bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II–III NSCLC (LungMate 002): an open-label, single-arm, phase 2 trial
Authors: Zhu Xinsheng , Sun Liangdong , Song Nan , He Wenxin , Xie Boxiong , Hu Junjie , Zhang Jing , Yang Jie , Dai Jie , Bian Dongliang , Xia Haoran , Sun Fenghuan , Xiong Anwen , Luo Jie , Zhang Lele , Yu Huansha , Liu Ming , Liu Hongcheng , Wang Haifeng , Zhang Haiping , Chen Chang , Wu Chunyan , Duan Liang , Zhu Yuming , Zhang Peng , Jiang Gening
Published: December 2022

Background

This trial aimed to analyse the safety, effectiveness and transcriptomic characteristics of neoadjuvant toripalimab plus chemotherapy in II–III non-small-cell lung cancer (NSCLC).

Methods

Patient eligibility mainly involved treatment-naive, clinical stage II–III and wild-type EGFR/ALK NSCLC. The patients received 2–4 cycles of toripalimab (240 mg q3w) plus carboplatin-based chemotherapy. After the second treatment cycle, all patients were re-evaluated by a multidisciplinary team. Candidates eligible for surgery underwent surgery; otherwise, patients received the remaining treatment cycles. The primary endpoints were safety and major pathological response (MPR). Secondary endpoints were R0 resection rate, progression-free survival (PFS) and overall survival (OS). RNA sequencing of baseline and post-treatment samples was conducted to explore the transcriptomic characteristics of the therapeutic response.

Results

In total, 50 eligible patients were enrolled, including 12 (24.0%) with resectable disease (RD) and 38 (76.0%) with potentially resectable disease (PRD). Treatment-related adverse events (TRAEs) were recorded in 48 cases (96.0%). Severe TRAEs occurred in 3 (6.0%) cases, including myelosuppression, drug-induced liver injury and death related to haemoptysis. The objective response rate (ORR) was 76.0%, with 8 (16.0%) patients having a complete response (CR), 30 (60.0%) partial response (PR), 10 (20.0%) stable disease (SD) and 2 (4.0%) progressive disease (PD). Surgery could be achieved in 12 (100%) patients with RD and 25 (65.8%) with PRD; 1 (2.0%) with PRD refused surgery. Therefore, R0 resection was performed for all 36 (100%) patients who underwent surgery; 20 (55.6%) achieved MPR, including 10 (27.8%) with a complete pathological response (pCR). The CHI3L1 (chitinase-3-like protein 1) immunohistochemistry (IHC) expression of baseline tumour samples could predict the therapeutic response (AUC=0.732), OS (P=0.017) and PFS (P=0.001). Increased PD-1 expression, T cell abundance and immune-related pathway enrichment were observed in post-treatment samples compared to baseline in the response group (CR+PR) but not in the non-response group (SD+PD).

Conclusions

Neoadjuvant toripalimab plus chemotherapy was safe and effective, with a high MPR and manageable TRAEs for II–III NSCLC, even converting initially PRD to RD. Disparate transcriptomic characteristics of therapeutic efficiency were observed, and CHI3L1 expression predicted therapeutic response and survival.

Trial registration

ChiCTR1900024014, June 22, 2019.
Subannular repair for functional mitral regurgitation with reduced systolic ventricle function: rationale and design of REFORM-MR registry
Authors: Girdauskas Evaldas , Pausch Jonas , Reichenspurner Hermann , Kempfert Jörg , Kuntze Thomas , Owais Tamer , Holubec Tomas , Krane Markus , Vitanova Keti , Borger Michael , Eden Matthias , Hachaturyan Violetta , Bramlage Peter , Falk Volkmar
Published: December 2022

Background

Functional mitral regurgitation (FMR) is one of the most common heart valve diseases that is a sequel of left ventricular remodelling. Although mitral valve annuloplasty is a standard treatment of FMR, the recurrence of FMR is a major drawback and occurs in 10–50% of patients. The REFORM-MR registry aims to investigate the effectiveness of standardized papillary muscle relocation and ring annuloplasty and to identify the risk factors associated with recurrent FMR.

Methods

REFORM-MR is a prospective, multicenter registry that enrols consecutive FMR patients across five sites in Germany. All patients with FMR and restricted movement of leaflets during systole (i.e., type IIIb mitral regurgitation) undergoing standardized subannular repair in combination with mitral valve annuloplasty are included in the study. The primary objective is to examine the effect of combined papillary muscle relocation and ring annuloplasty on the recurrence of FMR at 2 years postoperatively. The secondary objectives are MACCE rate, reinterventions on the mitral valve and cardiac-related mortality in the study cohort. Echocardiography core-lab and MRI core-lab will provide anonymized analysis of the imaging data in the REFORM-MR registry. Student’s t-test or Mann–Whitney U test for continuous variables and the Chi-Square or Fisher exact test for categorical variables are used for group comparisons. Kaplan–Meier analyses is performed for survival and safety outcomes.

Results

As of May 2021, a total of 97 patients were enrolled across five sites in Germany.

Conclusions

The results of this study will help define the outcomes of combined papillary muscle relocation and ring annuloplasty in the FMR treatment in a multicentre setting and to improve the understanding of the limitations of subannular repair procedures while treating patients with type III FMR.

Trial registration clinicaltrials.gov Identifier: NCT03470155.
The impact of a postoperative multimodal analgesia pathway on opioid use and outcomes after cardiothoracic surgery
Authors: Ward Ceressa T. , Moll Vanessa , Boorman David W. , Ooroth Lijo , Groff Robert F. , Gillingham Trent D. , Pyronneau Laura , Prabhakar Amit
Published: December 2022

Objective

The Enhanced Recovery after Surgery Cardiac Society recommends using multimodal analgesia (MMA) for postoperative pain however, evidence-based guidelines have yet to be established. This study examines the impact of a standardized postoperative MMA pathway in reducing opioid consumption and related complications after cardiothoracic surgery (CTS).

Methods

Within a multicenter healthcare system, a postoperative MMA pathway was developed and implemented at two CTS intensive care units (ICU) while the other CTS ICU opted to maintain the existing opioid-based pathway. A retrospective chart review was conducted on patients admitted to a CTS ICU within this healthcare system after conventional coronary artery bypass grafting and/or valve surgery from September 1, 2018, to June 30, 2019. Comparative analysis was conducted on patients prescribed MMA versus those managed with an opioid-based pathway. The primary outcome was total opioid consumption, converted to morphine milligram equivalents, 72-h post-surgery. Secondary outcomes included mobility within one-day post-surgery, ICU length of stay (LOS), time to first bowel movement (BM), and time to first zero Richmond Agitation-Sedation Scale (RASS).

Results

Seven hundred sixty-two adults were included for final analysis. The MMA group had a higher body mass index, higher percentage of females, were more likely classified as African American and had higher scores for risk-adjusted complications. General Linear Model analysis revealed higher opioid consumption in the MMA group (Est. 0.22, p < 0.0009); however, this was not statistically significant after adjusting for differences in fentanyl usage. The MMA group was more likely to have mobility within one-day post-surgery (OR 0.44, p < 0.0001), have longer time to first BM (OR 1.93, p = 0.0011), and longer time to first zero RASS (OR 1.62, p = 0.0071). The analgesia groups were not a predictor for ICU LOS.

Conclusions

Opioid consumption was not reduced secondary to this postoperative MMA pathway. The MMA group was more likely to have mobility within one-day post-surgery. Patients in the MMA group were also more likely to have prolonged time to first BM and first zero RASS. Development and evaluation of a perioperative MMA pathway should be considered.
Copy number variation analysis in 189 Romanian patients with global developmental delay/intellectual disability
Authors: Miclea Diana , Osan Sergiu , Bucerzan Simona , Stefan Delia , Popp Radu , Mager Monica , Puiu Maria , Zimbru Cristian , Chirita-Emandi Adela , Alkhzouz Camelia
Published: December 2022

Background

Developmental delay and intellectual disability represent a common pathology in general population, involving about 3% of the pediatric age population, the genetic etiology being often involved. The aim of this study was to determine the clinically relevant copy number variants in patients diagnosed with global developmental delay/intellectual disability in our population, using the chromosomal microarray analysis.

Methods

We analyzed 189 patients diagnosed with global developmental delay/intellectual disability, presented in Clinical Emergency Hospital for Children, Cluj-Napoca. The patients were completely clinically investigated, including dysmorphic and internal malformations evaluation, psychiatric, neuropsychological and metabolic evaluation, standard karyotyping. Genomic analysis was done using chromosomal microarray analysis.

Results

Pathogenic findings (including uniparental disomy) and variants of unknown significance were detected in 53 of 189 patients (28.04%). Pathogenic copy number variants and uniparental disomy were observed in 35 of 189 patients (18.51%). Two patients presented uniparental disomy for chromosome 15, one with clinical phenotype of Prader-Willi syndrome and the other with clinical phenotype with Angelman syndrome. Within the category of pathogenic findings, the recurrent copy number variants were seen in 21 of 35 patients (60%).

Conclusions

The increased percentage of pathogenic structural variants observed in patients with global developmental delay/intellectual disability analyzed by chromosomal microarray technique supports its use in patients with a non-specific phenotype such as these neurodevelopmental disorders. The high percentage of recurrent pathogenic variants between these findings is a finding that support their initial evaluation when a genetic testing algorithm could be a useful option.
A one-year genomic investigation of Escherichia coli epidemiology and nosocomial spread at a large US healthcare network
Authors: Mills Emma G. , Martin Melissa J. , Luo Ting L. , Ong Ana C. , Maybank Rosslyn , Corey Brendan W. , Harless Casey , Preston Lan N. , Rosado-Mendez Joshua A. , Preston Scott B. , Kwak Yoon I. , Backlund Michael G. , Bennett Jason W. , Mc Gann Patrick T. , Lebreton Francois
Published: December 2022

Background

Extra-intestinal pathogenicEscherichia coli(ExPEC) are a leading cause of bloodstream and urinary tract infections worldwide. Over the last two decades, increased rates of antibiotic resistance inE. colihave been reported, further complicating treatment. Worryingly, specific lineages expressing extended-spectrumβ-lactamases (ESBLs) and fluoroquinolone resistance have proliferated and are now considered a serious threat. Obtaining contemporary information on the epidemiology and prevalence of these circulating lineages is critical for containing their spread globally and within the clinic.

Methods

Whole-genome sequencing (WGS), phylogenetic analysis, and antibiotic susceptibility testing were performed for a complete set of 2075E. coliclinical isolates collected from 1776 patients at a large tertiary healthcare network in the USA between October 2019 and September 2020.

Results

The isolates represented two main phylogenetic groups, B2 and D, with six lineages accounting for 53% of strains: ST-69, ST-73, ST-95, ST-131, ST-127, and ST-1193. Twenty-seven percent of the primary isolates were multidrug resistant (MDR) and 5% carried an ESBL gene. Importantly, 74% of the ESBL-E.coliwere co-resistant to fluoroquinolones and mostly belonged to pandemic ST-131 and emerging ST-1193. SNP-based detection of possible outbreaks identified 95 potential transmission clusters totaling 258 isolates (12% of the whole population) from ≥ 2 patients. While the proportion of MDR isolates was enriched in the set of putative transmission isolates compared to sporadic infections (35 vs 27%,p= 0.007), a large fraction (61%) of the predicted outbreaks (including the largest cluster grouping isolates from 12 patients) were caused by the transmission of non-MDR clones.

Conclusion

By coupling in-depth genomic characterization with a complete sampling of clinical isolates for a full year, this study provides a rare and contemporary survey on the epidemiology and spread ofE. coliin a large US healthcare network. While surveillance and infection control efforts often focus on ESBL and MDR lineages, our findings reveal that non-MDR isolates represent a large burden of infections, including those of predicted nosocomial origins. This increased awareness is key for implementing effective WGS-based surveillance as a routine technology for infection control.
Genome-wide placental DNA methylations in fetal overgrowth and associations with leptin, adiponectin and fetal growth factors
Authors: Yang Meng-Nan , Huang Rong , Zheng Tao , Dong Yu , Wang Wen-Juan , Xu Ya-Jie , Mehra Vrati , Zhou Guang-Di , Liu Xin , He Hua , Fang Fang , Li Fei , Fan Jian-Gao , Zhang Jun , Ouyang Fengxiu , Briollais Laurent , Li Jiong , Luo Zhong-Cheng ,   for the Shanghai Birth Cohort
Published: December 2022

Background

Fetal overgrowth “programs” an elevated risk of type 2 diabetes in adulthood. Epigenetic alterations may be a mechanism in programming the vulnerability. We sought to characterize genome-wide alterations in placental gene methylations in fetal overgrowth and the associations with metabolic health biomarkers including leptin, adiponectin and fetal growth factors.

Results

Comparing genome-wide placental gene DNA methylations in large-for-gestational-age (LGA, an indicator of fetal overgrowth, n = 30) versus optimal-for-gestational-age (OGA, control, n = 30) infants using the Illumina Infinium Human Methylation-EPIC BeadChip, we identified 543 differential methylation positions (DMPs; 397 hypermethylated, 146 hypomethylated) at false discovery rate < 5% and absolute methylation difference > 0.05 after adjusting for placental cell-type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. Twenty-five DMPs annotated to 20 genes (QSOX1, FCHSD2, LOC101928162, ADGRB3, GCNT1, TAP1, MYO16, NAV1, ATP8A2, LBXCOR1, EN2, INCA1, CAMTA2, SORCS2, SLC4A4, RPA3, UMAD1,USP53, OR2L13 and NR3C2) could explain 80% of the birth weight variations. Pathway analyses did not detect any statistically significant pathways after correcting for multiple tests. We validated a newly discovered differentially (hyper-)methylated gene-visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (LGA 47, OGA 47). Our data confirmed a hypermethylated gene—cadherin 13 (CDH13) reported in a previous epigenome-wide association study. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while leptin and fetal growth factors (insulin, IGF-1, IGF-2) were not.

Conclusions

Fetal overgrowth may be associated with a large number of altered placental gene methylations. Placental VSX1 and CDH13 genes are hypermethylated in fetal overgrowth. Placental ADIPOQ gene methylations and fetal circulating adiponectin levels were correlated, suggesting the contribution of placenta-originated adiponectin to cord blood adiponectin.
Cerebrovascular complications and outcomes of critically ill adult patients with infective endocarditis
Authors: Rambaud Thomas , de Montmollin Etienne , Jaquet Pierre , Gaudemer Augustin , Mariotte Eric , Abid Sonia , Para Marylou , Cimadevilla Claire , Iung Bernard , Duval Xavier , Wolff Michel , Bouadma Lila , Timsit Jean-François , Sonneville Romain
Published: December 2022

Background

Neurological complications are associated with poor outcome in patients with infective endocarditis (IE). Although guidelines recommend systematic brain imaging in the evaluation of IE patients, the association between early brain imaging findings and outcomes has never been evaluated in critically ill patients. We aimed to assess the association of CT-defined neurological complications with functional outcomes of critically ill IE patients.

Methods

This retrospective cohort study included consecutive patients with severe, left-sided IE hospitalized in the medical ICU of a tertiary care hospital. Patients with no baseline brain CT were excluded. Baseline CT-scans were classified in five mutually exclusive categories (normal, moderate-to-severe ischemic stroke, minor ischemic stroke, intracranial hemorrhage, other abnormal CT). The primary endpoint was 1-year favorable outcome, defined by a modified Rankin Scale score of 0–3.

Results

Between 06/01/2011 and 07/31/2018, 156 patients were included. Among them, 87/156 (56%) had a CT-defined neurological complication, including moderate-to-severe ischemic stroke (n = 33/156, 21%), intracranial hemorrhage (n = 24/156, 15%), minor ischemic stroke (n = 29/156, 19%), other (n = 3/156, 2%). At one year, 69 (45%) patients had a favorable outcome. Factors negatively associated with favorable outcome in multivariable analysis were moderate-to-severe ischemic stroke (OR 0.37, 95%CI 0.14 − 0.95) and age (OR 0.94, 95%CI 0.91–0.97). By contrast, the score on the Glasgow Coma Scale was positively associated with favorable outcome (per 1-point increment, OR 1.23, 95%CI 1.08–1.42). Sensitivity analyses conducted in operated patients revealed similar findings. Compared to normal CT, only moderate-to-severe ischemic stroke was associated with more frequent post-operative neurological complications (n = 8/23 (35%) vs n = 1/46 (2%), p < 0.01).

Conclusion

Moderate-to-severe ischemic stroke had an independent negative impact on 1-year functional outcome in critically ill IE patients; whereas other complications, including intracranial hemorrhage, had no such impact.
What drives mixed-species shoaling among wild zebrafish? The roles of predators, food access, abundance of conspecifics and familiarity
Authors: Mukherjee Ishani , Bhat Anuradha
Published: December 2022

Mixed-species groups occur across a wide range of faunal communities and provide several benefits to members. While zebrafish have often been observed to form mixed-species shoals with coexisting species, the factors determining their occurrence are not yet fully understood. Shoals comprising zebrafish (Danio rerio), flying barbs (Esomus danricus), and whitespots (Aplocheilus panchax) were collected from a stagnant canal at Haringhata (West Bengal, India), and using laboratory-based experiments, we deciphered likely drivers of mixed-species shoaling among zebrafish. Experiments assessing foraging efficiency revealed that the amount of food consumed by individual zebrafish in mixed shoals was comparable to the amount consumed by these individuals in conspecific shoals. Within mixed-species shoals, zebrafish individuals, despite being smaller than the other species, consumed a comparable amount of food as the other species. Shoal choice experiments revealed that under predator risk, zebrafish associate more with mixed shoals and showed comparable associations to shoals differing in the abundance of conspecifics. Furthermore, zebrafish preferred associating with familiar conspecifics over unfamiliar mixed and unfamiliar conspecific shoals. Therefore, equitable food consumption in mixed shoals, greater association with mixed shoals in the presence of predators, and familiarity were important in driving zebrafish towards mixed-species shoaling.

This article has an associated First Person interview with the first author of the paper.
Conflict and Intergroup Trade: Evidence from the 2014 Russia-Ukraine Crisis
Authors: Korovkin Vasily , Makarin Alexey
Published: December 2022

Does armed conflict reduce trade, even in noncombat areas, through the destruction of intergroup social capital? We analyze Ukrainian trade transactions before and after the 2014 Russia-Ukraine conflict. In a difference-in-differences framework, we find that Ukrainian firms from districts with fewer ethnic Russians experienced a deeper decline in trade with Russia. This decline is economically signifi-cant, persistent, and can be explained by erosion of intergroup trust. Affected Ukrainian firms suffered a decrease in performance and diverted trade to other countries. Our results suggest that, through social effects, conflict can be economically damaging even away from combat areas. (JEL D74, F14, F51, J15, P31, P33, Z13)
Unobserved-Offers Bargaining
Authors: Wolitzky Alexander
Published: December 2022

I study ultimatum bargaining with imperfectly observed offers. Imperfectly observed offers must be rejected with positive probability, even when the players’ preferences are common knowledge. Noisier observations imply a greater risk of rejection. In repeated ultimatum bargaining, the responding party can obtain a positive payoff if his signal of the opponent’s offer is also observed by the opponent herself, but not if his signal is private. In alternating-offers bargaining, a player is better off when her own offers are observed more precisely and her opponent’s offers are observed less precisely. Possible applications include international relations, regulation, principal-agency, and product quality provision. (JEL C73, C78, D82)
Temperature, Worker Productivity, and Adaptation: Evidence from Survey Data Production
Authors: LoPalo Melissa
Published: December 2022

This paper estimates the impact of daily weather on worker productivity by using household survey data to study interviewers. Using data from over 9,000 Demographic and Health Surveys interviewers in 46 countries, I find that interviewers complete 13.6 percent fewer interviews per hour on the hottest and most humid days. Workers maintain the same total output by starting earlier in the day and spending more time on each interview at the expense of spending more hours in the field with the same total pay. In addition, interviewers become differentially less productive on tasks that are less easily monitored. (JEL C83, J22, J24, J81, O12, Q54)
Strategic Formal Layoffs: Unemployment Insurance and Informal Labor Markets
Authors: Van Doornik Bernardus , Schoenherr David , Skrastins Janis
Published: December 2022

Exploiting an unemployment insurance reform in Brazil, we study incentive effects of UI in the presence of informal labor markets. We find that eligibility for UI benefits increases formal layoffs by 11 percent. Most of the additional layoffs are related to workers transitioning to informal employment. We further document formal layoff and recall patterns consistent with rent extraction from the UI system. Workers are laid off as they become eligible for UI benefits and recalled when benefits cease. These patterns are stronger for industries and municipalities with a high degree of labor market informality. (JEL J22, J46, J63, J65, K31, O15)
The Effects of Working While in School: Evidence from Employment Lotteries
Authors: Le Barbanchon Thomas , Ubfal Diego , Araya Federico
Published: December 2022

Does working while in school smooth students’ transition into the labor market? We provide evidence on this question by leveraging a one-year work-study program that randomized job offers among over 90,000 student applicants in Uruguay. Program rules forbade employers from employing participants in the same job after program completion, and less than 5 percent of participants ever worked in the same firm again. Two years after the program, participants had 8 percent higher earnings. Our results suggest that the program’s focus on work-related skills was a key mechanism for earnings impacts. (JEL I21, I26, J13, J24, J31, O15)
Learning about Debt Crises
Authors: Paluszynski Radoslaw
Published: December 2022

The European debt crisis presents a challenge to our understanding of the relationship between government bond yields and economic fundamentals. I argue that information frictions are an important missing element and support that claim with evidence on the evolution of GDP forecast errors after 2008. I build a quantitative model of sovereign default where output features rare disasters and agents learn about their realizations. Debt crises coincide with economic depressions and develop gradually while markets update their expectations about future income. Calibrated to the Portuguese economy, the model replicates the comovement of bond spreads and output before and after 2008. (JEL E23, E27, E32, E43, F34, H63)
A Risky Venture: Income Dynamics among Pass-Through Business Owners
Authors: DeBacker Jason , Panousi Vasia , Ramnath Shanthi
Published: December 2022

We employ a large panel of US income tax returns for the period 1987–2018 to extensively characterize and quantify business income risk. Our findings show business income to be much riskier than labor income. Business income is less persistent and is characterized by higher tail risk. Furthermore, when compared to labor income, heterogeneity across households is less important in explaining the cross-sectional variation in business income, and within-household income variation is more important. Our results underscore the income risks business owners face and provide stylized facts and parameter estimates useful for quantitative macroeconomic models and policy analysis. (JEL D31, G51, H24, J23, J31, K34, L26)
Consumption Heterogeneity: Micro Drivers and Macro Implications
Authors: Crawley Edmund , Kuchler Andreas
Published: December 2022

We document heterogeneity in the marginal propensity to consume (MPC) across household characteristics relevant to understanding heterogeneous agent models and monetary policy transmission. We find a strong negative relationship between household liquid wealth and MPC. We show that household liquid wealth predicts MPC closely for every other household characteristic we look at. We use a new empirical method that overcomes sources of bias found in the existing literature, along with administrative data from Denmark that allow us to identify heterogeneous behavior. We use our results to analyze monetary policy transmission mechanisms in both Denmark and the United States. (JEL D12, D31, E21, E43, E52, G51)
Uncovering the Effects of the Zero Lower Bound with an Endogenous Financial Wedge
Authors: Cao Dan , Luo Wenlan , Nie Guangyu
Published: December 2022

We study the effects of the zero lower bound (ZLB) on the severity of financial crises using an incomplete markets New Keynesian model with two occasionally binding constraints: a ZLB on the nominal interest rate and a borrowing constraint tied to an asset price. The model’s financial wedge corresponds to an endogenous multiplier on the borrowing constraint. Binding ZLB exacerbates financial crises through its interaction with the asset fire sale vicious cycle, driving up the financial wedge. Our results offer a novel reinterpretation of the negligible effect of the ZLB in representative agent New Keynesian models with exogenous wedges. (JEL E12, E31, E32, E43, E52, G01)
Caderneta da Criança: análise situacional de sua utilização por profissionais no nordeste brasileiro
Authors: Nobre Caroline Soares , Oliveira Francisco Ariclene , Arruda Carlos André Moura , Aquino Camila Machado de , Fernandes Ruanna Lorna Vieira , Silva Jaqueline Brito , Sousa Maria do Socorro de , Machado Marcia Maria Tavares
Published: December 2022

Objetivo: analisar as habilidades e as práticas de profissionais de saúde da Estratégia Saúde da Família e demais áreas, educação e serviço social em municípios do nordeste brasileiro (Rio Grande do Norte, Maranhão e Piauí), precedente à formação acerca da utilização da Caderneta da Criança. Métodos: Estudo transversal que faz parte de um projeto de Formação de profissionais para o uso da Caderneta da Criança. A população do estudo foi constituída de 140 profissionais que atuam na atenção à criança, em saúde, educação e assistência social. O instrumento de coleta de dados foi formulário Google Forms, com questionário estruturado com 55 questões. A pesquisa tem Parecer Nº3554302. Resultados: observa-se que 15,71% avaliam como ruim a capacidade de conhecê-la de forma minuciosa, e apenas 45% e 3,57% como bom e excelente. Quarenta e seis por cento (46,43%) dos profissionais consideram que utilizam muito a caderneta em sua rotina, porém 24,29% dizem que não a utilizam. Apenas 0,71% sempre preenche a CC com dados relativos à aferição da pressão arterial das crianças e 6,45% sempre registram na CC as intercorrências relativas às doenças, os relatórios de internações, acidentes, as alergias e outros agravos da criança. Conclusões: o estudo aponta ser necessário que haja uma formação de profissionais das unidades de saúde, utilizando metodologias mais criativas, de forma alusiva acerca da necessidade de compreensão da CC como um documento de cidadania, com registros de todas as etapas de crescimento e desenvolvimento da criança, além do acompanhamento da vigilância das vacinas administradas.
Indonesian provincial clustering using Elbow method for the national food security during pandemic
Authors: Trimanto Rido , Yustari Eryka , Nafisah Zulfatin , Carolina Nona , Irsalinda Nursyiva , Setyorini Arifah Indah
Published: December 2022

The Covid-19 pandemic had an impact on the joints of socio-economic life, especially in fulfilling the basic needs. It also caused the declining of global food security, especially in Indonesia. This study aims to develop regional mapping to determine food security priorities and to achieve equal distribution of food security throughout Indonesia. The research method used in this research is quantitative research with the Elbow method. The Elbow method is used to find the optimal cluster size. The data used are from the Food Security Agency of the Indonesian Ministry of Agriculture and Central Statistics Agency in a range of 2020 to 2021. In the process to identify priority areas in Indonesia, it is necessary to have provincial clustering. It is also necessary to minimize food budget allocations that are not well-targeted, causing losses, and not achieving an equal distribution of food security programs. Looking from a more visionary perspective, the success of clustering provides an opportunity for the government to focus more on allocating budget, resources, and time according to the results of the clustering. Based on the results of the provincial clustering, two clusters were obtained, namely provinces with high food security (Cluster 1) and low food security (Cluster 2). Cluster 1 has lower constituent components than Cluster 2.
Forces for good
Authors: Russell Meredith Jones
Published: December 2022

What can be done to help children separated from parents serving in the military? Meredith Jones Russell has some answers
Wellbeing
Authors: O'Sullivan June
Published: December 2022

In the first of a new series, June O'Sullivan, CEO of London Early Years Foundation, considers how staff support children in the group's settings to feel happy
In a good place
Authors: Russell Meredith Jones
Published: December 2022

Why does the early years remain a healthy sector in terms of business deals? Meredith Jones Russell speaks to market experts about the hive of M&A activity
Childcare Counsel: Workplace Nursery Schemes
Authors: Manners Andrew
Published: December 2022

Andrew Manners at Morgan LaRoche advises nurseries to be mindful of updated HMRC guidance
The Implications of COVID-19 Infection on Hematologic Parameters and Coagulation Activity: A Review
Authors: Rayyan Walid Abu , Hazzaa Waffaa Abu , Seder Nesrin , Al-Fawares O'la , Fararjeh Abdul Fattah Salah
Published: December 2022

Wuhan, China, substantially is the epicenter of the COVID-19 pandemic in December 2019. Coronavirus, the confounder virus, a zoonotic in origin was the causative agent of the disseminated disease worldwide. Structural similarities and convergence points were demonstrated between the coronavirus, SARS, and MERS viruses. Aberrantly, a subset of patients developed a serious acute respiratory distress syndrome or diffuse alveolar injury whereas the rest of the patients encountered mild or no symptoms. The pathological clinical laboratory findings are not only critical in the diagnosis of the COVID-19 infection, on the contrary, but they are also crucial in the prognostic predictions about disease prognosis and therapeutic response. This review aims to give some historical context for the pandemic, demonstrate the laboratory's important role in the screening of COVID-19 infection, and review the current phase of biomarker examination in COVID-19 infection, focusing on markers derived directly from the hematological laboratory, reflecting the implications of COVID-19 on the hematological system and coagulation pathways. In conclusion, there is a direct significant correlation between infection severity, the death rate in COVID-19 patients, and the low number of either WBCs or a high number of WBCs with a low number of lymphocytes.
Survival Rate Estimation of Cervix Cancer Patients Using K-M and W-K-M
Authors: Sharma Anurag , K Komal
Published: December 2022

In clinical practice, survival curves show the fraction of patients who experienced the outcome of interest. Survival rates are estimated using survival curves which are determined using Kaplan- Meier method. However, when in case of large number of censored observations, Kaplan- Meier method tends to provide biased estimates. This research article compares widely used Kaplan-Meier (K-M) method & Weighted Kaplan-Meier (WKM) method as a suitable substitute of KM while dealing with the issue of heavy-censoring by applying them on real life data of 900 Cervix Cancer patients diagnosed and treated during 2012-2018 at Rajiv Gandhi Cancer Institute and Research Center, Delhi are analyzed. Then, Five year survival rate of the patients is estimated by using K-M and WKM methods. It was observed that out of 900, 547 (60.78%) patients experienced the event till last follow up and rest of the patients (39.22%) patients were censored of which 187 are lost to follow up and 166 are alive. Median survival time is found to be 65.33 months. Subsequently, 1 year, 2 year, 3 year, 4 year and 5 year survival rates are found to be 81%, 66%, 47%, 33% and 21% respectively by K-M whereas they are found to be 78%, 63%, 63%, 44%, 29% and 19% by WKM. The result of this study shows that in absence of censoring assumption of Kaplan- Meier, Kaplan-Meier method gives biased survival estimations. These estimates are higher than the real estimates. In such cases, Bias can be decreased by using WKM which gives suitable weights to the observations and results in precise understanding.
Public Awareness and Perception about Drug Safety in the Population Residing in Western India - A Questionnaire Based Cross Sectional Survey.
Authors: Munshi Renuka , Maurya Miteshkumar , Pawaskar Pranesh
Published: December 2022

Drug safety is an important health concern for every individual on medications. Pharmacovigilance programme focuses on the reporting, evaluation and prevention of any adverse drug reactions and needs the equal support from every stakeholder that includes health care professionals, pharmacists and public patients as well. Public participation for reporting Adverse Drug Reactions [ADR] is quite low in developing country, India. Therefore, this study was planned with objective to evaluate awareness and perception about drug safety practice and adverse drug reactions reporting system among the lay population. A validated and ethics committee approved questionnaire was distributed to consenting participants residing in the Mumbai region by reaching to the lay public through the community centers and the responses were collected from year 2019 to 2021 to assess awareness and understanding about drug safety and adverse drug reaction reporting among lay public. A total of 1876 questionnaires were collected with a response rate of 75%. 86.7% of the participants believed drugs can have both benefit and adverse effects. 62.41% participants were unaware of any common drug related side effects. Only 8.04% of the public were aware of adverse drug reactions and reporting same to adverse event Monitoring Centre and 98.3% participants never heard of adverse event monitoring center. 66.57% participants learnt about the Pharmacovigilance program through our survey. Also, it was the patient asking the doctor about potential drug related side effects [37.58%] rather than the other way round [24%]. Although the educational survey created awareness among all participants, a greater impact was seen among the younger generation [18-30 years’ age group] irrespective of their literacy status [p<0.001]. We concluded that the Pharmacovigilance program of any nation needs health care professionals to sensitize the lay public to participate in ADR reporting thereby promote patient safety.
Assessment of Analgesic and Anti-inflammatory Activity of Double-layered Diclofenac Diethylamine Transdermal Patch
Authors: Sharma Aditya , Verma Navneet
Published: December 2022

Diclofenac Diethylamine has been used generally in the management of pain and inflammation caused by musculoskeletal disorders. The current study revealed the preliminary investigation into the analgesic and anti-inflammatory activities of an optimized double-layered transdermal patch of Diclofenac Diethylamine. The patch was prepared by using the hydrophobic acrylic polymer Eudragit RL 100 and the hydrophilic polymer Polyvinyl pyrrolidone K-30 in combination as the first layer of matrix type and pressure-sensitive acrylic adhesive Duro Tak 387-2510 as the second layer of drug-in-adhesive type patch. The solvent casting method was employed to prepare the transdermal patch over the backing membrane. We optimized the patch in terms of its concentration based on results exhibited by ex-vivo and in-vitro studies using FDC and the rat’s skin. This study was designed to assess the analgesic and anti-inflammatory effects of an optimized patch with the respective models in laboratory animals. In a comparison of the developed transdermal patch with commercially available Diclofenac Diethylamine gel (Volini gel), the developed patch was found to be statistically significant (p < 0.01) and effective for decreasing pain and inflammation symptoms. The findings of the study suggest that the prepared double-layered transdermal patch of Diclofenac Diethylamine can serve as the best carrier to provide a sustained effect for the management of pain and inflammation.
Prediction and Identification of Signature Genes Expressed in Different Brain Regions through RNA-Seq Data Analysis
Authors: Yadav Ruchi , Sharma Akanksha , Prakash Jyoti
Published: December 2022

Brain is one of the most intricate organs in the human body that works with billions of cells. A brain tumor emerges when there is uncontrolled division of cells shaping a strange gathering of cells around or inside the cerebrum. To understand the complexity of brain function and gene expression in different regions of brain is most challenging and crucial. RNAseq techniques along with computational analysis has made this task much easier and accurate. In this current research RNAseq data of brain regions have been used to predict functional genes in different regions of brains. Differential expression of genes in different regions of brain highlights the function of genes and associated pathways in brain function. The aim of this study was to identify differentially expressed gene in the brain tumor samples. RNA-seq data was retrieved from ENA database with the accession no.- PRJNA294929. Total 5 samples were retrieved in fastq format, out of which 4 samples were of corpous callosum and 1 sample was of frontal cortex. Differentially Expressed Genes (DEG) analysis was done using Galaxy platform and R software, functional enrichment of DEGs was done using DAVID and GO databases. The RNA-seq data analysis shows the up regulation of PHGDH, TUBB4A, HSPA2, GFAP, NKX3-1, COX3 genes and three genes PHGDH, COX3 and MT3 shows significant difference in their gene expression. This result can have importance in understanding the complexity of brain transcriptomics and DEGs can be further studied to evaluate their expression in brain cells and associated diseases. Further wet lab verification is required as these genes can be used as potential drug target and can be used for drug designing for brain tumor.
The Effect of Cement Dust Exposure on Lung Function among Cement Factory Workers
Authors: Alnawaiseh Nedal , El-Gamal Fathi M.
Published: December 2022

Background: Previous studies reported equivocal results about effects of cement dust on the lung. The objective of the present study was to assess the impact of cement dust on the respiratory health of exposed workers. Methods: A cross-sectional study was conducted on 300 cement exposed production workers from the crusher and packing sections, and 303 controls not exposed to any noxious materials that could affect their chest. All subjects were asked personal, occupational and BMRC questionnaire on respiratory symptoms and smoking habits. Forced spirometry and anthropometry were conducted on each subject. Multiple linear regression as well as other statistical tests were used. The level of significance for the present study was considered 0.05. Results: Chronic cough was significantly more encountered among the cement exposed workers (22.7%), compared to the unexposed workers (13.9%) where p-value was < 0.005. Chronic bronchitis was, also, significantly more encountered among the cement exposed workers compared to the unexposed workers (19.0% and 9.9% respectively) where p-value was <0.001. Multiple linear regression analysis revealed that, after allowing for the age, height, weight and the smoking habit, the mean values of FVC, and FEV1 were significantly lower in the cement exposed workers compared to the unexposed group; and the mean value of FEV1% was higher in the cement exposed workers compared to the unexposed group. The mean values for FEF25%-75%, PEFR, FEF75, FEF50, and FEF25 were significantly lower among the cement exposed workers compared to the unexposed group. These effects in the exposed group were found duration of exposure related. Conclusion: It is suggested that workplace exposure to cement dust may lead to increased occurrence of chronic bronchitis and impairment of lung function. It is recommended that more effort should be implemented to protect respiratory systems of workers in cement factories.
Magnetic Field Exposure to Clinical Isolates of Acinitobacter baumanii
Authors: Abed Suha Maher , Farhan Mohamed Ghadban , Madhloom Nahidah Kzar , Dheeb Batol Imran
Published: December 2022

This paper presents the isolation of Acinitobacter baumanii from clinical dources such as wounds, burns and urinary tract infection. A total of 15 isolates of the studied bacteria were collected and identified by using macroscopic features, biochemical tests and the Vitek2 technique. The diagnosis was then confirmed at the species level. Antibiotics susceptibility test was performed following Kirby-Bauer procedure using 12 antibiotics before and after exposing the bacteria to a static magnetic field, to notice changes related to resistance or sensitivity of the antibiotic, in addition to experimenting with the bacterial viable count before and after exposure to the field as well. The results showed that the isolates had a high resistance to antibiotics, so that all the isolates were 100% resistant to both the third generation cephalosporin and ampicillin, while the most effective antibiotic against the isolates was Imipenem giving only 50% susceptibility. When the isolates were exposed to a magnetic field of 0.3 Tesla and for a period of 24 hours incubation at a temperature of 37 ° C, it was observed a decrease in the number of colony forming unit. Concerning with antibiotic testing after exposure, results indicated that Doxycycline was the most variable in the inhibition zone readings, as it increased significantly. We conclude from our study that the magnetic field can change the vital activity of bacteria by reducing its resistance to antibiotics, which is considered a health problem for the life of humans and their animals.
Microbiota and Potential Asthma Markers: A Case Control Study in a Sample of Egyptian Children
Authors: Abdelhamid Enas R. , El Refay Amira S. , ElKhatib Alshaimaa A. , Armaneous Ayman F. , Sherif Lobna S. , M. Hussien Shahinaz , Hashish Adel , Mehanna Nayra
Published: December 2022

Background: It is well known that allergy development is linked to alteration in microbiome and cytokines levels. colonization of children gut by wide array of microbes and bacteria is associated with mucosal and systemic immune responses as well as allergy development. Investigating the role of gut microbiota and serum cytokines clarifies the pathophysiology of the disease and enhance development of management plan. This study aimed to assess fecal microbiota in asthmatic children and correlate it with serum CXCL8 and p38 MAPK as potential asthma severity markers. Results: This case control study enrolled 56 asthmatic children aged 2-8 years, and 20 non asthmatic children of matched sex and age group as a control. Fresh stool samples were obtained from enrolled children for analysis of gut microbiota through DNA extraction and Real time PCR, using species-specific primers, serum CXCL8 and P38MAPK levels were estimated by ELISA. Higher level of Bifidobacterium and lower level of Lactobacillus was reported in asthmatic compared to non-asthmatic children, current results showed significant difference between asthmatic and non-asthmatic subgroups regarding CXCL 8 serum level. Study reported significant negative correlation between presence of asthma and serum markers CXCL8 and p38MAPK while significant positive correlation between presence of asthma and Bifidobacterium Log. Conclusions: the association between CXCL8 level, p38 MAPK and microbiome suggesting a link between gut bacteria and inflammatory status. Moreover, elevated CXCL8 , and p38 MAPK level increase symptoms severity. The alteration of microbiome level associated with elevated markers level suggesting the protective role of gut microbiome in asthma control.
Design of single-layer color echelle grating optical waveguide for augmented-reality display
Authors: Guo Qinghao , Zhang Shanwen , Zhang Jun , Chen Chao Ping
Published: December 2022

We proposed a single-layer color echelle grating combined optical waveguide structure for an augmented-reality display. In this structure, we used echelle gratings with super-wavelength periodic scale as in-coupling, relay, and out-coupling elements. The combined propagation of three light beams in the waveguide was realized by overlapping different high diffraction orders of the RGB three primary colors, and deflection of the beam direction between gratings was achieved by conical diffraction generated by the inclined grating. Using the vector diffraction theory, the structural parameters and tolerance ranges of the three types of gratings were optimized, rendering average diffraction efficiencies of the three primary colors of the in-coupling, relay, and out-coupling gratings greater than 74%, 21%, and 35%, respectively. As a result, we obtained dual-channel one-dimensional pupil dilation of the original image and a field-of-view angle of h18.9° × v36.87°.