bluuebunny/crossref_metadata_2025 huggingface dataset:
Human umbilical cord‐derived mesenchymal stem cells affect urea synthesis and the cell apoptosis of human induced hepatocytes by secreting IL‐6 in a serum‐free co‐culture system
Authors: Gu Ce , Du Wenjing , Chai Miaomiao , Jin Ziyang , Zhou Yi , Guo Pan , Zhou Yan , Tan Wen‐Song
Published: August 2021

Background

Bioartificial livers (BALs) are emerging as a potential supportive therapy for liver diseases. However, the maintenance of hepatocyte function and viability in vitro is a major challenge. Mesenchymal stem cells (MSCs) have attracted extensive attention for providing trophic support to hepatocytes, but only few studies have explored the interaction between human MSCs and human hepatocytes, and very little is known about the underlying molecular mechanisms whereby MSCs affect hepatocyte function, especially in serum‐free medium (SFM).

Method and Results

This study aims to explore the effects of human umbilical cord‐derived MSCs (hUMSCs) on human‐induced hepatocytes (hiHeps) function and viability, and know about the underlying molecular mechanism of interaction in SFM. The liver‐specific function of hiHeps was evaluated by analysis of albumin secretion, urea synthesis, and metabolic enzyme activity. hiHeps apoptosis was mainly characterized by live/dead staining assay, JC‐1 mitochondrial membrane potential assay, reactive oxygen species (ROS) generation, and cell apoptosis detection. The expression of related genes and proteins were measured by qRT‐PCR and western blotting. The results indicate that co‐culture with hUMSCs improved hiHep urea synthesis and reduced cell apoptosis compared to monoculture in SFM, and this effect was found to be mediated by secreted interleukin‐6 (IL‐6). Further, studies revealed that IL‐6 reduced hiHep apoptosis via the activation of the JAK‐Stat3‐Ref‐1 and JAK‐Stat3‐Bcl‐2/Bax‐Caspase3 pathways by binding to the IL‐6 receptor. IL‐6 also enhanced hiHep urea synthesis through the JAK‐Akt‐P53‐ARG1 pathway. Finally, hiHep‐specific functions were further prolonged and increased when co‐cultured with hUMSCs on 3D polyethylene terephthalate (PET) fibrous scaffolds.

Conclusion

The SFM co‐culture strategy showed major advantages in maintaining hiHep function and viability in vitro, which is of great significance for the clinical application of hiHeps in BALs.
Highly Conductive Tellurium and Telluride in Energy Storage
Authors: Han Manshu , Zhou Zhihao , Li Yu , Chen Qingguo , Chen Minghua
Published: August 2021

Enhancing energy/power density of electrochemical energy storage devices is a hot topic in the present‐day science community. The electrochemical performance of these devices is strongly bound by the fundamental nature of the electrodes in terms of reaction mechanism, crystal structure, electrons/ions transfer kinetics and so on. These features are also the main challenge for the previously investigated electrodes (e. g. carbon, metal oxides/sulfides). Recently, tellurium and telluride‐based materials have aroused increasing interest in the energy storage field due to their high electronic conductivity, conducive crystal structure, and superior volumetric capacity. To provide a better understanding of the fundamental properties and energy storage performance of tellurium and telluride‐based materials, we first introduced the various physical‐chemical properties of telluride‐based materials. Then, we summarize the latest research advances in the field of energy storage with these materials, including essential physical‐chemical properties, synthetic methods, design strategies, and electrochemical performances. The future perspectives and challenges of tellurides aiming for practical application are discussed at last.
Supported Vanadium Oxide as a Photocatalyst in the Liquid Phase: Dissolution Studies and Selective Laser Excitation
Authors: Kortewille Bianca , Pfingsten Oliver , Bacher Gerd , Strunk Jennifer
Published: August 2021

Supported vanadium oxide species are tested for their capability to perform photocatalytic methyl orange degradation in the aqueous phase. Excitation is performed with a frequency‐tripled (λ=270 nm) or frequency‐doubled (λ=405 nm) Ti:sapphire laser in a newly designed 15 ml photoreactor. Photocatalytic activity in dye degradation is only observed at 270 nm excitation, indicating that larger vanadium oxide structures (V2O5 nanoparticles, decavanadates) are either not present in sufficient quantities, or not active in the reaction. Reference experiments exclude pure photodegradation of the dye. It is found that a major part of the supported vanadium oxide species becomes detached from the silica support, and a very small fraction detaches from alumina. Considerations of the aqueous phase chemistry of dissolved vanadate ions allow to identify the formed dissolved species to be predominantly H2VO4− ions. These doubly protonated monovanadates are the main active species in the photocatalytic reaction, together with small anchored species on alumina.
Reducing Antisolvent Use in the STRAP Process by Enabling a Temperature‐Controlled Polymer Dissolution and Precipitation for the Recycling of Multilayer Plastic Films
Authors: Sánchez‐Rivera Kevin L. , Zhou Panzheng , Kim Min Soo , González Chávez Leonardo D. , Grey Steve , Nelson Kevin , Wang Shao‐Chun , Hermans Ive , Zavala Victor M. , Van Lehn Reid C. , Huber G. W.
Published: August 2021

The recently reported processing strategy called solvent‐targeted recovery and precipitation (STRAP) enables deconstruction of multilayer plastic packaging films into their constituent resins by selective dissolution. It uses a series of solvent washes that are guided by thermodynamic calculations of polymer solubility. In this work, the use of antisolvents in the STRAP process was reduced and solvent mixtures were considered to enable the temperature‐controlled dissolution and precipitation of the target polymers in multilayer films. This was considered as a means to further improve the STRAP process and its estimated costs. Two STRAP approaches were compared based on different polymer precipitation techniques: precipitation by the addition of an antisolvent (STRAP‐A) and precipitation by decreasing the solvent temperature (STRAP‐B). Both approaches were able to separate the constituent polymers in a post‐industrial film composed primarily of polyethylene (PE), ethylene vinyl alcohol (EVOH), and polyethylene terephthalate (PET) with near 100 % material efficiency. Technoeconomic analysis indicates that the minimum selling price (MSP) of the recycled resins with STRAP‐B is 21.0 % lower than that achieved with STRAP‐A. This provides evidence that thermally driven polymer precipitation is an option to reduce the use of antisolvents, making the STRAP process more economically and environmentally attractive. A third process, STRAP‐C, was demonstrated with another post‐industrial multilayer film of a different composition. The results demonstrate that this process can also recover polymers at similar costs to those of virgin resins, indicating that the STRAP technology is flexible and can remain economically competitive as the plastic feed complexity is increased.
Detection of Treponema pallidum by immunocytochemistry of cervical smear: A case report
Authors: Noguchi Hiroshi , Tokumitsu Takako , Kuroki Eiteru , Minematsu Eiko , Asada Yujiro , Kuroda Sayaka , Ochiai Shoko , Kikuchi Masao , Fujimoto Shouichi , Onishi Junji , Kawagoe Yasuyuki , Sameshima Hiroshi , Katsuragi Shinji , Sato Yuichiro
Published: August 2021

Syphilis is an infectious disease caused by Treponema pallidum (T. pallidum). A cervical smear is useful when screening for sexually transmitted diseases; however, T. pallidum is not detected in the usual Papanicolaou smear. We report the detection of T. pallidum by immunocytological examination of a cervical smear. A 22‐year‐old woman presented with nephrotic syndrome. On admission, we performed screening tests for infections, and her serology was positive for syphilis. A Papanicolaou cervical smear (Thin‐Prep) showed slight nuclear enlargement, nuclear irregularity, and mild hyperchromasia in the superficial cells, but no organism was detected. T. pallidum was detected in the remaining specimen using immunocytochemistry. We also detected the T. pallidum DNA in a cervical biopsy specimen by polymerase chain reaction (PCR). Our findings suggest that immunocytological examination and PCR assay examination are useful tests for syphilis diagnosis.
In vitro and in vivo metabolism of the anabolic‐androgenic steroid oxandrolone in the horse
Authors: Harding Caitlin , Viljanto Marjaana , Cutler Charlotte , Habershon‐Butcher Jocelyn , Biddle Simon , Scarth James
Published: August 2021

Oxandrolone is an anabolic‐androgenic steroid with favourable anabolic to androgenic ratio, making it an effective anabolic agent with less androgenic side effects. Although its metabolism has been studied in humans, its phase I and II metabolism has not been previously reported in the horse. The purpose of this study was to investigate the in vitro metabolism of oxandrolone (using both equine liver microsomes and S9) and in vivo metabolism following oral administration (three daily doses of 50 mg of oxandrolone to a single Thoroughbred horse), using both gas and liquid chromatography‐mass spectrometry techniques. The in vitro phase I transformations observed included 16‐hydroxylated (two epimers), 17‐methyl‐hydroxylated and 16‐keto metabolites. In addition to parent oxandrolone and these hydroxylated metabolites, the 17‐epimer and a 17,17‐dimethyl‐18‐norandrost‐13‐ene analogue were detected in biological samples following the administration. 16‐keto‐oxandrolone was only observed in urine. The 16‐ and 17‐methyl‐hydroxylated oxandrolone metabolites were predominantly excreted as sulfate conjugates in urine, whereas parent oxandrolone, its epimer and 17,17‐dimethyl‐18‐norandrost‐13‐ene derivative were found predominantly in the unconjugated urine fraction. The most abundant analyte detected in both plasma and urine was parent oxandrolone. However, the longest detection period using the developed analytical method was provided by 17‐hydroxymethyl‐oxandrolone in both matrices. The results of this study provided knowledge of how best to detect the use of oxandrolone in regulatory samples.
Three‐dimensional analysis of mesonephric tubules remodeling into efferent tubules in the male mouse embryo
Authors: Omotehara Takuya , Nakata Hiroki , Itoh Masahiro
Published: August 2021

Background

Spermatozoa are transported to the epididymal duct through efferent tubules. Although the origin of the efferent tubules is thought to be mesonephric tubules (MTs), their detailed developmental process, for example, where the rete testis and efferent tubules are connected, is unclear. We investigated the structural changes of the MTs in the male mouse embryo using a three‐dimensional reconstruction method.

Results

Three to six MTs were connected to the Wolffian duct, and some of them branched, resulting in five to nine tips. Rete cells contacted the three to six tips. The MTs showed a folded shape when the gonadal fate was determined. After the testis development started, they became short and straight but emerged as long and twisting by birth. Before birth, the efferent duct was composed of MTs and a cranial portion of the folded Wolffian duct.

Conclusions

The contact between the rete testis and efferent tubules is possibly established at the tip of each MT. The MTs regress after gonadal fate is determined but is remodeled to the twisting efferent tubules by birth. The efferent tubules are composed of the MTs but also a cranial portion of the folded Wolffian duct in the mouse.
Torii‐Type Electrosynthesis of α,β‐Unsaturated Esters from Furfurylated Ethylene Glycols and Amino Alcohols
Authors: Darzina Madara , Lielpetere Anna , Jirgensons Aigars
Published: August 2021

Electrosynthesis of unsaturated esters from furan derivatives, reported by Torii et al. in 1976, is an attractive method for the valorization of furanoic platform chemicals. Nevertheless, it has received practically no attention, presumably due to specific reaction conditions including the use of expensive Pt electrodes. With the aim of expanding the application of Torii‐type ester electrosynthesis, we explored the electrochemical transformation of O‐furfuryl ethylene glycols and N‐furfuryl amino alcohols to esters 5. These can be obtained in two consecutive electrochemical steps: bis‐alkoxylation of the furan derived substrates 3 to give spirocycles 4, followed by ring‐opening involving oxidative fragmentation of the C−C bond. Both steps can be carried out at ambient conditions, using inexpensive graphite electrodes; however, each step required a different supporting electrolyte and acidic additive to achieve good yields of the product. Additionally, conditions were found for efficient one‐pot transformation of N‐furfuryl amino alcohols to esters 5 while O‐furfuryl ethylene glycols under the same conditions gave esters 5 in moderate yields.
Greenhouse and field experiments revealed that clove oil can effectively reduce bacterial blight and increase yield in pomegranate
Authors: Kumar Pavan , Lokesh Veeresh , Doddaraju Pushpa , Kumari Aprajita , Singh Pooja , Meti Bharati S. , Sharma Jyotsana , Gupta Kapuganti Jagadis , Manjunatha Girigowda
Published: August 2021

Bacterial blight in pomegranate is a devastating disease caused by bacterial pathogen Xanthomonas axonopodis pv. punicae (XAP), recording huge damage to pomegranate crop worldwide. Antibiotics and copper‐based chemicals are being used for the management of this blight, while in this present work, we investigated the effect of eugenol and clove oil either singly or in combination with copper oxychloride (COC) on the induction of plant defense responses and concomitant prevention of bacterial blight. Our results provided evidence that clove oil (0.2%–1%) and eugenol (0.1% and 0.2%) successfully inhibit the growth of XAP in paper disk diffusion assay. Strikingly under the greenhouse condition, clove oil (0.2%) as foliar application 24 h before XAP inoculation recorded the lowest disease severity of 7.34%, whereas eugenol (0.2%) recorded maximum disease severity of 14.56%. However, the combination of clove oil (0.2%) and copper oxychloride (0.3%) recorded the least disease severity of 2.38%. A similar trend was observed in field conditions. Prophylactic application of clove oil leads to enhanced nitrate reductase activity and nitric oxide production which was further enhanced in clove oil pre‐treated plants challenged with XAP. Strikingly, the total ROS and H2O2 levels were reduced in response to clove oil application. Clove oil also induced the systemic response by inducing expression levels of defense genes. The reduction of disease severity by clove oil and COC combination also reflected on total yield recording via large‐scale field experiments where maximum yield of 14.04 tonnes/acre was observed, whereas streptocycline application recorded 11.12 tonnes/acre. Application of COC and clove oil resulted in a high remunerative value of ₹ 1:5.6, compared to streptocycline (1:4.85) and control (1:1.85). The present study revealed that clove oil as a plant derivative and eugenol as a synthetic option can be effectively used for the successful management of bacterial blight in pomegranate.
Merging Scientific Silos: Integrating Specialized Approaches for Thinking about and Using Spatial Data That Can Provide New Directions for Persistent Fisheries Problems
Authors: Mather Martha E , Smith Joseph M , Boles Kayla M , Taylor Ryland B , Kennedy Cristina G , Hitchman Sean M , Rogosch Jane S , Frank Holly J
Published: August 2021

By merging our specialization silos, fisheries professionals can expand the options that are available to them to address difficult fisheries and aquatic conservation problems, which require an understanding of spatial patterns in geographically large systems. Our purpose is to start a profession-wide conversation about additional ways to think about and use spatial data. We use case studies to illustrate how identifying and merging multiple specialized approaches (e.g., fish tracking, fish surveys, geomorphology, social science, jurisdictional viewpoints) can create an ensemble that has advantages over the use of any single approach alone. Thus, our perspective is not about solving a specific technical problem with a new tool, but about the benefits of identifying gaps in data from one specialized approach, and filling those gaps with data from other specialized approaches. If multiple approaches are coordinated through a larger, problem-specific planning strategy, the result can be better outcomes for difficult problems through creative integration. We encourage others to add constructive ideas to the views initiated here.
The role of education and income for cognitive functioning in old age: A cross‐country comparison
Authors: Rodriguez Francisca S. , Hofbauer Lena M. , Röhr Susanne
Published: August 2021

Objectives

Previous studies have shown that higher education promotes cognitive health. This effect, however, is embedded in the living conditions of a particular country. Since it is not clear to what extent the country and its specific living standards are necessary preconditions for the observed effect, we investigated whether the impact of education and income on cognitive functioning differs between countries.

Methods

Analyses were based on harmonized data from the World Health Organization's multi‐country Study on global AGEing and adult health, the Health and Retirement Study, and the Survey of Health, Ageing and Retirement in Europe of over 85,000 individuals aged 50 years and older. Analyses were conducted via multivariate regression analyses and structural equation modeling adjusted for age, gender, marital status, health status, and depression.

Results

The effect of education was twice as large as the effect of income on cognitive functioning and indirectly moderated the effect of income on cognitive functioning. The effect sizes varied strongly between countries. The country's gross domestic product per capita seems to influence cognitive functioning.

Conclusions

Our findings indicate that education has a dominant effect on cognitive functioning in people aged 50 years and older, which might even offset the adverse implications of living with low income on cognitive health. Therefore, expanding efforts to achieve universal education are essential to mitigate health disparities due to low income and early life disadvantages, including chances for good cognitive functioning over the life‐span.
Influences of local hydroclimatology and teleconnections on Florida's precipitation and temperature variability
Authors: Sharma Priyank J. , Teegavarapu Ramesh S. V.
Published: August 2021

Understanding the influences of local hydroclimatology and two large‐scale oceanic‐atmospheric oscillations (i.e., Atlantic Multidecadal Oscillation (AMO) and El Niño‐Southern Oscillation (ENSO)) on seasonal precipitation (P) and temperature (T) relationships for a tropical region (i.e., Florida) is the focus of this study. The warm and cool phases of AMO and ENSO are initially identified using sea surface temperatures (SSTs). The associations of SSTs and regional minimum, maximum and average surface air temperatures (SATs) with precipitation are then evaluated. The seasonal variations in P‐SATs and P‐SSTs associations considering AMO and ENSO phases for sites in (1) two soil temperature regimes (i.e., thermic and hyperthermic); (2) urban and non‐urban regions; and (3) regions with and without water bodies, are analysed using two monthly datasets. The analyses are carried out using trend tests, two association measures, nonparametric and parametric statistical hypothesis tests and kernel density estimates. Decreasing (increasing) trend in precipitation (SATs) is noted in the recent multi‐decadal period (1985–2019) compared to the previous one (1950–1984) indicating a progression towards warmer and drier climatic conditions across Florida. Spatially and temporally non‐uniform variations in the associations of precipitation with SATs and SSTs are noted. Strong positive (weak negative) P–T associations are noted during the wet (dry) season for both AMO phases and El Niño, while significant (positive) P–T associations are observed across southern Florida during La Niña in the dry season. The seasonal influences are predominant in governing the P–T relationship over the regions with and without water bodies; however, considerable variations between El Niño and La Niña are noted during the dry season. The climate variability influences on P–T correlations for hyperthermic and thermic soil zones are found to be insignificant (significant) during the wet (dry) season. Nonparametric clustering is performed to identify the spatial clusters exhibiting homogeneous P–T relationships considering seasonal and climate variability influences.
NICU music therapy effects on maternal mental health and preterm infant's emotional arousal
Authors: Palazzi Ambra , Meschini Rita , Piccinini Cesar Augusto
Published: August 2021

In recent decades, music therapy in the Neonatal Intensive Care Unit (NICU) has been shown to regulate preterm infant's physiological responses and improve maternal mental health. This study investigated the effects of the music therapy intervention for the mother–preterm infant dyad (MUSIP) for maternal anxiety, postnatal depression, and stress, and preterm infants’ weight gain, length of hospitalization, heart rate (HR), and oxygen saturation (So2). A pre‐experimental design was used with 33 mother–preterm infant dyads in a Brazilian NICU: 16 dyads in the Music Therapy Group (MTG) and 17 dyads in the Control Group (CG). The MTG took part in the MUSIP, aimed at supporting maternal singing with the preterm baby. Infants’ HR and So2 were recorded at each minute from 10 min before to 10 min after sessions 1, 3, and 6. Before infants’ discharge, maternal anxiety and depression scores were lower in the MTG compared to the CG. Anxiety, depression, and stress levels decreased significantly after the intervention in the MTG. With regard to infants, HR and So2 ranges were higher during music therapy, compared to before and after sessions. MUSIP improved maternal mental health and affected preterm infants’ emotional arousal, with positive trends in decreasing HR, stabilizing So2, and reducing length of hospitalization.
Depression‐related emotional problems mediate the relation between hopelessness and suicidal ideation severity
Authors: López Roberto , Follet Lia , Defayette Annamarie B. , Whitmyre Emma D. , Wolff Jennifer , Spirito Anthony , Esposito‐Smythers Christianne
Published: August 2021

Objective

Cross‐sectional research with adult samples suggests that hopelessness may indirectly affect suicidal ideation (SI) through overall depressive symptom severity. However, particular depressive symptom constellations, rather than overall symptoms, may underlie the association between hopelessness and SI. Yet, the cross‐sectional nature of these studies precludes examination of the temporal associations among these constructs.

Methods

Using path analysis, the present study examined whether depression‐related emotional problems mediate the relation between hopelessness and SI in a clinical sample of 110 adolescents over a 6‐month period. The specificity of depression‐related emotional problems as a mediator was also evaluated.

Results

After accounting for covariates, results supported the specificity of 3‐month depression‐related emotional problems as a mediator of the association between baseline levels of hopelessness and 6‐month SI.

Conclusion

Results suggest that treatment targeted specifically at hopelessness may help reduce depression‐related emotional problems and lower SI, and ultimately, adolescent suicide risk.
Mental health and discrimination among migrants from Africa: An Italian cross‐sectional study
Authors: Voglino Gianluca , Gualano Maria Rosaria , Lo Moro Giuseppina , Forghieri Pietro , Caprioli Marco , Elhadidy Heba Safwat Mhmoued Abdo , Bert Fabrizio , Siliquini Roberta
Published: August 2021

This study aimed to assess depression, anxiety, posttraumatic stress disorder (PTSD) and discrimination in African migrants and investigate determinants. A cross‐sectional study was conducted in Italy (July 2019–February 2020). Inclusion criteria: being a citizen of an African country or having parents who are citizens of an African country. Questionnaires included tests for depression, anxiety, PTSD, discrimination. Multivariable regressions were performed. Participants were 293. The prevalence of depression, anxiety, and PTSD was: 12.1%, 12.1%, and 24.4%. Only 7.2% declared not to be discriminated. Among significantly associated factors, waiting for/being in possession of temporary permits and discrimination were associated with all mental outcomes. Being (or having parents from) Sub‐Saharan Africa increased the likelihood of discrimination. A relevant prevalence of mental illnesses was reported. Particularly, Sub‐Saharan Africans potentially offer a unique point of view. Migrants' mental health should be a priority for national and international programs of health monitoring.
Connection between interannual variation of spring precipitation in Northeast China and preceding winter sea ice over the Barents Sea
Authors: Zhang Shiyue , Zeng Gang , Yang Xiaoye , Iyakaremye Vedaste , Hao Zhixin
Published: August 2021

This study discusses the interannual variation of spring precipitation in Northeast China (NECSP) from 1980 to 2016 and its relationship with Arctic sea ice based on observation data and numerical experiments. The observed results reveal that the leading mode of NECSP mainly exhibits a homogenous pattern with a significant interannual variation. The NECSP has a significant negative correlation with the preceding winter Barents Sea ice concentration (BSIC) at the interannual scale. In the preceding winter, the decreased BSIC resulted in positive geopotential height anomalies over the polar region, which could weaken the polar vortex and westerly winds, forming a cyclonic anomaly indirectly over West Siberia. The circulation anomalies resulted in a zonal dipole pattern of preceding winter snow water equivalent (SWE) anomalies in the mid‐high latitudes of Eurasia with less SWE over Eastern Europe and more SWE over West Siberia. The SWE anomalies in winter could persist to the subsequent spring and facilitate more precipitation over Northeast China (NEC) by local thermal processes affecting circulation anomalies over Eurasia. On the other hand, the negative preceding winter BSIC anomalies can persist to spring, increasing the NECSP by strengthening the cyclonic anomalies over NEC. In this study, the response of the atmosphere to the thermal effect of SWE is further verified by using the linear baroclinic model (LBM). The response of NECSP to BSIC loss is tested by using the Community Atmosphere Model version 5.3 (CAM5.3).
A comparison of different approaches for the definition of seasons in the Mediterranean region
Authors: Kotsias George , Lolis Christos J. , Hatzianastassiou Nikolaos , Lionello Piero , Bartzokas Aristides
Published: August 2021

Α new method, based on the definition of weather types (WTs), for the determination of seasons in the Mediterranean region is adopted. This method combines principal component analysis and k‐means Cluster Analysis on daily grid point meteorological data for the 70‐year period 1949–2018 obtained from the NCEP/NCAR database. At first, the method is applied to the classification of WTs and subsequently to the definition of seasons based on the mean intra‐annual variations of the WTs' frequency. The resulting seasons are compared to a previous method of the seasons' definition, based on the long‐term mean intra‐annual variations of climatological parameters. Furthermore, a synthesis of the two methods is proposed. The analysis is applied not only to the 70‐year period 1949–2018, but also to the five overlapping 30‐year sub‐periods 1949–1978, 1959–1988, 1969–1998, 1979–2008, 1989–2018 in order to investigate possible long‐term changes of the seasons' characteristics. Four seasons are identified for all periods and for both methodological approaches. These seasons broadly correspond to the four conventional ones, but they differ in their onset and cessation dates as well as their duration. For the composite method, it is found that winter lasts about 4 months, summer is a little longer than 3 months and spring and autumn last around 2.5 months. The most remarkable findings regarding the seasons' characteristics are: (a) the start/end dates and duration of winter are almost identical in all three approaches, while summers' characteristics differ; (b) shortening of winter and spring in recent periods, associated with the delayed start and expedited end dates, respectively; and (c) the prolongation of autumn and summer, due to the delay of its end date, and the earlier onset and delayed end dates, respectively.
Does central nervous system dysfunction underlie patellofemoral pain in young females? Examining brain functional connectivity in association with patient‐reported outcomes
Authors: Diekfuss Jed A. , Grooms Dustin R. , Nissen Katharine S. , Coghill Robert C. , Bonnette Scott , Barber Foss Kim D. , Dudley Jonathan A. , Berz Kate , Logan Kelsey , Gubanich Paul , Saltman Anna J. , Slutsky‐Ganesh Alexis B. , Hansen Emma , Leach James , Yuan Weihong , Myer Gregory D.
Published: August 2021

Patellofemoral pain (PFP) is defined as retro‐ or peri‐patellar knee pain without a clear structural abnormality. Unfortunately, many current treatment approaches fail to provide long‐term pain relief, potentially due to an incomplete understanding of pain‐disrupted sensorimotor dysfunction within the central nervous system. The purposes of this study were to evaluate brain functional connectivity in participants with and without PFP, and to determine the relationship between altered brain functional connectivity in association with patient‐reported outcomes. Young female patients with PFP (n = 15; 14.3 ± 3.2 years) completed resting‐state functional magnetic resonance imaging (rs‐fMRI) and patient‐reported outcome measures. Each patient with PFP was matched with two controls (n = 30, 15.5 ± 1.4 years) who also completed identical rs‐fMRI testing. Six bilateral seeds important for pain and sensorimotor control were created, and seed‐to‐voxel analyses were conducted to compare functional connectivity between the two groups, as well as to determine the relationship between connectivity alterations and patient‐reported outcomes. Relative to controls, patients with PFP exhibited altered functional connectivity between regions important for pain, psychological functioning, and sensorimotor control, and the connectivity alterations were related to perceived disability, dysfunction, and kinesiophobia. The present results support emergent evidence that PFP is not localized to structural knee dysfunction, but may actually be resultant to altered central neural processes. Clinical significance: These data provide potential neuro‐therapeutic targets for novel therapies aimed to reorganize neural processes, improve neuromuscular function, and restore an active pain‐free lifestyle in young females with PFP.
Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1‐13C]pyruvate magnetic resonance spectroscopy
Authors: Tougaard Rasmus Stilling , Laustsen Christoffer , Lassen Thomas Ravn , Qi Haiyun , Lindhardt Jakob Lykke , Schroeder Marie , Jespersen Nichlas Riise , Hansen Esben Søvsø Szocska , Ringgaard Steffen , Bøtker Hans Erik , Kim Won Yong , Stødkilde‐Jørgensen Hans , Wiggers Henrik
Published: August 2021

Purpose

Hyperpolarized [1‐13C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1‐13C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long‐term left ventricular effects of heart failure medication, and could identify responders to treatment.

Methods

Thirty‐five rats were scanned with hyperpolarized [1‐13C]pyruvate MRS 3 days after MI or sham surgery. The animals were re‐examined after 30 days of therapy with β‐blockers and ACE‐inhibitors (active group, n = 12), placebo treatment (placebo group, n = 13) or no treatment (sham group, n = 10). Furthermore, heart tissue mitochondrial respiratory capacity was assessed by high‐resolution respirometry. Metabolic results were compared between groups, over time and correlated to functional MR data at each time point.

Results

At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P < .001). Cardiac metabolism, measured by both hyperpolarized [1‐13C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow‐up. Three days post MI, low bicarbonate + CO2/pyruvate ratio was associated with low LVEF. At follow‐up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO2/pyruvate ratio, as measured by hyperpolarized MRS.

Conclusion

In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1‐13C]pyruvate flux as measured by MRS; however, responders to heart failure medication had reduced capacity for carbohydrate metabolism.
Toward proteome‐wide exploration of proteins in dried blood spots using liquid chromatography‐coupled mass spectrometry
Authors: Nakajima Daisuke , Ohara Osamu , Kawashima Yusuke
Published: August 2021

Dried blood spot (DBS) sampling is a method with advantages over conventional blood sampling in relation to collection, cost, storage, and transportation. Such advantages have led to its wide use in newborn screening (NBS). Although target analysis of various biomolecules is conducted in NBS, protein quantification‐based NBS is still in its infancy. Thus, it is important to clarify how many proteins could be quantitatively detected in DBS samples using advanced liquid chromatography–mass spectrometry (LC–MS/MS) technologies; a catalogue of proteins detectable in DBSs by LC–MS/MS will enable us to judge which causative proteins in genetic diseases can be monitored at the protein level in NBS. In this review, we outline conventional proteome analyses of DBSs with a distinction between target and nontarget approaches. Additionally, we discuss the future perspectives for proteome analysis of DBSs in NBS of genetic diseases.
Understanding care needs of cancer patients with depressive symptoms: The importance of patients' recognition of depressive symptoms
Authors: Bickel Esmée A. , Auener Anouk M. , Ranchor Adelita V. , Fleer Joke , Schroevers Maya J.
Published: August 2021

Objective

The majority of cancer patients with depressive symptoms does not perceive a need for psychological care. Reasons for this are still unclear. We examined the mediating role of cancer patients' perceptions of depressive symptoms in the relationship between depressive symptoms and perceived need for psychological care.

Methods

For this cross‐sectional study, we recruited 127 Dutch cancer patients with moderate to severe levels of depressive symptoms (Patient Health Questionnaire [PHQ]‐9≥10) who did not receive professional psychological care. Depressive symptoms were measured with the PHQ‐9 questionnaire, by using three different depression score operationalizations. We used mediation analyses to test the mediating role of patients' illness perceptions (measured with subscales of the Brief Illness Perception Questionnaire) in the relation between depressive symptoms and need for care.

Results

Whilst results did not show significant direct associations between depressive symptoms and perceived need for psychological care, we found positive indirect effects of severity (B = 0.07, SE = 0.04, p < 0.02), meeting the DSM‐5 diagnosis (B = 0.45, SE = 0.26, p < 0.02) and having relatively more affective symptoms (B = 2.37, SE = 1.10, p < 0.02) on need for care through the identity perception.

Conclusions

Including assessments of patients' recognition of depressive symptoms and their perceptions of depression treatment efficacy might improve depression screening in cancer patients by more accurately identifying those with a need for psychological care. Moreover, improving patients' knowledge and recognition of symptoms as being depressive symptoms might be a possible target point in increasing care needs and hereby optimizing the uptake of psychological care in cancer patients with depressive symptoms.
Association of time of first corticosteroid treatment with bronchopulmonary dysplasia in preterm infants
Authors: Cuna Alain , Lagatta Joanne M. , Savani Rashmin C. , Vyas‐Read Shilpa , Engle William A. , Rose Rebecca S. , DiGeronimo Robert , Logan J. Wells , Mikhael Michel , Natarajan Girija , Truog William E. , Kielt Matthew , Murthy Karna , Zaniletti Isabella , Lewis Tamorah R. ,   Children's Hospitals Neonatal Consortium (CHNC) Severe BPD Focus Group
Published: August 2021

Objective

To evaluate the association between the time of first systemic corticosteroid initiation and bronchopulmonary dysplasia (BPD) in preterm infants.

Study design

A multi‐center retrospective cohort study from January 2010 to December 2016 using the Children's Hospitals Neonatal Database and Pediatric Health Information System database was conducted. The study population included preterm infants <32 weeks' gestation treated with systemic corticosteroids after 7 days of age and before 34 weeks' postmenstrual age. Stepwise multivariable logistic regression was used to assess the association between timing of corticosteroid initiation and the development of Grade 2 or 3 BPD as defined by the 2019 Neonatal Research Network criteria.

Results

We identified 598 corticosteroid‐treated infants (median gestational age 25 weeks, median birth weight 760 g). Of these, 47% (280 of 598) were first treated at 8–21 days, 25% (148 of 598) were first treated at 22–35 days, 14% (86 of 598) were first treated at 36–49 days, and 14% (84 of 598) were first treated at >50 days. Infants first treated at 36‐49 days (aOR 2.0, 95% CI 1.1–3.7) and >50 days (aOR 1.9, 95% CI 1.04–3.3) had higher independent odds of developing Grade 2 or 3 BPD when compared to infants treated at 8–21 days after adjusting for birth characteristics, admission characteristics, center, and co‐morbidities.

Conclusions

Among preterm infants treated with systemic corticosteroids in routine clinical practice, later initiation of treatment was associated with a higher likelihood to develop Grade 2 or 3 BPD when compared to earlier treatment.
Empty Valence‐Band Pocket in p‐Type Cu2O(111) Probed with Scanning Tunneling Spectroscopy
Authors: Gloystein Alexander , Nilius Niklas
Published: August 2021

Scanning tunneling spectroscopy is used to probe the surface electronic structure of (√3×√3)‐reconstructed cuprous oxide films on Au(111). In analogy to bulk Cu2O(111), the films show a pronounced p‐type nature with the valence‐band top pinned to the Fermi level and the conduction‐band onset located at +2.0 V. A conductance dip appears directly at zero bias in the dI/dV spectra, followed by an asymmetric dI/dV maximum inside the lower half of the bandgap. Several scenarios are considered to explain this unusual conductance behavior. The most likely interpretation is based on the accumulation of hole states in the p‐type material in response to the tip‐electric field and the development of an empty valence‐band pocket directly below the tip. Tunneling into these states leads to a finite dI/dV intensity even inside the Cu2O bandgap. A 1D tunneling model that accounts for this field‐dependent transport mechanism successfully reproduces the experimental data and rationalizes the impact of current setpoint, oxide thickness, and surface reconstruction on the observed spectral response.
Effectiveness of Pistacia atlantica on older adult knee osteoarthritis, a randomized triple blind clinical trial
Authors: Khamevar Ali , Ebrahimzadeh Mohammad Ali , Moosazadeh Mahmood , Shayesteh Azar Masoud , Saeedi Majid , Bakhtiary Far Adel , Yousefi Seyde Sedighe
Published: August 2021

Osteoarthritis is the most common cause of disability and aging is the major risk factor. One of the low‐risk herbal medicines for reducing pain and inflammation in persian medicine is Pistacia atlantica gum. A triple‐blind placebo‐controlled clinical trial was performed in order to evaluate the efficacy of P. atlantica gum ointment on knee osteoarthritis in elderly people. A total of 60 patients were randomly allocated to two groups. The intervention group used 4% P. atlantica ointment and the control group used placebo, topically applied three times a day, for 8 weeks. The patients were evaluated before and after the intervention using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale. There were significant differences (p < .001) between two the groups in terms of joint stiffness and pain as well as function. Within groups, regarding the effect size (EF) in joint stiffness was 2.82 and 0.74 in the Pistacia and placebo groups, respectively. Regarding pain, the effect size of the intervention and placebo groups were 3.90 and 0.99, respectively. In addition, regarding function, the effect size of the intervention and the placebo groups were 4.33 and 1.17, respectively. Therefore, it seems that topical P. atlantica is significantly better than the placebo in the old patients with knee osteoarthritis.
Synergistic effect of combined treatment with baicalin and emodin on DSS‐induced colitis in mouse
Authors: Xu Bo , Huang Shaowei , Chen Yanping , Wang Qing , Luo Shuang , Li Yanyang , Wang Xiaojing , Chen Jinyan , Luo Xia , Zhou Lian
Published: August 2021

The treatment of combination drugs in complex diseases has been spotlighted. Ulcerative colitis (UC) is a chronic inflammatory disease that has made progress in combination therapy. Baicalin, a flavone from Scutellaria baicalensis Georgi. (Lamiaceae), and emodin, an anthraquinone derivative from Rhei Radix et Rhizoma. (Polygonaceae), both have been reported to possess antiinflammatory activities. Our study investigated whether combined treatment with baicalin and emodin had a synergistic effect in inhibiting colitis inflammation. The results showed that baicalin combined with emodin at a lower dose had the same effect as the two drugs alone significantly alleviated the symptoms of dextran sulfate sodium (DSS)‐induced colitis mice, involving the prevention of the loss of body weight and colon shortening, the decrease in the disease activity index (DAI), and intestinal damages. The combined treatment decreased the expression of CD14/TLR4/NF‐κB pathway proteins and increased the expression of PPAR‐γ protein in the colon of colitis mice. Further study in vitro has shown that baicalin decreased the expression of CD14, whereas emodin increased the expression of PPAR‐γ, both of which inhibited the activity of NF‐κB and exerted antiinflammatory effects. Furthermore, compared to the treatment using the two drugs individually, baicalin combined with emodin had more significant effects on the expression of CD14 and PPAR‐γ. Therefore, emodin combined with baicalin had a synergistic effect on DSS‐induced colitis.
IL‐21 regulates macrophage activation in human monocytic THP‐1‐derived macrophages
Authors: Jian Leilei , Li Changhong , Sun Lin , Ma Zhenzhen , Wang Xinyu , Yu Ruohan , Liu Xiangyuan , Zhao Jinxia
Published: August 2021

Background: Interleukin‐21 (IL‐21) has a regulatory effect on various immune cells. Its effect on macrophage function remains unclear.

Aims: This study aimed to investigate the effect of IL‐21 on the macrophages‐mediated inflammatory response and explore its mechanism.

Materials & Methods: Phorbol myristate acetate was used to induce THP‐1‐derived macrophages. Then, cells were stimulated with IL‐21 and/or lipopolysaccharide (LPS). To determine the effect of IL‐21 on the production of inflammatory factors in THP‐1‐derived macrophages, the messenger RNA (mRNA) and protein levels of IL‐6, tumor necrosis factor‐α (TNF‐α), IL‐8, and IL‐10 were detected by real‐time polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA), respectively. Meanwhile, to explore the effect of IL‐21 on macrophage polarization, macrophage phenotype, gene expression, and cytokine secretion mediated by THP‐1‐derived macrophage were detected by flow cytometry, RT‐PCR, and ELISA.

Results: First, we found that the IL‐21 receptor was expressed in THP‐1‐derived macrophages. IL‐21 enhanced LPS‐mediated TNF‐α, IL‐6, and IL‐10 production in THP‐1‐derived macrophages. During the polarization of THP‐1‐derived macrophages to M1‐like macrophages, IL‐21 induced the expression of macrophage surface markers CD86 and CD80, and related genes, such as TNF‐α, IL‐6, IL‐1β, and DC‐SIGN mRNA, inhibited Dectin‐1 mRNA expression and promoted the secretion of TNF‐α. During the polarization of THP‐1‐derived macrophages to M2‐like macrophages, IL‐21 enhanced the expression of macrophage surface markers CD86 and CD163, and related genes, such as TNF‐α, IL‐1β, IL‐10, Dectin‐1, and DC‐SIGN mRNA, and promoted the secretion of IL‐10.

Conclusion: IL‐21 promotes LPS‐mediated production of inflammatory cytokines by THP‐1‐derived macrophages; IL‐21 plays a two‐way regulatory role in THP‐1‐derived macrophage polarization.
Duration‐adjusted betas
Authors: Varela Oscar
Published: August 2021

This paper proposes duration‐adjusted betas for the three‐factor model betas that include risk associated with the firm's dividend policy. It extends Varela (Journal of Portfolio Management, 41, 2015, 122) who shows dividend policy as relevant to the stock's risk even in perfect markets, because the stock's duration is lower when cash dividends are higher. The three‐factor model's betas measure the effects of the market portfolio, size, and value premiums on the stock's required return. The stock's duration measures its required return's effects on its price. In combination, adjusting the stock's three‐factor betas for duration accounts not only for the effects of each factor on its required return, but also for the effect of the required return on its price. Overall, investors seeking lower risks, that is lower duration‐adjusted betas, should consider firms with policies that promote higher cash dividends.
Remodeling of Tumor Microenvironment by Tumor‐Targeting Nanozymes Enhances Immune Activation of CAR T Cells for Combination Therapy
Authors: Zhu Lipeng , Liu Jie , Zhou Guangyu , Liu Tzu‐Ming , Dai Yunlu , Nie Guangjun , Zhao Qi
Published: August 2021

Targeting B7‐H3 chimeric antigen receptor (CAR) T cells has antitumor potential for therapy of non‐small cell lung cancer (NSCLC) in preclinical studies. However, CAR T cell therapy remains a formidable challenge for the treatment of solid tumors due to the heterogeneous and immunosuppressive tumor microenvironment (TME). Nanozymes exhibit merits modulating the immunosuppression of the tumor milieu. Here, a synergetic strategy by combination of nanozymes and CAR T cells in solid tumors is described. This nanozyme with dual photothermal‐nanocatalytic properties is endowed to remodel TME by destroying its compact structure. It is found that the B7‐H3 CAR T cells infused in mice engrafted with the NSCLC cells have superior antitumor activity after nanozyme ablation of the tumor. Importantly, it is found that the changes altered immune‐hostile cancer environment, resulting in enhanced activation and infiltration of B7‐H3 CAR T cells. The first evidence that the process of combination nanozyme therapy effectively improves the therapeutic index of CAR T cells is presented. Thus, this study clearly supports that the TME‐immunomodulated nanozyme is a promising tool to improve the therapeutic obstacles of CAR T cells against solid tumors.