bluuebunny/crossref_metadata_2025 huggingface dataset:
Standing flank laparotomy for colic: 37 cases
Authors: Lopes Marco A. F. , Hardy Joanne , Farnsworth Kelly , Labens Raphael , Lam W. Y. Eunice , Noschka Erik , Afonso Tiago , Cruz Villagrán Claudia , Santos Luiz C. P. , Saulez Montague , Kelmer Gal
Published: September 2021

Background

Standing flank laparotomy can be an alternative to ventral midline laparotomy in horses with colic. Standing flank laparotomy avoids general anaesthesia, provides excellent access to some regions of the abdominopelvic cavity and costs less than ventral midline laparotomy.

Objective

To report a series of cases of peritoneal and intestinal diseases other than SC diseases managed with standing flank laparotomy.

Study design

Retrospective case series.

Methods

Records from equids with colic subjected to standing flank laparotomy at five hospitals (2003‐2020) were reviewed. Descriptive data analysis was performed.

Results

Thirty horses (sixteen survived to discharge), six ponies (four survived) and one donkey (euthanised) were subjected to standing flank laparotomy via the left flank (n = 31), right flank (n = 2) or both flanks (n = 4). The primary disease affected the peritoneum (0/5 survived), SI (5/9 survived) and caecum and/or LC (15/23 survived). Enterotomy was performed in four animals (all survived). Partial typhlectomy was performed in one horse (euthanised). Resection‐anastomosis of the SI or LC was performed in three animals (one survived). Three animals had intraoperative complications that negatively affected the outcome: Two ponies had intolerance to abdominopelvic exploration; one mare had spontaneous exteriorisation of a long segment of the SI leading to a large tear in the mesentery. In seven cases, severe/extensive lesions found during standing flank laparotomy warranted immediate euthanasia. The survival rate was 54%. All owners were satisfied with the decision to perform standing flank laparotomy.

Main limitations

The retrospective design, lack of a control group, small number of cases and lack of standardised protocols between hospitals.

Conclusions

Although ventral midline laparotomy is the standard of care for horses with colic, standing flank laparotomy is a viable approach for some types of colic. Systemic administration of analgesics may not produce sufficient peritoneal analgesia, which can lead to intolerance to abdominopelvic exploration during standing flank laparotomy in horses with colic and may negatively affect the outcome.
Role of the MOZ/MLL‐mediated transcriptional activation system for self‐renewal in normal hematopoiesis and leukemogenesis
Authors: Yokoyama Akihiko
Published: September 2021

Homeostasis in the blood system is maintained by the balance between self‐renewing stem cells and nonstem cells. To promote self‐renewal, transcriptional regulators maintain epigenetic information during multiple rounds of cell division. Mutations in such transcriptional regulators cause aberrant self‐renewal, leading to leukemia. MOZ, a histone acetyltransferase, and MLL, a histone methyltransferase, are transcriptional regulators that promote the self‐renewal of hematopoietic stem cells. Gene rearrangements of MOZ and MLL generate chimeric genes encoding fusion proteins that function as constitutively active forms. These MOZ and MLL fusion proteins constitutively activate transcription of their target genes and cause aberrant self‐renewal in committed hematopoietic progenitors, which normally do not self‐renew. Recent progress in the field suggests that MOZ and MLL are part of a transcriptional activation system that activates the transcription of genes with nonmethylated CpG‐rich promoters. The nonmethylated state of CpGs is normally maintained during cell divisions from the mother cell to the daughter cells. Thus, the MOZ/MLL‐mediated transcriptional activation system replicates the expression profile of mother cells in daughter cells by activating the transcription of genes previously transcribed in the mother cell. This review summarizes the functions of the components of the MOZ/MLL‐mediated transcriptional activation system and their roles in the promotion of self‐renewal.
Protease‐sensitive regions in amyloid light chains: what a common pattern of fragmentation across organs suggests about aggregation
Authors: Mazzini Giulia , Ricagno Stefano , Caminito Serena , Rognoni Paola , Milani Paolo , Nuvolone Mario , Basset Marco , Foli Andrea , Russo Rosaria , Merlini Giampaolo , Palladini Giovanni , Lavatelli Francesca
Published: September 2021

Light‐chain (AL) amyloidosis is characterized by deposition of immunoglobulin light chains (LC) as fibrils in target organs. Alongside the full‐length protein, abundant LC fragments are always present in AL deposits. Herein, by combining gel‐based and mass spectrometry analyses, we identified and compared the fragmentation sites of amyloid LCs from multiple organs of an AL λ amyloidosis patient (AL‐55). The positions pinpointed here in kidney and subcutaneous fat, alongside those previously detected in heart of the same patient, were aligned and mapped on the LC’s dimeric and fibrillar states. All tissues contain fragmented LCs along with the full‐length protein; the fragment pattern is coincident across organs, although microheterogeneity exists. Multiple cleavage positions were detected; some are shared, whereas some are organ‐specific, likely due to a complex of proteases. Cleavage sites are concentrated in ‘proteolysis‐prone’ regions, common to all tissues. Several proteolytic sites are not accessible on native dimers, while they are compatible with fibrils. Overall, data suggest that the heterogeneous ensemble of LC fragments originates in tissues and is consistent with digestion of preformed fibrils, or with the hypothesis that initial proteolytic cleavage of the constant domain triggers the amyloidogenic potential of LCs, followed by subsequent proteolytic degradation. This work provides a unique set of molecular data on proteolysis from ex vivo amyloid, which allows discussing hypotheses on role and timing of proteolytic events occurring along amyloid formation and accumulation in AL patients.
Coral adaptation to climate change: Meta‐analysis reveals high heritability across multiple traits
Authors: Bairos‐Novak Kevin R. , Hoogenboom Mia O. , van Oppen Madeleine J. H. , Connolly Sean R.
Published: September 2021

Anthropogenic climate change is a rapidly intensifying selection pressure on biodiversity across the globe and, particularly, on the world's coral reefs. The rate of adaptation to climate change is proportional to the amount of phenotypic variation that can be inherited by subsequent generations (i.e., narrow‐sense heritability, h2). Thus, traits that have higher heritability (e.g., h2 > 0.5) are likely to adapt to future conditions faster than traits with lower heritability (e.g., h2 < 0.1). Here, we synthesize 95 heritability estimates across 19 species of reef‐building corals. Our meta‐analysis reveals low heritability (h2 < 0.25) of gene expression metrics, intermediate heritability (h2 = 0.25–0.50) of photochemistry, growth, and bleaching, and high heritability (h2 > 0.50) for metrics related to survival and immune responses. Some of these values are higher than typically observed in other taxa, such as survival and growth, while others were more comparable, such as gene expression and photochemistry. There was no detectable effect of temperature on heritability, but narrow‐sense heritability estimates were generally lower than broad‐sense estimates, indicative of significant non‐additive genetic variation across traits. Trait heritability also varied depending on coral life stage, with bleaching and growth in juveniles generally having lower heritability compared to bleaching and growth in larvae and adults. These differences may be the result of previous stabilizing selection on juveniles or may be due to constrained evolution resulting from genetic trade‐offs or genetic correlations between growth and thermotolerance. While we find no evidence that heritability decreases under temperature stress, explicit tests of the heritability of thermal tolerance itself—such as coral thermal reaction norm shape—are lacking. Nevertheless, our findings overall reveal high trait heritability for the majority of coral traits, suggesting corals may have a greater potential to adapt to climate change than has been assumed in recent evolutionary models.
Crustal anorthosite formation by deep‐seated hydrothermal circulation beneath fast‐spreading axis: Constraints from chronological approach, Sr isotope, and fluid–chromite inclusion investigation
Authors: Akizawa Norikatsu , Miyake Akira , Igami Yohei , Tsuchiyama Akira , Asanuma Hisashi , Kogiso Tetsu , Wakaki Shigeyuki , Ishikawa Tsuyoshi , Arai Shoji , Eom Jiwon , Kawahata Hodaka , Aze Takahiro , Yokoyama Yusuke
Published: September 2021

Hydrothermal circulation beneath the spreading axis plays a significant role in the exchange of energy and mass between the solid Earth and the oceans. Deep‐seated hydrothermal circulation down to the crust/mantle boundary in the fast‐spreading axis has been introduced by a number of studies regarding geological investigations and numerical models. In order to assess a reaction between hydrothermal fluid and host rock around the crust/mantle boundary, we conducted bulk trace element and Sr isotope analyses with a series of in situ investigations for crustal anorthosite, a reaction product between hydrothermal fluid and gabbro in the lowermost crustal section along Wadi Fizh, northern Oman ophiolite. In addition, we conducted titanite U–Pb isotope analyses to evaluate timing of the crustal anorthosite formation in the framework of the evolutional process of the Oman ophiolite. We estimated the formation age of the crustal anorthosite at 97.5 Ma ± 5.0 Ma, overlapping with the timing of the crust formation in the paleo spreading axis. The crustal anorthosite shows high‐Th/U ratio (~2.5) and high‐initial 87Sr/86Sr ratio (0.7050) due to seawater‐derived hydrothermal fluid ingress into the precursor gabbro. With using analytical technique of micro‐excavation at cryo‐temperature, we detected Cl from a few micrometer‐sized inclusion of aqueous fluid and chromite grains. The solubility of Cr was enhanced by complexation reactions with Cl in the hydrothermal fluid. Regarding reconstructed three‐dimensional mass distribution of the inclusion and chromite composition, maximum Cr content of parental fluid was estimated at ~69 000 μg/g. The exceptionally high‐Cr content was achieved locally by leaking of fluid and synchronous chromite crystallization during fluid entrapment. Presence of the deep‐seated hydrothermal circulation could be assigned to the segment end, where cold seawater penetrates into the lowermost crust and extract heat along widely spaced network‐like fluid channel.
Intraluminal diamond‐like carbon coating with anti‐adhesion and anti‐biofilm effects for uropathogens: A novel technology applicable to urinary catheters
Authors: Watari Shogo , Wada Koichiro , Araki Motoo , Sadahira Takuya , Ousaka Daiki , Oozawa Susumu , Nakatani Tatsuyuki , Imai Yuichi , Kato Junichi , Kariyama Reiko , Watanabe Toyohiko , Nasu Yasutomo
Published: September 2021

Objectives

To examine anti‐adhesion and anti‐biofilm effects of a diamond‐like carbon coating deposited via a novel technique on the inner surface of a thin silicon tube.

Methods

Diamond‐like carbon coatings were deposited into the lumen of a silicon tube with inner diameters of 2 mm. The surface of the diamond‐like carbon was evaluated using physicochemical methods. We used three clinical isolates including green fluorescent protein‐expressing Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus. We employed a continuous flow system for evaluation of both bacterial adhesion and biofilm formation. Bacterial adhesion assays consisted of counting the number of colony‐forming units and visualization of adhered bacterial cells by scanning electron microscope to evaluate the diamond‐like carbon‐coated/uncoated samples. The biofilm structure was analyzed by confocal laser scanning microscopy on days 3, 5, 7 and 14 for green fluorescent protein‐expressing Pseudomonas aeruginosa.

Results

The smooth and carbon‐rich structure of the intraluminal diamond‐like carbon film remained unchanged after the experiments. The numbers of colony‐forming units suggested lower adherence of green fluorescent protein‐expressing Pseudomonas aeruginosa and Escherichia coli in the diamond‐like carbon‐coated samples compared with the uncoated samples. The scanning electron microscope images showed adhered green fluorescent protein‐expressing Pseudomonas aeruginosa cells without formation of microcolonies on the diamond‐like carbon‐coated samples. Finally, biofilm formation on the diamond‐like carbon‐coated samples was lower until at least day 14 compared with the uncoated samples.

Conclusions

Intraluminal diamond‐like carbon coating on a silicone tube has anti‐adhesion and anti‐biofilm effects. This technology can be applied to urinary catheters made from various materials.
Fine‐tuning language discrimination: Bilingual and monolingual infants’ detection of language switching
Authors: Schott Esther , Mastroberardino Meghan , Fourakis Eva , Lew‐Williams Casey , Byers‐Heinlein Krista
Published: September 2021

The ability to differentiate between two languages sets the stage for bilingual learning. Infants can discriminate languages when hearing long passages, but language switches often occur on short time scales with few cues to language identity. As bilingual infants begin learning sequences of sounds and words, how do they detect the dynamics of two languages? In two studies using the head‐turn preference procedure, we investigated whether infants (n = 44) can discriminate languages at the level of individual words. In Study 1, bilingual and monolingual 8‐ to 12‐month‐olds were tested on their detection of single‐word language switching in lists of words (e.g., “dog… lait [fr. milk]”). In Study 2, they were tested on language switching within sentences (e.g., “Do you like the lait?”). We found that infants were unable to detect language switching in lists of words, but the results were inconclusive about infants’ ability to detect language switching within sentences. No differences were observed between bilinguals and monolinguals. Given that bilingual proficiency eventually requires detection of sound sequences across two languages, more research will be needed to conclusively understand when and how this skill emerges. Materials, data, and analysis scripts are available at https://osf.io/9dtwn/.
An integrated review of the barriers and facilitators for accessing and engaging with mental health in a rural setting
Authors: Ferris‐Day Philip , Hoare Karen , Wilson Rhonda L. , Minton Claire , Donaldson Andrea
Published: September 2021

The review investigated the barriers and facilitators associated with assessing and engaging with mental health in a rural setting. The aim is to describe and synthesize the literature that examines the experiences of adults who access or attempt to access mental health services in rural settings. A systematic search from 2010 to 2020 was conducted using CINAHL, PsycINFO, Web of Science Core Collection, PubMed, Psychology and Behavioural Sciences Collection, Google Scholar, and Scopus. PRISMA protocols located 32 relevant papers from the overall 573 first selected. Braun and Clarke (Qualitative Research in Psychology, 3:77–101, 2006) thematic analysis methodology was applied to the data resulting in two themes: first theme identified help‐seeking with subthemes of stigma and locality of health services. The second theme was connectedness, inclusive of subthemes of support systems and personal identity. The review identified gender‐related perspectives concerning accessing mental health support, exposing the need for more research to examine the diverse social connections and support networks in rural communities. The findings suggest the need to further explore the impediments that reduce the likelihood of accessing mental health services in rural communities.
Can intercropping be an adaptation to drought? A model‐based analysis for pearl millet–cowpea
Authors: Nelson William C. D. , Hoffmann Munir P. , Vadez Vincent , Rötter Reimund P. , Koch Marian , Whitbread Anthony M.
Published: September 2021

Cereal–legume intercropping is promoted within semi‐arid regions as an adaptation strategy to water scarcity and drought for low‐input systems. Our objectives were firstly to evaluate the crop model APSIM for pearl millet (Pennisetum glaucum (L.))—cowpea (Vigna unguiculata (L.) Walp) intercropping—and secondly to investigate the hypothesis that intercropping provides complimentary yield under drought conditions. The APSIM model was evaluated against data from a two year on station field experiment during the dry season of a semi‐arid environment in Patancheru, India, with severe, partial and no water deficit stress (well‐watered); densities of 17 and 33 plants per m−2, and intercrop and sole crop production of pearl millet and cowpea. Overall, APSIM captured the dynamics of grain yields, indicated by the Willmott Index of Agreement (IA: 1 optimal, 0 the worst) 0.91 from 36 data points (n), total biomass (IA: 0.90, n = 144), leaf area index (LAI, IA = 0.77, n = 66), plant height (IA 0.96, n = 104 pearl millet) and cowpea (IA 0.81, n = 102), as well as soil water (IA 0.73, n = 126). Model accuracy was reasonable in absolute terms (RMSE pearl millet 469 kg/ha and cowpea 322 kg/ha). However, due to low observed values (observed mean yield pearl millet 1,280 kg/ha and cowpea 555 kg/ha), the relative error was high, a known aspect for simulation accuracy in low‐yielding environments. The simulation experiment compared the effect of intercropping pearl millet and cowpea versus sole cropping under different plant densities and water supplies. A key finding was that intercropping pearl millet and cowpea resulted in similar total yields to the sole pearl millet. Both sole and intercrop systems responded strongly to increasing water supply, except sole cropped cowpea, which performed relatively better under low water supply. High plant density had a consistent effect, leading to lower yields under low water supply. Higher yields were achieved under high density, but only when water supply was high: absolute highest total intercrop yields were 4,000 (high density) and 3,500 kg/ha (low density). This confirms the suitability of the common practice among farmers who use the low planting density under water scarce conditions. Overall, this study confirms that intercropping is no silver bullet, i.e. not per se a way to achieve high yield production or reduce risk under drought. It does, however, provide an opportunity to diversify food production by additionally integrating protein rich crops, such as cowpea.
Examining the phase evolution of lithium disilicate glass‐ceramics with lithium tantalate as a secondary phase
Authors: DeCeanne Anthony V. , Fry Aubrey L. , Wilkinson Collin J. , Dittmer Marc , Ritzberger Christian , Rampf Markus , Mauro John C.
Published: September 2021

Lithium disilicate glass‐ceramics were discovered in the 1950s, and the evolution of the main target phase of these materials is well known. However, the lithium disilicate system is still an area of active research, especially when a secondary phase is introduced since the phase evolution of secondary phases is not currently understood. The present study examines the main target phases, as well as a secondary phase of lithium tantalate, via X‐ray diffraction. A large data set is obtained to investigate the evolution of all phases. It is found that the nucleation of the precursor lithium metasilicate phase is coupled to both the nucleation of the primary target phase, lithium disilicate, and the nucleation of lithium tantalate. A reaction equation describing this relationship is proposed.
Enhanced 3D printed alumina ceramic cores via impregnation
Authors: Li He , Liu Yongsheng , Colombo Paolo , Li Wenbo , Liu Yansong , Hu Kehui , Lu Zhigang
Published: September 2021

3D‐printed alumina ceramic cores often face the problem of low flexural strength at its application temperature of 1500℃, and the requirements on porosity and strength limit its fabrication process. In this research, three types of solutions were employed to impregnate the ceramics to improve the strength of the 3D‐printed alumina ceramic cores. The results showed that silica sol (SS), tetraethyl orthosilicate (TO), and 3‐(Trimethoxysilyl)propyl methacrylate (PM) all could improve the (room temperature) flexural strength of the 3D printed ceramics effectively compared to the control sample (CS) without impregnation, and the SS solution could improve the high temperature flexural strength at 1500℃ greatly compared to other solutions. The improvement in strength was due to the introduction of Si, which formed a stable mullite phase during the sintering process. Computed tomography (CT) analysis showed there is no cracks formed in the ceramic cores impregnated with the SS solution, and they exhibited the overall best performance (21.2 ± 0.8 vol% open porosity, shrinkage of 3.2 ± 0.3% in the X direction, 3.4 ± 0.2% in the Y direction, 2.1 ± 0.4% in the Z direction, room temperature flexural strength of 85.7 ± 6.9 MPa, and 1500℃ flexural strength of 19.2 ± 1.1 MPa).
Tungsten‐doped foam g‐C3N4 with improved photocatalytic properties for degradation of pollutant and hydrogen evolution
Authors: Zong Yi , Peng Zixing , Dong Qian , Hu Wanbing , Yang Dandan , Guo Qianyi , Chen Zhiwu , Dong Guoping
Published: September 2021

As a potential material applied in the photocatalytic field, graphitic carbon nitride (g‐C3N4) has attracted extensive attention for its advantages of visible‐light response, excellent thermodynamic, and chemical stability. However, the photocatalytic performance of g‐C3N4 is still limited in practical applications. Here, using a facile thermal polymerization method, unique W‐doped foam g‐C3N4 was synthesized to realize enhanced photocatalytic performance for the degradation of Rhodamine B and the evolution of hydrogen. Compared with pure foam g‐C3N4, tungsten doping modified the foam g‐C3N4 and efficiently improved its specific surface area, leading to enhanced photocatalytic performance. The average rate of hydrogen evolution was as high as 8818 μmol·h−1·g−1, which was better than most photocatalysts. This work proposes a new effective method and idea to modify g‐C3N4 for improving its photocatalytic performance.
Improving luminescence behavior and glass stability of tellurium‐doped germanate glasses by modifying network topology
Authors: Huang Ling , Li Lihua , Peng Mingying , Tan Linling , Ma Zhijun
Published: September 2021

Broadband near‐infrared (NIR) luminescent materials are of great interest for their potential application in optical communication, remote sensing, imaging, and homeland security. Tellurium (Te) doped glasses were recently recognized as such a promising candidate due to their broadband NIR emission (700–1700 nm). However, the achievement of Te‐doped glasses with high luminescence efficiency and glass stability (GS) remains a daunting challenge. Here, the luminescence behavior and GS of Te‐doped germanate glasses are manipulated by tailoring the glass network topology. Te NIR luminescence is enhanced by tailoring topological cages in germanate glass network structure through varying glass network modifiers. Meanwhile, the GS of potassium germanate glass is significantly enhanced due to increased network connectivity caused by the co‐introduction of alkaline earth oxides. Finally, NIR luminescence intensity of the glass was further enhanced by optimizing the doping concentration of TeO2. The findings here could contribute to designing Te‐activated glasses with improved performance for application in optical amplifiers and tunable fiber lasers.
Long non‐coding RNA TNK2 AS1/microRNA‐125a‐5p axis promotes tumor growth and modulated phosphatidylinositol 3 kinase/AKT pathway
Authors: Guo Liuqing , Ma Hanwei , Kong Yin , Leng Guangxian , Liu Guiyuan , Zhang Youcheng
Published: September 2021

Background and Aim

Long non‐coding RNA (lncRNA) TNK2 AS1 is a noncoding RNA with the capability of affecting microRNAs (miRNAs) levels and gene expression. The study was designed to investigate the mechanism of TNK2 AS1 in gastric cancer.

Methods

The loss and gain of function of TNK2 AS1 were investigated by analyzing the malignant behavior of AGS cells including the abilities of migration, invasion, and epithelial‐mesenchymal transition (EMT) process via wound healing and transwell assay, as well as western blot. The targeting relationship of LncRNA TNK2 AS1 was analyzed through searching bioinformatics database, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. Tumor‐bearing experiment in nude mice was performed to further confirm the regulatory role of TNK2 AS1 in vivo. Immunofluorescence assay for Ki67 expression was carried out in tumor tissues of mice model.

Results

The results showed that TNK2 AS1 overexpression promoted the malignant behaviors of AGS cells, which could be weakened by miR‐125a‐5p mimic addition. In addition, Jumonji, At‐rich interaction domain (JARID2), and phosphatidylinositol 3 kinase (PI3K)/AKT pathway were regulated by TNK2‐AS1/miR‐125a‐5p axis. In vivo, TNK2 AS1/miR‐125a‐5p axis promoted tumor growth and led to increases in green fluorescence intensity and vimentin expression and a decrease in E‐cadherin level, which could be mediated by JARID2 and PI3K/AKT pathway.

Conclusion

Therefore, a conclusion was drawn that TNK2‐AS1/miR‐125a‐5p promoted the progression of gastric cancer.
Impact of a dietitian in general practice: Care of the frail and malnourished
Authors: Hickson Mary , Child Jenny , Collinson Avril
Published: September 2021

Background

There is an increased demand in primary healthcare but general practitioner (GP) numbers are declining, creating significant challenges. Dietitians are ideal professionals to lead the treatment of patients with conditions that are amenable to dietary manipulation, including the management of malnutrition and frailty. The present study evaluated the benefits of a model of care in which a dietitian, working as a first contact practitioner within a general practice, provided care to patients at risk of malnutrition and frailty, aiming to reduce GP workload, improve patient care and make cost savings.

Methods

A service evaluation with a dietitian employed 6 h per week for 6 months. The practice database was screened for patients aged ≥65 years and electronic Frailty index 0.26–0.36 or body mass index  <19 kg m–2. These patients were triaged by the dietitian and those at risk of malnutrition offered consultations. Patients prescribed oral nutritional supplements (ONS) and not under dietetic management were also seen.

Results

Approximately 1200 patients met the screening criteria; 189 (16%) patients were triaged by the dietitian. Most (75%) were at risk of malnutrition and 63 of these were seen. Improvements in strength, frailty and nutrition status were observed, and changes to ONS prescriptions in 27 patients equated to annual cost savings of £15,379. Patient satisfaction was high.

Conclusions

Dietitians, acting as first contact practitioners, can deliver significant improvements in care for older people at risk of malnutrition and frailty as part of the practice multi‐disciplinary team. Cost savings for ONS were made and other potential cost saving were evident.
Neurosteroids: A novel promise for the treatment of stroke and post‐stroke complications
Authors: Xu Jiawei , Zhou Yunxiang , Yan Caochong , Wang Xiaoyu , Lou Jianyao , Luo Yi , Gao Shiqi , Wang Junjie , Wu Liang , Gao Xiangfu , Shao Anwen
Published: September 2021

Stroke is the primary reason for death and disability worldwide, with few treatment strategies to date. Neurosteroids, which are natural molecules in the brain, have aroused great interest in the field of stroke. Neurosteroids are a kind of steroid that acts on the nervous system, and are synthesized in the mitochondria of neurons or glial cells using cholesterol or other steroidal precursors. Neurosteroids mainly include estrogen, progesterone (PROG), allopregnanolone, dehydroepiandrosterone (DHEA), and vitamin D (VD). Most of the preclinical studies have confirmed that neurosteroids can decrease the risk of stroke, and improve stroke outcomes. In the meantime, neurosteroids have been shown to have a positive therapeutic significance in some post‐stroke complications, such as epilepsy, depression, anxiety, cardiac complications, movement disorders, and post‐stroke pain. In this review, we report the historical background, modulatory mechanisms of neurosteroids in stroke and post‐stroke complications, and emphasize on the application prospect of neurosteroids in stroke therapy.

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Palmitate‐mediated induction of neuropeptide Y expression occurs through intracellular metabolites and not direct exposure to proinflammatory cytokines
Authors: Tran Andy , He Wenyuan , Chen Jim T. C. , Wellhauser Leigh , Hopperton Kathyrn E. , Bazinet Richard P. , Belsham Denise D.
Published: September 2021

A contributing factor to the development of obesity is the consumption of a diet high in saturated fatty acids, such as palmitate. These fats induce hypothalamic neuroinflammation, which dysregulates neuronal function and induces orexigenic neuropeptide Y (Npy) to promote food intake. An inflammatory cytokine array identified multiple candidates that could mediate palmitate‐induced up‐regulation of Npy mRNA levels. Of these, visfatin or nicotinamide phosphoribosyltransferase (NAMPT), macrophage migratory inhibitory factor (MIF), and IL‐17F were chosen for further study. Direct treatment of the neuropeptide Y/agouti‐related peptide (NPY/AgRP)‐expressing mHypoE‐46 neuronal cell line with the aforementioned cytokines demonstrated that visfatin could directly induce Npy mRNA expression. Preventing the intracellular metabolism of palmitate through long‐chain acyl‐CoA synthetase (ACSL) inhibition was sufficient to block the palmitate‐mediated increase in Npy gene expression. Furthermore, thin‐layer chromatography revealed that in neurons, palmitate is readily incorporated into ceramides and defined species of phospholipids. Exogenous C16 ceramide, dipalmitoyl‐phosphatidylcholine, and dipalmitoyl‐phosphatidylethanolamine were sufficient to significantly induce Npy expression. This study suggests that the intracellular metabolism of palmitate and elevation of metabolites, including ceramide and phospholipids, are responsible for the palmitate‐mediated induction of the potent orexigen Npy. Furthermore, this suggests that the regulation of Npy expression is less reliant on inflammatory cytokines per se than palmitate metabolites in a model of NPY/AgRP neurons. These lipid species likely induce detrimental downstream cellular signaling events ultimately causing an increase in feeding, resulting in an overweight phenotype and/or obesity.

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Immunohistochemical expression of SOX2 in non‐melanoma skin cancer
Authors: Abdou Asmaa Gaber , Mostafa Amal Farid , Gafar Samar , Farag Azza Gaber Antar
Published: September 2021

Background

Basal cell carcinoma (BCC) followed by squamous cell carcinoma (SCC) are the most common non‐melanoma skin cancer (NMSC). SOX2 is a transcription factor that acts on various phases of embryonic development and its overexpression in many tumors has been reported.

Aim

This work aimed to evaluate the possible role of SOX2 in pathogenesis of non‐melanoma skin cancer through its immunohistochemical assessment in BCC and SCC compared to normal skin and correlating its expression with the established prognostic factors.

Methods

The investigated cases were 24 BCC, 21 SCC, and 26 normal skin specimens.

Results

SOX2 was not expressed in normal skin, but it was upregulated in SCC (85.7%) and BCC (66.7%), with a significant difference between malignant cases and normal skin (p < 0.001). However, SOX2 expression did not differ between SCC and BCC. SOX2 expression was associated with large‐sized tumors in all malignant cases (BCC plus SCC) (p = 0.02) and in SCC (p = 0.043) alone together with its liability to be expressed in advanced stage in SCC (p = 0.063).

Conclusions

SOX2 was over‐expressed in cutaneous SCC and BCC without a significant difference. SOX2 may enhance progression of NMSC manifested by its association with large tumor size and advanced stage.
Menstrual and reproductive factors and limitations in activities of daily living: A case–control study within the Japan Public Health Center‐based Prospective Study
Authors: Nakamura Kazutoshi , Sawada Norie , Kitamura Kaori , Watanabe Yumi , Tsugane Shoichiro ,   Japan Public Health Center‐based Prospective Study Group
Published: September 2021

Aim

Although menstrual/reproductive factors are known to be associated with physical disability, little is known about these associations in relation to activities of daily living (ADL). This study aimed to clarify associations between menstrual/reproductive factors and ADL limitations in peri‐ and postmenopausal women.

Study design

A nested case–control study of the Japan Public Health Center‐based Prospective (JPHC) Study.

Methods

The main outcome measure was self‐reported ADL levels in the 10‐year follow‐up questionnaire survey of the JPHC Study conducted between 2000 and 2004 (N = 36 460). Women who “live inside almost independently, but go out with assistance” or had a lower level of activity were considered to have ADL limitations (“cases”), and all others served as controls. Candidate menstrual/reproductive predictors were as follows: menarcheal age, menopausal status, menopausal age, regularity of menses, menstrual cycle, number of pregnancies, age at first pregnancy, number of deliveries, age at first delivery, and breast feeding. Multiple logistic regression analyses were conducted, and odds ratios adjusted for age and past lifestyle were calculated.

Results

Mean ages of cases (N = 592) and controls (N = 38 656) were 68.3 (SD = 7.6) and 61.1 (SD = 7.7) years, respectively. With respect to menopausal age, groups aged <45 and ≥55 years had significantly higher adjusted ORs (1.44, 95% CI: 1.09–1.90 and 1.55, 95%CI: 1.09–2.18, respectively) than the reference group (50–54 years). Multiparous women had significantly lower ORs than nulliparous women.

Conclusion

Our findings suggest that menopausal age and parity may predict future ADL limitations in women.
Efficacy and safety of autologous platelet‐rich fibrin for the treatment of infertility with intrauterine adhesions
Authors: Wang Zijun , Yang Mukun , Mao Lele , Wang Xiaoxue , Wang Shuowen , Cui Guangxia , Hou Zhaoxi , Yang Min , Cui Lei , Bai Wenpei
Published: September 2021

Aim

To evaluate the efficacy and safety of autologous platelet‐rich fibrin (PRF) for the treatment of infertility with intrauterine adhesions.

Methods

Forty patients who suffered from infertility with intrauterine adhesions (IUAs) were enrolled in this prospective trial from October 2018 to December 2019. They were randomly divided into a PRF group and a control group. Both groups underwent transcervical resection of adhesions (TCRA) during the follicular phase. PRF group: PRF prepared from autologous venous blood was placed in the uterine cavity after TCRA and after the first menstrual re‐fluid; control group: no PRF insertion. After the second menstrual re‐fluid, both groups underwent hysteroscopy to reevaluate adhesion severity. Pregnancy rate, intrauterine adhesion score, menstrual volume and duration, and endometrial thickness were assessed and adverse events were recorded.

Results

(1) PRF group pregnancy rate was significantly higher than the control group (55.0% vs. 20.0%). Mean follow‐up time was (17.63 ± 2.33) months. All patients fell pregnant naturally. Four (PRF) and one (control) patients delivered live births without placental complications. (2) Intrauterine adhesion scores decreased compared with treatment‐before. (3) In the pictorial blood loss assessment chart, score and menstrual duration during the 3rd menstrual cycle showed significant improvements for both groups. (4) Endometrial thickness also showed an increasing trend, and subendometrial bloodflow improved. (5) No treatment‐related serious adverse events were noted.

Conclusion

Placing PRF into the uterine cavity of infertility patients with IUAs following TCRA is a safe and effective therapeutic method.
Cardiovascular risk factors before and during pregnancy: Does pregnancy unmask or initiate risk?
Authors: Harville Emily W. , Crook Carrie E. , Bazzano Lydia A. , Woo Jessica G. , Burns Trudy L. , Raitakari Olli , Urbina Elaine M. , Venn Alison , Jacobs David R. , Steinberger Julia , Sinaiko Alan , Dwyer Terence , Juonala Markus ,   the i3C Consortium
Published: September 2021

Objectives

To understand if pregnancy unmasks previously silent cardiovascular (CV) adverse factors, or initiates lasting injury.

Methods

Pre‐pregnancy and during pregnancy CV risk factors (blood pressure, fasting lipids, and glucose) from 296 women belonging to studies in the International Childhood Cardiovascular Cohort (i3C) Consortium, a group of studies assessing the relationship between child and adolescent CV risk factors and adult outcomes, were used. Correlation coefficients between the pre‐ and during pregnancy measures were calculated, and the mean difference between the measures was modeled with adjustment for age, body mass index, race, smoking, and study.

Results

Measures were strongly correlated at pre‐ and during‐pregnancy visits (p < 0.01), with r of between 0.30 and 0.55. In most cases, the difference between pre‐pregnancy and during‐pregnancy did not differ significantly from 0 after adjustment for confounders. Stratification by gestational age indicated stronger correlations with measurements obtained during the first and second trimesters than the third. The correlation did not differ by the time elapsed between the pre‐pregnancy and pregnancy visits.

Conclusions

Pre‐ and during‐pregnancy CV risk factors are moderately well correlated. This may indicate that susceptible women enter pregnancy with higher risk rather than pregnancy inducing new vascular or metabolic effects.
Zinc supplementation during chemotherapy for gynecological malignancy
Authors: Yanazume Shintaro , Ushiwaka Takashi , Yorouki Honami , Onigahara Motohisa , Fukuda Mika , Togami Shinichi , Kamio Masaki , Kobayashi Hiroaki
Published: September 2021

Objective

To determine the significance of zinc supplementation for zinc deficiency during chemotherapy for gynecologic malignancies.

Methods

Twenty‐eight patients suspected of zinc deficiency before chemotherapy were prospectively evaluated. Gustatory test, serum zinc, blood count, and biochemical examinations were made pre‐chemotherapy at 3‐ and 6‐week intervals. Patients with serum zinc levels <70 μg were prescribed oral zinc acetate hydrate (167.8 mg/day) for 3 weeks. The primary outcome was efficacy of zinc supplementation, the secondary outcomes were zinc deficiency rates and adverse effects of the zinc supplement.

Results

Fifteen (mean serum zinc level: 67.4 ± 6.2 μg/dL) out of 28 patients were administered zinc supplementation pre‐chemotherapy, and subsequent serum zinc levels reached 83.2 ± 15.3 μg/dL in 3 weeks. Factors associated with chemotherapy (vs. chemoradiation, p = 0.041) and taxane + platinum (p = 0.048) were significant risk factors for decreasing zinc levels following chemotherapy. Although patients that required zinc supplementation showed decreased serum zinc levels after chemotherapy and tended to experience taste alteration (sour: p = 0.041), zinc supplementation for zinc deficiency during chemotherapy did not alter taste perception.

Conclusion

Zinc supplementation promptly increased serum levels without major complications and may prevent an alteration in taste perception.
Downregulation of GTSE1 leads to the inhibition of proliferation, migration, and Warburg effect in cervical cancer by blocking LHDA expression
Authors: Chen Longyi , Zhong Youwen , Yang Xiuwei , Zhang Qingyue , Wu Xiaoling
Published: September 2021

Aim

G2 and S phase‐expressed‐1 (GTSE1) has been identified to play a vital role in several kinds of cancers, but its role in cervical cancer development remains unknown. Herein, we aimed to reveal the role and underlying mechanism of GTSE1 in cervical cancer cell growth, migration, and aerobic glycolysis.

Methods

GTSE1 expression levels in cervical cancer tissues and normal cervical tissues were determined by real time PCR and immunohistochemistry. Human short hairpin RNA was used to downregulate GTSE1 level in cervical cancer cells SiHa and HeLa cells. Colony formation, cell counting kit‐8, and wound‐healing assays were used for cell function evaluation. Lactate production, lactate dehydrogenase activity, and glucose concentration were tested to assess the Warburg effect.

Results

GTSE1 expressions at both mRNA and protein levels were significantly elevated in cervical cancer tissues compared with normal tissues. Downregulation of GTSE1 induced significant repressions in cell colony formation, viability and migration, and Warburg effect, as well as reduced expression of lactate dehydrogenase isoform A (LDHA) at mRNA and protein levels. Additionally, downregulation of GTSE1 weakened the tumorigenesis of HeLa and SiHa cells in vivo.

Conclusion

This study demonstrated that downregulation of GTSE1 led to significant inhibitions in cell proliferation, migration, tumorigenesis, and Warburg effect in cervical cancer by blocking the expression of LHDA.
Crizotinib‐induced anti‐cancer activity in human cervical carcinoma cells via ROS‐dependent mitochondrial depolarization and induction of apoptotic pathway
Authors: Varma Diksha A. , Tiwari Manisha
Published: September 2021

Introduction

Cervical cancer is one of the leading causes of mortality among women population worldwide. In spite of recurrent screening, vaccination, and chemotherapeutic interventions, combating cervical cancer still remains a challenge. Crizotinib is a small molecule inhibitor that targets mesenchymal epithelial transition factor (c‐MET) and has been successfully studied for its anti‐cancer effects in non‐small cell lung cancer, pancreatic, gastric, renal, prostate, and breast carcinomas. Although c‐MET is a well‐known prognostic, diagnostic, and therapeutic target in cervical cancer, anti‐cancer properties of its inhibitor crizotinib against cervical carcinoma, has not been explored yet.

Methods

In the present study, the anti‐cancer effects of crizotinib on cervical cancer cells were evaluated using various in vitro cell‐based assays, such as labelling drug‐treated cells with MTT, H2DCFDA, Annexin V5‐fluorescein isothiocyanate (FITC) antibody, JC‐1, PI, and analysis using fluorescence‐activated cell sorting (FACS).

Results

The molecule was found to effectively inhibit proliferation of cervical cancer cells HeLa and SiHa with an IC50 of 0.641 ± 0.0724 and 0.871 ± 0.104 μM, respectively, and induce apoptosis in a dose‐dependent manner. Further investigations showed that crizotinib‐induced production of reactive oxygen species (ROS) with increasing concentrations further resulted in mitochondrial membrane depolarization. However, the drug had no effect on cell cycle progression of HeLa and SiHa cells.

Conclusion

Thus, the study elucidates the cytotoxic effects of crizotinib in cervical cancer cells by activation of ROS‐dependent apoptotic pathway via mitochondrial depolarization. These findings will further aid the evaluation of other molecular mechanisms of crizotinib and would pave the way for its implication as a chemotherapeutic option in cervical cancer.
Manual removal of the placenta and postpartum hemorrhage: A multicenter retrospective study
Authors: Fujita Kei , Ushida Takafumi , Imai Kenji , Nakano‐Kobayashi Tomoko , Iitani Yukako , Matsuo Seiko , Yoshida Shigeru , Yamashita Mamoru , Kajiyama Hiroaki , Kotani Tomomi
Published: September 2021

Aim

In postpartum women, retained placenta is diagnosed in the absence of signs of placental separation and expulsion, and requires manual removal of the placenta (MROP). MROP may lead to massive hemorrhage, hemodynamic instability, and the need for emergency interventions including blood transfusion, interventional radiology, and hysterectomy. In this study, we aimed to identify the risk factors for retained placenta requiring MROP after vaginal delivery and postpartum hemorrhage (PPH) following MROP.

Methods

A multicenter retrospective study was performed using data from women who delivered at term between 2010 and 2018 at 13 facilities in Japan. Of 36 454 eligible women, 112 women who required MROP were identified. Multivariate logistic regression analyses were conducted to evaluate the risk factors for retained placenta and PPH following MROP.

Results

A history of abortion, assisted reproductive technology (ART), instrumental delivery, and delivery of small‐for‐gestational‐age infant were independent risk factors for MROP (adjusted odds ratios [95% confidence intervals]: 1.93 [1.28–2.92], 8.41 [5.43–13.05], 1.80 [1.14–2.82], and 4.32 [1.97–9.48], respectively). ART was identified as an independent risk factor for PPH (adjusted odds ratio [95% confidence interval]: 6.67 [2.42–18.36]) in patients who underwent MROP.

Conclusion

ART pregnancies significantly increased the risk of retained placenta requiring MROP and PPH. Our results suggest that clinicians need consider patient transfer to a higher‐level facility and preparation of sufficient blood products before initiating MROP in cases of ART pregnancies. Our study may assist in identifying high‐risk women for PPH before MROP and in guiding treatment decisions, especially in facilities without a blood bank.
Surgically treated genital chronic graft‐versus‐host disease in women: A report of three cases
Authors: Kamada Yasuhiko , Kusumoto Rie , Kashino Chiaki , Kubo Kotaro , Mitsui Takashi , Masuyama Hisashi
Published: September 2021

Hematopoietic stem cell transplantation (HSCT) is a crucial treatment for hematological malignancy. Gonadal dysfunction occurs at an early stage after this treatment, and such patients may require hormone replacement therapy. Genital chronic graft‐versus‐host disease is a lesser‐known complication of HSCT that begins with vulvar discomfort and dysuria and progresses to sexual dysfunction and retention of menstrual blood due to vaginal stenosis and obstruction; thus, significantly impairing the patient's quality of life. We describe three women who underwent vaginal reconstruction because of genital chronic graft‐versus‐host disease. We discuss the surgical techniques, including double cross plasty that were performed in each case. Surgical interventions enabled the continuation of HRT and facilitated sexual intercourse. In conclusion, gynecologists should be aware that genital chronic graft‐versus‐host disease can occur after HSCT, and that surgical treatment options are available to improve patients' symptoms and quality of life.