bluuebunny/crossref_metadata_2025_split huggingface dataset:
JAK2V617F positive polycythemia vera with paroxysmal nocturnal hemoglobinuria and visceral thromboses: a case report and review of the literature
Authors: Chatzidavid Sevastianos , Giannakopoulou Nefeli , Diamantopoulos Panagiotis Theodorou , Gavriilaki Eleni , Katsiampoura Panagiota , Lakiotaki Eleftheria , Sakellariou Stratigoula , Viniou Nora-Athina , Dryllis Georgios 
Published: March 2021

Abstract
Background
Polycythemia vera (PV) is characterized by red cell mass expansion in the peripheral blood and can be complicated with thrombosis, bleeding, evolution to acute myeloid leukemia (AML) or a fibrotic phase. Paroxysmal nocturnal hemoglobinuria (PNH) in an acquired clonal haematopoietic stem cell disorder associated with chronic intravascular hemolysis, venous thrombosis, defective hematopoiesis, frequent episodes of infection and, rarely, leukemic transformation. Herein, we report an interesting case of a patient with coexistence of PNH clones and a JAK2V617F positive PV, with unusual thromboses without hemolysis.

Case presentation
A 51-year-old woman presented with increased levels of hematocrit, multiple liver, spleen, and left kidney infarctions and ascites; further investigation revealed a JAK2V617F-positive polycythemia vera and the presence of a significant PNH population (more than 90% CD55– CD59– cells among both granulocytes and red blood cells). Interestingly, the patient has experienced severe thrombotic events without any signs or symptoms of hemolysis.

Conclusions
This case raises questions over uncharted aspects of the PNH etiopathogenesis and its potential association with myeloproliferative neoplasms (MPN) and highlights the difficulty of diagnosing and managing patients with more than one potentially thrombophilic conditions, especially with established and severe thromboses.
The V-BRCH Project: building clinical trial research capacity for HIV and noncommunicable diseases in Nigeria
Authors: Aliyu Muktar H. , Sani Mahmoud U. , Ingles Donna J. , Tsiga-Ahmed Fatimah I. , Musa Baba M. , Audet Carolyn M. , Wester C. William 
Published: March 2021

AbstractAntiretroviral therapy has turned HIV into a chronic condition, with morbidity from HIV-associated noncommunicable diseases (NCDs) becoming more common as HIV-infected individuals live longer. In Nigeria, the additional challenge of an under-capacitated health system highlights the need for skilled clinical investigators who can generate evidence to tackle the double burden of HIV and NCDs. The Vanderbilt-Nigeria Building Research Capacity in HIV and Non-communicable Diseases (V-BRCH) programme is a training platform to create a cohort of skilled Nigerian investigators with the capacity to lead independent clinical trial research focused on the intersection of HIV and NCDs. V-BRCH will solidify an atmosphere of continuous mentoring and skills acquisition for physician faculty at the Aminu Kano Teaching Hospital via short- and medium-term learning opportunities, paired mentoring arrangements, and mentored research projects. Trainees will attend an annual faculty enrichment programme in Nashville, in addition to on-site workshops in Nigeria on HIV-associated NCD epidemiology, clinical trials methodology, evidence synthesis, qualitative research methods, stakeholder engagement, knowledge translation, and grant writing. Research-oriented junior faculty will undergo focused training in clinical trials administration and regulatory oversight. Scholars will share best practices through mentoring panels, regular ‘Works in Progress’ meetings, and monthly career development seminars. Competitive seed grants will be provided to mentor–mentee teams to promote targeted in-country pilot studies focused on HIV-associated NCDs. For long-term training, physician scientists will be supported to undergo enhanced Master of Public Health (MPH) training at Bayero University in Nigeria and Master of Science in Clinical Investigation (MSCI) training at Vanderbilt. Short-term regional courses, staff development workshops, and MPH curriculum refinement will help to strengthen institutional capacity in HIV-associated NCD clinical trial research. V-BRCH will create a cohort of skilled Nigerian scientists who will be able to compete for independent funding and design and implement high quality research that will generate evidence to inform policy and practice and lead to improved outcomes for Nigerians impacted by HIV-associated NCDs.
Incidence, causes, and maternofetal outcomes of obstructed labor in Ethiopia: systematic review and meta-analysis
Authors: Ayenew Asteray Assmie 
Published: March 2021

Abstract
Background
Obstructed labor is a preventable obstetric complication. However, it is an important cause of maternal mortality and morbidity and of adverse outcomes for newborns in resource-limited countries in which undernutrition is common resulting in a small pelvis in which there is no easy access to functioning health facilities with a capacity to carry out operative deliveries. Therefore, this systematic review and meta-analysis aimed to estimate the incidence, causes, and maternofetal outcomes of obstructed labor among mothers who gave birth in Ethiopia.

Method
for this review, we used the standard PRISMA checklist guideline. Different online databases were used for the review: PubMed, Google Scholar, EMBASE, Cochrane Library, HINARI, AFRO Library Databases, and African Online Journals. Based on the adapted PICO principles, different search terms were applied to achieve and access the essential articles. The search included all published and unpublished observational studies written only in the English language and conducted in Ethiopia. Microsoft Excel 16 was used for data entrance, and Stata version 11.0 (Stata Corporation, College Station, Texas, USA) was used for data analysis.

Results
I included sixteen (16) primary studies with twenty-eight thousand five hundred ninety-one (28,591) mothers who gave birth in Ethiopia. The pooled incidence of obstructed labor in Ethiopia was 12.93% (95% CI: 10.44–15.42, I2 = 98.0%, p < 0.001). Out of these, 67.3% (95% CI: 33.32–101.28) did not have antenatal care follow-up, 77.86% (95% CI: 63.07–92.66) were from the rural area, and 58.52% (95% CI: 35.73– 82.31) were referred from health centers and visited hospitals after 12 h of labor. The major causes of obstructed labor were cephalo-pelvic disproportion 64.65% (95% CI: 57.15– 72.14), and malpresentation and malposition in 27.24% (95% CI: 22.05–32.42) of the cases. The commonest complications were sepsis in 38.59% (95% CI: 25.49–51.68), stillbirth in 38.08% (95% CI: 29.55–46.61), postpartum hemorrhage in 33.54% (95% CI:12.06– 55.02), uterine rupture in 29.84% (95% CI: 21.09–38.58), and maternal death in 17.27% (95% CI: 13.47–48.02) of mothers who gave birth in Ethiopia.

Conclusion
This systematic review and meta-analysis showed that the incidence of obstructed labor was high in Ethiopia. Not having antenatal care follow-up, rural residency, and visiting hospitals after 12 h of labor increased the incidence of obstructed labor. The major causes of obstructed labor were cephalo-pelvic disproportion, and malpresentation and malpresentation. Additionally, the commonest complications were sepsis, stillbirth, postpartum hemorrhage, uterine rupture, and maternal death. Thus, promoting antenatal care service utilization, a good referral system, and availing comprehensive obstetric care in nearby health institutions are recommended to prevent the incidence of obstructed labor and its complications.
Comment: difference between assessment of upper limb movement and upper limb associated reactions during walking
Authors: Meyns Pieter 
Published: March 2021

Abstract
Background
While walking, people swing their arms in a specific pattern. This specific arm swing pattern during walking has shown to have a beneficial effect on gait as it reduces walking energy cost and optimizes balance. In several patient populations the arm movements can be directly affected (e.g. in patients with acquired brain injury (ABI)), which in turn has a negative effect on their gait pattern, balance and energy cost of walking.

Main
text
In
December 2019, Kahn et al. published a paper in JNER concerning the
quantification of upper limb associated reactions (ARs) during walking in people
with ABI. ARs are defined as “an effort-dependent phenomenon causing an
involuntary increase in upper limb muscle tone, with awkward and uncomfortable
postures”. These upper limb ARs appear often in patients with ABI and can have
an important effect on their gait. The authors calculated kinematic measures
using three-dimensional gait analysis relating to range of motion, variability
and mean position over the gait cycle for the different upper limb joints
(shoulder, elbow, wrist) during self-selected steady-state walking. Based on
differences they found between an ABI cohort and healthy control cohort, the
authors concluded that they were able to quantify ARs during walking in this
population. This calculation, however, is not specific for upper limb ARs. In
fact, the authors calculated general measures of arm posture (e.g. mean position
over the gait cycle) or arm movement (e.g. range of motion and variability)
during gait. Previous research has already indicated that other factors than
ARs can influence the posture or movement of the arm during gait in patients
with brain injury, such as voluntary compensations for gait instability and
contractures or spasticity of upper arm muscles. Yet, it is not possible to disentangle
the different causes of the altered arm posture during steady-state walking
based on the proposed measures.

Conclusion
The kinematic arm measures proposed by Kahn et al. (J Neuroeng Rehabil 16(1):160, 2019) are not a
direct measure of ARs, but provide a quantification of overall deviation of arm
posture or movement during gait. Depending on the specific study design these
measures may provide insights in ARs.
A nonlinear association of total cholesterol with all-cause and cause-specific mortality
Authors: He Guo-dong , Liu Xiao-cong , Liu Lin , Yu Yu-ling , Chen Chao-lei , Huang Jia-yi , Lo Kenneth , Huang Yu-qing , Feng Ying-qing 
Published: March 2021

Abstract
Background
The link between total cholesterol (TC) and all-cause and specific mortality has not been elucidated. Herein, we aimed to evaluate the effect of TC levels on all-cause, cardiovascular disease (CVD), and cancer mortality.

Methods
All data analyzed were obtained from the National Health and Nutrition Examination Survey 1999–2014. The relationship between levels of TC and mortality was determined through Cox proportional hazard regression analysis coupled with multivariable adjustments. Two-piecewise linear regression models and Cox models with penalized splines were applied to explore nonlinear and irregular shape relationships. Kaplan–Meier survival curve and subgroup analyses were conducted.

Results
The sample studied comprised 14,662 men and 16,025 women, categorized as 25,429 adults aged 18–65 and 5,258 adults over 65 years old. A total of 2,570 deaths were recorded. All-cause, cardiovascular, and cancer mortality showed U-curve associations after adjusting for confounding variables in the restricted cubic spline analysis. Hazard ratios (HRs) of all-cause and cancer mortality were particularly negatively related to TC levels in the lower range < 200 mg/dL, especially in the range < 120 mg/dL (HR 1.97; 95% CI 1.38, 2.83, HR 2.39; 95% CI 1.21, 4.71, respectively). However, the HRs of cardiovascular disease mortality in the range < 120 mg/dL were the lowest (HR 0.60; 95% CI 0.15, 2.42). In the upper range, a TC range of ≥ 280 mg/dL was correlated with mortality as a result of CVD and cancer (HR 1.31; 95% CI 0.87, 1.97 and HR 1.22; 95% CI 0.82, 1.79). The lowest cumulative survival rate of all-cause mortality was recorded in the lowest TC-level group, while the lowest cumulative survival rate of CVD mortality was recorded in the highest TC-level group.

Conclusions
A nonlinear association of TC level with all-cause, cancer, and CVD mortality in the American population was observed, suggesting that too low or too high serum total cholesterol levels might correlate with adverse outcomes.
Integrative proteomic and lipidomic analysis of Kaili Sour Soup-mediated attenuation of high-fat diet-induced nonalcoholic fatty liver disease in a rat model
Authors: Cong Shuo , Li Zhengchao , Yu Lei , Liu Yongmei , Hu Yaxin , Bi Ying , Cheng Mingliang 
Published: March 2021

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and is characterized by excessive fat accumulation. Kaili Sour Soup, a food typical of Guizhou Province, is believed to have significant health benefits. Thus, we aimed to identify and assess the impact of Kaili Sour Soup on NAFLD and its underlying mechanism using integrative proteomic and lipidomic analysis.

Methods
A high-fat diet and male Wistar rats were used to construct a NAFLD rat model. Haematoxylin and eosin (HE) and Oil Red O staining analyses were used to perform the histologic examination. Proteomic analysis was utilized to systematically identify the global protein profile in NAFLD with and without Kaili Sour Soup treatment. Western blot assays were used to verify the expression of proteins screened by proteomic analysis. Lipidomic analysis was performed to screen lipid metabolism in NAFLD with and without Kaili Sour Soup treatment.

Results
Kaili Sour Soup alleviated high-fat diet (HFD)-induced fatty liver and had a normalizing effect on physiological and biochemical indicators of NAFLD, including body weight, liver weight, liver index, total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and insulin resistance level of homeostasis model assessment (HOMA-IR). Kaili Sour Soup decreased the levels of 13 proteins (Tmem44, Rnaseh2b, Gstm6l, LOC100910877, Rufy4, Slc12a2, Pcif1, P4503A1, Sult1e1, Nop53, AABR07065656.4, AABR07065789.3) that were upregulated by HFD and increased the levels of 3 proteins (Sult1c2, Sult1c2a, Snrnp48) that were downregulated by HFD. Kaili Sour Soup attenuated the HFD-induced increase in acyl carnitine (AcCa) and enhanced the HFD-induced decreases in gangliosides (GM3) and lysophosphatidylserine (LPS) in the NAFLD rat model.

Conclusions
Altogether, this study revealed that Kaili Sour Soup attenuated HFD-induced fatty liver and systematically identified abnormal proteins and lipids involved in the role of Kaili Sour Soup in a NAFLD rat model.
Homocystinuria patient and caregiver survey: experiences of diagnosis and patient satisfaction
Authors: Morrison T. , Bösch F. , Landolt M. A. , Kožich V. , Huemer M. , Morris A. A. M. 
Published: March 2021

Abstract
Background
The main genetic causes of homocystinuria are cystathionine beta-synthase (CBS) deficiency and the remethylation defects. Many patients present in childhood but milder forms may present later in life. Some countries have newborn screening programs for the homocystinurias but these do not detect all patients.

Results
HCU Network Australia is one of the very few support groups for patients with homocystinurias. Here we report the results of its survey of 143 patients and caregivers from 22 countries, evaluating current diagnostic pathways and management for the homocystinurias. Most (110) of the responses related to patients with CBS deficiency. The diagnosis was made by newborn screening in 20% of patients and in 50% of the others within 1 year of the initial symptom but in 12.5% it took over 15 years. The delay was attributed mainly to ignorance of the disease. Physicians need to learn to measure homocysteine concentrations in children with neurodevelopmental problems, and in patients with heterogeneous symptoms such as thromboembolism, dislocation of the optic lens, haemolytic uraemic syndrome, and psychiatric disease. Even when the diagnosis is made, the way it is communicated is sometimes poor. Early-onset CBS deficiency usually requires a low-protein diet with amino acid supplements. More than a third of the participants reported problems with the availability or cost of treatment. Only half of the patients always took their amino acid mixture. In contrast, good adherence to the protein restriction was reported in 98% but 80% said it was hard, time-consuming and caused unhappiness.

Conclusions
There is often a long delay in diagnosing the homocystinurias unless this is achieved by newborn screening; this survey also highlights problems with the availability and cost of treatment and the palatability of protein substitutes.
Diuretics decrease fluid balance in patients on invasive mechanical ventilation: the randomized-controlled single blind, IRIHS study
Authors: Cinotti Raphaël , Lascarrou Jean-Baptiste , Azais Marie-Ange , Colin Gwenhaël , Quenot Jean-Pierre , Mahé Pierre-Joachim , Roquilly Antoine , Gaultier Aurélie , Asehnoune Karim , Reignier Jean 
Published: March 2021

Abstract
Background
Fluid overload has been associated with increased morbidity and mortality in critically ill patients. The goal of this study was to assess the efficacy and safety of a diuretic strategy to overcome positive fluid balance in patients on invasive mechanical ventilation.

Methods
Design: Multicenter, single-blind, randomized-controlled study. Patients were randomized into a diuretic (furosemide) or a control group. Patients were eligible in case of fluid overload defined as in-ICU weight increase ≥ 3%, invasive mechanical ventilation (FiO2 ≤ 60% and PEEP ≤ 10 cm H2O on inclusion) and hemodynamic stabilization. The primary outcome was fluid balance, defined as weight variation from reference weight to successful extubation. The main secondary outcome was the safety of diuretic.

Results
171 patients were randomized. After 5 exclusions, 166 patients were included in the analysis: 77 in the diuretic and 89 in the control group. Fluid balance was 1.4 [− 2.5 to 4.5] kg in the diuretic and 6.4 [0.5–11.2] kg in the control group (p < 0.001). In the multiple imputation analysis, fluid balance was significantly decreased in the diuretic group (mean difference = − 4.8 95% CI [− 7.3 to − 2.5], p < 0.001). Eleven (14%) patients died in the diuretic group and 16 (18%) patients in the control group (p = 0.5). There was a worsening of Acute Kidney Injury in 67 (75.3%) patients of the control group versus 46 (59.7%) patients in the diuretic group (p = 0.03).

Conclusions
In this multicenter randomized-controlled study, protocolized diuretic therapy reduced fluid accumulation in patients receiving mechanical ventilation and was well tolerated with a favorable safety profile.
Trial registration NCT 02345681, Registered January 26 2015, Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT02345681?term=02345681&draw=2&rank=1.
Statistical consideration when adding new arms to ongoing clinical trials: the potentials and the caveats
Authors: Lee Kim May , Brown Louise C. , Jaki Thomas , Stallard Nigel , Wason James 
Published: March 2021

AbstractBackgroundPlatform trials improve the efficiency of the drug development process through flexible features such as adding and dropping arms as evidence emerges. The benefits and practical challenges of implementing novel trial designs have been discussed widely in the literature, yet less consideration has been given to the statistical implications of adding arms.MainWe explain different statistical considerations that arise from allowing new research interventions to be added in for ongoing studies. We present recent methodology development on addressing these issues and illustrate design and analysis approaches that might be enhanced to provide robust inference from platform trials. We also discuss the implication of changing the control arm, how patient eligibility for different arms may complicate the trial design and analysis, and how operational bias may arise when revealing some results of the trials. Lastly, we comment on the appropriateness and the application of platform trials in phase II and phase III settings, as well as publicly versus industry-funded trials.ConclusionPlatform trials provide great opportunities for improving the efficiency of evaluating interventions. Although several statistical issues are present, there are a range of methods available that allow robust and efficient design and analysis of these trials.
Association of glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS): a cross-sectional study
Authors: Miyawaki Yoshia , Shimizu Sayaka , Ogawa Yusuke , Sada Ken-ei , Katayama Yu , Asano Yosuke , Hayashi Keigo , Yamamura Yuriko , Hiramatsu-Asano Sumie , Ohashi Keiji , Morishita Michiko , Watanabe Haruki , Takano-Narazaki Mariko , Matsumoto Yoshinori , Yajima Nobuyuki , Yoshimi Ryusuke , Shimojima Yasuhiro , Ohno Shigeru , Kajiyama Hiroshi , Ichinose Kunihiro , Sato Shuzo , Fujiwara Michio , Yamazaki Hajime , Yamamoto Yosuke , Wada Jun , Fukuhara Shunichi 
Published: March 2021

Abstract
Background
While survival of systemic lupus erythematosus (SLE) patients has improved substantially, problems remain in the management of their emotional health. Medium to high-dose glucocorticoid doses are known to worsen emotional health; the effect is unclear among patients receiving relatively low-dose glucocorticoids. This study aims to investigate the association between low glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS).

Methods
This cross-sectional study drew on data from SLE patients in 10 Japanese institutions. The participants were adult patients with SLE duration of ≥ 1 year who met LLDAS criteria at the study visit from April 2018 through September 2019. The exposure was the daily glucocorticoid dose (mg oral prednisolone). The outcome was the emotional health score of the lupus patient-reported outcome scale (range: 0 to 100). Multiple linear regression analysis was performed with adjustment for confounders including disease-related damage, activity, and psychotropic drug use.

Results
Of 192 patients enrolled, 175 were included in the analysis. Their characteristics were as follows: female, 89.7%; median age, 47 years (interquartile range (IQR): 37.0, 61.0). Median glucocorticoid dose was 4.0 mg (IQR 2.0, 5.0), and median emotional health score 79.2 (IQR 58.3, 91.7). Multiple linear regression analysis showed daily glucocorticoid doses to be associated with worse emotional health (β coefficient = − 2.54 [95% confidence interval − 4.48 to − 0.60], P = 0.01).

Conclusions
Daily glucocorticoid doses were inversely associated with emotional health among SLE patients in LLDAS. Further studies are needed to determine whether glucocorticoid tapering leads to clinically significant improvements in emotional health.