bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iodine status in women attending Mnazi Mmoja Hospital in Zanzibar: a matched case-control study
Authors: Bysheim Olivia , Vogt Elinor Margrethe Chelsom , Engebretsen Ingunn Marie S , Kassim Mohammed Naufal , Storaas Torgeir , Rosendahl-Riise Hanne 
Published: May 2021

BackgroundIodine deficiency can have adverse health effects in all age groups affecting growth, development and cognitive functions as well as the incidence of goitre. Worldwide, the most important dietary source of iodine is iodised salt. In Tanzania, iodine intake has varied due to multiple salt suppliers producing iodised salt with varying quality. Zanzibar has faced challenges with the packing, storing and monitoring of salt iodisation, and universal salt iodisation has not been achieved. Furthermore, the number of available studies on the iodine status in Zanzibar are sparse.ObjectiveThe main objective of this study is to describe the iodine status of euthyroid female adult patients with and without goitre in Zanzibar.Design and methodsA single-centre matched case-control study was conducted among 48 female patients at the ear, nose and throat clinic of Mnazi Mmoja Hospital, Zanzibar. Blood samples were drawn for serum-analysis of the thyroid hormone profile to confirm that all patients were euthyroid prior to inclusion. Urinary iodine concentrations and the iodine concentration in household salt samples were analysed. A semiquantitative food frequency questionnaire (FFQ) was used to describe trends in the dietary intake of iodine-rich and goitrogenic foods. Clinical examinations were conducted, and the patients were categorised into goitre (cases) and non-goitre (controls) groups.ResultsA moderate iodine deficiency (median urinary iodine concentration between 20 and 49 µg/L) was found in patients both with and without goitre. In total, only 35 % of the salt samples were adequately iodised. The salt samples from the cases had a lower average concentration of iodine compared with the controls. The FFQ revealed that the daily consumption of marine fish and the weekly consumption of raw cassava were more frequent in the cases than the controls.ConclusionThese findings suggest that iodine deficiency may be a problem in both patients with and without goitre in Zanzibar. The salt iodisation programme may require monitoring and implementation of satisfactory quality control practices as universal salt iodisation is yet to be achieved in Zanzibar.
Development of social contact and loneliness measures with validation in social prescribing
Authors: Benson Tim , Seers Helen , Webb Nicola , McMahon Philippa 
Published: May 2021

AimsThis paper describes two patient-reported measures of social contact and loneliness, which are closely related concepts. The first measure (R-Outcomes Social Contact measure) was developed from scratch, based on customer needs and literature review. It covers emotional and social aspects using positive terms. The second measure (R-Outcomes Loneliness measure) is adapted from the GSS Loneliness Harmonised Standard. Both measures are patient-reported outcome measures, based on patients’ own perception of how they feel.MethodThis development started in 2016 in response to customers’ requests to measure social contact/loneliness for patients in social prescribing projects.Both measures are compared with three other loneliness measures (the GSS Loneliness Harmonised Standard, De Jong Gierveld and Campaign to End Loneliness). Both measures are short (36 and 21 words, respectively). Mean improvement is reported as a positive number on a 0–100 scale (where high is good).We tested the psychometric performance and construct validity of the R-Outcomes Social Contact measure using secondary analysis of anonymised data collected before and after social prescribing interventions in one part of Southern England.ResultsIn the validation study, 728 responses, collected during 2019–2020, were analysed. 90% were over 70 years old and 62% women. Cronbach’s α=0.76, which suggests that it is appropriate to use a single summary score. Mean Social Contact scores before and after social prescribing intervention were 59.9 (before) and 66.7 (after, p<0.001).Exploratory factor analysis shows that measures for social contact, health status, health confidence, patient experience, personal well-being, medication adherence and social determinants of health are correlated but distinct factors. Construct validation shows that the results are consistent with nine hypotheses, based on the loneliness literature.ConclusionThe R-Outcomes Social Contact measure has good psychometric and construct validation results in a population referred to social prescribing. It is complementary to other R-Outcomes measures.
Exercise capacity in patients with repaired Tetralogy of Fallot aged 6 to 63 years
Authors: Eshuis Graziella , Hock Julia , Marchie du Sarvaas Gideon , van Duinen Hiske , Neidenbach Rhoia , van den Heuvel Freek , Hillege Hans , Berger Rolf MF , Hager Alfred 
Published: May 2021

ObjectivesThis study aimed to provide a perspective for the interpretation of exercise capacity (peakVO2) in patients with repaired Tetralogy of Fallot (patients with rTOF) by describing the course of peakVO2from patients aged 6–63 years.MethodsA retrospective study was performed between September 2001 and December 2016 in the German Heart Centre Munich, Germany, and in the University Medical Centre Groningen, the Netherlands. A total of 1175 cardiopulmonary exercise tests (CPETs) were collected from 586 patients with rTOF, 46% female. Maximal exertion was verified using a respiratory exchange ratio ≥1.00. PeakVO2was modelled using time-dependent multilevel models for repeated measurements (n=889 in 300 patients), and compared with subject-specific reference values calculated by the models of Bongerset aland Myliuset al.ResultsThe peakVO2of patients with rTOF was reduced at all ages. At the age of 6, the peakVO2was 614 mL/min (70% of predicted (95% CI 67 to 73)). The reduced increase in peakVO2during adolescence resulted in a significant lower maximum peakVO2of 1209 mL/min at 25 years (65% predicted, p<0.001). A linear decline after 25 years was observed in patients and references, although patients showed an accelerated decline, with a -0.24% point of predicted (95% CI 0.11 to 0.38) per year without differences between sexes (p=0.263).ConclusionsThis study provides a context for peakVO2across ages in patients with rTOF under contemporary treatment strategies. It showed that the reduction in peakVO2originates from childhood and declines over time. Sex differences in patients with rTOF were similar to natural existing sex differences.
Solidification transformations in liquid phase separated metastable monotectic Cu-50 at. % Co alloy
Authors: Jegede Oluwatoyin E. , Haque Nafisul , Mullis Andrew M. , Cochrane Robert F. 
Published: May 2021

Metastable monotectic Cu-50 at. % Co alloy produced by arc melting has been processed under micro gravity condition using a drop tube and subjected to differential thermal analysis (DTA). Microstructural evidence from the as solidified sample revealed that rapid cooling of the arc melt process was enough to incite liquid phase separation in the alloy. In the drop tube samples, the melting temperature of the β-phase (Cu-rich) was determined to be 1294.8 K, whereas that of the α-phase (Co-rich) was found to vary with cobalt content.
Successional change, restoration success, and resilience in boreal mixedwood vegetation communities over three decades
Authors: Haeussler Sybille , Kabzems Richard , McClarnon John , Bedford Lorne 
Published: May 2021

Long-term studies of vegetation succession can inform restoration of degraded forests. We examined resilience of a boreal mixedwood vegetation community, asking whether treatments employed to restore wood production in a degraded ecosystem could also restore diversity and composition of vegetation communities. The Inga Lake trial, established in 1987 in northeastern British Columbia, used mechanical, fire, and chemical and manual treatments, encompassing a gradient of restoration effort, and tree planting to restore a shrubland to white spruce (Picea glauca (Moench) Voss) forest. We monitored vascular plant, bryophyte, and macrolichen composition five times over 31 years on five to seven treatments replicated five times. We used mixed-effects models and nonmetric multidimensional scaling to compare diversity and composition among treatments and with mature reference forests. Low- to high-effort restoration created a gradient from broadleaf- to spruce-dominated overstories. Diversity increased with restoration effort. Four of 253 taxa occurred in mature forests only. There was no evidence that lower versus higher effort treatments followed divergent successional pathways toward broadleaved versus spruce reference communities. Our results suggest that these mixedwood vegetation communities lie within a broad domain of successional attraction that confers high ecological resilience to disturbance. Gap cuttings to stimulate understory re-initiation and provide woody debris are recommended to complete the restoration.
Late Pleistocene microlithic industries in the Ayodhya Hills, Purulia, West Bengal: insights from geoarchaeological exploration
Authors: Basak Bishnupriya , Dasgupta Sujit , Paul Ashis K. 
Published: May 2021

Abstract

New evidence from the Ayodhya Hills, located in the western upland of West Bengal, has expanded knowledge of Late Pleistocene microlithic technology spanning 42–25 ka in South Asia. Continuous exploration for the past two decades has resulted in substantial information on technology, distribution of sites and the colluvial context. It is now clear from surface exploration and excavations that there are localized differences in the formation of the colluvial context. At the Mahadebbera and Kana sites, which have yielded optically stimulated luminescence (OSL) dates, the
in situ
occurrence of artefacts in the excavated sections confirm their association with the colluvial context. The occurrence of microliths for a prolonged period (25–34 ka) at Mahadebbera indicates that the colluvial deposition must have followed a slower rate during the course of occupation at the site. At Khududih-Chauniya, a site currently being investigated, excavation and surface exploration indicate that the artefacts are mostly scattered over the regolith surface capping the bedrock; much of the colluvial material from the site has been eroded and transported downslope, exposing the lithic artefacts over the regolithic badland surface. Added interest in this site ensues from recent finds of Middle Paleolithic cores and a Lower Paleolithic core from the badland rain gullies. This promises to complement the already published results from the region, which has emerged as an important zone in understanding the behaviour patterns of anatomically modern humans in South Asia.
Hypoxia-Driven Oncometabolite L-2HG Maintains Stemness-Differentiation Balance and Facilitates Immune Evasion in Pancreatic Cancer
Authors: Gupta Vineet K. , Sharma Nikita S. , Durden Brittany , Garrido Vanessa T. , Kesh Kousik , Edwards Dujon , Wang Dezhen , Myer Ciara , Mateo-Victoriano Beatriz , Kollala Sai Sundeep , Ban Yuguang , Gao Zhen , Bhattacharya Sanjoy K. , Saluja Ashok , Singh Pankaj K. , Banerjee Sulagna 
Published: May 2021

Abstract

In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intratumoral metabolic pathways and leading to poor survival. One metabolic enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate (L-2HG), an epigenetic modifier, that regulates the tumor transcriptome. However, the role of L-2HG in remodeling the pancreatic tumor microenvironment is not known. Here we used mass spectrometry to detect L-2HG in serum samples from patients with pancreatic cancer, comprising tumor cells as well as stromal cells. Both hypoxic pancreatic tumors as well as serum from patients with pancreatic cancer accumulated L-2HG as a result of promiscuous activity of LDHA. This abnormally accumulated L-2HG led to H3 hypermethylation and altered gene expression, which regulated a critical balance between stemness and differentiation in pancreatic tumors. Secreted L-2HG inhibited T-cell proliferation and migration, suppressing antitumor immunity. In a syngeneic orthotopic model of pancreatic cancer, inhibition of LDH with GSK2837808A decreased L-2HG, induced tumor regression, and sensitized tumors to anti-PD1 therapy. In conclusion, hypoxia-mediated promiscuous activity of LDH produces L-2HG in pancreatic tumor cells, regulating the stemness-differentiation balance and contributing to immune evasion. Targeting LDH can be developed as a potential therapy to sensitize pancreatic tumors to checkpoint inhibitor therapy.

Significance:
This study shows that promiscuous LDH activity produces L-2HG in pancreatic tumor and stromal cells, modulating tumor stemness and immune cell function and infiltration in the tumor microenvironment.
Acute Kidney Injury–Induced Systemic Inflammation and Risk of Kidney Cancer Formation
Authors: Kusmartsev Sergei 
Published: May 2021

Abstract
In this issue of Cancer Research, Zhou and colleagues investigate the role of acute kidney injury (AKI) and AKI-associated systemic inflammation in the development of kidney cancer. They demonstrate a positive association between the formation of clear-cell renal cell carcinoma and AKI induced by ischemia-reperfusion injury in genetically modified mice. In parallel with the emergence of kidney tumors, mice with ischemic injury develop systemic inflammation associated with tissue infiltration by neutrophils and fibroblasts and upregulated expression of several inflammatory factors, with CXCL1 displaying the highest levels of upregulation. Accordingly, blockade of CXCL1-mediated signaling inhibited the emergence of kidney tumors in mice subjected to ischemic kidney injury. The study provides evidence for a new experimental approach to prevent the formation of clear-cell renal cell carcinoma and reduce kidney cancer incidence through modulation of the AKI-induced inflammatory response using inhibitors of CXC/CXCR2 axis. As the incidence of kidney cancer continues to increase, new treatment strategies for this devastating disease are urgently needed. Zhou and colleagues provide preclinical proof of concept for a new therapeutic strategy and address an unmet need for this difficult to prevent and treat cancer disease.
See related article by Zhou et al., p. 2690
Tumor Immunity and Immunotherapy for HPV-Related Cancers
Authors: Shamseddine Achraf A. , Burman Bharat , Lee Nancy Y. , Zamarin Dmitriy , Riaz Nadeem 
Published: May 2021

Abstract

Human papillomavirus (HPV) infection drives tumorigenesis in the majority of cervical, oropharyngeal, anal, and vulvar cancers. Genetic and epidemiologic evidence has highlighted the role of immunosuppression in the oncogenesis of HPV-related malignancies. Here we review how HPV modulates the immune microenvironment and subsequent therapeutic implications. We describe the landscape of immunotherapies for these cancers with a focus on findings from early-phase studies exploring antigen-specific treatments, and discuss future directions. Although responses across these studies have been modest to date, a deeper understanding of HPV-related tumor biology and immunology may prove instrumental for the development of more efficacious immunotherapeutic approaches.

Significance:
HPV modulates the microenvironment to create a protumorigenic state of immune suppression and evasion. Our understanding of these mechanisms has led to the development of immunomodulatory treatments that have shown early clinical promise in patients with HPV-related malignancies. This review summarizes our current understanding of the interactions of HPV and its microenvironment and provides insight into the progress and challenges of developing immunotherapies for HPV-related malignancies.
Serum‐Derived Small Extracellular Vesicles From Diabetic Mice Impair Angiogenic Property of Microvascular Endothelial Cells: Role of EZH2
Authors: Cheng Zhongjian , Naga Srikanth Garikipati Venkata , Truongcao May M. , Cimini Maria , Huang Grace , Wang Chunlin , Benedict Cindy , Gonzalez Carolina , Mallaredy Vandana , Goukassian David A. , Verma Suresh K. , Kishore Raj 
Published: May 2021

Background
Impaired angiogenic abilities of the microvascular endothelial cell (MVEC) play a crucial role in diabetes mellitus–impaired ischemic tissue repair. However, the underlying mechanisms of diabetes mellitus–impaired MVEC function remain unclear. We studied the role of serum‐derived small extracellular vesicles (ssEVs) in diabetes mellitus–impaired MVEC function.

Methods and Results
ssEVs were isolated from 8‐week‐old male db/db and db/+ mice by ultracentrifugation and size/number were determined by the Nano‐sight tracking system. Diabetic ssEVs significantly impaired tube formation and migration abilities of human MVECs. Furthermore, local transplantation of diabetic ssEVs strikingly reduced blood perfusion and capillary/arteriole density in ischemic hind limb of wildtype C57BL/6J mice. Diabetic ssEVs decreased secretion/expression of several pro‐angiogenic factors in human MVECs. Mechanistically, expression of enhancer of zest homolog 2 (EZH2), the major methyltransferase responsible for catalyzing H3K27me3 (a transcription repressive maker), and H3K27me3 was increased in MVECs from db/db mice. Diabetic ssEVs increased EZH2 and H3K27me3 expression/activity in human MVECs. Expression of EZH2 mRNA was increased in diabetic ssEVs. EZH2‐specific inhibitor significantly reversed diabetic ssEVs‐enhanced expression of EZH2 and H3K27me3, impaired expression of angiogenic factors, and improved blood perfusion and vessel density in ischemic hind limb of C57BL/6J mice. Finally, EZH2 inactivation repressed diabetic ssEVs‐induced H3K27me3 expression at promoter of pro‐angiogenic genes.

Conclusions
Diabetic ssEVs impair the angiogenic property of MVECs via, at least partially, transferring EZH2 mRNA to MVECs, thus inducing the epigenetic mechanism involving EZH2‐enhanced expression of H3K27me3 and consequent silencing of pro‐angiogenic genes. Our findings unravel the cellular mechanism and expand the scope of bloodborne substances that impair MVEC function in diabetes mellitus.
Factors that contribute to urban–rural gradients in risk of schizophrenia: Comparing Danish and Western Australian registers
Authors: Plana-Ripoll Oleguer , Di Prinzio Patsy , McGrath John J , Mortensen Preben B , Morgan Vera A 
Published: May 2021

Introduction: An association between schizophrenia and urbanicity has long been observed, with studies in many countries, including several from Denmark, reporting that individuals born/raised in densely populated urban settings have an increased risk of developing schizophrenia compared to those born/raised in rural settings. However, these findings have not been replicated in all studies. In particular, a Western Australian study showed a gradient in the opposite direction which disappeared after adjustment for covariates. Given the different findings for Denmark and Western Australia, our aim was to investigate the relationship between schizophrenia and urbanicity in these two regions to determine which factors may be influencing the relationship. Methods: We used population-based cohorts of children born alive between 1980 and 2001 in Western Australia ( N = 428,784) and Denmark ( N = 1,357,874). Children were categorised according to the level of urbanicity of their mother’s residence at time of birth and followed-up through to 30 June 2015. Linkage to State-based registers provided information on schizophrenia diagnosis and a range of covariates. Rates of being diagnosed with schizophrenia for each category of urbanicity were estimated using Cox proportional hazards models adjusted for covariates. Results: During follow-up, 1618 (0.4%) children in Western Australia and 11,875 (0.9%) children in Denmark were diagnosed with schizophrenia. In Western Australia, those born in the most remote areas did not experience lower rates of schizophrenia than those born in the most urban areas (hazard ratio = 1.02 [95% confidence interval: 0.81, 1.29]), unlike their Danish counterparts (hazard ratio = 0.62 [95% confidence interval: 0.58, 0.66]). However, when the Western Australian cohort was restricted to children of non-Aboriginal Indigenous status, results were consistent with Danish findings (hazard ratio = 0.46 [95% confidence interval: 0.29, 0.72]). Discussion: Our study highlights the potential for disadvantaged subgroups to mask the contribution of urban-related risk factors to risk of schizophrenia and the importance of stratified analysis in such cases.
Lajan lajan ’ayatik or “Walking in Complementary Pairs” in the Zapatista Women’s Struggle
Authors: Barbosa Lia Pinheiro 
Published: May 2021

The women’s struggle as articulated by women of the Zapatista movement in their Women’s Revolutionary Law is an insurgent, revolutionary, rebel, and autonomous feminism—a feminism in dialogue with popular feminisms in Latin America such as peasant and popular feminism and communitarian feminism. La lucha articulada por las mujeres del movimiento zapatista en su Ley Revolucionaria de la Mujer constituye un feminismo insurgente, revolucionario, rebelde y autónomo. Es también un feminismo en diálogo con otros feminismos populares en América Latina, tales como el feminismo campesino y popular y el feminismo comunitario.
Can we successfully predict the outcome for extracorporeal shock wave lithotripsy (ESWL) for medium size renal stones? A single-center experience
Authors: Elawady Hossam , Mahmoud Mahmoud A , Samir Mohamed 
Published: May 2021

Background: Extracorporeal shock wave lithotripsy (ESWL) is one of the most used modalities in treatment of renal stones, but its effectiveness can be influenced by many factors related to the patient or the stone itself which may affect the success of stone disintegration. The aim of our study was to investigate the predictive value of some patient and stone-related factors for ESWL success for renal stones. Methods: A total of 100 patients with single radiopaque renal stone 10–20 mm in diameter, undergoing ESWL were enrolled in this study. All patients had non contrast computed tomography (NCCT) done before ESWL. We evaluated body mass index (BMI), skin-to-stone distance (SSD), stone size and Hounsfield density comparing these values between stone free (SF) and residual stone (RS) groups. Results: Of the 100 patients, 70% had successful disintegration. There was no significant difference between stone free (SF) and residual stone (RS) groups as regard age or BMI. Meanwhile, there was a significant difference between SF and RS groups as regard stones’ density and SSD, with higher values in RS group but there was statistically insignificant difference as regard stone size ( p = 0.522). Using logistic regression analysis, we found that Hounsfield unit (HU) was better in predicting successful disintegration than SSD but without statistical significance. Conclusion: HU and SSD are the independent predictive factors for ESWL outcome, and they should be considered when planning ESWL in treatment of medium size renal stones.