bluuebunny/crossref_metadata_2025 huggingface dataset:
Examination of refractory discoid lateral meniscus injury
Authors: Kawashima Fumiyoshi , Takagi Hiroshi
Published: June 2021

Background:

Lateral discoid meniscus (LDM) should be treated and preserved with saucerization and/or suture repair. However, repair of the meniscal hoop structure is sometimes difficult due to displacement or large defects. In this study, we aimed to examine tear patterns based on the Ahn classification in those requiring meniscal repair and those undergoing subtotal meniscectomy.

Methods:

Twenty-three patients were evaluated (mean age, 27.4 years; mean follow-up period, 2.5 years). The following were evaluated: displacement morphology based on the Ahn classification, site of tear under arthroscopy, morphology, surgical procedure, Lysholm score at final postoperative follow-up, and clinical outcome of meniscus using Barrett’s criteria.

Result:

There were 16 knees without displacement (saucerization with suture repair, 13 knees; subtotal meniscectomy, 3 knees) and 10 knees with displacement (reduction with suture repair, 3 knees; subtotal meniscectomy, 7 knees). Subtotal meniscectomy was performed more often in cases with dislocation, especially in the central shift type as defined by the Ahn classification. The mean Lysholm score was 65.0 points preoperatively and 95.3 points postoperatively. Twenty-three knees (88%) were postoperatively categorized under the Barrett’s criteria as healing and 3 knees (12%) were categorized as non-healing. The number of non-healing cases that underwent subtotal meniscectomy was relatively small (1 of 10 knees), and the short-term results were not poor.

Conclusion:

Localized peripheral longitudinal tears tended to be repairable even with displacement, while peripheral tears covering the entire meniscus or with severe defects/tears in the body of the meniscus tended to be difficult to repair, leading to subtotal meniscectomy.
Long-term Outcomes of Anterior Cruciate Ligament Reconstruction Using Quadriceps Tendon–Patellar Bone Autograft
Authors: Lee Do Weon , Lee Joonhee , Jang Seonpyo , Ro Du Hyun , Lee Myung Chul , Han Hyuk-Soo
Published: June 2021

Background:

To date, there have been few studies on the outcomes of anterior cruciate ligament reconstruction (ACLR) using quadriceps tendon–patellar bone (QTPB) autograft.

Purpose:

To evaluate the long-term clinical outcomes of ACLR using QTPB autograft.

Study Design:

Case series; Level of evidence, 4.

Methods:

We retrospectively reviewed 139 patients who underwent primary ACLR with QTPB autografts and had at least 7 years of postoperative follow-up data. Instability, clinical scores, donor-site morbidity, radiographic progression of osteoarthritis, and any associated complications were assessed.

Results:

The proportion of knees classified as grade >1 on the anterior drawer, Lachman, and pivot-shift tests decreased significantly postsurgically (from 47.4% to 5.0%, 48.9% to 4.3%, and 53.3% to 5.0%, respectively; P < .001 for all). The mean clinical scores at the final follow-up were 89.8, 81.0, and 4.4 for the Lysholm, International Knee Documentation Committee, and Tegner Activity Scale, respectively. The results of the Cybex II dynamometer isokinetic test showed decreases in flexion and extension strength at both 60° and 180° per second, which persisted until the final follow-up visit. About one-fifth (19.4%) of the patients had osteoarthritis (Kellgren-Lawrence grade ≥1) before surgery, which increased to 33.8% at the final follow-up. The overall complication rate was 23.2%, and about one-third of the patients who experienced complications underwent revision surgery as a result of graft rupture and residual instability.

Conclusion:

In the current study, ACLR using QTPB autograft provided satisfactory long-term clinical results, with acceptable rates of complication and donor-site morbidity.
Survival of a Free Jejunal Flap with Early Venous Obstruction
Authors: Yamochi Ryo , Numajiri Toshiaki , Tsujiko Syoko , Nakamura Hiroko , Morita Daiki , Sowa Yoshihiro
Published: June 2021

Free jejunal flap transfer is common in head and neck reconstruction, but necrosis remains a complication. A 77-year-old man underwent total pharyngo-laryngo-esophagectomy, bilateral neck dissection, and free jejunal flap transfer. We anastomosed 3 arteries (facial, transverse cervical, and superior thyroid) and 1 vein (jejunal) because the recipient site’s arterial status was poor. On day 2, ultrasonography and visualization revealed that the anastomosed vein was obstructed in the cranial jejunum but the remainder was viable. The region recovered by day 7 and the patient began oral intake on day 30. Ultrasonography revealed that the anastomosed jejunal vein showed no waveform, the facial and transverse cervical arteries showed arterial waveforms, and the superior thyroid artery showed a retrograde venous waveform. The flap had survived because the blood exited through the superior thyroid artery and vein. Thus, additional vascular and arterial anastomoses are options for free flap survival if the vascular status is poor.
Bariatric and metabolic endoscopy: impact on obesity and related comorbidities
Authors: Mehta Amit , Sharaiha Reem Z.
Published: June 2021

The global obesity pandemic is among the most significant public health crises today. Furthermore, obesity remains a major risk factor for many weight-related comorbid conditions including cardiovascular disease, type 2 diabetes mellitus, liver disease, and cancer. Endoscopic bariatric therapies are currently on the rise as a new tool in the fight against the obesity epidemic, offering patients an alternative to more invasive surgery and a more effective option than diet and lifestyle modifications. The aim of this review article is to summarize the current literature regarding endoscopic bariatric therapies and their impact on obesity and its associated metabolic complications.
U–Pb geochronology of calcite carbonatites and jacupirangite from the Guli alkaline complex, Polar Siberia, Russia
Authors: Reguir Ekaterina P. , Salnikova Ekaterina B. , Yang Panseok , Chakhmouradian Anton R. , Stifeeva Maria V. , Rass Irina T. , Kotov Aleksandr B.
Published: June 2021

This work is the first in situ U–Pb geochronological study of perovskite and calcic garnet (andradite) from the Guli complex in the Maimecha–Kotuy alkaline province (Polar Siberia, Russia). The U–Pb isotopic compositions of perovskite from contact zones of the two carbonatite stocks (Southern and Northern) and from jacupirangite separating the stocks were determined by laser-ablation inductively-coupled-plasma mass-spectrometry (LA-ICPMS) and isotope-dilution thermal-ionisation mass-spectrometry (ID-TIMS). The LA-ICPMS and ID-TIMS data for perovskite from the Northern carbonatite stock are in good agreement, yielding 206Pb/238U ages of 250.4 ± 1.1 Ma and 249 ± 2 Ma, respectively. These ages are also within the analytical uncertainty from the ID-TIMS results for perovskite from jacupirangites (250 ± 1 Ma). The LA-ICPMS results for perovskite from the Southern carbonatite stock indicate its somewhat older age (255.3 ± 2.4 Ma), implying the possibility of small-volume mantle magmatism predating the eruption of the Siberian flood basalts at ca. 252–251 Ma. This interpretation is supported by reports of pre-flood magmatism elsewhere in eastern Siberia. Andradite crystals from the contact between the Southern stock and metasomatised melilitolite were analysed by ID-TIMS. These measurements are inconclusive (247 ± 6 Ma) and could not be used to constrain further the timing of carbonatitic magmatism in the southern part of the complex. The present contribution also presents a refined methodology for LA-ICPMS geochronological studies of perovskite with elevated levels of common lead, and addresses some of the problems with previously proposed calibration standards.
Prevalence of increased transaminases and its association with sex, age, and metabolic parameters in children and adolescents with obesity – a nationwide cross-sectional cohort study
Authors: Putri Resthie R. , Casswall Thomas , Hagman Emilia
Published: June 2021

Background

Childhood obesity increases the risk of non-alcoholic fatty liver disease marked by elevated alanine aminotransferase (ALT). This study investigated the prevalence of increased ALT in children and adolescents with obesity, and its associations with sex, age, degree of obesity, and metabolic parameters.

Methods

Individuals between 5 and 17.99 years of age enrolled in the Swedish Childhood Obesity Treatment Register (BORIS) before March 2020 were included. Mildly increased ALT was defined by ALT 27–51 U/L (males) and 23–43 U/L (females), while markedly increased ALT by levels above. Multiple logistic regression models were used for statistical analysis.

Results

Among 11,776 individuals (age 11.0 ± 3.3 years, 53.5% males), the prevalence of mildly and markedly increased ALT were 37.9 and 10.6%, respectively. A sex-age interaction was found, where increasing age strengthened the odds of markedly increased ALT in males (OR, 99% CI: 1.34, 1.29–1.4 for each year) while the corresponding pattern in females with was minuscule (1.09, 1.02–1.10). Compared to class I obesity, class II and III obesity had greater odds ratios for mildly increased ALT (class II obesity OR, 99% CI: 1.51, 1.35–1.70; class III obesity OR, 99% CI: 2.17, 1.66–2.61) and for markedly increased ALT (class II obesity OR, 99% CI: 1.82, 1.51–2.20; class III obesity OR, 99% CI 3.38, 2.71–4.23). Dyslipidemia was associated with both mildly and markedly increased ALT, all p < 0.001. Prevalence of impaired fasting glucose was 19.1% in normal ALT group, 20.4% in mildly increased ALT group, and 29.0% in markedly increased ALT group.

Conclusions

The risk of markedly increased ALT increased exponentially with age among boys, but not among girls. Higher degree of obesity was observed in individuals with mildly and markedly increased ALT. Further, metabolic derangements were more prevalent among individuals with mildly and markedly increased ALT.
Intersectional (in) equities in contact coverage of maternal and newborn health services in Nepal: insights from a nationwide cross-sectional household survey
Authors: Khatri Resham B. , Alemu Yibeltal , Protani Melinda M. , Karkee Rajendra , Durham Jo
Published: June 2021

Background

Persistent inequities in coverage of maternal and newborn health (MNH) services continue to pose a major challenge to the health-care system in Nepal. This paper uses a novel composite indicator of intersectional (dis) advantages to examine how different (in) equity markers intersect to create (in) equities in contact coverage of MNH services across the continuum of care (CoC) in Nepal.

Methods

A secondary analysis was conducted among 1978 women aged 15–49 years who had a live birth in the two years preceding the survey. Data were derived from the Nepal Demographic and Health Survey (NDHS) 2016. The three outcome variables included were 1) at least four antenatal care (4ANC) visits, 2) institutional delivery, and 3) postnatal care (PNC) consult for newborns and mothers within 48 h of childbirth. Independent variables were wealth status, education, ethnicity, languages, residence, and marginalisation status. Intersectional (dis) advantages were created using three socioeconomic variables (wealth status, level of education and ethnicity of women). Binomial logistic regression analysis was employed to identify the patterns of (in) equities in contact coverage of MNH services across the CoC.

Results

The contact coverage of 4ANC visits, institutional delivery, and PNC visit was 72, 64, and 51% respectively. Relative to women with triple disadvantage, the odds of contact coverage of 4ANC visits was more than five-fold higher (Adjusted Odds Ratio (aOR) = 5.51; 95% CI: 2.85, 10.64) among women with triple forms of advantages (literate and advantaged ethnicity and higher wealth status). Women with triple advantages were seven-fold more likely to give birth in a health institution (aOR = 7.32; 95% CI: 3.66, 14.63). They were also four times more likely (aOR = 4.18; 95% CI: 2.40, 7.28) to receive PNC visit compared to their triple disadvantaged counterparts.

Conclusions

The contact coverage of routine MNH visits was low among women with social disadvantages and lowest among women with multiple forms of socioeconomic disadvantages. Tracking health service coverage among women with multiple forms of (dis) advantage can provide crucial information for designing contextual and targeted approaches to actions towards universal coverage of MNH services and improving health equity.
Correction to: Efects of high-flow oxygen therapy on patients with hypoxemia after extubation and predictors of reintubation: a retrospective study based on the MIMIC-IV database
Authors: Liu Taotao , Zhao Qinyu , Du Bin
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
Distance education during COVID 19: an Italian survey on the university teachers’ perspectives and their emotional conditions
Authors: Casacchia Massimo , Cifone Maria Grazia , Giusti Laura , Fabiani Leila , Gatto Roberto , Lancia Loreto , Cinque Benedetta , Petrucci Cristina , Giannoni Mario , Ippoliti Rodolfo , Frattaroli Anna Rita , Macchiarelli Guido , Roncone Rita
Published: June 2021

Background

Following the COVID-19 pandemic, distance education (DE) replaced traditional “face-to-face” teaching and has become the main method of teaching. The aim of this study was to 1) evaluate the impact of DE by teachers in our department during the second semester of the 2019–20 academic year following the March–May 2020 Italian national lockdown and 2) evaluate the relationship between DE and the emotional well-being of teachers during the period of home confinement.

Methods

Ninety-seven university teachers (51.5% women; most represented age group 60–69 years range, 40.2%) responded to an anonymous online cross-sectional survey between July 15 – September 30, 2020, on the advantages and disadvantages of DE, developed by one online teacher focus group. The emotional conditions were assessed by a short version of the Beck Depression Inventory-II (BDI-II). The internal consistency reliability survey and the 10-item BDI-II were measured by Cronbach’s alpha. A correlation analysis (r-Pearson) was conducted between the overall evaluation of the experience of DE and the variables included in the study.

Results

Teachers reported difficulties in technical aspects, and in psychological factors, as the discomfort of “speaking in the void” (64.7%). The absence of “face-to-face” eye contact with the students was complained by 81% of teachers.

Significant impairments in sleep patterns and loss of energy were reported, with female teachers having greater difficulty concentrating than their male colleagues. A quarter of teachers showed depressive symptoms of varying severity.

The most satisfied teachers were those most stimulated by DE (r = 0.752, p < 0.000), who showed a lower impact of depressive symptoms (r = − 0.289, p = 0.005). The teaching load in hours influenced the perception of disadvantages (r = 0.214, p = 0.035) and contributed to a lower appreciation of the challenges of DE.

The more significant the manifestation of depressive symptoms during the lockdown was, the greater the subjective recovery of a good emotional condition once the domestic confinement was over (r = 0.344, p = 0.001), despite maintaining DE.

Conclusions

Our study highlights the impact of technical, didactic, and psychological difficulties of DE, reported by our teachers. The appreciation of their new learning promoted by DE seemed related to better emotional well-being of university teachers accepting this “challenge” in their important role in the high-education system, influencing good learning and promoting students’ professional success.
Constrained transformer network for ECG signal processing and arrhythmia classification
Authors: Che Chao , Zhang Peiliang , Zhu Min , Qu Yue , Jin Bo
Published: June 2021

Background

Heart disease diagnosis is a challenging task and it is important to explore useful information from the massive amount of electrocardiogram (ECG) records of patients. The high-precision diagnostic identification of ECG can save clinicians and cardiologists considerable time while helping reduce the possibility of misdiagnosis at the same time.Currently, some deep learning-based methods can effectively perform feature selection and classification prediction, reducing the consumption of manpower.

Methods

In this work, an end-to-end deep learning framework based on convolutional neural network (CNN) is proposed for ECG signal processing and arrhythmia classification. In the framework, a transformer network is embedded in CNN to capture the temporal information of ECG signals and a new link constraint is introduced to the loss function to enhance the classification ability of the embedding vector.

Results

To evaluate the proposed method, extensive experiments based on real-world data were conducted. Experimental results show that the proposed model achieve better performance than most baselines. The experiment results also proved that the transformer network pays more attention to the temporal continuity of the data and captures the hidden deep features of the data well. The link constraint strengthens the constraint on the embedded features and effectively suppresses the effect of data imbalance on the results.

Conclusions

In this paper, an end-to-end model is used to process ECG signal and classify arrhythmia. The model combine CNN and Transformer network to extract temporal information in ECG signal and is capable of performing arrhythmia classification with acceptable accuracy. The model can help cardiologists perform assisted diagnosis of heart disease and improve the efficiency of healthcare delivery.
Correction to: SGLT2 inhibitors and lower limb complications: an updated meta-analysis
Authors: Lin Chu , Zhu Xingyun , Cai Xiaoling , Yang Wenjia , Lv Fang , Nie Lin , Ji Linong
Published: June 2021

An amendment to this paper has been published and can be accessed via the original article.
A mixed methods evaluation of the Paediatric Musculoskeletal Matters (PMM) online portfolio
Authors: Smith Nicola , Foster Helen E. , Jandial Sharmila
Published: June 2021

Background

The PMM Portfolio is comprised of the Paediatric Musculoskeletal Matters (PMM) website, the paediatric Gait, Arms, Legs and Spine (pGALS) app and e-learning modules (ELM). The target audiences are non-specialists in paediatric musculoskeletal medicine. Our study aimed to evaluate impact on learning and clinical practice.

Methods

Mixed methods (analytics, online survey, interviews) were used with PMM and ELM registered users and purposive sampling of users using international contacts within paediatrics and paediatric rheumatology. Data was analysed using descriptive statistics and qualitative techniques. A Paired T-Test compared self-rated confidence before and after use of the PMM Portfolio.

Results

There has been wide reach for all the e-resources; PMM website (662,827 hits, 262,476 users, 214 countries, data 31st July 2020); pGALS app (12,670 downloads, 70 countries, data 31st July 2020); ELM (150 users, 30 countries, data 30th May 2019). There were 164 responses (students, trainees and health care professionals) to the survey from 25 countries. Most responders deemed the PMM Portfolio useful / very useful for their learning with significantly increased self-rated confidence in their clinical examination and reasoning skills following access to the PMM website, p = < 0.01, pGALS app, p = < 0.01 and ELM, p = < 0.01. The most popular PMM website pages related to clinical assessment techniques (especially pGALS). There was high uptake of the pGALS app and pGALS ELM especially from trainees and allied health professionals. Many clinicians reported the PMM Portfolio to be useful when used to teach others. User feedback reported that easy navigation, open access, clinical images and cases were the most valued features. User feedback highlighted need to increase awareness of the e-resources through training programmes.

Conclusions

The PMM Portfolio was developed to aid learning for clinicians who are not specialists in paediatric MSK medicine. Our evaluation demonstrates wide international reach and positive feedback on learning. The PMM Portfolio is a highly useful e-resource for paediatric rheumatologists in their teaching of others to raise awareness, facilitate early diagnosis and referral of children with suspected disease. The wide user engagement informed future PMM Portfolio development and the mixed method of evaluation is transferable to other e-resources.
Genetic transformation technologies for the common dandelion, Taraxacum officinale
Authors: Dinkeloo Kasia , Cantero Araceli Maria , Paik Inyup , Vulgamott Alexa , Ellington Andrew D , Lloyd Alan
Published: June 2021

Background

Taraxacum officinale, or the common dandelion, is a widespread perennial species recognized worldwide as a common lawn and garden weed. Common dandelion is also cultivated for use in teas, as edible greens, and for use in traditional medicine. It produces latex and is closely related to the Russian dandelion, T. kok-saghyz, which is being developed as a rubber crop. Additionally, the vast majority of extant common dandelions reproduce asexually through apomictically derived seeds- an important goal for many major crops in modern agriculture. As such, there is increasing interest in the molecular control of important pathways as well as basic molecular biology and reproduction of common dandelion.

Results

Here we present an improved Agrobacterium-based genetic transformation and regeneration protocol, a protocol for generation and transformation of protoplasts using free DNA, and a protocol for leaf Agrobacterium infiltration for transient gene expression. These protocols use easily obtainable leaf explants from soil-grown plants and reagents common to most molecular plant laboratories. We show that common markers used in many plant transformation systems function as expected in common dandelion including fluorescent proteins, GUS, and anthocyanin regulation, as well as resistance to kanamycin, Basta, and hygromycin.

Conclusion

Reproducible, stable and transient transformation methods are presented that will allow for needed molecular structure and function studies of genes and proteins in T. officinale.
Interobserver variability in target volume delineation in definitive radiotherapy for thoracic esophageal cancer: a multi-center study from China
Authors: Chang Xiao , Deng Wei , Wang Xin , Zhou Zongmei , Yang Jun , Guo Wenling , Liu Miaoling , Qi Xiaolu , Li Ling , Zhang Kaixian , Zhang Min , Shi Yonggang , Liu Ke , Zhao Yidian , Wang Huitao , Yu Zhilong , Zhang Jihong , Wang Lihua , Qiao Xueying , Han Chun , Zhu Shuchai , Zhang Ruohui , Chen Junqiang , Hu Cairong , Zhang Fuquan , Hou Xiaorong , Pang Qingsong , Zhang Wencheng , Li Gaofeng , Lin Hailei , Sun Xinchen , Ge Xiaolin , Li Caihong , Ge Hong , Li Dingjie , Wang Yadi , Lu Na , Gao Xianshu , Qin Shangbin , Tian Yuan , Xiao Zefen
Published: June 2021

Purpose

To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies.

Methods

Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC).

Results

Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32–0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45–0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases.

Conclusion

Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.
Clinical outcome of femoral neck system versus cannulated compression screws for fixation of femoral neck fracture in younger patients
Authors: Hu Huaijian , Cheng Jingbo , Feng Mingli , Gao Zhihua , Wu Jingwei , Lu Shibao
Published: June 2021

Background

The clinical outcome of a new fixation device (femoral neck system, FNS) for femoral neck fractures remains unclear. The main purpose of this study was to evaluate two different internal fixation methods for the treatment of femoral neck fractures in patients aged under 60 years.

Methods

We retrospectively studied patients who underwent internal fixation surgery in our hospital for femoral neck fractures between January 2017 and January 2020. Cannulated compression screws (CCS) and FNS groups were divided according to different internal fixation methods. General data (such as sex, age, body mass index, type of fracture) of all patienFemoral neck shorteningts were collected, and joint function was evaluated using the Harris Hip Score (HHS) before and 1 year after surgery. We recorded related surgical complications, including femoral head necrosis, nonunion, and femoral neck shortening.

Results

There were no significant differences in age, sex, or body mass index between the two groups. There was no statistical difference in HHSs between the two groups before surgery. Patients who underwent FNS treatment had longer surgery time (79.75 ± 26.35 min vs. 64.58 ± 18.56 min, p = 0.031) and more blood loss (69.45 ± 50.47 mL vs. 23.71 ± 28.13 mL, p < 0.001). The degree of femoral neck shortening in the FNS group was significantly lower than that in the CCS group (10.0% vs 37.5%, p = 0.036). Regarding postoperative complications, there was no statistical difference in the incidence of femoral head necrosis and fracture nonunion between the two groups.

Conclusion

Patients younger than 60 with femoral neck fractures can obtain satisfactory clinical results with CCS or FNS treatment. FNS has excellent biomechanical properties and shows significantly higher overall construct stability.
CAR-T therapy alters synthesis of platelet-activating factor in multiple myeloma patients
Authors: Ke Mengying , Kang Liqing , Wang Ling , Yang Shu , Wang Yajun , Liu Haiyan , Gu Chunyan , Huang Hongming , Yang Ye
Published: June 2021

The chimera antigen receptor (CAR) T cell therapy is a novel and potential targeted therapy and has achieved satisfactory efficacy in patients with relapsed or refractory multiple myeloma (MM) in recent years. However, cytokine release syndrome (CRS) and clinical efficacy have become the major obstacles which limit the application of CAR-T in clinics. To explore the potential biomarkers in plasma for evaluating CRS and clinical efficacy, we performed metabolomic and lipidomic profiling of plasma samples from 17 relapsed or refractory MM patients received CAR-T therapy. Our study showed that glycerophosphocholine (GPC), an intermediate of platelet-activating factor (PAF)-like molecule, was significantly decreased when the participants underwent CRS, and the remarkable elevation of lysophosphatidylcholines (lysoPCs), which were catalyzed by lysoPC acyltransferase (LPCAT) was a distinct metabolism signature of relapsed or refractory MM patients with prognostic value post-CAR-T therapy. Both GPC and lysoPC are involved in platelet-activating factor (PAF) remodeling pathway. Besides, these findings were validated by LPCAT1 expression, a key factor in the PAF pathway, associated with poor outcome in three MM GEP datasets of MM. In conclusion, CAR-T therapy alters PAF synthesis in MM patients, and targeting PAF remodeling may be a promising strategy to enhance MM CAR-T therapy.
Applications of single-cell sequencing in cancer research: progress and perspectives
Authors: Lei Yalan , Tang Rong , Xu Jin , Wang Wei , Zhang Bo , Liu Jiang , Yu Xianjun , Shi Si
Published: June 2021

Single-cell sequencing, including genomics, transcriptomics, epigenomics, proteomics and metabolomics sequencing, is a powerful tool to decipher the cellular and molecular landscape at a single-cell resolution, unlike bulk sequencing, which provides averaged data. The use of single-cell sequencing in cancer research has revolutionized our understanding of the biological characteristics and dynamics within cancer lesions. In this review, we summarize emerging single-cell sequencing technologies and recent cancer research progress obtained by single-cell sequencing, including information related to the landscapes of malignant cells and immune cells, tumor heterogeneity, circulating tumor cells and the underlying mechanisms of tumor biological behaviors. Overall, the prospects of single-cell sequencing in facilitating diagnosis, targeted therapy and prognostic prediction among a spectrum of tumors are bright. In the near future, advances in single-cell sequencing will undoubtedly improve our understanding of the biological characteristics of tumors and highlight potential precise therapeutic targets for patients.
Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ
Authors: Cai Jing , Yi Mei , Tan Yixin , Li Xiaoling , Li Guiyuan , Zeng Zhaoyang , Xiong Wei , Xiang Bo
Published: June 2021

Background

Pyroptosis is a lytic cell death form executed by gasdermins family proteins. Induction of tumor pyroptosis promotes anti-tumor immunity and is a potential cancer treatment strategy. Triptolide (TPL) is a natural product isolated from the traditional Chinese herb which possesses potent anti-tumor activity in human cancers. However, its role in pyroptosis remains to be elucidated.

Methods

Cell survival was measured by colony formation assay. Cell apoptosis was determined by Annexin V assay. Pyroptosis was evaluated by morphological features and release of interleukin 1β and lactate dehydrogenase A (LDHA). Immunofluorescence staining was employed to measure subcellular localization of proteins. Tumorigenicity was assessed by a xenograft tumor model. Expression levels of mRNAs or proteins were determined by qPCR or western blot assay, respectively.

Results

Triptolide eliminates head and neck cancer cells through inducing gasdermin E (GSDME) mediated pyroptosis. Silencing GSDME attenuates the cytotoxicity of TPL against cancer cells. TPL treatment suppresses expression of c-myc and mitochondrial hexokinase II (HK-II) in cancer cells, leading to activation of the BAD/BAX-caspase 3 cascade and cleavage of GSDME by active caspase 3. Silencing HK-II sensitizes cancer cells to TPL induced pyroptosis, whereas enforced expression of HK-II prevents TPL induced pyroptosis. Mechanistically, HK-II prevents mitochondrial translocation of BAD, BAX proteins and activation of caspase 3, thus attenuating cleavage of GSDME and pyroptosis upon TPL treatment. Furthermore, TPL treatment suppresses NRF2/SLC7A11 (also known as xCT) axis and induces reactive oxygen species (ROS) accumulation, regardless of the status of GSDME. Combination of TPL with erastin, an inhibitor of SLC7A11, exerts robust synergistic effect in suppression of tumor survival in vitro and in a nude mice model.

Conclusions

This study not only provides a new paradigm of TPL in cancer therapy, but also highlights a crucial role of mitochondrial HK-II in linking glucose metabolism with pyroptosis.
Genetic and morphological estimates of androgen exposure predict social deficits in multiple neurodevelopmental disorder cohorts
Authors: McKenna Brooke G. , Huang Yongchao , Vervier Kévin , Hofammann Dabney , Cafferata Mary , Al-Momani Seima , Lowenthal Florencia , Zhang Angela , Koh Jin-Young , Thenuwara Savantha , Brueggeman Leo , Bahl Ethan , Koomar Tanner , Pottschmidt Natalie , Kalmus Taylor , Casten Lucas , Thomas Taylor R. , Michaelson Jacob J.
Published: June 2021

Background

Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) display a strong male bias. Androgen exposure is profoundly increased in typical male development, but it also varies within the sexes, and previous work has sought to connect morphological proxies of androgen exposure, including digit ratio and facial morphology, to neurodevelopmental outcomes. The results of these studies have been mixed, and the relationships between androgen exposure and behavior remain unclear.

Methods

Here, we measured both digit ratio masculinity (DRM) and facial landmark masculinity (FLM) in the same neurodevelopmental cohort (N = 763) and compared these proxies of androgen exposure to clinical and parent-reported features as well as polygenic risk scores.

Results

We found that FLM was significantly associated with NDD diagnosis (ASD, ADHD, ID; all $$p<0.05$$

p
<
0.05

), while DRM was not. When testing for association with parent-reported problems, we found that both FLM and DRM were positively associated with concerns about social behavior ($$\rho =0.19$$

ρ
=
0.19

, $$p=0.004$$

p
=
0.004

; $$\rho =0.2$$

ρ
=
0.2

, $$p=0.004$$

p
=
0.004

, respectively). Furthermore, we found evidence via polygenic risk scores (PRS) that DRM indexes masculinity via testosterone levels ($$t=4.0$$

t
=
4.0

, $$p=8.8\times 10^{-5}$$

p
=
8.8
×

10

-
5

), while FLM indexes masculinity through a negative relationship with sex hormone binding globulin (SHBG) levels ($$t=-3.3$$

t
=
-
3.3

, $$p=0.001$$

p
=
0.001

). Finally, using the SPARK cohort (N = 9419) we replicated the observed relationship between polygenic estimates of testosterone, SHBG, and social functioning ($$t=-2.3$$

t
=
-
2.3

, $$p=0.02$$

p
=
0.02

, and $$t=4.2$$

t
=
4.2

, $$p={3.2\times 10^{-5}}$$

p
=

3.2
×

10

-
5

for testosterone and SHBG, respectively). Remarkably, when considered over the extremes of each variable, these quantitative sex effects on social functioning were comparable to the effect of binary sex itself (binary male: $$-0.22\pm 0.05$$

-
0.22
±
0.05

; testosterone: $$-0.35\pm 0.15$$

-
0.35
±
0.15

from 0.1%-ile to 99.9%-ile; SHBG: $$0.64\pm 0.15$$

0.64
±
0.15

from 0.1%-ile to 99.9%-ile).

Limitations

In the devGenes and SPARK cohorts, our analyses rely on indirect, rather than direct measurement of androgens and related molecules.

Conclusions

These findings and their replication in the large SPARK cohort lend support to the hypothesis that increasing net androgen exposure diminishes capacity for social functioning in both males and females.
GNINA 1.0: molecular docking with deep learning
Authors: McNutt Andrew T. , Francoeur Paul , Aggarwal Rishal , Masuda Tomohide , Meli Rocco , Ragoza Matthew , Sunseri Jocelyn , Koes David Ryan
Published: June 2021

Molecular docking computationally predicts the conformation of a small molecule when binding to a receptor. Scoring functions are a vital piece of any molecular docking pipeline as they determine the fitness of sampled poses. Here we describe and evaluate the 1.0 release of the Gnina docking software, which utilizes an ensemble of convolutional neural networks (CNNs) as a scoring function. We also explore an array of parameter values for Gnina 1.0 to optimize docking performance and computational cost. Docking performance, as evaluated by the percentage of targets where the top pose is better than 2Å root mean square deviation (Top1), is compared to AutoDock Vina scoring when utilizing explicitly defined binding pockets or whole protein docking.Gnina, utilizing a CNN scoring function to rescore the output poses, outperforms AutoDock Vina scoring on redocking and cross-docking tasks when the binding pocket is defined (Top1 increases from 58% to 73% and from 27% to 37%, respectively) and when the whole protein defines the binding pocket (Top1 increases from 31% to 38% and from 12% to 16%, respectively). The derived ensemble of CNNs generalizes to unseen proteins and ligands and produces scores that correlate well with the root mean square deviation to the known binding pose. We provide the 1.0 version ofGninaunder an open source license for use as a molecular docking tool athttps://github.com/gnina/gnina.
Niclosamide ethanolamine ameliorates diabetes-related muscle wasting by inhibiting autophagy
Authors: Cai Yuchun , Zhan Hongyue , Weng Wenci , Wang Yao , Han Pengxun , Yu Xuewen , Shao Mumin , Sun Huili
Published: June 2021

Background

Diabetes-related muscle wasting is one of the devastating complications of diabetes, which is associated with muscle autophagy due to insulin-mediated glucose starvation. However, treatment for diabetes-related muscle wasting is limited. Our previous study already found that niclosamide ethanolamine salt has the therapeutic effects on insulin deficiency of type 1 diabetes mice and muscle wasting induced by doxorubicin. Therefore, we aim to investigate the therapeutic effects of niclosamide ethanolamine salt on diabetes-induced muscle wasting and to explore whether the mechanism is associated with muscle autophagy.

Methods

Type 1 diabetes mice were induced by intraperitoneal injection of streptozotocin, then were fed with regular diet supplemented with 10 g/kg niclosamide ethanolamine salt. The whole experiment lasted for 8 weeks. At the end of the study, grip strength, weights of tibialis anterior, gastrocnemius, soleus, and extensor digitorum longus muscle were measured. Tibialis anterior muscles stained with PAS were used for evaluating the fiber cross sectional area. Immunofluorescence analysis of myosin heavy chain expression in extensor digitorum longus and soleus muscle was used for determining the composition of the muscle fiber type. Electronic microscopy was applied to observe the autophagy in the atrophied muscle. Serum insulin levels and fasting blood glucose were also measured. Tissues of gastrocnemius muscle were used for detecting the expression of the proteins related to autophagy.

Results

In this study, we found that niclosamide ethanolamine salt could ameliorate muscle atrophy in the type 1 diabetes mice as well, such as enhancing the declined grip strength, improving limb weight and increasing the numbers of glycolytic muscle fiber. Electron microscopy also confirmed that there did exist abundant autophagic vacuoles in the atrophied muscle of the type 1 diabetes mice. Specifically, niclosamide ethanolamine salt could reduce the over expression of autophagy-related proteins, including p-AMPK (Thr172), FoxO3a, p-ULK1 (Ser555), LC3B II, and p-p38 in gastrocnemius muscle of the type 1 diabetes mice.

Conclusion

Niclosamide ethanolamine salt could ameliorate muscle wasting. The mechanisms underlying might be associated with inhibition of muscle autophagy.
Risk factors for nonvisualization of the sentinel lymph node on lymphoscintigraphy in breast cancer patients
Authors: Chahid Youssef , Qiu Xinbo , van de Garde Ewoudt M. W. , Verberne Hein J. , Booij Jan
Published: June 2021

Background

Accurate sentinel lymph node (SLN) staging is essential for both prognosis and treatment in patients with breast cancer. However, the preoperative lymphoscintigraphy may fail to visualize the SLN in some patients. The purpose of this retrospective study was to identify risk factors associated with SLN nonvisualization on lymphoscintigraphy. For this single-center retrospective study, all data of lymphoscintigraphy of SLN procedures from March 2011 to April 2021 were collected and reviewed from the Amsterdam UMC database.

Results

A total of 1886 SLN procedures were included in this study. The SLN nonvisualization rate was 25.1% on lymphoscintigraphy at 4 h post-injection. The SLN nonvisualization rate decreased to 9.4% after reinjection. Multivariable analysis showed that age ≥ 70 years (P < 0.001; OR: 2.27; 95% CI: 1.46–3.53), BMI ≥ 30 kg/m2 (P = 0.031; OR: 1.48; 95% CI: 1.04–2.12) and nonpalpable tumors (P = 0.004; OR: 1.54; 95% CI: 1.15–2.07) were independent predictors of SLN nonvisualization. Tumor location, brand of radiopharmaceutical, injected dose and volume, experience of preparer and administrator were not associated with SLN nonvisualization. None of the patient, tumor or tracer characteristics were associated with SLN nonvisualization after radiotracer reinjection.

Conclusions

This study shows that risk factors for SLN nonvisualization in breast cancer patients during preoperative lymphoscintigraphy are age ≥ 70 years, BMI ≥ 30 kg/m2 and nonpalpable tumors. Our results support the notion that SLN lymphoscintigraphy is a very robust technique that does not depend on the experience of the preparer or administrator of the radiotracer.
Evaluation of 18F-AlF-NOTA-octreotide for imaging neuroendocrine neoplasms: comparison with 68Ga-DOTATATE PET/CT
Authors: Hou Jiale , Long Tingting , He Zhiyou , Zhou Ming , Yang Nengan , Chen Dengming , Zeng Shan , Hu Shuo
Published: June 2021

Objective

To evaluate the diagnostic efficacy of 18F-AlF-NOTA-octreotide (18F-OC) PET/CT compared with that of 68Ga-DOTATATE PET/CT.

Materials and methods

Twenty patients (mean age: 52.65 years, range: 24–70 years) with biopsy-proven neuroendocrine neoplasms (NENs) were enrolled in this prospective study. We compared the biodistribution profiles in normal organs based on the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean), and uptake in NEN lesions by measuring the SUVmax on 18F-OC and 68Ga-DOTATATE PET/CT images. The tumor-to-liver ratio (TLR) and tumor-to-spleen ratio were calculated by dividing the SUVmax of different tumor lesions by the SUVmean of the liver and spleen, respectively. The Wilcoxon signed-rank test was used to compare nonparametric data. Data were expressed as the median (interquartile range).

Results

In most organs, there were no significant differences in the biodistribution of 68Ga-DOTATATE and 18F-OC. 18F-OC had significantly lower uptake in the salivary glands and liver than 68Ga-DOTATATE. 18F-OC detected more lesions than 68Ga-DOTATATE. The uptake of 18F-OC in the tumors was higher in most patients, but the difference was not statistically significant relative to that of 68Ga-DOTATATE. However, the TLRs of 18F-OC were higher in most patients, including for lesions in the liver (p = 0.02) and lymph nodes (p = 0.02).

Conclusion

Relative to 68Ga-DOTATATE, 18F-OC possesses favorable characteristics with similar image quality and satisfactory NEN lesion detection rates, especially in the liver due to its low background uptake. 18F-OC therefore offers a promising clinical alternative for 68Ga-DOTATATE.
The influence of single nucleotide polymorphisms of NOD2 or CD14 on the risk of Mycobacterium tuberculosis diseases: a systematic review
Authors: Cubillos-Angulo Juan M. , Fernandes Catarina D. , Araújo Davi N. , Carmo Cristinna A. , Arriaga María B. , Andrade Bruno B.
Published: June 2021

Background

Tuberculosis (TB) is still one of the leading causes of death worldwide. Genetic studies have pointed to the relevance of the NOD2 and CD14 polymorphic alleles in association with the risk of diseases caused by Mycobacterium tuberculosis (Mtb) infection.

Methods

A systematic review was performed on PubMed, EMBASE, Scientific Electronic Library Online (SciELO), and Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) to examine the association between single nucleotide polymorphisms (SNP) and risk of Mtb diseases. Study quality was evaluated using the Newcastle-Ottawa Quality Scale (NOQS), and the linkage disequilibrium was calculated for all SNPs using a webtool (Package LDpop).

Results

Thirteen studies matched the selection criteria. Of those, 9 investigated CD14 SNPs, and 6 reported a significant association between the T allele and TT genotypes of the rs2569190 SNP and increased risk of Mtb diseases. The genotype CC was found to be protective against TB disease. Furthermore, in two studies, the CD14 rs2569191 SNP with the G allele was significantly associated with increased risk of Mtb diseases. Four studies reported data uncovering the relationship between NOD2 SNPs and risk of Mtb diseases, with two reporting significant associations of rs1861759 and rs7194886 and higher risk of Mtb diseases in a Chinese Han population. Paradoxically, minor allele carriers (CG or GG) of rs2066842 and rs2066844 NOD2 SNPs were associated with lower risk of Mtb diseases in African Americans.

Conclusions

The CD14 rs2569190 and rs2569191 polymorphisms may influence risk of Mtb diseases depending on the allele. Furthermore, there is significant association between NOD2 SNPs rs1861759 and rs7194886 and augmented risk of Mtb diseases, especially in persons of Chinese ethnicity. The referred polymorphisms of CD14 and NOD2 genes likely play an important role in risk of Mtb diseases and pathology and may be affected by ethnicity.

Systematic review registration

CRD42020186523
Assessing the performance of a Northeast Asia Japan-centered 3-D ionosphere specification technique during the 2015 St. Patrick’s day geomagnetic storm
Authors: Ssessanga Nicholas , Yamamoto Mamoru , Saito Susumu
Published: June 2021

This paper demonstrates and assesses the capability of the advanced three-dimensional (3-D) ionosphere tomography technique, during severe conditions. The study area is northeast Asia and quasi-Japan-centred. Reconstructions are based on total electron content data from a dense ground-based global navigation satellite system receiver network and parameters from operational ionosondes. We used observations from ionosondes, Swarm satellites and radio occultation (RO) to assess the 3-D picture. Specifically, we focus on St. Patrick’s day geomagnetic storm (17–19 March 2015), the most intense in solar cycle 24. During this event, the energy ingested into the ionosphere resulted in Dst and Kp and reaching values  ~  − 223 nT and 8, respectively, and the region of interest, the East Asian sector, was characterized by a  ~ 60% reduction in electron densities. Results show that the reconstructed densities follow the physical dynamics previously discussed in earlier publications about storm events. Moreover, even when ionosonde data were not available, the technique could still provide a consistent picture of the ionosphere vertical structure. Furthermore, analyses show that there is a profound agreement between the RO profiles/in-situ densities and the reconstructions. Therefore, the technique is a potential candidate for applications that are sensitive to ionospheric corrections.