bluuebunny/crossref_metadata_2025 huggingface dataset:
Variants in TPO rs2048722, PTCSC2 rs925489 and SEMA4G rs4919510 affect thyroid carcinoma susceptibility risk
Authors: Shen Zhen , Sun Yingjun , Niu Guohua
Published: February 2023

Background

Thyroid carcinoma (THCA) is a malignant endocrine tumor all around the world, which is influenced by genetic and environmental factors.

Objective

To explore the association between TPO rs2048722, PTCSC2 rs925489, SEMA4G rs4919510 polymorphisms and THCA susceptibility in Chinese population.

Methods

We recruited 365 THCA patients and 498 normal controls for the study. Logistic regression analysis was used to evaluate the association between TPO rs2048722, PTCSC2 rs925489, SEMA4G rs4919510 polymorphisms and THCA susceptibility. MDR was used to assess the genetic interactions among the three SNPs.

Results

Overall analysis demonstrated that rs925489 of PTCSC2 was evidently associated with increased risk of THCA in multiple genetic models (OR = 1.59, 95%CI = 1.12–2.24, p = 0.009). The results of stratified analysis illustrated that rs2048722 of TPO can significantly increase the THCA susceptibility of participants less than or equal to 44 years old and smokers. Similarly, rs925489 of PTCSC2 obviously improved the risk of THCA among participants older than 44 years, males, smokers and drinkers. However, rs4919510 of SEMA4G has a protective effect on the development of THCA among participants with less than or equal to 44 years old and non-drinkers. Interestingly, there was a strong genetic interaction among the three SNPs in the occurrence of THCA risk.

Conclusion

TPO rs2048722, PTCSC2 rs925489 and SEMA4G rs4919510 polymorphisms were evidently associated with the risk of THCA in the Chinese population, which was affected by age, gender, smoking and drinking consumption.
Automatic characterization of stroke patients’ posturography based on probability density analysis
Authors: Wang Ying , Hu Zhen , Chen Kai , Yang Ying
Published: February 2023

Objective

The probability density analysis was applied to automatically characterize the center of pressure (COP) data for evaluation of the stroke patients’ balance ability.

Methods

The real-time COP coordinates of 38 stroke patients with eyes open and closed during quiet standing were obtained, respectively, from a precision force platform. The COP data were analyzed and characterized by the commonly used parameters: total sway length (SL), sway radius (SR), envelope sway area (EA), and the probability density analysis based parameters: projection area (PA), skewness (SK) and kurtosis (KT), and their statistical correlations were analyzed. The differences of both conventional parameters and probability density parameters under the conditions of eyes open (EO) and eyes closed (EC) were compared.

Results

The PA from probability density analysis is strongly correlated with SL and SR. Both the traditional parameters and probability density parameters in the EC state are significantly different from those in the EO state. The obtained various statokinesigrams were calculated and categorized into typical sway types through probability density function for clinical evaluation of the balance ability of stroke patients.

Conclusions

The probability density analysis of COP data can be used to characterize the posturography for evaluation of the balance ability of stroke patients.
Acoustofluidic assembly of primary tumor-derived organotypic cell clusters for rapid evaluation of cancer immunotherapy
Authors: Wu Zhuhao , Ao Zheng , Cai Hongwei , Li Xiang , Chen Bin , Tu Honglei , Wang Yijie , Lu Rongze Olivia , Gu Mingxia , Cheng Liang , Lu Xin , Guo Feng
Published: February 2023

Cancer immunotherapy shows promising potential for treating breast cancer. While patients may have heterogeneous treatment responses for adjuvant therapy, it is challenging to predict an individual patient’s response to cancer immunotherapy. Here, we report primary tumor-derived organotypic cell clusters (POCCs) for rapid and reliable evaluation of cancer immunotherapy. By using a label-free, contactless, and highly biocompatible acoustofluidic method, hundreds of cell clusters could be assembled from patient primary breast tumor dissociation within 2 min. Through the incorporation of time-lapse living cell imaging, the POCCs could faithfully recapitulate the cancer-immune interaction dynamics as well as their response to checkpoint inhibitors. Superior to current tumor organoids that usually take more than two weeks to develop, the POCCs can be established and used for evaluation of cancer immunotherapy within 12 h. The POCCs can preserve the cell components from the primary tumor due to the short culture time. Moreover, the POCCs can be assembled with uniform fabricate size and cell composition and served as an open platform for manipulating cell composition and ratio under controlled treatment conditions with a short turnaround time. Thus, we provide a new method to identify potentially immunogenic breast tumors and test immunotherapy, promoting personalized cancer therapy.
AMH independently predicts aneuploidy but not live birth per transfer in IVF PGT-A cycles
Authors: Li Howard J. , Seifer David B. , Tal Reshef
Published: February 2023

Background

While anti-Müllerian hormone (AMH) predicts quantitative IVF outcomes such as oocyte yield, it is not certain whether AMH predicts markers of oocyte quality such as aneuploidy.

Methods

Retrospective case–control analysis of the SART-CORS database, 2014–2016, to determine whether anti-Müllerian hormone (AMH) predicts aneuploidy and live birth in IVF cycles utilizing preimplantation genetic testing for aneuploidy (PGT-A).

Results

Of 51,273 cycles utilizing PGT-A for all embryos, 10,878 cycles were included in the final analysis; of these, 2,100 cycles resulted in canceled transfer due to lack of normal embryos and 8,778 cycles resulted in primary FET. AMH levels of cycles with ≥ 1 euploid embryo were greater than those of cycles with no normal embryos, stratifying by number of embryos biopsied (1–2, 3–4, 5–6, and ≥ 7), P < 0.017 for each stratum. Adjusting for age and number of embryos biopsied, AMH was a significant independent predictor of ≥ 1 euploid embryo for all age groups: < 35 yrs (aOR 1.074; 95%CI 1.005–1.163), 35–37 years (aOR 1.085; 95%CI 1.018–1.165) and ≥ 38 years (aOR 1.055; 95%CI 1.020–1.093). In comparative model analysis, AMH was superior to age as a predictor of  ≥ 1 euploid embryo for age groups < 35 years and 35–37 years, but not  ≥ 38 years. Across all cycles, age (aOR 0.945, 95% CI 0.935–0.956) and number of embryos (aOR 1.144, 95%CI 1.127–1.162) were associated with live birth per transfer, but AMH was not (aOR 0.995, 95%CI 0.983–1.008). In the subset of cycles resulting in ≥ 1 euploid embryo for transfer, neither age nor AMH were associated with live birth.

Conclusions

Adjusting for age and number of embryos biopsied, AMH independently predicted likelihood of obtaining ≥ 1 euploid embryo for transfer in IVF PGT-A cycles. However, neither age nor AMH were predictive of live birth once a euploid embryo was identified by PGT-A for transfer. This analysis suggests a predictive role of AMH for oocyte quality (aneuploidy risk), but not live birth per transfer once a euploid embryo is identified following PGT-A.
Prognostic value of genetic aberrations and tumor immune microenvironment in primary acral melanoma
Authors: Huang Rong , Shen Gaigai , Ren Yu , Zheng Kelin , Wang Jiayu , Shi Yan , Yin Jiani C. , Qin Lanqun , Zhang Guiying , Zhao Mengke , Su Xinyu , Li Luqiao , Wang Fufeng , Shao Yang , Liu Baorui , Zou Zhengyun
Published: February 2023

Background

Acral melanoma (AM) is the most common subtype in Chinese melanoma patients with a very poor prognosis. However, our understanding of the disease pathogenesis and molecular landscape is limited by the few studies that have been conducted. Here, we profiled the clinical characteristics, mutational landscapes and tumor immune microenvironment of AM patients to gain insights into disease characteristics and potential treatment strategies.

Methods

A total of 90 AM patients were enrolled and their tissue samples were subjected to next-generation sequencing and multiplexed immunohistochemistry tests. Kaplan–Meier curves and log-rank tests were used to analyze the prognostic potential of various genetic aberrations and immune cell compositions in AM.

Results

The median disease-free survival was 21.3 months and estimated median overall survival (OS) was 60 months. More advanced stages, older ages and thickness of greater than 4 mm were associated with worse prognosis in AM patients (HR = 2.57, 95% CI 1.25–5.29, p = 0.01; HR = 2.77, 95% CI 1.22–6.28, p = 0.02; HR = 3.43, 95% CI 1.51–7.82, p < 0.01, respectively), while patients who received post-surgical treatments had better survival (HR = 0.36, 95% CI 0.17–0.76, p = 0.01). The most frequently altered genes included BRAF (14.5%), KIT (16.9%), NRAS (12%), NF1 (10.8%), APC (7.2%), and ARID2 (6%). Copy number variations (CNV) were commonly found in CCND1 (19.3%), CDK4 (19.3%), MDM2 (14.5%) and FGF19 (12%). CDK4 amplifications was independently associated with shorter OS in AM patients (HR = 3.61, 95% CI 1.38–9.46, p = 0.01). CD8 + T cells (p < 0.001) and M1 macrophages (p = 0.05) were more highly enriched in the invasive margin than in the tumor center. Patients with higher levels of M1 macrophage infiltration in the invasive margin derived markedly longer OS (HR = 0.43, 95% CI 0.20–0.95, p = 0.03). Interestingly, in CDK4-amplified patients, there tended to be a low level of M1 macrophage infiltration in the invasive margin (p = 0.06), which likely explains the poor prognosis in such patients.

Conclusions

Our study provided a comprehensive portrait of the clinicopathological features, genetic aberrations and tumor microenvironment profiles in AM patients and identified candidate prognostic factors, which may facilitate development of additional therapeutic options and better inform clinical management of AM patients. Based on these prognostic factors, further studies should focus on enhancing the infiltration of M1 macrophages, especially in CDK4-amplified AM patients.
Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM
Authors: Wang Weijun , Tang Xuelian , Duan Caihan , Tian Shuxin , Han Chaoqun , Qian Wei , Jiang Xin , Hou Xiaohua , Lin Rong
Published: February 2023

Background

Our previous study showed that fucosyltransferase 2 (Fut2) deficiency is closely related to colitis. Colitis increases the risk for the development of colorectal cancer (CRC). This study aimed to investigate the effect and underlying mechanism of action of Fut2 in CRC.

Methods

Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice were used in this study. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Immunofluorescence was used to examine the fucosylation levels. Proteomics and N-glycoproteomics analyses, Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, and rescue assay were used to investigate the mechanism of Fut2 in CRC.

Results

The expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissues than in the adjacent normal tissues of AOM/DSS-induced CRC mice. More colorectal tumors were detected in Fut2△IEC mice than in control mice, and significant downregulation of melanoma cell adhesion molecule (MCAM) fucosylation was detected in the colorectal tumor tissues of Fut2△IEC mice. Overexpression of Fut2 inhibited cell proliferation, invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells. Moreover, fucosylation of MCAM may be a mediator of Fut2 in CRC. Peracetylated 2-F-Fuc, a fucosyltransferase inhibitor, repressed fucosylation modification of MCAM and reversed the inhibitory effects of Fut2 overexpression on SW480 cell proliferation, migration, and invasion. Our results indicate that Fut2 deficiency in the intestinal epithelium promotes CRC by downregulating the fucosylation of MCAM.

Conclusions

The regulation of fucosylation may be an potential therapy for CRC, especially in patients with Fut2 gene defects.
Cancer functional states-based molecular subtypes of gastric cancer
Authors: Zhou Qi , Yuan Yiwu , Lu Hao , Li Xueqin , Liu Ziyang , Gan Jinheng , Yue Zhenqi , Wu Jiping , Sheng Jie , Xin Lin
Published: February 2023

Background

The treatment of gastric cancer remains a challenge.

Methods

We divided gastric cancer into three subtypes based on 14 cancer functional states. We investigated differences between subtypes through multi-omics data, especially at the single-cell level, which allowed us to analyze differences from the perspective of each type of cell rather than the whole.

Results

The cluster 1 is characterized by high levels of tumor progression-related cancer functional status, worst survival outcomes, low metabolic level, high infiltration of immunosuppressive cells, high copy number variations (CNV), and low tumor mutational burden (TMB). The cluster 2 is characterized by low levels of tumor progression-related cancer functional status, favorable prognosis, moderate metabolic level, low immune cell infiltration, high CNV, and moderate TMB. Then, the cluster 3 is characterized by the high level of all cancer functional status, high metabolic level, low CNV, high TMB, high infiltration of immune cells with high cytotoxicity, and better response to immunotherapy. We also established a prognostic model based on cancer functional status and validated its robustness.

Conclusions

Collectively, our study identified gastric cancer subtypes and provided new insights into the clinical treatment of gastric cancer.
Sirt3 restricts tumor initiation via promoting LONP1 deacetylation and K63 ubiquitination
Authors: Wu Liyi , Yan Xinyi , Sun Ruibo , Ma Ye , Yao Wanyu , Gao Baogui , Zhang Qingyuan , You Junxiong , Wang Hao , Han Qinrui , Sun Xuegang
Published: February 2023

Background

Sirtuin 3 (Sirt3) is a controversial regulator of carcinogenesis. It residents in the mitochondria and gradually decays during aging. In this study, we tried to investigate the role of Sirt3 in carcinogenesis and to explore its involvement in metabolic alteration.

Methods

We generated conditional intestinal epithelium Sirt3-knockout mice by crossing ApcMin/+; Villin-Cre with Sirt3fl/fl (AVS) mice. The deacetylation site of Lon protease-1 (LONP1) was identified with Mass spectrometry. The metabolic flux phenotype was determined by Seahorse bioanalyzer.

Results

We found that intestinal epithelial cell-specific ablation of Sirt3 promotes primary tumor growth via stabilizing mitochondrial LONP1. Notably, we newly identified that Sirt3 deacetylates human oncogene LONP1 at N terminal residue lysine 145 (K145). The LONP1 hyperacetylation-mutant K145Q enhances oxidative phosphorylation to accelerate tumor growth, whereas the deacetylation-mutant K145R produces calorie-restriction like phenotype to restrain tumorigenesis. Sirt3 deacetylates LONP1 at K145 and subsequently facilitates the ESCRT0 complex sorting and K63-ubiquitination that resulted in the degradation of LONP1. Our results sustain the notion that Sirt3 is a tumor-suppressor to maintain the appropriate ubiquitination and degradation of oncogene LONP1.

Conclusion

Sirt3 represents a targetable metabolic checkpoint of oncogenesis, which produces energy restriction effects via maintaining LONP1 K145 deacetylation and subsequent K63 ubiquitination.
Pertussis toxin-induced inhibition of Wnt/β-catenin signaling in dendritic cells promotes an autoimmune response in experimental autoimmune uveitis
Authors: Zhang Zhihui , Li Yongtao , Chen Nu , Li Huan , Chen Shuang , Cui Xuexue , Shao Hui , Wei Lai , Ma Jianxing , Zhang Song , Li Xiaorong , Zhang Xiaomin
Published: February 2023

Background

Previous reports have indicated that disrupting the Wnt/β-catenin pathway in dendritic cells (DCs) may affect the progression of autoimmune inflammation; however, the factors and timing that regulate Wnt/β-catenin signaling have not been clearly understood.

Methods

Experimental autoimmune uveitis (EAU) mice and Vogt–Koyanagi–Harada disease (VKH) patient samples were used to detect the expression of Wnt/β-catenin pathway genes. Western blot, real-time PCR, flow cytometry, and ELISA were performed to examine the expression of components of the Wnt/β-catenin pathway and inflammatory factors. DC-specific β-catenin knockout mice and 6-bromoindirubin-3′-oxime (BIO) administered mice were used to observe the effect of disrupting the Wnt pathway on EAU pathogenesis.

Results

Wnt/β-catenin signaling was inhibited in DCs during the induction phase of EAU. The inhibition was mediated by pertussis toxin (PTX), which promoted DC maturation, in turn promoting pathogenic T cell proliferation and differentiation. In vivo experiments confirmed that deleting β-catenin in DCs enhanced EAU severity, and pre-injection of PTX advanced EAU onset. Administration of a Wnt activator (BIO) limited the effects of PTX, in turn ameliorating EAU.

Conclusions

Our results demonstrate that PTX plays a key role as a virulence factor in initiating autoimmune inflammation via DCs by inhibiting Wnt/β-catenin signaling in EAU, and highlight the potential mechanism by which infection can trigger apparent autoimmunity.
Human herpesvirus-6 in hematopoietic stem cell transplant recipients: a prospective cohort study in Egypt
Authors: Raouf May Moheb Eldin , Ouf Nancy Mohammed , Elsorady Manal Abdel Sattar , Ghoneim Faika Mahmoud
Published: February 2023

Background

Immunocompromised patients face reactivation of latent viruses that increase the risk of morbidity.

Aim

The study aimed to detect human herpes virus 6 (HHV-6) reactivation among allogeneic (allo) and autologous (auto) hematopoietic stem cell transplant (HSCT) recipients and to correlate potentially attributed clinical manifestations to HHV-6 DNA plasma level.

Methods

A prospective study included all (forty) patients undergoing allo and auto-HSCT from Jan 2020 till June 2022. Plasma samples were collected for HHV-6 serology, and for HHV-6 quantitative PCR at post-transplantation weeks 2, 4, 6. Demographic and clinical data were recorded.

Results

Out of 40 peripheral blood stem cell transplant (PBSCT) recipients, 34 (85%) were HHV-6 IgG positive pre-HSCT. Of which, fourteen patients (14/34, 41.2%) showed positive HHV-6 DNaemia. HHV-6 DNAemia (15/40, 37.5%) was significantly higher among allo (8/12, 66.7%) versus auto (7/28, 25%) HSCT recipients (p = 0.030). Patients with HHV-6 DNAemia developed fever, delayed engraftment and bone marrow suppression in 6/15, 40%, thrombocytopenia (5/15, 33.3%), rash and pneumonitis (2/15, 13.3%), acute GVHD (aGVHD) (1/15, 6.7%). HHV-6 DNAemia ranged from 101 to 102,000 copies/mL. Univariate analysis identified conditioning with busulfan–cyclophosphamide as a significant risk (p = 0.043), while receiving BEAM protocol was a protective factor (p = 0.045). In multivariate analysis, receiving BEAM protocol retained significance (p = 0.040).

Conclusion

Frequent HHV-6 reactivation was detected after HSCT, especially in allo-HSCT recipients with clinical manifestations which could not be otherwise explained. To our best knowledge this is the first study of HHV6 reactivation in HSCT recipients from Egypt. Raising awareness for HHV-6 reactivation manifestations and screening in HSCT recipients could be lifesaving.
Mammary mucinous cystadenocarcinoma with long-term follow-up: molecular information and literature review
Authors: Lei Ting , Shi Yong Qiang , Chen Tong Bing
Published: February 2023

Background

Mucinous cystadenocarcinoma (MCA) is a very rare form of breast cancer that was first described in 1998. Only 33 cases of primary MCA, including our present case, have been reported thus far. As a consequence, its molecular features, prognosis and treatment regimen are poorly known. Here, we describe a less common presentation of MCA, detail its molecular features, discuss the major differential diagnosis, and provide a brief review of the literature.

Case presentation

A 59-year-old woman presented with a breast lump in which mammography showed a well-defined nodule. Core needle biopsy (CNB) revealed several lesions lined by tall columnar cells with stratification and abundant mucinous secretion; excision was recommended for final diagnosis. The resected specimens showed cavities of different sizes without surrounding myoepithelial cells. The cavities were rich in mucus, and the nuclei were located at the base of the cells, containing intracellular mucus. Immunohistochemical analysis revealed that it was triple-negative breast cancer (TNBC). Next-generation sequencing (NGS) revealed pathogenic mutations in the PIK3CA, KRAS, MAP2K4, RB1, KDR, PKHD1, TERT, and TP53 genes. A diagnosis of MCA was rendered. The patient has been followed up for 108 months to date and showed no signs of recurrence or metastasis.

Conclusion

Our study presents the gene profile of an MCA case with no recurrence or metastatic tendency after 108 months of follow-up, and a review of the literature helps us better understand the clinical, pathologic, and molecular features of this tumor.
The rapid-tome, a 3D-printed microtome, and an updated hand-sectioning method for high-quality plant sectioning
Authors: Thomas David J. , Rainbow Jordan , Bartley Laura E.
Published: February 2023

Background

Microscopic analysis of plant anatomy is a common procedure in biology to study structure and function that requires high-quality sections for accurate measurements. Hand sectioning of specimens is typically limited to moderately soft tissue while harder samples prohibit sectioning by hand and/or result in inconsistent thicknesses.

Results

Here we present both a clearly described hand-sectioning method and a novel microtome design that together provide the means to section a variety of plant sample types. The described hand-sectioning method for herbaceous stems works well for softer subjects but is less suitable for samples with secondary growth (e.g., wood production). Instead, the “Rapid-Tome” is a novel tool for sectioning both soft and tougher high-aspect-ratio samples, such as stems and roots, with excellent sample control. The Rapid-Tome can be 3D-printed in approximately 18 h on a mid-quality printer common at university maker spaces. After printing and trimming, Rapid-Tome assembly takes a few minutes with five metal parts common at hardware stores. Users sectioned a variety of plant samples including the hollow internodes of switchgrass (Panicum virgatum), fibrous switchgrass roots containing aerenchyma, and woody branches of eastern red cedar (Juniperus virginiana) and American sycamore (Platanus occidentalis). A comparative analyses with Rapid-Tome-produced sections readily revealed a significant difference in seasonal growth of sycamore xylem vessel area in spring (49%) vs. summer (23%). Additionally, high school students with no prior experience produced sections with the Rapid-Tome adequate for comparative analyses of various plant samples in less than an hour.

Conclusions

The described hand-sectioning method is suitable for softer tissues, including hollow-stemmed grasses and similar samples. In addition, the Rapid-Tome provides capacity to safely produce high-quality sections of tougher plant materials at a fraction of the cost of traditional microtomes combined with excellent sample control. The Rapid-Tome features rapid sectioning, sample advancement, blade changes, and sample changes; it is highly portable and can be used easily with minimal training making production of thin sections accessible for classroom and outreach use, in addition to research.
Association of phase angle with sarcopenia in chronic musculoskeletal pain patients: a retrospective study
Authors: Tsuji Hironori , Tetsunaga Tomoko , Misawa Haruo , Nishida Keiichiro , Ozaki Toshifumi
Published: February 2023

Background

In chronic musculoskeletal pain patients, detection of sarcopenia is of significant clinical interest. Phase angle, which can be measured through bioelectrical impedance analysis (BIA), can detect sarcopenia; however, the evidence in chronic musculoskeletal pain patients is limited. This study aimed to assess the relationship between phase angle and sarcopenia in patients with chronic musculoskeletal pain. Our hypothesis was that phase angle would be a useful indicator to identify sarcopenia in patients with chronic musculoskeletal pain.

Methods

A total of 190 patients (51 men and 139 women) with chronic musculoskeletal pain were included in this retrospective cross-sectional study. Patient data of backgrounds, numeric rating scale score for pain, skeletal muscle index, and phase angle assessed using BIA were retrospectively reviewed. Sarcopenia was diagnosed using the Asian Working Group for Sarcopenia criteria 2019.

Results

A total of 51 patients (26.7%), including 10 men (19.6%) and 41 women (29.5%), were diagnosed with sarcopenia. Phase angle, sarcopenia-related factors, age, and body mass index (BMI) differed significantly in patients with and without sarcopenia. On multiple logistic regression analysis, the prevalence of sarcopenia was significantly correlated with phase angle and BMI. The areas under the curve exhibited high accuracy in discriminating sarcopenia in men and moderate accuracy in both sexes and in women.

Conclusions

Phase angle may be a valid discriminator of sarcopenia in patients with chronic musculoskeletal pain.
Airway management in “tubeless” spontaneous-ventilation video-assisted thoracoscopic tracheal surgery: a retrospective observational case series study
Authors: Liu Yuying , Liang Lixia , Yang Hanyu
Published: February 2023

Background

Surgeon and anesthetist share the airway in a simpler way in the resection and reconstruction phase of tracheal surgery in tubeless spontaneous-ventilation video-assisted thoracoscopic surgery (SV-VATS). Tubeless SV-VATS means stable spontaneous ventilation in the resection and reconstruction phase to anesthesiologist, and unobstructed surgical field to surgeon. What’s the ideal airway management strategy during “Visual Field tubeless” SV-VATS for tracheal surgery is still an open question in the field.

Methods

We retrospectively reviewed 33 patients without sleeve and carina resections during the study period (2018–2020) in our hospital. The initial management strategy for these patients was spontaneous ventilation for intrathoracic tracheal resection and reconstruction. We obtained and reviewed medical records from our institution’s clinical medical records system to evaluate the airway management strategy and device failure rate for tracheal resection in Tubeless SV-VATS.

Results

Between 2018 and 2020, SV-VATS was first attempted in the 33 patients who had intrathoracic tracheal surgery but without sleeve and carina resections. All patients underwent bronchoscopy (33/33) and 8 patients (8/33) received partial resection before surgery. During the surgery, the airway device comprised either a ProSeal laryngeal mask airway (ProSeal LMA) (n = 27) or single lumen endotracheal tube (n = 6). During the resection and reconstruction phase, Visual Field tubeless SV-VATS failed in 9 patients, and breathing support switched to plan B which is traditional ventilation of a single lumen endotracheal tube for cross field intubation (n = 4) and ProSeal LMA alongside a high-frequency catheter (high-frequency jet ventilation, HFJV) (n = 5) into the distal trachea ventilation. Preoperative respiratory failure or other ventilation-related complications were not observed in this cohort.

Conclusion

Base on current analysis either ProSeal LMA or endotracheal tube is an effective airway management strategy for tubeless SV-VATS with appropriate patient selection. It also provides breathing support conversion option when there’s inadequate ventilation.
Pericardial tamponade, a diagnostic chameleon: from the historical perspectives to contemporary management
Authors: Kaemmerer Ann-Sophie , Alkhalaileh Khaleel , Suleiman Mathieu N. , Kopp Markus , Hauer Christine , May Matthias S. , Uder Michael , Weyand Michael , Harig Frank
Published: February 2023

Background

Pericardial tamponade (PT) early after cardiac surgery is a challenging clinical entity, not infrequently misrecognized and often only detected late in its course. Because the clinical signs of pericardial tamponade can be very unspecific, a high degree of initial suspicion is required to establish the diagnosis. In addition to clinical examination the deployment of imaging techniques is almost always mandatory in order to avoid delays in diagnosis and to initiate any necessary interventions, such as pericardiocentesis or direct cardiac surgical interventions. After a brief overview of how knowledge of PT has developed throughout history, we report on an atypical life-threatening cardiac tamponade after cardiac surgery. A 74-year-old woman was admitted for elective biological aortic valve replacement and aorto-coronary-bypass grafting (left internal mammary artery to left anterior descending artery, single vein graft to right coronary artery). On the 10th postoperative day, the patient unexpectedly deteriorated. She rapidly developed epigastric pain radiating to the left upper abdomen, and features of low peripheral perfusion and shock. There were no clear signs of pericardial tamponade either clinically or echocardiographically. Therefore, for further differential diagnosis, a contrast-enhanced computed tomography scan was performed under clinical suspicion of acute abdomen. Unexpectedly, active bleeding distally from the right coronary anastomosis was revealed. While the patient was prepared for operative revision, she needed cardiopulmonary resuscitation, which was successful. Intraoperatively, the source of bleeding was located and surgically relieved. The subsequent postoperative course was uneventful.

Conclusions

In the first days after cardiac surgery, the occurrence of life-threatening situations, such as cardiac tamponade, must be expected. Especially if the symptoms are atypical, the entire diagnostic armamentarium must be applied to identify the origin of the complaints, which may be cardiac, but also non-cardiac.

Central message

A high level of suspicion, immediate diagnostic confirmation, and rapid treatment are required to recognize and successfully treat such an emergency (Fig. 5).

Perspective

Pericardial tamponade should always be considered as a complication of cardiac surgery, even when symptoms are atypical. The full range of diagnostic tools must be used to identify the origin of the complaints, which may be cardiac, but also non-cardiac (Fig. 5).
Disruption to water supply and waterborne communicable diseases in northeast Syria: a spatiotemporal analysis
Authors: Tabor Ruby , Almhawish Naser , Aladhan Ibrahim , Tarnas Maia , Sullivan Richard , Karah Nabil , Zeitoun Mark , Ratnayake Ruwan , Abbara Aula
Published: February 2023

Background

In Syria, disruption to water and sanitation systems, together with poor access to vaccination, forced displacement and overcrowding contribute to increases in waterborne diseases (WBDs). The aim of this study is to perform a spatiotemporal analysis to investigate potential associations between interruptions to water, sanitation, and hygiene (WASH) and WBDs in northeast Syria using data collected by the Early Warning Alert and Response Network (EWARN) from Deir-ez-Zor, Raqqa, Hassakeh and parts of Aleppo governorates.

Methods

We reviewed the literature databases of MEDLINE and Google Scholar and the updates of ReliefWeb to obtain information on acute disruptions and attacks against water infrastructure in northeast Syria between January 2015 and June 2021. The EWARN weekly trends of five syndromes representing waterborne diseases were plotted and analysed to identify time trends and the influence of these disruptions. To investigate a potential relationship, the Wilcoxon rank sum test was used to compare districts with and without disruptions. Time series analyses were carried out on major disruptions to analyse their effect on WBD incidence.

Results

The literature review found several instances where water infrastructure was attacked or disrupted, suggesting that water has been deliberately targeted by both state and non-state actors in northeast Syria throughout the conflict. Over time, there was an overall upwards trend of other acute diarrhoea (OAD, p < 0.001), but downwards trends for acute jaundice syndrome, suspected typhoid fever and acute bloody diarrhoea. For the major disruption of the Alouk water plant, an interrupted time series analysis did not find a strong correlation between the disruption and changes in disease incidence in the weeks following the incident, but long-term increases in WBD were observed.

Conclusions

While no strong immediate correlation could be established between disruptions to WASH and WBDs in northeast Syria, further research is essential to explore the impact of conflict-associated damage to civil infrastructure including WASH. This is vital though challenging given confounding factors which affect both WASH and WBDs in contexts like northeast Syria. As such, research which includes exploration of mitigation after damage to WASH is essential to improve understanding of impacts on quantity and quality of WASH. More granular research which explores the origin of cases of WBDs and how such communities are affected by challenges to WASH is needed. One step towards research on this, is the implementation of adequate reporting mechanisms for real time tracking of the WASH attacks, damages, direct effects, and likely impact in conjunction with environmental and public health bodies and surveillance systems.
Molecular identification and genetic characteristics of Cryptosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi in human immunodeficiency virus/acquired immunodeficiency syndrome patients in Shanghai, China
Authors: Jiang Yanyan , Liu Li , Yuan Zhongying , Liu Aiqin , Cao Jianping , Shen Yujuan
Published: February 2023

Background

Opportunistic infections are a ubiquitous complication in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients.Cryptosporidiumspp.,Giardia duodenalis, andEnterocytozoon bieneusiare common opportunistic intestinal pathogens in humans. In China, despite the number of HIV/AIDS patients being extremely large, only a few studies have investigated opportunistic infections caused by intestinal pathogens in this patient population. The aims of this study were to elucidate the occurrence and genetic characteristics ofCryptosporidiumspp.,G. duodenalis, andE. bieneusiin HIV/AIDS patients.

Methods

We collected fecal specimens from 155 HIV/AIDS patients (one from each patient). All of the specimens were examined for the presence of the pathogens by genotyping using polymerase chain reaction and sequencing of the small subunit ribosomal RNA gene forCryptosporidiumspp.; the triosephosphate isomerase, β-giardin and glutamate dehydrogenase genes forG. duodenalis; and the internal transcribed spacer region of the rRNA gene forE. bieneusi. TheCryptosporidium-positive specimens were further subtyped by polymerase chain reacion and sequencing of the 60-kDa glycoprotein gene.

Results

Six (3.9%), three (1.9%), and eight (5.2%) HIV/AIDS patients were positive forCryptosporidiumspp.,G. duodenalis, andE. bieneusi, respectively. No statistical differences were observed in occurrence rate between the groups by gender, clinical symptom (diarrhea), and CD4+cell count. FourCryptosporidiumspecies were identified:Cryptosporidium hominis(n = 2),Cryptosporidium parvum(n = 1),Cryptosporidium meleagridis(n = 1), andCryptosporidium andersoni(n = 2). Furthermore, twoC. hominissubtypes (IeA12G3T3 and IaA28R4) were detected. ThreeG. duodenalis-positive specimens were successfully amplified and sequenced at the triosephosphate isomerase and β-giardin loci, which led to the identification of assemblages C and B, respectively. Seven genotypes (D, Type IV, EbpC, Peru11, EbpD, A, and I) were identified inE. bieneusi-positive specimens.

Conclusions

Our findings should increase awareness of AIDS-related opportunistic intestinal pathogens, and indicate the need for routine examination in clinical practice for the detection ofCryptosporidiumspp.,G. duodenalis, andE. bieneusi. Homology analyses of the three intestinal pathogens at the nucleotide and/or amino acid levels indicated their zoonotic potential.

Graphical Abstract
The impact of spatial correlation on methylation entropy with application to mouse brain methylome
Authors: Wu Xiaowei , Choi Joung Min
Published: February 2023

Background

With the advance of bisulfite sequencing technologies, massive amount of methylation data have been generated, which provide unprecedented opportunities to study the epigenetic mechanism and its relationship to other biological processes. A commonly seen feature of the methylation data is the correlation between nearby CpG sites. Although such a spatial correlation was utilized in several epigenetic studies, its interaction to other characteristics of the methylation data has not been fully investigated.

Results

We filled this research gap from an information theoretic perspective, by exploring the impact of the spatial correlation on the methylation entropy (ME). With the spatial correlation taken into account, we derived the analytical relation between the ME and another key parameter, the methylation probability. By comparing it to the empirical relation between the two corresponding statistics, the observed ME and the mean methylation level, genomic loci under strong epigenetic control can be identified, which may serve as potential markers for cell-type specific methylation. The proposed method was validated by simulation studies, and applied to analyze a published dataset of mouse brain methylome.

Conclusions

Compared to other sophisticated methods developed in literature, the proposed method provides a simple but effective way to detect CpG segments under strong epigenetic control (e.g., with bipolar methylation pattern). Findings from this study shed light on the identification of cell-type specific genes/pathways based on methylation data from a mixed cell population.
Validity of using perceived exertion to assess muscle fatigue during back squat exercise
Authors: Zhao Hanye , Seo Dasom , Okada Junichi
Published: February 2023

The rating of perceived exertion (RPE) scale has been found to reflect physiological responses, and this study aimed to assess the validity of using the Borg CR-10 scale and velocity loss to evaluate muscle fatigue quantified by surface electromyography during back squat (BS) exercise. A total of 15 collegiate male athletes underwent three non-explosive BS tasks comprising low, medium, and high volumes at 65% of their one-repetition maximum. RPEs, spectral fatigue index (SFI), and velocity loss during BS exercise were assessed throughout the trials. Significant differences in overall RPE (p < 0.001) and average SFI (p < 0.05) were observed between the conditions, whereas no significant difference was observed in average velocity loss. Significant increases in RPE and SFI (p < 0.001) were observed within the exercise process, whereas a significant increase in velocity loss was not observed. Correlation analyses indicated a significant correlation between RPE and SFI obtained during exercise (r = 0.573, p < 0.001). However, no significant correlation was observed between velocity loss and SFI. These results demonstrated that RPE could be used as a muscle fatigue predictor in BS exercise, but that velocity loss may not reflect muscle fatigue correctly when participants cannot and/or are not required to perform BS explosively. Furthermore, practitioners should not use velocity loss as a muscle fatigue indicator in some resistance exercise situations, such as rehabilitation, beginner, and hypertrophy programs.
The first genetically authenticated case of Leber hereditary optic neuropathy in Sri Lanka: a case report and review of the literature
Authors: Gunawardena Kawmadi , Dissanayake Vajira H. W. , Chang Thashi
Published: February 2023

Introduction

Leber hereditary optic neuropathy is a genetic disease of mitochondrial inheritance characterized by bilateral irreversible vision loss, predominantly affecting males. We report the first genetically authenticated Sri Lankan case of Leber hereditary optic neuropathy, illustrating its characteristic features of male predominance and variable penetrance.

Case presentation

A 15-year-old previously healthy Sri Lankan boy presented with painless progressive vision loss in his right eye, followed by vision loss in his left eye within 3 months. There was no history of drug or toxin exposure, or a family history of vision loss. His parents were nonconsanguineous. On examination, he could only perceive light. Funduscopy revealed bilateral optic atrophy. Routine hematological and biochemical blood tests, including inflammatory markers, were normal. Cranial magnetic resonance imaging was unremarkable. Optical coherence tomography, and the clinical presentation, suggested a diagnosis of Leber hereditary optic neuropathy, which was confirmed by detection of m.14484T > C pathogenic variant in the MT-ND6 gene through targeted genetic analysis for the three common pathogenic variants in mitochondrial deoxyribonucleic acid. He was homoplasmic for the variant, and his asymptomatic mother and two female siblings were also found to be harboring the variant with homoplasmy.

Conclusions

This case report is intended to increase awareness of Leber hereditary optic neuropathy, and highlights the need to consider this rare diagnosis in the appropriate clinical context. It also illustrates the phenomena of incomplete penetrance and male predominance, and suggests the possibility of an X-linked gene governing Leber hereditary optic neuropathy disease expression, which warrants further investigation.
Ang-(1–7)/MasR axis promotes functional recovery after spinal cord injury by regulating microglia/macrophage polarization
Authors: Gu Guangjin , Zhu Bin , Ren Jie , Song Xiaomeng , Fan Baoyou , Ding Han , Shang Jun , Wu Heng , Li Junjin , Wang Hongda , Li Jinze , Wei Zhijian , Feng Shiqing
Published: February 2023

Background

Inflammatory response is an essential part of secondary injury after spinal cord injury (SCI). During this period, the injury may be exacerbated through the release of a large number of inflammatory factors and the polarization of infiltrating macrophages and microglia towards M1. Ang-(1–7), mainly generated by Ang II via angiotensin-converting enzyme 2 (ACE2), can specifically bind to the G protein-coupled receptor Mas (MasR) and plays an important role in regulating inflammation and alleviating oxidative stress.

Methods

We aimed to investigate whether activating the Ang-(1–7)/MasR axis in rats after SCI can regulate local neuroinflammation to achieve functional recovery and obtain its potential mechanism. MasR expression of bone marrow-derived macrophages was determined by Western blot. Immunofluorescence, Western blot, Flow cytometry, and RT-qPCR were applied to evaluate the polarization of Ang-(1–7) on macrophages and the regulation of inflammatory cytokines. Previous evaluation of the spinal cord and bladder after SCI was conducted by hematoxylin–eosin staining, Basso, Beattie, and Bresnahan (BBB) score, inclined plate test, electrophysiology, and catwalk were used to evaluate the functional recovery of rats.

Results

MasR expression increased in macrophages under inflammatory conditions and further elevated after Ang-(1–7) treatment. Both in vivo and in vitro results confirmed that Ang-(1–7) could regulate the expression of inflammatory cytokines by down-regulating proinflammatory cytokines and up-regulating anti-inflammatory cytokines, and bias the polarization direction of microglia/macrophages to M2 phenotypic. After SCI, Ang-(1–7) administration in situ led to better histological and functional recovery in rats, and this recovery at least partly involved the TLR4/NF-κB signaling pathway.

Conclusion

As shown in our data, activating Ang-(1–7)/MasR axis can effectively improve the inflammatory microenvironment after spinal cord injury, promote the polarization of microglia/macrophages towards the M2 phenotype, and finally support the recovery of motor function. Therefore, we suggest using Ang-(1–7) as a feasible treatment strategy for spinal cord injury to minimize the negative consequences of the inflammatory microenvironment after spinal cord injury.
Modulating phenylalanine metabolism by L. acidophilus alleviates alcohol-related liver disease through enhancing intestinal barrier function
Authors: Chen Liuying , Yang Pengcheng , Hu Lilin , Yang Ling , Chu Huikuan , Hou Xiaohua
Published: February 2023

Background

Impaired metabolic functions of gut microbiota have been demonstrated in alcohol-related liver disease (ALD), but little is known about changes in phenylalanine metabolism.

Methods

Bacterial genomics and fecal metabolomics analysis were used to recognize the changes of phenylalanine metabolism and its relationship with intestinal flora. Intestinal barrier function was detected by intestinal alkaline phosphatase (IAP) activity, levels of tight junction protein expression, colonic inflammation and levels of serum LPS. Lactobacillus acidophilus was chosen to correct phenylalanine metabolism of ALD mice by redundancy analysis and Pearson correlation analysis.

Results

Using 16S rRNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods, we identified elevated levels of phenylalanine and its’ metabolites in the gut of alcohol-fed mice compared to control mice and were negatively correlated with the abundance of Lactobacillus, which mainly metabolized phenylalanine. The intestinal phenylalanine level was positively correlated with the colon inflammatory factors TNF-α and IL-6, and negatively correlated with ZO-1 and Occludin. While intestinal alkaline phosphatase (IAP) activity was negatively correlated with the colon inflammatory factors TNF-α, IL-6 and MCP-1, and positively correlated with ZO-1 and Occludin. Increased phenylalanine inhibited IAP activity, blocked LPS dephosphorylation, increased colonic inflammation and bacterial translocation. Phenylalanine supplementation aggravated alcohol-induced liver injury and intestinal barrier dysfunction. Among the 37 Lactobacillus species, the abundance of Lactobacillus acidophilus was most significantly decreased in ALD mice. Supplementation with L. acidophilus recovered phenylalanine metabolism and protected mice from alcohol-induced steatohepatitis.

Conclusions

Recovery of phenylalanine metabolism through the oral supplementation of L. acidophilus boosted intestinal barrier integrity and ameliorated experimental ALD.
QoS prediction in intelligent edge computing based on feature learning
Authors: Zhang Hongxia , Wang Dengyue , Zhang Wei , Tan Lizhuang , Kibalya Godfrey , Zhang Peiying , Igorevich Kostromitin Konstantin
Published: February 2023

With the development of 5G and 6G, more computing and network resources on edge nodes are deployed close to the terminal. Meanwhile, the number of smart devices and intelligent services has grown significantly, which makes it difficult for users to choose a suitable service. The rich contextual information plays an important role in the prediction of service quality. In this paper, we propose a quality of service(QoS) prediction approach based on feature learning, the contextual information represented as the explicit features and underlying relationship hidden in the implicit features are fully considered. Then, the multi-head self-attention mechanism is used in the interacting layer to determine which features should be combined to form meaningful high-order features interaction. We have implemented our proposed approach with experiments based on real-world datasets. Experimental results show that our approach achieved a better performance of service QoS prediction in an intelligent edge computing environment for future communication.