of the transition phase. The transition phase was divided into two periods in two studies: the early period (parenteral energy intake > 50% of total energy intake) and the late period (enteral energy intake > 50% of the total energy intake). The cumulative protein intake in the transition phase was generally lower in preterm infants with extrauterine growth restriction or inadequate weight growth velocity, especially in the early transition phase. The deficiency of energy and protein intake during the transition phase cannot be explicitly determined due to differences in growth indicators and definitions of the transition phase. However, enteral protein intake should be closely monitored in the early transition phase to ensure a better growth rate for preterm infants. To elucidate potential associations, further well-designed research will be required.
Clinician perceptions of the impact of ICU family visiting restrictions during the COVID-19 pandemic: an international investigation
Authors: McPeake Joanne , Kentish-Barnes Nancy , Banse Emilie , Anderson Lynne , Cuzco Cecilia , Azoulay Elie , Quasim Tara , Castro Pedro , Puxty Kathryn
Published: January 2023

Purpose

To guarantee the safety of the public, clinicians and patients during the COVID-19 pandemic, hospital visits were severely restricted internationally. There are limited data on the precise impact of these visiting restrictions on Intensive Care Unit clinicians. Our objectives therefore were to explore the impact of family visitation restrictions on clinicians and care delivery and describe innovation alongside areas for potential improvement.

Methods

A qualitative approach using focus groups was employed. We recruited members of the multi-disciplinary team from Spain, France and the UK. Framework analysis was used to synthesize and interpret data.

Results

In total, 28 staff from multiple international sites contributed to data across six focus groups: 12 from the UK, 9 from France and 7 from Spain. In relation to the key aims, we derived four themes: the emergence of new technologies, relationships and rapport establishment, communication challenges and end-of-life care provision. Across each theme, the overarching concepts of clinician emotional exhaustion and emotional distress emerged alongside the negative impact on job satisfaction.

Conclusion

The impact of COVID-19 family visitation restrictions is far reaching. Future research should examine the wider impact of family presence in the ICU.
Smartphone imaging repository: a novel method for creating a CT image bank
Authors: Dula Adrienne N. , Milling Truman J. , Johnston S. Claiborne , Aydelotte Jayson , Peil Gary W. , Robinson Alec , Asif Kaiz , Pan Stephen , Parekh Sohan , Warach Steven
Published: January 2023

Background

Imaging repositories are commonly attached to ongoing clinical trials, but capturing, transmitting, and storing images can be complicated and labor-intensive. Typical methods include outdated technologies such as compact discs. Electronic file transfer is becoming more common, but even this requires hours of staff time on dedicated computers in the radiology department.

Methods

We describe and test an image capture method using smartphone camera video-derived images of brain computed tomography (CT) scans of traumatic intracranial hemorrhage. The deidentified videos are emailed or uploaded from the emergency department for central adjudication. We selected eight scans, mild moderate, and severe subdural and multicompartmental hematomas and mild and moderate intraparenchymal hematomas. Ten users acquired data using seven different smartphones. We measured the time in seconds it took to capture and send the files. The primary outcomes were hematoma volume measured by ABC/2, Marshall scale, midline shift measurement, image quality by a contrast-to-noise ratio (CNR), and time to capture. A radiologist and an imaging scientist applied the ABC/2 method and calculated the Marshall scale and midline shift on the data acquired on different smartphones and the PACS in a randomized order. We calculate the intraclass correlation coefficient (ICC). We measured image quality by calculating the contrast-to-noise ratio (CNR). We report summary statistics on time to capture in the smartphone group without a comparator.

Results

ICC for lesion volume, midline shift, and Marshall score were 0.973 (95% CI 0.931, 0.994), 0.998 (95% CI: 0.996, 0.999), and 0.973 (0.931, 0.994), respectively. Lesion conspicuity was not different among the image types via assessment of CNR using the Friedman test, $${\lambda }^{2}$$

λ

2

of 24.8, P =  < .001, with a small Kendall’s W effect size (0.591). Mean (standard deviation) time to capture and email the video was 60.1 (24.3) s.

Conclusions

Typical smartphones may produce video image quality high enough for use in a clinical trial imaging repository. Video capture and transfer takes only seconds, and hematoma volumes, Marshall scales, and image quality measured on the videos did not differ significantly from those calculated on the PACS.
Heterogeneous separation consistency training for adaptation of unsupervised speech separation
Authors: Han Jiangyu , Long Yanhua
Published: January 2023

Recently, supervised speech separation has made great progress. However, limited by the nature of supervised training, most existing separation methods require ground-truth sources and are trained on synthetic datasets. This ground-truth reliance is problematic, because the ground-truth signals are usually unavailable in real conditions. Moreover, in many industry scenarios, the real acoustic characteristics deviate far from the ones in simulated datasets. Therefore, the performance usually degrades significantly when applying the supervised speech separation models to real applications. To address these problems, in this study, we propose a novel separation consistency training, termed SCT, to exploit the real-world unlabeled mixtures for improving cross-domain unsupervised speech separation in an iterative manner, by leveraging upon the complementary information obtained from heterogeneous (structurally distinct but behaviorally complementary) models. SCT follows a framework using two heterogeneous neural networks (HNNs) to produce high confidence pseudo labels of unlabeled real speech mixtures. These labels are then updated and used to refine the HNNs to produce more reliable consistent separation results for real mixture pseudo-labeling. To maximally utilize the large complementary information between different separation networks, a cross-knowledge adaptation is further proposed. Together with simulated dataset, those real mixtures with high confidence pseudo labels are then used to update the HNN separation models iteratively. In addition, we find that combing the heterogeneous separation outputs by a simple linear fusion can further slightly improve the final system performance. In this paper, we use cross-dataset to simulate the cross-domain situation in real-life. The term of “source domain” and “target domain” refer to the simulation set for model pre-training and the real unlabeled mixture for model adaptation. The proposed SCT is evaluated on both public reverberant English and anechoic Mandarin cross-domain separation tasks. Results show that, without any available ground-truth of target domain mixtures, the SCT can still significantly outperform our two strong baselines with up to 1.61 dB and 3.44 dB scale-invariant signal-to-noise ratio (SI-SNR) improvements, on the English and Mandarin cross-domain conditions, respectively.
Unintended pregnancies among HIV-positive women in sub-Saharan Africa: a scoping review protocol
Authors: Oguntade Racheal Tomilola , Ojewole Elizabeth Bolanle , Ogunrombi Modupe Olufunmilayo
Published: January 2023

Background

Unintended pregnancies pose a severe threat to the well-being of HIV-positive women and their unborn children. Factors contributing to the high incidence of unintended pregnancies include contraceptive failure, low uptake of contraceptives, and misuse of contraceptives. Despite various contraceptive options, an increased incidence of unintended pregnancies is rampant among HIV-positive women in the region of sub-Saharan Africa. This study seeks to present evidence of unintended pregnancies among women living with HIV in sub-Saharan Africa, including those using contraceptives.

Method

This study entails a scoping review to survey and interrogate the literature to provide evidence for the incidence of unintended pregnancies among HIV-positive women in sub-Saharan Africa. A proposed framework by Arksey and O’Malley will guide this scoping review. Peer-reviewed articles which address the research questions will constitute the main search. Electronic databases such as EBSCOhost, Cochrane Library, World of Science, World Health Organization (WHO) library databases, Science Direct, Google Scholar PubMed, and gray literature search will be involved. Reference list from studies included will also be searched. The investigation of articles will be done employing keywords from the studies included. The inclusion and exclusion criteria will guide two separate reviewers with the screening of abstracts and full papers. To summarize the findings from this review, thematic content analysis will be done using NVivo version 11.

Discussion

We expect that this review will add to the current body of knowledge on the incidence of unintended pregnancies among HIV-positive women, identify gaps for further future research, and show evidence that may contribute to strengthening the health system’s regulations, guidelines, and policies that may help prevent unintended pregnancies among HIV-positive women.

Systematic review registration

10.17605/OSF.IO/EY3R5
Predicting the total Unified Parkinson’s Disease Rating Scale (UPDRS) based on ML techniques and cloud-based update
Authors: Hamzehei Sahand , Akbarzadeh Omid , Attar Hani , Rezaee Khosro , Fasihihour Nazanin , Khosravi Mohammad R.
Published: January 2023

Nowadays, smart health technologies are used in different life and environmental areas, such as smart life, healthcare, cognitive smart cities, and social systems. Intelligent, reliable, and ubiquitous healthcare systems are a part of the modern developing technology that should be more seriously considered. Data collection through different ways, such as the Internet of things (IoT)-assisted sensors, enables physicians to predict, prevent and treat diseases. Machine Learning (ML) algorithms may lead to higher accuracy in medical diagnosis/prognosis based on health data provided by the sensors to help physicians in tracking symptom significance and treatment steps. In this study, we applied four ML methods to the data on Parkinson’s disease to assess the methods’ performance and identify the essential features that may be used to predict the total Unified Parkinson’s disease Rating Scale (UPDRS). Since accessibility and high-performance decision-making are so vital for updating physicians and supporting IoT nodes (e.g., wearable sensors), all the data is stored, updated as rule-based, and protected in the cloud. Moreover, by assigning more computational equipment and memory in use, cloud computing makes it possible to reduce the time complexity of the training phase of ML algorithms in the cases we want to create a complete structure of cloud/edge architecture. In this situation, it is possible to investigate the approaches with varying iterations without concern for system configuration, temporal complexity, and real-time performance. Analyzing the coefficient of determination and Mean Square Error (MSE) reveals that the outcomes of the applied methods are mostly at an acceptable performance level. Moreover, the algorithm’s estimated weight indicates that Motor UPDRS is the most significant predictor of Total UPDRS.