bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing the upper age limit for blood donation: Perspectives from older donors
Authors: Quee Franke A. , Lathori Asghar Zeinali , Sijtsma Berdine , Bruijns Sanne , van den Hurk Katja 
Published: April 2024

AbstractBackground and ObjectivesIn the Netherlands, as of April 2018, the upper age limit for blood donation has been raised from 69 to 79 years, providing an opportunity to study older donors' perspectives regarding donating at older age. This study aims to explore whether older donors agree with the increase of the age limit, if they feel obliged to continue donating, to identify their motivators and barriers for donating blood and describe donation‐related experiences and complications.Materials and MethodsAn online survey was distributed among Dutch blood donors aged 68–73 years. The survey contained questions regarding the increase of the upper age limit, motivations and barriers for donating, donation‐related experiences and obligatory feelings to continue donating.ResultsSix hundred sixty donors (55%) were included in the analyses, including 38 stopped donors. Most donors (92%) agreed with the increase of the upper age limit. Approximately 63% of participating donors felt obliged to continue donating, especially women with high education. Donors indicated they felt healthy enough to keep donating (95%), and 72% thought it is good for their health to keep donating. Few donors reported that they found it hard to keep donating (5%) or indicated that they did not feel healthy enough to donate or thought it was not safe for them anymore (3.4%).ConclusionMost of the older donors agree with the increase of the upper age limit for blood donation, report only few and minor donation‐related experiences or complications and are highly motivated to continue their donor career at an older age.
Extended blood stage sensitivity profiles of
Plasmodium cynomolgi
to doxycycline and tafenoquine, as a model for
Plasmodium vivax
Authors: Christensen Peter , Cinzah Rosy , Suwanarusk Rossarin , Chua Adeline Chiew Yen , Kaneko Osamu , Kyle Dennis E. , Aung Htin Lin , Matheson Jessica , Bifani Pablo , Rénia Laurent , Cook Gregory M. , Snounou Georges , Russell Bruce 
Published: April 2024

ABSTRACT

Testing
Plasmodium vivax
antimicrobial sensitivity is limited to
ex vivo
schizont maturation assays, which preclude determining the IC50s of delayed action antimalarials such as doxycycline. Using
Plasmodium cynomolgi
as a model for
P. vivax
, we determined the physiologically significant delayed death effect induced by doxycycline [IC
50(96 h)
, 1,401 ± 607 nM]. As expected, IC
50(96 h)
to chloroquine (20.4 nM), piperaquine (12.6 µM), and tafenoquine (1,424 nM) were not affected by extended exposure.
Inhibition of influenza A virus and SARS-CoV-2 infection or co-infection by griffithsin and griffithsin-based bivalent entry inhibitor
Authors: Cao Najing , Cai Yanxing , Huang Xin , Jiang Hanxiao , Huang Ziqi , Xing Lixiao , Lu Lu , Jiang Shibo , Xu Wei 
Published: April 2024

ABSTRACT

Outbreaks of acute respiratory viral diseases, such as influenza and COVID-19 caused by influenza A virus (IAV) and SARS-CoV-2, pose a serious threat to global public health, economic security, and social stability. This calls for the development of broad-spectrum antivirals to prevent or treat infection or co-infection of IAV and SARS-CoV-2. Hemagglutinin (HA) on IAV and spike (S) protein on SARS-CoV-2, which contain various types of glycans, play crucial roles in mediating viral entry into host cells. Therefore, they are key targets for the development of carbohydrate-binding protein-based antivirals. This study demonstrated that griffithsin (GRFT) and the GRFT-based bivalent entry inhibitor GL25E (GRFT-L25-EK1) showed broad-spectrum antiviral effects against IAV infection
in vitro
by binding to HA in a carbohydrate-dependent manner and effectively protected mice from lethal IAV infection. Although both GRFT and GL25E could inhibit infection of SARS-CoV-2 Omicron variants, GL25E proved to be significantly more effective than GRFT and EK1 alone. Furthermore, GL25E effectively inhibited
in vitro
co-infection of IAV and SARS-CoV-2 and demonstrated good druggability, including favorable safety and stability profiles. These findings suggest that GL25E is a promising candidate for further development as a broad-spectrum antiviral drug for the prevention and treatment of infection or co-infection from IAV and SARS-CoV-2.

IMPORTANCE
Influenza and COVID-19 are highly contagious respiratory illnesses caused by the influenza A virus (IAV) and SARS-CoV-2, respectively. IAV and SARS-CoV-2 co-infection exacerbates damage to lung tissue and leads to more severe clinical symptoms, thus calling for the development of broad-spectrum antivirals for combating IAV and SARS-CoV-2 infection or co-infection. Here we found that griffithsin (GRFT), a carbohydrate-binding protein, and GL25E, a recombinant protein consisting of GRFT, a 25 amino acid linker, and EK1, a broad-spectrum coronavirus inhibitor, could effectively inhibit IAV and SARS-CoV-2 infection and co-infection by targeting glycans on HA of IAV and spike (S) protein of SARS-CoV-2. GL25E is more effective than GRFT because GL25E can also interact with the HR1 domain in SARS-CoV-2 S protein. Furthermore, GL25E possesses favorable safety and stability profiles, suggesting that it is a promising candidate for development as a drug to prevent and treat IAV and SARS-CoV-2 infection or co-infection.
Disease severity impacts perceived quality of life in congenital diaphragmatic hernia: a prospective observational study
Authors: Dimmer Alexandra , Meehan Madison , Beauseigle Sabrina , Koclas Louise , Paquette Katryn , Michel Macias Carolina , Moore Shiran S , Sant'Anna Ana , Shapiro Adam , Simoneau Jessica , Villegas Martinez Daniela , Altit Gabriel , Puligandla Pramod 
Published: April 2024

Background
While research indicates comparable quality of life (QOL) in congenital diaphragmatic hernia (CDH) and healthy populations, the effect of CDH severity on patients’ health perceptions remains unexplored. We aimed to assess QOL perception in CDH, hypothesising a decline correlated with increased disease severity.

Methods
In this prospective observational study, we analysed patients with CDH aged 5 years and above participating in a longitudinal outpatient programme. We excluded bilateral CDH, genetic/syndromic conditions, prematurity and late diagnosis. Participants self-administered the age-adapted Pediatric Quality of Life Inventory (PedsQL) survey, covering four domains (physical, emotional, social, school). After enrolment, data were collected blind to severity status (larger defects denoting significant/‘severe’ disease). Repeated measurements were managed using a random mixed-effects model.

Results
Of 34 participants (50% males) who completed the PedsQL, 10 provided measurements at two visits. Eight required a patch (type C), while 26 had primary repairs (type A=8; type B=18). Age at first evaluation was comparable across groups (no patch: median 11 (7–16), patch: 13 (8–15) years, p=0.78). Severe CDH correlated significantly with lower PedsQL scores (adjusted β: −18%, 95% CI −28%; −7%, adjusted for age at visit and sex). Lower scores specifically occurred in walking, exercising, social and academic functioning.

Conclusion
Severe CDH significantly lowers QOL. This finding is crucial for resource allocation in long-term CDH health surveillance and advocates for regular inclusion of patient experiences in quality improvement efforts.
Mortality variability and differentials by age and causes of death in rural South Africa, 1994–2018
Authors: Houle Brian , Kabudula Chodziwadziwa , Mojola Sanyu A , Angotti Nicole , Gómez-Olivé Francesc Xavier , Gareta Dickman , Herbst Kobus , Clark Samuel J , Menken Jane , Canudas-Romo Vladimir 
Published: April 2024

IntroductionUnderstanding mortality variability by age and cause is critical to identifying intervention and prevention actions to support disadvantaged populations. We assessed mortality changes in two rural South African populations over 25 years covering pre-AIDS and peak AIDS epidemic and subsequent antiretroviral therapy (ART) availability.MethodsUsing population surveillance data from the Agincourt Health and Socio-Demographic Surveillance System (AHDSS; 1994–2018) and Africa Health Research Institute (AHRI; 2000–2018) for 5-year periods, we calculated life expectancy from birth to age 85, mortality age distributions and variation, and life-years lost (LYL) decomposed into four cause-of-death groups.ResultsThe AIDS epidemic shifted the age-at-death distribution to younger ages and increased LYL. For AHDSS, between 1994–1998 and 1999–2003 LYL increased for females from 13.6 years (95% CI 12.7 to 14.4) to 22.1 (95% CI 21.2 to 23.0) and for males from 19.9 (95% CI 18.8 to 20.8) to 27.1 (95% CI 26.2 to 28.0). AHRI LYL in 2000–2003 was extremely high (females=40.7 years (95% CI 39.8 to 41.5), males=44.8 years (95% CI 44.1 to 45.5)). Subsequent widespread ART availability reduced LYL (2014–2018) for women (AHDSS=15.7 (95% CI 15.0 to 16.3); AHRI=22.4 (95% CI 21.7 to 23.1)) and men (AHDSS=21.2 (95% CI 20.5 to 22.0); AHRI=27.4 (95% CI 26.7 to 28.2)), primarily due to reduced HIV/AIDS/TB deaths in mid-life and other communicable disease deaths in children. External causes increased as a proportion of LYL for men (2014–2018: AHRI=25%, AHDSS=17%). The share of AHDSS LYL 2014–2018 due to non-communicable diseases exceeded pre-HIV levels: females=43%; males=40%.ConclusionsOur findings highlight shifting burdens in cause-specific LYL and persistent mortality differentials in two populations experiencing complex epidemiological transitions. Results show high contributions of child deaths to LYL at the height of the AIDS epidemic. Reductions in LYL were primarily driven by lowered HIV/AIDS/TB and other communicable disease mortality during the ART periods. LYL differentials persist despite widespread ART availability, highlighting the contributions of other communicable diseases in children, HIV/AIDS/TB and external causes in mid-life and non-communicable diseases in older ages.
Healthy lifestyle and the risk of depression recurrence requiring hospitalisation and mortality among adults with pre-existing depression: a prospective cohort study
Authors: Cao Zhi , Min Jiahao , Xiang Yu-Tao , Wang Xiaohe , Xu Chenjie 
Published: April 2024

BackgroundAlthough lifestyle-based treatment approaches are recommended as important aspects of depression care, the quantitative influence of aggregated healthy lifestyles on depression recurrence and mortality remains unknown.ObjectiveTo investigate the association between healthy lifestyle and the risks of first-time hospitalisation for recurrent depression and mortality.Methods26 164 adults with depression (mean (SD) age, 56.0 (7.9) years) were included from UK Biobank between 2006 and 2010 and followed up until 2022. Depression was defined as a physician’s diagnosis in hospital admissions or the use of prescribed antidepressant medication. A weighted healthy lifestyle score (HLS) was calculated based on smoking, alcohol consumption, diet, sleep pattern, physical activity, social health, employment status and greenspace interaction.FindingsOver a 13.3-year follow-up, 9740 cases of first-time hospitalisation due to depression recurrence and 1527 deaths were documented. Compared with the lowest HLS tertile, the highest tertile was associated with a 27% lower risk (HR=0.73, 95% CI 0.69 to 0.77) of first-time hospitalisation for depression recurrence and a 22% (HR=0.78, 95% CI 0.68 to 0.91) lower risk of mortality among adults with depression. Lower risks of first-time hospitalisation for depression recurrence were observed among those who smoked less, drank more alcohol, followed healthier diets and sleep patterns, spent more time employed in current job or had greater exposure to greenspace.Conclusion and implicationsGreater adherence to healthy lifestyle was associated with a lower risk of hospitalisation and mortality among adults with pre-existing depression. Incorporating behaviour modification as an essential part of clinical practice for depressed patients could complement medication-based therapies.
Characterisation of clinical response and transcriptional profiling of proliferating CD8 T cells in the blood of cancer patients after PD-1 monotherapy or combination therapy
Authors: Obeng Rebecca C , Nasti Tahseen H , Martens Kylee , Li Peng , Mariniello Annapaola , Chang Daniel Y , Eberhardt Christiane S , McGuire Donald , Kissick Haydn , Daugherty Candace , Zhang Yuzi , Wieland Andreas , Chen Zhengjia , Switchenko Jeffrey M , Pillai Rathi , Kamphorst Alice O , Leonard Warren J , Ahmed Rafi , Ramalingam Suresh S 
Published: April 2024

ObjectiveImmune checkpoint inhibitors (ICI) that block the programmed cell death 1 (PD-1) pathway have shown promise with limited benefit. We and others have shown in small patient cohorts that an early proliferative CD8 T-cell response in the blood may be predictive of clinical response. However, these studies lack detailed analyses and comparisons between monotherapy and combination therapies.Methods and analysisWe analysed longitudinal blood samples from 103 patients with cancer who received αPD-1 monotherapy or combined with anti-cytotoxic T lymphocyte-associated protein 4 (αCTLA-4) or chemotherapy. Transcriptional analysis of CD8 T cells after the first treatment cycle with effector cells generated following yellow fever virus (YFV-17D) vaccine-induced infection was also compared.ResultsAn early proliferative (Ki-67+) CD8 T-cell response was observed after cycle 1 in 60 patients (58.3%). Patients with early-and-sustained proliferative responses (cycle 1 and beyond) had better clinical responses and survival than patients with an early-but-limited response (p=0.02). The proliferating cells had an effector-like phenotype. The transcriptional profiles of the effector-like CD8 T cells were similar irrespective of treatment type or clinical response but distinct from that of YFV-specific effector CD8 T cells.ConclusionsOur data suggest that early proliferative CD8 T-cell response in the blood is predictive, and that an early-and-sustained proliferative response may further identify patients with prolonged survival. The ICI-induced effector-like CD8 T cells are transcriptionally distinct from highly functional YFV-specific cells, suggesting opportunities for improved T-cell effector function with combination therapies for better clinical outcome.
Implementing the practice of early skin-to-skin contact among infants ≥35 weeks gestation born vaginally: a quality improvement study
Authors: Bhardwaj Naveen Kumar , Sasidharan Rohit , Toteja Nisha , Yadav Bharti , Prasanna KL , Bishnoi Birkha , Gupta Neeraj , Singh Pratibha , Singh Kuldeep , Singh Arun 
Published: April 2024

BackgroundEarly skin-to-skin contact (SSC) at birth has been shown to improve neonatal outcomes due to enhanced cardiorespiratory stability, thermoregulation and breastfeeding success.Local problemThe practice of early SSC was virtually non-existent in our delivery room (DR).Methods and interventionsThe study was conducted in a newly established tertiary care teaching hospital in Western Rajasthan, India. We aimed to improve the median duration of early SSC from 0 min to at least 60 min over 24 weeks in our DR. A quality improvement (QI) team was formed, and all inborn infants ≥35 weeks born vaginally from 9 March 2017 were included. Using the tools of point-of-care QI, we found the lack of standard operating procedure, lack of knowledge among nursing staff regarding early SSC, routine shifting of all infants to radiant warmer, the practice of prioritising birthweight documentation and vitamin K administration as the major hindrances to early SSC. Various change ideas were implemented and tested sequentially through multiple plan–do–study–act (PDSA) cycles to improve the duration of early SSC. Interventions included framing a written policy for SSC, sensitising the nursing staff and resident doctors, actively delaying the alternate priorities, making early SSC a shared responsibility among paediatricians, obstetricians, nursing staff and family members, and continuing SSC in the recovery area of the DR complex.ResultsThe duration of early SSC increased from 0 to 67 min without any additional resources. The practice of SSC got well established in the system as reflected by a sustained improvement of 63 min and 72 min, respectively, at the end of 2 months and 4 years after study completion.ConclusionUsing the QI approach, we established and sustained the practice of early SSC for more than 60 min in our unit by using system analysis and testing change ideas in sequential PDSA cycles.
Digital interventions for adolescents with type 1 diabetes to promote health literacy? A qualitative study on physicians’ perspective in Germany
Authors: Naef Aurélia Naoko , Fischbock Nadine , Tezcan-Güntekin Hürrem , Amelung Volker Eric 
Published: April 2024

IntroductionAdolescents with type 1 diabetes mellitus (T1D) require a high level of health literacy (HL) to prevent complications. It remains unclear what potential digital interventions have for promoting HL among adolescents with T1D, as viewed by physicians working with this target group. Additionally, it is unclear how the institutions (inpatient care and outpatient care) can support and facilitate the use of digital interventions to promote HL.Research design and methodsAn exploratory study was conducted using semistructured interviews with physicians (n=12) in Germany. The interview questions are based on a previous systematic review. The coding was conducted deductively and inductively using MAXQDA software. Subsequently, the interviews were analysed systematically through an iterative process of content analyses in line with Kuckartzet al.ResultsIt was reported by the physicians that digital interventions are underused due to technical resources, lack of structural conditions, information and legal constraints. The utilisation of digital interventions to promote HL was heterogeneous and depended primarily on the willingness of the physicians. Communication strategy techniques were widely employed to motivate patients, an activity occurring mainly in-person, thus limiting the opportunity for the deployment of digital interventions.ConclusionsTo increase the use of digital interventions and improve HL, support for digital literacy skills could be implemented. Capacity building through patient-centred, interdisciplinary and participatory culture should be considered. The findings of this study can provide valuable insights for practice, research and policy.
Discerning clinicopathological features of congenital neutropenia syndromes: an approach to diagnostically challenging differential diagnoses
Authors: Parisi Xenia , Bledsoe Jacob R 
Published: April 2024

The congenital neutropenia syndromes are rare haematological conditions defined by impaired myeloid precursor differentiation or function. Patients are prone to severe infections with high mortality rates in early life. While some patients benefit from granulocyte colony-stimulating factor treatment, they may still face an increased risk of bone marrow failure, myelodysplastic syndrome and acute leukaemia. Accurate diagnosis is crucial for improved outcomes; however, diagnosis depends on familiarity with a heterogeneous group of rare disorders that remain incompletely characterised. The clinical and pathological overlap between reactive conditions, primary and congenital neutropenias, bone marrow failure, and myelodysplastic syndromes further clouds diagnostic clarity.We review the diagnostically useful clinicopathological and morphological features of reactive causes of neutropenia and the most common primary neutropenia disorders: constitutional/benign ethnic neutropenia, chronic idiopathic neutropenia, cyclic neutropenia, severe congenital neutropenia (due to mutations inELANE,GFI1,HAX1,G6PC3,VPS45,JAGN1,CSF3R,SRP54,CLPBandWAS), GATA2 deficiency, Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome, Shwachman-Diamond Syndrome, the lysosomal storage disorders with neutropenia: Chediak-Higashi, Hermansky-Pudlak, and Griscelli syndromes, Cohen, and Barth syndromes. We also detail characteristic cytogenetic and molecular factors at diagnosis and in progression to myelodysplastic syndrome/leukaemia.
Intersectional inequalities in paediatric infectious diseases: a national cohort study in Sweden
Authors: Videholm Samuel , Silfverdal Sven Arne , Gustafsson Per E 
Published: April 2024

BackgroundIt is well known that socially deprived children are more likely to be hospitalised for infections. Less is known about how different social disadvantages interact. Therefore, we examine intersectional inequalities in overall, upper respiratory, lower respiratory, enteric and genitourinary infections in the first 5 years of life.MethodsWe conducted a population-based retrospective cohort study of Swedish children born between 1998 and 2015. Inequalities were examined using analysis of individual heterogeneity and discriminatory accuracy as the analytical framework. A variable with 60 intersectional strata was created by combining information on maternal education, household income, sex/gender and maternal migration status. We estimated the incidence rates of infectious disease hospitalisation for each intersectional strata and the associations between intersectional strata and infectious disease hospitalisations using logistic regression models. We furthermore quantified the discriminatory ability of the intersectional strata with respect to infectious disease hospitalisation.ResultsThe study included 1785 588 children and 318 080 hospital admissions. The highest overall incidence of hospitalisations for infections was found in boys born to low-educated mothers who lived in families with the lowest household income. The overall incidence of infections was unrelated to household income in children born to highly educated mothers. The ability of the intersectional strata to discriminate between children with and without infections was poor.ConclusionWe found that inequalities in paediatric infectious diseases were shaped by the intersections of different social disadvantages. These inequalities should be addressed by public health policies that reach all children.