bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between nonalcoholic fatty liver disease and incident diabetes mellitus among Japanese: a retrospective cohort study using propensity score matching
Authors: Zheng Xiaodan , Cao Changchun , He Yongcheng , Wang Xinyu , Wu Jun , Hu Haofei 
Published: June 2021

Abstract
Background
Previous studies have demonstrated that nonalcoholic fatty liver disease (NAFLD) is a significant risk factor for diabetes mellitus (DM). However, these studies did not completely determine the relationship between NAFLD and DM due to unbalanced confounding factors. The propensity score (PS) is the conditional probability of having a particular exposure, given a set of baseline measured covariates. Propensity score matching (PSM) analysis could minimise the effects of potential confounders. Thus, this study aimed to use PSM analysis to explore the association between NAFLD and DM in a large Japanese cohort.

Methods
This retrospective PSM cohort study was performed on 14,280 Japanese participants without DM at baseline in Murakami Memorial Hospital between 2004 and 2015. The independent variable was NAFLD at baseline, and the outcome was the incidence of DM during follow-up. One-to-one PSM revealed 1671 participants with and without NAFLD. A doubly robust estimation method was applied to verify the correlation between NAFLD and DM.

Results
The risk of developing DM in participants with NAFLD increased by 98% according to the PSM analysis (HR = 1.98, 95% confidence interval [CI]: 1.41–2.80, P < 0.0001). The risk of developing DM in the NAFLD participants was 2.33 times that of the non-NAFLD participants in the PSM cohort after adjusting for the demographic and laboratory biochemical variables (HR = 2.33, 95% CI: 1.63–3.32, P < 0.0001). The participants with NAFLD had a 95% increased risk of DM after adjusting for PS (HR = 1.95, 95% CI: 1.39–2.75, P = 0.0001). All potential confounding variables were not significantly associated with NAFLD and DM after PSM in the subgroup analysis. In the sensitivity analysis, the participants with NAFLD had a 2.17-fold higher risk of developing DM in the original cohort (HR = 2.17, 95% CI: 1.63–2.88, P < 0.0001) and were 2.27-fold more likely to develop DM in the weighted cohort (HR = 2.27, 95% CI: 1.91–2.69, P < 0.00001).

Conclusions
NAFLD was an independent risk factor for the development of DM. The risk of developing DM in the NAFLD participants was 2.33 times that of the non-NAFLD participants in the PSM cohort after adjusting for the demographic and laboratory biochemical variables. The participants with NAFLD had a 95% increased risk of DM after adjusting for PS.
Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy
Authors: Fei Weidong , Zhao Yunchun , Wu Xiaodong , Sun Dongli , Yao Yao , Wang Fengmei , Zhang Meng , Li Chaoqun , Qin Jiale , Zheng Caihong 
Published: June 2021

AbstractGestational trophoblastic tumors seriously endanger child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides a novel strategy for the treatment of trophoblastic tumors. Focusing on the overexpression of human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), cytarabine (Cy, a substrate of ENT1)-grafted liposomes (Cy-Lipo) were introduced for the targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. ENT1 has a high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transportation function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations showed high tumor accumulation and retention in biodistribution studies. More importantly, the designed DSPE-PEG2k-Cy conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, Cy-Lipo@MTX exerted an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds great potential as a high-efficiency target for the rational design of active targeting nanotherapeutics.Graphic abstract
Childbearing vs. clinical trial participation: is it one or the other?
Authors: Hernandez Sarah J. , Hohsfield Lindsay A. 
Published: June 2021

AbstractRecent advances have shed light on the importance of early therapeutic intervention for neurodegenerative diseases. Primary prevention trials present a potential disease-modifying strategy for pre-symptomatic patients of autosomal dominant neurodegenerative diseases (ADND), such as early onset familial Alzheimer’s disease (AD) and Huntington’s disease (HD). As trials target earlier disease stages, however, prospective participants face new ethical and logistical challenges, namely childbearing and reproductive health decisions. Since pregnancy is an exclusion criteria for such trials, participants of reproductive age must choose between participating in research and having a family. Such decisions carry significant burdens for ADND patients that if left unaddressed could impact patient well-being and the field as whole. We use our perspective as scientists, advocates, and ADND family members to highlight current shortcomings in the field regarding trial participation and family planning issues for ADND patients and call for the establishment of a normative standard to address these concerns.
Comparison of the effects of transcranial direct current stimulation and mindfulness-based stress reduction on mental fatigue, quality of life and aggression in mild traumatic brain injury patients: a randomized clinical trial
Authors: Shirvani Sheida , Davoudi Mohammadreza , Shirvani Masoud , Koleini Peiman , Hojat Panah Safora , Shoshtari Fatemeh , Omidi Abdollah 
Published: June 2021

Abstract
Background
The rate of traumatic brain injuries (TBIs) due to the accidents is high around the world. Patients with mild TBIs may suffer from some psychological disorders, including aggression, and mental fatigue, and thus their quality of life decreased. Among different treatments for TBI, two treatments, namely transcranial direct current stimulation (tDCS), and mindfulness-based stress reduction (MBSR) have shown to be effective. Therefore, this study aimed to compare the effects of these two treatments on mental fatigue, aggression and quality of life in mTBI patients.

Materials and methods
This randomized controlled trial study was conducted on 48 TBI patients referred to emergency and neurosurgery departments of Shahid Beheshti Hospital, Kashan, Iran. They were selected using the convenience sampling method. Data were collected using the mental fatigue scale, the World Health Organization Quality of Life-BREF (short version), and the Buss–Perry Aggression Questionnaires. Then, the data were analyzed using a Mixed Repeated Measures ANOVAs, and the Levene and Kolmogorov–Smirnov tests by SPSS-23 software.

Results
The mean age of patients in the three groups of MBSR, tDCS and control were 69.38 + 6.11 (25% male), 25.40 + 12.11 (25% male) and 69.37 + 0.2 (18.8% male), respectively. There was no significant difference between the three groups in terms of mental fatigue, quality of life and aggression (P < 0.05). In addition, the results showed that there was a significant difference between the main effect of time and the interaction between time and group (P < 0.001).

Conclusions
Both MBSR and tDCS methods are effective in reducing the mental fatigue and aggression and increasing quality of life of mTBI patients; MBSR treatment, as indicated in the present study, can be more effective than tDCS in patients with mTBI.
Trial registration : Thailand Registry of Clinical Trials, TCTR20180827003 Registered on August 24, 2018.
Sustainable healthcare – Time for ‘Green Podiatry’
Authors: Evans Angela Margaret 
Published: June 2021

AbstractBackgroundHealthcare aims to promote good health and yet demonstrably contributes to climate change, which is purported to be ‘the biggest global health threat of the 21st century’. This is happening now, with healthcare as an industry representing 4.4% of global carbon dioxide emissions.Main bodyClimate change promotes health deficits from many angles; however, primarily it is the use of fossil fuels which increases atmospheric carbon dioxide (also nitrous oxide, and methane). These greenhouse gases prevent the earth from cooling, resulting in the higher temperatures and rising sea levels, which then cause ‘wild weather’ patterns, including floods, storms, and droughts.Particular vulnerability is afforded to those already health compromised (older people, pregnant women, children, wider health co‐morbidities) as well as populations closer to equatorial zones, which encompasses many low‐and‐middle‐income‐countries. The paradox here, is that poorer nations by spending less on healthcare, have lower carbon emissions from health‐related activity, and yet will suffer most from global warming effects, with scant resources to off‐set the increasing health care needs.Global recognition has forged the Paris agreement, the United Nations sustainable developments goals, and the World Health Organisation climate change action plan. It is agreed that most healthcare impact comes from consumption of energy and resources, and the production of greenhouse gases into the environment.Many professional associations of medicine and allied health professionals are advocating for their members to lead on environmental sustainability; the Australian Podiatry Association is incorporating climate change into its strategic direction.ConclusionPodiatrists, as allied health professionals, have wide community engagement, and hence, can model positive environmental practices, which may be effective in changing wider community behaviours, as occurred last century when doctors stopped smoking.As foot health consumers, our patients are increasingly likely to expect more sustainable practices and products, including ‘green footwear’ options. Green Podiatry, as a part of sustainable healthcare, directs us to be responsible energy and product consumers, and reduce our workplace emissions.
Early onset of clinical leishmaniosis in a litter of pups with evidence of in utero transmission
Authors: Salant Harold , Nachum‑Biala Yaarit , Feinmesser Barbara , Perelmutter Maya , Baneth Gad 
Published: June 2021

Abstract
Background
Canine leishmaniosis (CanL) is a zoonotic disease caused by Leishmania infantum. Although usually transmitted by phlebotomine sand flies, infection by vertical transmission and by blood transfusion have also been reported.

Methods
We describe the very early onset of clinical leishmaniosis, starting from 2 months of age, in a litter of pups born to an infected dam and sire. Seven pups from the litter of nine living in different households showed alopecic, exfoliative dermatitis and ulcerative cutaneous lesions. All pups and both parents were tested on at least one occasion both serologically, by enzyme-linked immunosorbent assay (ELISA), and by polymerase chain reaction (PCR) targeting the Leishmania ribosomal operon internal transcribed spacer 1 region and a short fragment of the kinetoplast minicircle; positive amplicons were sequenced.

Results
All nine pups were PCR positive for L. infantum verified by DNA sequencing, seven were positive by conjunctival, five by blood, four by lymph node, and one by skin PCR from an ulcerative lesion. Both pups with no clinical signs were seronegative, while five of the seven pups with dermatologic abnormalities were seropositive by ELISA. The sire had typical clinical dermatologic and visceral findings of CanL, was seropositive and PCR positive for L. infantum in the lymph node and fluid from the vas deferens tested after the testes were removed by castration. The dam was sub-clinically infected and seronegative, but positive by blood, lymph node and conjunctival PCR for L. infantum. Allopurinol administered to all clinically affected dogs resulted in clinical recovery.

Conclusions
Infection with L. infantum in both parents, the very early age of clinical onset among most of the pups, and the fact that the puppies were born and detected with signs of leishmaniosis in the winter, which is a season without sand fly activity in Israel, strongly suggest vertical transmission. Awareness of the possibility of vertical transmission of L. infantum and infection in littermates should be increased. It is recommended that littermates of young dogs with clinical leishmaniosis should be tested for sub-clinical infection as they may also be infectious to sand flies and thus to other dogs and to humans. Restricting the mating of infected bitches should also be considered to prevent the vertical transmission of the infection.

Graphic abstract
Exploring early combination strategy in Latin American patients with newly diagnosed type 2 diabetes: a sub-analysis of the VERIFY study
Authors: Vencio Sérgio , Manosalva Juan P. , Mathieu Chantal , Proot Pieter , Lozno Hernan Yupanqui , Paldánius Päivi M. 
Published: June 2021

Abstract
Background
Patients with type 2 diabetes mellitus (T2DM) from Latin American countries face challenges in access to healthcare, leading to under-diagnosis, under-achievement of glycemic target, and long-term complications. Early diagnosis and treatment initiation are of paramount importance in this population due to the high prevalence of risk factors such as obesity and metabolic syndrome. The VERIFY study in patients with newly diagnosed T2DM (across 34 countries), assessed the normoglycemic durability (5 years), with early combination (EC) therapy approach versus the traditional stepwise approach of initiating treatment with metformin monotherapy (MET). Here we present the results from the VERIFY study for participants from eight countries in Latin America.

Methods
Newly diagnosed adult patients with T2DM, HbA1c 6.5–7.5% and body-mass index (BMI) of 22–40 kg/m2 were enrolled. The primary endpoint was time to initial treatment failure (TF; HbA1c ≥ 7.0% at two consecutive scheduled visits 13 weeks apart). Time to second TF was evaluated when patients in both groups were receiving and failing on the vildagliptin combination. Safety and tolerability were also assessed for both treatment approaches during the study.

Results
A total of 537 eligible patients (female, 58.8%) were randomly assigned to receive either EC (n = 266) or MET (n = 271). EC significantly reduced the relative risk of time to initial TF by 47% versus MET [HR (95% CI) 0.53 (0.4, 0.7) p < 0.0001]. Overall, 46.4% versus 66.3% of patients achieved the primary endpoint in the EC and MET groups, with a median [interquartile range (IQR)] time to TF of 59.8 (27.5, not evaluable) and 33.4 (12.2, 60.1) months, respectively. The risk for time to second TF was 31% lower with EC (p < 0.0092). A higher proportion of patients receiving EC maintained durable HbA1c < 7.0%, < 6.5%, and < 6.0%. Both treatment approaches were well tolerated, and only 3.2% of participants discontinued the study due to adverse events. All hypoglycemic events (EC: n = 7 and MET: n = 3) were single, mild episodes and did not lead to study discontinuation.

Conclusion
Similar to the global population, long-term clinical benefits were achieved more frequently and without tolerability issues with EC versus standard-of-care MET in this Latin American sub-population.
This study is registered with ClinicalTrials.gov, NCT01528254.
The association between opioids, environmental, demographic, and socioeconomic indicators and COVID-19 mortality rates in the United States: an ecological study at the county level
Authors: Qeadan Fares , Mensah Nana Akofua , Tingey Benjamin , Bern Rona , Rees Tracy , Madden Erin Fanning , Porucznik Christina A. , English Kevin , Honda Trenton 
Published: June 2021

Abstract
Background
The spread of the COVID-19 pandemic throughout the world presents an unprecedented challenge to public health inequities. People who use opioids may be a vulnerable group disproportionately impacted by the current pandemic, however, the limited prior research in this area makes it unclear whether COVID-19 and opioid use outcomes may be related, and whether other environmental and socioeconomic factors might play a role in explaining COVID-19 mortality. The objective of this study is to evaluate the association between opioid-related mortality and COVID-19 mortality across U.S. counties.

Methods
Data from 3142 counties across the U.S. were used to model the cumulative count of deaths due to COVID-19 up to June 2, 2020. A multivariable negative-binomial regression model was employed to evaluate the adjusted COVID-19 mortality rate ratios (aMRR).

Results
After controlling for covariates, counties with higher rates of opioid-related mortality per 100,000 persons were found to be significantly associated with higher rates of COVID-19 mortality (aMRR: 1.0134; 95% CI [1.0054, 1.0214]; P = 0.001). Counties with higher average daily Particulate Matter (PM2.5) exposure also saw significantly higher rates of COVID-19 mortality. Analyses revealed rural counties, counties with higher percentages of non-Hispanic whites, and counties with increased average maximum temperatures are significantly associated with lower mortality rates from COVID-19.

Conclusions
This study indicates need for public health efforts in hard hit COVID-19 regions to also focus prevention efforts on overdose risk among people who use opioids. Future studies using individual-level data are needed to allow for detailed inferences.
The Maudsley Anorexia Nervosa Treatment for Adults (MANTRA): a feasibility case series of an integrated group based approach
Authors: Startup Helen , Franklin-Smith Mary , Barber William , Gilbert Nicola , Brown Yael , Glennon Danielle , Fukutomi Akira , Schmidt Ulrike 
Published: June 2021

AbstractBackgroundIndividuals with Anorexia Nervosa (AN) typically struggle in social and emotional contexts. An Integrated Group Based approach for the delivery of MANTRA - The Maudsley Anorexia Nervosa Treatment for Adults – extends current NICE recommended therapy by augmenting treatment with opportunities for experiential practice in a group context. A feasibility case series, delivered across three NHS community services is presented.MethodsThe design was a case series of four Integrated Group MANTRA treatments delivered across three NHS sites (N = 29). Feasibility data of: retention, acceptability and effectiveness; alongside the qualitative capture of participant experiences of treatment is presented.ResultsPrimary outcomes suggest treatment acceptability. Participants committed to treatment with only 2 dropouts. There was significant change with medium effect sizes for eating disorder cognitions and symptoms (as measured by the global score on EDEQ) and BMI. Core themes emerging from qualitative analysis captured the value of the relational aspect of the treatment, the incorporation of experiential methods, and the opportunity to draw on the support of the group members to reduce shame and stigma.ConclusionsAn Integrated Group based MANTRA approach is a feasible and effective alternative intervention for community Eating Disorder services.
Autotaxin levels in serum and bronchoalveolar lavage fluid are associated with inflammatory and fibrotic biomarkers and the clinical outcome in patients with acute respiratory distress syndrome
Authors: Gao Lijuan , Li Xiaoou , Wang Hao , Liao Yue , Zhou Yongfang , Wang Ke , Hu Jun , Cheng Mengxin , Zeng Zijian , Wang Tao , Wen Fuqiang 
Published: June 2021

Abstract
Background
Autotaxin (ATX) is a secreted glycoprotein that is widely present in extracellular biological fluids and has been implicated in many inflammatory and fibrotic diseases. However, the clinical impact of the release of ATX in patients with acute respiratory distress syndrome (ARDS) remains unclear.

Methods
Serum and bronchoalveolar lavage fluid (BALF) levels of ATX, interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-7, fibronectin, oncostatin M (OSM), and SPARC (secreted protein acidic and rich in cysteine) were collected from 52 patients with ARDS within 24 h of diagnosis. All cytokines were measured by Magnetic Luminex Assay. BALF albumin (BA) and serum albumin (SA) were measured by enzyme-linked immunosorbent assay.

Results
Serum ATX, MMP-7, and BALF IL-8 levels were significantly higher in patients who did not survive than in those who survived up to 28 days after diagnosis of ARDS (P < 0.05). BALF and serum ATX levels were correlated with IL-6, IL-8, and MMP-7 levels in BALF and serum, respectively. In addition, BALF ATX was positively correlated with BALF TNF-α, fibronectin, OSM, and SPARC as well as the BA/SA ratio, while serum ATX was correlated with severity of illness based on the SOFA score and PaO2/FIO2 ratio. Furthermore, serum ATX was better able to predict 28-day ARDS-related mortality (area under the curve 0.744, P < 0.01) than the SOFA score, APACHE II score, or PaO2/FIO2 ratio. Serum ATX independently predicted mortality in a univariate Cox regression model (P < 0.0001).

Conclusion
The serum ATX level is a potential prognostic biomarker in patients with ARDS. BALF ATX is associated with pulmonary biomarkers of inflammation and fibrosis, suggesting a role of ATX in the pathogenesis of ARDS.
Association between increased mortality and bronchial fibroscopy in intensive care units and intermediate care units during COPD exacerbations: an analysis of the 2014 and 2015 National French Medical-based Information System Databases (PMSI)
Authors: Amalric Matthieu , Ahmed Engi , Jung Boris , Suehs Carey , Molinari Nicolas , Bourdin Arnaud , Charriot Jeremy 
Published: June 2021

Abstract
Background
The course of chronic obstructive pulmonary disease (COPD) is punctuated by exacerbations, most often of infectious origin, responsible for many intensive care unit (ICU) and intermediate care unit (IMCU) admissions. Our objective was to study in-hospital mortality during severe COPD exacerbations in ICU and IMCU based on the performance of bronchoscopy.

Methods
A retrospective analysis was carried out on stays in ICUs for COPD exacerbation from the French Programme for the Medicalisation of Information Systems databases for the years 2014 and 2015. Propensity score matching of stays made it possible to constitute two comparable groups on the factors of excess mortality described in the literature (age, sex, SAPS 2, type of admission and bronchial tumour).

Results
We identified 14,491 stays for COPD exacerbation in ICUs, 2586 of which received a bronchoscopy. Mortality was significantly higher in the fibroscopy group (31.32% versus 19.8%). After propensity score matching, we found an excess of mortality in the intervention group (OR = 1.749 [1.516–2.017]) associated with a significantly longer length of stay. The main diagnoses associated with an increased risk of death were pulmonary embolism (OR = 3.251 [1.126–9.384]), bacterial pneumonia (OR = 1.906 [1.173–3.098]) and acute respiratory failure (OR = 1.840 [1.486–2.278]).

Conclusions
Performing bronchoscopy during ICU hospitalisations for severe COPD exacerbations was associated with increased mortality. This increased mortality appears to be related to a bias in patient selection with a procedure reserved for patients with the adverse course.