bluuebunny/crossref_metadata_2025 huggingface dataset:
High Serum Anti-Müllerian Hormone Concentrations Are Associated With Poor Pregnancy Outcome in Fresh IVF/ICSI Cycle but Not Cumulative Live Birth Rate in PCOS Patients
Authors: Guo Yaxin , Liu Shuai , Hu Shiqiao , Li Fei , Jin Lei
Published: May 2021

Objective

To investigate the association between baseline serum Anti-Müllerian hormone (AMH) levels and IVF/ICSI outcomes in women with polycystic ovary syndrome (PCOS).

Design

Retrospective study.

Setting

Reproductive medicine center in a hospital.

Population

2436 PCOS patients (Rotterdam criteria) who underwent their first fresh IVF/ICSI cycles were divided into three groups on the basis of the <25th (Group 1, n=611), 25 to 75th (Group 2, n=1216), or >75th (Group 3, n=609) percentile of baseline serum AMH level.

Intervention(s)

Baseline serum AMH levels measured on the 2-3 days of spontaneous menstrual cycle before IVF/ICSI treatment.

Main Outcome Measure(s)

Live birth rate (LBR), cumulative live birth rate (CLBR), clinical pregnancy rate (CPR), and normal fertilization rate (FR).

Result(s)

The LBR, CPR, and FR were significantly increased in Group 1 than Group 2 and Group 3, however, CLBR was similar between the three groups. The LBR were 46.6%, 40.5%, and 39.4% in Group 1, Group 2, and Group 3 respectively. The CPR were 53.0%, 47.0%, and 45.5%, respectively. The FR was highest in Group 1 (61.7%, P<0.05), but there was no uniform reverse trend with the AMH level. CLBR were 68.7%, 70.4%, and 71.3%, respectively. Although women in Group 1 were older (p < 0.05) and had higher body mass index (BMI) (p < 0.05), binomial logistic regression analysis used age, BMI, FSH, and AMH as independent variables indicated that only AMH was significantly associated with LBR and CPR. Nevertheless, binomial logistic regression analysis used age, BMI, FSH, AMH, and the number of retrieved oocytes as independent variables indicated that only the number of retrieved oocytes was significantly correlated with CLBR. After stratifying by age, the negative relationship between baseline AMH level and LBR and CPR remained only in the patients <30 years old.

Conclusion(s)

Higher baseline AMH level in PCOS women resulted in lower LBR, CPR, and FR but did not influence CLBR.
Next-Generation Sequencing in Newborn Screening: A Review of Current State
Authors: Remec Ziga I. , Trebusak Podkrajsek Katarina , Repic Lampret Barbka , Kovac Jernej , Groselj Urh , Tesovnik Tine , Battelino Tadej , Debeljak Marusa
Published: May 2021

Newborn screening was first introduced at the beginning of the 1960s with the successful implementation of the first phenylketonuria screening programs. Early expansion of the included disorders was slow because each additional disorder screened required a separate test. Subsequently, the technological advancements of biochemical methodology enabled the scaling-up of newborn screening, most notably with the implementation of tandem mass spectrometry. In recent years, we have witnessed a remarkable progression of high-throughput sequencing technologies, which has resulted in a continuous decrease of both cost and time required for genetic analysis. This has enabled more widespread use of the massive multiparallel sequencing. Genomic sequencing is now frequently used in clinical applications, and its implementation in newborn screening has been intensively advocated. The expansion of newborn screening has raised many clinical, ethical, legal, psychological, sociological, and technological concerns over time. This review provides an overview of the current state of next-generation sequencing regarding newborn screening including current recommendations and potential challenges for the use of such technologies in newborn screening.
Stakeholders' Perspectives on the Challenges of Emergency Obstetric Referrals and the Feasibility and Acceptability of an mHealth Intervention in Northern Iraq
Authors: Relyea Bridget , Wringe Alison , Afaneh Osama , Malamas Ioannis , Teodoro Nicholas , Ghafour Mohammed , Scott Jennifer
Published: May 2021

The health system in northern Iraq has been weakened by conflict and the internal displacement of over three million people. Mobile phone-based interventions (mHealth) may improve maternal and neonatal health outcomes by enabling emergency referrals, facilitating communication between patients and providers, and improving patient data management; however, they have not been sufficiently studied in conflict-affected settings. We explored stakeholders' perspectives on challenges to obstetric referrals and the feasibility and acceptability of a mobile phone-based application to reduce delays in reaching emergency obstetric care in order to inform its development. We conducted a qualitative study in the Kurdistan region of northern Iraq from May to July, 2018. Using purposive sampling, we carried out 15 semi-structured interviews with coordination actors including healthcare management staff, government health officials, non-government health program managers and ambulance staff. The interviews explored obstetric care delivery, referral processes, mobile phone usage and mHealth implementation strategies. Eleven focus group discussions, which incorporated participatory activities on similar topics, were conducted with ambulance drivers, hospital and primary health center staff. Audio-recorded, transcribed and translated data were coded iteratively to identify emerging concepts, and analyzed thematically. Sixty-eight stakeholders (36 women and 32 men) participated. Challenges regarding the referral system included resource limitations, security concerns, costs and women's reluctance to be transported in male-staffed ambulances. In terms of obstetric care and decision-making, participants noted gaps in communication and coordination of services with the current paper-based system between health care providers, ambulance drivers, and hospital staff. Ambulance drivers reported incurring delays through lack of patient information, poor road conditions, and security issues. A prototype mobile phone application was found to be acceptable based on perceived usefulness to address some of the challenges to safe obstetric care and focused on phone usage, access to information, Global Positioning System (GPS), connectivity, cost, and user-friendliness. However, the feasibility of the innovation was considered in relation to implementation challenges that were identified, including poor connectivity, and digital literacy. Implementation of the app would need to account for the humanitarian context, cultural and gender norms regarding obstetric care, and would require substantial commitment and engagement from policymakers and practitioners.
Association Between COVID-19 Pregnant Women Symptoms Severity and Placental Morphologic Features
Authors: Rebutini Patricia Zadorosnei , Zanchettin Aline Cristina , Stonoga Emanuele Therezinha Schueda , Prá Daniele Margarita Marani , de Oliveira André Luiz Parmegiani , Dezidério Felipe da Silva , Fonseca Aline Simoneti , Dagostini Júlio César Honório , Hlatchuk Elisa Carolina , Furuie Isabella Naomi , Longo Jessica da Silva , Cavalli Bárbara Maria , Dino Carolina Lumi Tanaka , Dias Viviane Maria de Carvalho Hessel , Percicote Ana Paula , Nogueira Meri Bordignon , Raboni Sonia Mara , de Carvalho Newton Sergio , Machado-Souza Cleber , de Noronha Lucia
Published: May 2021

Since the beginning of the pandemic, few papers describe the placenta’s morphological and morphometrical features in SARS-CoV-2–positive pregnant women. Alterations, such as low placental weight, accelerated villous maturation, decidual vasculopathy, infarcts, thrombosis of fetal placental vessels, and chronic histiocytic intervillositis (CHI), have been described.

Objective

To analyze clinical data and the placental morphological and morphometric changes of pregnant women infected with SARS-CoV-2 (COVID-19 group) in comparison with the placentas of non-infected pregnant women, matched for maternal age and comorbidities, besides gestational age of delivery (Control group).

Method

The patients in the COVID-19 and the Control group were matched for maternal age, gestational age, and comorbidities. The morphological analysis of placentas was performed using Amsterdam Placental Workshop Group Consensus Statement. The quantitative morphometric evaluation included perimeter diameter and number of tertiary villi, number of sprouts and knots, evaluation of deposition of villous fibrin, and deposition of intra-villous collagen I and III by Sirius Red. Additionally, Hofbauer cells (HC) were counted within villi by immunohistochemistry with CD68 marker.

Results

Compared to controls, symptomatic women in the COVID-19 group were more likely to have at least one comorbidity, to evolve to preterm labor and infant death, and to have positive SARS-CoV-2 RNA testing in their concepts. Compared to controls, placentas in the COVID-19 group were more likely to show features of maternal and fetal vascular malperfusion. In the COVID-19 group, placentas of symptomatic women were more likely to show CHI. No significant results were found after morphometric analysis.

Conclusion

Pregnant women with symptomatic SARS-CoV-2 infection, particularly with the severe course, are more likely to exhibit an adverse fetal outcome, with slightly more frequent histopathologic findings of maternal and fetal vascular malperfusion, and CHI. The morphometric changes found in the placentas of the COVID-19 group do not seem to be different from those observed in the Control group, as far as maternal age, gestational age, and comorbidities are paired. Only the deposition of villous fibrin could be more accentuated in the COVID-19 group (p = 0.08 borderline). The number of HC/villous evaluated with CD68 immunohistochemistry did not show a difference between both groups.
Isotopic Tracers Suggest Limited Trans-Oceanic Movements and Regional Residency in North Pacific Blue Sharks (Prionace glauca)
Authors: Madigan Daniel J. , Shipley Oliver N. , Carlisle Aaron B. , Dewar Heidi , Snodgrass Owyn E. , Hussey Nigel E.
Published: May 2021

Blue sharks (Prionace glauca) are globally distributed, large-bodied pelagic sharks that make extensive migrations throughout their range. In the North Pacific, mark-recapture studies have showntrans-Pacific migrations, but knowledge gaps in migration frequency hinder understanding of regional connectivity and assessments of regional demography for stock assessments. Here, we use oceanographic gradients of stable isotope ratios (i.e., regional isoscapes) to determine exchange rates of blue sharks between the East and West North Pacific Ocean (EPO and WPO). We generated regional δ13C and δ15N distributions for blue sharks from published values in the North Pacific (n= 180; both sexes, juveniles and adults combined). Discriminant analysis suggested lowtrans-Pacific exchange, categorizing all western (100%) and most eastern (95.3%) blue sharks as resident to their sampling region, with isotopic niche overlap of WPO and EPO highly distinct (0.01–5.6% overlap). Limitedtrans-Pacific movements suggest that other mechanisms maintain genetic mixing of the North Pacific blue shark population. Potential finer scale movement structure was indicated by isotopic differences in sub-regions of the eastern and western Pacific, though application of mixing models are currently limited by aberrantly low blue shark δ13C values across studies. Our results suggest that blue shark population dynamics may be effectively assessed on a regional basis (i.e., WPO and EPO). We recommend further studies to provide size- and sex-specific movement patterns based on empirical isotopic values with large sample sizes from targeted regions. Strategically applied stable isotope approaches can continue to elucidate migration dynamics of mobile marine predators, complementing traditional approaches to fisheries biology and ecology.
Out of the Pacific: A New Alvinellid Worm (Annelida: Terebellida) From the Northern Indian Ocean Hydrothermal Vents
Authors: Han Yuru , Zhang Dongsheng , Wang Chunsheng , Zhou Yadong
Published: May 2021

Alvinellids have long been considered to be endemic to Pacific vents until recent discovery of their presence in the Indian Ocean. Here, a new alvinellid is characterized and formally named from recently discovered vents, Wocan, and Daxi, in the northern Indian Ocean. Both morphological and molecular evidences support its placement in the genusParalvinella, representing the first characterized alvinellid species out of the Pacific. The new species, formally described asParalvinella miran. sp. herein, is morphologically most similar toParalvinella hesslerifrom the northwest Pacific, but the two species differ in three aspects: (1), the first three chaetigers are not fused inP. miran. sp., whereas fused inP. hessleri; (2), paired buccal tentacles short and pointed inP. mirabut large and strongly pointed inP. hessleri; (3), numerous slender oral tentacles ungrouped inP. mirabut two groups inP. hessleri. Phylogenetic inference using the concatenated alignments of the cytochrome c oxidase I (COI), 16S rRNA and 18S rRNA genes strongly supports the clustering ofP. mirawith two West Pacific congeners,P. hessleriand an undescribed species (Paralvinellasp. ZMBN). The resulting Indian/West Pacific lineage suggests a possible invasion into the Indian Ocean from the West Pacific. This is the third polychaete reported from Wocan hydrothermal field. Among the three species, two includingP. miraandHesiolyra heteropoda(Annelida:Hesionidae) are present in high abundance, forming an alvinellids/hesionids-dominated polychaete assemblage distinct from that at all other Central Indian Ridge and Southwest Indian Ridge vents. Thus, this study expands our understanding of alvinellid biogeography beyond the Pacific, and adds to the unique biodiversity of the northern Indian Ocean vents, with implications for biogeographic subdivision across the Indian Ocean ridges.
Impact of Thermohaline Conditions on Vertical Variability of Optical Properties in the Gulf of Finland (Baltic Sea): Implications for Water Quality Remote Sensing
Authors: Aavaste Age , Sipelgas Liis , Uiboupin Rivo , Uudeberg Kristi
Published: May 2021

Vertical variability of inherent optical properties (IOPs) affect the water quality retrievals from remote sensing data. Here, we studied the vertical variability of IOPs and simulated apparent optical properties (AOPs) in the Gulf of Finland (Baltic Sea) under three characteristic (non)stratification conditions. In the case of mixed water column, the vertical variability of optically significant constituents (OSC) and IOPs was relatively small. While in case of stratified water column the IOPs of surface layer were three times higher compared to the IOPs below the thermocline and the IOPs were strongly correlated with the physical parameters (temperature, salinity). Measurements of IOPs in stratified water column showed that the ratio of scattering (b(440)) to absorption (a(440)) changed under the thermocline (b(440)/a(440) < 1) i.e., absorption became the dominant component of attenuation under thermocline while the opposite is true for the upper layer. Simulated (from IOPs) spectral irradiance reflectance (R(λ)) and spectral diffuse attenuation coefficient (Kd(λ)) from deeper layers (below thermocline) have significantly smaller magnitude and smoother shape. This becomes relevant during upwelling events—a common process in the coastal Baltic Sea. We quantified the effect of upwelling on surface water properties using simulated AOPs. The simulated AOPs (from IOPs measurements) showed a decrease of the signal up to 68.8% and an increase of optical depth (z90(λ)) from 2.3 to 4.3 m in the green part of the spectrum in case upwelled water mass reaches the surface. In the coastal waters a vertical decrease of Kd(λ) in the PAR region (400–700 nm) by 6.8% (surface to 20 m depth) was observed, while vertical decrease of chlorophyll-a (Chl-a) and total suspended matter (TSM) was 31.7 and 42.1%, respectively. The ratio R(490)/R(560)≥0.77 indicates also the upwelled water mass. The study showed that upwelling is a process that, in addition to biological activity, horizontal transport of OSC, and temperature changes, alters the optical signal of surface water measured by a remote sensor. Knowledge about the vertical variability of IOPs and AOPs relation to upwelling can help the parametrisation of remote sensing algorithms for retrieving water quality estimates in the coastal regions.
Decreased Low-Density Lipoprotein Cholesterol Level Indicates Poor Prognosis of Severe and Critical COVID-19 Patients: A Retrospective, Single-Center Study
Authors: Zhao Mengmeng , Luo Zhen , He Hua , Shen Bo , Liang Jinjun , Zhang Jishou , Ye Jing , Xu Yao , Wang Zhen , Ye Di , Wang Menglong , Wan Jun
Published: May 2021

Coronavirus disease 2019 (COVID-19) has become a global public health crisis. Reduced low-density lipoprotein cholesterol (LDL-C) levels were observed in COVID-19 patients. The present study aimed to explore the relationship between LDL-C levels and the prognosis of severe and critical COVID-19 patients. A total of 211 severe and critical COVID-19 patients were enrolled and divided into four groups according to the LDL-C levels, including 53 patients in Group A (LDL-C ≥ 2.71 mmol/L), 53 patients in Group B (2.28 ≤ LDL-C < 2.71 mmol/L), 53 patients in Group C (1.83 ≤ LDL-C < 2.28 mmol/L) and 52 patients in Group D (LDL-C < 1.83 mmol/L). LDL-C levels were lower in critically ill patients than in severe patients. The main symptoms before admission, characteristics on admission and comorbidities of enrolled patients did not differ among the four groups. Compared with patients with high LDL-C levels, patients with low LDL-C levels were more likely to have immune and inflammation dysfunction, renal dysfunction, liver dysfunction and cardiac dysfunction on admission. The proportions of patients with shock and acute cardiac injury, of those admitted to intensive care unit (ICU) and of those treated with mechanical ventilation were inversely related to LDL-C level. The mortality of COVID-19 patients increased with LDL-C reduction. Serum LDL-C levels of COVID-19 patients was negatively correlated with CRP level, but positively correlated with lymphocyte count, as shown by Pearson correlation analysis. Proportional hazard models showed that low LDL-C levels were associated with increased risk of hospitalization death, cardiac injury and admission to the ICU. Taken together, these results suggest that decreased LDL-C levels indicate poor prognosis of severe and critical COVID-19 patients.
Impacts of COVID-19 Pandemic on Psychological Well-Being of Older Chronic Kidney Disease Patients
Authors: Chan Alex Siu Wing , Ho Jacqueline Mei Chi , Li Jane Siu Fan , Tam Hon Lon , Tang Patrick Ming Kuen
Published: May 2021

COVID-19 pandemic has been a major global issue, its eventual influences on the population welfare, global markets, public security, and everyday activities remain uncertain. Indeed, the pandemic has arisen a significant global threat. Its psychological impact is predicted to be severe and enduring, but the absolute magnitude is still largely unclear. Chronic kidney disease (CKD) is a complication markedly contributes to the mortality of COVID-19 cases, meanwhile several studies have demonstrated the high frequency and seriousness of the COVID-19 in CKD patients receiving dialysis. Importantly, the influence of COVID-19 among CKD patients without dialysis is still largely unexplored. Thus, we systemically summarized how mental health affects the spreading of COVID-19 to virtually worldwide, covering perspectives from several countries across a wide range of fields and clinical contexts. This review aims to provide the latest details and reveal potential concerns on the public health including psychological well-being of the older patients with CKD.
MicroRNA-1-3p Suppresses Malignant Phenotypes of Ameloblastoma Through Down-Regulating Lysosomal Associated Membrane Protein 2-Mediated Autophagy
Authors: Niu Xing , Huang Biying , Qiao Xue , Liu Jinwen , Chen Lijie , Zhong Ming
Published: May 2021

Objective: Several clinical trials have suggested that autophagy inhibition is a promising approach for cancer therapy. However, the implications of autophagy in ameloblastoma (AB) remain undiscovered. This study investigated the dysregulated autophagy and its regulatory mechanisms in AB.

Methods: The expression and distribution of autophagy-related proteins including B-cell lymphoma-2-interacting protein-1 (Beclin1), microtubule-associated protein 1 light chain 3 (LC3) II/I and lysosomal associated membrane protein 2 (LAMP2) were detected in AB and normal oral mucosa (NOM) tissues by immunohistochemistry and western blot analyses. Under transmission electron microscopy, the autophagy of AB was observed. LAMP2 was a potential target mRNA of miR-1-3p. Quantitative Real-time PCR (qRT-PCR) analysis was utilized for examining LAMP2 and miR-1-3p in AB tissues as well as AM-1 cells. The correlation between LAMP2 and miR-1-3p was analyzed in AB. After transfection with miR-1-3p mimic or inhibitor, LAMP2 expression, proliferation, migration, and invasion were separately detected in AM-1 cells. Rescue assays were finally presented.

Results: Our results showed that Beclin1 was lowly expressed as well as LC3II/I and LAMP2 were highly expressed in AB. Autophagosomes were observed in AB. MiR-1-3p was lowly expressed in AB, which exhibited negative correlations to LAMP2 expression. MiR-1-3p up-regulation significantly lowered LAMP2 expression in AM-1 cells. Furthermore, miR-1-3p overexpression restrained proliferative, migrated, and invasive capacities of AM-1 cells, which were ameliorated by LAMP2 overexpression.

Conclusion: Our findings demonstrated that miR-1-3p suppressed malignant phenotypes of AB through down-regulating LAMP2-mediated autophagy, which could become an underlying target for AB therapy.
Synovial Fibrosis Involvement in Osteoarthritis
Authors: Zhang Li , Xing Runlin , Huang Zhengquan , Ding Liang , Zhang Li , Li Mingchao , Li Xiaochen , Wang Peimin , Mao Jun
Published: May 2021

Bone changes have always been the focus of research on osteoarthritis, but the number of studies on synovitis has increased only over the last 10 years. Our current understanding is that the mechanism of osteoarthritis involves all the tissues that make up the joints, including nerve sprouting, pannus formation, and extracellular matrix environmental changes in the synovium. These factors together determine synovial fibrosis and may be closely associated with the clinical symptoms of pain, hyperalgesia, and stiffness in osteoarthritis. In this review, we summarize the consensus of clinical work, the potential pathological mechanisms, the possible therapeutic targets, and the available therapeutic strategies for synovial fibrosis in osteoarthritis to gain insight and provide a foundation for further study.
Appraisals of the Bangladeshi Medicinal Plant Calotropis gigantea Used by Folk Medicine Practitioners in the Management of COVID-19: A Biochemical and Computational Approach
Authors: Dutta Mycal , Nezam Mohammad , Chowdhury Subrata , Rakib Ahmed , Paul Arkajyoti , Sami Saad Ahmed , Uddin Md. Zia , Rana Md. Sohel , Hossain Shahadat , Effendi Yunus , Idroes Rinaldi , Tallei Trina , Alqahtani Ali M. , Emran Talha Bin
Published: May 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognized in Wuhan in late 2019 and, since then, had spread globally, eventually culminating in the ongoing pandemic. As there is a lack of targeted therapeutics, there is certain opportunity for the scientific community to develop new drugs or vaccines against COVID-19 and so many synthetic bioactive compounds are undergoing clinical trials. In most of the countries, due to the broad therapeutic spectrum and minimal side effects, medicinal plants have been used widely throughout history as traditional healing remedy. Because of the unavailability of synthetic bioactive antiviral drugs, hence all possible efforts have been focused on the search for new drugs and alternative medicines from different herbal formulations. In recent times, it has been assured that the Mpro, also called 3CLpro, is the SARS-CoV-2 main protease enzyme responsible for viral reproduction and thereby impeding the host’s immune response. As such, Mpro represents a highly specified target for drugs capable of inhibitory action against coronavirus disease 2019 (COVID-19). As there continue to be no clear options for the treatment of COVID-19, the identification of potential candidates has become a necessity. The present investigation focuses on the in silico pharmacological activity of Calotropis gigantea, a large shrub, as a potential option for COVID-19 Mpro inhibition and includes an ADME/T profile analysis of that ligand. For this study, with the help of gas chromatography–mass spectrometry analysis of C. gigantea methanolic leaf extract, a total of 30 bioactive compounds were selected. Our analyses unveiled the top four options that might turn out to be prospective anti–SARS-CoV-2 lead molecules; these warrant further exploration as well as possible application in processes of drug development to combat COVID-19.
Spoken Digit Classification by In-Materio Reservoir Computing With Neuromorphic Atomic Switch Networks
Authors: Lilak Sam , Woods Walt , Scharnhorst Kelsey , Dunham Christopher , Teuscher Christof , Stieg Adam Z. , Gimzewski James K.
Published: May 2021

Atomic Switch Networks comprising silver iodide (AgI) junctions, a material previously unexplored as functional memristive elements within highly interconnected nanowire networks, were employed as a neuromorphic substrate for physical Reservoir Computing This new class of ASN-based devices has been physically characterized and utilized to classify spoken digit audio data, demonstrating the utility of substrate-based device architectures where intrinsic material properties can be exploited to perform computation in-materio. This work demonstrates high accuracy in the classification of temporally analyzed Free-Spoken Digit Data These results expand upon the class of viable memristive materials available for the production of functional nanowire networks and bolster the utility of ASN-based devices as unique hardware platforms for neuromorphic computing applications involving memory, adaptation and learning.
Detrimental Effects of Restricted Cage Size on Reproductive Performance, Exploration Ability, and Anxiety but Not Working Memory of Kunming Mice
Authors: An Wenzhen , Zhang Ying , Zhou Aibao , Hu Yuzheng
Published: May 2021

A suboptimal housing environment such as small cage size can adversely influence many aspects of the biology of laboratory animals including their response in behavioral tests. However, the effect of cage size on the mental and physical conditions of Kunming mice, which have been widely used to develop models of depression, anxiety, and many other diseases in China, are still far from clear. The purpose of this study was to investigate the effects of cage size on reproductive ability, exploratory behavior, anxiety, and working memory of Kunming mice. Two cage sizes were used, including a standard cage (20 × 30 × 25 cm3) and a restricted cage (10 × 20 × 25 cm3). The results revealed that compared with mice in the standard cages, mice in the restricted cages showed: (I) a decreased delivery rate of dams (P < 0.05) and a lower survival rate of offspring (P < 0.05), specifically in females (P < 0.05); (II) a decreased exploratory behavior (P < 0.01) and an increased anxiety level (P < 0.01); and (III) higher working memory in the T-maze test (P < 0.05). These results indicated that a restricted cage size has detrimental effects on the reproductive ability and anxiety level, but its effect on cognitive ability is complex and warrants further study. In short, these results provide empirical evidence for better practices in caring for Kunming mice, with some cautions about the effects of cage size on behavioral tests.
Cholinergic-Induced Specific Oscillations in the Medial Prefrontal Cortex to Reverse Propofol Anesthesia
Authors: Wang Lieju , Zhang Weijie , Wu Ying , Gao Yibo , Sun Na , Ding Hao , Ren Jinxuan , Yu Lina , Wang Liangliang , Yang Fen , Xi Wang , Yan Min
Published: May 2021

General anesthesia is a drug-induced reversible state comprised of altered states of consciousness, amnesia, analgesia, and immobility. The medial frontal cortex (mPFC) has been discovered to modulate the level of consciousness through cholinergic and glutamatergic pathways. The optogenetic tools combined with in vivo electrophysiological recording were used to study the neural oscillatory modulation mechanisms in mPFC underlying the loss of consciousness (LOC) and emergence. We found that optogenetic activation of both cholinergic and glutamatergic neurons in the basal forebrain (BF) reversed the hypnotic effect of propofol and accelerated the emergence from propofol-induced unconsciousness. The cholinergic light-activation during propofol anesthesia increased the power in the β (12–20 Hz) and low γ (20–30 Hz) bands. Conversely, glutamatergic activation increased the power at less specific broad (1–150 Hz) bands. The cholinergic-induced alteration to specific power bands after LOC had opposite effects to that of propofol. These results suggested that the cholinergic system might act on more specific cortical neural circuits related to propofol anesthesia.
Effects of Dietary Yucca Schidigera Extract and Oral Candida utilis on Growth Performance and Intestinal Health of Weaned Piglets
Authors: Yang Zhenguo , Wang Yao , He Tianle , Ziema Bumbie Gifty , Wu Liuting , Sun Zhihong , Sun Weizhong , Tang Zhiru
Published: May 2021

Weaning piglets experienced the transformation from breast milk to solid feed and present the proliferation of pathogens, the presence of diarrhea, poor growth performance and even death. Plant extracts and probiotics have certain potential in improving animal growth performance, antioxidant capacity and immune function. The purpose of this study was to explore the effects of dietary yucca schidigera extract (YSE) and oral Candida utilis (CU) on growth performance and intestinal health weaned piglets. According to a 2 × 2 factorial design with the main factors being CU (orally administered 1 mL of 0.85% saline with or without CU; fed basal diet with or without 120 mg/kg YSE), forty 28 d healthy weaned piglets were randomly allocated into four groups of 10 barrows each: (1) piglets fed basal diet and orally administered 1 mL of 0.85% saline (CON); (2) piglets fed basal diet and orally administered 1 mL 1 × 109 cfu/mL C. utilis in 0.85% saline (CU); (3) piglets fed the basal diet containing YSE (120 mg/kg) and orally administered 1 mL of 0.85% saline (YSE); (4) Piglets fed the basal diet containing 120 mg/kg YSE and 1 mL 1 × 109 cfu/mL C. utilis in 0.85% saline (YSE+CU). This study lasted 28 days and evaluated the effects of dietary YSE and oral CU on growth performance, immunity, antioxidant function, ileal morphology, and intestinal microflora in weaned piglets. Dietary YSE increased ADG, the spleen and lymph node indexes, serum GLU, BUN, T-SOD, T-AOC, CAT concentrations, ileal villus height and villus height/crypt depth, jejunal occludin, and β-definsin-2 concentrations and ileal occludin concentration in weaned piglets (P < 0.05); decreased the diarrhea rate and mortality, rectal pH and urine pH, the BUN and MDA concentrations, crypt depth (P < 0.05); improved the diversity of cecal microflora. Orally CU increased ADG, and ADFI, the T-SOD, T-AOC, and CAT activity, ileal villus height, villus height/crypt depth, jejunum occludin, and β-definsin-2 concentrations (P < 0.05); reduced the diarrhea rate and mortality, urine pH, the BUN and MDA concentrations, crypt depth (P < 0.05); improved the diversity of cecal microflora. Dietary YSE and orally CU increased the T-SOD, T-AOC, and CAT activity, villus height/crypt depth, jejunal occludin concentration; reduced the diarrhea rate of weaned piglets by 28%, gastric pH, ileal pH, cecal pH and urine pH, MDA, crypt depth; improved the diversity of cecal microflora. YSE and CU could improve the growth performance, reduce the diarrhea rate, improve intestinal health, and increase the diversity and abundance of cecal microflora in weaned piglets and expected to be used as antibiotics alternative feed additives in the production of weaned piglets.
Comparison of Different Machine Models Based on Contrast-Enhanced Computed Tomography Radiomic Features to Differentiate High From Low Grade Clear Cell Renal Cell Carcinomas
Authors: Pei Xu , Wang Ping , Ren Jia-Liang , Yin Xiao-Ping , Ma Lu-Yao , Wang Yun , Ma Xi , Gao Bu-Lang
Published: May 2021

Purpose

This study was to investigate the role of different radiomics models with enhanced computed tomography (CT) scan in differentiating low from high grade renal clear cell carcinomas.

Materials and Methods

CT data of 190 cases with pathologically confirmed renal cell carcinomas were collected and divided into the training set and testing set according to different time periods, with 122 cases in the training set and 68 cases in the testing set. The region of interest (ROI) was delineated layer by layer.

Results

A total of 402 radiomics features were extracted for analysis. Six of the radiomic parameters were deemed very valuable by univariate analysis, rank sum test, LASSO cross validation and correlation analysis. From these six features, multivariate logistic regression model, support vector machine (SVM), and decision tree model were established for analysis. The performance of each model was evaluated by AUC value on the ROC curve and decision curve analysis (DCA). Among the three prediction models, the SVM model showed a high predictive efficiency. The AUC values of the training set and the testing set were 0.84 and 0.83, respectively, which were significantly higher than those of the decision tree model and the multivariate logistic regression model. The DCA revealed a better predictive performance in the SVM model that possessed the highest degree of coincidence.

Conclusion

Radiomics analysis using the SVM radiomics model has highly efficiency in discriminating high- and low-grade clear cell renal cell carcinomas.
Precision Breast-Conserving Surgery With Microwave Ablation Guidance: A Pilot Single-Center, Prospective Cohort Study
Authors: Pan Hong , Qian Mengjia , Chen Hao , Wang Hui , Yu Muxin , Zhang Kai , Wang Siqi , Deng Jing , Xu Yi , Ling Lijun , Ding Qiang , Xie Hui , Wang Shui , Zhou Wenbin
Published: May 2021

Introduction

Negative margins in breast-conserving surgery (BCS) are essential for preventing recurrence. The aim of this study was to determine the use of preoperative microwave ablation (MWA) in the guidance of BCS for early-stage breast cancer and access whether MWA could influence the rates of positive resection margins.

Methods

From 2016 to 2018, 22 women with T1/T2 invasive breast cancer were enrolled for MWA prospectively in the guidance of BCS. US-guided MWA was performed under local anesthesia, followed by BCS and sentinel lymph node biopsy (SLNB) one week after ablation. Women who underwent palpation-guided BCS directly were included as control, and propensity score matching analysis was applied.

Results

MWA was performed in 22 patients. Of the 21 MWA cases with effect information, the mean tumor size in US was 20.9 ± 6.2 mm (6-37 mm). Compared with control group (BCS directly), a lower rate of positive/close margins was observed in MWA guidance group (P = 0.018), and MWA caused a higher rate of accurate surgery (the largest margin ≤ 3 cm and the smallest margin ≥ 1mm, P = 0.042). Of these 21 patients treated with MWA, 18 were candidates for SLNB. And sentinel lymph nodes were successfully identified in all cases, and no recurrence was found with a mean follow-up of 23 months.

Conclusion

For patients with T1/T2 breast cancer, the application of preoperative MWA could guide BCS accurately without impairing SLNB. Clinical trials with long-term results are required to validate MWA in the guidance for breast cancer excision.
Immunotherapy in the Treatment of Urothelial Bladder Cancer: Insights From Single-Cell Analysis
Authors: Zang Jingyu , Ye Kaiyan , Fei Yang , Zhang Ruiyun , Chen Haige , Zhuang Guanglei
Published: May 2021

Urothelial bladder cancer (UBC) is a global challenge of public health with limited therapeutic options. Although the emergence of cancer immunotherapy, most notably immune checkpoint inhibitors, represents a major breakthrough in the past decade, many patients still suffer from unsatisfactory clinical outcome. A thorough understanding of the fundamental cellular and molecular mechanisms responsible for antitumor immunity may lead to optimized treatment guidelines and new immunotherapeutic strategies. With technological developments and protocol refinements, single-cell approaches have become powerful tools that provide unprecedented insights into the kaleidoscopic tumor microenvironment and intricate cell-cell communications. In this review, we summarize recent applications of single-cell analysis in characterizing the UBC multicellular ecosystem, and discuss how to leverage the high-resolution information for more effective immune-based therapies.
Management of Ineffective Esophageal Hypomotility
Authors: Jandee Sawangpong , Geeraerts Annelies , Geysen Hannelore , Rommel Nathalie , Tack Jan , Vanuytsel Tim
Published: May 2021

Esophageal hypomotility in general and especially ineffective esophageal motility according to the Chicago criteria of primary motility disorders of the esophagus, is one of the most frequently diagnosed motility disorders on high resolution manometry and results in a large number of patients visiting gastroenterologists. Most patients with esophageal hypomotility present with gastroesophageal reflux symptoms or dysphagia. The clinical relevance of the motility pattern, however, is not well established but seems to be correlated with disease severity in reflux patients. The correlation with dysphagia is less clear. Prokinetic agents are commonly prescribed as first line pharmacologic intervention to target esophageal smooth muscle contractility and improve esophageal motor functions. However, the beneficial effects of these medications are limited and only confined to some specific drugs. Serotonergic agents, including buspirone, mosapride and prucalopride have been shown to improve parameters of esophageal motility although the effect on symptoms is less clear. Understanding on the complex correlation between esophageal hypomotility and esophageal symptoms as well as the limited evidence of prokinetic agents is necessary for physicians to appropriately manage patients with Ineffective Esophageal Motility (IEM).
The Therapeutic Effect of Traditional Chinese Medicine on Inflammatory Diseases Caused by Virus, Especially on Those Caused by COVID-19
Authors: Li Peng , Hu Shuang , Qian Cheng , Yao Yan , Li Liang-yun , Yang Jun-fa , Yang Li , Yang Chen-chen , Zhou Hong , Wang Shu-xian , Hu Ying , Zhu Xing-yu , Zhou Jing , Pan Lin-xin , Shen Chuan-pu , Zhou Huan
Published: May 2021

Inflammasomes are large multimolecular complexes best recognized because of their ability to control activation of caspase-1, which in turn regulates the maturation of interleukin-18 (IL-18) and interleukin-1 β (IL-1β). IL-1β was originally identified as a pro-inflammatory cytokine, capable of inducing local and systemic inflammation as well as a fever response reaction in response to infection or injury. Excessive production of IL-1β is related to inflammatory and autoimmune diseases. Both coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome (SARS) are characterized by excessive inflammatory response. For SARS, there is no correlation between viral load and worsening symptoms. However, there is no specific medicine which is available to treat the disease. As an important part of medical practice, TCM showed an obvious therapeutic effect in SARS-CoV-infected patients. In this article, we summarize the current applications of TCM in the treatment of COVID-19 patients. Herein, we also offer an insight into the underlying mechanisms of the therapeutic effects of TCM, as well as introduce new naturally occurring compounds with anti-coronavirus activity, in order to provide a new and potential drug development strategy for the treatment of COVID-19.
Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer
Authors: Sun Dan , Li Ying-Chun , Zhang Xiao-Yu
Published: May 2021

Ovarian and breast cancer are prevalent female malignancies with increasing occurrence incidence and metastasis, significantly affecting the health and life quality of women globally. Anesthetic lidocaine has presented anti-tumor activities in the experimental conditions. However, the effect of lidocaine on ovarian and breast cancer remains elusive. We identified the important function of lidocaine in enhancing ferroptosis and repressing progression of ovarian and breast cancer. Our data showed that lidocaine further repressed erastin-inhibited ovarian and breast cancer cell viabilities. The treatment of lidocaine induced accumulation of Fe2+, iron and lipid reactive oxygen species (ROS) in ovarian and breast cancer cells. The ovarian and breast cancer cell proliferation was suppressed while cell apoptosis was induced by lidocaine in vitro. Lidocaine attenuated invasion and migration of ovarian and breast cancer cells as well. Regarding the mechanism, we found that lidocaine downregulated solute carrier family 7 member 11 (SLC7A11) expression by enhancing microRNA-382-5p (miR-382-5p) in the cells. The inhibition of miR-382-5p blocked lidocaine-induced ferroptosis of ovarian and breast cancer cells. MiR-382-5p/SLC7A11 axis was involved in lidocaine-mediated inhibition of ovarian and breast cancer cell proliferation in vitro. The miR-382-5p expression was down-regulated but SLC7A11 expression was up-regulated in clinical ovarian and breast cancer samples. Furthermore, the treatment of lidocaine repressed tumor growth of ovarian cancer cells in vivo, in which the miR-382-5p expression was increased while SLC7A11 expression was decreased. Consequently, we concluded that the lidocaine promoted ferroptosis by miR-382-5p/SLC7A11 axis in ovarian and breast cancer cells. The clinical value of lidocaine in the treatment of ovarian and breast cancer deserves to be proved in detail.
Nanoparticles: A Hope for the Treatment of Inflammation in CNS
Authors: Zhu Feng-Dan , Hu Yu-Jiao , Yu Lu , Zhou Xiao-Gang , Wu Jian-Ming , Tang Yong , Qin Da-Lian , Fan Qing-Ze , Wu An-Guo
Published: May 2021

Neuroinflammation, an inflammatory response within the central nervous system (CNS), is a main hallmark of common neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), among others. The over-activated microglia release pro-inflammatory cytokines, which induces neuronal death and accelerates neurodegeneration. Therefore, inhibition of microglia over-activation and microglia-mediated neuroinflammation has been a promising strategy for the treatment of neurodegenerative diseases. Many drugs have shown promising therapeutic effects on microglia and inflammation. However, the blood–brain barrier (BBB)—a natural barrier preventing brain tissue from contact with harmful plasma components—seriously hinders drug delivery to the microglial cells in CNS. As an emerging useful therapeutic tool in CNS-related diseases, nanoparticles (NPs) have been widely applied in biomedical fields for use in diagnosis, biosensing and drug delivery. Recently, many NPs have been reported to be useful vehicles for anti-inflammatory drugs across the BBB to inhibit the over-activation of microglia and neuroinflammation. Therefore, NPs with good biodegradability and biocompatibility have the potential to be developed as an effective and minimally invasive carrier to help other drugs cross the BBB or as a therapeutic agent for the treatment of neuroinflammation-mediated neurodegenerative diseases. In this review, we summarized various nanoparticles applied in CNS, and their mechanisms and effects in the modulation of inflammation responses in neurodegenerative diseases, providing insights and suggestions for the use of NPs in the treatment of neuroinflammation-related neurodegenerative diseases.
Accuracy of the Radiographic Assessment of Lung Edema Score for the Diagnosis of ARDS
Authors: Zimatore Claudio , Pisani Luigi , Lippolis Valeria , Warren Melissa A. , Calfee Carolyn S. , Ware Lorraine B. , Algera Anna Geke , Smit Marry R. , Grasso Salvatore , Schultz Marcus J.
Published: May 2021

Background: Bilateral opacities on chest radiographs are part of the Berlin Definition for Acute Respiratory Distress Syndrome (ARDS) but have poor interobserver reliability. The “Radiographic Assessment of Lung Edema” (RALE) score was recently proposed for evaluation of the extent and density of alveolar opacities on chest radiographs of ARDS patients. The current study determined the accuracy of the RALE score for the diagnosis and the prognosis of ARDS.

Methods:Post-hoc analysis of a cohort of invasively ventilated intensive care unit (ICU) patients expected to need invasive ventilation for >24 h. The Berlin Definition was used as the gold standard. The RALE score was calculated for the first available chest radiograph after start of ventilation in the ICU. The primary endpoint was the diagnostic accuracy for ARDS of the RALE score. Secondary endpoints included the prognostic value of the RALE score for ICU and hospital mortality, and the association with ARDS severity, and the PaO2/FiO2. Receiver operating characteristic (ROC) curves were constructed, and the optimal cutoff was used to determine sensitivity, specificity and the negative and positive predictive value of the RALE score for ARDS.

Results: The study included 131 patients, of whom 30 had ARDS (11 mild, 15 moderate, and 4 severe ARDS). The first available chest radiograph was obtained median 0 [0 to 1] days after start of invasive ventilation in ICU. Compared to patients without ARDS, a higher RALE score was found in patients with ARDS (24 [interquartile range (IQR) 16–30] vs. 6 [IQR 3–11]; P < 0.001), with RALE scores of 20 [IQR 14–24], 26 [IQR 16–32], and 32 [IQR 19–36] for mild, moderate and severe ARDS, respectively, (P = 0.166). The area under the ROC for ARDS was excellent (0.91 [0.86–0.96]). The best cutoff for ARDS diagnosis was 10 with 100% sensitivity, 71% specificity, 51% positive predictive value and 100% negative predictive value. The RALE score was not associated with ICU or hospital mortality, and weakly correlated with the PaO2/FiO2.

Conclusion: In this cohort of invasively ventilated ICU patients, the RALE score had excellent diagnostic accuracy for ARDS.
Hypoxia and Inflammation: Insights From High-Altitude Physiology
Authors: Pham Kathy , Parikh Keval , Heinrich Erica C.
Published: May 2021

The key regulators of the transcriptional response to hypoxia and inflammation (hypoxia inducible factor, HIF, and nuclear factor-kappa B, NF-κB, respectively) are evolutionarily conserved and share significant crosstalk. Tissues often experience hypoxia and inflammation concurrently at the site of infection or injury due to fluid retention and immune cell recruitment that ultimately reduces the rate of oxygen delivery to tissues. Inflammation can induce activity of HIF-pathway genes, and hypoxia may modulate inflammatory signaling. While it is clear that these molecular pathways function in concert, the physiological consequences of hypoxia-induced inflammation and how hypoxia modulates inflammatory signaling and immune function are not well established. In this review, we summarize known mechanisms of HIF and NF-κB crosstalk and highlight the physiological consequences that can arise from maladaptive hypoxia-induced inflammation. Finally, we discuss what can be learned about adaptive regulation of inflammation under chronic hypoxia by examining adaptive and maladaptive inflammatory phenotypes observed in human populations at high altitude. We aim to provide insight into the time domains of hypoxia-induced inflammation and highlight the importance of hypoxia-induced inflammatory sensitization in immune function, pathologies, and environmental adaptation.