bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the prevalence of kidney disease by proteinuria and decreased estimated glomerular filtration rate determined using three creatinine-based equations among patients admitted on medical wards of Masaka Regional Referral Hospital in Uganda: a prospective study
Authors: Ronny SSenabulya F. , Joaniter Nankabirwa I. , Robert Kalyesubula , Bonnie Wandera , Bruce Kirenga , James Kayima , Posiano Ocama , Peace Bagasha
Published: July 2022

Background

Despite estimated glomerular filtration rate (eGFR) being the best marker for kidney function, there are no studies in sub-Saharan Africa comparing the performance of various equations used to determine eGFR. We compared prevalence of kidney disease determined by proteinuria of ≥  + 1 and or kidney disease improving global outcomes (KDIGO) eGFR criteria of < 60 ml/minute/1.73m2 determined using three creatinine-based equations among patients admitted on medical ward of Masaka Regional Referral Hospital.

Methods

This was a prospective study conducted among adult patients admitted on medical wards between September 2020 to March 2021. Spot urine samples were collected to assess for proteinuria and blood samples were collected to assess serum creatinine levels. Kidney disease was defined as proteinuria of ≥ 1 + on spot urine dipstick and or KDIGO eGFR criteria of < 60 ml/minute/1.73m2. Estimated glomerular filtration rate was calculated using three creatinine-based equations: a) Full Age Spectrum equation (FAS), b) chronic kidney disease-Epidemiology collaboration (CKD-EPI) 2021 equation, c) CKD EPI 2009 (without and with race factor) equation. CKD was determined after followed up at 90 days post enrollment to determine the chronicity of proteinuria of ≥  + 1 and or KDIGO eGFR criteria of < 60mls /minute/1.73m2. We also compared prevalence of CKD determined by KDIGO eGFR criteria of < 60mls /minute/1.73m2 vs age adapted eGFR threshold criteria for defining CKD.

Results

Among the 357 patients enrolled in the study, KDIGO eGFR criteria of < 60mls / minute determined using FAS and CKD-EPI 2009 without race factor equations and or proteinuria of ≥  + 1 showed the highest overall prevalence of kidney disease at 27.2%.

Prevalence of confirmed CKD at 90 days was highest with proteinuria ≥  + 1 and or KDIGO eGFR criteria of < 60mls/min determined using CKD EPI 2009 without race factor Equation (15.1%).

Conclusions

Use of KDIGO eGFR criteria of < 60mls / minute /1.73m2 using FAS and CKD-EPI 2009 without race equations identifies the largest number of patients with CKD. Health care systems in sub-Saharan Africa should calculate eGFR using FAS equations or CKD-EPI 2009 without race equations during basic screening and management protocols.
Garbage codes in the Norwegian Cause of Death Registry 1996–2019
Authors: Ellingsen Christian Lycke , Alfsen G. Cecilie , Ebbing Marta , Pedersen Anne Gro , Sulo Gerhard , Vollset Stein Emil , Braut Geir Sverre
Published: July 2022

Background

Reliable statistics on the underlying cause of death are essential for monitoring the health in a population. When there is insufficient information to identify the true underlying cause of death, the death will be classified using less informative codes, garbage codes. If many deaths are assigned a garbage code, the information value of the cause-of-death statistics is reduced. The aim of this study was to analyse the use of garbage codes in the Norwegian Cause of Death Registry (NCoDR).

Methods

Data from NCoDR on all deaths among Norwegian residents in the years 1996–2019 were used to describe the occurrence of garbage codes. We used logistic regression analyses to identify determinants for the use of garbage codes. Possible explanatory factors were year of death, sex, age of death, place of death and whether an autopsy was performed.

Results

A total of 29.0% (290,469/1,000,128) of the deaths were coded with a garbage code; 14.1% (140,804/1,000,128) with a major and 15.0% (149,665/1,000,128) with a minor garbage code. The five most common major garbage codes overall were ICD-10 codes I50 (heart failure), R96 (sudden death), R54 (senility), X59 (exposure to unspecified factor), and A41 (other sepsis). The most prevalent minor garbage codes were I64 (unspecified stroke), J18 (unspecified pneumonia), C80 (malignant neoplasm with unknown primary site), E14 (unspecified diabetes mellitus), and I69 (sequelae of cerebrovascular disease).

The most important determinants for the use of garbage codes were the age of the deceased (OR 17.4 for age ≥ 90 vs age < 1) and death outside hospital (OR 2.08 for unknown place of death vs hospital).

Conclusion

Over a 24-year period, garbage codes were used in 29.0% of all deaths. The most important determinants of a death to be assigned a garbage code were advanced age and place of death outside hospital. Knowledge of the national epidemiological situation, as well as the rules and guidelines for mortality coding, is essential for understanding the prevalence and distribution of garbage codes, in order to rely on vital statistics.
Rubus idaeus extract improves symptoms in knee osteoarthritis patients: results from a phase II double-blind randomized controlled trial
Authors: Henrotin Yves , Cozannet Romain Le , Fança-Berthon Pascale , Truillet Romain , Cohen-Solhal Martine , DunnGalvin Gillian , Grouin Jean-Marie , Doolan Andrea
Published: July 2022

Background

Osteoarthritis (OA) is the most frequent cause of disability in elderly people. In daily practice, the main objective of the physician is to reduce patient symptoms using treatments without adverse effects. However, the most prescribed treatment to manage OA symptoms remains nonsteroidal anti-inflammatory drugs which are associated with severe adverse effects. Therefore, we need a safe alternative to managing OA. One candidate is Rubus idaeus leaf extracts known to inhibit inflammatory responses.

Objective

This study aimed to evaluate the effects of a 12-weeks intervention with an ethanolic extract from Rubus idaeus leaf on symptoms of knee osteoarthritis.

Method

The study was a randomized, double-blind, placebo-controlled, monocentric trial of 198 participants with femorotibial osteoarthritis. Participants were randomized equally to receive one daily during 3 months either 1 capsule of Rubus idaeus leaf extract 400 mg, 1 capsule of Rubus idaeus leaf extract 200 mg, or 1 capsule of placebo. The participants were assessed at baseline and after one and three months of treatment. The primary endpoint was an absolute change of the Western Ontario McMaster osteoarthritis index (WOMAC) pain subscale. The secondary endpoints were WOMAC global score, stiffness and function sub-scales, knee pain VAS score at walking, the Short Form (SF)-36, the Short Physical Performance Battery (SPPB), the 20-m walk test, and the International Physical Activity Questionnaire (IPAQ) and Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) responders rate. Statistical analyses were conducted on the intent-to-treat (ITT) population.

Results

In the Intention-to-treat population, WOMAC pain was not significantly modified by Rubus idaeus leaf extract compared to placebo. In contrast, Rubus idaeus leaf extract 400 mg after 12 weeks of treatment significantly reduced pain measured by the VAS. The mean pain decrease induced by Rubus ideaus leaf extract was over -7 mm which is clinically relevant and reached a clinically statistical difference compared to placebo with the highest dose. Rubus Ideaus was not significantly more efficient than the placebo on WOMAC global score, stiffness, and physical function subscores, IPAQ, SF-36, walking distance in treadmill test, SPPB, and evaluation of associated treatments needed to manage OA.

Conclusion

Rubus idaeus leaf extract was well tolerated and effective to relieve pain in a patient with knee osteoarthritis.

Trial registration

NCT03703024 (11/10/2018).
Association between history of abortion and current use of contraceptives among Mongolian Women
Authors: Phiri Yohane V. A. , Nyam Gunchmaa , Wardani Yuniar , Phiri Doreen , Chuang Kun-Yang , Chao Hsing Jasmine , Nkoka Owen
Published: July 2022

Background

Understanding the factors associated with the adoption of contraceptive methods among women of childbearing age is imperative to improving maternal health outcomes. This study aimed at exploring the association between history of abortion and contraceptive use among Mongolian women.

Materials and methods

We analyzed cross-sectional data of 8373 women aged 15–49 years from the 2018 Mongolian Social Indicator Sample Survey (MSISS). Binary logistic regression models were used to assess the association between abortion history and current contraceptive use while accounting for both individual- and community- level factors.

Results

A total of 4347 (51.92%) and 2525 (30.16%) reported current use of various contraceptive methods and a history of abortion in their lifetime, respectively. Women with a history of abortion were less likely to report current use of contraceptives (adjusted odds ratio (AOR) = 0.72, 95% confidence interval (CI) [0.58–0.89]). Specifically, women with a history of abortion were less likely to report use of IUD (AOR = 0.79, 95% CI [0.71–0.90)]) and injectables (AOR = 0.59, 95% CI [0.41–0.84]). History of abortion was associated with increased likelihood of using abstinence (OR = 1.82, 95% CI [1.31–2.53]) as a contraceptive method.

Conclusion

Our results demonstrated a significant association between history of abortion and contraceptive use. Public health interventions aiming to improve maternal health outcomes through contraceptive use should target women with a history of abortion to improve their uptake.
Oridonin attenuates low shear stress-induced endothelial cell dysfunction and oxidative stress by activating the nuclear factor erythroid 2-related factor 2 pathway
Authors: Chen Zhipeng , Liu Heqian , Zhao Xiaoqi , Mamateli Subinur , Liu Cheng , Wang Lei , Yu Jing , Liu Yutong , Cai Jing , Qiao Tong
Published: July 2022

Background

Atherosclerosis (AS) is the primary cause of cardiovascular disease and the incidence is extremely common; however, there are currently few drugs that can effectively treat AS. Although oridonin has been widely used to treat inflammation and cancer for numerous years, to the best of our knowledge, its protective effect against AS has not been reported. Therefore, the present study aimed to investigate whether oridonin attenuated AS.

Methods

By using text mining, chemometric and chemogenomic methods, oridonin was predicted to be a beneficial agent for the treatment of AS. A parallel flow chamber was used to establish a low shear stress (LSS)-induced endothelial cell (EC) dysfunction model. Briefly, ECs were exposed to 3 dyn/cm2 LSS for 30 min and subsequently treated with oridonin or transfected with a small interfering RNA (siRNA) targeting nuclear factor erythroid 2-related factor 2 (NRF2). Reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and glutathione disulfide (GSSG) in EA.hy926 cells were analyzed to determine the level of oxidative stress. The nitric oxide (NO) levels and mRNA expression levels of endothelial NO synthase (eNOS), endothelin-1 (ET-1) and prostaglandin synthase (PGIS) in EA.hy926 cells were analyzed to determine EC dysfunction. Furthermore, the mRNA and protein expression levels of NRF2 were analyzed using reverse transcription-quantitative PCR and western blot. In addition, zebrafish were fed with a high-cholesterol diet to establish a zebrafish AS model, which was used to observe lipid accumulation and inflammation under a fluorescence microscope.

Results

We found LSS led to oxidative stress and EC dysfunction; this was primarily indicated through the significantly decreased SOD and GSH content, the significantly increased MDA, GSSG and ROS content, the upregulated mRNA expression levels of ET-1, and the downregulated NO levels and mRNA expression levels of eNOS and PGIS in ECs. Notably, oridonin could improve LSS-induced oxidative stress and EC dysfunction, and the effects of oridonin were reversed by the transfection with NRF2 siRNA. Oridonin also attenuated lipid accumulation and neutrophil recruitment at the LSS regions in the zebrafish AS model.

Conclusions

In conclusion, the results of the present study suggested that oridonin may ameliorate LSS-induced EC dysfunction and oxidative stress by activating NRF2, thereby attenuating AS.
Determinants of drug expenditure in the Swiss healthcare market in 2006
Authors: Eggli Yves , Decollogny Anne , Piaget-Rossel Romain , Taffé Patrick
Published: July 2022

Background

Several measures are in force in Switzerland to control the cost of drugs, but are not effective enough. There are many determinants influencing these expenditures, related to treatments, markets, physicians, patients and regions, but their impact on costs is not clear.

Methods

We applied a Bayesian multilevel model with five levels to adjust for patients, drugs’ market, and physicians ‘characteristics, treatment type, and district (i.e. Swiss canton). We used data of the Swiss drugs’ market in 2006, offering real choices for doctors and patients (multiple products for similar active substances), with a neutral position of pharmacists (no financial incentives).

Results

Variance partitioning of yearly drugs’ cost per insured showed that market level (delivered substance) contributed to 76% of the variance, treatment level (delivered product) to 20%, whereas patients’ and physicians’ levels accounted for only 2% each, without significant differences between Swiss cantons. After adjusting for covariables at each level, the model explained about 51% of the variation at the market and 20% at the treatment levels. We found that older but substitutable drugs, generics, larger size of the market and physician’s specialty were associated with lower expenditure, whereas drugs requiring a physician’s prescription, the number of prescribers per patient, patient’ age, male gender, and comorbidities increased expenditure. Our results show that for a specific medication the yearly cost of recently released drugs was 36 CHF higher than for similar and substitutable drugs introduced 15 years earlier, corresponding to one third of the average annual treatment cost observed in our dataset. Competition did not seem to be effective to reduce expenditure on the drug market.

Conclusion

The main finding of this study is that recentness of drugs was associated with an increase in drug expenditure in 2006, even after adjustment for all non-controllable determinants. Further research is recommended to confirm those results with updated data.
First-in-human phase I study of CLL-1 CAR-T cells in adults with relapsed/refractory acute myeloid leukemia
Authors: Jin Xin , Zhang Meng , Sun Rui , Lyu Hairong , Xiao Xia , Zhang Xiaomei , Li Fan , Xie Danni , Xiong Xia , Wang Jiaxi , Lu Wenyi , Zhang Hongkai , Zhao Mingfeng
Published: July 2022

Relapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis. In this study, we evaluated chimeric antigen receptor (CAR) T cell therapy targeting CLL-1 in adults with R/R AML patients. Patients received conditioning chemotherapy with cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days and an infusion of a dose of 1–2 × 106 CAR-T cells/kg. The incidence of dose-limiting toxicity was the primary endpoint. Ten patients were treated, and all developed cytokine release syndrome (CRS); 4 cases were low-grade, while the remaining 6 were considered high-grade CRS. No patient developed CAR-T cell-related encephalopathy syndrome (CRES). Severe pancytopenia occurred in all patients. Two patients died of severe infection due to chronic agranulocytosis. The complete response (CR)/CR with incomplete hematologic recovery (CRi) rate was 70% (n = 7/10). The median follow-up time was 173 days (15–488), and 6 patients were alive at the end of the last follow-up. CAR-T cells showed peak expansion within 2 weeks. Notably, CLL-1 is also highly expressed in normal granulocytes, so bridging hematopoietic stem cell transplantation (HSCT) may be a viable strategy to rescue long-term agranulocytosis due to off-target toxicity. In conclusion, this study is the first to demonstrate the positive efficacy and tolerable safety of CLL-1 CAR-T cell therapy in adult R/R AML.
Time course of lung ultrasound findings in patients with COVID-19 pneumonia and cardiac dysfunction
Authors: Leote Joao , Judas Tiago , Broa Ana Luísa , Lopes Miguel , Abecasis Francisca , Pintassilgo Inês , Gonçalves Afonso , Gonzalez Filipe
Published: July 2022

Background

Lung ultrasound (LUS) is a valuable tool to predict and monitor the COVID-19 pneumonia course. However, the influence of cardiac dysfunction (CD) on LUS findings remains to be studied. Our objective was to determine the effect of CD on LUS in hospitalized patients with COVID-19 pneumonia.

Material and methods

Fifty-one patients with COVID-19 pneumonia participated in the study. Focused echocardiography (FoCUS) was carried out on day 1 to separate patients into two groups depending on whether they had FoCUS signs of CD (CD+ vs CD−). LUS scores, based on the thickness of the pleural line, the B-line characteristics, and the presence or not of consolidations, were obtained three times along the patient’s admission (D1, D5, D10) and compared between CD+ and CD− patients. A correlation analysis was carried out between LUS scores and the ratio of the arterial partial pressure of oxygen to the fraction of the inspired oxygen (P/F ratio).

Results

Twenty-two patients were CD+ and 29 patients were CD−. Among the CD+ patients, 19 were admitted to the intensive care unit (ICU), seven received invasive mechanical ventilation (IMV), and one did not survive. Among the CD− patients, 11 were admitted to the ICU, one received IMV and seven did not survive. CD+ patients showed a significantly lower P/F ratio than CD− patients. However, LUS scores showed no between-group differences, except for fewer subpleural consolidations in the upper quadrants of CD+ than on CD− patients.

Conclusion

In patients with COVID-19, CD contributed to a worse clinical course, but it did not induce significant changes in LUS. Our findings suggest that pathophysiological factors other than those reflected by LUS may be responsible for the differences in clinical condition between CD+ and CD− patients.
Fixed point results for generalized rational type $$\alpha$$ -admissible contractive mappings in the setting of partially ordered b-metric spaces
Authors: Haji Kedir Husen , Tola Kidane Koyas , Mamud Mustefa Abduletif
Published: July 2022

Objectives

In this paper we introduce fixed point theorems for generalized rational type $$\alpha$$
α
-admissible contractive mappings in partially ordered b-metric spaces and prove the existence and uniqueness of fixed points for self-mappings satisfying the established theorems. Finally, we provide examples in support of our main findings in the setting of partially ordered b-metric spaces.

Result

New fixed point results have been obtained for generalized rational type $$\alpha$$
α
-admissible contractive mappings in the setting of partially ordered b-metric space and we applied one of our results to determine a solution to an integral equation.
Level-wise aligned dual networks for text–video retrieval
Authors: Lin Qiubin , Cao Wenming , He Zhiquan
Published: July 2022

The vast amount of videos on the Internet makes efficient and accurate text–video retrieval tasks increasingly important. The current methods leverage a high-dimensional space to align video and text for these tasks. However, a high-dimensional space cannot fully use different levels of information in videos and text. In this paper, we put forward a method called level-wise aligned dual networks (LADNs) for text–video retrieval. LADN uses four common latent spaces to improve the performance of text–video retrieval and utilizes the semantic concept space to increase the interpretability of the model. Specifically, LADN first extracts different levels of information, including global, local, temporal, and spatial–temporal information, from videos and text. Then, they are mapped into four different latent spaces and one semantic space. Finally, LADN aligns different levels of information in various spaces. Extensive experiments conducted on three widely used datasets, including MSR-VTT, VATEX, and TRECVID AVS 2016-2018, demonstrate that our proposed approach is superior to several state-of-the-art text–video retrieval approaches.
Characterization and mitigation option of greenhouse gas emissions from lactating Holstein dairy cows in East China
Authors: Jia Peng , Tu Yan , Liu Zhihao , Lai Qi , Li Fadi , Dong Lifeng , Diao Qiyu
Published: July 2022

Background

This study investigated greenhouse gas (GHG) emission characteristics of lactating Holstein dairy cows in East China and provided a basis for formulating GHG emission reduction measures. GreenFeed system was used to measure the amount of methane (CH4) and carbon dioxide (CO2) emitted by the cows through respiration. Data from a commercial cow farm were used to observe the effects of parity, body weight, milk yield, and milk component yield on CH4 and CO2 emissions.

Results

Mean herd responses throughout the study were as follows: 111 cows completed all experimental processes, while 42 cows were rejected because they were sick or had not visited the GreenFeed system 20 times. On average, lactating days of cows was 138 ± 19.04 d, metabolic weight was 136.5 ± 9.5 kg, parity was 2.8 ± 1.0, dry matter intake (DMI) was 23.1 ± 2.6 kg/d, and milk yield was 38.1 ± 6.9 kg/d. The GreenFeed system revealed that CH4 production (expressed in CO2 equivalent, CO2-eq) was found to be 8304 g/d, $$ {\mathrm{CH}}_{4\left({\mathrm{CO}}_2-\mathrm{eq}\right)} $$

C
H

4
(

C
O

2

−

e
q

)

/DMI was 359 g/kg, $$ {\mathrm{CH}}_{4\left({\mathrm{CO}}_2-\mathrm{eq}\right)} $$

C
H

4
(

C
O

2

−

e
q

)

/energy-corrected milk (ECM) was 229.5 g/kg, total CO2 production (CH4 production plus CO2 production) was 19,201 g/d, total CO2/DMI was 831 g/kg, and total CO2/ECM was 531 g/kg. The parity and metabolic weight of cows had no significant effect on total CO2 emissions (P > 0.05). Cows with high milk yield, milk fat yield, milk protein yield, and total milk solids yield produced more total CO2 (P < 0.05), but their total CO2 production per kg of ECM was low (P < 0.05). The total CO2/ECM of the medium and high milk yield groups was 17% and 27% lower than that of the low milk yield group, respectively.

Conclusions

The parity and body condition had no effect on total CO2 emissions, while the total CO2/ECM was negatively correlated with milk yield, milk fat yield, milk protein yield, and total milk solids yield in lactating Holstein dairy cows. Measurement of total CO2 emissions of dairy cows in the Chinese production system will help establish regional or national GHG inventories and develop mitigation approaches to dairy production regimes.
Establishment of a male fertility prediction model with sperm RNA markers in pigs as a translational animal model
Authors: Pang Won-Ki , Amjad Shehreen , Ryu Do-Yeal , Adegoke Elikanah Olusayo , Rahman Md Saidur , Park Yoo-Jin , Pang Myung-Geol
Published: July 2022

Background

Male infertility is an important issue that causes low production in the animal industry. To solve the male fertility crisis in the animal industry, the prediction of sperm quality is the most important step. Sperm RNA is the potential marker for male fertility prediction. We hypothesized that the expression of functional genes related to fertilization will be the best target for male fertility prediction markers. To investigate optimum male fertility prediction marker, we compared target genes expression level and a wide range of field data acquired from artificial insemination of boar semen.

Results

Among the genes related to acrosomal vesicle exocytosis and sperm–oocyte fusion, equatorin (EQTN), zona pellucida sperm-binding protein 4 (ZP4), and sperm acrosome membrane-associated protein 3 exhibited high accuracy (70%, 90%, and 70%, respectively) as markers to evaluate male fertility. Combinations of EQTN-ZP4, ZP4-protein unc-13 homolog B, and ZP4-regulating synaptic membrane exocytosis protein 1 (RIMS1) showed the highest prediction value, and all these markers are involved in the acrosome reaction.

Conclusion

The EQTN-ZP4 model was efficient in clustering the high-fertility group and may be useful for selection of animal that has superior fertility in the livestock industry. Compared to the EQTN-ZP4 model, the ZP4-RIMS1 model was more efficient in clustering the low-fertility group and may be useful in the diagnosis of male infertility in humans and other animals. The appointed translational animal model and established biomarker combination can be widely used in various scientific fields such as biomedical science.
13C tracer analysis suggests extensive recycling of endogenous CO2 in vivo
Authors: Duan Likun , Cooper Daniel E. , Scheidemantle Grace , Locasale Jason W. , Kirsch David G. , Liu Xiaojing
Published: July 2022

Background

13C tracer analysis is increasingly used to monitor cellular metabolism in vivo and in intact cells, but data interpretation is still the key element to unveil the complexity of metabolic activities. The distinct 13C labeling patterns (e.g., M + 1 species in vivo but not in vitro) of metabolites from [U-13C]-glucose or [U-13C]-glutamine tracing in vivo and in vitro have been previously reported by multiple groups. However, the reason for the difference in the M + 1 species between in vivo and in vitro experiments remains poorly understood.

Methods

We have performed [U-13C]-glucose and [U-13C]-glutamine tracing in sarcoma-bearing mice (in vivo) and in cancer cell lines (in vitro). 13C enrichment of metabolites in cultured cells and tissues was determined by LC coupled with high-resolution mass spectrometry (LC-HRMS). All p-values are obtained from the Student’s t-test two-tailed using GraphPad Prism 8 unless otherwise noted.

Results

We observed distinct enrichment patterns of tricarboxylic acid cycle intermediates in vivo and in vitro. As expected, citrate M + 2 or M + 4 was the dominant mass isotopologue in vitro. However, citrate M + 1 was unexpectedly the dominant isotopologue in mice receiving [U-13C]-glucose or [U-13C]-glutamine infusion, but not in cultured cells. Our results are consistent with a model where the difference in M + 1 species is due to the different sources of CO2 in vivo and in vitro, which was largely overlooked in the past. In addition, a time course study shows the generation of high abundance citrate M + 1 in plasma of mice as early as few minutes after [U-13C]-glucose infusion.

Conclusions

Altogether, our results show that recycling of endogenous CO2 is substantial in vivo. The production and recycling of 13CO2 from the decarboxylation of [U-13C]-glucose or [U-13C]-glutamine is negligible in vitro partially due to dilution by the exogenous HCO3−/CO2 source, but in vivo incorporation of endogenous 13CO2 into M + 1 metabolites is substantial and should be considered. These findings provide a new paradigm to understand carbon atom transformations in vivo and should be taken into account when developing mathematical models to better reflect carbon flux.
Distinct cell type-specific protein signatures in GRN and MAPT genetic subtypes of frontotemporal dementia
Authors: Miedema Suzanne S. M. , Mol Merel O. , Koopmans Frank T. W. , Hondius David C. , van Nierop Pim , Menden Kevin , de Veij Mestdagh Christina F. , van Rooij Jeroen , Ganz Andrea B. , Paliukhovich Iryna , Melhem Shamiram , Li Ka Wan , Holstege Henne , Rizzu Patrizia , van Kesteren Ronald E. , van Swieten John C. , Heutink Peter , Smit August B.
Published: July 2022

Frontotemporal dementia is characterized by progressive atrophy of frontal and/or temporal cortices at an early age of onset. The disorder shows considerable clinical, pathological, and genetic heterogeneity. Here we investigated the proteomic signatures of frontal and temporal cortex from brains with frontotemporal dementia due to GRN and MAPT mutations to identify the key cell types and molecular pathways in their pathophysiology. We compared patients with mutations in the GRN gene (n = 9) or with mutations in the MAPT gene (n = 13) with non-demented controls (n = 11). Using quantitative proteomic analysis on laser-dissected tissues we identified brain region-specific protein signatures for both genetic subtypes. Using published single cell RNA expression data resources we deduced the involvement of major brain cell types in driving these different protein signatures. Subsequent gene ontology analysis identified distinct genetic subtype- and cell type-specific biological processes. For the GRN subtype, we observed a distinct role for immune processes related to endothelial cells and for mitochondrial dysregulation in neurons. For the MAPT subtype, we observed distinct involvement of dysregulated RNA processing, oligodendrocyte dysfunction, and axonal impairments. Comparison with an in-house protein signature of Alzheimer’s disease brains indicated that the observed alterations in RNA processing and oligodendrocyte function are distinct for the frontotemporal dementia MAPT subtype. Taken together, our results indicate the involvement of different brain cell types and biological mechanisms in genetic subtypes of frontotemporal dementia. Furthermore, we demonstrate that comparison of proteomic profiles of different disease entities can separate general neurodegenerative processes from disease-specific pathways, which may aid the development of disease subtype-specific treatment strategies.
Identification of mRNA vaccines and conserved ferroptosis related immune landscape for individual precision treatment in bladder cancer
Authors: Gui Cheng-Peng , Li Jia-Ying , Fu Liang-Min , Luo Cheng-Gong , Zhang Chi , Tang Yi-Ming , Zhang Li-zhen , Shu Guan-nan , Wu Rong-Pei , Luo Jun-Hang
Published: July 2022

Background

The aim of this study was to identify the ferroptosis induced tumor microenvironment (FeME) landscape in bladder cancer (BCa) for mRNA vaccine development and selecting suitable patients for precision treatment.

Methods

Gene expression profiles and clinical information of 1216 BCa patients were extracted from TCGA-BLCA, three GEO databases and IMvigor210 cohort. We comprehensively established the FeME landscape of 1216 BCa samples based on 290 ferroptosis related genes (FRGs), and systematically correlated these regulation patterns with TME cell-infiltrating characteristics. Besides, we identified the patients’ ferroptosis risk index (FRI) to predict the prognosis of BCa for precise treatment.

Results

Six over-expressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in BCa. Furthermore, we demonstrated the evaluation of FeME within individual tumors could predict stages of tumor inflammation, subtypes, genetic variation, and patient prognosis. Then, 5-lncRNA signature was mined to produce the FRI. Low FRI was also linked to increased mutation load, better prognosis and enhanced response to anti-PD-L1 immunotherapy. Besides, an immunotherapy cohort confirmed patients with lower FRI demonstrated significant therapeutic advantages and clinical benefits.

Conclusions

TFRC, SCD, G6PD, FADS2, SQLE, and SLC3A2 are potent antigens for developing anti-BCa mRNA vaccine. Establishment of FRI will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies and selecting appropriate patients for tumor vaccine therapy.
High tibial osteotomy for medial meniscus posterior root tears in knees with moderate varus alignment can achieve favorable clinical outcomes
Authors: Itou Junya , Kuwashima Umito , Itoh Masafumi , Okazaki Ken
Published: July 2022

Purpose

Favorable clinical results have been reported following high tibial osteotomy (HTO) for medial meniscus posterior root tear (MMPRT) in knees with varus alignment. However, the effect on the preoperative neutral alignment of the knee is not known. This study sought to evaluate the clinical outcomes of medial open-wedge HTO for MMPRT with neutral alignment.

Methods

We retrospectively reviewed 119 medial open-wedge HTOs and analyzed 22 knees with MMPRT. The knees were divided according to the preoperative hip-knee-ankle angle into a moderate varus alignment group (≤4° of varus alignment) and a varus alignment group (> 4° of varus alignment). The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Forgotten Joint Score-12 (FJS-12) values were evaluated preoperatively and at the latest follow-up. The healing status of MMPRT at the time of second-look arthroscopy, performed at a mean of 15.4 ± 4.2 months, was compared with that after the primary HTO.

Results

There were 11 knees in the moderate varus alignment group and 11 in the varus alignment group. In terms of perioperative patient-reported outcome measures, there was no significant difference in the preoperative or postoperative KOOS subscale score or FJS-12 score between the moderate varus and varus alignment groups. The healing rate was significantly higher in the moderate varus alignment group.

Conclusion

Favorable clinical results were obtained by medial open-wedge HTO in knees with MMPRT and moderate varus alignment in the short term. Surgeons should consider the indications for medial open-wedge HTO, even with moderate varus alignment, when planning treatment for MMPRT with persistent knee pain.

Level of evidence

IV
Plugging efficiency of pouring aggregates through multiple boreholes into an inundated tunnel to prevent groundwater inrush disasters
Authors: Hui Shuang , Sui Wanghua , Zhang Gailing , Chen Jiaxing , Yu Shibo
Published: July 2022

This paper presents an experimental investigation of the plugging efficiency of aggregate pouring through multiple boreholes under flowing water conditions into an inundated mine tunnel. Aggregate pouring into an inundated mine tunnel has been widely used and constitutes the premise for the salvage of flooded underground mines through further grouting. However, corresponding in-depth research is relatively limited due to the concealment of underground engineering. A visual experimental setup for aggregate pouring into a tunnel replica was built based on the theory of similarity between sediment movement and slurry pipeline transportation. Four factors, each with four levels, including the aggregate particle size (0.25–0.5, 0.5–1, 1–2 and 2–5 mm), distance between boreholes (0.5, 0.75, 1 and 1.5 m), initial water flow rate (0, 1.5 × 10−2 m/s, 2.4 × 10−2 m/s and 3 × 10−2 m/s) and tunnel inclination (0°, 3°, 5° and 8°) were selected in orthogonal experiments to investigate the plugging efficiency. Range and variance analysis of the four-level orthogonal array experimental results indicated that the factors influencing the plugging efficiency, varying between 83.96 and 98.15%, could be ranked in descending order as the initial water flow rate, aggregate particle size, distance between boreholes and tunnel inclination. The former two factors yielded a more significant influence than that of the latter two factors. The measured water pressure difference ranging from 16 to 32% between the front and back ends of the formed aggregate mass in the pouring process indicated that there remained a high resistance to water flow, even if the aggregate mass was not capped but reached a certain length. Plugging criteria for aggregate pouring into horizontal and inclined tunnels were then proposed. Moreover, the optimal distance between boreholes to form an effective bulkhead was determined, which could be defined as the distance between boreholes when the aggregate mass exhibits the fastest build-up and the plugging capacity is reached.
Over-prescription of short-acting β2-agonists and asthma management in the Gulf region: a multicountry observational study
Authors: Alzaabi Ashraf , Al Busaidi Nasser , Pradhan Rohit , Shandy Fathelrahman , Ibrahim Naseem , Ashtar Moulham , Khudadah Khaled , Hegazy Khaled , Samir Mohamed , Negm Mohamed , Farouk Hisham , Al Khalidi Arwa , Beekman Maarten
Published: July 2022

Background

The overuse of short-acting β2-agonists (SABA) is associated with poor asthma control. However, data on SABA use in the Gulf region are limited. Herein, we describe SABA prescription practices and clinical outcomes in patients with asthma from the Gulf cohort of the SABA use IN Asthma (SABINA) III study.

Methods

In this cross-sectional study conducted at 16 sites across Kuwait, Oman, and the United Arab Emirates, eligible patients (aged ≥ 12 years) with asthma were classified based on investigator-defined disease severity guided by the 2017 Global Initiative for Asthma report and by practice type, i.e., respiratory specialist or primary care physician. Data on demographics, disease characteristics, and prescribed asthma treatments, including SABA, in the 12 months prior to a single, prospective, study visit were transcribed onto electronic case report forms (eCRFs). All analyses were descriptive in nature. Continuous variables were summarized by the number of non-missing values, given as mean (standard deviation [SD]) and median (range). Categorical variables were summarized by frequency counts and percentages.

Results

This study analyzed data from 301 patients with asthma, 54.5% of whom were treated by respiratory specialists. Most patients were female (61.8%), with a mean age of 43.9 years, and 84.4% were classified with moderate-to-severe disease, with a mean (SD) asthma duration of 14.8 (10.8) years. Asthma was partly controlled or uncontrolled in 51.2% of patients, with 41.9% experiencing ≥ 1 severe exacerbation in the 12 months preceding their study visit. Overall, 58.5% of patients were prescribed ≥ 3 SABA canisters, 19.3% were prescribed ≥ 10 canisters, and 13.3% purchased SABA over-the-counter (OTC) in the 12 months before the study visit. Most patients who purchased OTC SABA (92.5%) also received SABA prescriptions. Inhaled corticosteroid/long-acting β2-agonist combinations and oral corticosteroid bursts were prescribed to 87.7% and 22.6% of patients, respectively.

Conclusions

SABA over-prescription was highly prevalent in the Gulf region, compounded by purchases of nonprescription SABA and suboptimal asthma-related outcomes. Increased awareness among policymakers and healthcare practitioners is needed to ensure implementation of current, evidence-based, treatment recommendations to optimize asthma management in this region.

Trial registration

NCT03857178 (ClinicalTrials.gov).
Muscle activation patterns around knee following neuromuscular training in patients with knee osteoarthritis: secondary analysis of a randomized clinical trial
Authors: Rashid Shahzada Aadil , Hussain Mohammad Ejaz , Bhati Pooja , Veqar Zubia , Parveen Adila , Amin Insha , Rashid Shahzada Mudasir
Published: July 2022

Objective

To compare the effects of neuromuscular training (NMT) to a quadriceps strength training (QT) program on co-contraction index (CCI) of knee muscles in patients with knee osteoarthritis (OA).

Methods

Sixty-six knee OA patients with varus malalignment were recruited from the physiotherapy outpatient department of the university. After baseline measurements, they were randomly assigned into two groups: NMT (n = 33) and QT (n = 33). Patients in NMT group received neuromuscular exercises whereas QT group received conventional strengthening exercises for a period of 12 weeks, three times per week. Electromyographic (EMG) activity of quadriceps, hamstring and gastrocnemius muscle was evaluated during treadmill walking before and after 12 weeks of intervention period and CCI of medial quadriceps-medial hamstring (med QH), lateral quadriceps-lateral hamstring (lat QH), medial quadriceps-medial gastrocnemius (med QG) and, lateral quadriceps and lateral gastrocnemius (lat QG) was calculated.

Results

There was a significantly greater reduction in CCI of med QH (p = 0.02) and lat QH (p = 0.01) in the NMT group than the QT group. Whereas both NMT and QT led to statistically similar reductions in CCI of med QG (p = 0.08) and lat QG (p = 0.66).

Conclusion

Findings of this study suggest that NMT led to a greater reduction in CCI of knee muscles than QT which indicates that enhanced sensori-motor control attained by NMT could reduce knee loading in knee OA patients with varus malalignment.
Pediatric vs. adult stroke: comparative study in a tertiary referral hospital, Cairo, Egypt
Authors: Alloush Ramy , Eldin Nahed Salah , El-Khawas Hala , Shatla Rania , Nada Maha , Mohammed Maha Z. , Alloush Adel
Published: July 2022

Background

Even though stroke is rare in children, it is associated with serious or life-threatening consequences. Despite its rarity, the occurrence of stroke in children has age-related differences in risk factors, etiopathogenesis, and clinical presentations. Unlike adults, who have arteriosclerosis as the major cause of stroke, risk factors for pediatric strokes are multiple, including cardiac disorders, infection, prothrombotic disorders, moyamoya disease, moyamoya syndrome, and others. The goal of the current study was to compare the characteristics, clinical features, etiology, subtypes, and workup of pediatric and adult strokes.

Methods

This was a hospital-based observational study conducted on 222 participants. All patients underwent a full clinical and neurological examination, full laboratory study, cardiac evaluation, and neuroimaging; CT scan, MRI, MRA, MRV, carotid duplex, and transcranial Doppler (TCD). Ischemic stroke (IS) etiology was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, the "proposed classification for subtypes of arterial ischemic stroke in children," and the Oxfordshire Community Stroke Project (OCSP). Stroke severity was determined by the National Institutes of Health Stroke Scale (NIHSS) and PedNIHSS on admission.

Results

The proportion of pediatric ischemic strokes in the current study was 63.4 percent, while hemorrhagic strokes were 36.5%. The majority of the adult patients had ischemic strokes (84.1%), while hemorrhagic strokes were noted in 15.8% of the patients. According to the original TOAST classification, in the current study, the etiology of pediatric IS was other determined causes in 63.6%, undetermined etiology in 27.2%, and cardioembolic in 9.0%. For the adult group, the major stroke subtypes were large artery disease, small vessel disease, cardioembolic, other determined causes, and undetermined etiology at 49.6%, 28.6%, 6.9%, 0.6%, and 12.5%, respectively.

Conclusions

There is a greater etiological role for non-atherosclerotic arteriopathies, coagulopathies, and hematological disorders in pediatric stroke, while adults have more atherothrombotic causes. The co-existence of multiple risk factors in pediatric ischemic stroke is noticed. Thrombophilia evaluation is helpful in every case of childhood stroke. Children who have had a stroke should undergo vascular imaging as soon as possible. Imaging modalities include TCD and Doppler ultrasound, CT, MRI, MRA, and MRV, and cerebral angiography.
The relationship between myasthenia gravis and COVID-19: a systematic review
Authors: Tugasworo Dodik , Kurnianto Aditya , Retnaningsih  , Andhitara Yovita , Ardhini Rahmi , Budiman Jethro
Published: July 2022

Introduction

Viral infection such as coronavirus disease 2019 (COVID-19) can exacerbate and aggravate neurological disorders due to autoimmune etiology like myasthenia gravis (MG). Experimental therapies used in COVID-19 are also factors that can cause the worsening of MG symptoms. This review aimed to assess and conclude the research-based study systematically to analyze the relationship of MG and COVID-19.

Method

This study was conducted in accordance to Cochrane handbook for systematic reviews and the guideline of preferred reporting items for systematic review and meta-analysis (PRISMA) and synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. Inclusion criteria in this review were primary studies of every design, articles published in English around January 2000–October 2021, and the study used human as subject. A systematic literature finding was applied in 15 electronic scientific resources. The authors evaluated the study quality and risk of bias of each retrieved article.

Results

The authors found the study through electronic scientific resources that met inclusion and exclusion criteria. The authors evaluated 362 articles identified in literature searching, 22 articles met the criteria for this review and then underwent the evaluation of study quality and risk of bias.

Conclusion

COVID-19 infection can increase the risk of new-onset MG, myasthenic crisis, respiratory failure, and mortality rate due to cytokine storm in MG patients. The management of COVID-19 patients with MG is tailored to each person and based on national guidelines and local expert recommendations.
Childhood depression and oxidative stress
Authors: Yıldız Miniksar Dilşad , Göçmen Ayşe Yeşim
Published: July 2022

Background

Oxidative stress is a contributing factor in the etiopathogenesis of major depressive disorder (MDD). Pediatric studies regarding MDD-oxidative stress relationship are insufficient. In this study, we aimed to compare oxidative stress parameters of pediatric MDD patients with those of the control group and to examine factors affecting these parameters.

Results

Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), malondialdehyde (MDA) and superoxide dismutase (SOD) activities of 42 patients with MDD and 38 healthy controls were evaluated. Children depression inventory (CDI) was applied to all participants. In the MDD group, serum levels of TOS, OSI and MDA were higher, while TAS and SOD levels were lower (p < 0.001). When all participants were examined, oxidative stress increased as the CDI score increased, but in the MDD group, SOD increased as the CDI score increased. Increase in body mass index (BMI) percentile increased the oxidative stress in the MDD group. When factors affecting the presence of MDD were analyzed by binary logistic regression analysis, a one-unit increase in SOD decreased depression by 0.190 times.

Conclusions

This study showed that oxidative stress increases in children and adolescents with MDD, and the increase in the severity of depression further increases oxidative stress, but when the depression becomes very severe, level of SOD increases compensatorily. It has been observed that high BMI in MDD patients creates an additional burden on oxidative stress. The role of oxidative stress in the etiopathogenesis of MDD in children and adolescents should be evaluated more comprehensively.