bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of mucosal flora and enterochromaffin cells of the caecum and descending colon in diarrhoea-predominant irritable bowel syndrome
Authors: Yang Jingze , Wang Peng , Liu Tong , Lin Lin , Li Lixiang , Kou Guanjun , Zhou Ruchen , Li Pan , Li Yanqing
Published: November 2021

Background

Accumulating evidence supports the pivotal role of intestinal flora in irritable bowel syndrome (IBS). Serotonin synthesis by enterochromaffin (EC) cells is influenced by the gut microbiota and has been reported to have an interaction with IBS. The comparison between the microbiota of the caecal and colonic mucosa in IBS has rarely been studied. The aim of this study was to investigate the relationship between the gut microbiota, EC cells in caecum and descending colon, and diarrhoea-predominant IBS (IBS-D) symptoms.

Results

A total of 22 IBS-D patients and 22 healthy controls (HCs) were enrolled in our study. Hamilton anxiety (HAM-A) and Hamilton depression (HAM-D) grades increased significantly in IBS-D patients. In addition, the frequency of defecation in IBS-D patients was higher than that in HCs. Among the preponderant bacterial genera, the relative abundance of the Ruminococcus_torques_ group increased in IBS-D patients in caecum samples while Raoultella and Fusobacterium were less abundant. In the descending colon, the abundance of the Ruminococcus_torques_group and Dorea increased in IBS-D patients and Fusobacterium decreased. No difference was observed between the descending colon and caecum in regards to the mucosal-associated microbiota. The number of EC cells in the caecum of IBS-D patients was higher than in HCs and the expression of TPH1 was higher in IBS-D patients both in the caecum and in the descending colon both at the mRNA and protein level. Correlation analysis showed that the Ruminococcus_torques_group was positively associated with HAM-A, HAM-D, EC cell number, IBS-SSS, degree of abdominal pain, frequency of abdominal pain and frequency of defecation. The abundance of Dorea was positively associated with EC cell number, IBS-SSS, HAM-A, HAM-D and frequency of abdominal pain.

Conclusions

EC cell numbers increased in IBS-D patients and the expression of TPH1 was higher than in HCs. The Ruminococcus torques group and Dorea furthermore seem like promising targets for future research into the treatment of IBS-D patients.
The legume-specific transcription factor E1 controls leaf morphology in soybean
Authors: Li Yongli , Hou Zhihong , Li Weiwei , Li Haiyang , Lu Sijia , Gan Zhuoran , Du Hao , Li Tai , Zhang Yuhang , Kong Fanjiang , Cheng Yuhan , He Milan , Ma Lixin , Liao Chunmei , Li Yaru , Dong Lidong , Liu Baohui , Cheng Qun
Published: November 2021

Background

The leaf is a determinate organ essential for photosynthesis, whose size and shape determine plant architecture and strongly affect agronomic traits. In soybean, the molecular mechanism of leaf development is not well understood. The flowering repressor gene E1, which encodes a legume-specific B3-like protein, is known to be the gene with the largest influence on soybean flowering and maturity. However, knowledge of its potential other functions remains poor.

Results

Here, we identified a novel function of E1 protein in leaf development. Unifoliolate leaves of E1-overexpression (E1-OE) lines were smaller and curlier than those of wild type DongNong 50 (DN50) and Williams 82 (W82). Transverse histological sections showed disorganized cells and significantly elevated palisade tissue number, spongy tissue number, and bulliform cell number in E1-OE lines. Our results indicate that E1 binds to the promoters of the leaf- development-related CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor genes to negatively regulate their expression.

Conclusions

Our findings identify E1 as an important new factor in soybean leaf development.
Leaf reflectance and functional traits as environmental indicators of urban dust deposition
Authors: Zhu Jiyou , Xu Jingliang , Cao Yujuan , Fu Jing , Li Benling , Sun Guangpeng , Zhang Xinna , Xu Chengyang
Published: November 2021

Background

How to quickly predict and evaluate urban dust deposition is the key to the control of urban atmospheric environment. Here, we focus on changes of plant reflectance and plant functional traits due to dust deposition, and develop a prediction model of dust deposition based on these traits.

Results

The results showed that (1) The average dust deposition per unit area of Ligustrum quihoui leaves was significantly different among urban environments (street (18.1001 g/m2), community (14.5597 g/m2) and park (9.7661 g/m2)). Among different urban environments, leaf reflectance curves tends to be consistent, but there were significant differences in leaf reflectance values (park (0.052–0.585) > community (0.028–0.477) > street (0.025–0.203)). (2) There were five major reflection peaks and five major absorption valleys. (3) The spectral reflectances before and after dust removal were significantly different (clean leaves > dust-stagnant leaves). 695 ~ 1400 nm was the sensitive range of spectral response. (4) Dust deposition has significant influence on slope and position of red edge. Red edge slope was park > community > street. After dust deposition, the red edge position has obviously “blue shift”. The moving distance of the red edge position increases with the increase of dust deposition. The forecast model of dust deposition amount established by simple ratio index (y = 2.517x + 0.381, R2 = 0.787, RMSE (root-mean-square error) = 0.187. In the model, y refers to dust retention, x refers to simple ratio index.) has an average accuracy of 99.98%. (5) With the increase of dust deposition, the specific leaf area and chlorophyll content index decreased gradually. The leaf dry matter content, leaf tissue density and leaf thickness increased gradually.

Conclusion

In the dust-polluted environment, L. quihoui generally presents a combination of characters with lower specific leaf area, chlorophyll content index, and higher leaf dry matter content, leaf tissue density and leaf thickness. Leaf reflectance spectroscopy and functional traits have been proved to be effective in evaluating the changes of urban dust deposition.
Frequent ploidy changes in Salicaceae indicates widespread sharing of the salicoid whole genome duplication by the relatives of Populus L. and Salix L.
Authors: Zhang Zhong-Shuai , Zeng Qing-Yin , Liu Yan-Jing
Published: November 2021

Backgrounds

Populus and Salix belong to Salicaceae and are used as models to investigate woody plant physiology. The variation of karyotype and nuclear DNA content can partly reflect the evolutionary history of the whole genome, and can provide critical information for understanding, predicting, and potentially ameliorating the woody plant traits. Therefore, it is essential to study the chromosome number (CN) and genome size in detail to provide information for revealing the evolutionary process of Salicaceae.

Results

In this study, we report the somatic CNs of seventeen species from eight genera in Salicaceae. Of these, CNs for twelve species and for five genera are reported for the first time. Among the three subfamilies of Salicaceae, the available data indicate CN in Samydoideae is n = 21, 22, 42. The only two genera, Dianyuea and Scyphostegia, in Scyphostegioideae respectively have n = 9 and 18. In Salicoideae, Populus, Salix and five genera closely related to them (Bennettiodendron, Idesia, Carrierea, Poliothyrsis, Itoa) are based on relatively high CNs from n = 19, 20, 21, 22 to n = 95 in Salix. However, the other genera of Salicoideae are mainly based on relatively low CNs of n = 9, 10, 11. The genome sizes of 35 taxa belonging to 14 genera of Salicaceae were estimated. Of these, the genome sizes of 12 genera and all taxa except Populus euphratica are first reported. Except for Dianyuea, Idesia and Bennettiodendron, all examined species have relatively small genome sizes of less than 1 pg, although polyploidization exists.

Conclusions

The variation of CN and genome size across Salicaceae indicates frequent ploidy changes and a widespread sharing of the salicoid whole genome duplication (WGD) by the relatives of Populus and Salix. The shrinkage of genome size after WGD indicates massive loss of genomic components. The phylogenetic asymmetry in clade of Populus, Salix, and their close relatives suggests that there is a lag-time for the subsequent radiations after the salicoid WGD event. Our results provide useful data for studying the evolutionary events of Salicaceae.
Severe COVID-19 acute respiratory distress syndrome in an adult with single-ventricle physiology: a case report
Authors: Schmidt Götz , Koch Christian , Wolff Matthias , Sander Michael
Published: November 2021

Background

COVID-19 can induce acute respiratory distress syndrome (ARDS). In patients with congenital heart disease, established treatment strategies are often limited due to their unique cardiovascular anatomy and passive pulmonary perfusion.

Case presentation

We report the first case of an adult with single-ventricle physiology and bidirectional cavopulmonary shunt who suffered from severe COVID-19 ARDS. Treatment strategies were successfully adopted, and pulmonary vascular resistance was reduced, both medically and through prone positioning, leading to a favorable outcome.

Conclusion

ARDS treatment strategies including ventilatory settings, prone positioning therapy and cannulation techniques for extracorporeal oxygenation must be adopted carefully considering the passive venous return in patients with single-ventricle physiology.
Intravenous patient-controlled analgesia plus psychoeducational intervention for acute postoperative pain in patients with pulmonary nodules after thoracoscopic surgery: a retrospective cohort study
Authors: Li Sha , Ding Xian , Zhao Yong , Chen Xiao , Huang Jianfeng
Published: November 2021

Background

The association of psychological factors with postoperative pain has been well documented. The incorporation of psychoeducational intervention into a standard analgesia protocol seems to be an attractive approach for the management of acute postoperative pain. Our study aimed to evaluate the impact of psychoeducational intervention on acute postoperative pain in pulmonary nodule (PN) patients treated with thoracoscopic surgery.

Methods

In this study, 76 PN patients treated with thoracoscopic surgery and intravenous patient-controlled analgesia (IV-PCA) plus psychoeducational evaluation and intervention were selected as the psychoeducational intervention group (PG). Another 76 PN patients receiving IV-PCA without psychoeducational intervention after thoracoscopic surgery, treated as the control group (CG), were identified from the hospital database and matched pairwise with PG patients according to age, sex, preoperative body mass index (BMI), opioid medications used for IV-PCA and the educational attainment of patients.

Results

The most common psychological disorders were anxiety and interpersonal sensitivity, which were recorded from 82.9% (63/76) and 63.2% (48/76) of PG patients. The numerical rating scale (NRS) pain scores of the PG patients were significantly lower than those of the CG patients at 2 and 24 h after surgery (P < 0.001). Total opioid consumption for acute postoperative pain in the PG was 52.1 mg of morphine equivalent, which was significantly lower than that (67.8 mg) in the CG (P = 0.038). PG patients had a significantly lower incidence of rescue analgesia than CG patients (28.9% vs. 44.7%, P = 0.044). Nausea/vomiting was the most common side effect of opioid medications, recorded for 3 (3.9%) PG patients and 10 (13.2%) CG patients (P = 0.042). In addition, no significant difference was observed between PG and CG patients in terms of grade 2 or higher postoperative complications (10.5% vs. 17.1%, P = 0.240).

Conclusions

Psychoeducational intervention for PN patients treated with thoracoscopic surgery resulted in reduced acute postoperative pain, less opioid consumption and fewer opioid-related side effects.
Timely intubation with early prediction of respiratory exacerbation in acute traumatic cervical spinal cord injury
Authors: Yonemitsu Takafumi , Kinoshita Azuna , Nagata Keiji , Morishita Mika , Yamaguchi Tomoyuki , Kato Seiya
Published: November 2021

Background

Early routine intubation in motor-complete cervical spinal cord injury (CSCI) above the C5 level is a conventional protocol to prevent unexpected respiratory exacerbation (RE). However, in the context of recent advances in multidisciplinary respiratory management, the absolute indication for intubation in patients with CSCI based on initial neurologic assessment is controversial because of the drawbacks of intubation. This study aimed to redetermine the most important predictor of RE following CSCI after admission without routine intubation among patients admitted with motor-complete injury and/or injury above the C5 level to ensure timely intubation.

Methods

We performed a retrospective review of patients with acute traumatic CSCI admitted to our hospital without an initial routine intubation protocol from January 2013 to December 2017. CSCI patients who developed RE (defined as unexpected emergent intubation for respiratory resuscitation) were compared with those who did not. Baseline characteristics and severity of trauma data were collected. Univariate analyses were performed to compare treatment data and clinical outcomes between the two groups. Further, multivariate logistic regression was performed with clinically important independent variables: motor-complete injury, neurologic level above C5, atelectasis, and copious airway secretion (CAS).

Results

Among 58 patients with CSCI, 35 (60.3%) required post-injury intubation and 1 (1.7%) died during hospitalization. Thirteen (22.4%) had RE 3.5 days (mean) post-injury; 3 (37.5%) of eight patients with motor-complete CSCI above C5 developed RE. Eleven of the 27 (40.7%) patients with motor-complete injury and five of the 22 (22.7%) patients with neurologic injury above C5 required emergency intubation at RE. Three of the eight CSCI patients with both risk factors (motor-complete injury above C5) resulted in emergent RE intubation (37.5%). CAS was an independent predictor for RE (odds ratio 7.19, 95% confidence interval 1.48–42.72,P = 0.0144) in multivariate analyses.

Conclusion

Timely intubation post-CSCI based on close attention to CAS during the acute 3-day phase may prevent RE and reduce unnecessary invasive airway control even without immediate routine intubation in motor-complete injury above C5.
Detection and follow-up of chronic health conditions in Rio de Janeiro – the impact of residency training in family medicine
Authors: Jantsch Adelson Guaraci , Burström Bo , Nilsson Gunnar , de Leon Antônio Ponce
Published: November 2021

Background

There is a need for evidence that residency training in family medicine can benefit the care of patients in primary care in low- and middle-income countries. We tested the hypothesis that two years of residency training in family medicine enables doctors to better detect chronic health conditions while requesting fewer laboratory tests and providing more follow-up visits.

Methods

We performed a retrospective longitudinal observational analysis of medical consultations from 2013 to 2018 in primary care in Rio de Janeiro, comparing doctors without residency training in family medicine (Generalists) versus family physicians (FPs). Multivariate multilevel binomial regression models estimated the risks of patients being diagnosed for a list of 31 chronic health conditions, having a follow-up visit for these conditions, and having laboratory tests ordered from a list of 30 exams.

Results

569.289 patients had 2.908.864 medical consultations performed by 734 generalists and 231 FPs. Patients seen by FPs were at a higher risk of being detected for most of the chronic health conditions, at a lower risk of having any of the 30 laboratory tests requested, and at a higher risk of having a follow-up visit in primary care.

Conclusions

Residency training in family medicine can make physicians more skilled to work in primary care. Policymakers must prioritize investments in capacity building of healthcare workforce to make primary care truly comprehensive.
Follow-up care delivery in community-based hypertension and type 2 diabetes management: a multi-centre, survey study among rural primary care physicians in China
Authors: Wang Yi , Hu Xiu-Jing , Wang Harry H. X. , Duan Hong-Yan , Chen Ying , Li Yu-Ting , Luo Zi-Lin , Li Xin , Wang Jia-Ji , Mercer Stewart W.
Published: November 2021

Background

Follow-up care is crucial but challenging for disease management particularly in rural areas with limited healthcare resources and clinical capacity, yet few studies have been conducted from the perspective of rural primary care physicians (PCPs). We assessed the frequency of follow-up care delivered by rural PCPs for hypertension and type 2 diabetes – the two most common long-term conditions.

Methods

We conducted a multi-centre, self-administered survey study built upon existing general practice course programmes for rural PCPs in four provinces. Information on follow-up care delivery were collected from rural PCPs attending centralised in-class teaching sessions using a set of close-ended, multiple choice questions. Binary logistic regression analysis was performed to examine physician-level factors associated with non-attainment of the target frequency of follow-up care for hypertension and type 2 diabetes, respectively. The final sample consisted of rural PCPs from 52 township-level regions. The Complex Samples module was used in the statistical analysis to account for the multistage sample design.

Results

The overall response rate was 91.4%. Around one fifth of PCPs in rural practices did not achieve the target frequency of follow-up care delivery (18.7% for hypertension; 21.6% for type 2 diabetes). Higher education level of physicians, increased volume of daily patients seen, and no provision of home visits were risk factors for non-attainment of the target frequency of follow-up care for both conditions. Moreover, village physicians with less working experiences tended to have less frequent follow-up care delivery in type 2 diabetes management.

Conclusions

Efforts that are solely devoted to enhancing rural physicians’ education may not directly translate into strong motivation and active commitment to service provision given the possible existence of clinical inertia and workload-related factors. Risk factors identified for target non-attainment in the follow-up care delivery may provide areas for capacity building programmes in rural primary care practice.
A case report of an isolated superior mesenteric artery dissection caused by childbirth
Authors: Feng Qian , Zhao Jingrun , Zang Lina , Chen Yuanyuan , Li Senlin
Published: November 2021

Background

The isolated superior mesenteric artery dissection (SMAD) is a rare and sporadic cause of acute abdominal pain. It most frequently affects male patients in their fifth to sixth decades, while our patient was a young woman who delivered a baby before the onset of abdominal pain. Possible risk factors for SMAD include hypertension, arteriosclerosis, abnormalities in elastic fibres, trauma, and pregnancy. In our case, delivery was suggested as a risk factor, which has not been reported previously.

Case presentation

A 27-year-old woman complained of acute severe upper abdominal pain and vomiting for 2 days after delivery. The patient had no significant medical history. Physical examination revealed epigastric mild tenderness. All routine blood tests, blood coagulation analysis, liver function tests and abdomen computed tomography showed no remarkable findings. Computed tomography angiography revealed a marked dissection 3.5 cm below the superior mesenteric artery ostium. Since distal blood flow existed and the patient was in a puerperal state with no evidences of mesenteric ischemia, she was managed conservatively, including intestinal rest by fasting, parenteral nutritional support and antibioticis, without anticoagulants or antiplatelet agents. Fortunately, she recovered smoothly and had no recurrence.

Conclusions

SMAD is a rare and sporadic cause of acute abdominal pain that occurs in young women after delivery.
Development and validation of the 3D U-Net algorithm for segmentation of pelvic lymph nodes on diffusion-weighted images
Authors: Liu Xiang , Sun Zhaonan , Han Chao , Cui Yingpu , Huang Jiahao , Wang Xiangpeng , Zhang Xiaodong , Wang Xiaoying
Published: November 2021

Background

The 3D U-Net model has been proved to perform well in the automatic organ segmentation. The aim of this study is to evaluate the feasibility of the 3D U-Net algorithm for the automated detection and segmentation of lymph nodes (LNs) on pelvic diffusion-weighted imaging (DWI) images.

Methods

A total of 393 DWI images of patients suspected of having prostate cancer (PCa) between January 2019 and December 2020 were collected for model development. Seventy-seven DWI images from another group of PCa patients imaged between January 2021 and April 2021 were collected for temporal validation. Segmentation performance was assessed using the Dice score, positive predictive value (PPV), true positive rate (TPR), and volumetric similarity (VS), Hausdorff distance (HD), the Average distance (AVD), and the Mahalanobis distance (MHD) with manual annotation of pelvic LNs as the reference. The accuracy with which the suspicious metastatic LNs (short diameter > 0.8 cm) were detected was evaluated using the area under the curve (AUC) at the patient level, and the precision, recall, and F1-score were determined at the lesion level. The consistency of LN staging on an hold-out test dataset between the model and radiologist was assessed using Cohen’s kappa coefficient.

Results

In the testing set used for model development, the Dice score, TPR, PPV, VS, HD, AVD and MHD values for the segmentation of suspicious LNs were 0.85, 0.82, 0.80, 0.86, 2.02 (mm), 2.01 (mm), and 1.54 (mm) respectively. The precision, recall, and F1-score for the detection of suspicious LNs were 0.97, 0.98 and 0.97, respectively. In the temporal validation dataset, the AUC of the model for identifying PCa patients with suspicious LNs was 0.963 (95% CI: 0.892–0.993). High consistency of LN staging (Kappa = 0.922) was achieved between the model and expert radiologist.

Conclusion

The 3D U-Net algorithm can accurately detect and segment pelvic LNs based on DWI images.
A disease-causing variant of COL4A5 in a Chinese family with Alport syndrome: a case series
Authors: Wu Jing , Zhang Jun , Liu Li , Zhang Bo , Yamamura Tomohiko , Nozu Kandai , Matsuo Masafumi , Zhao Jinghong
Published: November 2021

Background

Alport syndrome (AS), which is a rare hereditary disease caused by mutations of genes including COL4A3, COL4A4 and COL4A5, has a wide spectrum of phenotypes. Most disease-causing variants of AS are located in the exons or the conservative splicing sites of these genes, while little is known about the intronic disease-causing variants.

Methods

A Chinese AS family was recruited in this study. All the clinical data of AS patient were collected from medical records. After pedigree analysis, the pathogenic variants were studied by the whole exome sequencing (WES). Minigene assay and in vivo RT-PCR analysis were performed to validate the functions of the variants.

Results

Renal biopsy showed a typical histopathology changes of AS. WES revealed compound heterozygous substitution, NM_033380 c.991–14(IVS17) A > G, in the intron 17 of the COL4A5 gene, which were confirmed by Sanger sequencing. Moreover, the variant was co-segregated with the phenotype in this family. Minigene assay in cultured cell lines showed that a splicing error was induced by this intronic variant, which further confirmed by in vivo RT-PCR analysis.

Conclusion

A novel intronic disease-causing variant in COL4A5 gene was identified by WES, which was the molecular pathogenic basis of AS.
Fusobacterium nucleatum and oral cancer: a critical review
Authors: McIlvanna Emily , Linden Gerard J. , Craig Stephanie G. , Lundy Fionnuala T. , James Jacqueline A.
Published: November 2021

There is a growing level of interest in the potential role inflammation has on the initiation and progression of malignancy. Notable examples include Helicobacter pylori-mediated inflammation in gastric cancer and more recently Fusobacterium nucleatum-mediated inflammation in colorectal cancer. Fusobacterium nucleatum is a Gram-negative anaerobic bacterium that was first isolated from the oral cavity and identified as a periodontal pathogen. Biofilms on oral squamous cell carcinomas are enriched with anaerobic periodontal pathogens, including F. nucleatum, which has prompted hypotheses that this bacterium could contribute to oral cancer development. Recent studies have demonstrated that F. nucleatum can promote cancer by several mechanisms; activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation and immune evasion. This review provides an update on the association between F. nucleatum and oral carcinogenesis, and provides insights into the possible mechanisms underlying it.
Dnmt3a is downregulated by Stat5a and mediates G0/G1 arrest by suppressing the miR-17-5p/Cdkn1a axis in Jak2V617F cells
Authors: Zhou Jie , Guo Cheng , Wu Hao , Li Bing , Zhou Li-Li , Liang Ai-Bin , Fu Jian-Fei
Published: November 2021

Background

Despite of the frequently reported Dnmt3a abormality in classical myeloproliferative neoplasms (cMPNs) patients, few research explores how the Dnmt3a is regulated by Jak2V617F mutation. In this study, we have investigated how the Dnmt3a is regulated by Jak2V617F mutation and its effects on downstream signaling pathways in cMPNs.

Methods

Specimens of Jak2V617F positive cMPN patients and normal controls were collected. Murine BaF3 cell line was used to construct cell models. Dual-Glo luciferase assays and chromatin immunoprecipitation (ChIP)-qPCR were performed to detect the impact of Stat5a on transcription activity of Dnmt3a. Soft agar colony formation assay and cell counting assay were performed to detect cell proliferation. BrdU staining and flow cytometry were used to investigate cell cycle distribution. Western blotting and quantitative reverse-transcription PCR (qPCR) were performed to detect the expression levels of genes.

Results

Firstly, the results of western blotting and qPCR revealed that compared with the control samples, Dnmt3a is downregulated in Jak2V617F positive samples. Then we explored the mechanism behind it and found that Dnmt3a is a downstream target of Stat5a, the transcription and translation of Dnmt3a is suppressed by the binding of aberrantly activated Stat5a with Dnmt3a promoter in Jak2V617F positive samples. We further revealed the region approximately 800 bp upstream of the first exon of the Dnmt3a promoter, which includes a gamma-activated sequence (GAS) motif of Stat5a, is the specific site that Stat5a binds to. Soft agar colony formation assay, cell counting assay, and BrdU staining and flow cytometry assay found that Dnmt3a in Jak2V617F-BaF3 cells significantly affected the cell proliferation capacity and cell cycle distribution by suppressing Cdkn1a via miR-17-5p/Cdkn1a axis and mediated G0/G1 arrest.

Conclusions

Transcription and translation of Dnmt3a is downregulated by the binding of Stat5a with Dnmt3a promoter in Jak2V617F cells. The GAS motif at promoter of Dnmt3a is the exact site where the Stat5a binds to. Dnmt3a conducted G0/G1 arrest through regulating miR-17-5p/Cdkn1a axis. The axis of Stat5a/Dnmt3a/miR-17-5p/Cdkn1a potentially provides a treatment target for cMPNs.
Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M
Authors: Wang Yurong , Zheng Ruipan , Hu Peizhu , Zhang Ziheng , Shen Shujing , Li Xingya
Published: November 2021

Background

In the existing next generation sequencing (NGS) system, epidermal growth factor receptor (EGFR) exon 19 deletion-insertion (19delins) is still interpreted into the category of EGFR exon 19 deletion (19del). However, the controversy exists whether the two mutation types have the similar responses and resistant mechanisms to first-generation EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients.

Methods

We successively and retrospectively reviewed the NGS data of 3054 patients diagnosed as advanced NSCLC from November 2017 to September 2020. Finally, 41 patients with EGFR 19delins mutation and 41 patients with EGFR 19del mutation who received first-generation EGFR TKIs as first-line therapy were included in the study.

Results

A total of 17 genotypes were identified in this study, including L747_P753delinsS (10/41), L747_A750delinsP (9/41), L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, the population of EGFR 19delins respond well to first line EGFR TKIs as well as those of EGFR 19del, with little difference in median progression-free survival (mPFS): 10.4 months vs. 13.1 months, p = 0.1076). Interestingly, patients with L747_T751delinsP seem to have a better mPFS than others (18.7 months vs. 13.1 months, p = 0.035). After the disease progression, both EGFR 19delins and EGFR 19del had similar rates of developing EGFR T790M mutation resistance (45.8% vs. 57.8%), and those receiving osimeritinib as second-line treatment obtain the similar survival benefits (mPFS: 12.0 months vs. 12.2 months (p = 0.97).

Conclusions

This retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.
Impact of skeletal muscle mass in patients with unresectable gastric cancer who received palliative first-line chemotherapy based on 5-fluorouracil
Authors: Matsunaga Tomoyuki , Saito Hiroaki , Miyauchi Wataru , Shishido Yuji , Miyatani Kozo , Morimoto Masaki , Murakami Yuki , Hanaki Takehiko , Kihara Kyoichi , Yamamoto Manabu , Tokuyasu Naruo , Takano Shuichi , Sakamoto Teruhisa , Hasegawa Toshimichi , Fujiwara Yoshiyuki
Published: November 2021

Background

The mortality rate of patients with unresectable gastric cancer (UGC) has decreased with the development of chemotherapies and surgical techniques. However, the survival rate remains low. We retrospectively examined the prognostic significance of the pretreatment skeletal muscle mass index (SMI) and nutritional and inflammatory factors in patients with UGC.

Methods

This study included 83 patients diagnosed with UGC at Tottori University Hospital who received palliative chemotherapy based on 5-fluorouracil. Pretreatment computed tomography (CT) measured overall skeletal muscle mass (SMM) and cross-sectional SMM at the third lumbar vertebra (L3). We focused on the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and platelet-to-lymphocyte ratio (PLR) as nutritional and inflammatory factors.

Results

Receiver operating characteristic curve analysis was performed for median survival time (MST) after palliative chemotherapy. SMIs for males and females (43.9 cm2/m2 and 34.7 cm2/m2, respectively) were the cutoff values, and patients were divided into high (SMIHigh; n = 41) and low SMI groups (SMILow; n = 42). Body mass index (BMI) was significantly higher in patients in the SMIHigh group than in the SMILow group (p < 0.001). The number of patients who received third-line chemotherapy was significantly higher in the SMIHigh group than in the SMILow group (p = 0.037). The MST was significantly higher in the SMIHigh group than in the SMILow group (17.3 vs. 13.8 months; p = 0.008). The incidence of grade 3 or 4 side effects was significantly higher in patients with SMILow UGC (p = 0.028). NLR was significantly higher in patients with SMILow than it was in those with SMIHigh. (p = 0.047). In the univariate analysis, performance status, SMI, histological type, lines of chemotherapy, and NLR were prognostic indicators. The multivariate analysis identified SMI (p = 0.037), NLR (p = 0.002), and lines of chemotherapy (p < 0.001) as independent prognostic factors.

Conclusions

The SMILow group had significantly more grade 3 or 4 side effects, were related to high NLR, and had a significantly worse prognosis than the SMIHigh group.

Trial registration

Retrospectively registerd.
Identification of risk factors associated with oral 5-aminolevulinic acid-induced hypotension in photodynamic diagnosis for non-muscle invasive bladder cancer: a multicenter retrospective study
Authors: Fukuhara Hideo , Nohara Takahiro , Nishimoto Koshiro , Hatakeyama Yutaka , Hyodo Yuki , Okuhara Yoshiyasu , Oyama Masafumi , Mizokami Atsushi , Inoue Keiji , Matsuyama Hideyasu ,   on behalf of the Japan Urological Photodynamic Society
Published: November 2021

Background

To investigate risk factors for orally administered 5-aminolevulinic acid (ALA)-induced hypotension for bladder cancer patients receiving photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT).

Methods

Patients were categorized into two groups intraoperatively: a hypotensive group (minimum systolic blood pressure (SBP) ≤80 mmHg) and a non-hypotensive group (minimum SBP > 80 mmHg). We examined differences between the hypotensive group and non-hypotensive groups to identify clinical risk of ALA-induced hypotension using multivariate logistic regression analysis and decision tree analysis.

Results

Among 282 cases with ALA-PDD-assisted TURBT from three institutions who were screened, 245 patients were included in the final analysis. In total, 156 patients (63.7%) showed any grade of hypotension during ALA-PDD-assisted TURBT. General anesthesia and spinal anesthesia were induced intraoperatively in 113 patients (46.1%) and 132 patients (53.9%), respectively. Median SBP at baseline (before taking ALA) and at the beginning of anesthesia was 127 mmHg (range, 69–186 mmHg) and 124 mmHg (range, 69–186 mmHg), respectively. Median minimum SBP during ALA-PDD-assisted TURBT was 75 mmHg (range, 43–140 mmHg). Multivariate logistic regression analysis revealed that history of hypertension (odds ratio (OR) 7.568, p < 0.05) and general anesthesia (OR 14.435, p < 0.05) as significantly associated with an increased risk of hypotension incidence. Use of calcium antagonist showed significant negative associations with hypotension (OR 0.183, p < 0.05). Decision tree analysis showed presence of general anesthesia, age ≥ 74 years and American Society of Anesthesiologists physical status (ASA-PS) ≥2 as the most important discriminators.

Conclusions

General anesthesia and hypertension were independent risk factors related to ALA-induced hypotension. In contrast, use of calcium antagonists was identified as a factor associated with reduced risk of ALA-induced hypotension.
Novel type of references for weight aligned for onset of puberty – using the QEPS growth model
Authors: Albertsson-Wikland Kerstin , Niklasson Aimon , Gelander Lars , Holmgren Anton , Nierop Andreas F. M.
Published: November 2021

Background

Growth references are traditionally constructed relative to chronological age, despite inter-individual variations in pubertal timing. A new type of height reference was recently developed allowing growth to be aligned based on onset of pubertal height growth. We here aim to develop a corresponding reference for pubertal weight.

Methods

To model QEPS-weight, 3595 subjects (1779 girls) from GrowUp1974Gothenburg and GrowUp1990Gothenburg were used. The QEPS-height-model was transformed to a corresponding QEPS-weight-model; thereafter, QEPS-weight was modified by an individual, constitutional weight-height-factor. Longitudinal weight and length/height measurements from 1418 individuals (698 girls) from GrowUp1990Gothenburg were then used to create weight references aligned for height at pubertal onset (the age at 5% of P-function growth, AgeP5). GrowUp1974Gothenburg subgroups based on pubertal timing, stature at pubertal onset, and childhood body composition were assessed using the references.

Results

References (median, SDS) for total weight (QEPS-functions), weight specific to puberty (P-function), and weight gain in the absence of specific pubertal growth (basic weight, QES-functions), allowing alignment of individual growth based on age at pubertal onset. For both sexes, basic weight was greater than average for late maturing, tall and high-BMI subgroups. The P-function-related weight was greater than average in short and lower than average in tall children, in those with high BMI, and in girls but not boys with low BMI.

Conclusions

New pubertal weight references allow individual variations in pubertal timing to be taken into consideration when evaluating growth. When used together with the comparable pubertal height reference, this will improve growth monitoring in clinical practice for identifying abnormal growth and serve as a valuable research tool providing insight into human growth.
Development and psychometric properties of the Knowledge and Attitudes to Mental Health Scales (KAMHS): a psychometric measure of mental health literacy in children and adolescents
Authors: Simkiss Nicola J. , Gray Nicola S. , Dunne Chris , Snowden Robert J.
Published: November 2021

Background

Adolescence is a crucial period for the acquisition of good mental health behaviours, which are the foundation for health and wellbeing in later life. Improved knowledge about mental health and improved help-seeking behaviours have been shown to lead to better mental health outcomes. Mental health literacy (MHL) is multifaceted (e.g., knowledge about symptoms, the stigma around mental health, good mental health practices, etc.). Measures are needed that can assess these different aspects of MHL. Measurement of mental health literacy is currently limited due to a lack of reported psychometric instruments with known psychometric properties. Given that most mental health problems start in early adolescence, a scale is needed that is reliable and valid in this age group.

Methods

The development and validation of the psychometric instrument (termed the Knowledge and Attitudes to Mental Health Scales: KAMHS) entailed two phases: 1) item generation based on an evidence-based intervention programme: The Guide; and 2) item reduction through exploratory factor analysis (EFA), and confirmatory factor analysis (CFA) for factor structure and psychometric assessment. Participants were 559 Year 9 pupils in secondary schools across Wales aged between 13 and 14 years.

Results

Results from the CFA indicated an acceptable fit of the model to the data. The KAMHS showed good internal constancy and moderate test-retest validity (.40–.64).

Conclusions

The final version of the KAMHS contains 50 items that are appropriate for use in children and adolescents. These results suggest that the KAMHS can be used over time to assess the efficacy of interventions aimed at increasing the mental health literacy of adolescent populations.
Effectiveness and acceptability of a novel school-based healthy eating program among primary school children in urban Sri Lanka
Authors: Seneviratne Sumudu Nimali , Sachchithananthan Sanathanee , Gamage Pavithra Sewwandi Angulugaha , Peiris Renuka , Wickramasinghe Vithanage Pujitha , Somasundaram Noel
Published: November 2021

Background

Obesity rates are rising rapidly in low-middle-income-countries (LMICs). School-based interventions have shown moderate efficacy in improving diet and lifestyle associated with obesity in high-income countries. However, there is little data available on effective interventions suitable for LMICs. We devised a novel program for primary school children including a simple storybook and sticker-based food-diary (FD) and conducted a pilot study to evaluate the acceptability and short-term effectiveness of the program.

Methods

This pre-post intervention study included grade 1 and 2 students from four public schools in Colombo, Sri Lanka. Weight and height were assessed, and participating children self-monitored their diet using sticker-based FDs for one week at baseline (pre-test). The following week, class teachers discussed the storybook, which incorporated the benefits/disadvantages of a healthy/unhealthy diet and lifestyle in classrooms. At the end of the intervention, participating children were self-monitoring their diet again for a week (post-test). A simple scoring system was used to derive a weekly score based on the healthiness of the meals consumed each week (FD-score). The primary outcome of the study was change in eating habits following the story book discussion (post-test FD score - pre-test FD score). Acceptability and effectiveness were also assessed by anonymized feedback questionnaires for parents and teachers.

Results

One thousand and forty-two students completed the program. There was an improvement in eating habits of participating children, with FD scores improving by 12% from 51 ± 23 at baseline to 63 ± 24 following the intervention (p < 0.001). Further, when considering BMI category of participants: 69.1% were normal weight (NW), 18.3% underweight (UW), 7.4% overweight (OW) and 5.2% obese (OB). Improvement in eating habits were seen among children of all BMI categories (change in FD-score: UW 13.2%, NW 12.3%, OW 10.4% and OB 12.4% (p < 0.001)).

Furthermore,> 90% parents(n = 1028) and > 95% teachers(n = 39) strongly agreed/agreed that the intervention was easy to implement, motivated children and led to an observable improvement in healthy eating.

Conclusion

This novel program led to an immediate improvement in eating habits and was well accepted by parents and teachers making it a potentially suitable intervention for wider implementation in primary schools in urban Sri Lanka.
Revisiting COVID-19 policies: 10 evidence-based recommendations for where to go from here
Authors: Halperin Daniel T. , Hearst Norman , Hodgins Stephen , Bailey Robert C. , Klausner Jeffrey D. , Jackson Helen , Wamai Richard G. , Ladapo Joseph A. , Over Mead , Baral Stefan , Escandón Kevin , Gandhi Monica
Published: November 2021

Background

Strategies to control coronavirus 2019 disease (COVID-19) have often been based on preliminary and limited data and have tended to be slow to evolve as new evidence emerges. Yet knowledge about COVID-19 has grown exponentially, and the expanding rollout of vaccines presents further opportunity to reassess the response to the pandemic more broadly.

Main text

We review the latest evidence concerning 10 key COVID-19 policy and strategic areas, specifically addressing: 1) the expansion of equitable vaccine distribution, 2) the need to ease restrictions as hospitalization and mortality rates eventually fall, 3) the advantages of emphasizing educational and harm reduction approaches over coercive and punitive measures, 4) the need to encourage outdoor activities, 5) the imperative to reopen schools, 6) the far-reaching and long-term economic and psychosocial consequences of sustained lockdowns, 7) the excessive focus on surface disinfection and other ineffective measures, 8) the importance of reassessing testing policies and practices, 9) the need for increasing access to outpatient therapies and prophylactics, and 10) the necessity to better prepare for future pandemics.

Conclusions

While remarkably effective vaccines have engendered great hope, some widely held assumptions underlying current policy approaches call for an evidence-based reassessment. COVID-19 will require ongoing mitigation for the foreseeable future as it transforms from a pandemic into an endemic infection, but maintaining a constant state of emergency is not viable. A more realistic public health approach is to adjust current mitigation goals to be more data-driven and to minimize unintended harms associated with unfocused or ineffective control efforts. Based on the latest evidence, we therefore present recommendations for refining 10 key policy areas, and for applying lessons learned from COVID-19 to prevent and prepare for future pandemics.
A systematic review and meta-analysis of the effect of treadmill desks on energy expenditure, sitting time and cardiometabolic health in adults
Authors: Oye-Somefun Akinkunle , Azizi Zahra , Ardern Chris I. , Rotondi Michael A.
Published: November 2021

Background

As the health risks of sedentary working environments become more clear, greater emphasis on the implementation of walking interventions to reduce sitting time is needed. In this systematic review and meta-analysis, we investigate the role of treadmill-desk interventions on energy expenditure, sitting time, and cardiometabolic health in adults with sedentary occupations.

Methods

Relevant studies published in English were identified using CINAHL, EMBASE, MEDLINE, Web of Science, Scopus, and PubMed databases up to December 2020. Random effects meta-analysis models were used to pool study results.

Results

Thirteen relevant studies (six workplaces and seven laboratories) were found with a total of 351 participants. Pooled analysis of laboratory studies showed a significant increase in energy expenditure (105.23 kcal per hour, 95% confidence interval [CI]: 90.41 to 120.4), as well as metabolic rate (5.0 mL/kg/min, 95% CI: 3.35 to 6.64), among treadmill desk users compared to sitting conditions. No evidence of significant differences in blood pressure were found. In workplace studies, we observed a significant reduction in sitting time over a 24-h period (− 1.73 min per hour, 95% CI: − 3.3 to − 0.17) among users of treadmill desks, compared to a conventional desk. However, there were no evidence of statistically significant changes in other metabolic outcomes.

Conclusions

Treadmill desks offer a feasible and effective intervention to increase energy expenditure and metabolic rate and reduce sitting time while performing work-related tasks. Future studies are needed to increase generalizability to different workplace settings and further evaluate their impact on cardiometabolic health.
A qualitative exploration of perspectives of physical activity and sedentary behaviour among Indian migrants in Melbourne, Australia: how are they defined and what can we learn?
Authors: Fernandes Siona , Caperchione Cristina M. , Thornton Lukar E. , Timperio Anna
Published: November 2021

Background

Although perceptions of what constitutes physical activity (PA) may vary between culturally diverse populations, very little research has explored the perceptions of PA among Indian migrants. This study aimed to identify how PA and sedentary behaviour (SB) are defined and describe how these definitions are shaped by cultural background and migration among a sample of Indian migrants living in Australia.

Methods

Using an exploratory qualitative approach, semi-structured interviews were conducted with twenty-one Indian migrants living in Melbourne (10 men and 11 women; age range: 18 to 65 years). Interviews were audio-recorded and transcribed verbatim. Data were coded and analysed inductively using thematic analyses.

Results

Data revealed two emerging themes: 1) Holistic perspectives related to PA, where although the majority of participants described PA as “any sort of movement”, or “physical exercise”, several of these descriptions had interwoven ideas related to the mind (mind-body connect), social, cultural, and to the outdoor environment; 2) Broader perspectives for SB, where descriptions of SB as “not having movement”, “doing nothing” or “being lazy”, were shaped with ideas of purpose and duration. Women spoke about how their perspectives of PA and SB may be shaped by native Indian experiences, particularly the gender roles, social caste, and regional subcultural norms which they perceived were important to consider among women who migrate to western settings.

Conclusions

Cultural background is important in shaping the perspectives of PA and SB among Indian migrants in Australia. Practitioners and researchers should consider the varying perspectives of PA to communicate and promote PA among migrant populations more effectively.