bluuebunny/crossref_metadata_2025 huggingface dataset:
Revolutionizing cancer immunotherapy: unleashing the potential of bispecific antibodies for targeted treatment
Authors: Guo Xiaohan , Wu Yi , Xue Ying , Xie Na , Shen Guobo
Published: December 2023

Recent progressions in immunotherapy have transformed cancer treatment, providing a promising strategy that activates the immune system of the patient to find and eliminate cancerous cells. Bispecific antibodies, which engage two separate antigens or one antigen with two distinct epitopes, are of tremendous concern in immunotherapy. The bi-targeting idea enabled by bispecific antibodies (BsAbs) is especially attractive from a medical standpoint since most diseases are complex, involving several receptors, ligands, and signaling pathways. Several research look into the processes in which BsAbs identify different cancer targets such angiogenesis, reproduction, metastasis, and immune regulation. By rerouting cells or altering other pathways, the bispecific proteins perform effector activities in addition to those of natural antibodies. This opens up a wide range of clinical applications and helps patients with resistant tumors respond better to medication. Yet, further study is necessary to identify the best conditions where to use these medications for treating tumor, their appropriate combination partners, and methods to reduce toxicity. In this review, we provide insights into the BsAb format classification based on their composition and symmetry, as well as the delivery mode, focus on the action mechanism of the molecule, and discuss the challenges and future perspectives in BsAb development.
Advances in tumor immunomodulation based on nanodrug delivery systems
Authors: Wang Bo , Zhang Yue , Yin Xunzhe
Published: December 2023

Immunotherapy is a therapeutic approach that employs immunological principles and techniques to enhance and amplify the body’s immune response, thereby eradicating tumor cells. Immunotherapy has demonstrated effective antitumor effects on a variety of malignant tumors. However, when applied to humans, many immunotherapy drugs fail to target lesions with precision, leading to an array of adverse immune-related reactions that profoundly limit the clinical application of immunotherapy. Nanodrug delivery systems enable the precise delivery of immunotherapeutic drugs to targeted tissues or specific immune cells, enhancing the immune antitumor effect while reducing the number of adverse reactions. A nanodrug delivery system provides a feasible strategy for activating the antitumor immune response by the following mechanisms: 1) increased targeting and uptake of vaccines by DCs, which enhances the efficacy of the immune response; 2) increased tumor cell immunogenicity; 3) regulation of TAMs and other cells by, for example, regulating the polarization of TAMs and interfering with TAN formation, and ECM remodeling by CAFs; and 4) interference with tumor immune escape signaling pathways, namely, the PD-1/PD-L1, FGL1/LAG-3 and IDO signaling pathways. This paper reviews the progress of nanodrug delivery system research with respect to tumor immunotherapy based on tumor immunomodulation over the last few years, discussing the promising future of these delivery systems under this domain.
Comparative analysis of glucose and fructose tolerance in two marine fishes: effects on insulin secretion and acute hypoxia tolerance
Authors: Ma Qiang , Xu Houguo , Limbu Samwel Mchele , Wei Yuliang , Liang Mengqing
Published: December 2023

Carbohydrates are a common and economical energy source in animal feeds. However, most fish show a persistent postprandial hyperglycemia after intake of a high-carbohydrate diet. Unfortunately, the mechanism of glucose metabolism in fish is still unclear. In the present study, tiger puffer (Takifugu rubripes) and turbot (Scophthalmus maximus) were intraperitoneally injected or orally administered with glucose or fructose (500 mg/kg body weight) to evaluate the ability of fish to utilize carbohydrates. Afterwards, serum glucose, fructose, pyruvate, insulin levels, and acute hypoxia tolerance were measured. Our results showed increased serum glucose level and then decreased post intraperitoneal injection with glucose, and reached a peak after 0.5 hours in turbot and 1 hour in tiger puffer. Tiger puffer had significantly lower liver glycogen, serum glucose, fructose, pyruvate, and insulin contents than turbot. Glucose and fructose only induced insulin secretion in turbot, but did not change serum insulin level in tiger puffer. Glucose was a stronger stimulator of insulin than fructose in the two marine species. Both intraperitoneal injection and oral fructose intake increased serum glucose level, while intraperitoneal or oral glucose also increased serum fructose level. Intraperitoneal injection of glucose promoted absorption and utilization of glucose in the blood more effectively than oral glucose intake. In addition, turbot and tiger puffer were intolerant to acute hypoxia, whereas supplementation with glucose or fructose improved hypoxia tolerance in the two marine fishes by activating anaerobic glycolysis. Taken together, our results provide important scientific information for understanding the mechanism for glucose and fructose utilization and improving hypoxia tolerance in fish.
Management perspectives from patients with fibromyalgia experiences with the healthcare pathway: a qualitative study
Authors: Kachaner Alexandra , Harim Magda , Combier Alice , Trouvin Anne Priscille , Avouac Jérôme , Ranque Brigitte , Piot Marie-Aude
Published: December 2023

Background

Fibromyalgia is a prevalent condition affecting 1–2% of the general population and can result in significant disability. Physicians and patients frequently encounter challenges in managing this condition.

Aim

The aim of this study was to explore novel management approaches through a qualitative analysis of the doctor-patient relationship.

Design and setting

Telephonic interviews were conducted with fibromyalgia patients to investigate their healthcare experiences.

Methods

Qualitative analysis was performed on patients' narratives using interpretative phenomenological analysis, a methodology that delves into each individual's subjectivity.

Results

A total of 19 adult patients with fibromyalgia, primarily middle-aged women (84% women, mean age 49.8 years), recruited from two university centers in Paris, were included in the study. The narratives of participants revealed substantial suffering and considerable functional impairment, which is paradoxical for a condition often considered benign. They reported an ongoing sense of loss of control, exacerbated by an imbalanced patient-doctor relationship. Patients constantly feared not being heard or believed, and they frequently sought attention from their caregivers. Most participants displayed significant ambivalence toward the nature of their condition and actively sought causal links. Patients' adaptive strategies sometimes worsened their symptoms, as in the case of muscular deconditioning. The healthcare system appeared deficient in managing these patients, characterized by a lack of health professional training, frequent inappropriate responses from healthcare providers, and stigmatization of psychological conditions.

Conclusion

Despite its perceived benign nature, fibromyalgia should be regarded as a severe condition due to its substantial long-term consequences. Participants reported a challenging experience with the doctor-patient relationship, marked by a strong sense of dependence and a lack of recognition. The care pathway for these patients appeared unsuitable and disorderly, potentially resulting in iatrogenic consequences. The management of patients with fibromyalgia should be enhanced and directed toward a patient-centered approach. The study provides practical recommendations regarding communication methods and patient care.
TMP269, a small molecule inhibitor of class IIa HDAC, suppresses RABV replication in vitro
Authors: Yin Juanbin , Wang Shasha , Ren Shanhui , Liang Zhengji , Ge Junwei , Sun Yuefeng , Yin Xiangping , Wang Xiangwei
Published: December 2023

TMP269, a small molecular inhibitor of IIa histone deacetylase, plays a vital role in cancer therapeutic. However, the effect of TMP269 on the regulation of viral replication has not been studied. In the present study, we found that TMP269 treatment significantly inhibited RABV replication at concentrations without significant cytotoxicity in a dose-dependent manner. In addition, TMP269 can reduce the viral titers and protein levels of RABV at an early stage in the viral life cycle. RNA sequencing data revealed that immune-related pathways and autophagy-related genes were significantly downregulated after RABV infection treated with TMP269. Further exploration shows that autophagy enhances RABV replication in HEK-293T cells, while TMP269 can inhibit autophagy to decrease RABV replication. Together, these results provide a novel treatment strategy for rabies.
Assessment of ethanol and nicotine interactions using a reinforcer demand modeling with grouped and individual levels of analyses in a long-access self-administration model using male rats
Authors: Robison Christopher L. , Cova Nicole , Madore Victoria , Allen Tyler , Barrett Scott , Charntikov Sergios
Published: December 2023

Previous reports have indicated the reciprocal effects of nicotine and ethanol on their rewarding and reinforcing properties, but studies using methodological approaches resembling substance use in vulnerable populations are lacking. In our study, rats first self-administered ethanol, and their sensitivity to ethanol’s reinforcing effects was assessed using a reinforcer demand modeling approach. Subsequently, rats were equipped with intravenous catheters to self-administer nicotine, and their sensitivity to nicotine’s reinforcing effects was evaluated using the same approach. In the final phase, rats were allowed to self-administer ethanol and nicotine concurrently, investigating the influence of one substance on the rate of responding for the other substance. Group analyses revealed notable differences in demand among sucrose, sweetened ethanol, and ethanol-alone, with sucrose demonstrating the highest demand and ethanol-alone exhibiting greater sensitivity to changes in cost. At the individual level, our study finds significant correlations between rats’ demand for sucrose and sweetened ethanol, suggesting parallel efforts for both substances. Our individual data also suggest interconnections in the elasticity of demand for sweetened ethanol and ethanol-alone, as well as a potential relationship in price response patterns between ethanol and nicotine. Furthermore, concurrent self-administration of ethanol and nicotine at the group level displayed reciprocal effects, with reduced responding for nicotine in the presence of ethanol and increased responding for ethanol in the presence of nicotine. This study provides valuable insights into modeling the co-use of ethanol and nicotine and assessing their interaction effects using reinforcer demand modeling and concurrent self-administration or noncontingent administration tests. These findings contribute to our understanding of the complex interplay between ethanol and nicotine and have implications for elucidating the underlying mechanisms involved in polydrug use.
Involvement of orexin type-2 receptors in genetic absence epilepsy rats
Authors: Toplu Aylin , Mutlu Nursima , Erdeve Elif Tuğçe , Sariyildiz Özge , Çelik Musa , Öz-Arslan Devrim , Akman Özlem , Molnár Zoltan , Çarçak Nihan , Onat Filiz
Published: December 2023

Introduction

Orexin is a neuropeptide neurotransmitter that regulates the sleep/wake cycle produced by the lateral hypothalamus neurons. Recent studies have shown the involvement of orexin system in epilepsy. Limited data is available about the possible role of orexins in the pathophysiology of absence seizures. This study aims to understand the role of orexinergic signaling through the orexin-type 2 receptor (OX2R) in the pathophysiology of absence epilepsy. The pharmacological effect of a selective OX2R agonist, YNT-185 on spike-and-wave-discharges (SWDs) and the OX2R receptor protein levels in the cortex and thalamus in adult GAERS were investigated.

Methods

The effect of intracerebroventricular (ICV) (100, 300, and 600 nmol/10 μL), intrathalamic (30 and 40 nmol/500 nL), and intracortical (40 nmol/500 nL) microinjections of YNT-185 on the duration and number of spontaneous SWDs were evaluated in adult GAERS. The percentage of slow-wave sleep (SWS) and spectral characteristics of background EEG were analyzed after the ICV application of 600 nmol YNT-185. The level of OX2R expression in the somatosensory cortex and projecting thalamic nuclei of adult GAERS were examined by Western blot and compared with the non-epileptic Wistar rats.

Results

We showed that ICV administration of YNT-185 suppressed the cumulative duration of SWDs in GAERS compared to the saline-administered control group (p < 0.05). However, intrathalamic and intracortical microinjections of YNT-185 did not show a significant effect on SWDs. ICV microinjections of YNT-185 affect sleep states by increasing the percentage of SWS and showed a significant treatment effect on the 1–4 Hz delta frequency band power during the 1–2 h post-injection period where YNT-185 significantly decreased the SWDs. OXR2 protein levels were significantly reduced in the cortex and thalamus of GAERS when compared to Wistar rats.

Conclusion

This study investigated the efficacy of YNT-185 for the first time on absence epilepsy in GAERS and revealed a suppressive effect of OX2R agonist on SWDs as evidenced by the significantly reduced expression of OX2R in the cortex and thalamus. YNT-185 effect on SWDs could be attributed to its regulation of wake/sleep states. The results constitute a step toward understanding the effectiveness of orexin neuropeptides on absence seizures in GAERS and might be targeted by therapeutic intervention for absence epilepsy.
Is ChatGPT accurate and reliable in answering questions regarding head and neck cancer?
Authors: Kuşcu Oğuz , Pamuk A. Erim , Sütay Süslü Nilda , Hosal Sefik
Published: December 2023

Background and objective

Chat Generative Pre-trained Transformer (ChatGPT) is an artificial intelligence (AI)-based language processing model using deep learning to create human-like text dialogue. It has been a popular source of information covering vast number of topics including medicine. Patient education in head and neck cancer (HNC) is crucial to enhance the understanding of patients about their medical condition, diagnosis, and treatment options. Therefore, this study aims to examine the accuracy and reliability of ChatGPT in answering questions regarding HNC.

Methods

154 head and neck cancer-related questions were compiled from sources including professional societies, institutions, patient support groups, and social media. These questions were categorized into topics like basic knowledge, diagnosis, treatment, recovery, operative risks, complications, follow-up, and cancer prevention. ChatGPT was queried with each question, and two experienced head and neck surgeons assessed each response independently for accuracy and reproducibility. Responses were rated on a scale: (1) comprehensive/correct, (2) incomplete/partially correct, (3) a mix of accurate and inaccurate/misleading, and (4) completely inaccurate/irrelevant. Discrepancies in grading were resolved by a third reviewer. Reproducibility was evaluated by repeating questions and analyzing grading consistency.

Results

ChatGPT yielded “comprehensive/correct” responses to 133/154 (86.4%) of the questions whereas, rates of “incomplete/partially correct” and “mixed with accurate and inaccurate data/misleading” responses were 11% and 2.6%, respectively. There were no “completely inaccurate/irrelevant” responses. According to category, the model provided “comprehensive/correct” answers to 80.6% of questions regarding “basic knowledge”, 92.6% related to “diagnosis”, 88.9% related to “treatment”, 80% related to “recovery – operative risks – complications – follow-up”, 100% related to “cancer prevention” and 92.9% related to “other”. There was not any significant difference between the categories regarding the grades of ChatGPT responses (p=0.88). The rate of reproducibility was 94.1% (145 of 154 questions).

Conclusion

ChatGPT generated substantially accurate and reproducible information to diverse medical queries related to HNC. Despite its limitations, it can be a useful source of information for both patients and medical professionals. With further developments in the model, ChatGPT can also play a crucial role in clinical decision support to provide the clinicians with up-to-date information.
Therapeutic potential and pharmacological significance of extracellular vesicles derived from traditional medicinal plants
Authors: Wu Peijie , Wu Wenjun , Zhang Shu , Han Jun , Liu Chao , Yu Han , Chen Xiping , Chen Xiaofeng
Published: December 2023

Medicinal plants are the primary sources for the discovery of novel medicines and the basis of ethnopharmacological research. While existing studies mainly focus on the chemical compounds, there is little research about the functions of other contents in medicinal plants. Extracellular vesicles (EVs) are functionally active, nanoscale, membrane-bound vesicles secreted by almost all eukaryotic cells. Intriguingly, plant-derived extracellular vesicles (PDEVs) also have been implicated to play an important role in therapeutic application. PDEVs were reported to have physical and chemical properties similar to mammalian EVs, which are rich in lipids, proteins, nucleic acids, and pharmacologically active compounds. Besides these properties, PDEVs also exhibit unique advantages, especially intrinsic bioactivity, high stability, and easy absorption. PDEVs were found to be transferred into recipient cells and significantly affect their biological process involved in many diseases, such as inflammation and tumors. PDEVs also could offer unique morphological and compositional characteristics as natural nanocarriers by innately shuttling bioactive lipids, RNA, proteins, and other pharmacologically active substances. In addition, PDEVs could effectively encapsulate hydrophobic and hydrophilic chemicals, remain stable, and cross stringent biological barriers. Thus, this study focuses on the pharmacological action and mechanisms of PDEVs in therapeutic applications. We also systemically deal with facets of PDEVs, ranging from their isolation to composition, biological functions, and biotherapeutic roles. Efforts are also made to elucidate recent advances in re-engineering PDEVs applied as stable, effective, and non-immunogenic therapeutic applications to meet the ever-stringent demands. Considering its unique advantages, these studies not only provide relevant scientific evidence on therapeutic applications but could also replenish and inherit precious cultural heritage.
Energy transfer in reactive movements as a function of individual stretch load
Authors: Waldvogel Janice , Freyler Kathrin , Ritzmann Ramona , Gollhofer Albert
Published: December 2023

Background: By directly recording electromyographic activity profiles and muscle-tendon interaction, this study aimed to elucidate the mechanisms why well-trained track and field athletes (experts) are able to outperform untrained individuals without former systematic experience in reactive jump training (novices). In particular, reactive power output and the elastic recoil properties of the muscle-tendon unit (MTU) were of special interest. For this purpose, stiffness regulation on muscle and joint level, energy management in terms of storing or dissipating elastic energy were compared between experts and novices during various stretch loads.

Methods: Experts were compared with novices during reactive drop jumps (DJs) from drop heights ranging between 25 and 61 cm. Delta kinetic energy (Ekin) was calculated as the difference between the Ekin at take-off and ground contact (GC) to determine energy management. By recording electromyography of the lower limb muscles, in vivo fascicle dynamics (gastrocnemius medialis) and by combining kinematics and kinetics in a 3D inverse dynamics approach to compute ankle and knee joint kinetics, this study aimed to compare reactive jump performance, the neuromuscular activity and muscle-tendon interaction between experts and novices among the tested stretch loads.

Results: Experts demonstrated significantly higher power output during DJs. Among all drop heights experts realized higher delta Ekin compared to novices. Consequently, higher reactive jump performance shown for experts was characterized by shorter GC time (GCT), higher jump heights and higher neuromuscular activity before and during the GC phase compared to novices. Concomitantly, experts were able to realize highest leg stiffness and delta Ekin in the lowest stretch load; however, both groups compensated the highest stretch load by prolonged GCT and greater joint flexion. On muscle level, experts work quasi-isometrically in the highest stretch load, while in novices GM fascicles were forcefully stretched.

Conclusion: Group-specific stiffness regulation and elastic recoil properties are primarily influenced by the neuromuscular system. Due to their higher neuromuscular activity prior and during the GC phase, experts demonstrate higher force generating capacity. A functionally stiffer myotendinous system through enhanced neuromuscular input enables the experts loading their elastic recoil system more efficiently, thus realizing higher reactive power output and allowing a higher amount of energy storage and return. This mechanism is regulated in a stretch load dependent manner.
Genome-wide association analysis of time to heading and maturity in bread wheat using 55K microarrays
Authors: Ding Yindeng , Fang Hui , Gao Yonghong , Fan Guiqiang , Shi Xiaolei , Yu Shan , Ding Sunlei , Huang Tianrong , Wang Wei , Song Jikun
Published: December 2023

To investigate the genetic mechanisms underlying the reproductive traits (time to flowering and maturity) in wheat and identify candidate genes associated, a phenotypic analysis was conducted on 239 wheat accessions (lines) from around the world. A genome-wide association study (GWAS) of wheat heading and maturity phases was performed using the MLM (Q+K) model in the TASSLE software, combined with the Wheat 55K SNP array. The results revealed significant phenotypic variation in heading and maturity among the wheat accessions across different years, with coefficients of variation ranging from 0.96% to 1.97%. The phenotypic data from different years exhibited excellent correlation, with a genome-wide linkage disequilibrium (LD) attenuation distance of 3 Mb. Population structure analysis, evolutionary tree analysis, and principal component analysis indicated that the 239 wheat accessions formed a relatively homogeneous natural population, which could be divided into three subgroups. The GWAS results identified a total of 293 SNP marker loci that were significantly associated with wheat heading and maturity stages (P ≤ 0.001) in different environments. Among them, nine stable SNP marker loci were consistently detected in multiple environments. These marker loci were distributed on wheat chromosomes 1A、1B、2D、3A、5B、6D and 7A. Each individual locus explained 4.03%-16.06% of the phenotypic variation. Furthermore, through careful analysis of the associated loci with large phenotypic effect values and stable inheritance, a total of nine candidate genes related to wheat heading and maturity stages were identified. These findings have implications for molecular marker-assisted selection breeding programs targeting specific wheat traits at the heading and maturity stages. In summary, this study conducted a comprehensive GWAS of wheat heading and maturity phases, revealing significant associations between genetic markers and key developmental stages in wheat. The identification of candidate genes and marker loci provides valuable information for further studies on wheat breeding and genetic improvement targeted at enhancing heading and maturity traits.
How does self-efficacy, learner personality, and learner anxiety affect critical thinking of students
Authors: Fu Jing , Ding Yi , Nie Kaihua , Zaigham Ghulam Hussain Khan
Published: December 2023

The goal of critical thinking for students is to help them learn how to think critically and systematically so they can solve problems and make informed decisions. It aids students in developing their capacity for independent thought, allowing them to generate their own conclusions and base those decisions on facts and evidence. Therefore, one of the key goals of this study was to explore the factors affecting critical thinking of English as foreign language (EFL) learners. This article used social cognitive theory (SCT) to investigate how personal and cognitive factors affect EFL learners’ critical thinking. Data from 305 Chinese EFL learners were collected online, and structural equation modeling (SEM) was used to evaluate the data. The results showed that metacognitive learning strategies (MLS) were positively related to critical thinking and that self-efficacy, self-oriented learning perfectionism, and learner anxiety were significantly related to MLS. Moreover, MLS mediated the link between self-efficacy, self-oriented learning perfectionism, learner anxiety, and critical thinking. The findings further indicated that learner proactivity moderated the association between MLS and critical thinking. By applying social cognitive theory to examine the variables influencing EFL learners’ critical thinking, this study adds uniqueness. It does this by emphasizing the moderating influence of learner proactivity and the mediating function of metacognitive learning strategies. The findings of the research have significant ramifications for educators since they emphasize how vital it is to support metacognitive strategies for learning in order to improve EFL learners’ critical thinking abilities. Additionally, to create an atmosphere that is favorable for the development of critical thinking skills in EFL education, policymakers should think about implementing support systems and interventions that focus on learner anxiety, learner proactivity, and self-efficacy.
Serum and urinary essential trace elements in association with major depressive disorders: a case–control study
Authors: Fu Jiyong , Wang Qinqin , Wang Na , Li Shilong , Zhang Hongwei , Zhu Yuxing , Guo Hua , Wang Fukun , He Lei , Xia Shuang , Cao Bing
Published: December 2023

Introduction

The etiology and pathophysiology of major depressive disorders (MDDs) remain unclear. Increasing evidence has demonstrated that essential trace elements (ETEs), such as iodine (I), zinc (Zn), copper (Cu), selenium (Se), cobalt (Co), and molybdenum (Mo), play vital roles in MDDs.

Methods

In total, 72 patients with MDD and 75 healthy controls (HCs) in the Zhumadian Second People's Hospital, Henan Province, China were recruited in our study. The levels of different ETEs were examined in both serum and urine, using an inductively coupled plasma mass spectrometer (ICP-MS), for both the MDD patients and HCs.

Results

The serum levels of I, Se, Cu, and Mo were significantly lower in the MDD patients compared to the HCs (p < 0.05), and the urinary levels of I and Zn were significantly higher in the MDD patients compared to the HCs (p < 0.05). The serum concentration of I (Q3: OR = 0.210, Q4: OR = 0.272) was negatively associated with MDD after adjusting for potential confounders, including age, gender, and BMI, and the urinary concentration of I (Q4: OR = 2.952) was positively associated.

Conclusions

The higher levels of I, Se, Cu, and Mo in serum might be protective against the development of MDD, and the excess I and Zn in urine may be associated with MDD pathogenesis. Future research needs to gain a deeper understanding of the metabolic pathways of ETEs, especially I, Se, Zn, Cu, and Mo, in MDD, and their role in the pathogenesis of depression.
Acute air pollution and temperature exposure as independent and joint triggers of spontaneous preterm birth in New South Wales, Australia: a time-to-event analysis
Authors: Singh Tanya , Jalaludin Bin , Hajat Shakoor , Morgan Geoffrey G. , Meissner Katrin , Kaldor John , Green Donna , Jegasothy Edward
Published: December 2023

Introduction

Exposure to high ambient temperatures and air pollution has been shown to increase the risk of spontaneous preterm birth (sPTB). Less clear are the effects of cold and the joint effects of air pollution and temperature.

Methods

Using a Cox proportional hazard regression model, we assessed the risk of independent and combined short-term exposure to ambient daily mean temperature and PM2.5 associated with sPTB in the last week before delivery on overall sPTB (weeks 23–36) and three subtypes: extremely sPTB, very sPTB, and moderate-to-late sPTB for a birth cohort of 1,318,570 births from Australia (Jan 2001–Dec 2019), while controlling for chronic exposure (i.e., throughout pregnancy except the last week before delivery) to PM2.5 and temperature. The temperature was modeled as a natural cubic spline, PM2.5 as a linear term, and the interaction effect was estimated using a multiplicative term. For short-term exposure to temperature hazard ratios reported are relative to the median temperature (18.1°C).

Results

Hazard ratios at low temperature [5th percentile(11.5°C)] were 0.95 (95% CI: 0.90, 1.00), 1.08 (95% CI: 0.84, 1.4), 0.87 (95% CI: 0.71, 1.06), and 1.00 (95% CI: 0.94, 1.06) and greater for high temperature [95th percentile (24.5°C)]: 1.22 (95% CI: 1.16, 1.28), 1.27 (95% CI: 1.03, 1.57), and 1.26 (95% CI: 1.05, 1.5) and 1.05 (1.00, 1.11), respectively, for overall, extremely, very, and moderate-to-late sPTBs. While chronic exposure to PM2.5 had adverse effects on sPTB, short-term exposure to PM2.5 appeared to have a negative association with all types of sPTB, with hazard ratios ranging from 0.86 (95th CI: 0.80, 0.94) to 0.98 (95th CI: 0.97, 1.00) per 5 μg/m3 increase in PM2.5.

Discussion

The risk of sPTB was found to increase following acute exposure to hot and cold ambient temperatures. Earlier sPTB subtypes seemed to be the most vulnerable. This study adds to the evidence that short-term exposure to ambient cold and heat and longer term gestational exposure to ambient PM2.5 are associated with an elevated risk of sPTB.
Unraveling the effects of maternal breastfeeding duration and exclusive breast milk on children’s cognitive abilities in early childhood
Authors: Garon-Carrier Gabrielle , Tiraboschi Gabriel Arantes , Bernard Jonathan Y. , Matte-Gagné Célia , Laurent Angélique , Lemieux Annie , Fitzpatrick Caroline
Published: December 2023

Background

This study investigated the putative associations between mothers’ use of exclusive breast milk and the duration of breastfeeding with child cognitive development.

Methods

This study is based on 2,210 Canadian families with children assessed longitudinally from age 4 to 7 years on their memory-span and math skills. These cognitive abilities were measured with standardized tasks. Breastfeeding practices were collected via maternal reports. We applied propensity scores to control the social selection bias for breastfeeding.

Results

Results adjusted for propensity scores and sample weight revealed no significant differences between non-breastfed children with those being non-exclusively breastfed for 5 months or less, and with children being exclusively breastfed for 9.2 months on average, on their early math skills and memory-span. We found that children who were non-exclusively breastfed for 6.8 months on average had a slightly higher levels of memory-span at age 4 than children who were never breastfed, and this small but significant difference lasted up to age 7.

Conclusion

Our findings suggest no significant differences between children being exclusively breastfed and those fed with formula on their early math skills and memory-span. The encouragement of breastfeeding to promote child cognitive school readiness may, in some case (non-exclusive breastfeeding for more than 5 months), show a small but long-lasting advantage in early memory-span.
The impact of SARS-CoV-2 on healthcare workers of a large University Hospital in the Veneto Region: risk of infection and clinical presentation in relation to different pandemic phases and some relevant determinants
Authors: Liviero Filippo , Volpin Anna , Furlan Patrizia , Battistella Monica , Broggio Alessia , Fabris Laura , Favretto Francesco , Mason Paola , Cocchio Silvia , Cozzolino Claudia , Baldo Vincenzo , Moretto Angelo , Scapellato Maria Luisa
Published: December 2023

Aim

The aim of this study is to evaluate the incidence of SARS-CoV-2 infection and the prevalence of COVID-19-related symptoms in relation to pandemic phases and some relevant variables in a cohort of 8,029 HCWs from one of the largest Italian University Hospitals.

Methods

A single-center retrospective study was performed on data collected during SARS-CoV-2 infection surveillance of HCWs. Cox’s multiple regression was performed to estimate hazard ratios of SARS-CoV-2 infection. Logistic multivariate regression was used to assess the risk of asymptomatic infections and the onset of the most frequent symptoms. All analyses were adjusted for sociodemographic and occupational factors, pandemic phases, vaccination status, and previous infections.

Results

A total of 3,760 HCWs resulted positive (2.0%–18.6% across five study phases). The total incidence rate of SARS-CoV-2 infection was 7.31 cases per 10,000 person-days, significantly lower in phase 1 and higher in phases 4 and 5, compared to phase 3. Younger HCWs, healthcare personnel, and unvaccinated subjects showed a higher risk of infection. Overall, 24.5% were asymptomatic infections, with a higher probability for men, physicians, and HCWs tested for screening, fully vaccinated, and those with previous infection. The clinical presentation changed over the phases in relation to vaccination status and the emergence of new variants.

Conclusion

The screening activities of HCWs allowed for the early detection of asymptomatic cases, limiting the epidemic clusters inside the hospital wards. SARS-CoV-2 vaccination reduced infections and symptomatic cases, demonstrating again its paramount value as a preventive tool for occupational and public health.
Successful treatment of nivolumab and ipilimumab triggered type 1 diabetes by using sodium-glucose transporter 2 inhibitor: a case report and systematic review
Authors: Fujiwara Makoto , Shimizu Masaru , Okano Tatsuya , Maejima Yuko , Shimomura Kenju
Published: December 2023

Objective

Checkpoint inhibitors (CPIs) can trigger complications related to the autoimmune process such as CPI-triggered diabetes mellitus. The typical treatment for CPI-triggered diabetes is insulin, but a detailed therapeutic method has not yet been established. To prevent severe symptoms and mortality of diabetic ketoacidosis in advanced-stage cancer patients, the establishment of effective treatment of CPI-triggered diabetes, other than insulin therapy, is required.

Methods

We present a case of a 76-year-old man with CPI-triggered diabetes who was treated with nivolumab and ipilimumab for lung cancer. We also conducted a systematic review of 48 case reports of type 1 diabetes associated with nivolumab and ipilimumab therapy before June 2023.

Results

The patient’s hyperglycemia was not sufficiently controlled by insulin therapy, and after the remission of ketoacidosis, the addition of a sodium-glucose transporter (SGLT) 2 inhibitor, dapagliflozin, improved glycemic control. Most of the reported nivolumab/ipilimumab-induced type 1 diabetes was treatable with insulin, but very few cases required additional oral anti-diabetic agents to obtain good glucose control.

Conclusion

Although SGLT2 inhibitors have been reported to have adverse effects on ketoacidosis, recent studies indicate that the occurrence of ketoacidosis is relatively rare. Considering the pathological mechanism of CPI-triggered diabetes, SGLT2 inhibitors could be an effective choice if they are administered while carefully monitoring the patient’s ketoacidosis.
Has the consistency evaluation policy of generic drugs promoted the innovation quality of Chinese pharmaceutical manufacturing industry? An empirical study based on the difference-in-differences model
Authors: Liu Qiang , Huang Zhe , Mao Zhenbin
Published: December 2023

Introduction

In March 2016, the Chinese government officially launched a nationwide consistency evaluation of the quality and efficacy of generic drugs.

Methods

This paper conducted an empirical study using the Difference-in-Differences method to explore the effect of this policy on the innovation quality of China’s pharmaceutical manufacturing industry and further analyzed the underlying mechanism of action.

Results

The results of the study show that the generic consistency evaluation policy has a significant promotion effect on the innovation quality of China’s pharmaceutical manufacturing industry, and the promotion effect is the largest for non-state-owned enterprises and enterprises in the central region; in addition, the intensity of R&D capital investment and R&D personnel investment which play a mediating role.

Discussion

Therefore, we should fully recognize the positive effect of generic drug consistency evaluation policy on improving the innovation quality of the pharmaceutical manufacturing industry and pay attention to the necessity of regional coordination and unification in policy implementation and the formulation of supporting policy tools. This study provides empirical evidence for the implementation effect of the generic drug consistency evaluation policy, which can provide an essential reference for the further improvement of the procedure and the R&D decision-making of pharmaceutical enterprises.
Insights into the epidemiology, risk factors, and clinical outcomes of carbapenem-resistant Acinetobacter baumannii infections in critically ill children
Authors: Zhang Yufei , Xu Guifeng , Miao Fei , Huang Weichun , Wang Haiying , Wang Xing
Published: December 2023

Background and aims

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a leading cause of nosocomial infections with an increasing impact on critically ill patients, yet there is limited data on contributing factors. This study was aim to evaluate the prevalence and risk factors, and clinical outcomes of CRAB infections among critically ill children in a tertiary university teaching hospital in China.

Methods

From January 2016 to December 2021, all children diagnosed with nosocomial Acinetobacter baumannii (A. baumannii) infections in the pediatric intensive care unit (PICU) were identified through the computerized microbiology laboratory databases. Among them, children suffering from CRAB infection were designated as a case group, while children with carbapenem susceptible A. baumannii (CSAB) infection were assigned to a control group. This retrospective case-control study was based on two groups of patients to determine potential clinical factors contributing to CRAB infection and death among critically ill children via univariate and multivariate analyses.

Results

During the 6-year study period, a total of 372 episodes of nosocomial A. baumannii infection in the PICU were eligible and included in the study. These isolates displayed moderate or high rates of resistance to all tested antimicrobials except colistin. The overall prevalence of CRAB and MDRAB (multidrug-resistant A. baumannii) was 78.0% and 80.9%, respectively. Several risk factors found to significantly increase CRAB infection included receiving invasive operation (OR = 9.412, p = 0.001), gastric intubation (OR = 2.478, p = 0.026), prior carbapenems exposure (OR = 2.543, p = 0.003), severe pneumonia (OR = 3.235, p = 0.001), and hemoglobin <110g/L (OR = 3.049, p = 0.005). Of 372 patients with CRAB infection, the mortality rate was 30.9% (115/372) and mortality did not differ between children with CRAB and CSAB infections. Septic shock (OR = 2.992, p = 0.001), AST > 46U/L (OR = 2.015, p = 0.005), bone marrow aspiration (OR = 2.704, p = 0.008), lymphocyte <20 % (OR = 1.992, p = 0.006) and age (OR = 1.094, p = 0.002) were independent risk factors for the death of A. baumanni infection.

Conclusions

This study highlights considerable incidence rate and remarkable mortality of children with A. baumanni (especially CRAB) infections, and identifies age-specific risk factors for CRAB infection and mortality in critically ill children. These risk factors should be taken into account in pediatric hospitals in order to establish early intervention and rational treatment to improve clinical outcomes.
Should robots be polite? Expectations about politeness in human–robot interaction
Authors: Lumer Eleonore , Buschmeier Hendrik
Published: December 2023

Interaction with artificial social agents is often designed based on models of human interaction and dialogue. While this is certainly useful for basic interaction mechanisms, it has been argued that social communication strategies and social language use, a “particularly human” ability, may not be appropriate and transferable to interaction with artificial conversational agents. In this paper, we present qualitative research exploring whether users expect artificial agents to use politeness—a fundamental mechanism of social communication—in language-based human-robot interaction. Based on semi-structured interviews, we found that humans mostly ascribe a functional, rule-based use of polite language to humanoid robots and do not expect them to apply socially motivated politeness strategies that they expect in human interaction. This study 1) provides insights for interaction design for social robots’ politeness use from a user perspective, and 2) contributes to politeness research based on the analysis of our participants’ perspectives on politeness.
Mapping the knowledge structure and trends in Australian Indigenous health and wellbeing research from 2003 to 2022: a scientometric analysis
Authors: Krahe Michelle A. , Hall Kerry K. , Anderson Peter J. , Shannon Cindy
Published: December 2023

The health and wellbeing of Australian Indigenous peoples is a nationally sanctioned priority, but despite this, few studies have comprehensively analyzed the features and characteristics of the research in the field. In this regard, a comprehensive scientometric analysis and knowledge mapping to systematically summarize and discuss the current state of research, research trends, and emerging areas of research were conducted. Original articles and reviews published between 2003 and 2022 were obtained from the Web of Science Core Collection. CiteSpace and VOSviewer software were used to perform scientometric analysis and knowledge mapping. An examination of document and citation trends, authors, institutions, countries/regions, journals, and keywords was untaken, while co-citation, co-occurrence, and burst analysis provide insights and future development in this area. A total of 2,468 documents in this field were retrieved. A gradual increase in the number of documents over the past two decades is observed, with the number of documents doubling every ~7.5 years. Author Thompson SC and Charles Darwin University published the most documents, and 85.6% were affiliated with only Australian-based researchers. The Australian and New Zealand Journal of Public Health is the most prominent journal publishing in the field. The most commonly co-occurring keyword was “health,” and the keyword “risk” had the longest citation burst. Five keyword clusters were identified; “cultural safety” was the largest. This study articulates the knowledge structure of the research, revealing a shift from population-level and data-driven studies to more applied research that informs Indigenous peoples health and wellbeing. Based on this review, we anticipate emergent research areas to (1) reflect a more comprehensive understanding of the multidimensional factors that shape Indigenous health and wellbeing; (2) move beyond a deficit-based perspective; (3) respect cultural protocols and protect the rights and privacy of Indigenous participants; (4) address racism and discrimination within the healthcare system; (5) foster respectful, equitable, and collaborative research practices with Indigenous peoples; (6) provide culturally appropriate and effective interventions for prevention, early intervention, and treatment; and (7) ensure equitable change in systems to enhance access, quality, and outcomes in health and wellbeing.
Machine learning approaches to predict and detect early-onset of digital dermatitis in dairy cows using sensor data
Authors: Magana Jennifer , Gavojdian Dinu , Menahem Yakir , Lazebnik Teddy , Zamansky Anna , Adams-Progar Amber
Published: December 2023

The present study aimed to employ machine learning algorithms based on sensor behavior data for (1) early-onset detection of digital dermatitis (DD) and (2) DD prediction in dairy cows. Our machine learning model, which was based on the Tree-Based Pipeline Optimization Tool (TPOT) automatic machine learning method, for DD detection on day 0 of the appearance of the clinical signs has reached an accuracy of 79% on the test set, while the model for the prediction of DD 2 days prior to the appearance of the first clinical signs, which was a combination of K-means and TPOT, has reached an accuracy of 64%. The proposed machine learning models have the potential to help achieve a real-time automated tool for monitoring and diagnosing DD in lactating dairy cows based on sensor data in conventional dairy barn environments. Our results suggest that alterations in behavioral patterns can be used as inputs in an early warning system for herd management in order to detect variances in the health and wellbeing of individual cows.
A Novel Approach for Train Tracking in Virtual Coupling Based on Soft Actor-Critic
Authors: Chen Bin , Zhang Lei , Cheng Gaoyun , Liu Yiqing , Chen Junjie
Published: December 2023

The development of virtual coupling technology provides solutions to the challenges faced by urban rail transit systems. Train tracking control is a crucial component in the operation of virtual coupling, which plays a pivotal role in ensuring the safe and efficient movement of trains within the train and along the rail network. In order to ensure the high efficiency and safety of train tracking control in virtual coupling, this paper proposes an optimization algorithm based on Soft Actor-Critic for train tracking control in virtual coupling. Firstly, we construct the train tracking model under the reinforcement learning architecture using the operation states of the train, Proportional Integral Derivative (PID) controller output, and train tracking spacing and speed difference as elements of reinforcement learning. The train tracking control reward function is designed. Then, the Soft Actor-Critic (SAC) algorithm is used to train the virtual coupling train tracking reinforcement learning model. Finally, we took the Deep Deterministic Policy Gradient as the comparison algorithm to verify the superiority of the algorithm proposed in this paper.
Initial Identification of Thrust and Orbit Elements for Continuous Thrust Spacecraft in Circular Orbit
Authors: Zhao Shuailong , Tao Xuefeng , Li Zhi
Published: December 2023

Continuous thrust spacecraft in circular orbits have had a great influence on the identification and cataloging of space targets. Gaussian-type orbital element variational equations are simplified and approximated. Ground-based radar observation datasets are transformed into orbit elements datasets. The initial thrust and orbit elements are obtained by optimally solving the spatial parameter error sum of squares minimization problem with the Levenberg–Marquardt method. The simulation analysis is carried out under the high-precision orbit model, and the solution error of tangential acceleration is around 5 × 10−7 m/s2, and that of normal acceleration is around 3 × 10−6 m/s2; the accuracy of the semi-major axis is 350 m, and the accuracy of inclination is 0.095°. The method is applicable to the preliminary identification of thrust and orbit elements for circular orbit continuous thrust spacecraft and can provide reliable initial values for the subsequent precision orbit determination of such spacecraft.