bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of emerging and re-emerging zoonotic and vector-borne diseases in countries of the Eastern Mediterranean Region
Authors: Chughtai Abrar Ahmad , Kodama Chiori , Joshi Rohina , Tayyab Muhammad , Paiman Mohammad Akbar , Abubakar Abdinasir
Published: September 2023

Despite improvements in the detection and control of infectious diseases, many new pathogens are emerging and re-emerging in various parts of the world. Most of these emerging and re-emerging infections are of zoonotic origin, which highlights the importance of the human–animal interface. Similarly, the rate of vector-borne diseases has increased recently due to changes in human habitats, climate change, deforestation, changes in food production practices, and increased population movement. The risk of spread of these zoonotic and vector-borne diseases is higher in the Eastern Mediterranean Region (EMR) of the World Health Organization due to its topography and geopolitical situation, fragile health systems, complex humanitarian emergencies, and, in some countries, other socioeconomic risk factors. Many countries in the region have reported outbreaks of zoonotic and vector-borne diseases over the last few decades, and some of these diseases have spread to other WHO regions as well. Avian influenza A (H5N1) and Middle East respiratory syndrome coronavirus (MERS-CoV) are among the greatest threats to global health security and both viruses are endemic in the EMR. Countries in the EMR have made significant progress toward the control of zoonotic and vector-borne diseases in recent years, and prevention, preparedness, and response capacities have been improved. However, there are still many challenges associated with the control of these diseases in the EMR, particularly in countries facing humanitarian emergencies. In this paper, we present the current situation of emerging and re-emerging infections in the EMR and discuss progress, challenges, and ways forward.
Identifying the wetlands of international importance in Beibu Gulf along the East Asian – Australasian Flyway, based on multiple citizen science datasets
Authors: Tang Ningxin , Ma Yanju , Li Sixin , Yan Yizhu ,   and Citizen Science Project Team of Guangxi Biodiversity Research Conservation Association, Cheng Cheng , Lu Gang , Li Fei , Lv Liuxuan , Qin Peilin , Nguyen Hoai Bao , Nguyen Quang Hao , Le Trong Trai , Wee Shelby Qi Wei , He Tao , Yong Ding Li , Choi Chi-Yeung
Published: September 2023

The Beibu Gulf (Gulf of Tonkin, Vinh Bac Bo in Vietnamese), located midway along the East Asian-Australasian Flyway (EAAF), is a critical stopover and wintering region for migratory waterbirds. This transboundary coastal region, spanning between China and Vietnam, harbors diverse wetland habitats that provide refuge to waterbird species, including highly threatened species such as the spoon-billed sandpiper (CR) and the black-faced spoonbill (EN). However, the scarcity of comprehensive assessments regarding waterbird abundances, distribution, key wetland habitats, and regional threats hinders our understanding of its conservation significance at the flyway level. Further research is needed to address these knowledge gaps and facilitate effective conservation efforts in the Beibu Gulf. By synthesizing accessible citizen science datasets and published records from wetland sites in south China and northeast Vietnam, we concluded that at least 97 waterbird species used the Gulf’s wetlands during their annual cycle. Among surveys conducted from 2014 to 2022, 5 and 11 waterbird species were considered as first and second class protected species under the National Key Protected Wild Animal List in China; 2 species were listed as Critically Endangered on the IUCN Red List, 4 as Endangered and 2 as Vulnerable, underlying the critical importance of the Beibu Gulf for the survival of these species. Our study identified 25 sites in the Beibu Gulf that met the criteria for designation as internationally important wetlands. Alarmingly, less than a quarter (n = 5, or 20%) of these sites benefit from national or international protection. Localized threats, including aquatic resource harvesting, hunting, and aquaculture/fisheries, were widespread in the region. This study provides a crucial scientific baseline for continued waterbird monitoring, site prioritization, and the development of effective habitat management plans to conserve vital coastal wetland habitats in the Beibu Gulf in China and Vietnam.
Establishment and parameter analysis of the elasto-visco-plastic constitutive model for straw-potato residue mixture
Authors: Guo Wenbin , Jiang Xinyang , De Xuehong , Zhai Shuo , Shi Tianyu , Yang Jian , Zhang Xuhui , Wang Zhipeng
Published: September 2023

In an attempt to characterize the non-linear augmentation of stress as a function of strain during the compression molding process of the straw-potato residue mixture, and to analyze the impact of elasto-visco-plastic deformation on energy consumption and product quality, the present study has established an elasto-visco-plastic constitutive model for the straw-potato residue mixture based on stress-strain test data. The model parameters were obtained through curve fitting, including the elastic modulus E, viscous coefficient K, viscous index n, friction stress σf, and plastic coefficient R1/m. The effects of test factors such as moisture content, feeding amount, compression temperature, and compression speed on these model parameters were analyzed to decipher the elasto-visco-plastic deformation process of the mixture. Additionally, specific energy consumption (SEC) and relaxation ratio (Rr) were employed as test indicators and were subjected to correlation analysis with the model parameters, culminating in the establishment of a multivariate regression equation. The results indicate that the correlation between SEC and the model parameters is quite significant under different test conditions, while Rr is significantly correlated with n, σf, and R1/m only under different moisture contents. This suggests that the energy consumption in the molding of the straw-potato residue mixture is primarily due to overcoming the resistance of elasto-visco-plastic deformation and friction, while the quality of the molding is mainly influenced by the moisture content, thereby establishing a connection with the elasto-visco-plastic parameters. The multivariate regression equation ultimately derived can be used to discern the degree of influence of elastic deformation, viscous deformation and plastic deformation on the specific energy consumption during the compression of the straw-potato residue mixture.
Sevoflurane sedation in COVID-19 acute respiratory distress syndrome: an observational study with a propensity score matching model
Authors: Consales Guglielmo , Cappellini Iacopo , Freschi Benedetta , Campiglia Laura , Parise Maddalena , Zamidei Lucia
Published: September 2023

Introduction

The management of severe COVID-19-induced acute respiratory distress syndrome (C-ARDS) often involves deep sedation. This study evaluated the efficacy of sevoflurane, a volatile anesthetic, as an alternative to traditional intravenous sedation in this patient population.

Methods

This single-center, retrospective cohort study enrolled 112 patients with C-ARDS requiring invasive mechanical ventilation. A propensity score matching model was utilized to pair 56 patients receiving sevoflurane sedation with 56 patients receiving intravenous sedation. The primary outcome was mortality, with secondary outcomes being changes in oxygenation (PaO2/FiO2 ratio), pulmonary compliance, and levels of D-Dimer, CRP, and creatinine.

Results

The use of sevoflurane was associated with a statistically significant reduction in mortality (OR 0.40, 95% CI 0.18–0.87, beta = −0.9, p = 0.02). In terms of secondary outcomes, an increase in the PaO2/FiO2 ratio and pulmonary static compliance was observed, although the results were not statistically significant. No significant differences were noted in the levels of D-Dimer, CRP, and creatinine between the two groups.

Conclusion

Our findings suggest an association between the use of sevoflurane and improved outcomes in C-ARDS patients requiring invasive mechanical ventilation. However, due to the single-center, retrospective design of the study, caution should be taken in interpreting these results, and further research is needed to corroborate these findings. The study offers promising insights into potential alternative sedation strategies in the management of severe C-ARDS.
Research and development of the sOLVe Tube™ dual lumen endobronchial tube: from concept to construct
Authors: Nwajuaku Patricia , Barjaktarevic Igor , Hoftman Nir
Published: September 2023

Introduction

Dual lumen endobronchial tubes (DLTs) are frequently used for lung isolation and one lung ventilation in thoracic surgery and other specialized clinical scenarios. Modern DLTs are large and rigid, and account for half of all tracheobronchial injuries. Their 70 year old design has numerous flaws which limit their safety and clinical utility. Our research team set out to design a new and improved DLT to mitigate these shortcomings, and then test the proposed device to ensure proper function.

Methods

Using published airway anatomy data and computed tomography imaging from 195 thoracic surgery patients, we designed a new DLT with a single size/configuration that would fit into adult surgery patients. This single “Universal design” was intended to replace both left and right sided 35Fr-41Fr DLTs (8 total products), while remaining small in diameter (35Fr). Other design goals included: 1) making intubation easier and safer, 2) allowing full sized therapeutic bronchoscopes to fit into this tube, 3) making the DLT more resistant to dislodgement. After design process completion the proposed dimensions were tested against 195 patients' left and right mainstem bronchi for radiographic fit. Once production prototypes were manufactured, they were tested in large adult Yorkshire pigs and fresh human cadavers for anatomic fit and performance.

Results

The proposed design passed the radiographic fit test in all 195 patients for both left and right mainstem endobronchial placement. Intubation was successful and deemed atraumatic in all pigs and cadavers, and the device appropriately fit in both the right and left mainstem bronchi. Lung isolation was successfully achieved and the device proved resistant to axial force dislodgement.

Conclusion

We propose a new design for a novel DLT meant to replace 8 currently supplied adult configurations with a single, one size/configuration fits all product that allows for large bore bronchoscopy and resists axial force dislodgement.
Soil microbiota plays a key regulatory role in the outbreak of tobacco root rot
Authors: Li Pengfei , Gu Songsong , Zhu Yanmei , Xu Tianyang , Yang Yishuai , Wang Zhengqiang , Deng Xiangdong , Wang Bin , Li Wei , Mei Wenqiang , Hu Qiulong
Published: September 2023

Introduction

Root rot caused by the fungal pathogenFusariumsp. poses significant challenges to tobacco cultivation in China, leading to major economic setbacks. The interplay between this pathogen and the wider soil microbial community remains poorly understood.

Methods

High-throughput sequencing technology was utilized to evaluate soil prokaryotic, fungal, and protistan communities. We compared microbial communities in infected soils to those in healthy soils from the same field. Additionally, the influence of pH on the microbial communities was assessed.

Results

Infected soils displayed elevated levels of soil nutrients but diminished observed richness across prokaryotic, fungal, and protistan groups. The pathogenic fungiFusarium solani fsp.eumartii’sabundance was notably increased in infected soils. Infection withF. solanisignificantly altered the soil’s microbial community structure and interactions, manifested as a decrease in network scale and the number of keystone species. An evaluation of prokaryotes’ role inF. solani’sinvasion revealed an increased number of connecting nodes in infected soils. Additionally, relationships between predatory protists and fungi were augmented, whereas predation onF. solanideclined.

Discussion

The study underscores the significance of comprehending the interactions among soil microorganisms and brings to light the susceptibility of soil microbial communities to pathogen invasion. It offers insights into the multifaceted relationships and potential vulnerabilities within the soil ecosystem in the context ofFusariumsp. invasion.
Character variation of root space microbial community composition in the response of drought-tolerant spring wheat to drought stress
Authors: Fang Jing , Wei Shuli , Gao Yanrong , Zhang Xiangqian , Cheng Yuchen , Wang Jianguo , Ma Jie , Shi Gongfu , Bai Lanfang , Xie Rui , Zhao Xiaoqing , Ren Yongfeng , Lu Zhanyuan
Published: September 2023

Drought is the most prevalent environmental stress in crop production, posing a significant danger to food security. Microorganisms in the crop root zone affect crop growth and development, enhance effective nutrient use, and resist adversity hazards. To analyze the changes and functional differences of root space microbial (endosphere-rhizosphere-bulk soil) communities in spring wheat under drought stress. In this study, the root, rhizosphere, and bulk soil of the drought-tolerant group (DTG, three varieties) and drought-sensitive group (DSG, three varieties) were collected. The control (CK, 25–28%), moderate drought (MD, 15–18%), and severe drought (SD, 9–12%) were analyzed by high-throughput sequencing and bioinformatics. The results showed significant differences in the diversity of Bacteria and Fungi in the root space of spring wheat under drought stress (P < 0.05), with the drought-tolerant group exhibiting higher microbial diversity. The microbial community change in spring wheat root space was mainly determined by the niche differentiation of endosphere, rhizosphere, and bulk soil and declined from endosphere to bulk soil due to drought. The antagonism between microbial and root-space species increased, and the community’s complexity and stability deteriorated. Enriching drought-resistant preference groups like Actinobaciota, Variovorax, Streptomyces, and Conocybe altered the structure and function of the microbial community in the root space of spring wheat. Spring wheat’s root space Bacteria and Fungi have different strategies to respond to drought.
Novel variants in the CLCN4 gene associated with syndromic X-linked intellectual disability
Authors: Li Sinan , Zhang Wenxin , Liang Piao , Zhu Min , Zheng Bixia , Zhou Wei , Wang Chunli , Zhao Xiaoke
Published: September 2023

Objective

The dysfunction of the CLCN4 gene can lead to X-linked intellectual disability and Raynaud–Claes syndrome (MRXSRC), characterized by severe cognitive impairment and mental disorders. This study aimed to investigate the genetic defects and clinical features of Chinese children with CLCN4 variants and explore the effect of mutant ClC-4 on the protein expression level and subcellular localization through in vitro experiments.

Methods

A total of 401 children with intellectual disabilities were screened for genetic variability using whole-exome sequencing (WES). Clinical data, including age, sex, perinatal conditions, and environmental exposure, were collected. Cognitive, verbal, motor, and social behavioral abilities were evaluated. Candidate variants were verified using Sanger sequencing, and their pathogenicity and conservation were analyzed using in silico prediction tools. Protein expression and localization of mutant ClC-4 were measured using Western blotting (WB) and immunofluorescence microscopy. The impact of a splice site variant was assessed with a minigene assay.

Results

Exome analysis identified five rare CLCN4 variants in six unrelated patients with intellectual disabilities, including two recurrent heterozygous de novo missense variants (p.D89N and p.A555V) in three female patients, and two hemizygous missense variants (p.N141S and p.R694Q) and a splicing variant (c.1390-12T > G) that are maternally inherited in three male patients. The p.N141S variant and the splicing variant c.1390-12(T > G were novel, while p.R694Q was identified in two asymptomatic heterozygous female patients. The six children with CLCN4 variants exhibited a neurodevelopmental spectrum disease characterized by intellectual disability (ID), delayed speech, autism spectrum disorders (ASD), microcephaly, hypertonia, and abnormal imaging findings. The minigene splicing result indicated that the c.1390-12T > G did not affect the splicing of CLCN4 mRNA. In vitro experiments showed that the mutant protein level and localization of mutant protein are similar to the wild type.

Conclusion

The study identified six probands with CLCN4 gene variants associated with X-linked ID. It expanded the gene and phenotype spectrum of CLCN4 variants. The bioinformatic analysis supported the pathogenicity of CLCN4 variants. However, these CLCN4 gene variants did not affect the ClC-4 expression levels and protein location, consistent with previous studies. Further investigations are necessary to investigate the pathogenetic mechanism.
Role of hypoxic exosomes and the mechanisms of exosome release in the CNS under hypoxic conditions
Authors: Yang Rong , Li Zheng , Xu Jing , Luo Juan , Qu Zhichuang , Chen Xin , Yu Sixun , Shu Haifeng
Published: September 2023

Hypoxia is characterized by low oxygen levels in the body or environment, resulting in various physiological and pathological changes. The brain, which has the highest oxygen consumption of any organ, is particularly susceptible to hypoxic injury. Exposure to low-pressure hypoxic environments can cause irreversible brain damage. Hypoxia can occur in healthy individuals at high altitudes or in pathological conditions such as trauma, stroke, inflammation, and autoimmune and neurodegenerative diseases, leading to severe brain damage and impairments in cognitive, learning, and memory functions. Exosomes may play a role in the mechanisms of hypoxic injury and adaptation and are a current focus of research. Investigating changes in exosomes in the central nervous system under hypoxic conditions may aid in preventing secondary damage caused by hypoxia. This paper provides a brief overview of central nervous system injury resulting from hypoxia, and aimed to conduct a comprehensive literature review to assess the pathophysio-logical impact of exosomes on the central nervous system under hypoxic conditions.
Posterior spinal decompression in adults with spinal cord injury without traumatic compromise of the spinal canal: what is the data?
Authors: Solou Mary , Politis Anastasios A. , Ydreos Ιoannis , Papadopoulos Evangelos K. , Banos Stamatios , Savvanis Georgios , Gavra Maria M. , Boviatsis Efstathios J. , Stavrinou Lampis C.
Published: September 2023

Background

Spinal cord injury (SCI) can be caused by a variety of factors and its severity can range from a mild concussion to a complete severing of the spinal cord. Τreatment depends on the type and severity of injury, the patient’s age and overall health. Reduction of dislocated or fractured vertebrae via closed manipulation or surgical procedures, fixation and removal of bony fragments and debris that compromise the spinal canal are indicated for decompression of the spinal cord and stabilization of the spine. However, when there is no obvious traumatic obstruction of spinal canal, the question arises as to whether laminectomy is needed to be performed to improve neurological outcome.

Methods

A literature review covering all indexed studies published between 2013 and 2023 was performed using keywords to identify the patient group of interest (spinal cord injury, SCI, spinal cord trauma, cervical, thoracic, lumbar, thoracolumbar),central cord syndrome (CCS) and the interventions (laminectomy, laminoplasty, decompression, duroplasty).

Results

This review includes6 observational studies investigating the outcome of posterior spinal decompression in patients suffering from spinal cord injury without traumatic spinal cord stenosis. Most patients already had degenerative stenosis. From a total of 202, 151 patients (74.7%) improved neurologically by at least one grade at ASIA scale, after being treated with either laminectomy, laminoplasty, duroplasty or a combination of these techniques.

Conclusion

Early decompression in SCI patients remains a reasonable practice option and can be performed safely, but no specific evidence supports the use of laminectomy alone. There is emerging evidence that intended durotomy followed by extended meningoplasty may improve the neurological outcome in patients suffering from SCI when meta-traumatic edema is apparent. However, the lack of high-quality evidence and results support the need for further research.
Associations between psychotropic drugs and rsEEG connectivity and network characteristics: a cross-sectional study in hospital-admitted psychiatric patients
Authors: Zandstra Melissa G. , Meijs Hannah , Somers Metten , Stam Cornelis J. , de Wilde Bieke , van Hecke Jan , Niemegeers Peter , Luykx Jurjen J. , van Dellen Edwin
Published: September 2023

Introduction

Resting-state EEG (rsEEG) characteristics, such as functional connectivity and network topology, are studied as potential biomarkers in psychiatric research. However, the presence of psychopharmacological treatment in study participants poses a potential confounding factor in biomarker research. To address this concern, our study aims to explore the impact of both single and multi-class psychotropic treatments on aforementioned rsEEG characteristics in a psychiatric population.

Methods

RsEEG was analyzed in a real-world cross-sectional sample of 900 hospital-admitted psychiatric patients. Patients were clustered into eight psychopharmacological groups: unmedicated, single-class treatment with antipsychotics (AP), antidepressants (AD) or benzodiazepines (BDZ), and multi-class combinations of these treatments. To assess the associations between psychotropic treatments and the macroscale rsEEG characteristics mentioned above, we employed a general linear model with post-hoc tests. Additionally, Spearman’s rank correlation analyses were performed to explore potential dosage effects.

Results

Compared to unmedicated patients, single-class use of AD was associated with lower functional connectivity in the delta band, while AP was associated with lower functional connectivity in both the delta and alpha bands. Single-class use of BDZ was associated with widespread rsEEG differences, including lower functional connectivity across frequency bands and a different network topology within the beta band relative to unmedicated patients. All of the multi-class groups showed associations with functional connectivity or topology measures, but effects were most pronounced for concomitant use of all three classes of psychotropics. Differences were not only observed in comparison with unmedicated patients, but were also evident in comparisons between single-class, multi-class, and single/multi-class groups. Importantly, multi-class associations with rsEEG characteristics were found even in the absence of single-class associations, suggesting potential cumulative or interaction effects of different classes of psychotropics. Dosage correlations were only found for antipsychotics.

Conclusion

Our exploratory, cross-sectional study suggests small but significant associations between single and multi-class use of antidepressants, antipsychotics and benzodiazepines and macroscale rsEEG functional connectivity and network topology characteristics. These findings highlight the importance of considering the effects of specific psychotropics, as well as their interactions, when investigating rsEEG biomarkers in a medicated psychiatric population.
“What” and “when” predictions modulate auditory processing in a mutually congruent manner
Authors: Cappotto Drew , Luo Dan , Lai Hiu Wai , Peng Fei , Melloni Lucia , Schnupp Jan Wilbert Hendrik , Auksztulewicz Ryszard
Published: September 2023

Introduction

Extracting regularities from ongoing stimulus streams to form predictions is crucial for adaptive behavior. Such regularities exist in terms of the content of the stimuli and their timing, both of which are known to interactively modulate sensory processing. In real-world stimulus streams such as music, regularities can occur at multiple levels, both in terms of contents (e.g., predictions relating to individual notes vs. their more complex groups) and timing (e.g., pertaining to timing between intervals vs. the overall beat of a musical phrase). However, it is unknown whether the brain integrates predictions in a manner that is mutually congruent (e.g., if “beat” timing predictions selectively interact with “what” predictions falling on pulses which define the beat), and whether integrating predictions in different timing conditions relies on dissociable neural correlates.

Methods

To address these questions, our study manipulated “what” and “when” predictions at different levels – (local) interval-defining and (global) beat-defining – within the same stimulus stream, while neural activity was recorded using electroencephalogram (EEG) in participants (N = 20) performing a repetition detection task.

Results

Our results reveal that temporal predictions based on beat or interval timing modulated mismatch responses to violations of “what” predictions happening at the predicted time points, and that these modulations were shared between types of temporal predictions in terms of the spatiotemporal distribution of EEG signals. Effective connectivity analysis using dynamic causal modeling showed that the integration of “what” and “when” predictions selectively increased connectivity at relatively late cortical processing stages, between the superior temporal gyrus and the fronto-parietal network.

Discussion

Taken together, these results suggest that the brain integrates different predictions with a high degree of mutual congruence, but in a shared and distributed cortical network. This finding contrasts with recent studies indicating separable mechanisms for beat-based and memory-based predictive processing.
A preliminary study for the clinical effect of one combinational physiotherapy and its potential influence on gut microbial composition in children with Tourette syndrome
Authors: Bao Chun , Wei Meng , Pan Hongguo , Wen Ming , Liu Ziming , Xu Yue , Jiang Huihui
Published: September 2023

Introduction

Tourette syndrome (TS) is a chronic neuropsychiatric disorder with unknown causes and inadequate therapies. Inspired by the important roles of gut microbiota in some mental illnesses, the interactions between gut microbiota and TS via the gut-brain axis have gained more and more attention. This study aimed to characterize the gut microbial profiles in children with TS, and explore the clinical effects of one combinational physiotherapy and its potential influence on gut microbial composition.

Methods

The gut microbial profiles were depicted based on the sequence data of 32 patients and 29 matched health children by 16S rDNA amplicon pyrosequencing. Thirty of thirty-two patients underwent uninterrupted two 10-day courses of combinational physiotherapy, which included a 60-minute cranial electrotherapy stimulation (CES) training followed by a 30-minute biofeedback training per session, 2 sessions a day.

Results

Our results indicated that the gut microbial composition in children with TS was different from that in healthy controls. Multiple GBM neurotransmitter modules obtained through Picrust2 functional predictive analysis were significantly increased in patients, including Histamine degradation, Dopamine degradation, and DOPAC synthesis. Moreover, this combinational physiotherapy could significantly diminish tic activity, whose positive effects were first reported in children with TS. Lastly, different gut microbial compositions and predictive metabolic pathways were also observed between patients before and after this treatment, with lower abundances of the genera (e.g., Dorea) and significant decreases of GBM neurotransmitter modules (e.g. dopamine degradation) in patients after this treatment, indicating that improved clinical symptoms might be accompanied by an improvement of intestinal microenvironment.

Discussion

Children with TS showed a cognizable gut microbial profile, and certain enriched bacteria with pro-inflammatory potential might induce neuroinflammatory responses. This combinational physiotherapy could significantly diminish tic activity, and the gut microbial compositions in patients after this treatment were different from those without any treatment, indicating the existence of bidirectional communication of the gut-brain axis in TS. But studies on the gut microbial characteristics in TS patients, the influences of gut microbiota on tic severity, the efficacy and safety of this treatment, and the bidirectional regulatory mechanism between brain signals and gut microbiota in TS still need to be explored.
A pharmacist-led opioid de-escalation program after completion of chemoradiotherapy in locally advanced head and neck cancer
Authors: Horinouchi Ai , Enokida Tomohiro , Suzuki Shinya , Kamata Hayato , Kaneko Asumi , Matsuyama Chihiro , Fujisawa Takao , Ueda Yuri , Ito Kazue , Okano Susumu , Kawasaki Toshikatsu , Tahara Makoto
Published: September 2023

Background

Persistent opioid use frequently leads to substantial negative impacts on quality of life, and as the outlook for numerous cancer types continues to improve, these complications become increasingly crucial. It is essential to acknowledge that extended or excessive opioid use may result in adverse effects in patients who completed radiation therapy (RT).

Methods

In this time-series analysis, we compared the outcomes of patients who participated in the pharmacist-led opioid de-escalation (PLODE) program after completing concurrent radiotherapy (CRT) between June 2018 and February 2019 against patients who completed CRT between June 2017 and March 2018 and did not participate in the program.

Results

Among 61 patients, 16 (26%) used opioids after completing CRT and participated in the PLODE program. Before starting the program, 93 patients completed CRT between June 2017 and March 2018 and 32 (34%) used opioids at CRT completion. These patients were deemed the control group. In the PLODE group, outpatient pharmacist intervention was performed, with 29 total interventions related to opioid use, of which 16 (55%) recommended tapering or discontinuing opioids according to the definition of this program. Patients who participated in the PLODE program discontinued opioids significantly earlier than those in the control group (median time to opioid discontinuation 11 days vs. 24.5 days, p < 0.001). None of the patients in the PLODE group resumed opioid use following discontinuation or escalated opioid dosing due to worsening pain.

Conclusion

This study showed the utility of pharmacist-initiated interventions for opioid use in patients with head and neck cancer who had completed CRT.
Liver metastasis affects progression pattern during immune checkpoint inhibitors monotherapy in gastric cancer
Authors: Motoo Iori , Ando Takayuki , Hamashima Takeru , Kajiura Shinya , Sakumura Miho , Ueda Yuko , Murayama Aiko , Ogawa Kohei , Tsukada Kenichiro , Ueda Akira , Suzuki Nobuhiro , Nakada Naokatsu , Nakashima Koji , Hosokawa Ayumu , Yasuda Ichiro
Published: September 2023

Introduction

The efficacy of immune checkpoint inhibitors (ICIs) is heterogeneous at each metastatic site, and tumor progression pattern is associated with survival; however, it remains unclear in gastric cancer (GC). Therefore, we aimed to clarify the progression pattern in response to ICIs in patients with GC, and we analyzed its mechanism focusing on the intratumoral immune cells.

Methods

Patients who received ICIs were retrospectively classified into non-systemic and systemic progression groups based on their radiological assessments. Moreover, the best percentage change in target lesions from each organ was compared.

Results

Among 148 patients, the non-systemic progression group showed a significant improvement in overall survival (OS) compared with the systemic progression group (median, 5.6 months vs. 3.3 months; HR, 0.53; 95%CI, 0.32–0.89; p = 0.012). Poor performance status (HR, 1.73, 95%CI, 1.00–2.87) and systemic progression (HR, 3.09, 95%CI, 1.95–4.82) were associated with OS. Of all metastatic sites, the liver showed the poorest percentage change, and liver metastasis (OR, 2.99, 95%CI, 1.04–8.58) was associated with systemic progression. Hence, intratumoral CD8+ T-cell density was lower in patients with liver metastasis than in those without liver metastasis after ICIs, although the density of CD4+ T-cells (Th1, Th17, and Treg) and CD163+ cells (TAM) were not significantly different.

Conclusion

The new progression pattern was associated with OS in GC. Liver metastasis may be a predictive factor of systemic progression during ICIs by regulating intratumoral CD8+ T-cells.
Robot-assisted versus conventional laparoscopic surgery for endometrial cancer: long-term comparison of outcomes
Authors: Eoh Kyung Jin , Kim Tae-Joong , Park Jeong-Yeol , Kim Hee Seung , Paek Jiheum , Kim Young Tae
Published: September 2023

Objective

There is a lack of multi-institutional large-volume and long-term follow-up data on comparisons between robot-assisted surgery and conventional laparoscopic surgery. This study compared the surgical and long-term survival outcomes between patients who underwent robot-assisted or conventional laparoscopic surgery for endometrial cancer.

Methods

We retrospectively reviewed the data of patients from five large academic institutions who underwent either robot-assisted or conventional laparoscopic surgery for the treatment of endometrial cancer between 2012 and 2017, ensuring at least 5 years of potential follow-up. Intra- and postoperative outcomes, long-term disease-free survival, and overall survival were compared.

Results

The study cohort included 1,003 unselected patients: 551 and 452 patients received conventional laparoscopic and robot-assisted surgery, respectively. The median follow-up duration was 57 months. Postoperative complications were significantly less likely to occur in the robot-assisted surgery group compared to the laparoscopic surgery group (7.74% vs. 13.79%, P = 0.002), primarily limited to minor complications. There were no significant differences in survival: 5-year disease-free survival was 91.2% versus 90.0% (P = 0.628) and overall survival was 97.9% versus 96.8% (P = 0.285) in the robot-assisted and laparoscopic surgery cohorts, respectively. Cox proportional hazard regression models demonstrated that the mode of surgery was not associated with disease-free survival (hazard ratio, 0.897; confidence interval, 0.563–1.429) or overall survival (hazard ratio, 0.791; confidence interval, 0.330–1.895) after adjusting for confounding factors.

Conclusion

Robot-assisted surgery for endometrial cancer demonstrates comparable long-term survival outcomes and a reduced incidence of postoperative minor complications when compared to conventional laparoscopic surgery.
HPV16 E7 oncoprotein test as a triage strategy for HPV16-positive women in cervical cancer screening: long-term follow-up outcome
Authors: Wang Xinmei , Shuai Guangnan , Xu Junhui , Liu Meihua , Zhao Jianguo , Zhang Na , Zhang Wenwen , Qu Pengpeng
Published: September 2023

Background

Colposcopy is recommended once human papillomavirus (HPV)16/18 infection is detected. However, not all HPV16/18-positive women will necessarily develop cervical lesions. Therefore, this study aimed to investigate the application of quantitative HPV16 E7 oncoprotein detection as a cervical cancer screening method for more efficient screening while minimizing unnecessary colposcopy.

Methods

E7 oncoprotein (HPV16) was quantitatively detected in cervical exfoliated cells of HPV16-positive women. The levels of HPV16 E7 oncoprotein in different degrees of cervical lesions were compared, and the optimal cut-off value for identifying HSIL+ was determined by receiver operating characteristic (ROC) curve analysis. With a pathological diagnosis as the gold standard, the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Kappa value were calculated to verify the diagnostic value of the method. Women diagnosed with low-grade squamous intraepithelial lesions (LSIL) and normal women were followed up for 5 years to evaluate the predictive value of HPV16 E7 protein for disease progression/persistent infection.

Results

The expression level of HPV16 E7 oncoprotein was positively correlated with the degree of the cervical lesion (r = 0.589, P < 0.01). The area under the ROC curve (AUC) was 0.817 (confidence interval: 0.729–0.904). The cut-off value of E7 oncoprotein for identifying HSIL+ was 8.68 ng/ml. The SEN, SPE, PPV, NPV, and Kappa values of HPV16 E7 oncoprotein for the identification of HSIL+ were 87.1%,70.0%, 87.1%, 70.0%, and 0.571, respectively, which were higher than those of ThinPrep cytology test (TCT). The SEN, SPE, PPV, and NPV of HPV16 E7 oncoprotein in predicting disease progression/persistent infection were 93.75%, 91.30%, 88.24%, and 95.45%, respectively.

Conclusion

The quantitative detection of HPV 16 E7 oncoprotein can not only accurately screen cervical lesions but also achieve efficient colposcopy referral. Additionally, HPV16 E7 oncoprotein can accurately predict the progression of cervical lesions and persistent HPV infection.
Beyond liver cancer, more application scenarios for alpha-fetoprotein in clinical practice
Authors: Ma Chenyu , Jin Yuexinzi , Wang Yuhan , Xu Huaguo , Zhang Jiexin
Published: September 2023

Alpha-fetoprotein (AFP) is a commonly used clinical biomarker. Before 1970, the two-way agar diffusion method was mainly used, and the specificity of AFP in the diagnosis of primary liver cancer was satisfactory. However, its positivity rate was not very high. The diagnostic value of AFP is changing with the evolution of detection methods. Here, we performed a literature search to identify English-language publications. The search was performed from January 2015 to April 2023 using the PubMed database and the following terms in [Titles/Abstracts]: alpha-fetoprotein, clinical practice, detection, etc. The references of retrieved articles were also screened to broaden the search. Studies referring to liver cancer and AFP detection methods were excluded. In this review, several clinical application scenarios for AFP were systematically reviewed, and its potential detection value in the future was discussed.
Comparison of mortality and short-term outcomes between classic, intubation-surfactant-extubation, and less invasive surfactant administration methods of surfactant replacement therapy
Authors: Kim Seung Yeon , Lim Jiseun , Shim Gyu-Hong
Published: September 2023

Background

Intubation-Surfactant-Extubation (InSurE) and less invasive surfactant administration (LISA) are alternative surfactant replacement therapy methods for reducing the complications associated with invasive mechanical ventilation. This study aimed to compare the Classic, InSurE, and LISA methods in Very-Low-Birth-Weight infants (VLBWIs) in South Korea.

Methods

The Korean Neonatal Network (KNN) enrolled VLBWIs born between January 1, 2019 and December 31, 2020. They were analyzed retrospectively to compare the duration of respiratory support, length of hospitalization, mortality, and short-term outcomes of the three groups.

Results

The duration of invasive ventilator support was shorter in the following order: InSurE (3.99 ± 11.93 days), LISA (8.78 ± 29.32 days), and the Classic group (22.36 ± 29.94 days) (p = 0.014, p < 0.01) and InSurE had the shortest hospitalization (64.91 ± 24.07 days, p < 0.05) although the results couldn't adjust for confounding factor because of irregular distribution. InSurE had the lower risk of intraventricular hemorrhage (IVH) grade II–IV [odds ratio (OR) 0.524 [95% confidence interval (CI): 0.287–0.956], p = 0.035] than in the Classic group. Mortality was lower in the InSurE [OR 0.377 (95% CI: 0.146–0.978), p = 0.045] and LISA [OR 0.296 (95% CI: 0.102–0.862), p = 0.026] groups than in the Classic group. There was a reduced risk of moderate to severe bronchopulmonary dysplasia (BPD) [OR 0.691 (95% CI: 0.479–0.998, p = 0.049), OR 0.544 (95% CI: 0.355–0.831, p = 0.005), respectively], pulmonary hypertension [OR 0.350 (95% CI: 0.150–0.817, p = 0.015), OR 0.276 (95% CI: 0.107–0.713, p = 0.008), respectively], periventricular leukomalacia (PVL) [OR 0.382 (95% CI: 0.187–0.780, p = 0.008), OR 0.246 (95% CI: 0.096–0.627, p = 0.003), respectively], and patent ductus arteriosus (PDA) with treatment [OR 0.628 (95% CI: 0.454–0.868, p = 0.005), OR 0.467 (95% CI: 0.313–0.696, p < 0.001) respectively] in the InSurE and LISA groups compared to the Classic group.

Conclusion

InSurE showed the lowest duration of invasive ventilator support, length of hospitalization. InSurE and LISA exhibited reduced mortality and decreased risks of moderate to severe BPD, pulmonary hypertension, PVL, and PDA with treatment compared to the Classic group.
Approach to machine learning for extraction of real-world data variables from electronic health records
Authors: Adamson Blythe , Waskom Michael , Blarre Auriane , Kelly Jonathan , Krismer Konstantin , Nemeth Sheila , Gippetti James , Ritten John , Harrison Katherine , Ho George , Linzmayer Robin , Bansal Tarun , Wilkinson Samuel , Amster Guy , Estola Evan , Benedum Corey M. , Fidyk Erin , Estévez Melissa , Shapiro Will , Cohen Aaron B.
Published: September 2023

Background: As artificial intelligence (AI) continues to advance with breakthroughs in natural language processing (NLP) and machine learning (ML), such as the development of models like OpenAI’s ChatGPT, new opportunities are emerging for efficient curation of electronic health records (EHR) into real-world data (RWD) for evidence generation in oncology. Our objective is to describe the research and development of industry methods to promote transparency and explainability.

Methods: We applied NLP with ML techniques to train, validate, and test the extraction of information from unstructured documents (e.g., clinician notes, radiology reports, lab reports, etc.) to output a set of structured variables required for RWD analysis. This research used a nationwide electronic health record (EHR)-derived database. Models were selected based on performance. Variables curated with an approach using ML extraction are those where the value is determined solely based on an ML model (i.e. not confirmed by abstraction), which identifies key information from visit notes and documents. These models do not predict future events or infer missing information.

Results: We developed an approach using NLP and ML for extraction of clinically meaningful information from unstructured EHR documents and found high performance of output variables compared with variables curated by manually abstracted data. These extraction methods resulted in research-ready variables including initial cancer diagnosis with date, advanced/metastatic diagnosis with date, disease stage, histology, smoking status, surgery status with date, biomarker test results with dates, and oral treatments with dates.

Conclusion: NLP and ML enable the extraction of retrospective clinical data in EHR with speed and scalability to help researchers learn from the experience of every person with cancer.
Microbiome engineering optimized by Antarctic microbiota to support a plant host under water deficit
Authors: Rodríguez Rodrigo , Barra Patricio J. , Larama Giovanni , Carrion Víctor J. , de la Luz Mora María , Hale Lauren , Durán Paola
Published: September 2023

Climate change challenges modern agriculture to develop alternative and eco-friendly solutions to alleviate abiotic and/or biotic stresses. The use of soil microbiomes from extreme environments opens new avenues to discover novel microorganisms and microbial functions to protect plants. In this study we confirm the ability of a bioinoculant, generated by natural engineering, to promote host development under water stress. Microbiome engineering was mediated through three factors i) Antarctic soil donation, ii) water deficit and iii) multigenerational tomato host selection. We revealed that tomato plants growing in soils supplemented with Antarctic microbiota were tolerant to water deficit stress after 10 generations. A clear increase in tomato seedling tolerance against water deficit stress was observed in all soils over generations of Host Mediated Microbiome Engineering, being Fildes mixture the most representatives, which was evidenced by an increased survival time, plant stress index, biomass accumulation, and decreased leaf proline content. Microbial community analysis using 16s rRNA gene amplicon sequencing data suggested a microbiome restructuring that could be associated with increased tolerance of water deficit. Additionally, the results showed a significant increase in the relative abundance of Candidatus Nitrosocosmicus and Bacillus spp. which could be key taxa associated with the observed tolerance improvement. We proposed that in situ microbiota engineering through the evolution of three factors (long-standing extreme climate adaption and host and stress selection) could represent a promising strategy for novel generation of microbial inoculants.
Development of a plant-based oral vaccine candidate against the bovine respiratory pathogen Mannheimia haemolytica
Authors: Kaldis Angelo , Uddin Muhammed Salah , Guluarte Jose Ortiz , Martin Coby , Alexander Trevor W. , Menassa Rima
Published: September 2023

Bovine respiratory disease (BRD) affects feedlot cattle across North America, resulting in economic losses due to animal treatment and reduced performance. In an effort to develop a vaccine candidate targeting a primary bacterial agent contributing to BRD, we produced a tripartite antigen consisting of segments of the virulence factor Leukotoxin A (LktA) and lipoprotein PlpE fromMannheimia haemolytica, fused to a cholera toxin mucosal adjuvant (CTB). This recombinant subunit vaccine candidate was expressed in the leaves ofNicotiana benthamianaplants, with accumulation tested in five subcellular compartments. The recombinant protein was found to accumulate highest in the endoplasmic reticulum, but targeting to the chloroplast was employed for scaling up production due the absence of post-translational modification while still producing feasible levels. Leaves were freeze dried, then orally administered to mice to determine its immunogenicity. Sera from mice immunized with leaf tissue expressing the recombinant antigen contained IgG antibodies, specifically recognizing both LktA and PlpE. These mice also had a mucosal immune response to the CTB+LktA+PlpE protein as measured by the presence of LktA- and PlpE-specific IgA antibodies in lung and fecal material. Moreover, the antigen remained stable at room temperature with limited deterioration for up to one year when stored as lyophilized plant material. This study demonstrated that a recombinant antigen expressed in plant tissue elicited both humoral and mucosal immune responses when fed to mice, and warrants evaluation in cattle.