bluuebunny/crossref_metadata_2025_split huggingface dataset:
Everyday lives of middle-aged persons living with multimorbidity: protocol of a mixed-methods systematic review
Authors: Gonzalez-Gonzalez Ana Isabel , Brünn Robin , Nothacker Julia , Dinh Truc Sophia , Brueckle Maria-Sophie , Dieckelmann Mirjam , Müller Beate S , van den Akker Marjan 
Published: December 2021

IntroductionMultimorbidity is the simultaneous occurrence of several (chronic) diseases. Persons living with multimorbidity not only have complex care needs, but the burden of care often has a negative impact on their family lives, leisure time and professional activities. The aim of this project is to systematically review the literature to assess how multimorbidity affects the everyday lives of middle-aged persons, and to find out what abilities and resources help in the development of coping strategies to overcome the challenges of living with it.Methods and analysisWe will systematically search for studies reporting on the everyday life experiences of middle-aged persons (30–60 years) with multimorbidity (≥2 chronic conditions) in MEDLINE, CINAHL, PsycINFO, Social Sciences Citation Index, Social Sciences Citation Index Expanded, PSYNDEX and The Cochrane Library from inception. We will include all primary studies that use quantitative, qualitative and mixed methodologies, irrespective of publication date/study setting.Two independent reviewers will screen titles/abstracts/full texts, extract data from the selected studies and present evidence in terms of study/population characteristics, data collection method and the phenomenon of interest, that is, everyday life experiences of middle-aged persons with multimorbidity. Risk of bias will be independently assessed by two reviewers using the Mixed Methods Appraisal Tool. We will use a convergent integrated approach on qualitative/quantitative studies, whereby information will be synthesised narratively and, if possible, quantitatively.Ethics and disseminationEthical approval is not required due to the nature of the proposed systematic review. Results from this research will be disseminated at relevant (inter)national conferences and via publication in peer-reviewed journals.PROSPERO registration numberCRD42021226699.
Vitamin D deficiency, impaired lung function and total and respiratory mortality in a cohort of older men: cross-sectional and prospective findings from The British Regional Heart Study
Authors: Wannamethee S Goya , Welsh Paul , Papacosta Olia , Lennon Lucy , Whincup Peter 
Published: December 2021

ObjectivesVitamin D deficiency is associated with chronic obstructive pulmonary disease (COPD). We examined the cross-sectional association between 25-hydroxyvitamin D (25(OH)D) and lung function impairment and assessed whether vitamin D deficiency is related to long-term mortality in those with impaired lung function.DesignProspective studySettingGeneral practices in the UK.Participants3575 men aged 60–79 years with no prevalent heart failure.Outcome measuresAirway obstruction and mortality. The Global Initiative on Obstructive Lung diseases (GOLD) spirometry criteria was used to define airway obstruction.ResultsDuring the follow-up period of 20 years, there were 2327 deaths (114 COPD deaths). Vitamin D deficiency was defined as serum 25(OH)D levels<10 ng/mL; insufficiency as 25(OH)D 10–19 ng/mL; sufficient as 25(OH)D>20 ng/mL. In cross-sectional analysis, vitamin D deficiency was more prevalent in those with moderate COPD (FEV/FVC <70% and FEV150 to <80%; FEV1, forced expiratory volume in 1 s and FVC, forced vital capacity) and severe COPD (FEV/FVC <70% and FEV1<50%) but not in those with mild COPD (FEV/FVC <70% and FEV1>80%) or restrictive lung disease (FEV1/FVC>70% and FVC <80%) compared with men with normal lung function . Vitamin D deficiency was associated with increased risk of total and respiratory mortality in both men with COPD and men with restrictive lung disease after adjustment for confounders and inflammation. The adjusted HRs (95% CI) for total mortality comparing levels of 25(OH)D<10 ng/mL to 25(OH)D>=20 ng/mL were 1.39 (1.10 to 1.75), 1.52 (1.17 to 1.98), 1.58 (1.17 to 2.14) and 1.39 (0.83 to 2.33) for those with no lung impairment, restrictive lung function, mild/moderate COPD and severe COPD, respectively.ConclusionMen with COPD were more likely to be vitamin D deficient than those with normal lung function. Vitamin D deficiency is associated with increased all-cause mortality in older men with no lung impairment as well as in those with restrictive or obstructive lung impairment.
Consultation patterns and frequent attenders in UK primary care from 2000 to 2019: a retrospective cohort analysis of consultation events across 845 general practices
Authors: Kontopantelis Evangelos , Panagioti Maria , Farragher Tracey , Munford Luke A , Parisi Rosa , Planner Claire , Spooner Sharon , Tse Alice , Ashcroft Darren M , Esmail Aneez 
Published: December 2021

ObjectiveTo describe the distribution of consultations at the practice level and examine whether increases are uniform or driven by people who consult more frequently.DesignRetrospective cohort study.SettingUK general practice data from the Clinical Practice Research Datalink (CPRD) GOLD database.Participants1 699 709 314 consultation events from 12 330 545 patients, in 845 general practices (1 April 2000 to 31 March 2019).MethodsConsultation information was aggregated by financial year into: all consultations/all staff; all consultations/general practitioners (GPs); face-to-face consultations/all staff; face-to-face consultations/GPs. Patients with a number of consultations above the 90th centile, within each year, were classified as frequent attenders. Negative binomial regressions examined the association between available practice characteristics and consultation distribution.ResultsAmong frequent attenders, all consultations by GPs increased from a median (25th and 75th centile) of 13 (10 and 16) to 21 (18 and 25) and all consultations by all staff increased from 27 (23–30) to 60 (51–69) over the study period. Approximately four out of ten consultations of any type concerned frequent attenders and the proportion of consultations attributed to them increased over time, particularly for face-to-face consultations with GPs, from a median of 38.0% (35.9%–40.3%) in 2000–2001 to 43.0% (40.6%–46.4%) in 2018–2019. Regression analyses indicated decreasing trends over time for face-to-face consultations and increasing trends for all consultation types, for both GPs and all staff. Frequent attenders consulted approximately five times more than the rest of the practice population, on average, with adjusted incidence rate ratios ranging between 4.992 (95% CI 4.917 to 5.068) for face-to-face consultations with all staff and 5.603 (95% CI 5.560 to 5.647) for all consultations with GPs.ConclusionsFrequent attenders progressively contributed to increased workload in general practices across the UK from 2000 to 2019. Important knowledge gaps remain in terms of the demographic, social and health characteristics of frequent attenders and how UK general practices can be prepared to meet the needs of these patients.
Early disappearance of tumor antigen-reactive T cells from peripheral blood correlates with superior clinical outcomes in melanoma under anti-PD-1 therapy
Authors: Bochem Jonas , Zelba Henning , Spreuer Janine , Amaral Teresa , Wagner Nikolaus B , Gaissler Andrea , Pop Oltin T , Thiel Karolin , Yurttas Can , Soffel Daniel , Forchhammer Stephan , Sinnberg Tobias , Niessner Heike , Meier Friedegund , Terheyden Patrick , Königsrainer Alfred , Garbe Claus , Flatz Lukas , Pawelec Graham , Eigentler Thomas K , Löffler Markus W , Weide Benjamin , Wistuba-Hamprecht Kilian 
Published: December 2021

BackgroundAnti-programmed cell death protein 1 (PD-1) antibodies are now routinely administered for metastatic melanoma and for increasing numbers of other cancers, but still only a fraction of patients respond. Better understanding of the modes of action and predictive biomarkers for clinical outcome is urgently required. Cancer rejection is mostly T cell-mediated. We previously showed that the presence of NY-ESO-1-reactive and/or Melan-A-reactive T cells in the blood correlated with prolonged overall survival (OS) of patients with melanoma with a heterogeneous treatment background. Here, we investigated whether such reactive T cells can also be informative for clinical outcomes in metastatic melanoma under PD-1 immune-checkpoint blockade (ICB).MethodsPeripheral blood T cell stimulation by NY-ESO-1 and Melan-A overlapping peptide libraries was assessed before and during ICB in two independent cohorts of a total of 111 patients with stage IV melanoma. In certain cases, tumor-infiltrating lymphocytes could also be assessed for such responses. These were characterized using intracellular cytokine staining for interferon gamma (IFN-γ), tumor negrosis factor (TNF) and CD107a. Digital pathology analysis was performed to quantify NY-ESO-1 and Melan-A expression by tumors. Endpoints were OS and progression-free survival (PFS).ResultsThe initial presence in the circulation of NY-ESO-1- or Melan-A-reactive T cells which became no longer detectable during ICB correlated with validated, prolonged PFS (HR:0.1; p>0.0001) and OS (HR:0.2; p=0.021). An evaluation of melanoma tissue from selected cases suggested a correlation between tumor-resident NY-ESO-1- and Melan-A-reactive T cells and disease control, supporting the notion of a therapy-associated sequestration of cells from the periphery to the tumor predominantly in those patients benefitting from ICB.ConclusionsOur findings suggest a PD-1 blockade-dependent infiltration of melanoma-reactive T cells from the periphery into the tumor and imply that this seminally contributes to effective treatment.
Impaired right ventricular function in long-term survivors of allogeneic haematopoietic stem-cell transplantation
Authors: Massey Richard John , Diep Phoi Phoi , Burman Marta Maria , Kvaslerud Anette Borger , Brinch Lorentz , Aakhus Svend , Gullestad Lars , Ruud Ellen , Beitnes Jan Otto 
Published: December 2021

AimsSurvivors of allogeneic haematopoietic stem-cell transplantation (allo-HSCT) are at higher risk of cardiovascular disease. We aimed to describe right ventricular (RV) systolic function and risk factors for RV dysfunction in long-term survivors of allo-HSCT performed in their youth.Methods and resultsThis cohort included 103 survivors (53% female), aged (mean±SD) 17.6±9.5 years at allo-HSCT, with a follow-up time of 17.2±5.5 years. Anthracyclines were used as first-line therapy for 44.7% of the survivors. The RV was evaluated with echocardiography, and found survivors to have reduced RV function in comparison to a group of healthy control subjects: Tricuspid annular plane systolic excursion, (TAPSE, 20.8±3.7 mm vs 24.6±3.8 mm, p<0.001), RV peak systolic velocity (RV-s’, 11.2±2.3 cm/s vs 12.3±2.3 cm/s, p=0.001), fractional area change (FAC, 41.0±5.2% vs 42.2±5.1%, p=0.047) and RV free-wall strain (RVFWS, −27.1±4.2% vs −28.5±3.3%, p=0.043). RV systolic dysfunction (RVSD) was diagnosed in 14 (13.6%), and was strongly associated with progressive left ventricular systolic dysfunction (LVSD). High dosages of anthracyclines were associated with greater reductions in RV and LV function. Multivariable linear regressions confirmed global longitudinal strain to be a significant independent predictor for reduced RV function.ConclusionImpaired RV function was found in long-term survivors of allo-HSCT who were treated in their youth. This was associated with progressive left ventricle dysfunction, and pretransplant therapies with anthracyclines. The occurrence of RVSD was less frequent and was milder than coexisting LVSD in this cohort.
Comparison of six zero-till seed drill openers for establishment and persistence of sod-seeded alfalfa (Medicago sativa L.) in a cool-season perennial grass pasture
Authors: Jefferson Paul G. , Gregg Nathan , Hill Les , Lardner H.A. (Bart) 
Published: December 2021

Zero-till seed drills are readily available for crop seeding in the prairie region of western Canada but have not been evaluated for sod-seeding in perennial forage. Sod-seeding a legume, such as alfalfa (Medicago sativa L.), into the existing perennial grass vegetation improves forage yield and quality for ruminant livestock grazing and production. Suppression of the existing vegetation with herbicide has been reported to increase alfalfa seedling establishment. We evaluated six commercially available zero-till seed drill openers by sod-seeding alfalfa into a crested wheatgrass [Agropyron cristatum (L.) Gaertn.] pasture with or without glyphosate suppression of the existing vegetation in Lanigan Saskatchewan. Alfalfa seedling establishment (52.2 vs. 21.9 seedlings m−1 ± 6.8), alfalfa composition (42.5% vs. 0.2% ± 8.6), and alfalfa yield (1105 kg·ha−1 vs. 12 kg·ha−1 ± 206) in 2011 were increased by the application of herbicide. Seed drill openers performed similarly for all three variables. Nine years later, in June 2020, there was greater alfalfa composition (13.3% vs. 0% ± 2.3) and forage yield (1325 vs. 957 kg·ha−1 ± 127) in the sod-seeded plots than in the unseeded controls but the alfalfa plant cover, alfalfa composition, alfalfa yield and forage yield were similar among seed drill openers. There was also no difference in these variables due to herbicide application nine years prior. Livestock producers can utilize currently available zero-till seeding equipment for sod-seeding alfalfa to rejuvenate grass pastures in the thin Black soil zone of western Canada with the expectation of persistence of alfalfa for nine years.
Fractional Metric Dimension of Generalized Sunlet Networks
Authors: Javaid Muhammad , Zafar Hassan , Bonyah Ebenezer 
Published: December 2021

Let

N
=

V

N

,
E

N

be a connected network with vertex

V

N

and edge set

E

N

⊆

V

N

,
E

N

. For any two vertices

a

and

b

, the distance

d

a
,
b

is the length of the shortest path between them. The local resolving neighbourhood (LRN) set for any edge

e
=
ab

of

N

is a set of all those vertices whose distance varies from the end vertices

a

and

b

of the edge

e

. A real-valued function

Φ

from

V

N

to

0,1

is called a local resolving function (LRF) if the sum of all the labels of the elements of each LRN set remains greater or equal to 1. Thus, the local fractional metric dimension (LFMD) of a connected network

N

is

dim

lf

N

=
min

Φ

:
Φ

is minimal LRF of

N

. In this study, LFMD of various types of sunlet-related networks such as sunlet network (

S

m

), middle sunlet network (

MS

m

), and total sunlet network (

TS

m

) are studied in the form of exact values and sharp bounds under certain conditions. Furthermore, the unboundedness and boundedness of all the obtained results of LFMD of the sunlet networks are also checked.
Patients with Dipper and Nondipper High-Normal Blood Pressure Were Associated with Left Ventricular Mass
Authors: Xiao Fan-kai , Li Ping , Han Zhan-ying , Jing Li , Hua Shaohua , Zhao Luo-sha 
Published: December 2021

Purpose. High-normal blood pressure has been suggested to associate with target organ damage and higher left ventricular mass index (LVMI). Our aim is to find the association between people with high-normal blood pressure and their left ventricular mass index. Materials and Methods. Given a total of 181 people with office blood pressure, 24-hour ambulatory blood pressure monitoring, 35 of them are normotensive (BP < 130/85 mm Hg), and 146 people with high-normal blood pressure (BP 130–139/85–89 mm Hg), divide the high-normal blood pressure group into dipper and nondipper according to their ABPM in 24 hours. All of them were performed with echocardiography to calculate LVMI. Results. After adjusting for potential confounding factors, mean systolic blood pressure (BP) of the nondipper group is (119 + 9) mmHg in 24 h, which is significantly higher (

p

< 0.05) than in the dipper group (116 + 11) mmHg, indicating the mean systolic BP is associated with the dipper type (

p

< 0.05); furthermore, the higher nocturnal blood pressure is associated with the nondipper group significantly (

p

< 0.05), and LVMI ((121 ± 11) g/m2) of the nondipper group is also significantly higher than in the dipper group’s LVMI ((108 ± 12) g/m2) (

p

< 0.05). The multivariate linear regression analyses revealed significant and independent associations of LVMI with these factors: triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL-C), and coefficient of variation of systolic and diastolic blood pressure in 24 hours. Conclusion. After multiple relevant clinical confounding factors were adjusted, patients with dipper and nondipper high-normal blood pressure had higher LVMI. Abnormalities in circadian blood pressure variability may be associated with the left ventricular hypertrophy.
New beginnings in post graduate medical education. Latin American Medical Education Leaders Forum
Authors: Puschel Klaus , Telesco Tai , Grez Marcela , Hoyl Trinidad , Ibañez Luis , Casiro Oscar Casiro 
Published: December 2021

Introduction: The consequences of the Covid-19 epidemic have been catastrophic for Latin America in 2021. This study explores experiences, lessons learned, and practice changes during this critical time in post-graduate medical education in Latin America. Methods: A panel of 53 post-graduate medical education leaders from 8 Latin American countries and Canada was invited to participate in the 2021 Latin American Medical Education Leaders Forum to share their experiences, lessons learned, and main educational practice changes given the Covid-19 pandemic scenario. Participants were selected following a snowball technique with the goal of obtaining a diverse group of experts. Small group discussions were conducted by bilingual facilitators based on a semi-structured questionnaire. The plenary session with the main conclusions of each group was recorded and fully transcribed for a thematic analysis using a framework methods approach. Results: Participants´ profiles included 13 experienced clinician-educators, 19 program directors, and 23 deans or organizational representatives. Seven specific themes emerged. They followed a pattern that went from an initial emotional reaction of surprise to a complex collective response. The responses highlighted the value of adaptability, the application of new digital skills, a renovated residents’ protagonism, the strengthening of humanism in medicine, the openness of new perspectives in wellness, and finally, an unresolved challenge of assessment in medical education in a virtual post-pandemic scenario. Conclusion: A diverse panel of medical educators from Latin America and Canada identified changes triggered by the Covid-19 pandemic that could transform postgraduate medical education in the region.
Association of Metabolic Health and Central Obesity with the Risk of Thyroid Cancer: Data from the Korean Genome and Epidemiology Study
Authors: Nguyen Dung N. , Kim Jin Hee , Kim Mi Kyung 
Published: December 2021

AbstractBackground:It is unknown whether the risk of thyroid cancer differs among metabolically healthy/unhealthy, normal-weight, or obese women. We aimed to assess the association of metabolic health and obesity with thyroid cancer risk.Methods:The Korean Genome and Epidemiology Study is a population-based prospective cohort study. Data were obtained from 173,343 participants (age ≥40 years) enrolled from 2004 to 2013. Obese participants were those with body mass index (BMI) ≥25 kg/m2. Participants with abnormalities in three of these indices were considered metabolically unhealthy: triglycerides, blood pressure, high-density lipoprotein cholesterol (HDL-cholesterol), waist circumference (WC), and fasting glucose levels. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer risk associated with metabolic health and obesity.Results:Compared with nonobese women without metabolic abnormalities, metabolically unhealthy women, either normal weight or obese, had an increased risk of thyroid cancer [HR (95% CI) = 1.57 (1.02–2.40) and 1.71 (1.21–2.41), respectively). Significant association was not observed in men. Thyroid cancer risk was higher among nonobese women with high WC [≥85 cm; HR (95% CI) = 1.62 (1.03–2.56)] than in nonobese women with low WC, and in obese women with low HDL-cholesterol [&lt;50 mg/dL; HR (95% CI) = 1.75 (1.26–2.42)] compared with nonobese women with high HDL-cholesterol.Conclusions:Metabolically unhealthy women or women with central adiposity may be at an increased thyroid cancer risk despite normal BMI.Impact:This study suggests that women with central obesity and metabolic abnormality despite normal BMI may constitute a target group for thyroid cancer prevention and control programs.
Hypoxia Drives Centrosome Amplification in Cancer Cells via HIF1α-dependent Induction of Polo-Like Kinase 4
Authors: Mittal Karuna , Kaur Jaspreet , Sharma Shaligram , Sharma Nivya , Wei Guanhao , Choudhary Ishita , Imhansi-Jacob Precious , Maganti Nagini , Pawar Shrikant , Rida Padmashree , Toss Michael S. , Aleskandarany Mohammed , Janssen Emiel A. , Søiland Håvard , Gupta Meenakshi. V. , Reid Michelle D. , Rakha Emad A. , Aneja Ritu 
Published: December 2021

Abstract

Centrosome amplification (CA) has been implicated in the progression of various cancer types. Although studies have shown that overexpression of PLK4 promotes CA, the effect of tumor microenvironment on polo-like kinase 4 (PLK4) regulation is understudied. The aim of this study was to examine the role of hypoxia in promoting CA via PLK4. We found that hypoxia induced CA via hypoxia-inducible factor-1α (HIF1α). We quantified the prevalence of CA in tumor cell lines and tissue sections from breast cancer, pancreatic ductal adenocarcinoma (PDAC), colorectal cancer, and prostate cancer and found that CA was prevalent in cells with increased HIF1α levels under normoxic conditions. HIF1α levels were correlated with the extent of CA and PLK4 expression in clinical samples. We analyzed the correlation between PLK4 and HIF1A mRNA levels in The Cancer Genome Atlas (TCGA) datasets to evaluate the role of PLK4 and HIF1α in breast cancer and PDAC prognosis. High HIF1A and PLK4 levels in patients with breast cancer and PDAC were associated with poor overall survival. We confirmed PLK4 as a transcriptional target of HIF1α and demonstrated that in PLK4 knockdown cells, hypoxia-mimicking agents did not affect CA and expression of CA-associated proteins, underscoring the necessity of PLK4 in HIF1α-related CA. To further dissect the HIF1α-PLK4 interplay, we used HIF1α-deficient cells overexpressing PLK4 and showed a significant increase in CA compared with HIF1α-deficient cells harboring wild-type PLK4. These findings suggest that HIF1α induces CA by directly upregulating PLK4 and could help us risk-stratify patients and design new therapies for CA-rich cancers.

Implications:
Hypoxia drives CA in cancer cells by regulating expression of PLK4, uncovering a novel HIF1α/PLK4 axis.