bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modified technique of closing the port site after multiport thoracoscopic surgery using the shingled suture technique: a single centre experience
Authors: Xu Haitao , Ren Shuai , She Tianyu , Zhang Jingyu , Zhang Lianguo , Jia Teng , Zhang Qingguang 
Published: April 2021

Abstract
Background
Due to improvements in operative techniques and medical equipment, video-assisted thoracoscopic surgery has become a mainstay of thoracic surgery. Nevertheless, in multiport thoracoscopic surgery, there have been no substantial advances related to the improvement of the esthetics of the site of the chest tube kept for postoperative drainage of intrathoracic fluid and decompression of air leak after thoracoscopic surgery. Leakage of fluid and air around the site of the chest tube can be extremely bothersome to patients.

Methods

From March 2019 to April 2020, we used a modified technique of closing the port site in 67 patients and the traditional method in 51 patients undergoing multiport thoracoscopic surgery due to lung disease or mediastinal disease. We recorded patients’ age, gender, body mass index, surgical method, postoperative drainage time, and postoperative complications.The NRS pain scale was used to score the pain in each patient on the day of extubation.The PSAS and the OSAS were used for the assessment of scars one month after surgery.

Results
In the modified technique group, only one patient (1.49%) had pleural effusion leakage, compared with five patients (9.80%) in the traditional method group (P < 0.05). There were no significant differences in the pain of extubating and wound dehiscence between the two groups. However,the incidence rates of wound dehiscence in the modified technique group were lower than in the traditional method group. There were no post-removal pneumothorax and wound infection in either of the groups. Significant differences in the PSAS and OSAS were observed between the groups,where the modified technique group was superior to the traditional method group.

Conclusions
The modified technique of port site closure is a leak-proof method of fixation of the chest tube after multiport thoracoscopic surgery. Moreover, it is effective and preserves the esthetic appearance of the skin.
Hyperspectral Imaging (HSI) as a new diagnostic tool in free flap monitoring for soft tissue reconstruction: a proof of concept study
Authors: Kohler Lukas H. , Köhler Hannes , Kohler Simon , Langer Stefan , Nuwayhid Rima , Gockel Ines , Spindler Nick , Osterhoff Georg 
Published: April 2021

Abstract
Objectives
Free flap surgery is an essential procedure in soft tissue reconstruction. Complications due to vascular compromise often require revision surgery or flap removal. We present hyperspectral imaging (HSI) as a new tool in flap monitoring to improve sensitivity compared to established monitoring tools.

Methods
We performed a prospective observational cohort study including 22 patients. Flap perfusion was assessed by standard clinical parameters, Doppler ultrasound, and HSI on t0 (0 h), t1 (16–28 h postoperatively), and t2 (39–77 h postoperatively). HSI records light spectra from 500 to 1000 nm and provides information on tissue morphology, composition, and physiology. These parameters contain tissue oxygenation (StO2), near-infrared perfusion- (NIR PI), tissue hemoglobin- (THI), and tissue water index (TWI).

Results
Total flap loss was seen in n = 4 and partial loss in n = 2 cases. Every patient with StO2 or NIR PI below 40 at t1 had to be revised. No single patient with StO2 or NIR PI above 40 at t1 had to be revised. Significant differences between feasable (StO2 = 49; NIR PI = 45; THI = 16; TWI = 56) and flaps with revision surgery [StO2 = 28 (p < 0.001); NIR PI = 26 (p = 0.002); THI = 56 (p = 0.002); TWI = 47 (p = 0.045)] were present in all HSI parameters at t1 and even more significant at t2 (p < 0.0001).

Conclusion
HSI provides valuable data in free flap monitoring. The technique seems to be superior to the gold standard of flap monitoring. StO2 and NIR PI deliver the most valuable data and 40 could be used as a future threshold in surgical decision making. Clinical Trial Register This study is registered at the German Clinical Trials Register (DRKS) under the registration number DRKS00020926.
Investigating the prevalence of primary thyroid dysfunction in obese and overweight individuals: Tehran thyroid study
Authors: Mahdavi Mahdi , Amouzegar Atieh , Mehran Ladan , Madreseh Elham , Tohidi Maryam , Azizi Fereidoun 
Published: April 2021

Abstract
Background
Due to the increasing worldwide prevalence of obesity, it is essential to determine the prevalence of obesity-related thyroid dysfunctions. The purpose of this study was to investigate the prevalence of thyroid dysfunctions, namely hypothyroidism and hyperthyroidism, and their association with BMI among adult Iranian overweight and obese individuals.

Method
This cross-sectional study was carried out within the framework of the Tehran Thyroid Study (TTS); 5353 participants (57.5% female) entered our study. Anthropometric measurements were performed. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) were assayed. We categorized individuals into 3 BMI groups (normal-weight, overweight and obese), then calculated prevalence rate, odds ratio (OR), and 95% confidence interval (CI) for outcomes in overweight and obese groups. The normal-weight group was used as the control group.

Results
We found a higher prevalence of hypothyroidism (11.6% vs 8.2% Total, 4.0% vs 1.1% overt and 7.6% vs 7.1% subclinical, P < 0.001) and TPOAb positivity (17.3% vs 11.6%, P < 0.001) in obese participants compared with normal-weight participants. Hyperthyroidism’s overall prevalence was 4.2, 5.7, and 4.9% in obese, overweight, and normal-weight groups, respectively. Obesity was associated with higher odds of overt hypothyroidism (OR: 2.0, 95% CI: 1.15–3.49, P < 0.05) and TPOAb positivity (OR: 1.29, 95% CI: 1.04–1.60, P < 0.05) after adjusting for confounding variables. In contrast, no association was observed between the overweight group and the odds of hypothyroidism and TPOAb positivity in the adjusted results.

Conclusions
Obesity was associated with an increased risk of overt hypothyroidism and TPOAb positivity.
Web-based formative assessment through clinical cases: role in pathophysiology teaching
Authors: Fernández Ros Nerea , Lucena Felipe , Iñarrairaegui Mercedes , Landecho Manuel F. , Sunsundegui Patricia , Jordán-Iborra Carlota , Pineda Iñigo , Quiroga Jorge , Herrero Jose Ignacio 
Published: April 2021

Abstract
Background
Active learning strategies such as formative assessment through clinical cases may help to get a deeper learning. We have studied the effect of this kind of online formative assessment in pathophysiology teaching.

Methods
Seven brief clinical cases were used to give formative assessment in the first semester of a pathophysiology course. To evaluate its effect on learning, we analyzed the proportion of students that passed the end of semester exam with a score above 60 over 100. We also analyzed the effect of the intervention according to the students’ previous academic performance.

Results
Ninety-six students participated in the study and sat the exam. Sixty-five of them passed it. Students that passed the exam had a higher previous academic performance and had done a higher number of exercises of formative assessment, both in univariate and multivariate analysis. The participants were divided in three groups, according to their previous academic performance. In the intermediate group, the number of cases done by the students who passed the exam was significantly higher than in those who did not pass it (median: 4 versus 0; P = 0.009).

Conclusion
Formative assessment through web-based clinical cases was followed by an improvement of the academic results in pathophysiology, mainly in students with intermediate performance.
Identification of significant climatic risk factors and machine learning models in dengue outbreak prediction
Authors: Yavari Nejad Felestin , Varathan Kasturi Dewi 
Published: April 2021

Abstract
Background
Dengue fever is a widespread viral disease and one of the world’s major pandemic vector-borne infections, causing serious hazard to humanity. The World Health Organisation (WHO) reported that the incidence of dengue fever has increased dramatically across the world in recent decades. WHO currently estimates an annual incidence of 50–100 million dengue infections worldwide. To date, no tested vaccine or treatment is available to stop or prevent dengue fever. Thus, the importance of predicting dengue outbreaks is significant. The current issue that should be addressed in dengue outbreak prediction is accuracy. A limited number of studies have conducted an in-depth analysis of climate factors in dengue outbreak prediction.

Methods
The most important climatic factors that contribute to dengue outbreaks were identified in the current work. Correlation analyses were performed in order to determine these factors and these factors were used as input parameters for machine learning models. Top five machine learning classification models (Bayes network (BN) models, support vector machine (SVM), RBF tree, decision table and naive Bayes) were chosen based on past research. The models were then tested and evaluated on the basis of 4-year data (January 2010 to December 2013) collected in Malaysia.

Results
This research has two major contributions. A new risk factor, called the TempeRain factor (TRF), was identified and used as an input parameter for the model of dengue outbreak prediction. Moreover, TRF was applied to demonstrate its strong impact on dengue outbreaks. Experimental results showed that the Bayes Network model with the new meteorological risk factor identified in this study increased accuracy to 92.35% for predicting dengue outbreaks.

Conclusions
This research explored the factors used in dengue outbreak prediction systems. The major contribution of this study is identifying new significant factors that contribute to dengue outbreak prediction. From the evaluation result, we obtained a significant improvement in the accuracy of a machine learning model for dengue outbreak prediction.
Traumatic brain injury does not disrupt costimulatory blockade-induced immunological tolerance to glial-restricted progenitor allografts
Authors: Wang Rui , Chu Chengyan , Wei Zhiliang , Chen Lin , Xu Jiadi , Liang Yajie , Janowski Miroslaw , Stevens Robert D. , Walczak Piotr 
Published: April 2021

Abstract
Background
Cell transplantation-based treatments for neurological disease are promising, yet graft rejection remains a major barrier to successful regenerative therapies. Our group and others have shown that long-lasting tolerance of transplanted stem cells can be achieved in the brain with systemic application of monoclonal antibodies blocking co-stimulation signaling. However, it is unknown if subsequent injury and the blood-brain barrier breach could expose the transplanted cells to systemic immune system spurring fulminant rejection and fatal encephalitis. Therefore, we investigated whether delayed traumatic brain injury (TBI) could trigger graft rejection.

Methods
Glial-restricted precursor cells (GRPs) were intracerebroventricularly transplanted in immunocompetent neonatal mice and co-stimulation blockade (CoB) was applied 0, 2, 4, and 6 days post-grafting. Bioluminescence imaging (BLI) was performed to monitor the grafted cell survival. Mice were subjected to TBI 12 weeks post-transplantation. MRI and open-field test were performed to assess the brain damage and behavioral change, respectively. The animals were decapitated at week 16 post-transplantation, and the brains were harvested. The survival and distribution of grafted cells were verified from brain sections. Hematoxylin and eosin staining (HE) was performed to observe TBI-induced brain legion, and neuroinflammation was evaluated immunohistochemically.

Results
BLI showed that grafted GRPs were rejected within 4 weeks after transplantation without CoB, while CoB administration resulted in long-term survival of allografts. BLI signal had a steep rise following TBI and subsequently declined but remained higher than the preinjury level. Open-field test showed TBI-induced anxiety for all animals but neither CoB nor GRP transplantation intensified the symptom. HE and MRI demonstrated a reduction in TBI-induced lesion volume in GRP-transplanted mice compared with non-transplanted mice. Brain sections further validated the survival of grafted GRPs and showed more GRPs surrounding the injured tissue. Furthermore, the brains of post-TBI shiverer mice had increased activation of microglia and astrocytes compared to post-TBI wildtype mice, but infiltration of CD45+ leukocytes remained low.

Conclusions
CoB induces sustained immunological tolerance towards allografted cerebral GRPs which is not disrupted following TBI, and unexpectedly TBI may enhance GRPs engraftment and contribute to post-injury brain tissue repair.
Simultaneous enterovirus EV-D68 and CVA6 infections causing acute respiratory distress syndrome and hand, foot and mouth disease
Authors: de Sousa Ivanildo Pedro , Giamberardino Heloísa Ihle , Raboni Sonia Mara , Debur Maria Carmo , de Lourdes Aguiar Oliveira Maria , Burlandy Fernanda Marcicano , da Silva Edson Elias 
Published: April 2021

Abstract
Background
Although most enterovirus (EV) infections can be asymptomatic, these viral agents can cause serious conditions associated with central nervous system, respiratory disease and uncommon manifestations of hand, foot and mouth disease (HFMD). EV-coinfections have been rarely reported with development of complications and severe clinical outcome. An atypical case of a child presenting HFMD and severe acute respiratory syndrome, co-infected with EV-D68 and CVA6, is reported herein.

Case presentation
A 3-year-old boy was admitted in the emergency department unit showing fever, abdominal pain and tachycardia. Twenty-four hours after hospitalization the child developed severe clinical symptoms associated with HFMD and was discharged after recovery. Two days later, the child was readmitted with fever, cough and respiratory distress. RT-PCR and Sanger sequencing confirmed positivity for EV-D68 and CVA6 in oro and nasopharynges swabs and vesicles fluid, respectively. Phylogenetic analysis based on VP1 gene sequences suggested that CVA6 was closely related with HFMD viruses circulating in Turkey, while EV-D68 was genetically related to a Chinese strain.

Conclusions
To the best of our knowledge, this case is the first report of a double infection caused by CVA6 and EV-D68, which shed light on the pathogenesis of enterovirus infections. Further studies must be conducted to ascertain the role and clinical significance of EV co-infections, as well as a potential synergistic pathway between these viruses.
FMRP attenuates activity dependent modifications in the mitochondrial proteome
Authors: Bülow Pernille , Zlatic Stephanie A. , Wenner Peter A. , Bassell Gary J. , Faundez Victor 
Published: April 2021

AbstractHomeostatic plasticity is necessary for the construction and maintenance of functional neuronal networks, but principal molecular mechanisms required for or modified by homeostatic plasticity are not well understood. We recently reported that homeostatic plasticity induced by activity deprivation is dysregulated in cortical neurons from Fragile X Mental Retardation protein (FMRP) knockout mice (Bulow et al. in Cell Rep 26: 1378-1388 e1373, 2019). These findings led us to hypothesize that identifying proteins sensitive to activity deprivation and/or FMRP expression could reveal pathways required for or modified by homeostatic plasticity. Here, we report an unbiased quantitative mass spectrometry used to quantify steady-state proteome changes following chronic activity deprivation in wild type and Fmr1−/y cortical neurons. Proteome hits responsive to both activity deprivation and the Fmr1−/y genotype were significantly annotated to mitochondria. We found an increased number of mitochondria annotated proteins whose expression was sensitive to activity deprivation in Fmr1−/y cortical neurons as compared to wild type neurons. These findings support a novel role of FMRP in attenuating mitochondrial proteome modifications induced by activity deprivation.
Ablation of interleukin-19 improves motor function in a mouse model of amyotrophic lateral sclerosis
Authors: Komiya Hiroyasu , Takeuchi Hideyuki , Ogawa Yuki , Suzuki Kosuke , Ogasawara Akihiro , Takahashi Keita , Azuma Yasu-Taka , Doi Hiroshi , Tanaka Fumiaki 
Published: April 2021

AbstractNeuroinflammation by activated microglia and astrocytes plays a critical role in progression of amyotrophic lateral sclerosis (ALS). Interleukin-19 (IL-19) is a negative-feedback regulator that limits pro-inflammatory responses of microglia in an autocrine and paracrine manner, but it remains unclear how IL-19 contributes to ALS pathogenesis. We investigated the role of IL-19 in ALS using transgenic mice carrying human superoxide dismutase 1 with the G93A mutation (SOD1G93A Tg mice). We generated IL-19–deficient SOD1G93A Tg (IL-19−/−/SOD1G93A Tg) mice by crossing SOD1G93A Tg mice with IL-19−/− mice, and then evaluated disease progression, motor function, survival rate, and pathological and biochemical alternations in the resultant mice. In addition, we assessed the effect of IL-19 on glial cells using primary microglia and astrocyte cultures from the embryonic brains of SOD1G93A Tg mice and IL-19−/−/SOD1G93A Tg mice. Expression of IL-19 in primary microglia and lumbar spinal cord was higher in SOD1G93A Tg mice than in wild-type mice. Unexpectedly, IL-19−/−/SOD1G93A Tg mice exhibited significant improvement of motor function. Ablation of IL-19 in SOD1G93A Tg mice increased expression of both neurotoxic and neuroprotective factors, including tumor necrosis factor-α (TNF-α), IL-1β, glial cell line–derived neurotrophic factor (GDNF), and transforming growth factor β1, in lumbar spinal cord. Primary microglia and astrocytes from IL-19−/−/SOD1G93A Tg mice expressed higher levels of TNF-α, resulting in release of GDNF from astrocytes. Inhibition of IL-19 signaling may alleviate ALS symptoms.
ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF-β receptor II in breast cancer
Authors: Sun Xiaoqing , He Zhenyu , Guo Ling , Wang Caiqin , Lin Chuyong , Ye Liping , Wang Xiaoqing , Li Yue , Yang Meisongzhu , Liu Sailan , Hua Xin , Wen Wen , Lin Chao , Long Zhiqing , Zhang Wenwen , Li Han , Jian Yunting , Zhu Ziyuan , Wu Xianqiu , Lin Huanxin 
Published: April 2021

Abstract
Background
Radiotherapy is a conventional and effective local treatment for breast cancer. However, residual or recurrent tumors appears frequently because of radioresistance. Novel predictive marker and the potential therapeutic targets of breast cancer radioresistance needs to be investigated.

Methods
In this study, we screened all 10 asparagine-linked glycosylation (ALG) members in breast cancer patients’ samples by RT-PCR. Cell viability after irradiation (IR) was determined by CCK-8 assay and flow cytometry. The radiosensitivity of cell lines with different ALG3 expression was determined with the colony formation assay by fitting the multi-target single hit model to the surviving fractions. Cancer stem-like traits were assessed by RT-PCR, Western blot, and flow cytometry. The mechanisms of ALG3 influencing radiosensitivity was detected by Western blot and immunoprecipitation. And the effect of ALG3 on tumor growth after IR was verified in an orthotopic xenograft tumor models. The association of ALG3 with prognosis of breast cancer patients was confirmed by immunohistochemistry.

Results
ALG3 was the most significantly overexpressing gene among ALG family in radioresistant breast cancer tissue. Overexpression of ALG3 predicted poor clinicopathological characteristics and overall survival (OS), and early local recurrence-free survival (LRFS) in breast cancer patients. Upregulating ALG3 enhanced radioresistance and cancer stemness in vitro and in vivo. Conversely, silencing ALG3 increased the radiosensitivity and repressed cancer stemness in vitro, and more importantly inhibition of ALG3 effectively increased the radiosensitivity of breast cancer cells in vivo. Mechanistically, our results further revealed ALG3 promoted radioresistance and cancer stemness by inducing glycosylation of TGF-β receptor II (TGFBR2). Importantly, both attenuation of glycosylation using tunicamycin and inhibition of TGFBR2 using LY2109761 differentially abrogated the stimulatory effect of ALG3 overexpression on cancer stemness and radioresistance. Finally, our findings showed that radiation played an important role in preventing early recurrence in breast cancer patients with low ALG3 levels, but it had limited efficacy in ALG3-overexpressing breast cancer patients.

Conclusion
Our results suggest that ALG3 may serve as a potential radiosensitive marker, and an effective target to decrease radioresistance by regulating glycosylation of TGFBR2 in breast cancer. For patients with low ALG3 levels, radiation remains an effective mainstay therapy to prevent early recurrence in breast cancer.
ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis
Authors: Li Li , Gong Yijia , Xu Ke , Chen Weihong , Xia Jiuyi , Cheng Zhaobo , Li Lili , Yu Renjie , Mu Junhao , Le Xin , Xiang Qin , Peng Weiyan , Tang Junying , Xiang Tingxiu 
Published: April 2021

Abstract
Background
Among the common preventable cancers of women, cervical cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical cancer assessment.

Methods
Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical cancer cells was assessed by cellular and molecular analysis in vitro and in vivo.

Results
This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical cancer cell proliferation, apoptosis, autophagy, and tumorigenesis. Also, it increased cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical cancer cells. ZBTB28 induced cellular autophagy by the degradation of Bcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200.

Conclusion
These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related apoptosis in cervical cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical cancer screening.