bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative efficacy and safety of the artemisinin derivatives compared to quinine for treating severe malaria in children and adults: A systematic update of literature and network meta-analysis
Authors: Nyaaba Nicholas , Andoh Nana Efua , Amoh Gordon , Amuzu Dominic Selorm Yao , Ansong Mary , Ordóñez-Mena José M. , Hirst Jennifer 
Published: July 2022

Background
The artemisinin derivatives are the preferred antimalaria drugs for treating severe Plasmodium falciparum malaria. However, their clinical effectiveness compared to each other is unknown. Our objective, therefore, was to evaluate the efficacy and safety of the artemisinin derivatives and quinine for treating severe P. falciparum malaria in children and adults using a network meta-analysis.

Methods and findings
Review protocol was registered with PROSPERO, CRD42020218190. We updated the search strategies of three Cochrane systematic reviews which included published and unpublished randomised control trials (RCTs) that have compared specific artemisinin derivatives to quinine in treating severe malaria. Search included CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science and trial registries up to February 2021. We screened studies, extracted data, assessed risk of bias, and quality of evidence in duplicate. Separate network meta-analyses in the frequentist framework, using a random effects model, with quinine as reference, were conducted for adults and children, and rankings were produced using p-scores to assess mortality, parasite clearance, coma recovery, fever clearance, neurological sequela and adverse events.
Searches identified 818 citations, 33 RCTs were eligible. We pooled 7795 children and 3182 adults. The networks involved artesunate, artemether, rectal artemisinin, arteether and quinine. Compared to quinine, artesunate reduced mortality in children (risk ratio (RR), 0.76; 95%CI [0.65 to 0.89], moderate quality), adults (RR, 0.55; 95%CI [0.40 to 0.75], moderate quality) and in cerebral malaria (RR, 0.72; 95%CI [0.55 to 0.94], moderate quality).
Compared to rectal artemisinin and intramuscular arteether, the efficacy and safety of parenteral artesunate, and intramuscular artemether in treating severe malaria are not clear. Rankings showed that none of the artemisinin drugs were consistently superior in all the outcomes assessed. Indirect evidence produced were of very low ratings due to suspected publication bias and imprecision.

Conclusions
Artesunate reduces mortality compared to quinine for both adults and children in Asia and Africa including cerebral malaria. The artemisinin derivatives remain the best treatment for severe malaria but their comparative clinical effectiveness is yet to be fully explored.
Correlation between clinical presentations, radiological findings and high risk histopathological features of primary enucleated eyes with advanced retinoblastoma at Queen Sirikit National Institute of Child Health: 5 years result
Authors: Surukrattanaskul Supawan , Keyurapan Bungornrat , Wangtiraumnuay Nutsuchar 
Published: July 2022

Purpose
To evaluate the correlation between clinical presentations, radiological findings and high risk histopathological features of primary enucleated eyes in patients with advanced retinoblastoma at a tertiary child hospital in Thailand.

Materials and methods
We retrospectively reviewed the medical records of patients who were treated with primary enucleation of tumor eyes between 2015–2020. Demographic data, radiological assessment, and histopathological findings were collected. The association between clinical presentations and high-risk histopathological features in the primary enucleated eyes were evaluated. The radiological findings, which showed characteristic of high risk features, were compared with the histopathological findings.

Results
Thirty-three enucleated eyes were enrolled in this study. The mean age at diagnosis was 23.12 months. Most patients had unilateral group E retinoblastoma, with no difference in sex and laterality of the eye. Leukocoria was the most common presentation, followed by proptosis and uveitis. Older age at presentation were statistically associated with post laminar cribrosa optic nerve invasion (P-value 0.0027) and high-risk histopathological features in enucleated eyes (P-value 0.0032). Clinical presentations with proptosis were statistically associated with post laminar cribrosa optic nerve invasion, while leukocoria and uveitis were statistically associated with anterior segment invasion. Unifocal intraocular mass with necrosis was the most common histopathological finding. High-risk features were found in 45% of primary enucleated eye. The sensitivity and specificity of magnetic resonance imaging (MRI) for detected optic nerve invasion in retinoblastoma patients were 75% and 54%, respectively.

Conclusion
Patients with unilateral retinoblastoma who presented with older age related to high-risk features after enucleation. Ophthalmic examination with slitlamp is the best way for detection of anterior segment invasion. Choroidal invasion was unable to predict with clinical presentation. MRI was the better imaging for detection of post laminar cribrosa optic nerve invasion.
Correlation between tear film lipid layer thickness and transepidermal water loss from the ocular area in patients with dry eye disease and in healthy controls
Authors: Yoon Do Yeh , Hee Eun Jeon , Hyon Joon Young 
Published: July 2022

Purpose
This study aimed to evaluate the correlation between tear film lipid layer thickness and transepidermal water loss (TEWL) from the ocular area in patients with short tear break-up time (TBUT)-type dry eye and healthy controls.

Methods
This prospective study included 25 eyes of patients with short TBUT-type dry eye disease and 25 eyes of healthy controls.

Results
Tear film lipid layer thickness was measured using an interferometer, and TEWL from the ocular area was measured using a Tewameter TM300 with custom-made goggles. The correlation between tear film lipid layer thickness and TEWL was evaluated. Additionally, other parameters such as TBUT, Schirmer I score, ocular surface staining, the presence and type of meibomian gland dysfunction (MGD), ocular surface disease index (OSDI), and visual analog scale (VAS) scores were evaluated. Tear film lipid layer thickness did not show a significant correlation with TEWL from the ocular area measured using a Tewameter TM300. However, tear film lipid layer thickness was significantly correlated with tear break-up time (p = 0.004) and ocular surface staining by NEI (National Eye Institute) scheme (p = 0.03). TEWL showed positive correlation with the Schirmer I score (p = 0.004).

Conclusions
The tear film lipid layer affected the stability of the tear film more than the amount of TEWL in patients with short TBUT dry eye and healthy controls.
Exercise-induced myokines downregulates the ACE2 level in bronchial epithelial cells: Implications for SARS-CoV-2 prevention
Authors: Bhardwaj Vaishali , Dela Cruz Mart , Subramanyam Deepika , Kumar Rohit , Markan Sandeep , Parker Beth , Roy Hemant K. 
Published: July 2022

Background
The Covid-19 pandemic has emerged as the leading public health challenge of our time (20th century). While vaccinations have finally blunted the death rate, concern has remained about more virulent forms highlighting the need for alternative approaches. Epidemiological studies indicate that physical activity has been shown to decrease the risk of infection of some respiratory viruses. Part of the salutary effects of exercise is believed to be through the elaboration of cytokines by contracting skeletal muscles (termed myokines). The objective of this study was to investigate whether exercise-induced myokines would mitigate the SARS-CoV-2 infectivity of the bronchial epithelium through modulating the SARS-CoV-2 Covid-19 receptor (angiotensin-converting enzyme 2 -ACE2) its priming enzyme, transmembrane serine protease 2 (TMPRSS2).

Methods
We utilized a cell culture model of exercise to generate myokines by differentiating C2C12 cells into myotubules and inducing them to contract via low-frequency electric pulse stimulation. Condition media was concentrated via centrifugation and applied to human immortalized human bronchial epithelium cell line (6HBE14o) along with conditioned media from unstimulated myotubules as controls. Following exposure to myokines, the 16HBE14o cells were harvested and subjected to quantitative RT-PCR and Enzyme-Linked Immunosorbent Assay (ELISA) for assessment of mRNA and protein levels of ACE2 and TMPRSS2, respectively. Pilot proteomic data was performed with isotope barcoding and mass spectroscopy.

Results
Quantitative Real-Time PCR of 16HBE14o with 48 h treated unstimulated vs. stimulated myokine treatment revealed a reduction of ACE2 and TMPRSS2 mRNA by 32% (p<2.69x10-5) and 41% (p<4.57x10-5), respectively. The high sensitivity of ELISAs showed downregulation of ACE2 and TMPRSS2 protein expression in 16HBE14o cells by 53% (p<0.01) and 32% (p<0.03) respectively with 48 h treated. For rigor, this work was replicated in the human lung cancer cell line A549, which mirrored the downregulation. Proteomic analysis showed dramatic alteration in myokine profile between contracted and uncontracted C2C12 tubules.

Conclusions
The current study explores a novel approach of a modified exercise cell culture system and uses ACE2 and TMPRSS2 as a surrogate marker of SARS-CoV-2 infectivity. In conclusion, we demonstrated biological data supporting exercise’s protective effect against Covid-19. These further strengthen myokines’ beneficial role as potential therapeutic targets against SARS-CoV-2 and similar viruses albeit these preliminary cell culture studies will require future validation in animal models.
Socio-demographic profiles and obstetrics outcomes of pregnant women with epilepsy in a vulnerability State, Brazil
Authors: de Lima Leite Magnúcia , Toporcov Tatiana Natasha , Pai Janise Dal , da Silva José Claudio 
Published: July 2022

Introduction
The socio-demographic profile of pregnant women in low- and middle- income countries is characterized by low educational attainment and unemployment, leading to social and economic morbidity. characterized by limited opportunities for education, employment, and marriage, which are strongly related to the stigmatization of the disease. The study of the socio- profile and obstetric outcomes of pregnant women with epilepsy in Alagoas, Brazil, may help understand this scenario and facilitate the development of public policy strategies to reduce local morbidity.

Objectives
We aimed to describe the sociodemographic profile of pregnant women with epilepsy and obstetric outcomes in Alagoas, Brazil.

Methods
This cohort study was based on medical records of pregnant women with epilepsy in Brazilian high-risk maternity hospitals from 2008 to 2020. The following data were collected: age, race, education, marital status, occupation, number of pregnancies, delivery, and abortion. The inclusion criteria were pregnant women with and without epilepsy (control group) aged < 40 years.

Results
The prevalence of PWWE was 0.49% (n = 224/44,917). Cesarean delivery was more frequent in PWWE than in pregnant women without epilepsy (adjusted odds ratio [OR] = 22.0; 95% confidence interval [CI] = 14.35–33.73; p<0,01). Abortion was associated with PWWE (OR adjusted = 1.72; 95% CI = 1.13–2.61; p = 0.01). Pregnant women in the countryside were more likely to develop epilepsy than those born in the capital (OR = 1.55; 95% CI = 1.12–2.14; p <0.01).

Conclusion
The PWWE socio-demographic profile of the Alagoas had a predominance of brown- colored skin, single status, homemakers, and illiteracy with a high proportion residing in the interior of the state. The obstetrics data show a higher incidence of cesarean deliveries and miscarriages.
Trends in COVID-19 patient characteristics in a large electronic health record database in the United States: A cohort study
Authors: Liang Caihua , Ogilvie Rachel P. , Doherty Michael , Clifford C. Robin , Chomistek Andrea K. , Gately Robert , Song Jennifer , Enger Cheryl , Seeger John , Lin Nancy D. , Wang Florence T. 
Published: July 2022

Background
Electronic health record (EHR) databases provide an opportunity to facilitate characterization and trends in patients with COVID-19.

Methods
Patients with COVID-19 were identified based on an ICD-10 diagnosis code for COVID-19 (U07.1) and/or a positive SARS-CoV-2 viral lab result from January 2020 to November 2020. Patients were characterized in terms of demographics, healthcare utilization, clinical comorbidities, therapies, laboratory results, and procedures/care received, including critical care, intubation/ventilation, and occurrence of death were described, overall and by month.

Results
There were 393,773 patients with COVID-19 and 56,996 with a COVID-19 associated hospitalization. A greater percentage of patients hospitalized with COVID-19 relative to all COVID-19 cases were older, male, African American, and lived in the Northeast and South. The most common comorbidities before admission/infection date were hypertension (40.8%), diabetes (29.5%), and obesity (23.8%), and the most common diagnoses during hospitalization were pneumonia (59.6%), acute respiratory failure (44.8%), and dyspnea (28.0%). A total of 85.7% of patients hospitalized with COVID-19 had CRP values > 10 mg/L, 75.5% had fibrinogen values > 400 mg/dL, and 76.8% had D-dimer values > 250 ng/mL. Median values for platelets, CRP, lactate dehydrogenase, D-dimer, and fibrinogen tended to decrease from January-March to November. The use of chloroquine/hydroxychloroquine during hospitalization peaked by March (71.2%) and was used rarely by May (5.1%) and less than 1% afterwards, while the use of remdesivir had increased by May (10.0%) followed by dexamethasone by June (27.7%). All-cause mortality was 3.2% overall and 15.0% among those hospitalized; 21.0% received critical care and 16.0% received intubation/ventilation/ECMO.

Conclusions
This study characterizes US patients with COVID-19 and their management during hospitalization over the first eleven months of this disease pandemic.
Elevated Liver Enzymes in a Patient With Hepatocellular Carcinoma on Immune Checkpoint Inhibitor Therapy: A Diagnostic and Therapeutic Challenge
Authors: Abbas Daniyal , Zhu Lee-Ching , Moon Andrew M. 
Published: July 2022

ABSTRACT
We present a patient with untreated hepatitis C virus and metastatic hepatocellular carcinoma treated with combination immunotherapy who developed elevated liver enzymes. The immunotherapy was withheld, and the liver enzymes continued to rise. A liver biopsy was performed, which demonstrated findings consistent with chronic viral hepatitis. Direct-acting antiviral treatment was initiated, and the liver enzymes returned to normal limits. This case demonstrates the diagnostic dilemmas raised among patients with hepatocellular carcinoma on immunotherapy who develop elevated liver enzymes and some of the challenges regarding the use of these medications in patients with viremic hepatitis C virus.
To identify normovolemia in humans: The stroke volume response to passive leg raising vs. head‐down tilt
Authors: Sejersen Casper , Christiansen Till , Secher Niels H. 
Published: July 2022

AbstractVolume responsiveness can be evaluated by tilting maneuvers such as head‐down tilt (HDT) and passive leg raising (PLR), but the two procedures use different references (HDT the supine position; PLR the semi‐recumbent position). We tested whether the two procedures identify “normovolemia” by evaluating the stroke volume (SV) and cardiac output (CO) responses and whether the peripheral perfusion index (PPI) derived from pulse oximetry provides similar information. In randomized order, 10 healthy men were exposed to both HDT and PLR, and evaluations were made also when the subjects fasted. Central cardiovascular variables were derived by pulse contour analysis and changes in central blood volume assessed by thoracic electrical admittance (TEA). During HDT, SV remained stable (fasted 110 ± 16 vs. 109 ± 16 ml; control 113 ± 16 vs. 111 ± 16 ml, p > 0.05) with no change in CO, TEA, PPI, or SV variation (SVV). In contrast during PLR, SV increased (fasted 108 ± 17 vs. 117 ± 17 ml; control 108 ± 18 vs. 117 ± 18 ml, p < 0.05) followed by an increase in TEA (p < 0.05) and CO increased when subjects fasted (6.7 ± 1.5 vs. 7.1 ± 1.5, p = 0.007) with no change in PPI or SVV. In conclusion, SV has a maximal value for rest in supine men, while PLR restores SV as CBV is reduced in a semi‐recumbent position and the procedure thereby makes healthy volunteers seem fluid responsive.
Evaluation of the cardiovascular risk in patients undergoing major non-cardiac surgery: role of cardiac-specific biomarkers
Authors: Clerico Aldo , Zaninotto Martina , Aimo Alberto , Musetti Veronica , Perrone Marco , Padoan Andrea , Dittadi Ruggero , Sandri Maria Teresa , Bernardini Sergio , Sciacovelli Laura , Trenti Tommaso , Malloggi Lucia , Moretti Marco , Burgio Maria Aurora , Manno Massimiliano Luca , Migliardi Marco , Fortunato Antonio , Plebani Mario 
Published: July 2022

Abstract
Major adverse cardiovascular events are frequently observed in patients undergoing major non-cardiac surgery during the peri-operative period. At this time, the possibility to predict cardiovascular events remains limited, despite the introduction of several algorithms to calculate the risk of adverse events, mainly death and major adverse cardiovascular events (MACE) based on the clinical history, risk factors (sex, age, lipid profile, serum creatinine) and non-invasive cardiac exams (electrocardiogram, echocardiogram, stress tests). The cardiac-specific biomarkers natriuretic peptides (NPs) and cardiac troponins (cTn) have been proposed as additional tools for risk prediction in the peri-operative period, particularly for the identification of myocardial injury in patients undergoing major non-cardiac surgery. The prognostic information from the measurement of BNP/NT-proBNP and hs-cTn is independent and complementary to other important indicators of risk, also including ECG and imaging techniques. Elevated levels of cardiac-specific biomarkers before surgery are associated with a markedly higher risk of MACE during the peri-operative period. BNP/NT-proBNP and hs-cTn should be measured in all patients during the clinical evaluation before surgery, particularly during intermediate- or high-risk surgery, in patients aged >65 years and/or with comorbidities. Several questions remain to be assessed in dedicated clinical studies, such as how to optimize the management of patients with raised cardiac specific biomarkers before surgery, and whether a strategy based on biomarker measurement improves patient outcomes and is cost-effective.
The physiological insight of Coenzyme-Q10 administration in preventing the incidence of reperfusion arrhythmia among patients undergoing coronary artery bypass grafting surgery
Authors: Wardhani Louisa Fadjri Kusuma , Dewi Ivana Purnama , Putra Kresna Nugraha Setia , Andrianto Andrianto , Soemantri Djoko 
Published: July 2022

Abstract
Reperfusion arrhythmia following cardiac surgery has long been studied as part of myocardial damage. Reperfusion injury is thought to be exacerbated by oxygen-free radicals, whereas arrhythmogenic oscillations in membrane potential are mediated by reactive oxygen. Coenzyme Q10 is a lipid-soluble antioxidant that inhibits lipid peroxidation in biological membranes and supplies ATP cell synthesis, required as the organism’s primary energy source. This process explains how Coenzyme Q10 helps stabilize membranes and avoids critical metabolite depletion that may relate to reperfusion arrhythmia. There is a reduction of iatrogenic Coenzyme Q10 after coronary artery bypass surgery (CABG). On the other hand, there is an increased inflammatory process and cellular demand post CABG procedure. It leads to ischemia that can be manifested as arrhythmia. Reperfusion arrhythmia was less common in patients who took Coenzyme Q10. These findings suggest that Coenzyme Q10 supplementation might help patients with heart surgery avoid reperfusion arrhythmia. However, a higher-quality randomized controlled study is needed to determine the effect of Coenzyme Q10 in preventing reperfusion arrhythmia in cardiac surgery patients.
In vivo knee kinematics of an innovative prosthesis design
Authors: Worlicek Michael , Schaumburger Jens , Springorum Robert , Maderbacher Guenther , Zeman Florian , Grifka Joachim , Baier Clemens 
Published: July 2022

Abstract
Up to 20% of patients after total knee arthroplasty (TKA) are not satisfied with the result. Several designs of new implants try to rebuild natural knee kinematics. We hypothesized that an innovative implant design leads to better results concerning femoral rollback compared to an established implant design. For this pilot study, 21 patients were examined during TKA, receiving either an innovative (ATTUNETM Knee System (DePuy Inc.), n = 10) or an established (PFCTM (DePuy Inc.), n = 11) knee system. All patients underwent computer navigation. Knee kinematics was assessed after implantation. Outcome measure was anterior–posterior translation between femur and tibia. We were able to demonstrate a significantly higher femoral rollback in the innovative implant group (p < 0.001). The mean rollback of the innovative system was 11.00 mm (95%-confidence interval [CI], 10.77–11.24), of the established system 8.12 mm (95%-CI, 7.84–8.42). This study revealed a significantly increased lateral as well as medial femoral rollback of knees with the innovative prosthesis design. Our intraoperative finding needs to be confirmed using fluoroscopic or radiographic three-dimensional matching under full-weight-bearing conditions after complete recovery from surgery.
Protective effect of ghrelin on intestinal I/R injury in rats
Authors: Jiang Meng , Wan Shengxia , Dai Xiaoyong , Ye Youwen , Hua Wei , Ma Guoguang , Pang Xiufeng , Wang Huanhuan , Shi Bin 
Published: July 2022

Abstract
This study aimed to investigate whether ghrelin affected the autophagy and inflammatory response of intestinal intraepithelial lymphocytes (IELs) by regulating the NOD2/Beclin-1 pathway in an intestinal ischemia–reperfusion (I/R) injury model. Twenty hours after implementing the intestinal I/R injury rat model, the small intestine and both lungs were collected for histological analysis. The morphological changes in the intestinal mucosa epithelium and lung tissues were evaluated using hematoxylin-eosin staining. The activity of autophagic vacuoles and organ injury were evaluated using electron microscopy. The cytokine levels (IL-10 and TNF-α) in IEL cells and lung tissue were determined using enzyme-linked immunosorbent assay. RT-qPCR and western blot assays were conducted to check the NOD2, Beclin-1, and ATG16 levels. Ghrelin relieved the I/R-induced destruction of the intestinal mucosa epithelium and lung tissues. Moreover, ghrelin enhanced autophagy in the intestinal epithelium and lungs of I/R rats. In addition, the levels of autophagy-associated proteins (Beclin-1, ATG16, and NOD2) were higher in the ghrelin treatment group than in rats with I/R. Ghrelin reduced significantly the IL-10 and TNF-α levels. However, these changes were reversed by the NOD2 antagonist. In conclusion, ghrelin may relieve I/R-induced acute intestinal mucosal damage, autophagy disorder, and inflammatory response in IELs by regulating the NOD2/Beclin-1 pathway.