bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Production-Education Integration Performance of the High-Tech Industry: An Empirical Comparison between Three Urban Agglomerations in China
Authors: Zhang Quan , Zhang Zhen , Li Zhuomei , Li Sifeng , Tang Tianzhen
Published: September 2021

Deepening production-education integration (PEI) is a major strategy of China to reinforce education reform and promote industry transformation. Different from the traditional research perspective of colleges on the supple side, this paper chooses to evaluate the PEI performance of the high-tech industry from the angle of industry on the demand side. Firstly, the action mechanisms of the education system and industry system in PEI were expounded, and the design framework of the evaluation index system (EIS) was derived from the interactions between two elements (technologies and talents) and two market relationships (supply and demand), forming a two-dimensional four-quadrant EIS. On this basis, the correlation-entropy composite matter-element (CECME) model and coupling coordination degree (CCD) model were introduced to empirically compare the PEI performance of the high-tech industry between Guangdong-Hong Kong-Macao (GHKM) Greater Bay Area, Beijing-Tianjin-Hebei (BTH) Urban Agglomeration, and Yangtze River Delta (YRD) Urban Agglomeration. The main conclusions are as follows: (1) the GHKM Greater Bay Area is far better in education and industry development than YRD Urban Agglomeration and BTH Urban Agglomeration; (2) the PEI performance of the high-tech industry in GHKM Greater Bay Area was evaluated as high level with industry in lead, that in YRD Urban Agglomeration as moderate level with education in lead, and that in BTH Urban Agglomeration high-tech industry PEI as moderate level with industry in lag. Finally, several countermeasures were proposed for the urban agglomerations to further enhance the PEI performance of the high-tech industry: GHKM Greater Bay Area should improve the weak link of education development; YRD Urban Agglomeration should give full play to its advantages in higher education; BTH Urban Agglomeration should focus on high-quality industry development. From the practical level, this paper objectively evaluates the actual performance of PEI and provides a reference for scientific policymaking of PEI development.
Electroacupuncture and Moxibustion Modulate the BDNF and TrkB Expression in the Colon and Dorsal Root Ganglia of IBS Rats with Visceral Hypersensitivity
Authors: Jin Duiyin , Liu Yanan , Lv Siyi , Qi Qin , Li Mei , Wang Yuanyuan , Wang Xiaomei , Wu Huangan
Published: September 2021

Objective. To evaluate the effects of electroacupuncture and moxibustion on brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase receptor B (TrkB) protein and mRNA expressions in the colon and dorsal root ganglia of IBS rats with visceral hypersensitivity and to explore their underlying therapeutic mechanisms. Method. Forty Sprague Dawley rats were randomly divided into normal, model, model + mild moxibustion (MM), model + electroacupuncture (EA), and model + pinaverium bromide (PB) groups, with eight rats in each group. Chronic visceral hypersensitive IBS rat models were established by colorectal distension (CRD) with mustard oil clyster. Rats in the MM and EA groups, respectively, received moxibustion and electroacupuncture treatments on the Tianshu (ST25) and Shangjuxu (ST37) acupoints once daily for 7 days, and rats in the PB group received pinaverium bromide by oral gavage once daily for 7 consecutive days. After treatment, rats underwent abdominal withdrawal reflex (AWR) scoring under CRD and colon histopathological examination. Immunohistochemistry and real-time quantitative PCR (RT-qPCR) were used to study the protein and mRNA expressions of BDNF and TrkB in the rat colon and dorsal root ganglia. Results. Compared with the normal group, AWR scores and body weight were clearly increased in the model group rats (both

P
<
0.01

). The body weights were significantly elevated (

P
<
0.01

,

P
<
0.05

), but the AWR scores were reduced (

P
<
0.05

,

P
<
0.01

), after electroacupuncture and mild moxibustion treatment. Compared with levels in normal rats, BDNF and TrkB protein and mRNA expressions were significantly elevated in the IBS model rats (

P
<
0.01

) but were downregulated after mild moxibustion, electroacupuncture, and Western medicine treatment (

P
<
0.01

). Conclusion. Electroacupuncture and moxibustion improved visceral hypersensitivity of IBS rats possibly by reducing BDNF and TrkB protein and mRNA expressions in the colon and dorsal root ganglia.
The Efficacy and Safety of Acupuncture for Treating Osteoporotic Vertebral Compression Fracture- (OVCF-) Induced Pain: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Li Jia-Liang , Rong Sha , Zhou Zhen , Zhang Xiao-Bo , Tang Zhao-hui , Huang Qing-Song , Li Wei-Hong
Published: September 2021

Background. Osteoporotic vertebral compression fractures (OVCFs) are common health issues in the elderly that cause chronic pain in over one-third of patients. This study was sought to evaluate the efficacy and safety of acupuncture for alleviating pain caused by OVCFs. Methods. We performed a search of 8 electronic databases for publications from the inception to 30th March 2021. Eligible studies were randomized clinical trials (RCTs) that evaluated the effect of acupuncture for the treatment of OVCFs. Two investigators evaluated literature quality and extracted data independently. RevMan V.5.4.1 was used for data analyses, with pooled risk estimates presented as mean difference (MD) or relative risk (RR) along with corresponding 95% confidence intervals (CIs), as appropriate. Results. Fourteen RCTs involving 1,130 patients were included in this meta-analysis. Compared with the control group, acupuncture showed a greater benefit on pain reduction caused by OVCFs (1 week: MD = −1.26, 95% CI: (−1.82,−0.70); 1 month: MD = −1.63, 95% CI: (−1.82,−1.43); 6 months: MD = −1.13, 95% CI: (−1.55, −0.70)). Acupuncture treatment was also associated with fewer adverse events, lower ODI index, and higher bone density than the control group (safety: (RR: 0.30, 95% CI: 0.12–0.75); ODI: MD = −3.19, 95% CI: (−5.20, −1.19); bone density: MD = 0.15, 95% CI: (0.05, 0.26)). The GRADE quality of these results was assessed as low or very low. Conclusions. Compared with the control treatment, acupuncture was more effective and safer in relieving the pain caused by OVCF and made a greater improvement on patient’s ODI score and bone density. Given the low level of our study evidence, future high-quality studies are needed to verify our study findings.
Implementation of Structural Assemblies by Simultaneous Projection and Density-Based Topology Optimization
Authors: Saeed Nouman , Long Kai , Ansari Jamshed Ahmed , Jaffri Nasif Raza , Abrar Usama
Published: September 2021

This article proposed a methodology that combines two well-known projections and modified density-based optimized techniques in one formulation methodology. This methodology contains an effective explicit geometric entity identified by shape variables that provide easy control in desired particular regions; implicit density-based topological optimization entities utilized topological variables that offer critical design elsewhere. Our main attractive key point of this combined formulation approach is structural assemblies. Structure always manufactures in many patches and joins them by utilizing the structural assemblies such as welding and riveting. It is not easy to execute the structural patches at the required region without acknowledging their dimensions. This proposed approach demonstrates the competence to impose the restrictions related to shape and topological variables of interfaces among the specific patches. Numerous standard numerical examples make sure the validation of the introduced methodology. It remarked that the optimal design could minimize compliance and the minimum number of iterations through numerically performed, concerning computational cost minimized without any kind loss of accuracy of the final structure.
Correlation Measures for Cubic m-Polar Fuzzy Sets with Applications
Authors: Garg Harish , Riaz Muhammad , Khokhar Muhammad Abdullah , Saba Maryam
Published: September 2021

A cubic

m

-polar fuzzy set (CmPFS) is a new hybrid extension of

m

-polar fuzzy set and cubic set. A CmPFS is a robust model to express multipolar information in terms of

m

fuzzy intervals representing membership grades and

m

fuzzy numbers representing nonmembership grades. In this article, we explore some new operational laws of CmPFSs, produce some related results, and discuss their consequences. We propose relative informational coefficients and relative noninformational coefficients for CmPFSs. These coefficients are analyzed to investigate further properties of CmPFSs. Based on these coefficients, we introduce new correlation measures and their weighted versions for CmPFSs. The value of proposed correlation measures is symmetrical and lies between −1 and 1. Moreover, the applications of the proposed correlation in pattern recognition and medical diagnosis are developed. The feasibility and efficiency of suggested correlation measures is determined by respective illustrative examples.
Corrosion Predictive Model in Hot‐Dip Galvanized Steel Buried in Soil
Authors: Arriba-Rodríguez Lorena-De , Ortega-Fernández Francisco , Villanueva-Balsera Joaquín M. , Rodríguez-Montequín Vicente
Published: September 2021

Corrosion is one of the main concerns in the field of structural engineering due to its effect on steel buried in soil. Currently, there is no clearly established method that allows its calculation with precision and ensures the durability of this type of structures. Qualitative methods are commonly used rather than quantitative methods. The objective of this research is the development of a multivariate quantitative predictive model for estimating the loss of thickness that will occur in buried hot‐dip galvanized steel as a function of time. The technique used in the modelling is the Adaptive Regression of Multivariate Splines (MARS). The main drawback of this kind of studies is the lack of data since it is not possible to have a priori the corrosive behaviour that the buried material will have as a function of time. To solve this issue, a solid and reliable database was built from the analysis and treatment of the existing literature and with the results obtained from a predictive model to estimate the thickness loss of ungalvanized steel. The input variables of the model are 5 characteristics of the soil, the useful life of the structure, and the loss of corroded ungalvanized steel in the soil. This last data is the output variable of another previous predictive model to estimate the loss of thickness of bare steel in a soil. The objective variable of the model is the loss of thickness that hot‐dip galvanized steel will experience buried in the ground and expressed in g/m2. To evaluate the performance and applicability of the proposed model, the statistical metrics RMSE, R2, MAE, and RAE and the graphs of standardized residuals were used. The results indicated that the model offers a very high prediction performance. Specifically, the mean square error was 290.6 g/m2 (range of the objective variable is from 51.787 g/m2 to 5950.5 g/m2), R2 was 0.96, and from a relative error of 0.14, the success of the estimate was 100%. Therefore, the use of the proposed predictive model optimizes the relationship between the amount of hot‐dip galvanized steel and the useful life of the buried metal structure.
Values of Contrast-Enhanced Ultrasound in Classification and Diagnosis of Common Bile Duct and Superficial Organ Lesions under Compression Algorithm
Authors: Li Yezhao , Zhao Caihong , Qin Minpei , Zhang Xia , Liao Haizhen , Su Haiqing
Published: September 2021

This work aimed to investigate values of contrast-enhanced ultrasound (CEUS) under DEFLATE in the classification and diagnosis of the common bile duct and superficial lymphoid lesions. 88 patients with lower common bile duct lesions and 126 patients with superficial lymphoid lesions were selected as the subjects investigated and examined by CEUS under DEFLATE to compare characteristics and diagnostic efficiency of CEUS in different types of lesions. The time-intensity curve (TIC) was for quantitative analysis on CEUS results. The results showed that there were statistically significant differences in the comparison of time to peak (TTP), area under the curve (AUC), and gradient (Grad) of common bile duct walls in patients from the malignant group (

P

 < 0.05), while the comparison of three indicators of patients in the benign group was not statistically remarkable (

P

 > 0.05). In addition, there were statistically great differences in TTP, AUC, and Grad among patients in the benign and malignant groups (

P

 < 0.05). The sensitivity, specificity, accuracy, and positive/negative predictive value of CEUS + ultrasound (US) in the diagnosis of benign and malignant lymph nodes were 92.83%, 87.14%, 89.54%, 91.23%, and 86.43%, respectively. The values of maximal intensity (Imax) in the reactive hyperplasia group (group A), lymphoma group (group B), and metastatic lymph nodes group (group C) were compared, showing statistical differences (

P

 < 0.05). The TTP and AUC of group B were higher than those of groups A and C, respectively (

P

 < 0.05), and the base-to-peak ascending slope (KUP) and the absolute value of the semidescending slope (KDOWN) in group C increased hugely compared to group A (

P

 < 0.05). It indicated that CEUS examination under DEFLATE could be applied in the qualitative diagnosis of lower common bile duct lesions and superficial lymphoid lesions, which was worthy of clinical application.
Discovery and Pharmacological Characterization of JNJ-64619178, a Novel Small-Molecule Inhibitor of PRMT5 with Potent Antitumor Activity
Authors: Brehmer Dirk , Beke Lijs , Wu Tongfei , Millar Hillary J. , Moy Christopher , Sun Weimei , Mannens Geert , Pande Vineet , Boeckx An , van Heerde Erika , Nys Thomas , Gustin Emmanuel M. , Verbist Bie , Zhou Longen , Fan Yue , Bhargava Vipul , Safabakhsh Pegah , Vinken Petra , Verhulst Tinne , Gilbert Angelique , Rai Sumit , Graubert Timothy A. , Pastore Friederike , Fiore Danilo , Gu Junchen , Johnson Amy , Philippar Ulrike , Morschhäuser Barbara , Walker David , De Lange Desiree , Keersmaekers Vikki , Viellevoye Marcel , Diels Gaston , Schepens Wim , Thuring Jan Willem , Meerpoel Lieven , Packman Kathryn , Lorenzi Matthew V. , Laquerre Sylvie
Published: September 2021

The protein arginine methyltransferase 5 (PRMT5) methylates a variety of proteins involved in splicing, multiple signal transduction pathways, epigenetic control of gene expression, and mechanisms leading to protein expression required for cellular proliferation. Dysregulation of PRMT5 is associated with clinical features of several cancers, including lymphomas, lung cancer, and breast cancer. Here, we describe the characterization of JNJ-64619178, a novel, selective, and potent PRMT5 inhibitor, currently in clinical trials for patients with advanced solid tumors, non-Hodgkin's lymphoma, and lower-risk myelodysplastic syndrome. JNJ-64619178 demonstrated a prolonged inhibition of PRMT5 and potent antiproliferative activity in subsets of cancer cell lines derived from various histologies, including lung, breast, pancreatic, and hematological malignancies. In primary acute myelogenous leukemia samples, the presence of splicing factor mutations correlated with a higher ex vivo sensitivity to JNJ-64619178. Furthermore, the potent and unique mechanism of inhibition of JNJ-64619178, combined with highly optimized pharmacological properties, led to efficient tumor growth inhibition and regression in several xenograft models in vivo, with once-daily or intermittent oral-dosing schedules. An increase in splicing burden was observed upon JNJ-64619178 treatment. Overall, these observations support the continued clinical evaluation of JNJ-64619178 in patients with aberrant PRMT5 activity–driven tumors.
An Overlooked Link between IgA Nephropathy and Lithium Toxicity: A Case Report
Authors: Mehandru Sushil K. , Kaur Supreet , Ghias Aisha , Bakr Mohamed , Asif Arif , Vachharajani Tushar J.
Published: September 2021

Lithium is one of the first-line agents for treating bipolar disorder. Although this agent is highly effective in treating mood disorders, renal toxicity is a frequent side effect. Lithium metabolism is affected by sodium-lithium counter-transporter (SLC-T) in erythrocytes. The high activity of SLC-T can result in decreased urinary lithium clearance and may lead to accumulation of lithium in the distal renal tubular cells, causing lithium toxicity. SLC-T is a genetic marker in primary hypertension (HTN), HTN in pregnancy, diabetic nephropathy, and IgA nephropathy (IgA-N) with HTN. Patients with IgA-N have been reported to have enhanced SLC-T activity and are likely to have considerably lower renal fractional clearance of lithium. Therefore, patients taking lithium for bipolar disorder with coexisting IgA-N can have severe lithium-induced nephropathy and nephrotoxicity even at therapeutic serum levels. Serum lithium levels reflect only extracellular lithium concentration. However, lithium exerts its effects once it has moved to the intracellular compartment. This phenomenon illustrates the reason why patients with significantly elevated serum levels might be asymptomatic. Creatinine clearance is inversely related to the duration of lithium therapy. The degree of interstitial fibrosis on renal biopsy has been known to be associated with the duration of lithium therapy and cumulative dose. We present a case with a past medical history of bipolar disorder treated with lithium for almost 20 years. His family history was significant for HTN. The patient was diagnosed with renal insufficiency of unknown causes, for which he underwent renal biopsy. The renal biopsy showed a typical lithium-induced tubulointerstitial nephritis and a coincidental finding of IgA-N. We suspect a high activity of SLC-T seen in IgA-N, and the adverse effects of lithium on SLC-T activity might cause reduction of urinary lithium clearance and accumulation of lithium in distal renal tubular cells, contributing to nephrotoxicity. There is a lack of the literature on the coexistence of IgA-N and lithium nephrotoxicity. We recommend in patients with concomitant IgA-N, taking lithium, more frequent monitoring of renal functions, and dose adjustments may reduce the risk of lithium-induced nephrotoxicity.
Kosaki Overgrowth Syndrome: Report of a Family with a Novel PDGFRB Variant
Authors: Mutlu Albayrak Hatice , Calder Alistair D.
Published: September 2021

Heterozygous activating missense variants of PDGFRB are associated with the phenotype of Kosaki overgrowth syndrome (KOGS). Here, we present a family including a father and 2 siblings with a novel variant, c.2567A>T (p.Asn856Ile), localized in the cytoplasmic tyrosine kinase domain, exhibiting a KOGS phenotype. The coarsening of the facial features, enlargement of the hands/feet, and progressive scoliosis started to appear after an average age of 6. There were no signs of thin/fragile skin, premature aging appearance, myofibroma, white matter findings, and intellectual disability in any of them. Corneal pterygium and evidence of cerebral vasculopathy were only detected in the father. One sibling exhibited café-au-lait spots. Posterior fossa enlargement was revealed only in one sibling. KOGS is an extremely rare overgrowth syndrome. No familial cases of KOGS have been reported so far. Hereby, we demonstrated that the features of KOGS can show mild intrafamilial variability, and the risk of vascular complications may arise with age.
A Rare Cause of Acute Abdomen in a 59-Year-Old Male
Authors: Bangolo Ayrton , Pender Sarah , Sajja Chandini , Akhter Mahabuba , Govil Swati , Lo Abraham
Published: September 2021

Celiac artery dissection is often an inconspicuous cause of acute abdomen. Spontaneous celiac artery dissection is most often associated with aortic dissection, and thus isolated spontaneous celiac artery dissection is rare. Herein, we present a case of celiac artery dissection with no aortic involvement. This case emphasizes the importance of including such a condition in the differential diagnosis of patients presenting with acute abdomen.
Next-Generation Sequencing-Based Genetic Diagnostic Strategies of Inherited Kidney Diseases
Authors: Zhang Jiahui , Zhang Changming , Gao Erzhi , Zhou Qing
Published: September 2021

Background: At least 10% of adults and most of the children who receive renal replacement therapy have inherited kidney diseases. These disorders substantially decrease their life quality and have a large effect on the health-care system. Multisystem complications, with typical challenges for rare disorders, including variable phenotypes and fragmented clinical and biological data, make genetic diagnosis of inherited kidney disorders difficult. In current clinical practice, genetic diagnosis is important for clinical management, estimating disease development, and applying personal treatment for patients. Summary: Inherited kidney diseases comprise hundreds of different disorders. Here, we have summarized various monogenic kidney disorders. These disorders are caused by mutations in genes coding for a wide range of proteins including receptors, channels/transporters, enzymes, transcription factors, and structural components that might also have a role in extrarenal organs (bone, eyes, brain, skin, ear, etc.). With the development of next-generation sequencing technologies, genetic testing and analysis become more accessible, promoting our understanding of the pathophysiologic mechanisms of inherited kidney diseases. However, challenges exist in interpreting the significance of genetic variants and translating them to guide clinical managements. Alport syndrome is chosen as an example to introduce the practical application of genetic testing and diagnosis on inherited kidney diseases, considering its clinical features, genetic backgrounds, and genetic testing for making a genetic diagnosis. Key Messages: Recent advances in genomics have highlighted the complexity of Mendelian disorders, which is due to allelic heterogeneity (distinct mutations in the same gene produce distinct phenotypes), locus heterogeneity (mutations in distinct genes result in similar phenotypes), reduced penetrance, variable expressivity, modifier genes, and/or environmental factors. Implementation of precision medicine in clinical nephrology can improve the clinical diagnostic rate and treatment efficiency of kidney diseases, which requires a good understanding of genetics for nephrologists.
Detection of Major Human Herpesviruses in Iranian Patients with Suspected Encephalitis Using Multiplex Polymerase Chain Reaction
Authors: Golrokh Mofrad Morvarid , Samie Saeid , Lak Ramin , Faghihloo Ebrahim
Published: September 2021

Background: The Herpesviridae family plays a significant etiological role in central nervous system viral infections during primary infection or reactivation from a latent form. Early detection is crucial because prescribing some antivirals can prevent severe side effects or life-threatening conditions. Methods: In this study, 251 CSF specimens were collected from patients with clinical suspicion of viral encephalitis in Pars Hospital, Tehran, Iran. DNA was extracted, and a multiplex PCR was designed to investigate the presence of herpes simplex virus-1, herpes simplex virus-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus. Results: Overall, 59 cases of the 251 CSF samples were positive for multiplex PCR (23.5%). The most frequent positive findings were EBV and HSV, with a prevalence of 10.3% and 8.7% (5.5% HSV-1 and 3.1% HSV-2), respectively. Four co-infections were also seen in this study. Conclusions: This multiplex PCR assay detects simultaneously different herpesviruses in CSF samples of patients with suspected encephalitis in 2 rounds of PCR amplification; therefore, it is a reliable and cost-saving diagnostic method for evaluating patients infected with herpesvirus with neurological disorders.
Zu Risiken und Nebenwirkungen …? Anregung zur Diskussion über potenzielle Nebenwirkungen klinisch-psychologischer Diagnostik in der Psychotherapie
Authors: Hilbert Kevin , Ertle Andrea
Published: September 2021

Der Wert einer umfassenden, strukturierten Diagnostik für Therapieplanung und -durchführung ist unumstritten. Über mögliche Nebenwirkungen und Risiken wird aber selten diskutiert oder aufgeklärt. Ebenso steht die Bedeutung der Aufklärung von Patient:innen über die Psychotherapie außer Frage, während die Bedeutung der Diagnostik in der Auf­klärungsroutine weniger Raum einnimmt. Unter Heranziehen von zwei Fallbeispielen werden mögliche Nebenwirkungen eines umfangreichen diagnostischen Vorgehens beleuchtet, darunter soziale Konsequenzen, (Selbst-)Stigmatisierung und die Bedeutung von Lebenszeitdiagnosen. Eine bessere Aufklärung sowie gegebenenfalls eine Fo­kus­sierung angewandter diagnostischer Instrumente werden als Veränderungen des diagnostischen Prozesses vorgeschlagen. Gerne möchten wir eine weitere Diskussion zum Thema anregen.
Heterogeneity of Frailty Trajectories and Associated Factors in the Lothian Birth Cohort 1936
Authors: Welstead Miles , Luciano Michelle , Russ Tom C. , Muniz-Terrera Graciela
Published: September 2021

Introduction: Recent research suggests that the experience of frailty progression may be heterogeneous, with latent subpopulations of older adults following distinct trajectories of frailty. We aimed to investigate this notion and determine whether certain factors are associated with the membership of these subpopulations. Methods: Data from 5 data waves collected over 12 years in participants of the Lothian Birth Cohort 1936, aged 70 at baseline, were used to derive the frailty index (FI) (NW1 = 1,091, NW5 = 431). These were used in latent class mixed modelling to estimate subpopulations of frailty trajectories. Results: A quadratic latent class mixed model found 3 distinct groupings, which followed a low (61%, n = 632), medium (36%, n = 368), or high (3%, n = 28) FI trajectory. Each grouping had different intercepts and slopes, with the high grouping following the steepest trajectory indicating a rapid increase in frailty. Findings showed that in general, those in the low grouping were younger, had higher education, higher age 11 cognitive ability, and were from a higher social class than those in the medium and high groupings. Discussion/Conclusion: Our findings demonstrate heterogeneity in frailty trajectories over 12 years in individuals aged 70 years at baseline. Membership of higher frailty trajectory groupings was associated with lower social class, less education, and lower childhood cognitive ability, indicating the potential for future interventions to target individuals who are at the greatest risk of belonging to the high frailty trajectory. Future research is required to continue this line of inquiry by exploring other risk and protective factors, and importantly, to assess whether it is possible to realign an individual’s membership to a less detrimental grouping of frailty trajectory.
Trends of Corneal Transplantation in Adults from 2010 to 2019 in East China: A 10-Year Experience
Authors: Zhao Songjiao , Wan Xichen , Yao Wang , Xu Jianjiang , Le Qihua
Published: September 2021

Introduction: The aim of the study was to provide an overview of trends in the indications and surgical techniques for corneal transplantation in adults in East China from 2010 to 2019. Methods: The medical charts of all patients (aged ≥18 years old) undergoing keratoplasty at the Eye, Ear, Nose and Throat Hospital of Fudan University between January 2010 and December 2019 were retrospectively reviewed. The indications for keratoplasty and the surgical techniques were collected. Results: A total of 2,929 cases were included. Acquired nontraumatic corneal diseases (n = 1,927, 65.8%) have been the leading indication for corneal transplantation during the past decade. Although infectious keratitis was still the leading indication among acquired nontraumatic diseases, its absolute number and proportion gradually decreased during this decade (p < 0.001). In contrast, the proportion of endothelial dysfunction/bullous keratopathy increased from 7.8% in 2010 to 12.4% in 2019 (p = 0.029). Penetrating keratoplasty (PKP) has been the predominant surgical technique (n = 1,854, 63.3%), followed by deep anterior lamellar keratoplasty (DALK) (n = 361, 12.3%) and endothelial keratoplasty (EK) (n = 305, 10.4%). Nevertheless, the proportion of PKP decreased from 77.6% in 2010 to 56.9% in 2019 (p = 0.002) and was gradually replaced by DALK (from 7.8% to 16.3%, p < 0.001) and EK (from 3.4% to 10.4%, p = 0.009). Conclusions: Over the past decade, infectious keratitis and endothelial dysfunction/bullous keratopathy have been the leading indications for keratoplasty in adults. Preferred surgical techniques for keratoplasty have been shifting from PKP to more customized lamellar keratoplasties.
Are Post Hoc Analyses on Subgroups Sufficient to Support New Treatment Algorithms of Heart Failure? The Case of SGLT2 Inhibitors Associated with Sacubitril/Valsartan
Authors: Volpe Massimo , Gallo Giovanna , Zieroth Shelley
Published: September 2021

The use of sodium glucose cotransporter 2 inhibitors (SGLT2i) in heart failure (HF) with reduced ejection fraction (HFrEF) has been strongly supported by the results of recent randomized clinical trials. Upon this evidence, international recommendations and consensus documents propose the inclusion of SGLT2i among the first-line classes for HFrEF management. Subsequent analyses of treatment subgroups have been performed to investigate the effects of SGLT2i in patients treated with first-line classes including sacubitril/valsartan (Sac/Val), showing a consistent reduction of cardiovascular outcomes with a good safety profile of SGLT2i in combination with the other classes. Accordingly, SGLT2i are recommended also in combination with Sac/Val. This association, however, may require caution before being translated into guideline-directed medical therapy in clinical practice, since the proportion of patients receiving Sac/Val and SGLT2i in the available studies was poorly represented. In order to support an effective and safe sequencing or a simultaneous initiation of these 2 drug classes, pragmatic and real-world clinical studies would be helpful.
Ketone Ester D‐β‐Hydroxybutyrate‐(R)‐1,3 Butanediol Prevents Decline in Cardiac Function in Type 2 Diabetic Mice
Authors: Thai Phung N. , Miller Charles V. , King M. Todd , Schaefer Saul , Veech Richard L. , Chiamvimonvat Nipavan , Bers Donald M. , Dedkova Elena N.
Published: September 2021

Background

Heart failure is responsible for approximately 65% of deaths in patients with type 2 diabetes mellitus. However, existing therapeutics for type 2 diabetes mellitus have limited success on the prevention of diabetic cardiomyopathy. The aim of this study was to determine whether moderate elevation in D‐β‐hydroxybutyrate improves cardiac function in animals with type 2 diabetes mellitus.

Methods and Results

Type 2 diabetic (db/db) and their corresponding wild‐type mice were fed a control diet or a diet where carbohydrates were equicalorically replaced by D‐β‐hydroxybutyrate‐(R)‐1,3 butanediol monoester (ketone ester [KE]). After 4 weeks, echocardiography demonstrated that a KE diet improved systolic and diastolic function in db/db mice. A KE diet increased expression of mitochondrial succinyl‐CoA:3‐oxoacid‐CoA transferase and restored decreased expression of mitochondrial β‐hydroxybutyrate dehydrogenase, key enzymes in cardiac ketone metabolism. A KE diet significantly enhanced both basal and ADP‐mediated oxygen consumption in cardiac mitochondria from both wild‐type and db/db animals; however, it did not result in the increased mitochondrial respiratory control ratio. Additionally, db/db mice on a KE diet had increased resistance to oxidative and redox stress, with evidence of restoration of decreased expression of thioredoxin and glutathione peroxidase 4 and less permeability transition pore activity in mitochondria. Mitochondrial biogenesis, quality control, and elimination of dysfunctional mitochondria via mitophagy were significantly increased in cardiomyocytes from db/db mice on a KE diet. The increase in mitophagy was correlated with restoration of mitofusin 2 expression, which contributed to improved coupling between cytosolic E3 ubiquitin ligase translocation into mitochondria and microtubule‐associated protein 1 light chain 3–mediated autophagosome formation.

Conclusions

Moderate elevation in circulating D‐β‐hydroxybutyrate levels via KE supplementation enhances mitochondrial biogenesis, quality control, and oxygen consumption and increases resistance to oxidative/redox stress and mPTP opening, thus resulting in improvement of cardiac function in animals with type 2 diabetes mellitus.
Risk‐Attributable Burden of Ischemic Heart Disease in 137 Low‐ and Middle‐Income Countries From 2000 to 2019
Authors: Wang Chenran , Sun Yanghua , Jiang Di , Wang Chunping , Liu Shiwei
Published: September 2021

Background

Ischemic heart disease (IHD) imposes the greatest disease burden globally, especially in low‐ and middle‐income countries (LMICs). We aim to examine the population‐attributable fraction and risk‐attributable death and disability‐adjusted life years (DALYs) for IHD in 137 low‐ and middle‐income countries.

Methods and Results

Using comparative risk assessment framework from the 2019 Global Burden of Disease study, the population‐attributable fraction and IHD burden (death and DALYs) attributable to risk factors in low‐income countries, lower‐middle‐income countries (LMCs), and upper‐middle‐income countries were assessed from 2000 to 2019. In 2019, the population‐attributable fraction (%) of IHD deaths in relation to all modifiable risk factors combined was highest in lower‐middle‐income countries (94.2; 95% uncertainty interval, 91.9–96.2), followed by upper‐middle‐income countries (93.5; 90.4–95.8) and low‐income countries (92.5; 90.0–94.7). There was a >13‐fold difference between Peru and Uzbekistan in age‐standardized rates (per 100 000) of attributable death (44.3 versus 660.4) and DALYs (786.7 versus 10506.1). Dietary risks accounted for the largest proportion of IHD’s behavioral burden in low‐ and middle‐income countries, primarily attributable to diets low in whole grains. High systolic blood pressure and high low‐density lipoprotein cholesterol remained the 2 leading causes of DALYs, with the former topping the list in 116 countries, while the latter led in 21 of the 137 countries. Compared with 2000 to 2010, the increases in risk‐attributable deaths and DALYs among upper‐middle income countries were slower from 2010 to 2019, while the trends in low‐income countries and lower‐middle income countries were opposite.

Conclusions

IHD’s attributable burden remains high in low‐ and middle‐income countries. Considerable heterogeneity was observed among different income‐classified regions and countries.
Efficacy of Intravenous Mesenchymal Stem Cells for Motor Recovery After Ischemic Stroke: A Neuroimaging Study
Authors: Lee Jungsoo , Chang Won Hyuk , Chung Jong-Won , Kim Suk Jae , Kim Soo-Kyoung , Lee Jin Soo , Sohn Sung-Il , Kim Yun-Hee , Bang Oh Young , Kim Suk Jae , Cho Yeon Hee , Sung Ji Hee , Kim Eun Hee , Son Jeong Pyo , Kim Dong Hee , Choi Eun-Hyeok , Ryoo Sookyung , Kang Yoon Mi , Kim Yong Man , Kim Hyun Soo , Jang Jun Ho
Published: September 2021

Background and Purpose:

Stem cell–based therapy is a promising approach to repair brain damage after stroke. This study was conducted to investigate changes in neuroimaging measures using stem cell–based therapy in patients with ischemic stroke.

Methods:

In this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct were assigned to the autologous mesenchymal stem cell (MSC) treatment or control group. Of 54 patients who completed the intervention, 31 for the MSC and 13 for the control groups were included in this neuroimaging analysis. Motor function was assessed before the intervention and 90 days after randomization using the Fugl-Meyer assessment scale. Neuroimaging measures included fractional anisotropy values of the corticospinal tract and posterior limb of the internal capsule from diffusion tensor magnetic resonance imaging and strength of connectivity, efficiency, and density of the motor network from resting-state functional magnetic resonance imaging.

Results:

For motor function, the improvement ratio of the Fugl-Meyer assessment score was significantly higher in the MSC group compared with the control group. In neuroimaging, corticospinal tract and posterior limb of the internal capsule fractional anisotropy did not decrease in the MSC group but significantly decreased at 90 days after randomization in the control group. Interhemispheric connectivity and ipsilesional connectivity significantly increased in the MSC group. Change in interhemispheric connectivity showed a significant group difference.

Conclusions:

Stem cell–based therapy can protect corticospinal tract against degeneration and enhance positive changes in network reorganization to facilitate motor recovery after stroke.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01716481.
Musth and sexual selection in elephants: a review of signalling properties and potential fitness consequences
Authors: LaDue Chase A. , Schulte Bruce A. , Kiso Wendy K. , Freeman Elizabeth W.
Published: September 2021

Sexual selection mediated by multimodal signals is common among polygynous species, including seasonally breeding mammals. Indirect benefit models provide plausible explanations for how and why mate selection can occur in the absence of direct benefits. Musth — an asynchronous reproductive state in male elephants — facilitates both inter- and intrasexual selection via indirect benefits, and it is further communicated through a multimodal signal. In this review, we synthesise existing evidence that supports the hypothesis that musth is a multimodal signal subject to sexual selection and that male elephants increase their direct fitness by propagating this signal while females accrue indirect benefits. Musth is characterised by a suite of physiological and behavioural changes, serving to facilitate copulation between the sexes, and via multisensory modalities musth conveys honest information about the condition of a male. Female elephants mate preferentially with musth males, increasing their own fitness in the absence of direct benefits. In addition, musth resolves dynamic dominance hierarchies among male elephants and often eliminates the need for costly physical combat. Future work in this field should investigate potential postcopulatory selection mechanisms in elephants, including sperm competition and cryptic female choice. These topics join other fundamental questions related to sexual selection, signalling, and indirect benefits that are still unanswered in elephants.
Urban-nesting mountain chickadees have a reduced response to a simulated predator
Authors: Smith Blaire L. , Snell Cara L. , Reudink Matthew W. , Otter Ken A.
Published: September 2021

Anti-predator behaviour is common among birds, but little research exists on whether differences in the predator landscape between urban and rural habitats results in differential anti-predator behaviour. We compared nest-defence behaviour of mountain chickadees (Poecile gambeli) in urban and rural habitats in Kamloops, BC, Canada to a simulated predator model (snake) on top of nest boxes while incubating females were away from nests on foraging bouts. Upon their return, we recorded proximity to the predator model, latency to contact the nest box and enter the nest, and number of gargle and chick-a-dee calls as measures of anti-predator behaviour and compared multivariate “predator aversion scores” across birds occupying either rural or urban landscapes. Rural-nesting birds had more aversive reactions to the predator model than the urban-nesting birds, which may suggest differences in perceived threat of the model, in combination with increased boldness associated with urban-nesting birds.
On the applicability of eye movement desensitization and reprocessing (EMDR) as an intervention in dogs with fear and anxiety disorders after a traumatic event
Authors: Kapteijn C.M. , van der Borg J.A.M. , Vinke C.M. , Endenburg N.
Published: September 2021

Fear and anxiety disorders are prevalent in dogs. These disorders are not adequately resolved by current interventions, which urges exploration of additional interventions. In humans, fear and anxiety disorders such as post-traumatic stress disorder (PTSD), are effectively treated by Eye Movement Desensitization and Reprocessing (EMDR). EMDR is a non-invasive and non-pharmacological intervention involving bilateral sensory stimulation while memorizing the traumatic event, resulting in decreased emotionality of the memory. We argue EMDR might be applied as an intervention for fear and anxiety disorders in dogs, adding to the currently available interventions for the field of Clinical Ethology. Particularly nonverbal EMDR protocols used in preverbal children can be applied and the setup can be adapted for dogs. Future research should focus on the development of nonverbal EMDR protocols including proper controls, and on clinical effectiveness of such EMDR protocols for dogs. Apart from behavioural measures, psychophysiological variables should be incorporated as well.
The Role of Religious Experiences and Religious Institutions: Comparing Peter L. Berger’s and Hans Joas’ Approach to Religion
Authors: Deman Isaak
Published: September 2021

Hans Joas (born 1948) has repeatedly criticized Peter L. Berger (1929–2017) for placing religious experiences in the cognitive realm, where it runs the risk of being “contaminated” by secularization and pluralism. Instead, Joas has proposed to locate religious experiences in the “deeper layers” of the human person, where it is protected against mere cognitive reductionism and against contamination by secularization and pluralism. Despite his critique, Joas follows a similar path of Berger, as he explains the phenomenon of religion from an inductive point of view that originates in the experiential realm. This article demonstrates how Joas’ approach operates on a similar methodology like the one of Berger and ultimately results in similar theoretical conclusions despite their differing theoretical foundations. Moreover, this article illuminates an implicit methodological similarity between Joas and Berger that, on the one hand, differs from one of the taken-for-granted methodologies in the discipline of sociology (of religion), and, on the other hand, strongly influences the disposition of religious institutions in their definition of religion.
An Indigenous Jesus: Methodological and Theoretical Intersections in the Comparative Study of Religion
Authors: Joseph Simon J.
Published: September 2021

Indigeneity is a relational category that is predominantly, albeit not exclusively, applicable to Indigenous peoples. As a central theoretical site of discourse in Native Studies, indigeneity tends to be characterized by politicized relationships and provides powerful rhetorical strategies and counter-narratives. Facilitating decolonization as well as illuminating the structural and systemic relationships between the indigenous and the colonial, Indigenous theory recognizes the often complex inter-relationships attending the delineation of ethnic, social, and religious identity. The historical Black Elk, for example, illustrates how Lakota and Catholic religious identities co-exist in an ongoing site of discursive tension. This article argues that the historical figure of Jesus can be re-cognized as an indigenous Judean, complicating contemporary efforts in which the quest for the historical Jesus occurs in a predominantly Christian discursive context.
The Rents of the Dead: Growth and Entropy in African Cities
Authors: Brennan James R.
Published: September 2021

This article considers recent literature on contemporary urbanization in Africa that is united in its ‘post-normative’ orientation toward its subject, firmly discarding the ‘expectations’ of modernization that so deeply shaped twentieth-century research on African cities. Best typified by the work of urban anthropologists such as Abdoumaliq Simone, this scholarship instead focuses on the ‘vernacularization’ of urban structures and strategies in Africa. While such work has developed a host of new insights into the idiosyncratic nature of African urbanization, it has largely eschewed any comparative analysis of enduring economic strategies that lie at the heart of the massive growth of African cities. By focusing on the longer-term historical role of such processes – namely urban rents and urban price regulations – this article suggests that a more comparative framework can be generated for the study of urban Africa that still accounts for and partially explains the otherwise seemingly hyper-local and idiosyncratic forms of urban livelihoods and strategies. It also briefly reflects on notable trends in the five years since its original publication in 2013.
Space and Transformation: The Struggle for Architecture in Post Apartheid South Africa
Authors: Low Iain
Published: September 2021

The title and this essay, ‘Space and Transformation – the struggle for architecture in post-apartheid South Africa’ derive from the 2nd Annual Nelson Mandela Lecture delivered in Ghent in 2015. Its source as my topic is located in the intersection of three interrelated trajectories. The most obvious is the issue of my disciplinary grounding and the locus of intellectual thought, that of architecture and the complexity associated with the production of space, particularly under conditions of change. The other is the life work and philosophical teaching of this extraordinary man Nelson Rolihlahla Mandela and the third is the condition of the world, and South Africa in particular, as we experience it today at what appears to be this unique historic intersectional moment of globalization and expansive technological shift within our nations’ democratic emergence.

The essay draws on texts derived from other disciplines, such as literature and philosophy, particularly those that have relevance to conditions of the South, but resorts to the spatial disciplining associated with design. In so doing it reflects on architectural projects produced during the first decades of democratic rule. Most of these projects fall within the realm of human settlement, and have been selected in order to demonstrate transformation relative to the lived reality of ordinary South Africans, especially those marginalised and dispossessed by apartheid legislation. A semi structured longitudinal analysis has been conducted so as to reflect on the relations between the agency of design and the instrumentation of architecture as practice in determining spatial transformation.