bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolating together during COVID-19: Results from the Telehealth Intervention Program for older adults
Authors: Sekhon Harmehr , Lavin Paola , Vacaflor Blanca , Rigas Christina , Cinalioglu Karin , Su Chien-Lin , Bodenstein Katie , Dikaios Elena , Goodman Allana , Raymond Florence Coulombe , Ibrahim Marim , Bein Magnus , Gruber Johanna , Se Jade , Sasi Neeti , Walsh Chesley , Nazar Rim , Hanganu Cezara , Berkani Sonia , Royal Isabelle , Schiavetto Alessandra , Looper Karl , Launay Cyrille , McDonald Emily G. , Seitz Dallas , Kumar Sanjeev , Beauchet Olivier , Khoury Bassam , Bouchard Stephane , Battistini Bruno , Fallavollita Pascal , Miresco Marc , Bruneau Marie-Andrée , Vahia Ipsit , Bukhari Syeda , Rej Soham
Published: October 2022

Background

A pressing challenge during the COVID-19 pandemic and beyond is to provide accessible and scalable mental health support to isolated older adults in the community. The Telehealth Intervention Program for Older Adults (TIP-OA) is a large-scale, volunteer-based, friendly telephone support program designed to address this unmet need.

Methods

A prospective cohort study of 112 TIP-OA participants aged ≥60 years old was conducted in Quebec, Canada (October 2020–June 2021). The intervention consisted of weekly friendly phone calls from trained volunteers. The primary outcome measures included changes in scores of stress, depression, anxiety, and fear surrounding COVID-19, assessed at baseline, 4 and 8-weeks. Additional subgroup analyses were performed with participants with higher baseline scores.

Results

The subgroup of participants with higher baseline depression scores (PHQ9 ≥10) had significant improvements in depression scores over the 8-week period measured [mean change score = −2.27 (±4.76), 95%CI (−3.719, −0.827), p = 0.003]. Similarly, participants with higher baseline anxiety scores (GAD7 ≥10) had an improvement over the same period, which, approached significance (p = 0.06). Moreover, despite peaks in the pandemic and related stressors, our study found no significant (p ≥ 0.09) increase in stress, depression, anxiety or fear of COVID-19 scores.

Discussion

This scalable, volunteer-based, friendly telephone intervention program was associated with decreased scores of depression and anxiety in older adults who reported higher scores at baseline (PHQ 9 ≥10 and GAD7 ≥10).
Inhibition of growth, biofilm formation, virulence, and surface attachment of Agrobacterium tumefaciens by cinnamaldehyde derivatives
Authors: Ahmed Bilal , Jailani Afreen , Lee Jin-Hyung , Lee Jintae
Published: October 2022

Agrobacterium tumefaciens, a soil-borne, saprophytic plant pathogen that colonizes plant surfaces and induces tumors in a wide range of dicotyledonous plants by transferring and expressing its T-DNA genes. The limited availabilities and efficacies of current treatments necessitate the exploration of new anti-Agrobacterium agents. We examined the effects of trans-cinnamaldehyde (t-CNMA) and its derivatives on the cell surface hydrophobicity, exopolysaccharide and exo-protease production, swimming motility on agar, and biofilm forming ability of A. tumefaciens. Based on initial biofilm inhibition results and minimum inhibitory concentration (MIC) data, 4-nitro, 4-chloro, and 4-fluoro CNMAs were further tested. 4-Nitro, 4-chloro, and 4-fluoro CNMA at ≥150 μg/ml significantly inhibited biofilm formation by 94–99%. Similarly, biofilm formation on polystyrene or nylon was substantially reduced by 4-nitro and 4-chloro CNMAs as determined by optical microscopy and scanning electron microscopy (SEM) and 3-D spectrum plots. 4-Nitro and 4-chloro CNMAs induced cell shortening and concentration- and time-dependently reduced cell growth. Virulence factors were significantly and dose-dependently suppressed by 4-nitro and 4-chloro CNMAs (P ≤ 0.05). Gene expressional changes were greater after 4-nitro CNMA than t-CNMA treatment, as determined by qRT-PCR. Furthermore, some genes essential for biofilm formation, motility, and virulence genes significantly downregulated by 4-nitro CNMA. Seed germination of Raphanus sativus was not hindered by 4-nitro or 4-fluoro CNMA at concentrations ≤200 μg/ml, but root surface biofilm formation was severely inhibited. This study is the first to report the anti-Agrobacterium biofilm and anti-virulence effects of 4-nitro, 4-chloro, and 4-fluoro CNMAs and t-CNMA and indicates that they should be considered starting points for the development of anti-Agrobacterium agents.
Exosomes derived from M2 macrophages induce angiogenesis to promote wound healing
Authors: Lyu Leifeng , Cai Yuanqing , Zhang Guangyang , Jing Zhaopu , Liang Jialin , Zhang Rupeng , Dang Xiaoqian , Zhang Chen
Published: October 2022

There is an urgent clinical need for an appropriate method to shorten skin healing time. Among most factors related to wound healing, M2 macrophages will be recruited to the wound area and play a pivotal role in a time-limiting factor, angiogenesis. The exploration of exosomes derived from M2 in angiogenesis promotion is an attractive research field. In this project, we found that exosomes from M2 (M2-EXO) promoted the angiogenic ability of HUVECs in vitro. With a series of characteristic experiments, we demonstrated that M2-EXO inhibited PTEN expression in HUVECs by transferring miR-21, and further activated AKT/mTOR pathway. Then, using a full-thickness cutaneous wound mice model, we demonstrated that M2-EXO could be used as a promotor of angiogenesis and regeneration in vivo. Furthermore, M2-EXO-treated skin wounds exhibited regeneration of functional microstructures. These results demonstrate that M2-EXO can be used as a promising nanomedicine strategy for therapeutic exploration of skin healing with the potential to be translated into clinical practice.
Random forest classifier improving phenylketonuria screening performance in two Chinese populations
Authors: Song Yingnan , Yin Zhe , Zhang Chuan , Hao Shengju , Li Haibo , Wang Shifan , Yang Xiangchun , Li Qiong , Zhuang Danyan , Zhang Xinyuan , Cao Zongfu , Ma Xu
Published: October 2022

Phenylketonuria (PKU) is a genetic disorder with amino acid metabolic defect, which does great harms to the development of newborns and children. Early diagnosis and treatment can effectively prevent the disease progression. Here we developed a PKU screening model using random forest classifier (RFC) to improve PKU screening performance with excellent sensitivity, false positive rate (FPR) and positive predictive value (PPV) in all the validation dataset and two testing Chinese populations. RFC represented outstanding advantages comparing several different classification models based on machine learning and the traditional logistic regression model. RFC is promising to be applied to neonatal PKU screening.
Cardiac sympathetic denervation could be associated with dysphagia in Parkinson's disease
Authors: Youn Jinyoung , Umemoto George , Oh Eungseok , Park Jinse , Jang Wooyoung , Oh Yoon-Sang , Kim Hee-Tae , Cho Jin Whan , Fujioka Shinsuke , Tsuboi Yoshio
Published: October 2022

Background

Dysphagia is an important non-motor symptom that is closely associated with quality of living and mortality in Parkinson's disease (PD). However, the pathophysiology of dysphagia in PD remains inconclusive. We tried to confirm whether the occurrence of dysphagia could be related to sympathetic degeneration using cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy.

Methods

We prospectively recruited 27 PD patients and classified them into two groups (PD with dysphagia vs. PD without dysphagia) by Swallowing Disturbance Questionnaire (SDQ) score and compared the clinical characteristics, videofluoroscopic swallowing study (VFSS) findings and parameters from cardiac MIBG scintigraphy.

Results

The mean early and late H/M ratios were significantly lower in the PD with dysphagia group than those in the PD without dysphagia group (1.39 ± 0.21 vs. 1.86 ± 0.21, p < 0.01; 1.26 ± 0.18 vs. 1.82 ± 0.29, p < 0.01). In the correlation analysis, both the early and late H/M ratios were negatively correlated with the SDQ score and total VDS score (r = −0.65, p < 0.01; r = −0.53, p < 0.01; r = −0.65, p < 0.01, r = −0.58, p < 0.01).

Conclusion

We confirmed that cardiac sympathetic denervation might be associated with the presence and severity of dysphagia. This finding indicates that dysphagia in PD could be associated with a nondopaminergic mechanism.
Delayed filling of the superficial middle cerebral vein in acute large artery occlusion
Authors: Xu Jingsi , Zhang Zheyu , Jin Bo , Geng Yu , Lin Longting , Zhang Sheng
Published: October 2022

Objective

This study aimed to determine whether baseline delayed filling of the superficial middle cerebral vein (SMCV) was an independent cause of stroke prognosis in patients with acute anterior large vessel occlusion (LVO).

Methods

Consecutive patients with acute LVO [middle cerebral artery M1 ± intracranial internal carotid artery (ICA)] between March 2019 and May 2020 were included. Delayed SMCV was defined as delayed filling of SMCV in the affected side compared with the normal side throughout the venous phase on four-dimensional computed tomographic angiography (4D-CTA) reconstructed from CT perfusion imaging. The modified Rankin scale (mRS) was used to evaluate the prognosis of these patients 3 months after stroke.

Results

Of 54 patients in total, 47 (87.0%) patients presented with baseline delayed SMCV, and 36 (76.6%) patients achieved SMCV reversal (ipsilateral delayed SMCV reversed to bilateral symmetrical SMCV) after reperfusion therapy. Successful reperfusion was independently associated with SMCV reversal [odds ratio (OR) = 69.328, 95% confidence interval (CI) = 2.818–175.342]. A significant association between baseline SMCV delay and a 3-month poor outcome (OR = 19.623, 95% CI = 1.567–245.727, p = 0.021) was observed using a multivariable regression analysis. Compared with patients with persistent delayed SMCV, patients with reversed SMCV did not show a significant difference in the risk of a 3-month poor outcome (OR = 1.177, 95% CI = 0.147–9.448).

Conclusions

In patients with acute LVO, baseline delayed SMCV was an independent cause of poor stroke prognosis, and SMCV reversal cannot reverse the 3-month stroke prognosis. Therefore, the evaluation of baseline SMCV filling status should be strengthened in clinical practice.
Effects of acoustic stimulation intensity on air-conducted vestibular evoked myogenic potential in children
Authors: Xiao Qianwen , Zhang Qin , Wu Qiong , Shen Jiali , Wang Lu , Chen Yanfei , Lv Jingrong , Yang Jun , Jin Yulian , Zhang Qing
Published: October 2022

Objective

To investigate the effects of acoustic stimulation intensity on ocular and cervical vestibular evoked myogenic potential (oVEMP and cVEMP) responses elicited by air-conducted sound (ACS) in healthy children.

Methods

Thirteen healthy children aged 4–10 years and 20 healthy adults aged 20-40 years with normal hearing and tympanometry were enrolled in this study. All subjects received oVEMP and cVEMP tests under different acoustic stimulation intensities (131, 126, 121, 116, 111 and 106 dB SPL). Mean n1 latency, p1 latency, interpeak latency, amplitude and response rate were investigated and analyzed.

Results

As the acoustic stimulation intensity decreased, for oVEMP, the response rate of children decreased from 100% (131, 126 and 121 dB SPL) to 57.69% (116 dB SPL), 26.92% (111 dB SPL) and 11.54% (106 dB SPL). The response rate of adults decreased from 100% (131 and 126 dB SPL) to 95% (121 dB SPL), 55% (116 dB SPL), 12.5% (111 dB SPL) and 2.5% (106 dB SPL). There were lower n1 latency, p1 latency and higher amplitude in children when comparing by acoustic stimulation intensities (p < 0.05). Regarding cVEMP, the response rate of children decreased from 100% (131, 126 and 121 dB SPL) to 88.46% (116 dB SPL), 53.85% (111 dB SPL) and 26.92% (106 dB SPL). The response rate of adults decreased from 100% (131 and 126 dB SPL) to 95% (121 dB SPL), 85% (116 dB SPL), 37.5% (111 dB SPL) and 7.5% (106 dB SPL). A statistically significant difference was found in amplitude at different acoustic stimulation intensities in both children and adults (p < 0.05). When stimulated by 131 dB SPL acoustic stimulation, there were lower n1 latency, p1 latency and higher amplitude in children in oVEMP and cVEMP compared with adults (p < 0.05).

Conclusion

The response rate and amplitude of oVEMP and cVEMP in children and adults presented significant differences with a decrease in acoustic stimulation intensity. In this study, using 121 dB SPL for children and 126 dB SPL for adults during VEMP test could be regarded as safer stimulation intensities and thus reduced sound exposure.
A brain-like classification method for computed tomography images based on adaptive feature matching dual-source domain heterogeneous transfer learning
Authors: Chen Yehang , Chen Xiangmeng
Published: October 2022

Transfer learning can improve the robustness of deep learning in the case of small samples. However, when the semantic difference between the source domain data and the target domain data is large, transfer learning easily introduces redundant features and leads to negative transfer. According the mechanism of the human brain focusing on effective features while ignoring redundant features in recognition tasks, a brain-like classification method based on adaptive feature matching dual-source domain heterogeneous transfer learning is proposed for the preoperative aided diagnosis of lung granuloma and lung adenocarcinoma for patients with solitary pulmonary solid nodule in the case of small samples. The method includes two parts: (1) feature extraction and (2) feature classification. In the feature extraction part, first, By simulating the feature selection mechanism of the human brain in the process of drawing inferences about other cases from one instance, an adaptive selected-based dual-source domain feature matching network is proposed to determine the matching weight of each pair of feature maps and each pair of convolution layers between the two source networks and the target network, respectively. These two weights can, respectively, adaptive select the features in the source network that are conducive to the learning of the target task, and the destination of feature transfer to improve the robustness of the target network. Meanwhile, a target network based on diverse branch block is proposed, which made the target network have different receptive fields and complex paths to further improve the feature expression ability of the target network. Second, the convolution kernel of the target network is used as the feature extractor to extract features. In the feature classification part, an ensemble classifier based on sparse Bayesian extreme learning machine is proposed that can automatically decide how to combine the output of base classifiers to improve the classification performance. Finally, the experimental results (the AUCs were 0.9542 and 0.9356, respectively) on the data of two center data show that this method can provide a better diagnostic reference for doctors.
Does mental rotation emulate motor processes? An electrophysiological study of objects and body parts
Authors: Menéndez Granda Marta , Iannotti Giannina Rita , Darqué Alexandra , Ptak Radek
Published: October 2022

Several arguments suggest that motor planning may share embodied neural mechanisms with mental rotation (MR). However, it is not well established whether this overlap occurs regardless of the type of stimulus that is manipulated, in particular manipulable or non-manipulable objects and body parts. We here used high-density electroencephalography (EEG) to examine the cognitive similarity between MR of objects that do not afford specific hand actions (chairs) and bodily stimuli (hands). Participants had identical response options for both types of stimuli, and they gave responses orally in order to prevent possible interference with motor imagery. MR of hands and chairs generated very similar behavioral responses, time-courses and neural sources of evoked-response potentials (ERPs). ERP segmentation analysis revealed distinct time windows during which differential effects of stimulus type and angular disparity were observed. An early period (90–160 ms) differentiated only between stimulus types, and was associated with occipito-temporal activity. A later period (290–330 ms) revealed strong effects of angular disparity, associated with electrical sources in the right angular gyrus and primary motor/somatosensory cortex. These data suggest that spatial transformation processes and motor planning are recruited simultaneously, supporting the involvement of motor emulation processes in MR.
Single-cell sequencing reveals the cell map and transcriptional network of sporadic vestibular schwannoma
Authors: Yidian Chu , Chen Lin , Hongxia Deng , Yanguo Li , Zhisen Shen
Published: October 2022

In this study, based on three tumor samples obtained from patients with sporadic vestibular schwannoma, 32,011 cells were obtained by single-cell transcriptome sequencing, and 22,309 high-quality cells were obtained after quality control and double cells removal. Then, 18 cell clusters were obtained after cluster analysis, and each cluster was annotated as six types of cells. Afterward, an in-depth analysis was conducted based on the defined six cell clusters, including characterizing the functional characteristics of each cell subtype, describing the cell development and differentiation pathway, exploring the interaction between cells, and analyzing the transcriptional regulatory network within the clusters. Based on these four dimensions, various types of cells in sporadic vestibular schwannoma tumor tissues were described in detail. For the first time, we expanded on the functional state of cell clusters that have been reported and described Schwann cells in the peripheral nervous system, which have not been reported in previous studies. Combined with the data of sporadic vestibular schwannoma and normal tissues in the gene expression omnibus (GEO) database, the candidate biomarkers of sporadic vestibular schwannoma were explored. Overall, this study described the single-cell map of sporadic vestibular schwannoma for the first time, revealing the functional state and development trajectory of different cell types. Combined with the analysis of data in the GEO database and immunohistochemical verification, it was concluded that HLA-DPB1 and VSIG4 may be candidate biomarkers and potential therapeutic targets for patients with sporadic vestibular schwannoma.
Increased urinary B2-microglobulin is associated with poor prognosis of upper tract urothelial carcinoma
Authors: Han Jang Hee , Jeong Seung-hwan , Kim Si Hyun , Yuk Hyeong Dong , Jeong Chang Wook , Kwak Cheol , Ku Ja Hyeon
Published: October 2022

Background

Kidney tubular damage markers are biomarkers of acute or chronic kidney injury. Hypothetically, upper tract urothelial cancer (UTUC), which induces obstructive uropathy or direct invasion of the renal parenchyma, may also induce increased excretion of urinary tubular damage proteins. Therefore, this study aimed to investigate the use of tubular damage biomarker as prognostic markers for UTUC.

Methods

The records of 417 surgically resected patients with UTUC were obtained from the Seoul National University Prospectively Enrolled Registry for urothelial cancer-upper tract urothelial cancer (SUPER-UC-UTUC) between January 2016 and December 2020. Patients with non-urothelial cancer or without urinary tubular injury marker measurement were excluded, and finally, 296 patients were finally included. B2-microglobulin (B2-MG) was an injury marker, and a value higher than 0.3 was considered abnormally elevated, according to previous studies.

Results

The mean age was 70.9 years, and the male sex was predominant (n = 211, 71.3%). The incidences of renal pelvis and ureter cancer were similar (50.7% vs. 49.3%). Most patients had high-grade diseases (n = 254, 88.8%). The high urine B2-MG group was older, had decreased renal function, and had a higher pathologic T stage than did the low group. Multivariate Cox regression analysis of disease-free survival (DFS), open surgical method (Hazard ratio (HR) 1.52, p = 0.027), large tumor size (HR 1.06, p = 0.017), tumor multifocality (HR 1.90, p = 0.038), lymphovascular invasion (HR 2.19, p < 0.001), and high urine B2-MG (HR 1.57, p = 0.021) were significantly associated with shortened metastasis-free survival (MFS). Kaplan–Meier curve analysis revealed short DFS (median survival 15.5 months vs. unattained, log-rank p = 0.001) and MFS (unattained median survival in both groups, log-rank p = 0.003) for the high urine B2-MG group compared to the low urine B2-MG group.

Conclusion

Patients with UTUC presenting with increased pre-operative urine B2-MG levels were associated with disease recurrence and metastasis. This biomarker may aid in performing pre-operative risk stratification and in assessing the individual prognosis of patients with UTUC.
Comparison of customized 3D-printed prosthesis and screw-rod-cage system reconstruction following resection of periacetabular tumors
Authors: Zhu Dongze , Wang Lei , Fu Jun , Guo Zheng , Wang Zhen , Fan Hongbin
Published: October 2022

Background and purpose

Various operative methods are used for reconstructing pelvic girdle after resection of primary malignant periacetabular tumor has been reported. The objective of this study was to evaluate the accuracy, effectiveness, and safety of customized three dimensional-printed prosthesis (3DP) in the reconstruction of bone defects compared with conventional reconstruction using the screw-rod-cage system.

Methods

A retrospective case–control analysis of 40 patients who underwent pelvic tumor resection and reconstruction with a customized 3D-printed prosthesis (3DP), or screw-rod-cage system (SRCS) between January 2010 and December 2019 was performed. The minimum follow-up time for patients alive was 2 years. Blood loss, operation time, complications, surgical margin, local recurrence, distant metastases, status at time of latest follow-up, MSTS-93 score, Harris hip score, and postoperative radiographic parameters were recorded. Moreover, overall survival, tumor-free survival, and prosthesis survival rates in both groups were compared.

Results

Customized 3DP reconstruction was performed in 15 patients, and SRCS reconstruction was done in 25 patients. The group of patients treated with customized 3DP reconstruction had significantly shorter operation time (323.7 ± 83.7 vs. 393.6 ± 98.8 min; P = 0.028) and more precise (all P < 0.05) radiographic reconstruction parameters than patients in the SRCS group. Fewer complications (P = 0.026), better MSTS score (P = 0.030), and better Harris hip score (P = 0.016) were achieved in the 3DP group. Furthermore, the survival rate of prosthesis was also significantly better in the 3DP group (P = 0.039). However, blood loss, surgical margin, local recurrence, distant metastases, and status at time of latest follow-up had no significant difference between two groups.

Conclusion

Compared with the screw-rod-cage system reconstruction, the customized 3D-printed prosthesis reconstruction is equally safe and effective, but it is more accurate and time-saving and is associated with fewer complications.
Emerging therapies for the treatment of rare pediatric bone disorders
Authors: Thrailkill Kathryn M. , Kalaitzoglou Evangelia , Fowlkes John L.
Published: October 2022

In recent years, new therapies for the treatment of rare pediatric bone disorders have emerged, guided by an increasing understanding of the genetic and molecular etiology of these diseases. Herein, we review three such disorders, impacted by debilitating deficits in bone mineralization or cartilage ossification, as well as the novel disease-modifying drugs that are now available to treat these conditions. Specifically, we discuss asfotase alfa, burosumab-twza, and vosoritide, for the treatment of hypophosphatasia, X-linked hypophosphatemia and achondroplasia, respectively. For each skeletal disorder, an overview of the clinical phenotype and natural history of disease is provided, along with a discussion of the clinical pharmacology, mechanism of action and FDA indication for the relevant medication. In each case, a brief review of clinical trial data supporting drug development for each medication is provided. Additionally, guidance as to drug dosing and long-term monitoring of adverse events and pediatric efficacy is presented, to aid the clinician seeking to utilize these novel therapies in their practice, or to become familiar with the healthcare expectations for children receiving these medications through specialized multidisciplinary clinics. The availability of these targeted therapies now significantly augments treatment options for conditions in which past therapy has relied upon less specific, symptomatic medical and orthopedic care.
Pathogenic determinants of Kingella kingae disease
Authors: Porsch Eric A. , Hernandez Kevin A. , Morreale Daniel P. , Montoya Nina R. , Yount Taylor A. , St. Geme Joseph W.
Published: October 2022

Kingella kingae is an emerging pediatric pathogen and is increasingly recognized as a leading etiology of septic arthritis, osteomyelitis, and bacteremia and an occasional cause of endocarditis in young children. The pathogenesis of K. kingae disease begins with colonization of the upper respiratory tract followed by breach of the respiratory epithelial barrier and hematogenous spread to distant sites of infection, primarily the joints, bones, and endocardium. As recognition of K. kingae as a pathogen has increased, interest in defining the molecular determinants of K. kingae pathogenicity has grown. This effort has identified numerous bacterial surface factors that likely play key roles in the pathogenic process of K. kingae disease, including type IV pili and the Knh trimeric autotransporter (adherence to the host), a potent RTX-family toxin (epithelial barrier breach), and multiple surface polysaccharides (complement and neutrophil resistance). Herein, we review the current state of knowledge of each of these factors, providing insights into potential approaches to the prevention and/or treatment of K. kingae disease.
The development and validation of a predictive model for neonatal phototherapy outcome using admission indicators
Authors: Liu Qin , Tang Zaixiang , Li Huijun , Li Yongfu , Tian Qiuyan , Yang Zuming , Miao Po , Yang Xiaofeng , Li Mei , Xu Lixiao , Feng Xing , Ding Xin
Published: October 2022

Delayed exchange transfusion therapy (ETT) after phototherapy failure for newborns with severe hyperbilirubinemia could lead to serious complications such as bilirubin encephalopathy (BE). In this current manuscript we developed and validated a model using admission data for early prediction of phototherapy failure. We retrospectively examined the medical records of 292 newborns with severe hyperbilirubinemia as the training cohort and another 52 neonates as the validation cohort. Logistic regression modeling was employed to create a predictive model with seven significant admission indicators, i.e., age, past medical history, presence of hemolysis, hemoglobin, neutrophil proportion, albumin (ALB), and total serum bilirubin (TSB). To validate the model, two other models with conventional indicators were created, one incorporating the admission indicators and phototherapy failure outcome and the other using TSB decrease after phototherapy failure as a variable and phototherapy outcome as an outcome indicator. The area under the curve (AUC) of the predictive model was 0.958 [95% confidence interval (CI): 0.924–0.993] and 0.961 (95% CI: 0.914–1.000) in the training and validation cohorts, respectively. Compared with the conventional models, the new model had better predictive power and greater value for clinical decision-making by providing a possibly earlier and more accurate prediction of phototherapy failure. More rapid clinical decision-making and interventions may potentially minimize occurrence of serious complications of severe neonatal hyperbilirubinemia.
Significant advantages for first line treatment with TNF-alpha inhibitors in pediatric patients with inflammatory bowel disease – Data from the multicenter CEDATA-GPGE registry study
Authors: Claßen Merle , de Laffolie Jan , Claßen Martin , Schnell Alexander , Sohrabi Keywan , Hoerning André
Published: October 2022

Background and aims

In recent years, biological agents, such as anti-TNF-α blockers, have been introduced and have shown efficacy in pediatric patients with inflammatory bowel disease (IBD). Here, the prescription mode differentiated into a first/second line application, and efficacy and side effects are evaluated beginning from 2004 until today.

Methods

Statistical analyses of the prospective and ongoing CEDATA multicenter registry data from the Society of Pediatric Gastroenterology and Nutrition (GPGE) were performed for patients receiving a biological agent at least once during the period from June 2004 until November 2020 (n = 487). The analyzed parameters were patient demographics, disease extent and behavior, prior or concurrent therapies, duration and outcome of biological therapy, disease-associated complications, drug-related complications, laboratory parameters and treatment response as determined by the Physician’s Global Assessment.

Results

Crohn’s disease (CD) was present in 71.5% of patients, and 52% were boys. Patients showed high disease activity when receiving a first-line TNF-α blocker. After 2016, patients who failed to respond to anti-TNF-α induction therapy were treated with off-label biologics (vedolizumab 4.3% and ustekinumab 2.1%). Propensity score matching indicated that patients with CD and higher disease activity benefitted significantly more from early anti-TNF-α therapy. This assessment was based on a clinical evaluation and lab parameters related to inflammation compared to delayed second-line treatment. Additionally, first-line treatment resulted in less treatment failure and fewer extraintestinal manifestations during TNF-α blockade.

Conclusion

First-line treatment with anti-TNF-α drugs is effective and safe. An earlier start significantly reduces the risk of treatment failure and is associated with fewer extraintestinal manifestations during longitudinal follow-up.
Influence of early fluid overload on bronchopulmonary dysplasia in very low-birth-weight infants
Authors: Li Yu-Jie , Zhu Xiao-Fang , Liu Jian-Hong , Yi Xiao-Qian , He Hao
Published: October 2022

Objective

This study aimed to determine the influence of fluid overload on bronchopulmonary dysplasia (BPD) in very low-birth-weight infants (VLBWI) within 1 week after birth.

Methods

This was a retrospective case control study conducted in the Jingzhou Central Hospital. The clinical data of VLBWI (with a birth weight [BW] < 1,500 g and 26 weeks ≤ gestational age [GA] < 32 weeks) who were admitted to the neonatal intensive care unit of this hospital from January 2016 to December 2021 were analyzed retrospectively. A total of 157 cases were enrolled and divided into a BPD group (n = 60) and a non-BPD group (n = 97) according to whether BPD was present. The general condition, fluid intake, and fluid overload of the two groups of neonates within 1 week after birth were compared. The logistic regression was used to assess the association between infant characteristics and BPD. The ROC curve was used to assess how well the 7 day cumulative fluid overload predicted BPD, and to identify an optimal cut off for prediction.

Results

The comparison of the patients' general condition revealed that the neonates in the BPD group had a younger GA, lower BW, lower 5-min Apgar score, longer duration of invasive mechanical ventilation, and higher incidence of intrauterine infections and administration of surfactants (P < 0.05). The differences in the other indicators were not statistically significant between the two groups. The logistic regression analysis revealed that a younger GA, the presence of intrauterine infection, and a 7-day cumulative fluid overload were the risk factors for the development of BPD. A ROC curve was plotted with the 7-day cumulative fluid overload as the test variable and BPD as the status variable. The area under the curve was 0.75 (95% confidence interval: 0.664–0.826, P = 0.042), with a sensitivity of 76.7% and a specificity of 70.1%, corresponding to a 7-day cumulative fluid overload of 36.2%.

Conclusion

A younger GA, the presence of intrauterine infection, and a 7-day cumulative fluid overload were risk factors for the development of BPD. A 7 day cumulative fluid overload threshold of 36.2% best predicted the development of BPD.
Gene therapy for cystic fibrosis: Challenges and prospects
Authors: Sui Hongshu , Xu Xinghua , Su Yanping , Gong Zhaoqing , Yao Minhua , Liu Xiaocui , Zhang Ting , Jiang Ziyao , Bai Tianhao , Wang Junzuo , Zhang Jingjun , Xu Changlong , Luo Mingjiu
Published: October 2022

Cystic fibrosis (CF) is a life-threatening autosomal-recessive disease caused by mutations in a single gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). CF effects multiple organs, and lung disease is the primary cause of mortality. The median age at death from CF is in the early forties. CF was one of the first diseases to be considered for gene therapy, and efforts focused on treating CF lung disease began shortly after the CFTR gene was identified in 1989. However, despite the quickly established proof-of-concept for CFTR gene transfer in vitro and in clinical trials in 1990s, to date, 36 CF gene therapy clinical trials involving ∼600 patients with CF have yet to achieve their desired outcomes. The long journey to pursue gene therapy as a cure for CF encountered more difficulties than originally anticipated, but immense progress has been made in the past decade in the developments of next generation airway transduction viral vectors and CF animal models that reproduced human CF disease phenotypes. In this review, we look back at the history for the lessons learned from previous clinical trials and summarize the recent advances in the research for CF gene therapy, including the emerging CRISPR-based gene editing strategies. We also discuss the airway transduction vectors, large animal CF models, the complexity of CF pathogenesis and heterogeneity of CFTR expression in airway epithelium, which are the major challenges to the implementation of a successful CF gene therapy, and highlight the future opportunities and prospects.
Determination of (-)-epigallocatechin-3-gallate octaacetate and its metabolites in plasma of rats for pharmacokinetic study by ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry
Authors: Chu Kai On , Man Gene Chi Wai , Hung Sze Wan , Chan Tak Hang , Lee Wai Yip Thomas , Chan Kwok Ping , Pang Chi Pui , Wang Chi Chiu
Published: October 2022

(-)-Epigallocatechin-gallate octaacetate (pro-EGCG), a prodrug of epigallocatechin-gallate (EGCG), has been used for pre-clinical study for the treatment of endometriosis. A validated analytical method has been developed for the determination of plasma pro-EGCG and its metabolites after oral administration using ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry (UPLC-Qtof-MS). This method is more robust, rapid, sensitive, simpler, and able to detect pro-EGCG metabolites compared to our previous method. Pro-EGCG in the plasma was stabilized from rapid degradation by formic acid, extracted by isopropanol/methyl-tert-butyl ether mixture, separated by UPLC core column, and quantified by an exact mass method with Qtof-MS. The lower limit of quantification (LLOQ), intra-day and inter-day precision, and accuracy for the range of 0.01–2.5 μg/mL were within acceptable limits. The sensitivity was improved by 25 folds using pro-EGCG ammonium adduct [M + NH4]+. This is the first report on the pharmacokinetics of oral administration with maximum-concentration (Cmax) was 0.067 ± 0.04 μg/mL, time-of-maximum-concentration (Tmax) was 1.33 h, area-under-curve (AUC) was 0.20 ± 0.05 h × µg/mL, and elimination-rate was 0.20 ± 0.11 hr−1. The pharmacokinetic profiles of pro-EGCG metabolites, (-)-epigallocatechin-gallate (EGCG) diacetates and EGCG triacetates, were also presented. This method is robust, rapid, and sensitive for the pharmacokinetic study of pro-EGCG and metabolites.
Small airway dysfunction in idiopathic pulmonary fibrosis
Authors: Yin Chengsheng , Xie Huikang , He Xian , Zhang Yuan , Zhang Aihong , Li Huiping
Published: October 2022

It is generally accepted that the pathophysiology of idiopathic pulmonary fibrosis (IPF) can be attributed to impaired lung interstitium and alveoli, while airway involvement has rarely been reported. In the present study, we aimed to investigate the actual occurrence of IPF comorbid small airway dysfunction (SAD) and its impact on survival. Data from inpatients diagnosed with IPF at Shanghai Pulmonary Hospital (Shanghai, China) from 2011 to 2021 were retrospectively collected and analyzed. Lung function parameters were used to assess SAD. A total of 243 IPF patients were included in this retrospective study, and 84 cases (84/243, 34.57%) were diagnosed with SAD. The lung histopathology showed that all 48 cases undergoing lung transplantation presented various degrees of airway lesions, of which 18 patients (18/48, 37.5%) diagnosed with SAD before lung transplantation had a higher proportion of airway distortion and obliteration. The possible risk factors associated with IPF comorbid SAD were smoking, male, younger age, and high CT fibrosis and emphysema scores. By univariate Fine-Grey regression, the hazard ratio (HR) of IPF comorbid SAD was 1.725 (95% CI 1.071, 2.777, p < 0.05). After adjusting the CTPF model and GAP model, the value of HR was 1.714 (95% CI 1.043, 2.816, p < 0.05) and 1.731 (95% CI 1.074, 2.788, p < 0.05), respectively. These findings suggested that IPF comorbid SAD was an independent risk factor for the mortality of IPF patients.
A review of herb-induced liver injury in mainland china
Authors: Yang Yan , Ge Fei-Lin , Tang Jin-Fa , Qin Shuang-Lin , Zeng Rui , Yao Meng-Lin , Xiao Xiao-He , Bai Zhao-Fang , Tang Cheng-Lin
Published: October 2022

Traditional medicines have greatly contributed to people’s health worldwide. However, in recent years, the frequent occurrence of herb-induced liver injury (HILI) has raised public concerns regarding the safety of herbs. HILI not only severely impacts public health, thus increasing its medical burden, but also consumes medical resources. However, the pharmacoepidemiology and risk factors of HILI are still unclear due to the complexity of herbs (medication theory, drug composition, dual properties of drugs and food, etc.). China is the country with the most extensive use of herbs and cases of HILI worldwide. The safety profile of herbs (especially with respect to HILI) has also affected the use of herbs internationally. Therefore, this review focuses on the epidemic situation of HILI in mainland China to compile its characteristics, while focusing on the three main aspects of patients, drugs, and unreasonable prescriptions to explore the potential risk factors. Our objective was to provide a reference for HILI pharmacovigilance and risk prevention and control and contribute to Chinese knowledge of the realisation of the “Medication without Harm” global safe medication strategic goal of the World Health Organization.
Overestimation of maximal aerobic speed by the Université de Montréal track test and a 1500-m-time trial in soccer
Authors: Thron Maximiliane , Woll Alexander , Klos Leon , Härtel Sascha , Ruf Ludwig , Kloss Christian , Altmann Stefan
Published: October 2022

Introduction: Maximal aerobic speed (MAS), usually measured by cardiopulmonary exercise testing (CPET) on a treadmill, is gaining popularity in soccer to determine aerobic performance. Several field tests are used to estimate MAS, although, gold standard methods are still not clarified. Therefore, this work aims 1) to compare two different CPET based methods to assess MAS and 2) to investigate the convergent validity of two common field tests to estimate MAS in soccer.

Methods: Thirteen trained male soccer players completed an CPET on a treadmill to determine two VO2-kinetic based definitions of MAS (MASPlateau = speed at onset of VO2-plateau = gold standard; MAS30s = first speed of 30-s-interval of VO2max), the Université de Montreal Track Test (UMTT; VUMTT = speed of the last stage), and a 1500-m-time trial (1500-m-TT; V1500m = average speed). MASPlateau, MAS30s, VUMTT, and V1500m were compared using ANOVA. Additionally, limits of agreement analysis (LoA), Pearson’s r, and ICC were calculated between tests.

Results: MAS30s, VUMTT, and V1500m significantly overestimated MASPlateau by 0.99 km/h (ES = 1.61; p < 0.01), 1.61 km/h (ES = 2.03; p < 0.01) and 1.68 km/h (ES = 1.77; p < 0.01), respectively, with large LoA (-0.21 ≤ LoA≤3.55), however with large-to-very large correlations (0.65 ≤ r ≤ 0.87; p ≤ 0.02; 0.51 ≤ ICC≤ 0.85; p ≤ 0.03).

Discussion: The overestimation and large LoA of MASPlateau by all estimates indicate that 1) a uniform definition of MAS is needed and 2) the UMTT and a 1500-m-TT seem questionable for estimating MAS for trained soccer players on an individual basis, while regression equations might be suitable on a team level. The results of the present work contribute to the clarification of acquisition of MAS in soccer.
Coping with global warming: Adult thermal thresholds in four pestiferous Anastrepha species determined under experimental laboratory conditions and development/survival times of immatures and adults under natural field conditions
Authors: Guillén Larissa , Pascacio-Villafán Carlos , Osorio-Paz Ixchel , Ortega-Casas Rafael , Enciso-Ortíz Erick , Altúzar-Molina Alma , Velázquez Olinda , Aluja Martín
Published: October 2022

Climate change, particularly global warming, is disturbing biological processes in unexpected ways and forcing us to re-study/reanalyze the effects of varying temperatures, among them extreme ones, on insect functional traits such as lifespan and fecundity/fertility. Here we experimentally tested, under both laboratory and field conditions, the effects of an extreme range of temperatures (5, 10, 15, 20, 30, 40, and 45 °C, and the naturally varying conditions experienced in the field), on survivorship/lifespan, fecundity, and fertility of four pestiferous fruit fly species exhibiting contrasting life histories and belonging to two phylogenetic groups within the genus Anastrepha: A. ludens, A. obliqua, A. striata, and A. serpentina. In the field, we also measured the length of the entire life cycle (egg to adult), and in one species (A. ludens), the effect on the latter of the host plant (mango and grapefruit). Under laboratory conditions, none of the adults, independent of species, could survive a single day when exposed to a constant temperature of 45 °C, but A. striata and A. serpentina females/males survived at the highly contrasting temperatures of 5 and 40 °C at least 7 days. Maximum longevity was achieved in all species at 15 °C (375, 225, 175 and 160 days in A. ludens, A. serpentina, A. striata and A. obliqua females, respectively). Anastrepha ludens layed many eggs until late in life (368 days) at 15 °C, but none eclosed. Eclosion was only observed in all species at 20 and 30 °C. Under natural conditions, flies lived ca. 100 days less than in the laboratory at 15 °C, likely due to the physiological cost of dealing with the highly varying environmental patterns over 24 h (minimum and maximum temperatures and relative humidity of ca. 10–40 °C, and 22–100%, respectively). In the case of A. ludens, the immature’s developmental time was shorter in mango, but adult survival was longer than in grapefruit. We discuss our results considering the physiological processes regulating the traits measured and tie them to the increasing problem of global warming and its hidden effects on the physiology of insects, as well as the ecological and pest management implications.
QTL analysis for sodium removal ability in rice leaf sheaths under salinity using an IR-44595/318 F2 population
Authors: Goto Itsuki , Neang Sarin , Kuroki Ryuichi , Reyes Vincent Pamugas , Doi Kazuyuki , Skoulding Nicola Stephanie , Taniguchi Mitsutaka , Yamauchi Akira , Mitsuya Shiro
Published: October 2022

Over-accumulation of salt in rice plants is an effect of salt stress which decreases growth and grain yield. Salt removal ability in leaf sheaths is a tolerance mechanism to decrease salt entry and accumulation in leaf blades and maintain photosynthesis under salinity. In this study, a QTL analysis of removal ability of sodium ions (Na+) in leaf sheaths and Na+ accumulation-related traits, was conducted using F2 population between two rice varieties, IR-44595 with superior Na+ removal ability, and 318 with contrasting Na+ removal ability in leaf sheaths under salinity. Suggestive QTLs for Na+ removal ability in leaf sheaths were found on chromosomes 4 and 11. The suggestive QTL on chromosome 11 overlapped with other significant QTLs for Na+ concentration in shoots, leaf blades and leaf sheaths, and Na+/K+ ratio in leaf blades. Correlation analysis indicated that Na+ removal ability in leaf sheaths is important in reducing Na+ accumulation in leaf blades. The varietal difference of Na+ removal ability in leaf sheaths at the whole plant level was greater at lower NaCl concentrations and became smaller as the treatment NaCl concentration increased. Although the Na+ removal ability in leaf sheath was comparable between IR-44595 and 318 under high salinity at the whole plant level, the younger leaves of IR-44595 still showed a higher Na+ sheath-blade ratio than 318, which implied the Na+ removal ability functions in the younger leaves in IR-44595 to reduce Na+ entry in young leaf blades even under high salinity.
Identification and fine-mapping of a major QTL (PH1.1) conferring plant height in broomcorn millet (Panicum miliaceum)
Authors: Liu Tianpeng , Liu Xueying , He Jihong , Dong Kongjun , Pan Wanxiang , Zhang Lei , Ren Ruiyu , Zhang Zhengsheng , Yang Tianyu
Published: October 2022

The plant height of broomcorn millet (Panicum miliaceum) is a significant agronomic trait that is closely related to its plant architecture, lodging resistance, and final yield. However, the genes underlying the regulation of plant height in broomcorn millet are rarely reported. Here, an F2 population derived from a cross between a normal variety, “Longmi12,” and a dwarf mutant, “Zhang778,” was constructed. Genetic analysis for the F2 and F2:3 populations revealed that the plant height was controlled by more than one locus. A major quantitative trait locus (QTL), PH1.1, was preliminarily identified in chromosome 1 using bulked segregant analysis sequencing (BSA-seq). PH1.1 was fine-mapped to a 109-kb genomic region with 15 genes using a high-density map. Among them, longmi011482 and longmi011489, containing nonsynonymous variations in their coding regions, and longmi011496, covering multiple insertion/deletion sequences in the promoter regions, may be possible candidate genes for PH1.1. Three diagnostic markers closely linked to PH1.1 were developed to validate the PH1.1 region in broomcorn millet germplasm. These findings laid the foundation for further understanding of the molecular mechanism of plant height regulation in broomcorn millet and are also beneficial to the breeding program for developing new varieties with optimal height.