bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution and genetic diversity of Enterovirus G (EV-G) on pig farms in Thailand
Authors: Janetanakit Taveesak , Chaiyawong Supassama , Charoenkul Kamonpan , Tangwangvivat Ratanaporn , Chamsai Ekkapat , Udom Kitikhun , Jairak Waleemas , Amonsin Alongkorn
Published: August 2021

Background

Enterovirus G (EV-G) causes subclinical infections and is occasionally associated with diarrhea in pigs. In this study, we conducted a cross-sectional survey of EV-G in pigs from 73 pig farms in 20 provinces of Thailand from December 2014 to January 2018.

Results

Our results showed a high occurrence of EV-Gs which 71.6 % of fecal and intestinal samples (556/777) and 71.2 % of pig farms (52/73) were positive for EV-G by RT-PCR specific to the 5’UTR. EV-Gs could be detected in all age pig groups, and the percentage positivity was highest in the fattening group (89.7 %), followed by the nursery group (89.4 %). To characterize the viruses, 34 EV-G representatives were characterized by VP1 gene sequencing. Pairwise sequence comparison and phylogenetic analysis showed that Thai-EV-Gs belonged to the EV-G1, EV-G3, EV-G4, EV-G8, EV-G9 and EV-G10 genotypes, among which the EV-G3 was the predominant genotype in Thailand. Co-infection with different EV-G genotypes or with EV-Gs and porcine epidemic diarrhea virus (PEDV) or porcine deltacoronavirus (PDCoV) on the same pig farms was observed.

Conclusions

Our results confirmed that EV-G infection is endemic in Thailand, with a high genetic diversity of different genotypes. This study constitutes the first report of the genetic characterization of EV-GS in pigs in Thailand.
Nitric oxide-releasing micelles with intelligent targeting for enhanced anti-tumor effect of cisplatin in hypoxia
Authors: Chen Yan , Fang Lei , Zhou Weixin , Chang Jinghan , Zhang Xiaojuan , He Chuanchuan , Chen Chen , Yan Ruicong , Yan Yakai , Lu Yao , Xu Chuanrui , Xiang Guangya
Published: August 2021

Background

Hypoxic tumor microenvironment (TME) promotes tumor metastasis and drug resistance, leading to low efficiency of cancer chemotherapy. The development of targeted agents or multi-target therapies regulating hypoxic microenvironment is an important approach to overcome drug resistance and metastasis.

Methods

In this study, chitosan oligosaccharide (COS)-coated and sialic acid (SA) receptor-targeted nano-micelles were prepared using film dispersion method to co-deliver cisplatin (CDDP) and nitric oxide (NO) (denoted as CTP/CDDP). In addition, we explored the mechanisms by which NO reversed CDDP resistance as well as enhanced anti-metastatic efficacy in hypoxic cancer cells.

Results

Because of the different affinities of COS and SA to phenylboronic acid (PBA) under different pH regimes, CTP/CDDP micelles with intelligent targeting property increased cellular uptake of CDDP and enhanced cytotoxicity to tumors, but reduced systemic toxicity to normal organs or tissues. In addition, CTP/CDDP showed stimulus-responsive release in TME. In terms of anti-tumor mechanism, CTP/CDDP reduced CDDP efflux and inhibited epithelial-mesenchymal transition (EMT) process of tumor by down-regulating hypoxia-inducible factor-1α (HIF-1α), glutathione (GSH), multidrug resistance-associated protein 2 (MRP2) and matrix metalloproteinase 9 (MMP9) expression, thus reversing drug resistance and metastasis of hypoxic tumor cells.

Conclusions

The designed micelles significantly enhanced anti-tumor effects both in vitro and in vivo. These results suggested that CTP/CDDP represented a promising strategy to treat resistance and metastatic tumors.

Graphic abstract
Iliosacral Bone Tumor Resection Using Cannulated Screw-Guided Gigli Saw - A Novel Technique
Authors: Ji Tao , Chin Brian Z. J. , Tang Xiaodong , Yang Rongli , Guo Wei
Published: August 2021

Background

Adequate margins are technically difficult to achieve for malignant tumors involving the sacroiliac joint due to limited accessibility and viewing window. In order to address the technical difficulties faced in iliosacral tumor resection, we proposed a technique for precise osteotomy, which involved the use of canulated screws and Gigli saw (CSGS) that facilitated directional control, anteroposterior linkage of resection points and adequate surgical margins. The purpose of the current study was to evaluate whether CSGS technique facilitated sagittal osteotomy at sacral side, and were adequate surgical margins achieved? Also functional and oncological outcomes was determined along with the noteworthy complications.

Methods

From April 2018 to November 2019, we retrospectively reviewed 15 patients who underwent resections for primary tumors of pelvis or sacrum necessitating iliosacral joint removal using the proposed CSGS technique. Chondrosarcoma was the most common diagnosis. The osteotomy site within sacrum was at ipsilateral ventral sacral foramina in 8 cases, midline of sacrum in 5 cases, and contralateral ventral sacral foramina and sacral ala with 1 case each. The average intraoperative blood loss was 3640 mL (range, 1200 and 6000 mL) with a mean operation duration of 7.4 hours (range, 5 to 12 hours). The mean follow-up was 23.0 months (range, 18 and 39 months) for alive patients.

Results

Surgical margins were wide in 12 patients (80%), wide-contaminated in 1 patient (6.7%), and marginal in 2 patients (13.3%). R0 resection was achieved in 12 (80%) patients and R1 resection in 3 patients. There were three local recurrences (20%) occurred at a mean time of 11 months postoperatively. No local recurrence was observed at sacral osteotomy. The overall one-year and three-year survival rate was 86.7% and 72.7% respectively.Complications occurred in three patients.

Conclusions

The current study demonstrated that CSGS technique for tumor resection within the sacrum and pelvis was feasible and can achieve ideal resection accuracies. The use of CSGS was associated with high likelihood of negative margin resections in the current series. Intraoperative use of CSGS appeared to be technically straightforward and allowed achievement of planned surgical margins. It is worthwhile to consider the use of CSGS technique in resection of pelvic tumors with sacral invasion and iliosacral tumors, however further follow-up at mid to long-term is warranted to observe local recurrence rate.
Immunological repertoire linked to PSTPIP1-associated myeloid-related inflammatory (PAMI) syndrome
Authors: Mendonça Leonardo Oliveira , Terreri Maria Teresa , Osaku Fabiane Mitie , Barros Samar Freschi , Köhler Karen Francine , Prado Alex Isidoro , Barros Myrthes Toledo , Kalil Jorge , Castro Fabio Fernandes Morato
Published: August 2021

Background

Mutations along PSTPIP1 gene are associated to two specific conditions, PAPA syndrome and PAMI syndrome, both autoinflammatory disorders associated to disturbances in cytoskeleton formation. Immunological aspects of PAMI syndrome has not yet been reported neither the clinical impact on therapeutical decisions.

Methods

Clinical data of patients records were retrospectively accessed. Genomic DNA were extracted and sequenced following standard procedures. Peripheral lymphocytes were quantified in T, B e FOXP3 phenotypes.

Results

We describe two related patients with PAMI syndrome harboring the usual E250K mutation. Anti-IL1 therapy could partially control the disease in the index patient. A broad spectrum of immunological effects as well as an aberrant expression of FOXP3 could be observed.

Conclusions

Here we report two related brazilian patients with PAMI syndromes harboring the E250K mutation in PSTPIP1, their immunological aspects and the therapeutical response to canakinumab.
Impact of HIV-1 CRF55_01B infection on the evolution of CD4 count and plasma HIV RNA load in men who have sex with men prior to antiretroviral therapy
Authors: Wei Lan , Li Hao , Lv Xing , Zheng Chenli , Li Guilian , Yang Zhengrong , Chen Lin , Han Xiaoxu , Zou Huachun , Gao Yanxiao , Cheng Jinquan , Wang Hui , Zhao Jin
Published: August 2021

Background

CRF55_01B is a newly identified HIV-1 circulating recombinant form originated from MSM in China. However, its impact on the disease progression and transmission risk has not been investigated. This study aimed to determine the impact of CRF55_01B infection on viral dynamics and immunological status so as to provide scientific evidence for further control and prevention effort on CRF55_01B. Linear mixed effect models were applied to evaluate CD4 cell count decline and viral load increase by subtype.

Results

Of the 3418 blood samples, 1446 (42.3%) were CRF07_BC, 1169 (34.2%) CRF01_AE, 467 (13.7%) CRF55_01B, 249 (7.3%) type B, and 87 (2.5%) other subtypes (CRF_08BC, CRF_01B, C). CRF55_01B had become the third predominant strain since 2012 in Shenzhen, China. CRF55_01B-infected MSM showed lower median of CD4 count than CRF07_BC-infected MSM (349.5 [IQR, 250.2–474.8] vs. 370.0 [IQR, 278.0–501.0], P < 0.05). CRF55_01B infection was associated with slower loss of CD4 count than CRF01_AE (13.6 vs. 23.3 [cells/µl]¹/²/year, P < 0.05)among MSM with initial CD4 count of 200–350 cells/µl. On the other hand, those infected with CRF55_01B showed higher median plasma HIV RNA load (5.4 [IQR, 5.0–5.9]) than both CRF01_AE (5.3 [IQR, 4.8–5.7], P < 0.05) and CRF07_BC (5.0 log10 [IQR, 4.5–5.5], P < 0.001) at the initiation of antiretroviral therapy. Furthermore, the annual increasing rate of viral load for CRF55_01B infection was significantly higher than that of CRF07_BC (2.0 vs. 0.7 log10 copies/ml/year, P < 0.01).

Conclusions

The relatively lower CD4 count and faster increase of plasma HIV RNA load of CRF55_01B-infected MSM without antiretroviral therapy suggest that CRF55_01B may lead to longer asymptomatic phase and higher risk of HIV transmission. Strengthened surveillance, tailored prevention strategies and interventions, and in-depth research focusing on CRF55_01B are urgently needed to forestall potential epidemic.
Deep reinforcement learning for modeling human locomotion control in neuromechanical simulation
Authors: Song Seungmoon , Kidziński Łukasz , Peng Xue Bin , Ong Carmichael , Hicks Jennifer , Levine Sergey , Atkeson Christopher G. , Delp Scott L.
Published: August 2021

Modeling human motor control and predicting how humans will move in novel environments is a grand scientific challenge. Researchers in the fields of biomechanics and motor control have proposed and evaluated motor control models via neuromechanical simulations, which produce physically correct motions of a musculoskeletal model. Typically, researchers have developed control models that encode physiologically plausible motor control hypotheses and compared the resulting simulation behaviors to measurable human motion data. While such plausible control models were able to simulate and explain many basic locomotion behaviors (e.g. walking, running, and climbing stairs), modeling higher layer controls (e.g. processing environment cues, planning long-term motion strategies, and coordinating basic motor skills to navigate in dynamic and complex environments) remains a challenge. Recent advances in deep reinforcement learning lay a foundation for modeling these complex control processes and controlling a diverse repertoire of human movement; however, reinforcement learning has been rarely applied in neuromechanical simulation to model human control. In this paper, we review the current state of neuromechanical simulations, along with the fundamentals of reinforcement learning, as it applies to human locomotion. We also present a scientific competition and accompanying software platform, which we have organized to accelerate the use of reinforcement learning in neuromechanical simulations. This “Learn to Move” competition was an official competition at the NeurIPS conference from 2017 to 2019 and attracted over 1300 teams from around the world. Top teams adapted state-of-the-art deep reinforcement learning techniques and produced motions, such as quick turning and walk-to-stand transitions, that have not been demonstrated before in neuromechanical simulations without utilizing reference motion data. We close with a discussion of future opportunities at the intersection of human movement simulation and reinforcement learning and our plans to extend the Learn to Move competition to further facilitate interdisciplinary collaboration in modeling human motor control for biomechanics and rehabilitation research
German-speaking medical students on international electives: an analysis of popular elective destinations and disciplines
Authors: Storz Maximilian Andreas , Lederer Ann-Kathrin , Heymann Eric Pieter
Published: August 2021

Background

International medical electives are a well-established part of the curriculum of many western medical schools. It is widely accepted that these electives contribute to improved clinical examination and communication skills. Overseas electives also exert a strong influence over future career decisions and often pave the way for later international work. Whilst the positive outcomes are known, little information exists regarding elective preferences and destinations overall, information that could help optimise a safe learning experience and maximise the potential for one of the highlights of medical education. In order to obtain analytical data that could assist medical elective framework development, we systematically reviewed the two largest German online databases cataloguing abroad elective testimonies.

Results

We identified 856 overseas elective reports uploaded within the last five years. European destinations were the most sought-after choice among German-speaking medical students. Interest in abroad electives in the United States (U.S.), a traditionally popular destination, was much lower than expected. U.S. elective reports accounted for only 3 % of long-term electives. Electives in low- and middle-income countries were generally less popular than electives in high-income countries. General surgery was the most popular elective discipline, followed by Emergency Medicine and Gynaecology and Obstetrics.

Conclusions

We observed a large inhomogeneity in German-speaking medical students’ elective choices, potentially influenced by financial and organizational aspects as well as geopolitical developments. This highlights a crucial challenge for medical schools and other organizations involved in elective planning. In light of regional differences, our data suggest that a “one size fits all” preparation is not pertinent to optimize students’ elective experience. Country- or region-specific pre-departure trainings and more individualized elective frameworks might be necessary to address these differences and to ensure a safe learning experience for students.
Reliability and reproducibility of measurements in para-sagittal planes on sub-axial cervical vertebral bodies: a morphometric study of endplates in three-dimensional models
Authors: Wang Long , Luo Hao T. , Lu Wei , Cai Xing Bo , Yu Chen , Lu Sheng
Published: August 2021

Background

Dimensional measurements have been implemented on a variety of entities in morphological studies of the sub-axial cervical vertebral endplate. Despite great progress, little information between the mid-sagittal plane and bilateral uncinate processes has been acquired due to the lack of a reliable method to determine the para-sagittal planes. Also, few studies of this region are available. We proposed a new approach to defining the para-sagittal planes on a 3D cervical vertebral body model; in this approach, dimensions can be measured in a specific plane. The aim of this study was to assess the inter-observer and intra-observer reliability of the measurements in different sagittal planes on sub-axial cervical vertebral endplates of 3D models.

Methods

We established mid-sagittal and bilateral quarter para-sagittal planes on the 3D model of a sub-axial cervical vertebral body based on landmarks labeled on the surface. By intersecting the vertebral body with the planes, three curves located at the three para-sagittal planes were generated. Linear dimensions were measured on every curve by two observers separately, and in total, 24 sub-axial cervical spines were included in the study. The first observer (O1) performed the procedure twice with an interval of 2 weeks. The paired t test, Wilcoxon matched-pairs signed-rank test and the interclass correlation coefficient (ICC) were employed to evaluate the inter- and intra-observer reliability of the proposed method.

Results

There were no significant differences in most intra- and inter-observer comparisons, and higher non-significant proportions were found in the intra-observer comparisons than in comparisons between different observers. The interclass correlation coefficients (ICCs) in the measurements were excellent (> 0.75) in most circumstances, and the values in intra-observer comparisons were higher than those in inter-observer comparisons.

Conclusions

In this study, we proposed an approach to determine the bilateral quarter para-sagittal planes in a 3D cervical vertebral body model; the results demonstrated that the method is reproducible with high intra- and inter-observer agreement.
Is the fusion order of the cranial and caudal levels different in two-level anterior cervical discectomy and fusion for cervical spondylopathy? A retrospective study
Authors: Sheng Xia-Qing , Meng Yang , Liu Hao , Wang Bei-Yu , Yang Yi , Rong Xin , Hong Ying
Published: August 2021

Study design

Retrospective study.

Objective

This study aimed to compare the fusion order between the cranial and caudal levels in two-level anterior cervical discectomy and fusion (ACDF) with a zero-profile device in the treatment of cervical spondylopathy.

Summary of background data

Fusion is the standard used to judge the success of ACDF. However, the fusion order in two-level ACDF remains uncertain. The mechanical environment of different levels is different, which may affect the fusion rate or fusion order.

Methods

From 2014 to January 2019, data of consecutive patients with two-level cervical disk degenerative disease who underwent ACDF were retrospectively reviewed. Radiological assessments were based on the range of motion of the fusion level, segment slope, and disk height, and complications were assessed. Data were analyzed using the paired t, Mann-Whitney U, χ2, Fisher exact, and rank-sum tests and logistic regression analysis.

Results

In total, 118 patients were ultimately enrolled for analysis in the study. The respective fusion rates of the cranial and caudal levels were 26.27% and 10.17% (p < 0.05) at 3 months, 58.47% and 42.37% (p < 0.05) at 6 months, 86.44% and 82.20% (1 0.05) at 1 year, and 92.37% and 89.83% (p > 0.05) at the last follow-up. Multivariate logistic regression analysis indicated that the preoperative segmental slope and cranial level were independent risk factors for non-fusion. The adjacent segment degeneration (ASD) and subsidence rates were comparable between the two levels.

Conclusion

The caudal level had a slower fusion process than the cranial level. A higher preoperative segment slope was a risk factor for fusion. However, the subsidence and ASD rate were comparable between the caudal and cranial levels in the two-level ACDF.
Traditional herbal formula Wu-Mei-Wan alleviates TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3 O-GlcNAcylation
Authors: Wu Fan , Shao Qingqing , Cheng Zhe , Xiong Xinyu , Fang Ke , Zhao Yan , Dong Ruolan , Xu Lijun , Lu Fuer , Chen Guang
Published: August 2021

Background

Accumulating evidence indicated that necroptosis plays an essential role in the pathogenesis of inflammatory bowel disease (IBD). TheO-linked β-N-acetylglucosaminylation (O-GlcNAcylation) of necroptotic signal molecule receptor-interacting serine-threonine kinase 3 (RIPK3) was reported to exert a protective effect in gut inflammation. Our recent study suggested traditional Chinese herbal formula Wu-Mei-Wan (WMW) as an effective prescription in mouse colitis. However, the potential mechanisms are not fully understood. Considering the crucial role of necroptosis in the pathogenesis of IBD, therefore, this study was designed to explain whether the anti-colitis effect of WMW is mediated by modulating necroptosis and its related mechanisms.

Methods

The protective effects of WMW on colitis have been determined by detecting colitis mice body weight, disease activity index (DAI), survival rate and colon length. Colonic inflammation was examined by inflammatory cells infiltration and local cytokines levels. After then, we measured the levels of necroptosis andO-GlcNAcylation. CO-immunoprecipitation experiments were used to address whether elevatedO-GlcNAcylation can inhibit necroptotic signal transduction in the treatment of WMW. Finally, the key enzymes inO-GlcNAcylation:O-GlcNAc transferase (OGT) andO-GlcNAcase (OGA) were examined and molecular docking analysis was used to determine effective natural compounds in the regulation on OGT and OGA activities.

Results

Our results showed that WMW significantly improved mice body weight, survival rate and colon length, decreased DAI in TNBS-induced colitis. WMW obviously alleviated colonic inflammatory responses with reduced macrophages, neutrophils infiltration and local IL-1β, IL-6, TNF-α and IFN-γ levels. It was found that WMW increased colonicO-GlcNAcylation level and inhibited the activation of RIPK1, RIPK3 and MLKL. Then, further experiments revealed that WMW enhanced OGT activity and suppressed OGA activity, thereby increasing RIPK3O-GlcNAcylation and inhibiting the binding of RIPK3 and MLKL, which led to the inhibition of necroptosis. Additionally, docking analysis demonstrated that hesperidin, coptisine and ginsenoside Rb1 may exert a major role in the regulation on OGT and OGA activities by WMW.

Conclusion

Our work demonstrated that WMW can alleviate TNBS-induced colitis in mice by inhibiting necroptosis through increasing RIPK3O-GlcNAcylation.
SELP Asp603Asn and severe thrombosis in COVID-19 males
Authors: Fallerini Chiara , Daga Sergio , Benetti Elisa , Picchiotti Nicola , Zguro Kristina , Catapano Francesca , Baroni Virginia , Lanini Simone , Bucalossi Alessandro , Marotta Giuseppe , Colombo Francesca , Baldassarri Margherita , Fava Francesca , Beligni Giada , Di Sarno Laura , Alaverdian Diana , Palmieri Maria , Croci Susanna , Isidori Andrea M. , Furini Simone , Frullanti Elisa ,   GEN-COVID Multicenter Study, Renieri Alessandra , Mari Francesca
Published: August 2021

Thromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology of this phenomenon is not well understood. A cohort of 1186 subjects, from the GEN-COVID consortium, infected by SARS-CoV-2 with different severity was stratified by sex and adjusted by age. Then, common coding variants from whole exome sequencing were mined by LASSO logistic regression. The homozygosity of the cell adhesion molecule P-selectin gene (SELP) rs6127 (c.1807G > A; p.Asp603Asn) which has been already associated with thrombotic risk is found to be associated with severity in the male subcohort of 513 subjects (odds ratio = 2.27, 95% Confidence Interval 1.54–3.36). As the SELP gene is downregulated by testosterone, the odd ratio is increased in males older than 50 (OR 2.42, 95% CI 1.53–3.82). Asn/Asn homozygotes have increased D-dimers values especially when associated with poly Q ≥ 23 in the androgen receptor (OR 3.26, 95% CI 1.41–7.52). These results provide a rationale for the repurposing of antibodies against P-selectin as adjuvant therapy in rs6127 male homozygotes especially if older than 50 or with an impaired androgen receptor.
Altered proTGFα/cleaved TGFα ratios offer new therapeutic strategies in renal carcinoma
Authors: García-Alonso Sara , Romero-Pérez Inés , Gandullo-Sánchez Lucía , Chinchilla Luis , Ocaña Alberto , Montero Juan Carlos , Pandiella Atanasio
Published: August 2021

Background

Treatment of renal cancer has significantly improved with the arrival to the clinic of kinase inhibitors and immunotherapies. However, the disease is still incurable in advanced stages. The fact that several approved inhibitors for kidney cancer target receptor tyrosine kinases (RTKs) suggests that these proteins play a critical role in the pathophysiology of the disease. Based on these precedents, we decided to explore whether RTKs other than those targeted by approved drugs, contribute to the development of kidney cancer.

Methods

The activation status of 49 RTKs in 44 paired samples of normal and tumor kidney tissue was explored using antibody arrays, with validation by western blotting. Genetic and pharmacologic approaches were followed to study the biological implications of targeting the epidermal growth factor receptor (EGFR) and its ligand Transforming Growth Factor-α (TGFα).

Results

Activation of the EGFR was found in a substantial number of tumors. Moreover, kidney tumors expressed elevated levels of TGFα. Down-regulation of EGFR or TGFα using RNAi or their pharmacological targeting with blocking antibodies resulted in inhibition of the proliferation of in vitro cellular models of renal cancer. Importantly, differences in the molecular forms of TGFα expressed by tumors and normal tissues were found. In fact, tumor TGFα was membrane anchored, while that expressed by normal kidney tissue was proteolytically processed.

Conclusions

The EGFR-TGFα axis plays a relevant role in the pathophysiology of kidney cancer. This study unveils a distinctive feature in renal cell carcinomas, which is the presence of membrane-anchored TGFα. That characteristic could be exploited therapeutically to act on tumors expressing transmembrane TGFα, for example, with antibody drug conjugates that could recognize the extracellular region of that protein.
Pathogens distribution and antimicrobial resistance in bloodstream infections in twenty-five neonatal intensive care units in China, 2017–2019
Authors: Liu Jing , Fang Zengyu , Yu Yonghui , Ding Yanjie , Liu Zhijie , Zhang Chengyuan , He Haiying , Geng Hongli , Chen Weibing , Zhao Guoying , Liu Qiang , Wang Baoying , Sun Xueming , Wang Shaofeng , Sun Rongrong , Fu Delong , Liu Xinjian , Huang Lei , Li Jing , Xing Xuexue , Wang Xiaokang , Gao Yanling , Zhu Renxia , Han Meiying , Peng Fudong , Geng Min , Deng Liping
Published: August 2021

Background

Overcrowding, abuse of antibiotics and increasing antimicrobial resistance negatively affect neonatal survival rates in developing countries. We aimed to define pathogens and their antimicrobial resistance (AMR) of early-onset sepsis (EOS), hospital-acquired late-onset sepsis (HALOS) and community-acquired late-onset sepsis (CALOS) in 25 neonatal intensive care units (NICUs) in China.

Study design

This retrospective descriptive study included pathogens and their AMR from all neonates with bloodstream infections (BSIs) admitted to 25 tertiary hospitals in China from January 1, 2017, and December 31, 2019. We defined EOS as the occurrence of BSI at or before 72 h of life and late-onset sepsis (LOS) if BSI occurred after 72 h of life. LOS were classified as CALOS if occurrence of BSI was ≤ 48 h after admission, and HALOS, if occurrence was > 48 h after admission.

Results

We identified 1092 pathogens of BSIs in 1088 infants from 25 NICUs. Thirty-two percent of all pathogens were responsible for EOS, 64.3% HALOS, and 3.7% CALOS. Gram-negative (GN) bacteria accounted for a majority of pathogens in EOS (56.7%) and HALOS (62.2%). The most frequent pathogens causing EOS were Escherichia coli (27.2%) and group B streptococcus (GBS; 14.6%) whereas in CALOS they were GBS (46.3%) and Staphylococcus aureus (41.5%). Klebsiella pneumoniae (27.9%), Escherichia coli (15.7%) and Fungi (12.8%) were the top three isolates in HALOS. Third-generation cephalosporin resistance rates in GN bacteria ranged from 9.7 to 55.6% in EOS and 26% to 63.3% in HALOS. Carbapenem resistance rates in GN bacteria ranged from 2.7 to 31.3% in HALOS and only six isolates in EOS were carbapenem resistant. High rates of multidrug resistance were observed in Klebsiella pneumoniae (60.7%) in HALOS and in Escherichia coli (44.4%) in EOS. All gram-positive bacteria were susceptible to vancomycin except for three Enterococcus faecalis in HALOS. All-cause mortality was higher among neonates with EOS than HALOS (7.4% VS 4.4%, [OR] 0.577, 95% CI 0.337–0.989; P = 0.045).

Conclusions

Escherichia coli, Klebsiella pneumoniae and GBS were the leading pathogens in EOS, HALOS and CALOS, respectively. The high proportion of pathogens and high degree of antimicrobial resistance in HALOS underscore understanding of the pathogenesis and emphasise the need to devise effective interventions in developing countries.
Atezolizumab plus bevacizumab combination enables an unresectable hepatocellular carcinoma resectable and links immune exclusion and tumor dedifferentiation to acquired resistance
Authors: Wang Yulei , Lu Li-Chun , Guan Yinghui , Ho Ming-Chih , Lu Shan , Spahn Jessica , Hsu Chih-Hung
Published: August 2021

We reported a patient with unresectable hepatocellular carcinoma (HCC) who initially received 15 cycles of atezolizumab plus bevacizumab combination and had best tumor response of partial response, but later experienced disease progression. After subsequent surgical resection, the patient enjoyed long-term disease-free status at the last follow-up 19 months after surgery. By investigating paired tumor tissues (pretreatment and post-progression samples) with immunohistochemistry, multiplex immunofluorescence, RNA sequencing, and DNA sequencing, we explored the dynamic changes in the tumor microenvironment (TME) and potential mechanisms underlying acquired resistance to the combination. In the post-progression HCC tissue compared with the baseline tissue, the expression of PD-L1 in tumor-infiltrating immune cells and the abundance of CD8+ T cells in the tumor area had decreased, and an immune-excluded TME had emerged. Transcriptomic analysis revealed a gene expression signature representing progenitor/hepatoblast features in the post-progression tumor tissue, with an increased expression of imprinted genes and decreased expression of cytochrome P450 family genes. Finally, tumor mutational burden and MHC class I expression in tumor cells were both increased in the post-progression tissue, suggesting that neoantigen depletion or loss-of-antigen presentation were unlikely causes of acquired resistance in this patient. Atezolizumab plus bevacizumab combination therapy enabled our patient to receive hepatectomy and achieve long-term remission. A comparison of paired tumor tissues suggested that immune-excluded TME and tumor dedifferentiation may have contributed to acquired resistance to the combination.
High-resolution flow simulation in Typhoon 21, 2018: massive loss of submerged macrophytes in Lake Biwa
Authors: Nakada Satoshi , Haga Hiroki , Iwaki Maho , Mabuchi Kohji , Takamura Noriko
Published: August 2021

The global activities of typhoons and hurricanes are gradually changing, and these storms can drastically affect lake ecosystems through the recession of submerged macrophytes that regulate the water quality in lakes. Using an echosounder, we captured the short-term, massive loss of submerged macrophytes attributed to the abnormal fluctuation of the water level induced by the approach of a catastrophic super typhoon in the southern basin of Lake Biwa, Japan. This paper investigates the physical processes responsible for the loss of vegetation using a high-resolution circulation model in Lake Biwa as a pilot study area. The circulation model was coupled with dynamical models of the fluid force and erosion acting on the vegetation. Our simulation successfully reproduced the water level fluctuation and high-speed current (torrent) generated by the typhoon gale. The simulated results demonstrated that the fluid force driven by the gale-induced torrent uprooted submerged macrophytes during the typhoon approach and that this fluid force (rather than erosion) caused the outflow of vegetation. As a result, this uprooting attributed to the fluid force induced the massive loss of submerged macrophytes in a large area of the southern basin, which might have increased primary production and reduced the stock of fish such as bluegill in the lake. Our model can estimate the reduction in the macrophyte height within the range of − 1.3 to − 0.4 m, suggesting that fluid forces greater than the time-averaged value (1.24 × 10−4 N) were available. Flow speeds of approximately 0.8 m/s might be the critical value that induces the fluid force acting on the uprooting of the submerged macrophytes. Our approach is practical for evaluating changes in lake environments attributed to the massive outflow of submerged macrophytes under various climate change scenarios.
Digital Image Disintegration Analysis: a Novel Quality Control Method for Fast Disintegrating Tablets
Authors: Malallah Osamah , Rashid Zara , Li Chee Lok , Alqurshi Abdulmalik , Alhanan Mohamed A. , Forbes Ben , Royall Paul G.
Published: August 2021

Measuring tablet disintegration is essential for quality control purposes; however, no established method adequately accounts for the timeframe or small volumes of the medium associated with the dissipation process for fast disintegrating tablets (FDTs) in the mouth. We hypothesised that digital imaging to measure disintegration in a low volume of the medium might discriminate between different types of FTD formulation. A digital image disintegration analysis (DIDA) was designed to measure tablet disintegration in 0.05–0.7 mL of medium. A temperature-controlled black vessel was 3D-printed to match the dimensions of each tablet under investigation. An overhead camera recorded the mean grey value of the tablet as a measure of the percentage of the formulation which remained intact as a function of time. Imodium Instants, Nurofen Meltlets and a developmental freeze-dried pilocarpine formulation were investigated. The imaging approach proved effective in discriminating the disintegration of different tablets (p < 0.05). For example, 10 s after 0.7 mL of a saliva simulant was applied, 2.0 ± 0.3% of the new pilocarpine tablet remained, whereas at the same time point, 22 ± 9% of the Imodium Instants had not undergone disintegration (temperature within the vessel was 37 ± 0.5°C). Nurofen Meltlets were observed to swell and showed a percentage recovery of 120.7 ± 2.4% and 135.0 ± 6.1% when 0.05 mL and 0.7 mL volumes were used, respectively. Thus, the new digital image disintegration analysis, DIDA, reported here effectively evaluated fast disintegrating tablets and has the potential as a quality control method for such formulations.
Dorso-ventral heterogeneity in tracheal basal stem cells
Authors: Tadokoro Tomomi , Tanaka Keisuke , Osakabe Shun , Kato Mimoko , Kobayashi Hisato , Hogan Brigid L. M. , Taniguchi Hideki
Published: August 2021

The tracheal basal cells (BCs) function as stem cells to maintain the epithelium in steady state and repair it after injury. The airway is surrounded by cartilage ventrolaterally and smooth muscle dorsally. Lineage tracing using Krt5-CreER shows dorsal BCs produce more, larger, clones than ventral BCs. Large clones were found between cartilage and smooth muscle where subpopulation of dorsal BCs exists. Three-dimensional organoid culture of BCs demonstrated that dorsal BCs show higher colony forming efficacy to ventral BCs. Gene ontology analysis revealed that genes expressed in dorsal BCs are enriched in wound healing while ventral BCs are enriched in response to external stimulus and immune response. Significantly, ventral BCs express Myostatin, which inhibits the growth of smooth muscle cells, and HGF, which facilitates cartilage repair. The results support the hypothesis that BCs from the dorso-ventral airways have intrinsic molecular and behavioural differences relevant to their in vivo function.
RUIN THROUGH PHOTOGRAPH THE CASE OF KAZARMA: KAIAFAS, ILIA
Authors: Kolaiti Ioanna
Published: August 2021

This paper deals with the concept of ruin and abandonment through the accompanying photographic material as through also through the understanding of the reality of the photograph itself. Each ruin has its testimonies, traces, findings, photographic evidence, and more. All these unfold before us its history. The research along with the photographic material, compile the narration of the ruin. The main purpose its recognition in the world. Initially, the research site is located in the wider landscape of Lake Kaiaphas in the Gulf of Kyparissia. The events that contributed to the abandonment are recorded. The ruin of Kazarma on Kaiapha beach, in Ilia, is chosen as the main focus of the research. Then, are analyzed the aspects related with the meaning of the ruin and its value through the borrowing of its traces in the area. The photographic material is proposed as a methodology for understanding the ruins, so we can compose a narrative. Finally, as a result of the above, is presented the progression of the research, revealing facts and findings which… have a story to tell.
Molecular docking and dynamic simulation of conserved B cell epitope of SARS-CoV-2 glycoprotein Indonesian isolates: an immunoinformatic approach
Authors: Rantam Fedik Abdul , Kharisma Viol Dhea , Sumartono Christrijogo , Nugraha Jusak , Wijaya Andi Yasmin , Susilowati Helen , Kuncorojakti Suryo , Nugraha Alexander Patera
Published: August 2021

Background: An immunoinformatic approach may be useful to investigate the conserved region in the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Indonesia isolates. The aim of this study was to investigate Indonesian SARS-CoV-2 isolates based on B cell epitopes by targeting the conserved regions in the spike glycoprotein to trigger increased multi-variant virus neutralization and memory response for the development of vaccine seed candidates.

Methods: SARS-CoV-2 spike glycoprotein gene sequences originating from Indonesia were compared with Wuhan (China), the United Kingdom, South Africa, India, the United States, and Brazil isolates obtained from the NCBI and GISAID databases. The recognition of antigens was carried out directly using B cells through the B cell receptor (BCR). An indirect B cell activation by Cluster of Differentiation (CD)4+ T cells and major histocompatibility complex (MHC)-II was predicted through the binding with human leukocyte antigen (HLA) based on IC50 value. In addition, vaccine allergenicity and toxicity were investigated. During the molecular complex examination, the 3D peptide structure was investigated and the lowest amount of energy formed when the vaccine candidate peptide bound to BCR and MHC-II was calculated.

Results: As a result, the spike glycoprotein sequences of Indonesian SARS-CoV-2 isolates had conserved regions which were very similar to reference countries such as China, the United Kingdom, South Africa, India, the United States, and Brazil.

Conclusion: It was predicted that the conserved regions could be identified as the epitope of B and T CD4+ cells that produced the peptides for vaccine candidate with antigenic, non-allergen, and non-toxic properties.
Pulsed administration for physiological estrogen replacement in mice
Authors: Corciulo Carmen , Scheffler Julia M. , Gustafsson Karin L. , Drevinge Christina , Humeniuk Piotr , del Carpio Pons Alicia M. , Poutanen Matti , Ohlsson Claes , Lagerquist Marie K. , Islander Ulrika
Published: August 2021

Estrogens are important regulators of body physiology and have major effects on metabolism, bone, the immune- and central nervous systems. The specific mechanisms underlying the effects of estrogens on various cells, tissues and organs are unclear and mouse models constitute a powerful experimental tool to define the physiological and pathological properties of estrogens. Menopause can be mimicked in animal models by surgical removal of the ovaries and replacement therapy with 17β-estradiol in ovariectomized (OVX) mice is a common technique used to determine specific effects of the hormone. However, these studies are complicated by the non-monotonic dose-response of estradiol, when given as therapy. Increased knowledge of how to distribute estradiol in terms of solvent, dose, and administration frequency, is required in order to accurately mimic physiological conditions in studies where estradiol treatment is performed. In this study, mice were OVX and treated with physiological doses of 17β-estradiol-3-benzoate (E2) dissolved in miglyol or PBS. Subcutaneous injections were performed every 4 days to resemble the estrus cycle in mice. Results show that OVX induces an osteoporotic phenotype, fat accumulation and impairment of the locomotor ability, as expected. Pulsed administration of physiological doses of E2 dissolved in miglyol rescues the phenotypes induced by OVX. However, when E2 is dissolved in PBS the effects are less pronounced, possibly due to rapid wash out of the steroid.
A pragmatic trial of online interactive webtools for teaching biostatistics to first-year medical students: a constructivism-informed approach
Authors: Hardy Steven , McHugh Douglas
Published: August 2021

Background: Statistical reasoning is an important clinical skill that informs evidence-based medicine and is desirable for 21st century practice. Yet many physicians struggle to apply biostatistical techniques correctly, potentially undermining patient care decision-making and adversely affecting outcomes. The overarching concepts of foundational biostatistics and probabilistic reasoning can be challenging to teach and hard for students to internalize given time constraints, lack of intrinsic motivation, and varied pre-existing knowledge or cognitive schema. We investigated how supplemental, interactive online webtools affected first-year medical students’ learning of sensitivity, specificity, negative/positive predictive values, and prevalence.

Methods: Online webtool design was informed by constructivism and sought to have learners 1) build conceptual representations by connecting new information to existing knowledge, 2) interact with primary sources of biostatistical data, and 3) begin with whole concepts then explore component parts. A total of 59 students were assigned randomly to two cohorts that had access to the webtools before or after in-class teaching; an additional 35 students had no access and served as the control cohort. Access metrics, summative exam scores, prior knowledge measurements, and qualitative data on learners’ experiences from three focus groups (n = 6/group) were collected.

Results: Mean exam scores were 87.5 ± 10.8%, 90.7 ± 11.2%, and 88.9 7 ±12.9% for the before, after, and control cohorts (p = 0.49). Students repeatedly accessed the online webtools: mean access was 4.3 (± 2.6) (before) and 2.6 (± 1.5) (after). Qualitative data showed the webtools facilitated learning in a time-efficient manner.

Conclusions: Online interactive webtools facilitated a constructivism-informed learning model and were found by first-year medical student to supplement and enhance their learning experience without detracting from established biostatistical teaching or negatively affecting summative assessment outcomes.
Business strategies under the new marketing myopia perspective
Authors: Freitas Delapedra Ana Tereza , Domingues da Silva Juliano
Published: August 2021

The new marketing myopia portrays companies that focus excessively on the customer, neglecting other stakeholders' demands that can transform the market and lead companies to failure. Although this discussion is present in marketing literature, researchers and marketers miss trails to identify new marketing myopia. This study aims to analyze business strategies under the new marketing myopia perspective. Qualitative and descriptive research was undertaken through a multiple case study of five South American companies acknowledge by Forbes for the customer orientation. This study demonstrates the companies' difficulty to equilibrate customers and other stakeholders’ demands to define their business strategies.
Institutional logic of corruption
Authors: De Freitas Júnior Luiz Romeu , de Oliveira Medeiros Cíntia Rodrigues , Valadão Júnior Valdir , Costa Mayla Cristina
Published: August 2021

Our aim was to verify the ‘institutional logics’ of corruption through the discursive patterns of managers. We conducted an exploratory survey using a qualitative-quantitative method. The interviews were submitted to content analysis, using the Atlas.TI software and the questionnaire was applied by SurveyMonkey. As a methodological contribution, four categories and levels for analyzing the logic of corruption were constructed: Individual, Organization, Networks, and Interinstitutional System. We infer that understanding the institutional logic of corruption can promote a transformation of corrupt behavior and an institutional change by individual cognition that can lead to practical change in society.
LOS DIFERENTES DISCURSOS Y NARRATIVAS DEL FUTURO DE TRABAJO
Authors: Salvagni Julice , Brunetto Cesar Santos , Colomby Renato , Cheron Cibele
Published: August 2021

Con el objetivo de comparar diferentes discursos y narrativas sobre el futuro del trabajo, este artículo realizó un análisis de redes sociales a partir de la selección de 40 actores de organizaciones internacionales, organizaciones profesionales, sindicatos, partidos políticos, empresas de consultoría y de la academia, de diferentes países. A partir de la recopilación de datos disponibles en publicaciones de los actores seleccionados, fueron medidas 35 variables divididas entre los bloques Empleo, Tecnología, Mercado y Socioeconomía. Este artículo reconoce que una narrativa lineal y unidimensional puede no capturar y reflejar los heterogéneos significados de qué es trabajar en el mundo contemporáneo.
Falsos discursos mercadológicos
Authors: Pasquotto Andreoli Tais , Nogueira Ana Carolina
Published: August 2021

O trabalho teve como objetivo compreender a reação dos consumidores às peças publicitárias que contêm apelos caracterizados como greenwashing versus bluewashing. A revisão da literatura focou na discussão acerca do marketing verde e societal, posteriormente discorrendo sobre esses falsos discursos mercadológicos. Como procedimento metodológico, foi realizado um experimento online em duas etapas, ambos com monitoramento ocular (eyetracker). O procedimento consistiu na apresentação de uma peça publicitária fictícia, manipulada em três diferentes formatos (greenwashing, bluewashing e neutra), seguida pela resposta ao questionário. Como resultado, evidenciou-se uma capacidade de influência das práticas de greenwashing e bluewashing no comportamento do consumidor.
Naturalists’ Hike As a New Form of Environmental Education for Children
Authors: Golovina Ol'ga , Filatova I.
Published: August 2021

The article highlights the experience of conducting a naturalist hike - a new form of organizing environmental education for preschoolers and

primary schoolchildren. The purpose of the trip, carried out in the form of a travel game, meets the requirements for the formation of environmental literacy in children of this age group, which are stated in the standards of preschool and primary school education. Game “What can you see in a pine forest?” is intended to enrich the sensory experience of children in the process of observing plants and animals of the forest, to acquaint them with observation as a method of studying natural communities, to develop a cognitive interest in the flora and fauna of their native land, to foster a desire to protect the forest and its inhabitants by participating in nature conservation activities. The article is intended for preschool teachers, primary school teachers, and additional education specialists.