bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relevance of infections on the outcomes of patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia treated with hypomethylating agents: a cohort study from the GESMD
Authors: Vilorio-Marqués Laura , Castañón Fernández Christelle , Mora Elvira , Gutiérrez Lorena , Rey Bua Beatriz , Jiménez Lorenzo Maria José , Díaz Beya Marina , Vara Pampliega Miriam , Molero Antonieta , Sánchez-García Joaquín , Calabuig Marisa , Cedena Maria Teresa , Chen-Liang Tzu , Díaz Santa Johana Alejandra , Padilla Irene , Hernández Francisca , Díez Rosana , Asensi Pedro , Xicoy Blanca , Sanz Guillermo , Valcárcel David , Diez-Campelo María , Bernal Teresa 
Published: September 2022

Background: The consequences of infectious toxicity of hypomethylating agents (HMAs) on overall survival (OS) of patients diagnosed with high-risk myeloid neoplasms have not been thoroughly investigated. Objectives: We aimed to evaluate whether infectious events (IEs) negatively influenced the results of HMA treatment in a real-world setting. Design: Observational study. Methods: We obtained data from 412 non-selected consecutive patients from 23 Spanish hospitals who were diagnosed with high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia and were treated with HMA. HMAs received after chemotherapy or stem cell transplant were excluded. All IEs were recorded. Outcomes included OS, modifications to the pre-planned treatment, incidence and characteristics of IEs, hospitalization, red blood cell transfusions, and factors associated with infection. Results: The rate of infection was 1.2 per patient/year. Next-cycle delay ( p = 0.001) and hospitalizations ( p = 0.001) were significantly influenced by IEs. Transfusion requirements during each cycle were significantly higher after infection compared with cycles without infection (coefficient = 1.55 [95% confidence interval (CI) = 1.26–1.84], p < 0.001). The median number of cycles was lower in patients experiencing any infection during the first four cycles (5 [3–8] versu 8 [5–16], p < 0.001). In the multivariable analysis, factors associated with lower OS were having any infection during the first four cycles (hazard ratio (HR) = 1.43 [95% CI = 1.09–1.88], p = 0.01), bone marrow blasts ⩾30% (HR = 2.13 [95% CI = 1.14–3.96], p = 0.01), adverse cytogenetics (HR = 1.70 [95% CI = 1.30–2.24], p < 0.001), and platelet count <50 × 109/l (HR = 1.69 [95% CI = 1.3–2.2], p < 0.001). BM blasts >20% (HR = 1.57 [95% CI = 1.19–2.01], p < 0.001) and adverse cytogenetics (HR = 1.7 [95% CI = 1.35–2.14], p < 0.001) were associated with infection, whereas hemoglobin >9 g/dl (HR = 0.65 [95% CI = 0.51–0.82], p < 0.001) and higher platelet count (HR = 0.997 [95% CI = 0.996–0.998], p = 0.016) protected from it. Conclusion: HMA infectious toxicity worsens OS, hinders the adherence to antineoplastic treatment and results in significant morbidity. Preventive strategies are fundamental in vulnerable patients.
Single-cell analysis of immune cell transcriptome during HIV-1 infection and therapy
Authors: Pollara Justin , Khanal Santosh , Edwards R. Whitney , Hora Bhavna , Ferrari Guido , Haynes Barton F. , Bradley Todd 
Published: September 2022

Abstract
Background
Cellular immune responses are phenotypically and functionally perturbed during HIV-1 infection, with the majority of function restored upon antiretroviral therapy (ART). Despite ART, residual inflammation remains that can lead to HIV-related co-morbidities and mortality, indicating that ART does not fully restore normal immune cell function. Thus, understanding the dynamics of the immune cell landscape during HIV-1 infection and ART is critical to defining cellular dysfunction that occurs during HIV-1 infection and imprints during therapy.

Results
Here, we have applied single-cell transcriptome sequencing of peripheral blood immune cells from chronic untreated HIV-1 individuals, HIV-1-infected individuals receiving ART and HIV-1 negative individuals. We also applied single-cell transcriptome sequencing to a primary cell model of early HIV-1 infection using CD4+ T cells from healthy donors. We described changes in the transcriptome at high resolution that occurred during HIV-1 infection, and perturbations that remained during ART. We also determined transcriptional differences among T cells expressing HIV-1 transcripts that identified key regulators of HIV-1 infection that may serve as targets for future therapies to block HIV-1 infection.

Conclusions
This work identified key molecular pathways that are altered in immune cells during chronic HIV-1 infection that could remain despite therapy. We also identified key genes that are upregulated during early HIV-1 infection that provide insights on the mechanism of HIV-1 infection and could be targets for future therapy.
Dynamic transcriptome and network-based analysis of yellow leaf mutant Ginkgo biloba
Authors: Sun Yue , Bai Pan-Pan , Gu Kai-Jie , Yang Shao-Zong , Lin Han-Yang , Shi Cong-Guang , Zhao Yun-Peng 
Published: September 2022

Abstract
Background
Golden leaf in autumn is a prominent feature of deciduous tree species like Ginkgo biloba L., a landscape tree widely cultivated worldwide. However, little was known about the molecular mechanisms of leaf yellowing, especially its dynamic regulatory network. Here, we performed a suite of comparative physiological and dynamic transcriptional analyses on the golden-leaf cultivar and the wild type (WT) ginkgo to investigate the underlying mechanisms of leaf yellowing across different seasons.

Results
In the present study, we used the natural bud mutant cultivar with yellow leaves “Wannianjin” (YL) as materials. Physiological analysis revealed that higher ratios of chlorophyll a to chlorophyll b and carotenoid to chlorophyll b caused the leaf yellowing of YL. On the other hand, dynamic transcriptome analyses showed that genes related to chlorophyll metabolism played key a role in leaf coloration. Genes encoding non-yellow coloring 1 (NYC1), NYC1-like (NOL), and chlorophyllase (CLH) involved in the degradation of chlorophyll were up-regulated in spring. At the summer stage, down-regulated HEMA encoding glutamyl-tRNA reductase functioned in chlorophyll biosynthesis, while CLH involved in chlorophyll degradation was up-regulated, causing a lower chlorophyll accumulation. In carotenoid metabolism, genes encoding zeaxanthin epoxidase (ZEP) and 9-cis-epoxy carotenoid dioxygenase (NCED) showed significantly different expression levels in the WT and YL. Moreover, the weighted gene co-expression network analysis (WGCNA) suggested that the most associated transcriptional factor, which belongs to the AP2/ERF-ERF family, was engaged in regulating pigment metabolism. Furthermore, quantitative experiments validated the above results.

Conclusions
By comparing the golden-leaf cultivar and the wide type of ginkgo across three seasons, this study not only confirm the vital role of chlorophyll in leaf coloration of YL but also provided new insights into the seasonal transcriptome landscape and co-expression network. Our novel results pinpoint candidate genes for further wet-bench experiments in tree species.
Patient-initiated cardiovascular monitoring with commercially available devices: How useful is it in a cardiology outpatient setting? Mixed methods, observational study
Authors: A’Court Christine , Jenkins Wilfred , Reidy Claire , Papoutsi Chrysanthi 
Published: September 2022

Abstract
Background
The availability, affordability and utilisation of commercially available self-monitoring devices is increasing, but their impact on routine clinical decision-making remains little explored. We sought to examine how patient-generated cardiovascular data influenced clinical evaluation in UK cardiology outpatient clinics and to understand clinical attitudes and experiences with using data from commercially available self-monitoring devices.

Methods
Mixed methods study combining: a) quantitative and qualitative content analysis of 1373 community cardiology clinic letters, recording consultations between January–September 2020 including periods with different Covid-19 related restrictions, and b) semi-structured qualitative interviews and group discussions with 20 cardiology-affiliated clinicians at the same NHS Trust.

Results
Patient-generated cardiovascular data were described in 185/1373 (13.5%) clinic letters overall, with the proportion doubling following onset of the first Covid-19 lockdown in England, from 8.3% to 16.6% (p < 0.001). In 127/185 (69%) cases self-monitored data were found to: provide or facilitate cardiac diagnoses (34/127); assist management of previously diagnosed cardiac conditions (55/127); be deployed for cardiovascular prevention (16/127); or be recommended for heart rhythm evaluation (10/127). In 58/185 (31%) cases clinicians did not put the self-monitored data to any evident use and in 12/185 (6.5%) cases patient-generated data prompted an unnecessary referral. In interviews and discussions, clinicians expressed mixed views on patient-generated data but foresaw a need to embrace and plan for this information flow, and proactively address challenges with integration into traditional care pathways.

Conclusions
This study suggests patient-generated data are being used for clinical decision-making in ad hoc and opportunistic ways. Given shifts towards remote monitoring in clinical care, accelerated by the pandemic, there is a need to consider how best to incorporate patient-generated data in clinical processes, introduce relevant training, pathways and governance frameworks, and manage associated risks.
Secondary respiratory early and late infections in mechanically ventilated patients with COVID-19
Authors: Ceballos María Elena , Nuñez Carolina , Uribe Javier , Vera María Magdalena , Castro Ricardo , García Patricia , Arriata Gabriel , Gándara Vicente , Vargas Camila , Dominguez Angélica , Cerón Inés , Born Pablo , Espíndola Eduardo 
Published: September 2022

Abstract
Background
Patients with COVID-19 receiving mechanical ventilation may become aggravated with a secondary respiratory infection. The aim of this study was to describe secondary respiratory infections, their predictive factors, and outcomes in patients with COVID-19 requiring mechanical ventilation.

Methods
A cohort study was carried out in a single tertiary hospital in Santiago, Chile, from 1st June to 31st July 2020. All patients with COVID-19 admitted to the intensive care unit that required mechanical ventilation were included.

Results
A total of 175 patients were enrolled, of which 71 (40.6%) developed at least one secondary respiratory infection during follow-up. Early and late secondary infections were diagnosed in 1.7% and 31.4% respectively. Within late secondary infections, 88% were bacterial, 10% were fungal, and 2% were of viral origin. One-third of isolated bacteria were multidrug-resistant. Bivariate analysis showed that the history of corticosteroids used before admission and the use of dexamethasone during hospitalization were associated with a higher risk of secondary infections (p = 0.041 and p = 0.019 respectively). Multivariate analysis showed that for each additional day of mechanical ventilation, the risk of secondary infection increases 1.1 times (adOR = 1.07; 95% CI 1.02–1.13, p = 0.008)

Conclusions
Patients with COVID-19 admitted to the intensive care unit and requiring mechanical ventilation had a high rate of secondary infections during their hospital stay. The number of days on MV was a risk factor for acquiring secondary respiratory infections.
Exploring Iraqi people’s perception about early marriage: a qualitative study
Authors: Saleh Abubakir M. , Othman Samir M. , Ismail Kameran H. , Shabila Nazar P. 
Published: September 2022

AbstractBackground and objectiveEarly marriage is prevalent in Iraq, but the factors related to this behavior, especially people's attitudes about it, have not been well studied. It has been proven that early marriage seriously threatens young girls' lives and health. This study aimed to explore the perception of people about early marriage in the Iraqi Kurdistan region.MethodsA qualitative method was employed to carry out this study in 2020. Data were collected through 16 focus group discussions in different health centers in Erbil, Iraq. Each focus group included 8–12 participants who had the experience of early marriage. The transcripts of the focus groups were analyzed through the six methodological activities of Van Manen. The trustworthiness of the data was confirmed by using qualitative data evaluation criteria.ResultsDifferent themes and subthemes regarding the ideal age of marriage, attitudes toward marriage, reasons for early marriage, advantages and disadvantages of early marriage, and practice of early marriage in the community emerged from focus group discussions. Most participants identified early marriage as inappropriate social behavior that should not be practiced. Reasons for early marriage included poor economic status, protection of girls and boys, low educational level, and respect for old traditions of the community. Divorce and violence against women were the main disadvantages of early marriage.ConclusionThere is a generally negative attitude towards early marriage, and the practice's disadvantages and health and psychological consequences are well recognized in Iraqi Kurdistan Region. However, different social, traditional, economic, educational, and religious factors encourage early marriage in the region. Further research is recommended in other governorates in the area to have a more precise and representative idea about the topic.
Predictors of nonresponse and drop-out among children and adolescents receiving TF-CBT: investigation of client-, therapist-, and implementation factors
Authors: Skar Ane-Marthe Solheim , Braathu Nora , Jensen Tine K. , Ormhaug Silje Mørup 
Published: September 2022

Abstract
Background
There is a paucity of evidence about effective implementation strategies to increase treatment response and prevent drop-out among children receiving evidence-based treatment. This study examines patient, therapist, and implementation factors and their association to nonresponse and drop-out among youth receiving Trauma-Focused Cognitive Behavioral Therapy (TF-CBT).

Methods
Youth (n = 1240) aged 6–18 (M = 14.6) received TF-CBT delivered by 382 TF-CBT therapists at 66 clinics. Odds ratio analyses were used to investigate whether pretreatment child (age, gender, number of trauma experiences, post-traumatic stress symptoms (PTSS), therapist (education), and implementation strategy factors (high-low, low-low, low–high intensity therapist and leadership training respectively) or tele-mental health training during the Covid-19 pandemic are associated with nonresponse (above clinical PTSS level post-treatment) and drop-out (therapist-defined early termination). Fidelity checks were conducted to ensure that TF-CBT was used consistently.

Results
One fourth of the children (24.4%) were nonresponders and 13.3 percent dropped out. Exposure to three or more traumatic experiences were related to nonresponse and drop-out. Higher baseline PTSS was related to a higher probability of nonresponse. There was no effect of therapist education or child gender on nonresponse and drop-out, whereas children over 15 years had a higher likelihood of both. After controlling for baseline PTSS, the effect of age on nonresponse was no longer significant. Drop-out was related to fewer sessions, and most dropped out during the first two phases of TF-CBT. Fidelity was high throughout the different implementation phases. High-intensity therapist training was related to a lower probability of both nonresponse and drop-out, whereas low therapist and leadership training were related to a higher likelihood of both. Multivariate analysis revealed higher child age and higher PTSS baseline scores as significant predictors of nonresponse, and number of trauma experiences (> = 3) at baseline as the only predictor of drop-out.

Conclusions
High-intensity therapist training seem key to prevent patient nonresponse and drop-out. Leadership training might positively affect both, although not enough to compensate for less intensive therapist training. More complex cases (higher PTSS and exposure to more traumas) predict nonresponse and drop-out respectively, which underscores the importance of symptom assessment to tailor the treatment. The lack of predictive effect of therapist education increases the utilization of TF-CBT.

Trial registration
Retrospectively registered in ClinicalTrials, ref. nr. NCT05248971.
“Death audit is a fight” – provider perspectives on the ethics of the Maternal and Perinatal Death Surveillance and Response (MPDSR) system in Ethiopia
Authors: Cetin Kaya , Worku Dawit , Demtse Asrat , Melberg Andrea , Miljeteig Ingrid 
Published: September 2022

Abstract
Background
Maternal and neonatal health are regarded as important indicators of health in most countries. Death auditing through, for example, the Maternal and Perinatal Death Surveillance and Response (MPDSR) is viewed as key to preventing maternal and newborn mortality. However, little is known about the implications of implementing perinatal auditing for healthcare professionals in low-income contexts. This study aimed to explore the ethical and practical consequences clinicians experience concerning MPDSR reporting practices in Ethiopia.

Methods
Qualitative semi-structured in-depth individual interviews were conducted with 16 healthcare workers across professions at selected facilities in Ethiopia. The interview questions were related to clinicians’ experiences with, and perceptions of, death auditing. Their strategies for coping with newborn losses and the related reporting practices were also explored. The material was analyzed following systematic text condensation, and the NVivo11 software was used for organizing and coding the data material.

Results
Participants experienced fear of punishment and blame in relation to the perinatal death auditing process. They found that auditing did not contribute to reducing perinatal deaths and that their motivation to stick to the obligation was negatively affected by this. Performing audits without available resources to provide optimal care or support in the current system was perceived as unfair. Some hid information or misreported information in order to avoid accusations of misconduct when they felt they were not to blame for the baby’s death. Coping strategies such as engaging in exceedingly larger work efforts, overtreating patients, or avoiding complicated medical cases were described.

Conclusions
Experiencing perinatal death and death reporting constitutes a double burden for the involved healthcare workers. The preventability of perinatal death is perceived as context-dependent, and both clinicians and the healthcare system would benefit from a safe and blame-free reporting environment. To support these healthcare workers in a challenging clinical reality, guidelines and action plans that are specific to the Ethiopian context are needed.
Determining the influence of the primary and specialist network of care on patient and system outcomes among patients with a new diagnosis of chronic obstructive pulmonary disease (COPD)
Authors: Tranmer J. , Rotter T. , O’Donnell D. , Marciniuk D. , Green M. , Kinsman L. , Li W. 
Published: September 2022

Abstract
Introduction
Care for patients with chronic obstructive pulmonary disease (COPD) is provided by both family physicians (FP) and specialists. Ideally, patients receive comprehensive and coordinated care from this provider team. The objectives for this study were: 1) to describe the family and specialist physician network of care for Ontario patients newly diagnosed with COPD and 2) to determine the associations between selected characteristics of the physician network and unplanned healthcare utilization.

Methods
We conducted a retrospective cohort study using Ontario health administrative data housed at ICES (formerly the Institute for Clinical Evaluative Sciences). Ontario patients, ≥ 35 years, newly diagnosed with COPD were identified between 2005 and 2013. The FP and specialist network of care characteristics were described, and the relationship between selected characteristics (i.e., continuity of care) with unplanned healthcare utilization during the first 5 years after COPD diagnosis were determined in multivariate models.

Results
Our cohort consisted of 450,837 patients, mean age 61.5 (SD 14.6) years. The FP was the predominant provider of care for 86.4% of the patients. Using the Bice-Boxerman’s Continuity of Care Index (COCI), a measure reflecting care across different providers, 227,082 (50.4%) were categorized in a low COCI group based on a median cut-off. In adjusted analyses, patients in the low COCI group were more likely to have a hospital admission (OR = 2.27, 95% CI 2.20,2.22), 30-day readmission (OR = 2.44, 95% CI 2.39, 2.49) and ER visit (OR = 2.27, 95% CI 2.25, 2.29).

Conclusion
Higher indices of continuity of care are associated with reduced unplanned hospital use for patients with COPD. Primary care-based practice models to enhance continuity through coordination and integration of both primary and specialist care have the potential to enhance the health experience for patients with COPD and should be a health service planning priority.