bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a microfluidic photochemical flow reactor concept by rapid prototyping
Authors: Dinter Robin , Willems Suzanne , Nissalk Thilo , Hastürk Oguz , Brunschweiger Andreas , Kockmann Norbert
Published: August 2023

The transfer from batch to flow chemistry is often based on commercial microfluidic equipment, such as costly complete reactor systems, which cannot be easily tailored to specific requirements of technologies such as DNA-encoded library technology (DELT), in particular for increasingly important photochemical reactions. Customized photoreactor concepts using rapid prototyping technology offer a modular, flexible, and affordable design that allows for adaptation to various applications. In order to validate the prototype reactors, a photochemical pinacol coupling reaction at 368 nm was conducted to demonstrate the transfer from batch to flow chemistry. The conversion rates were optimized by adapting the design parameters of the microfluidic flow photoreactor module. Subsequently, the photoreactor module has been extended to an application with DNA-tagged substrates by switching to LEDs with a wavelength of 454 nm. The successful recovery of DNA confirmed the feasibility of the modular-designed flow photo reactor. This collaborative approach holds enormous potential to drive the development of DELT and flow equipment design.
Addressing illegal practices: intergenerational transfer and creative engagement as a way to compensate boomerang effects
Authors: Richter Isabell , Lim Voon Ching , Fadzil Kamal Solhaimi Bin , Riordan Oliver , Pahl Sabine , Goh Hong Ching
Published: August 2023

Introduction

This study investigates the effectiveness of using an educational comic book to facilitate the intergenerational transfer of knowledge and intentions concerning dynamite fishing in Borneo, Malaysia. The aim is to explore how children can influence their parents' understanding of the issue and their willingness to address it within the community. Additionally, the research examines unintended reactions within the participant groups.

Methods

The study employed a controlled experimental design with two groups: a treatment group exposed to the educational comic book and a control group without this intervention. Participants were families residing in communities where dynamite fishing is still practiced. Data collection included pre- and post-intervention surveys and follow-up measurements to assess short-term and long-term effects on knowledge and intentions.

Results

The findings revealed a successful intergenerational transfer of knowledge from children to parents, evident both in the short and long term. Furthermore, the intergenerational transfer of intentions demonstrated a two-fold pattern. The intention to discuss the dynamite fishing problem within the community was transferred from children to their parents at the second measurement point, highlighting the time required for the development of new intentions. A boomerang effect was observed for the intention to cease dynamite fishing among individuals reliant on fishing for their livelihood. This rebound effect was solely observed in the control group but was effectively mitigated in the treatment group, where engagement with the comic book influenced positive outcomes.

Discussion

The study's results underscore the power of intergenerational transfer of knowledge and intentions from younger to older generations, facilitated by educational comic books as a communication tool for addressing environmental issues. Moreover, a boomerang effect seen in the control group highlights the complexity of behavior change in economically motivated practices like dynamite fishing. Engaging interventions, such as educational materials, can play a crucial role in curbing these behaviors. Furthermore, the study emphasizes the necessity of carefully monitoring unintended reactions within participant groups, particularly in research related to sensitive topics.
Case report: Strong low-density-cholesterol reduction accompanied by shrinkage of low-attenuation coronary plaque during lipid-lowering treatment with bempedoic acid—serial evaluation by coronary computed tomography angiography
Authors: Korosoglou Grigorios , Giesen Alexander , Geiss Eva , Stach Ksenija
Published: August 2023

Here, we present a patient with coronary artery disease and prior percutaneous coronary interventions. This patient had to discontinue taking multiple statins and ezetimibe due to intolerance with musculoskeletal complaints and nausea. Monotherapy with bempedoic acid was well tolerated and was exceptionally effective at lipid lowering, enabling patients to achieve the low-density lipoprotein target of <55 mg/dl, as recommended by current guidelines. In addition, serial coronary computed tomography angiography performed upon clinical indications, during 20 months of lipid-lowering treatment with bempedoic acid, demonstrated signs of favorable plaque component modification, with shrinkage of the low-attenuation plaque component compared to baseline findings.
Artificial intelligence research strategy of the United States: critical assessment and policy recommendations
Authors: Gursoy Furkan , Kakadiaris Ioannis A.
Published: August 2023

The foundations of Artificial Intelligence (AI), a field whose applications are of great use and concern for society, can be traced back to the early years of the second half of the 20th century. Since then, the field has seen increased research output and funding cycles followed by setbacks. The new millennium has seen unprecedented interest in AI progress and expectations with significant financial investments from the public and private sectors. However, the continual acceleration of AI capabilities and real-world applications is not guaranteed. Mainly, accountability of AI systems in the context of the interplay between AI and the broader society is essential for adopting AI systems via the trust placed in them. Continual progress in AI research and development (R&D) can help tackle humanity's most significant challenges to improve social good. The authors of this paper suggest that the careful design of forward-looking research policies serves a crucial function in avoiding potential future setbacks in AI research, development, and use. The United States (US) has kept its leading role in R&D, mainly shaping the global trends in the field. Accordingly, this paper presents a critical assessment of the US National AI R&D Strategic Plan and prescribes six recommendations to improve future research strategies in the US and around the globe.
Being the finger pointing to the moon: how martial arts can provide a holistic perspective on teachers' role in tackling sustainability challenges
Authors: Shpak Guy , Vasques Ana
Published: August 2023

From social injustice to the climate crisis, our modern society currently faces an unprecedented magnitude of global challenges. To properly support future generations, long-term solutions must take into account the role of educational systems in developing necessary competencies needed for future world citizens. Pedagogical methodologies should reflect this need and adapt accordingly, focusing on developing intrapersonal and implementation capabilities that are acknowledged as sustainability-related competencies. While some educational approaches are better tuned to develop these skills, the deployment and effectiveness of these might be limited by the perception of the teacher's position in the classroom. Given the urgency of the situation, we propose to use educational principles that have already proved effective in developing similar skills for decades and centuries, and inspired by the world of martial arts. Rather than incorporating martial arts elements per se, we argue that by adopting key principles taken from traditional martial arts pedagogies, we can redefine the teacher's educational function, and by thus redefining the student's learning process to acquire sustainability competencies. We propose a conceptual framework that distills relevant elements from martial arts methodologies and defines ways to implement these in academic educational systems.
Pancreatic steatosis and iron overload increases cardiovascular risk in non-alcoholic fatty liver disease
Authors: Marti-Aguado David , Ten-Esteve Amadeo , Baracaldo-Silva Carlos Manuel , Crespo Ana , Coello Elena , Merino-Murgui Víctor , Fernandez-Paton Matias , Alfaro-Cervello Clara , Sánchez-Martín Alba , Bauza Mónica , Jimenez-Pastor Ana , Perez-Girbes Alexandre , Benlloch Salvador , Pérez-Rojas Judith , Puglia Víctor , Ferrández Antonio , Aguilera Victoria , Latorre Mercedes , Monton Cristina , Escudero-García Desamparados , Bosch-Roig Ignacio , Alberich-Bayarri Ángel , Marti-Bonmati Luis
Published: August 2023

Objective

To assess the prevalence of pancreatic steatosis and iron overload in non-alcoholic fatty liver disease (NAFLD) and their correlation with liver histology severity and the risk of cardiometabolic diseases.

Method

A prospective, multicenter study including NAFLD patients with biopsy and paired Magnetic Resonance Imaging (MRI) was performed. Liver biopsies were evaluated according to NASH Clinical Research Network, hepatic iron storages were scored, and digital pathology quantified the tissue proportionate areas of fat and iron. MRI-biomarkers of fat fraction (PDFF) and iron accumulation (R2*) were obtained from the liver and pancreas. Different metabolic traits were evaluated, cardiovascular disease (CVD) risk was estimated with the atherosclerotic CVD score, and the severity of iron metabolism alteration was determined by grading metabolic hiperferritinemia (MHF). Associations between CVD, histology and MRI were investigated.

Results

In total, 324 patients were included. MRI-determined pancreatic iron overload and moderate-to severe steatosis were present in 45% and 25%, respectively. Liver and pancreatic MRI-biomarkers showed a weak correlation (r=0.32 for PDFF, r=0.17 for R2*). Pancreatic PDFF increased with hepatic histologic steatosis grades and NASH diagnosis (p<0.001). Prevalence of pancreatic steatosis and iron overload increased with the number of metabolic traits (p<0.001). Liver R2* significantly correlated with MHF (AUC=0.77 [0.72-0.82]). MRI-determined pancreatic steatosis (OR=3.15 [1.63-6.09]), and iron overload (OR=2.39 [1.32-4.37]) were independently associated with high-risk CVD. Histologic diagnosis of NASH and advanced fibrosis were also associated with high-risk CVD.

Conclusion

Pancreatic steatosis and iron overload could be of utility in clinical decision-making and prognostication of NAFLD.
Enhancing Cushing’s disease diagnosis: exploring the impact of desmopressin on ACTH gradient during BIPSS
Authors: Almeida Tobias Skrebsky de , Rodrigues Ticiana da Costa , Costenaro Fabíola , Scaffaro Leandro Armani , Farenzena Maurício , Gastaldo Fernando , Czepielewski Mauro Antônio
Published: August 2023

Introduction

The differential diagnosis between Cushing’s disease (CD) and ectopic ACTH syndrome (EAS) is complex, and bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold-standard test. However, BIPSS with corticotropin-releasing hormone (CRH) stimulation is rarely available.

Objective

This retrospective cohort study aimed to assess the accuracy of the inferior petrosal sinus to peripheral ACTH gradient (IPS:P) before and after desmopressin stimulation for the differential diagnosis of ACTH-dependent Cushing’s syndrome (CS), applying different cutoff values.

Methods

A total of 50 patients (48 with CD and 2 with EAS) who underwent BIPSS were included in this study. The sensitivity and specificity of IPS:P in BIPSS before and after desmopressin stimulation were evaluated. Various cutoff values for IPS:P were examined to determine their diagnostic accuracy.

Results

Using the traditional IPS:P cutoff, the sensitivity was 85.1% before stimulation, 89.6% after stimulation, and a combined sensitivity of 91.7%. Applying cutoff values of IPS:P >1.4 before and >2.8 after stimulation, the sensitivity was 87.2% and 89.6%, respectively, with a combined sensitivity of 91.7%. Receiver operating characteristic (ROC) curve analysis determined optimal cutoff values of 1.2 before stimulation and 1.57 after stimulation, resulting in a sensitivity of 93.6% and 93.8%, respectively, with a combined sensitivity of 97.9%. Specificity remained at 100% throughout all analyses. Among the 43 patients who responded positively to stimulation, 42 (97.7%) did so within the first three minutes, and all 43 (100%) did so within the first five minutes. None of the assessed clinical variables predicted the ACTH response to stimulation in BIPSS with statistical significance.

Discussion

ACTH stimulation with desmopressin during BIPSS improves the accuracy of IPS:P, making it a valuable tool for investigating ACTH-dependent Cushing’s syndrome. Considering the low risk of complications, we recommend the use of desmopressin stimulation during BIPSS for the differential diagnosis of ACTH-dependent CS.
Data-driven identification of household-transformer relationships in power distribution networks using Hausdorff similarity assessment
Authors: Zhu Yuru , Yang Xiu , Yan Haitao
Published: August 2023

Precisely identifying the household-transformer relationship is of significant importance for both the stability of the power system and the quality of customer electricity consumption. However, the complex network structures and frequent reconfigurations may lead to inaccurate records of household-transformer relationships. In this paper, a novel data-driven similarity assessment solution is proposed to enhance the accuracy and scalability of identifying household-transformer relationships. Initially, a data processing method based on dynamic temporal regularization with sliding windows is employed to optimize dataset quality as well as enhance the efficiency of data processing. Then, a two-stage solution is proposed for identifying the household-transformer relationship. The first stage involves initial normalized clustering based on the basic information of power distribution substations, while the second stage assesses the similarity between households and transformer operational states based on Hausdorff distance. The superior performance of the proposed method is extensively assessed through real historical datasets, compared to benchmarks.
Unravelling the genetic framework associated with grain quality and yield-related traits in maize (Zea mays L.)
Authors: Sethi Mehak , Saini Dinesh Kumar , Devi Veena , Kaur Charanjeet , Singh Mohini Prabha , Singh Jasneet , Pruthi Gomsie , Kaur Amanpreet , Singh Alla , Chaudhary Dharam Paul
Published: August 2023

Maize serves as a crucial nutrient reservoir for a significant portion of the global population. However, to effectively address the growing world population’s hidden hunger, it is essential to focus on two key aspects: biofortification of maize and improving its yield potential through advanced breeding techniques. Moreover, the coordination of multiple targets within a single breeding program poses a complex challenge. This study compiled mapping studies conducted over the past decade, identifying quantitative trait loci associated with grain quality and yield related traits in maize. Meta-QTL analysis of 2,974 QTLs for 169 component traits (associated with quality and yield related traits) revealed 68 MQTLs across different genetic backgrounds and environments. Most of these MQTLs were further validated using the data from genome-wide association studies (GWAS). Further, ten MQTLs, referred to as breeding-friendly MQTLs (BF-MQTLs), with a significant phenotypic variation explained over 10% and confidence interval less than 2 Mb, were shortlisted. BF-MQTLs were further used to identify potential candidate genes, including 59 genes encoding important proteins/products involved in essential metabolic pathways. Five BF-MQTLs associated with both quality and yield traits were also recommended to be utilized in future breeding programs. Synteny analysis with wheat and rice genomes revealed conserved regions across the genomes, indicating these hotspot regions as validated targets for developing biofortified, high-yielding maize varieties in future breeding programs. After validation, the identified candidate genes can also be utilized to effectively model the plant architecture and enhance desirable quality traits through various approaches such as marker-assisted breeding, genetic engineering, and genome editing.
Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS)
Authors: Papendorf Jonas Johannes , Ebstein Frédéric , Alehashemi Sara , Piotto Daniela Gerent Petry , Kozlova Anna , Terreri Maria Teresa , Shcherbina Anna , Rastegar Andre , Rodrigues Marta , Pereira Renan , Park Sophia , Lin Bin , Uss Kat , Möller Sophie , da Silva Pina Ana Flávia , Sztajnbok Flavio , Torreggiani Sofia , Niemela Julie , Stoddard Jennifer , Rosenzweig Sergio D. , Oler Andrew J. , McNinch Colton , de Guzman Marietta M. , Fonseca Adriana , Micheloni Nicole , Fraga Melissa Mariti , Perazzio Sandro Félix , Goldbach-Mansky Raphaela , de Jesus Adriana A. , Krüger Elke
Published: August 2023

Mutations in genes coding for proteasome subunits and/or proteasome assembly helpers typically cause recurring autoinflammation referred to as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) or proteasome-associated autoinflammatory syndrome (PRAAS). Patients with CANDLE/PRAAS present with mostly chronically elevated type I interferon scores that emerge as a consequence of increased proteotoxic stress by mechanisms that are not fully understood. Here, we report on five unrelated patients with CANDLE/PRAAS carrying novel inherited proteasome missense and/or nonsense variants. Four patients were compound heterozygous for novel pathogenic variants in the known CANDLE/PRAAS associated genes, PSMB8 and PSMB10, whereas one patient showed additive loss-of-function mutations in PSMB8. Variants in two previously not associated proteasome genes, PSMA5 and PSMC5, were found in a patient who also carried the PSMB8 founder mutation, p.T75M. All newly identified mutations substantially impact the steady-state expression of the affected proteasome subunits and/or their incorporation into mature 26S proteasomes. Our observations expand the spectrum of PRAAS-associated genetic variants and improve a molecular diagnosis and genetic counseling of patients with sterile autoinflammation.
Rational use of drugs to alleviate adverse outcomes caused by COVID-19 quarantine in women with intrahepatic cholestasis of pregnancy
Authors: Cai Qin-Yu , Li Xia , Yang Yin , Luo Xin , Luo Shu-Juan , Xiong Jing , He Zong-Yan , Chen Yuan , Mou Yi-Wei , Hu Ji-Yuan , Yang Shu , Lan Xia , Liu Tai-Hang
Published: August 2023

Purpose

This study aimed to investigate the impacts of home quarantine on pregnancy outcomes of women with intrahepatic cholestasis of pregnancy (ICP) during the COVID-19 outbreak and whether the rational use of drugs will change these impacts.

Methods

This multi-center study was conducted to compare the pregnancy outcomes in women with ICP between the home quarantine group and the non-home quarantine group in southwest China. Propensity score matching was performed to confirm the pregnancy outcomes of the medication group and the non-medication group in women with ICP during the epidemic period.

Results

A total of 3,161 women with ICP were enrolled in this study, including 816 in the home quarantine group and 2,345 in the non-home quarantine group. Women with ICP in the home quarantine group had worse pregnancy outcomes, such as a growing risk of gestational diabetes mellitus A1, fetal growth restriction, pre-eclampsia, preterm delivery, and even stillbirth. Drug therapy could alleviate some adverse pregnancy outcomes caused by home quarantine, including pre-eclampsia, preterm delivery, and meconium-stained amniotic fluid.

Conclusion

COVID-19 quarantine would increase the incidence of ICP and lead to adverse pregnancy outcomes in women with ICP. The rational use of drugs reduced some obstetrical complications and improved partial pregnancy outcomes. Our findings suggested that the government and hospitals should enhance their management and life guidance for women with ICP and speed up developing home quarantine guidelines.
Oral microbiome and preterm birth
Authors: Vidmar Šimic Marijana , Maver Aleš , Zimani Ana Nyasha , Hočevar Keli , Peterlin Borut , Kovanda Anja , Premru-Sršen Tanja
Published: August 2023

Background

The etiology of preterm birth (PTB) is heterogeneous and not yet well known. Maternal periodontal disease has been investigated for decades and is a known risk factor for adverse pregnancy outcomes. However, no particular bacterial species or higher taxonomic order has been found as causative of PTB, leading to studies of the whole oral microbiome. In order to determine if and how the composition of the oral microbiome is associated with PTB, we performed a large case–control study including women with term (TB) and PTB.

Methods

We compared oral microbiomes in PTB to TB, to examine differences in the microbial richness, diversity, and differential abundance of specific taxa. We obtained oral swab samples from 152 Caucasian pregnant women who were classified as either PTB (≤36 6/7 weeks, n = 61) or TB (≥38 0/7 weeks, n = 91) in exclusion of any other major medical or obstetric conditions. The oral microbiomes of these women were characterized by 16S ribosomal RNA (rRNA) gene sequencing of the V3–V4 region on the MiSeq platform.

Results

The dominant microorganisms at the phylum level in all pregnant women regardless of birth week outcomes as belonging to Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, and Actinobacteria. The phyla Firmicutes and Bacteroidetes were relatively more abundant in women with a PTB than in women with a TB, while Proteobacteria was less prevalent in women with a PTB. At the genus level, Veillonella, Prevotella, and Capnocytophaga were enriched in the PTB, and while many of the members of these genera could not be resolved to the species level, Veillonella massillensis was shown to be increased in the PTB group.

Conclusion

We identified the genera Veillonella, Prevotella, and Capnocytophaga in the maternal oral microbiome as being associated with PTB independently of clinically apparent infection, uterine anomalies, and other pregnancy complications, including placenta previa, and placental abruption. The clarification of the role of those taxa in the etiology of PTB merits further research.
Case report: A case of sepsis caused by rickettsial infection-induced hemophagocytic syndrome
Authors: Cao Yanli , Liu Peijun , Song Qiuling , Wang Jing
Published: August 2023

Hemophagocytic lymphohistiocytosis (HLH) is a rare histiocytic disorder characterized by reactive hyperplasia of the mononuclear phagocytic system, which is primarily caused by dysfunction of cytotoxic killer cells and natural killer cells, leading to antigen clearance barriers and the overactivation of the mononuclear phagocytic system due to continuous antigen stimulation. HLH encompasses a group of clinical syndromes marked by the overproduction of inflammatory cytokines. A 68-year-old Chinese man presented with persistent fever, chills, nausea, and vomiting; the patient had no history of any underlying conditions. Laboratory investigations revealed decreased levels of red blood cells, white blood cells, and platelets, along with reduced natural killer cell activity, increased CD25, hyperferritinemia, and the detection of Rickettsia DNA in his blood, meeting the diagnostic criteria of the Histiocyte Society HLH-2004 guidelines. The patient was treated with antibiotics, improving anemia, glucocorticoid therapy, and continuous renal replacement therapy (CRRT), temporarily improving his condition. However, the patient died after 2 years from chronic renal failure caused by septic shock.
Colorectal cancer among inflammatory bowel disease patients: risk factors and prevalence compared to the general population
Authors: Abu-Freha Naim , Cohen Bracha , Gordon Michal , Weissmann Sarah , Kestenbaum Emily H. , Vosko Sergei , Abu-Tailakh Muhammad , Ben-Shoshan Liza , Cohen Daniel L. , Shirin Haim
Published: August 2023

Background

Colorectal cancer (CRC) is a feared complication of inflammatory bowel disease (IBD). We aimed to investigate the prevalence and risk factors of CRC among a large cohort of IBD patients.

Methods

Data on IBD patients free of CRC at baseline was extracted using the MDClone platform of the Clalit health maintenance organization in Israel. We investigated the frequency rate of CRC among IBD patients compared to a control group without IBD. Possible risk factors, including comorbidities and IBD-related medications, were investigated in a multivariate analysis.

Results

During a follow-up of 139,448 years among Crohn’s disease (CD) patients and 139,533 years among ulcerative colitis (UC) patients, a frequency rate of CRC was 1.5% (191) among 12,888 CD patients and 2.1% (261) among 12,381 UC patients compared to 1.2% among 57,334 controls. In a multivariate analysis of UC patients, age at diagnosis (OR 1.030, p < 0.001), primary sclerosing cholangitis (OR 2.487, p = 0.005), diabetes mellitus (OR 2.01, p < 0.001), and glucocorticoids treatment (OR 1.465, p = 0.008) were found to be predictors of CRC. For CD patients, age at diagnosis (OR 1.035, p < 0.001), primary sclerosing cholangitis (OR 2.25, p = 0.029), and glucocorticoids treatment (OR 2.07, p < 0.001) were found to be predictors for CRC, but not diabetes mellitus.

Conclusion

Despite the continuously decreasing rates of CRC among IBD patients, these are still higher in IBD patients compared to the general population. IBD patients, particularly those with risk factors, require special consideration in follow-up for CRC.
Connected health in US, EU, and China: opportunities to accelerate regulation of connected health technologies to optimize their role in medicines development
Authors: Awad Susan , Aljuburi Lina , Lumsden Rebecca S. , Mpandzou Marya , Marinus Roelie
Published: August 2023

Connected health technology is playing an increasingly important role in healthcare. The power, complexity, functionality, and accessibility of connected health technologies are increasing rapidly, showing promise for improved and more equitable healthcare outcomes. They are integral to the lifecycle of medical products, from discovery and development to manufacturing and ultimately to the patient. The spectrum of integration between medical products and digital technologies ranges from non-drug specific solutions for supporting adherence or patient monitoring, which may or may not require regulatory approval, to digital therapeutics and software-containing combination products, which make claims supported by clinical evidence. The exponential increase and rapid evolution of connected health technologies – and the accompanying possibilities for innovative healthcare interventions, delivery systems, and clinical trial designs – pose new and complicated regulatory challenges. Currently, connected health may involve the use of regulated medical devices, including software as a medical device, or consumer products, such as wearables or apps, that fall under regulatory discretion. In this paper we examine how connected health technologies intersect with the development and lifecycle of medical products, how they are impacted by existing regulatory frameworks in the US, EU, and China, and propose future focus areas of activity.
Ketoprofen as an emerging contaminant: occurrence, ecotoxicity and (bio)removal
Authors: Tyumina Elena , Subbotina Maria , Polygalov Maxim , Tyan Semyon , Ivshina Irina
Published: August 2023

Ketoprofen, a bicyclic non-steroidal anti-inflammatory drug commonly used in human and veterinary medicine, has recently been cited as an environmental contaminant that raises concerns for ecological well-being. It poses a growing threat due to its racemic mixture, enantiomers, and transformation products, which have ecotoxicological effects on various organisms, including invertebrates, vertebrates, plants, and microorganisms. Furthermore, ketoprofen is bioaccumulated and biomagnified throughout the food chain, threatening the ecosystem function. Surprisingly, despite these concerns, ketoprofen is not currently considered a priority substance. While targeted eco-pharmacovigilance for ketoprofen has been proposed, data on ketoprofen as a pharmaceutical contaminant are limited and incomplete. This review aims to provide a comprehensive summary of the most recent findings (from 2017 to March 2023) regarding the global distribution of ketoprofen in the environment, its ecotoxicity towards aquatic animals and plants, and available removal methods. Special emphasis is placed on understanding how ketoprofen affects microorganisms that play a pivotal role in Earth’s ecosystems. The review broadly covers various approaches to ketoprofen biodegradation, including whole-cell fungal and bacterial systems as well as enzyme biocatalysts. Additionally, it explores the potential of adsorption by algae and phytoremediation for removing ketoprofen. This review will be of interest to a wide range of readers, including ecologists, microbiologists, policymakers, and those concerned about pharmaceutical pollution.
Clinical features of Streptococcus intermedius infection in children: a case series study
Authors: Xu Zhufei , Gao Lichao , Xu Dan , Yang Dehua , Chen Zhimin , Wang Yingshuo
Published: August 2023

Introduction

Streptococcus intermedius is an opportunistic pathogen associated with prolonged hospital stays and high mortality rates in adults. However, little is currently known about the clinical features of Streptococcus intermedius infection in children.

Methods

This retrospective case series study included 40 children diagnosed with Streptococcus intermedius, confirmed through bacterial cultures or high-throughput sequencing. Antibiotic resistance was assessed through susceptibility testing. The site and clinical manifestations were evaluated for all patients.

Results

The common infection sites were the abdominal cavity, skin and soft tissue, intracranial, and invasive pulmonary, with the abdominal cavity being the most frequently affected. The drug susceptibility test showed 100% sensitivity to ceftriaxone, levofloxacin, chloramphenicol, vancomycin, and linezolid, 92.6% sensitivity to penicillin, 73.3% resistance to erythromycin, and 76.7% resistance to clindamycin. Besides antibiotic therapy, surgical intervention or pus drainage was often necessary. Lung imaging of four patients revealed pulmonary abscesses, nodules, or encapsulated pleura. Two cases yielded positive culture results, while three were identified as positive through high-throughput nucleotide sequencing of pleural effusion.

Discussion

In children with Streptococcus intermedius infection, emphasis should be placed on the risk of pus or abscess formation. In cases of pulmonary abscess and pleural effusion, especially in male children, Streptococcus intermedius should be suspected even if the culture is negative. Improvements in high-throughput nucleotide sequencing are required to reduce misdiagnosis rates.
Evaluation of the antibacterial activity of Elsholtzia ciliate essential oil against halitosis-related Fusobacterium nucleatum and Porphyromonas gingivalis
Authors: Li Fengjiao , Wang Chuandong , Xu Jing , Wang Xiaoyu , Cao Meng , Wang Shuhua , Zhang Tingting , Xu Yanyong , Wang Jing , Pan Shaobin , Hu Wei
Published: August 2023

The broad-spectrum antimicrobial activity of Elsholtzia ciliate essential oil (ECO) has been previously reported, but its effectiveness against halitosis-causing bacteria such as Fusobacterium nucleatum and Porphyromonas gingivalis is not well understood. In this study, we investigated the bacteriostatic activity of ECO against planktonic cells and biofilms of F. nucleatum and P. gingivalis, as well as its ability to inhibit bacterial metabolism and production of volatile sulfur compounds (VSCs) at sub-lethal concentrations. Our findings revealed that ECO exhibited comparable activities to chlorhexidine against these oral bacteria. Treatment with ECO significantly reduced the production of VSCs, including hydrogen sulfide, dimethyl disulfide, and methanethiol, which are major contributors to bad breath. As the major chemical components of ECO, carvacrol, p-cymene, and phellandrene, were demonstrated in vitro inhibitory effects on F. nucleatum and P. gingivalis, and their combined use showed synergistic and additive effects, suggesting that the overall activity of ECO is derived from the cumulative or synergistic effect of multiple active components. ECO was found to have a destructive effect on the bacterial cell membrane by examining the cell morphology and permeability. Furthermore, the application of ECO induced significant changes in the bacterial composition of saliva-derived biofilm, resulting in the elimination of bacterial species that contribute to halitosis, including Fusobacterium, Porphyromonas, and Prevotella. These results provide experimental evidence for the potential clinical applications of ECOs in the prevention and treatment of halitosis.
Effect of swab pooling on the Accula point-of-care RT-PCR for SARS-CoV-2 detection
Authors: Lancelot Moira , Fibben Kirby , Sullivan Julie , O’Sick William , McLendon Kaleb , Wu Huixia , Rao Anuradha , Bassit Leda C. , Greenleaf Morgan , Miller Pamela , Krull Wolfgang , Tyburski Erika , Roback John D. , Lam Wilbur A. , Damhorst Gregory L.
Published: August 2023

Introduction

Swab pooling may allow for more efficient use of point-of-care assays for SARS-CoV-2 detection in settings where widespread testing is warranted, but the effects of pooling on assay performance are not well described.

Methods

We tested the Thermo-Fisher Accula rapid point-of-care RT-PCR platform with contrived pooled nasal swab specimens.

Results

We observed a higher limit of detection of 3,750 copies/swab in pooled specimens compared to 2,250 copies/swab in individual specimens. Assay performance appeared worse in a specimen with visible nasal mucous and debris, although performance was improved when using a standard laboratory mechanical pipette compared to the transfer pipette included in the assay kit.

Conclusion

Clinicians and public health officials overseeing mass testing efforts must understand limitations and benefits of swab or sample pooling, including reduced assay performance from pooled specimens. We conclude that the Accula RT-PCR platform remains an attractive candidate assay for pooling strategies owing to the superior analytical sensitivity compared to most home use and point-of-care tests despite the inhibitory effects of pooled specimens we characterized.
Recent advances in poor HIV immune reconstitution: what will the future look like?
Authors: Zhang Wenyuan , Ruan Lianguo
Published: August 2023

Combination antiretroviral therapy has demonstrated proved effectiveness in suppressing viral replication and significantly recovering CD4+ T cell count in HIV type-1 (HIV-1)-infected patients, contributing to a dramatic reduction in AIDS morbidity and mortality. However, the factors affecting immune reconstitution are extremely complex. Demographic factors, co-infection, baseline CD4 cell level, abnormal immune activation, and cytokine dysregulation may all affect immune reconstitution. According to report, 10–40% of HIV-1-infected patients fail to restore the normalization of CD4+ T cell count and function. They are referred to as immunological non-responders (INRs) who fail to achieve complete immune reconstitution and have a higher mortality rate and higher risk of developing other non-AIDS diseases compared with those who achieve complete immune reconstitution. Heretofore, the mechanisms underlying incomplete immune reconstitution in HIV remain elusive, and INRs are not effectively treated or mitigated. This review discusses the recent progress of mechanisms and factors responsible for incomplete immune reconstitution in AIDS and summarizes the corresponding therapeutic strategies according to different mechanisms to improve the individual therapy.
How can we discover developable antibody-based biotherapeutics?
Authors: Bauer Joschka , Rajagopal Nandhini , Gupta Priyanka , Gupta Pankaj , Nixon Andrew E. , Kumar Sandeep
Published: August 2023

Antibody-based biotherapeutics have emerged as a successful class of pharmaceuticals despite significant challenges and risks to their discovery and development. This review discusses the most frequently encountered hurdles in the research and development (R&D) of antibody-based biotherapeutics and proposes a conceptual framework called biopharmaceutical informatics. Our vision advocates for the syncretic use of computation and experimentation at every stage of biologic drug discovery, considering developability (manufacturability, safety, efficacy, and pharmacology) of potential drug candidates from the earliest stages of the drug discovery phase. The computational advances in recent years allow for more precise formulation of disease concepts, rapid identification, and validation of targets suitable for therapeutic intervention and discovery of potential biotherapeutics that can agonize or antagonize them. Furthermore, computational methods for de novo and epitope-specific antibody design are increasingly being developed, opening novel computationally driven opportunities for biologic drug discovery. Here, we review the opportunities and limitations of emerging computational approaches for optimizing antigens to generate robust immune responses, in silico generation of antibody sequences, discovery of potential antibody binders through virtual screening, assessment of hits, identification of lead drug candidates and their affinity maturation, and optimization for developability. The adoption of biopharmaceutical informatics across all aspects of drug discovery and development cycles should help bring affordable and effective biotherapeutics to patients more quickly.
The computational power of the human brain
Authors: Gebicke-Haerter Peter J.
Published: August 2023

At the end of the 20th century, analog systems in computer science have been widely replaced by digital systems due to their higher computing power. Nevertheless, the question keeps being intriguing until now: is the brain analog or digital? Initially, the latter has been favored, considering it as a Turing machine that works like a digital computer. However, more recently, digital and analog processes have been combined to implant human behavior in robots, endowing them with artificial intelligence (AI). Therefore, we think it is timely to compare mathematical models with the biology of computation in the brain. To this end, digital and analog processes clearly identified in cellular and molecular interactions in the Central Nervous System are highlighted. But above that, we try to pinpoint reasons distinguishing in silico computation from salient features of biological computation. First, genuinely analog information processing has been observed in electrical synapses and through gap junctions, the latter both in neurons and astrocytes. Apparently opposed to that, neuronal action potentials (APs) or spikes represent clearly digital events, like the yes/no or 1/0 of a Turing machine. However, spikes are rarely uniform, but can vary in amplitude and widths, which has significant, differential effects on transmitter release at the presynaptic terminal, where notwithstanding the quantal (vesicular) release itself is digital. Conversely, at the dendritic site of the postsynaptic neuron, there are numerous analog events of computation. Moreover, synaptic transmission of information is not only neuronal, but heavily influenced by astrocytes tightly ensheathing the majority of synapses in brain (tripartite synapse). At least at this point, LTP and LTD modifying synaptic plasticity and believed to induce short and long-term memory processes including consolidation (equivalent to RAM and ROM in electronic devices) have to be discussed. The present knowledge of how the brain stores and retrieves memories includes a variety of options (e.g., neuronal network oscillations, engram cells, astrocytic syncytium). Also epigenetic features play crucial roles in memory formation and its consolidation, which necessarily guides to molecular events like gene transcription and translation. In conclusion, brain computation is not only digital or analog, or a combination of both, but encompasses features in parallel, and of higher orders of complexity.
DFA as a window into postural dynamics supporting task performance: does choice of step size matter?
Authors: Nordbeck Patric C. , Andrade Valéria , Silva Paula L. , Kuznetsov Nikita A.
Published: August 2023

Introduction: Detrended Fluctuation Analysis (DFA) has been used to investigate self-similarity in center of pressure (CoP) time series. For fractional gaussian noise (fGn) signals, the analysis returns a scaling exponent, DFA-α, whose value characterizes the temporal correlations as persistent, random, or anti-persistent. In the study of postural control, DFA has revealed two time scaling regions, one at the short-term and one at the long-term scaling regions in the diffusion plots, suggesting different types of postural dynamics. Much attention has been given to the selection of minimum and maximum scales, but the choice of spacing (step size) between the window sizes at which the fluctuation function is evaluated may also affect the estimates of scaling exponents. The aim of this study is twofold. First, to determine whether DFA can reveal postural adjustments supporting performance of an upper limb task under variable demands. Second, to compare evenly-spaced DFA with two different step sizes, 0.5 and 1.0 in log2 units, applied to CoP time series.

Methods: We analyzed time series of anterior-posterior (AP) and medial-lateral (ML) CoP displacement from healthy participants performing a sequential upper limb task under variable demand.

Results: DFA diffusion plots revealed two scaling regions in the AP and ML CoP time series. The short-term scaling region generally showed hyper-diffusive dynamics and long-term scaling revealed mildly persistent dynamics in the ML direction and random-like dynamics in the AP direction. There was a systematic tendency for higher estimates of DFA-α and lower estimates for crossover points for the 0.5-unit step size vs. 1.0-unit size.

Discussion: Results provide evidence that DFA-α captures task-related differences between postural adjustments in the AP and ML directions. Results also showed that DFA-α estimates and crossover points are sensitive to step size. A step size of 0.5 led to less variable DFA-α for the long-term scaling region, higher estimation for the short-term scaling region, lower estimate for crossover points, and revealed anomalous estimates at the very short range that had implications for choice of minimum window size. We, therefore, recommend the use of 0.5 step size in evenly spaced DFAs for CoP time series similar to ours.
JK5G postbiotics attenuate immune-related adverse events in NSCLC patients by regulating gut microbiota: a randomized controlled trial in China
Authors: Chen Mengting , Ma Liling , Yu Huiqing , Huang Shaoyi , Zhang Junhui , Gong Juan , Yang Liejun , Chen Lan , Luo Haojun , Tian Ling , Wang Sixiong
Published: August 2023

Scope

This study aimed to evaluate the effects of JK5G postbiotics to regulate imbalanced gut microbiota and its impacts on the efficacy and incidence rate of immune-related adverse events (irAEs) in non-small-cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).

Methods

This randomized, double-blind, placebo-controlled trial was conducted in China and included non-squamous or squamous NSCLC patients without EGFR, ROS1, and ALK alteration, treatment-naive, and stage IIIb-IV. Patients were randomly (1:1) divided into two groups to receive four cycles (three weeks for each cycle) of programmed cell death-1 (PD-1) plus chemotherapy plus placebo (control group, n = 30) or to receive PD-1 plus chemotherapy plus JK5G postbiotics (JK5G group, n = 30). The primary endpoint was objective response rate. The secondary endpoints were quality of life (QoL), adverse effects, and the 16S DNA sequencing of gut microbiota, blood inflammatory cytokines, and lymphocyte subsets. This study was registered at www.chictr.org.cn (ChiCTR2200064690).

Results

Sixty patients were enrolled. The objective response rate was 36.67% (11/30) in the control group and 50.00% (15/30) in the JK5G group (p = 0.297). The JK5G group had better QoL and nutritional levels, as well as lower depression symptoms than the control group (all p < 0.05). Moreover, the JK5G group had a lower incidence of anemia (63.33% vs. 13.33%, p < 0.001), decreased lymphocyte count (20.00% vs. 0%, p = 0.010), decreased appetite (53.33% vs. 16.67%, p = 0.003), nausea (33.33% vs. 6.67%, p = 0.010), and asthenia (30.00% vs. 6.67%, p = 0.017) than the control group. Moreover, JK5G attenuated gut microbiota imbalance, accompanied by increased Faecalibacterium, Ruminococcaceae, and fecal butyrate concentration, and diminished Escherichia-Shigella. Furthermore, JK5G administration significantly decreased the levels of pro-inflammatory markers, including TNF-α, IL-2, and C-reactive protein (CRP) (all p < 0.05). Significant increases in CD3+CD4+ T cells and CD4/CD8 ratio were observed in the peripheral blood of JK5G group patients (all p < 0.05). The enterotype data showed that patients were clustered into Blautia (E1) and Escherichia-Shigella (E2) enterotypes, and JK5G postbiotics intervention might be related to enterotype modulations.

Conclusion

Our current findings indicated that JK5G postbiotics might attenuate irAEs, and enhance the QoL and nutrition levels of advanced NSCLC patients who received ICIs. JK5G postbiotics could also improve the gut microbiota structures and ameliorate the tumor microenvironment and inflammation.

Clinical trial registration

www.chictr.org.cn, identifier ChiCTR2200064690.
Pearls and pitfalls in contemporary management of marginal velopharyngeal inadequacy among children with cleft palate
Authors: Mao Qirong , Li Jingtao , Yin Xing
Published: August 2023

Marginal velopharyngeal inadequacy (MVPI) is a particular status of velopharyngeal closure after cleft palate repair. The physiological and phonological characteristics of patients with MVPI are significantly different from those with typical velopharyngeal insufficiency. The pathological mechanisms and diagnostic criteria of MVPI are still controversial, and there is limited evidence to guide the selection of surgical and non- surgical management options and a lack of recognized standards for treatment protocols. Based on a systematic study of the relevant literatures, this review identifies specific problems that are currently under-recognized in the diagnosis and treatment of MVPI and provides guidelines for further exploration of standardized and reasonable intervention protocols for MVPI.