bluuebunny/crossref_metadata_2025 huggingface dataset:
Saúde Mental Materna e Retenção de Peso no Pós-Parto
Authors: Joia Izabel Cristina Oliveira da Silva , Silva Claudia Valeria Cardim da , Brito Flavia dos Santos Barbosa , Hasselmann Maria Helena
Published: April 2022

O objetivo do estudo foi avaliar o impacto da depressão pós-parto (DPP) na retenção de peso até o sexto mês pós-parto. Trata-se de um estudo longitudinal, com 563 mulheres acolhidas nas unidades de saúde do município do Rio de Janeiro, entre 2005 e 2009. Foram coletados peso, estatura, peso retido (15 dias, 1º, 2º, 4º e 6º mês) e peso pré-gestacional referido. A DPP foi avaliada a partir da Escala de Depressão Pós-parto de Edimburgo, aos 15 dias e no 2º mês pós-parto, usando 11/12 como ponto de corte. Considerou-se depressão recorrente quando houve presença de depressão nos dois momentos. Para as análises estatísticas do efeito da DPP sobre a retenção de peso pós-parto empregou-se o procmixed do pacote estatístico SAS. Mais de 30% iniciaram a gravidez com excesso de peso, 18,6% apresentaram depressão aos 15 dias pós-parto e 8,3% apresentaram depressão recorrente. Na análise de DPP recorrente, observa-se que mulheres com depressão recorrente tendem a perder menos peso que as sem depressão. O estudo aponta para a importância do monitoramento da DPP e da condição nutricional, pois mulheres com depressão recorrente apresentaram, potencialmente, maiores chances de desenvolver sobrepeso ou obesidade, ao manifestar uma menor perda de peso.
A tutela penal como fator de educação ambiental na sociedade brasileira
Authors: Ponte Luiz Eduardo de Paula , Dalmas Fabrício Bau , Filho Lair da Silva Loureiro , Bulbovas Patrícia
Published: April 2022

O meio ambiente se constitui como uma ideia fundante vinculada à própria necessidade de sobrevivência da própria humanidade, e assim sendo, se entremostra como uma forma de atuação com especial relevância de qualquer Estado. Por sua vez, o direito penal, como o braço mais intenso e incisivo de que dispõe o Poder Público para a busca da pacificação social, deve servir não somente como mecanismo puramente repressivo, mas também, e no caso ambiental de maneira mais destacada, como fator pedagógico visando a criação de uma consciência geral protetiva do bem jurídico ambiental, auxiliando a educação ambiental. Desse modo, com a junção, quase conflituosa, desses dois ramos do saber (a educação e o direito penal), podemos enxergar a possibilidade social de um movimento, de caráter imprescindível, na consolidação de um sentimento de todos pela tutela do meio ambiente, por meio de comportamentos focados na transversalidade da educação ambiental, e dessa forma atendendo a função ético-social do direito penal.
Counseling of Infectious Diseases Related to Stunting and Its Prevention in Koroncong Village, Keroncong District, Pandeglang Regency, Banten Province
Authors: Mardhiyah Dian , Widiyanti Dini , Maulidya Sari Siti , Ernawati Kholis , Susilowati R.W
Published: April 2022

Infectious disease is one of the direct causes of nutritional status problems in children age 0-59 months. Stunting is a chronic malnutrition problem that has received attention recently. The Koroncong village area had a total of 63 children age 0-24 months, with the incidence of stunting as many as 19 children (32%) in September 2019. Koroncong village was one of 10 locus stunting villages in Pandeglang. The purpose of this study was to increase the knowledge of mothers with children age 0-24 months about infectious diseases that contribute to disrupt child development and prevention, training cadres on how to anthropometric measurement children age 0-24 months to detect stunting. The method used One Groups Pretest-Posttest Design with counseling for mothers with children age 0-24 months and training of cadres and using total sampling for 63 mothers with children aged 0-24 months and 14 cadres. The results of research before and after counseling showed an increase in the knowledge of 50 respondents who attended, seen from the pretest and posttest mean value of 24.50 and also found p-value 0.000 with the Wilcoxon test. There was an increase in the cadres' ability to use early detection stunting mats (p-value 0,000) with the paired T test. The activities carried out are expected to increase knowledge and change the attitudes of mothers with children aged 0-24 months against infectious diseases related to stunting and their prevention, as well as improve cadres' skills in detecting stunting in children so that a healthy generation is created.
NUTRITION STATUS IN LOW NUTRITION CHILDREN AFTER NUTRITIONAL INTERVENTION IN COVID 19 PANDEMIC
Authors:   Student of Faculty of Medicine, Christian Indonesia University Indonesia, Henita Yolanda
Published: April 2022

Based on the results of the PSG (Nutritional Status Monitoring) in 2017, globally, the prevalence of malnourished children under five was 17.8%, especially in West Java Province, 7.4% of under-five malnutrition 210,155 people. Along with these problems, the government created a PMT (Supplementary Food) program to address nutritional problems in Indonesia. For this reason, this study aims to determine the relationship of supplementary feeding to the improvement of nutritional status of malnourished children under five at Posyandu Anyelir, Pancoranmas District, Depok, with a cross-sectional research design. The data were collected using a questionnaire tested for validity and reliability and carried out anthropometric measurements for toddlers from 0 to 60 months. The result was that 22 out of 33 children (66.7%) experienced malnutrition. There was a significant, significant, strong, unidirectional relationship between changes in nutritional status before and after supplementary feeding (p = 0.004)
ANTIBACTERIAL ACTIVITY OF ETHANOLIC EXTRACT OF KITOLOD (Hippobroma longiflora) LEAVES AGAINST STREPTOCOCCUS PYOGENES
Authors:   Student of Faculty of Medicine, Widya Mandala Surabaya Catholic University. Indonesia, Tanaja Grace Isabella , Isbandiati Endang ,   Department of Pharmacology, Faculty of Medicine, Widya Mandala Surabaya Catholic University Indonesia, Wattimena Inge ,   Department of Public Health Sciences, Faculty of Medicine, Widya Mandala Surabaya Catholic University Indonesia
Published: April 2022

Background: Antimicrobial resistance to antibiotics has been emerging as a serious issue in healthcare, hence the need to discover and develop new treatment alternatives. Chemical compunds found in medicinal plants can potentially be used to synthesize new antibiotic agents, one of which is the leaves of kitolod (Hippobroma longiflora). Phytochemical screening of kitolod leaves showed positive results for secondary metabolites presumed to have antibacterial effects. Objectives: The purpose of this study was to examine the antibacterial activity of ethanolic extract of kitolod leaves against Streptococcus pyogenes. Methods: Antibacterial activity of the ethanolic extract of various concentrations (0,25%, 1,75%, 3,25%, 4,75%, 6,25%) were evaluated by broth microdilution method on a 96-well microplate and by streaking on agar plates. Results: Minimium Bactericidal Concentration (MBC) of ethanolic extract of kitolod leaves against Streptococcus pyogenes was 1,75%. Minimum Inhibitory Concentration (MIC) of ethanolic extract of kitolod leaves against Streptococcus pyogenes could not be inferred. Conclusion: Ethanolic extract of kitolod leaves showed antibacterial activities against Streptococcus pyogenes.
Seven-year impact of white-nose syndrome on tri-colored bat (Perimyotis subflavus) populations in Georgia, USA
Authors: Perea S , Yearout JA , Ferrall EA , Morris KM , Pynne JT , Castleberry SB
Published: April 2022

White-nose syndrome (WNS) has emerged as the most serious threat to North American cave-dwelling bat species, with an estimated mortality of over 6 million since it was first documented in the USA in 2006. Tri-colored bat Perimyotis subflavus is one of the species most affected, with hibernaculum counts at caves in WNS-positive regions reduced by >90% from previous counts. While declines have been documented in hibernaculum surveys, long-term monitoring programs during active seasons provide a unique opportunity to examine population trends and impact of population declines post-WNS. We developed generalized linear mixed models using data from a state-wide, long-term (2011-2020) mobile bat acoustic monitoring program in Georgia, USA, to better understand P. subflavus population trends before and after disease detection and between WNS-negative and WNS-positive regions. We recorded 5046 P. subflavus passes across all acoustic routes during the 10 yr time period. We detected a significant decrease in activity 2 yr after disease detection in the WNS-positive region, whereas activity in the WNS-negative region remained stable over time. Understanding changes in bat populations as WNS spreads and measuring the magnitude of population declines to assess disease impacts is crucial for providing appropriate guidance for management. Our results provide evidence of the critical status of P. subflavus in the southernmost WNS-positive region, but also emphasize the importance of monitoring WNS spread to new regions, as those that remain WNS-free could provide refugia for the species and a potential source of recolonization to WNS-affected areas.
Job Talk: Candidate Sex and Presentation of Prior Experience in Televised Ads
Authors: Hansen Eric , Mautner Connor
Published: April 2022

Why do some candidates advertise their pre-office experience to voters while others do not? We ask whether the sex of the candidate makes a difference. Women often gain more qualifications than men before running for office. Female candidates have incentives to message those qualifications to voters to compensate for gendered expectations of prior experience. For evidence, we analyze the contents of 1044 televised advertisements from 2018 state legislative candidates from the Wesleyan Media Project. We find that women are no more likely than men to highlight their professional backgrounds in TV ads. However, we find that male candidates are significantly more likely to highlight prior political experience. The relationship is moderated by incumbency status, such that male challengers advertise their political experience more than female challengers. The results raise fresh questions about gender differences in campaign communication and voters’ expectations of male and female candidates.
The Role of State & National Institutional Evaluations in Fostering Collective Accountability Across the U.S. States
Authors: Algara Carlos , Specht Alexander
Published: April 2022

Theories of collective accountability in American elections center on the ability of voters to hold legislators accountable for the job performance of the president and their party in Congress. While this work finds that presidential and congressional approval finds that legislators pay an electoral penalty for low institutional approval ratings under their party’s control, little is none whether this form of collective accountability translates to the state legislative context. We argue that collective accountability in state legislative elections follows a two-tiered approach, with state legislators being held accountable for national and state policymaking institutions. Using new state-level measures of institutional approval for national and state institutions, along with voter-level data from the 2007-2020 Cooperative Election Study, we find that presidential approval is the principal growing motivator of state legislative partisan choice with other policymaking institutions playing a minimal role, at best. These findings suggest nationalization also shapes state-centric legislative elections.
NANOPARTICLE FOR SUSTAIN RELEASE OF ACYCLOVIR INVITRO AND INVIVO DRUG COMPARTMENT MODELLING
Authors:   Masters In Pharmaceutical Science From University Of Rajiv Gandhi Proudyogiki Vishwavidyalaya Bhopal (MP), India, KUSHWAH MAHENDRA SINGH
Published: April 2022

The main objective of this study was to organize the In-Vitro and In-Vivo correlation of immediate release Acyclovir tablets of 800 mg. In vitro and in vivo studies are done on the test product as Acyclovir Tablet USP 800 mg (containing Acyclovir 800 mg) of Cadila Medicinals Ltd., India versus Zovirax Tablet 800 mg (containing Acyclovir 800 mg) of GlaxoSmithKline, USA. In vivo studies are done in 36 healthy, adult, mortal subjects under fasting conditions. In vitro dissolution study was done using USP outfit II at 50 rpm in0.1 N HCL for 45 twinkles. The in vitro – in vivo interdependence of Acyclovir shows an R- squared value of0.9794 in the excel worksheet, which depicts a successful correlation between in vitro and in vivo characteristics of the medicine. In addition, PE AUC and PE Cmax were planted to be –4.604 and-11.19 independently for each expression. The present study shows a good correlation between in vivo and in vitro PK biographies of the expression used as the test medicine in the study. (12)
3D Bioprinting for Spinal Cord Injury Repair
Authors: Yuan Tian-Yang , Zhang Jun , Yu Tong , Wu Jiu-Ping , Liu Qin-Yi
Published: April 2022

Spinal cord injury (SCI) is considered to be one of the most challenging central nervous system injuries. The poor regeneration of nerve cells and the formation of scar tissue after injury make it difficult to recover the function of the nervous system. With the development of tissue engineering, three-dimensional (3D) bioprinting has attracted extensive attention because it can accurately print complex structures. At the same time, the technology of blending and printing cells and related cytokines has gradually been matured. Using this technology, complex biological scaffolds with accurate cell localization can be manufactured. Therefore, this technology has a certain potential in the repair of the nervous system, especially the spinal cord. So far, this review focuses on the progress of tissue engineering of the spinal cord, landmark 3D bioprinting methods, and landmark 3D bioprinting applications of the spinal cord in recent years.
Long Non-Coding RNAs in the Pathogenesis of Diabetic Kidney Disease
Authors: Hu Mengsi , Ma Qiqi , Liu Bing , Wang Qianhui , Zhang Tingwei , Huang Tongtong , Lv Zhimei
Published: April 2022

Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes mellitus, with relatively high morbidity and mortality globally but still in short therapeutic options. Over the decades, a large body of data has demonstrated that oxidative stress, inflammatory responses, and hemodynamic disorders might exert critical influence in the initiation and development of DKD, whereas the delicate pathogenesis of DKD remains profoundly elusive. Recently, long non-coding RNAs (lncRNAs), extensively studied in the field of cancer, are attracting increasing attentions on the development of diabetes mellitus and its complications including DKD, diabetic retinopathy, and diabetic cardiomyopathy. In this review, we chiefly focused on abnormal expression and function of lncRNAs in major resident cells (mesangial cell, endothelial cell, podocyte, and tubular epithelial cell) in the kidney, summarized the critical roles of lncRNAs in the pathogenesis of DKD, and elaborated their potential therapeutic significance, in order to advance our knowledge in this field, which might help in future research and clinical treatment for the disease.
Pedal to the Metal: Nuclear Splicing Bodies Turbo-Charge VSG mRNA Production in African Trypanosomes
Authors: Budzak James , Rudenko Gloria
Published: April 2022

The African trypanosome Trypanosoma brucei is a parasite of the mammalian bloodstream and tissues, where an antigenically variable Variant Surface Glycoprotein (VSG) coat protects it from immune attack. This dense layer comprised of ∼107 VSG proteins, makes VSG by far the most abundant mRNA (7–10% total) and protein (∼10% total) in the bloodstream form trypanosome. How can such prodigious amounts of VSG be produced from a single VSG gene? Extremely high levels of RNA polymerase I (Pol I) transcription of the active VSG provide part of the explanation. However, recent discoveries highlight the role of pre-mRNA processing, both in maintaining high levels of VSG transcription, as well as its monoallelic expression. Trypanosome mRNAs are matured through trans-splicing a spliced leader (SL) RNA to the 5’ end of precursor transcripts, meaning abundant SL RNA is required throughout the nucleus. However, requirement for SL RNA in the vicinity of the active VSG gene is so intense, that the cell reconfigures its chromatin architecture to facilitate interaction between the SL RNA genes and the active VSG. This presumably ensures that sufficient localised SL RNA is available, and not limiting for VSG mRNA expression. Recently, novel nuclear splicing bodies which appear to provide essential trans-splicing components, have been identified associating with the active VSG. These observations highlight the underappreciated role of pre-mRNA processing in modulating gene expression in trypanosomes. Dissecting the function of these nuclear RNA processing bodies should help us elucidate the mechanisms of both VSG expression and monoallelic exclusion in T. brucei.
Phthalimide Analogs Enhance Genotoxicity of Cyclophosphamide and Inhibit Its Associated Hypoxia
Authors: Gamal-Eldeen Amira M. , Agwa Hussein S. , Zahran Magdy A.-H. , Raafat Bassem M. , El-Daly Sherien M. , Banjer Hamsa J. , Almehmadi Mazen M. , Alharthi Afaf , Hawsawi Nahed M. , Althobaiti Fayez , Abo-Zeid Mona A. M.
Published: April 2022

Cyclophosphamide (CP) is a mutagen that is used in cancer chemotherapy, due to its genotoxicity and as an immunosuppressive agent. Thalidomide (TH) is another cancer chemotherapeutic drug. In this study, the cytogenotoxicity and hypoxia modulatory activities of two phthalimide analogs of TH have been evaluated with/without CP. Both analogs have increased CP-stimulated chromosomal aberrations than those induced by TH, including gaps, breaks/fragments, deletions, multiple aberrations, and tetraploidy. The analogs have elevated the cytotoxic effect of CP by inhibiting the mitotic activity, in which analog 2 showed higher mitosis inhibition. CP has induced binucleated and polynucleated bone marrow cells (BMCs), while micronuclei (MN) are absent. TH and analogs have elevated the CP-stimulated binucleated BMCs, while only analogs have increased the CP-induced polynucleated BMCs and inhibited the mononucleated BMCs. MN-BMCs were shown together with mononucleated, binucleated, and polynucleated cells in the CP group. Both analogs have elevated mononucleated and polynucleated MN-BMCs, whereas in presence of CP, TH and analogs have enhanced mononucleated and binucleated MN-BMCs. The analogs significantly induce DNA fragmentation in a comet assay, where analog 1 is the strongest inducer. The treatment of mice with CP has resulted in a high hypoxia status as indicated by high pimonidazole adducts and high HIF-1α and HIF-2α concentrations in lymphocytes. Analogs/CP-treated mice showed low pimonidazole adducts. Both analogs have inhibited HIF-1α concentration but not HIF-2α. Taken together, the study findings suggest that both analogs have a higher potential to induce CP-genotoxicity than TH and that both analogs inhibit CP-hypoxia via the HIF-1α-dependent mechanism, in which analog 1 is a more potent anti-hypoxic agent than analog 2. Analog 1 is suggested as an adjacent CP-complementary agent to induce CP-genotoxicity and to inhibit CP-associated hypoxia.
Standards for Collection, Preservation, and Transportation of Fecal Samples in TCM Clinical Trials
Authors: Su Wenquan , Du Yawei , Lian Fengmei , Wu Hui , Zhang Xinrong , Yang Wenli , Duan Yunfeng , Pan Yuanming , Liu Weijng , Wu Aiming , Zhao Bowen , Wu Chongming , Wu Shengxian
Published: April 2022

Background

Unlike chemical drugs with a single or a few kinds of active compounds, traditional Chinese medicines (TCMs)uses herbal formulas composed of numerous kinds of chemical constituents. Therefore, TCM clinical trials require unique and stricter standards for collecting, preserving, and transporting fecal samples than those used for chemical drugs. Unfortunately, there are no special standards for processing fecal samples in TCM clinical trials.

Methods

We invited interdisciplinary experts within TCM clinical trials and gut microbiome research to help formulate this standard. After more than a year’s in-depth discussion and amendments, we achieved a standard via expert interviews, literature research, questionnaire surveys, and public opinion solicitation. This standard has been reviewed and approved by the Standards Office of China of the Association of Chinese medicine.

Results

We established a sample information processing method prior to TCM clinical sample collection, which is adapted to the unique features of TCM. The method formulates detailed processing requirements for TCM information in addition to the factors that may disturb the gut microbiome. We also constructed a set of methods for collecting, preserving, and transporting fecal samples that meet the characteristics of TCM. These methods formulate detailed operating specifications on the collection approaches, storage conditions, transportation requirements, and management of fecal samples.

Conclusions

This standard guides the information processing prior to sample collection and the standard operating procedures for the collection, preservation, and transportation of fecal samples in TCM clinical trials, which also can be used as a reference by clinicians and researchers in modern medicines.
Elimination of Carryover Contamination in Real-Time Reverse Transcriptase Loop-Mediated Isothermal Amplification for Rapid Detection of the SARS-CoV-2 Virus in Point-of-Care Testing
Authors: Quyen Than Linh , Vinayaka Aaydha Chidambara , Golabi Mohsen , Ngoc Huynh Van , Bang Dang Duong , Wolff Anders
Published: April 2022

Loop-mediated isothermal amplification (LAMP) is being used as a robust rapid diagnostic tool to prevent the transmission of infectious diseases. However, carryover contamination of LAMP-amplified products originating from previous tests has been a problem in LAMP-based bio-analytical assays. In this study, we developed a Cod-uracil-DNA-glycosylase real-time reverse transcriptase LAMP assay (Cod-UNG-rRT-LAMP) for the elimination of carryover contamination and the rapid detection of SARS-CoV-2 in point-of-care (POC) testing. Using the Cod-UNG-rRT-LAMP assay, the SARS-CoV-2 virus could be detected as low as 2 copies/µl (8 copies/reaction) within 45 min of amplification and 2.63 ± 0.17 pg (equivalent to 2.296 × 109 copies) of contaminants per reaction could be eliminated. Analysis of clinical SARS-CoV-2 samples using the Cod-UNG-rRT-LAMP assay showed an excellent agreement with a relative accuracy of 98.2%, sensitivity of 97.1%, and specificity of 95.2% in comparison to rRT-PCR. The results obtained in this study clearly demonstrate the feasibility of the use of the Cod-UNG-rRT-LAMP assay for applications toward the POC diagnosis of SARS-CoV-2 and on-site testing of other pathogens.
Influence of the Number of Parallel-Joints on Size Effect of Elastic Modulus and Characteristic Elastic Modulus
Authors: Hu Gaojian , Ma Gang , Liang Wenxu , Song Leibo , Fu Wei
Published: April 2022

The number of joints existing in the rock affects the elastic modulus of the rock, and the relationship has not been obtained. In this paper, 10 numerical models are established by numerical simulations to study the effect of the number of parallel joints on the size effect of rock elastic modulus. The research shows that there is a power function relationship between the elastic modulus and the number of parallel joints, and a negative exponential relationship between the elastic modulus and the rock size, and their special mathematical models are given. The paper also obtains special form of the relationships between the characteristic size of rock elastic modulus, the characteristic elastic modulus and the number of parallel joints.
Susceptibility to Adrenal Crisis Is Associated With Differences in Cortisol Excretion in Patients With Secondary Adrenal Insufficiency
Authors: Vulto Annet , van Faassen Martijn , Kerstens Michiel N. , van Beek André P.
Published: April 2022

Objective

To compare cortisol pharmacokinetics and pharmacodynamics mapped through several glucocorticoid sensitive pathways in patients on hydrocortisone substitution with or without an adrenal crisis.

Design

A post-hoc analysis of a previously conducted randomized controlled trial in patients with secondary adrenal insufficiency examining the effects of 2 weight-adjusted hydrocortisone doses.

Methods

Comparisons were primarily made on a hydrocortisone dose of 0.2-0.3 mg/kg/day for plasma cortisol and cortisone, 24-hour urinary steroid profile, the glucocorticoid sensitive tryptophan-kynurenine pathway, the renin-angiotensin-aldosterone system and aspects of quality of life. Variables of interest were also analyzed on the hydrocortisone dose of 0.4-0.6 mg/kg/day.

Results

Out of 52 patients, 9 (17%) experienced at least one adrenal crisis (AC+ group) and 43 did not develop an adrenal crisis (AC- group) during an observation period of 10 years. 24-hour urinary excretion of cortisol and cortisone were lower in the AC+ group (0.05 [IQR 0.03; 0.05] vs. 0.09 [0.05; 0.12] µmol/24h, P=0.01and 0.13 [0.10; 0.23] vs. 0.24 [0.19; 0.38] µmol/24h, P=0.04, respectively). No differences in pharmacokinetics of cortisol were observed. Kynurenine concentrations were higher in the AC+ group (2.64 [2.43; 3.28] vs. 2.23 [1.82; 2.38] µmol/L, P=0.03) as was general fatigue (Z-scores 1.02 [-0.11; 1.42] vs. -0.16 [- 0.80; 0.28], P=0.04). On the higher hydrocortisone dose urinary excretion of cortisol and cortisone was still significantly lower between the AC- and AC + group. The differences in glucocorticoid sensitive variables disappeared.

Conclusion

Patients susceptible to an adrenal crisis demonstrated differences in cortisol and cortisone excretion as well as in pharmacodynamics when compared to patients who did not experience an adrenal crisis, suggesting a biological predisposition in certain patients for the development of an adrenal crisis.
Body Mass Index Has a Nonlinear Association With Postoperative 30-Day Mortality in Patients Undergoing Craniotomy for Tumors in Men: An Analysis of Data From the ACS NSQIP Database
Authors: Liu Yufei , Hu Haofei , Han Yong , Li Lunzou , Li Zongyang , Zhang Liwei , Luo Zhu , Huang Guodong , Lan Zhan
Published: April 2022

Background

The association between body mass index (BMI) and mortality is controversial. Thus, the purpose of our research was to survey the association between BMI and postoperative 30-day mortality in brain tumor patients undergoing craniotomy.

Methods

This study analyzed data collected in a multicenter, cross-sectional study that consecutively and nonselectively collected data from a total of 18,642 patients undergoing craniotomy for tumors in the ACS NSQIP from 2012 to 2015. We constructed three linear and non-linear binomial logistic models (the inflection point was set at 18.5) to evaluate the association between BMI and postoperative 30-day mortality, respectively. We also conducted subgroup analyses. Additionally, we compared non-linear models with vs. without interaction with sex.

Results

A total of 17,713 patients were included in this analysis. Of these, 47.38% were male. The postoperative 30-day mortality of the included cases was 2.39% (423/17,713), and the mean BMI was 28.41 ± 6.05 kg/m2. The linear logistic models suggested that after adjusting for the covariates, BMI was not associated with postoperative 30-day mortality (OR=0.999; 95% CI: 0.981, 1.017). The non-linear binomial logistic models suggested a nonlinear relationship between BMI and postoperative 30-day mortality. When BMI was < 18.5, we observed a stronger negative association between them after adjusting for covariates; the OR and 95% CI were 0.719, 0.576-0.896. When BMI was > 18.5, the relationship between them was not significant. We also found that a one-unit decrease in BMI for male patients with BMI < 18.5 kg/m2 was related to a 34.6% increase in the risk of postoperative 30-day mortality (OR=0.654, 95% CI (0.472, 0.907). There was no significant association between them in male patients with BMI > 18.5 kg/m2 or female patients.

Conclusions

This study demonstrates a non-linear relationship between BMI and the risk of postoperative death. Preoperative underweight (BMI < 18.5 kg/m2) would increase the risk of postoperative death in male patients (> 18 years old) undergoing craniotomy for brain tumors. Appropriate nutritional management prior to craniotomy for brain tumors may reduce the risk of postoperative 30-day mortality in underweight men.
Prediction of Fertilization Disorders in the In Vitro Fertilization/Intracytoplasmic Sperm Injection: A Retrospective Study of 106,728 Treatment Cycles
Authors: Tian Tian , Chen Lixue , Yang Rui , Long Xiaoyu , Li Qin , Hao Yongxiu , Kong Fei , Li Rong , Wang Yuanyuan , Qiao Jie
Published: April 2022

Purpose

This study aimed to develop a risk prediction of fertilization disorders during the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).

Methods

A retrospective study was performed with 106,728 fresh embryo IVF/ICSI cycles from 2009 to 2019. Basic characteristics of patients, clinical treatment data, and laboratory parameters were involved. The associations between the selected variables and risks for low fertilization rate (LFR) and total fertilization failure (TFF) were investigated. Ordinal logistic regression and the receiver operating characteristic curves (ROCs) were used to construct and evaluate the prediction models.

Results

A total of 97,181 controls, 4,343 LFR and 5,204 TFF cases were involved in this study. The model based on clinical characteristics (the ages of the couples, women’s BMI, types of infertility, ART failure history, the diminished ovarian reserve, sperm quality, insemination method, and the number of oocytes retrieved) had an AUC of 0.743 for TFF. The laboratory model showed that primary infertility, ART failure history, minimal-stimulation cycle/natural cycle, numbers of oocyte retrieved < 5, IVF, and Anti-Mullerian hormone (AMH) level < 1.1ng/ml are predictors of TFF, with an AUC of 0.742.

Conclusion

We established a clinical and a laboratory prediction model for LFR/TFF. Both of the models showed relatively high AUCs.
Single-Cell Transcriptome Analysis Reveals Inter-Tumor Heterogeneity in Bilateral Papillary Thyroid Carcinoma
Authors: Wang Tiantian , Shi Jinyuan , Li Luchuan , Zhou Xiaoming , Zhang Hui , Zhang Xiaofang , Wang Yong , Liu Lian , Sheng Lei
Published: April 2022

Background

The tumor microenvironment (TME) plays a pivotal role in cancer progression in papillary thyroid carcinoma (PTC), yet the composition and the phenotype of cells within the TME in bilateral PTC are poorly understood.

Methods

We performed unbiased transcriptome-wide single-cell RNA sequencing (scRNA-seq) analysis on 29,561 cells from 3 pairs of bilateral PTC and 1 non-tumor thyroid sample. The results of the analysis were validated by a large-scale bulk transcriptomic dataset deposited in The Cancer Genome Atlas (TCGA) database.

Results

Our integrative analysis of thyroid follicular cells revealed 42 signaling pathways enriched in malignant follicular cells, including cytokine–cytokine receptor interaction, PI3K/Akt signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. A 6-gene signature (CXCL3, CXCL1, IL1A, CCL5, TNFRSF12A, and IL18) in the cytokine–cytokine receptor interaction pathway was constructed to predict the prognosis of patients with PTC, with high risk scores being associated with decreased overall survival [hazard ratio (HR) = 3.863, 95% CI = 2.233−6.682, p < 0.001]. Gene set variation analysis (GSVA) indicated that the pathways enriched in bilateral PTC were significantly different, indicating great heterogeneity in bilateral PTC, even with the same BRAF V600E mutation. Comprehensive analysis of T cells revealed that the proportion of CD8+ tissue-resident memory T cells expressing IFNG decreased in tumor samples with advanced N stage. Within the myeloid compartment, the ratio of suppressive M2-like to pro-inflammatory M1-like macrophages increased with advanced disease stage, which was confirmed in the bulk dataset using transcriptomic profiles. In addition, we also identified numerous biologically critical interactions among myeloid cells, T cells, and follicular cells, which were related to T-cell recruitment, M2-like macrophage polarization, malignant follicular cell progression, and T-cell inhibitory signaling.

Conclusion

Our integrative analyses revealed great inter-tumor heterogeneity within the TME in bilateral PTC, which will offer assistance for precise diagnosis and treatment.
Defining Discriminatory Antibody Fingerprints in Active and Latent Tuberculosis
Authors: Nziza Nadege , Cizmeci Deniz , Davies Leela , Irvine Edward B. , Jung Wonyeong , Fenderson Brooke A. , de Kock Marwou , Hanekom Willem A. , Franken Kees L. M. C. , Day Cheryl L. , Ottenhoff Tom H. M. , Alter Galit
Published: April 2022

Tuberculosis (TB) is among the leading causes of death worldwide from a single infectious agent, second only to COVID-19 in 2020. TB is caused by infection with Mycobacterium tuberculosis (Mtb), that results either in a latent or active form of disease, the latter associated with Mtb spread. In the absence of an effective vaccine, epidemiologic modeling suggests that aggressive treatment of individuals with active TB (ATB) may curb spread. Yet, clinical discrimination between latent (LTB) and ATB remains a challenge. While antibodies are widely used to diagnose many infections, the utility of antibody-based tests to diagnose ATB has only regained significant traction recently. Specifically, recent interest in the humoral immune response to TB has pointed to potential differences in both targeted antigens and antibody features that can discriminate latent and active TB. Here we aimed to integrate these observations and broadly profile the humoral immune response across individuals with LTB or ATB, with and without HIV co-infection, to define the most discriminatory humoral properties and diagnose TB disease more easily. Using 209 Mtb antigens, striking differences in antigen-recognition were observed across latently and actively infected individuals that was modulated by HIV serostatus. However, ATB and LTB could be discriminated, irrespective of HIV-status, based on a combination of both antibody levels and Fc receptor-binding characteristics targeting both well characterized (like lipoarabinomannan, 38 kDa or antigen 85) but also novel Mtb antigens (including Rv1792, Rv1528, Rv2435C or Rv1508). These data reveal new Mtb-specific immunologic markers that can improve the classification of ATB versus LTB.
IL-9 Producing Tumor-Infiltrating Lymphocytes and Treg Subsets Drive Immune Escape of Tumor Cells in Non-Small Cell Lung Cancer
Authors: Heim Lisanne , Yang Zuqin , Tausche Patrick , Hohenberger Katja , Chiriac Mircea T. , Koelle Julia , Geppert Carol-Immanuel , Kachler Katerina , Miksch Sarah , Graser Anna , Friedrich Juliane , Kharwadkar Rakshin , Rieker Ralf J. , Trufa Denis I. , Sirbu Horia , Neurath Markus F. , Kaplan Mark H. , Finotto Susetta
Published: April 2022

Although lung cancer is the leading cause of cancer deaths worldwide, the mechanisms how lung cancer cells evade the immune system remain incompletely understood. Here, we discovered IL-9-dependent signaling mechanisms that drive immune evasion in non-small cell lung cancer (NSCLC). We found increased IL-9 and IL-21 production by T cells in the tumoral region of the lung of patients with NSCLC, suggesting the presence of Th9 cells in the lung tumor microenvironment. Moreover, we noted IL-9 producing Tregs in NSCLC. IL-9 target cells in NSCLC consisted of IL-9R+ tumor cells and tumor-infiltrating lymphocytes. In two murine experimental models of NSCLC, andin vitro, IL-9 prevented cell death and controlled growth of lung adenocarcinoma cells. Targeted deletion of IL-9 resulted in successful lung tumor rejectionin vivoassociated with an induction of IL-21 and reduction of Treg cells. Finally, anti-IL-9 antibody immunotherapy resulted in suppression of tumor development even in established experimental NSCLC and was associated with reduced IL-10 production in the lung. In conclusion, our findings indicate that IL-9 drives immune escape of lung tumor cellsviaeffects on tumor cell survival and tumor infiltrating T cells. Thus, strategies blocking IL-9 emerge as a new approach for clinical therapy of lung cancer.
Single-Cell Characterization of Hepatic CD8+ T Cells in a Murine Model of Primary Biliary Cholangitis
Authors: Han Yichen , Bian Zhen-Hua , Yang Si-Yu , Wang Cheng-Bo , Li Liang , Yang Yan-Qing , Ansari Aftab A. , Gershwin M. Eric , Zeng Xiaofeng , Lian Zhe-Xiong , Zhao Zhi-Bin
Published: April 2022

Primary biliary cholangitis (PBC), an organ-specific autoimmune disease, is characterized by injury to small bile ducts, inflammatory cell infiltrates within the liver, progressive cholestasis, and in some cases, cirrhosis with unclear pathogenesis. We aimed to clarify the importance role of hepatic immunce cells in the pathogenesis of human and experimental PBC.The dominant-negative TGFβ receptor type II transgenic (dnTGFβRII) mice, a well-studied and established murine model of PBC were used to identify changes of immune cells, especially the pathogenic CD8+ T cells. The high-throughput single-cell RNA sequencing technology were applied and found functional heterogeneity among the hepatic CD8+ T cells subsets in dnTGFβRII mice. CD8+ T cells were confirmed the key cells leading to the pathogenesis of PBC in dnTGFβRII mice, and identified the terminally differentiated CD8αα T cells and CD8αβ T cell subsets in the liver of dnTGFβRII mice. While terminally differentiated CD8αα T cells have higher cytokine production ability and cytotoxicity, the terminally differentiated CD8αβ T cells retain their proliferative profile. Our work suggests that there are developmental and differentiated trajectories of pathogenic CD8+ T cell subsets in the pathogenesis of PBC. A further clarification of their roles would be helpful to our understanding of the pathogenesis of PBC and may potentially lead to identifying novel therapeutic modalities.
Mapping Breast Cancer Microenvironment Through Single-Cell Omics
Authors: Tan Zhenya , Kan Chen , Sun Minqiong , Yang Fan , Wong Mandy , Wang Siying , Zheng Hong
Published: April 2022

Breast cancer development and progression rely not only on the proliferation of neoplastic cells but also on the significant heterogeneity in the surrounding tumor microenvironment. Its unique microenvironment, including tumor-infiltrating lymphocytes, complex myeloid cells, lipid-associated macrophages, cancer-associated fibroblasts (CAFs), and other molecules that promote the growth and migration of tumor cells, has been shown to play a crucial role in the occurrence, growth, and metastasis of breast cancer. However, a detailed understanding of the complex microenvironment in breast cancer remains largely unknown. The unique pattern of breast cancer microenvironment cells has been poorly studied, and neither has the supportive role of these cells in pathogenesis been assessed. Single-cell multiomics biotechnology, especially single-cell RNA sequencing (scRNA-seq) reveals single-cell expression levels at much higher resolution, finely dissecting the molecular characteristics of tumor microenvironment. Here, we review the recent literature on breast cancer microenvironment, focusing on scRNA-seq studies and analyzing heterogeneity and spatial location of different cells, including T and B cells, macrophages/monocytes, neutrophils, and stromal cells. This review aims to provide a more comprehensive perception of breast cancer microenvironment and annotation for their clinical classification, diagnosis, and treatment. Furthermore, we discuss the impact of novel single-cell omics technologies, such as abundant omics exploration strategies, multiomics conjoint analysis mode, and deep learning network architecture, on the future research of breast cancer immune microenvironment.
Case Report: Thrombotic-Thrombocytopenic Purpura Following Ipilimumab and Nivolumab Combination Immunotherapy for Metastatic Melanoma
Authors: Mullally W. J. , Cooke F. J. , Crosbie I. M. , Kumar S. , Abernethy V. E. , Jordan E. J. , O’Connor M. , Horgan A. M. , Landers R. , Naidoo J. , Calvert P. M.
Published: April 2022

A man in his early 50s presented with small bowel obstruction, requiring emergency laparoscopic small bowel resection for the metastatic melanoma of the jejunum with no identifiable primary lesion. One week after his first treatment with ipilimumab and nivolumab, he presented with diffuse abdominal pain, constipation, and fatigue. A computerized tomography scan did not identify a cause for his symptoms. This was rapidly followed by thrombocytopenia on day 11 and then anemia. He commenced intravenous corticosteroids for a suspected diagnosis of immune-related thrombocytopenia. On day 15, a generalized onset motor seizure occurred, and despite plasmapheresis later that day, the patient died from fatal immune-related thrombotic thrombocytopenic purpura (TTP). This was confirmed with suppressed ADAMTS13 (<5%) testing on day 14. Immune-related TTP is a rare and, in this case, fatal immune- related adverse event. Further studies are required to identify additional immunosuppressive management for immune-related TTP.
Evaluation of the Safety and Immunogenicity of Duck-Plague Virus gE Mutants
Authors: Ning Yaru , Huang Yalin , Wang Mingshu , Cheng Anchun , Jia Renyong , Liu Mafeng , Zhu Dekang , Chen Shun , Zhao Xinxin , Zhang Shaqiu , Yang Qiao , Wu Ying , Huang Juan , Tian Bin , Ou Xumin , Mao Sai , Gao Qun , Sun Di , Yu Yanlin , Zhang Ling
Published: April 2022

Duck plague (DP) is an acute infectious disease in the duck industry. The duck plague virus (DPV) is the pathogen, a subfamily of alphaherpesvirinae. gE is a type I membrane protein that contains three parts: an extracellular domain, a transmembrane domain, and a cytoplasmic domain. gE is the major virulence determinant of α-herpesvirus. However, the functions of the gE extracellular and cytoplasmic domains have not been reported in DPV. In this study, a gE extracellular domain deletion mutant and a gE cytoplasmic domain deletion mutant were constructed from DPV. Virus replication kinetics showed that the growth titers of both the gE ectodomain-deleted mutant virus and the gE cytoplasmic domain-deleted virus in DEFs were lower than that of the parental virus CHv-50. DPV CHv-gEΔET and DPV CHv-gEΔCT were continuously passed to the 20th passage in DEFs and the 10th in ducklings. The mutant virus DNA after passage was extracted for identification. The results showed that the gE ectodomain and gE cytoplasmic domain deletion mutant viruses have good genetic stability. The ducklings in each group (n=10) were inoculated with the same titers of DPV CHv-gEΔET, DPV CHv-gEΔCT, DPV CHv-ΔgE, and parental CHv-50, respectively. Clinical symptoms and serum antibody levels were detected after inoculation. The results showed that the virulence of DPV CHv-gEΔCT to ducklings was reduced compared with parental CHv-50, while the virulence of DPV CHv-gEΔET to ducklings was significantly reduced. 105 TCID50 DPV CHv-gEΔET or DPV CHv-ΔgE can induce ducklings to produce DPV-specific antibodies, protect the ducklings from virulent CHv challenge. Therefore, DPV CHv-gEΔET may serve as a promising vaccine candidate to prevent and control duck plague.
The Expanding Arsenal of Cytotoxic T Cells
Authors: Cassioli Chiara , Baldari Cosima T.
Published: April 2022

Cytotoxic T cells (CTLs) are the main cellular mediators of the adaptive immune defenses against intracellular pathogens and malignant cells. Upon recognition of specific antigen on their cellular target, CTLs assemble an immunological synapse where they mobilise their killing machinery that is released into the synaptic cleft to orchestrate the demise of their cell target. The arsenal of CTLs is stored in lysosome-like organelles that undergo exocytosis in response to signals triggered by the T cell antigen receptor following antigen recognition. These organelles include lytic granules carrying a cargo of cytotoxic proteins packed on a proteoglycan scaffold, multivesicular bodies carrying the death receptor ligand FasL, and the recently discovered supramolecular attack particles that carry a core of cytotoxic proteins encased in a non-membranous glycoprotein shell. Here we will briefly review the main features of these killing entities and discuss their interrelationship and interplay in CTL-mediated killing.
E Protein Transcription Factors as Suppressors of T Lymphocyte Acute Lymphoblastic Leukemia
Authors: Parriott Geoffrey , Kee Barbara L.
Published: April 2022

T Lymphocyte Acute Lymphoblastic Leukemia (ALL) is an aggressive disease arising from transformation of T lymphocytes during their development. The mutation spectrum of T-ALL has revealed critical regulators of the growth and differentiation of normal and leukemic T lymphocytes. Approximately, 60% of T-ALLs show aberrant expression of the hematopoietic stem cell-associated helix-loop-helix transcription factors TAL1 and LYL1. TAL1 and LYL1 function in multiprotein complexes that regulate gene expression in T-ALL but they also antagonize the function of the E protein homodimers that are critical regulators of T cell development. Mice lacking E2A, or ectopically expressing TAL1, LYL1, or other inhibitors of E protein function in T cell progenitors, also succumb to an aggressive T-ALL-like disease highlighting that E proteins promote T cell development and suppress leukemogenesis. In this review, we discuss the role of E2A in T cell development and how alterations in E protein function underlie leukemogenesis. We focus on the role of TAL1 and LYL1 and the genes that are dysregulated in E2a-/- T cell progenitors that contribute to human T-ALL. These studies reveal novel mechanisms of transformation and provide insights into potential therapeutic targets for intervention in this disease.
Seasonal Dynamics and Predilection Sites of Ticks (Acari: Ixodidae) Feeding on Cows in the Western Parts of the Djurdjura, Algeria
Authors: Bedouhene Amina , Kelanemer Rabah , Medrouh Bachir , Kernif Tahar , Saidi Fairouz , Tail Ghania , Ziam Hocine
Published: April 2022

The present study aimed to determine the phenology and predilection sites of ticks infesting cattle in the western region of Djurdjura (North Algeria) from November 2018 and October 2020. Nineteen cattle farms located in thirteen localities within four provinces were visited monthly for two years. Among the 289 examined cattle, 64.36 ± 2.81% (n=189) were infested by ticks. Of the 10,243 collected ticks, the most abundant tick species was Rhipicephalus bursa (31.57 ± 0.46%), followed by R. annulatus (31.26 ± 0.45%), Hyalomma marginatum (10.67 ± 0.30%), H. lusitanicum (7.02 ± 0.25%), H. excavatum (5.52±%0.22), H. scupense (4.27 ± 0.19%) and H. impeltatum (3.32 ± 0.17%). Ticks of the Hyalomma species were present throughout the year but in a limited number during the winter. H. scupense and H. impletatum showed similar activity from March to October and peaked in April and July, respectively (P<0.001). H. lusitanicum and H. excavatum were active from April to November and both peaked in September and October respectively. Rhipicephalus bursa was collected from April to August and R. annulatus from July to October. R. turanicus was active between April and June. Hyalomma genus had an affinity of attachment for the inguinal region (P<0.001). All parasitic stages of R. annulatus had an affinity for the necks (P<0.001). Nymphs of R. bursa prefer the neck (P<0.001), the adults attach to the perennial and inguinal regions (P<0.001). R. turanicus attach to the ears (P<0.001). As far as we know, this is the first study on the phenology and predilection sites of cattle ticks in the west region of Djurdjura in Algeria.