bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of switching to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG on cardiovascular risk and lipid profile in people living with HIV: a retrospective cohort study
Authors: Giacomelli Andrea , Conti Federico , Pezzati Laura , Oreni Letizia , Ridolfo Anna Lisa , Morena Valentina , Bonazzetti Cecilia , Pagani Gabriele , Formenti Tiziana , Galli Massimo , Rusconi Stefano
Published: June 2021

Background

We aimed to assess the overall cardiovascular and metabolic effect of the switch to three different single tablet regimens (STRs) [tenofovir alafenamide/emtricitabine/rilpivirine (TAF/FTC/RPV), TAF/FTC/elvitegravir/cobi (TAF/FTC/EVG/cobi) and ABC/lamivudine/dolutegravir (ABC/3TC/DTG)] in a cohort of people living with HIV/AIDS (PLWH) under effective ART.

Methods

All PLWH aged above 18 years on antiretroviral treatment with an HIV-RNA < 50 cp/mL at the time of the switch to TAF/FTC/RPV, TAF/FTC/EVG/cobi and ABC/3TC/DTG were retrospectively included in the analysis. Framingham risk score modification after 12 months from the switch such as lipid profile and body weight modification were assessed. The change from baseline to 12 months in mean cardiovascular risk and body weight in each of the STR’s group were assessed by means of Wilcoxon signed-rank test whereas a mixed regression model was used to assess variation in lipid levels.

Results

Five-hundred and sixty PLWH were switched to an STR regimen of whom 170 (30.4%) to TAF/FTC/EVG/cobi, 191 (34.1%) to TAF/FTC/RPV and 199 (35.5%) to ABC/3TC/DTG.

No difference in the Framingham cardiovascular risk score was observed after 12 months from the switch in each of the STR’s groups. No significant overtime variation in mean total cholesterol levels from baseline to 12 months was observed for PLWH switched to ABC/3TC/DTG [200 (SD 38) mg/dl vs 201 (SD 35) mg/dl; p = 0.610] whereas a significant increment was observed in PLWH switched to TAF/FTC/EVG/cobi [192 (SD 34) mg/dl vs 208 (SD 40) mg/dl; p < 0.0001] and TAF/FTC/RPV [187 (SD 34) mg/dl vs 195 (SD 35) mg/dl; p = 0.027]. In addition, a significant variation in the mean body weight from baseline to 12 months was observed in PLWH switched to TAF/FTC/EVG/cobi [72.2 (SD 13.5) kilograms vs 74.6 (SD 14.3) kilograms; p < 0.0001] and TAF/FTC/RPV [73.4 (SD 11.6) kilograms vs 75.6 (SD 11.8) kilograms; p < 0.0001] whereas no difference was observed in those switched to ABC/3TC/DTG [71.5 (SD 12.8) kilograms vs 72.1 (SD 12.6) kilograms; p = 0.478].

Conclusion

No difference in the cardiovascular risk after 1 year from the switch to these STRs were observed. PLWH switched to TAF/FTC/EVG/cobi and TAF/FTC/RPV showed an increase in total cholesterol levels and body weight 12 months after the switch.
Investigating efficacy of “microbiota modulation of the gut-lung Axis” combined with chemotherapy in patients with advanced NSCLC: study protocol for a multicenter, prospective, double blind, placebo controlled, randomized trial
Authors: Xia Qing , Chen Guojie , Ren Yanbei , Zheng Tiansheng , Shen Changxing , Li Ming , Chen Xiangyun , Zhai Hong , Li Zhuang , Xu Jianfang , Gu Aiqin , Jin Meiling , Fan Lihong
Published: June 2021

Background

Most NSCLCs metastasised out of the lungs at the time of diagnosis and cannot be surgically removed . Cytotoxic chemotherapy drugs have become the main treatment in recent decades, especially in patients with NSCLC without EGFR, ALK, and ROS gene mutations. The prognosis of lung cancer is poor, and the overall 5-year survival rate is only 9–13%. Therefore the treatment of advanced NSCLC remains a significant medical need. Recent studies have shown a significant relationship between the gut-lung axis microecology and malignant tumors. Intestinal probiotics are likely to play a role in inhibiting tumorigenesis through “intestinal-pulmonary axis microecological regulation”. This study will seek to investigate the efficacy of “Microbiota modulation of the Gut-Lung Axis” combined with chemotherapy in patients with advanced NSCLC.

Methods

The research is a multicenter, prospective, double blind, placebo controlled, randomized trial. Based on the theoretical basis of “intestinal and lung axis microecological adjustment”, combined with traditional platinum-containing two-drug chemotherapy, the efficacy of the new therapy on patients with advanced NSCLC was observed. Collect the basic information of the patient, and study the effect of platinum-based combined chemotherapy on the diversity of intestinal flora in patients with lung cancer after receiving chemotherapy treatment, feces before and after chemotherapy, and the status and extent of adverse reactions during chemotherapy . A total of 180 subjects were included, divided into a control group (platinum-containing dual-drug chemotherapy) and an intervention group (platinum-containing dual-drug chemotherapy combined with Bifico), and were randomly assigned to the group 1:1.

Discussion

As a result, intestinal-pulmonary microecological balance could become a new target for the treatment of lung cancer. This study explores the combination of intestinal microecological regulation and chemotherapy to provide new treatment strategies and basis for lung cancer patients. It can help prolong the survival time of lung cancer patients and improve the quality of life, thereby generating huge economic and social benefits. The results can be promoted and applied to units engaged in the treatment of lung cancer.

Trial registration number

NCT03642548, date: August 22, 2018, the first version protocol. The URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03642548?term=NCT03642548&draw=2&rank=1.
Economic burden of colorectal and breast cancers attributable to lack of physical activity in Brazil
Authors: Rezende Leandro F. M. , Ferrari Gerson , Bahia Luciana Ribeiro , Rosa Roger Dos Santos , da Rosa Michelle Quarti Machado , de Souza Romulo Cristovão , Lee Dong Hoon , Giovannucci Edward , Eluf-Neto José
Published: June 2021

Background

The increasing number of cancer patients has an escalating economic impact to public health systems (approximately, International dollars- Int$ 60 billion annually in Brazil). Physical activity is widely recognized as one important modifiable risk factor for cancer. Herein, we estimated the economic costs of colon and post-menopausal breast cancers in the Brazilian Unified Health System (SUS) attributable to lack of physical activity.

Methods

Population attributable fractions were calculated using prevalence data from 57,962 adults who answered a physical activity questionnaire in the Brazilian National Health Survey, and relative risks of colon and breast cancer from a meta-analysis. Annual costs (1 Int$ = 2.1 reais) with hospitalization, chemotherapy and radiotherapy were obtained from the Hospital and Ambulatory Information Systems of the Brazilian SUS. Two counterfactual scenarios were considered: theoretical minimum risk exposure level (≥8000 MET-min/week) and physical activity guidelines (≥600 MET-min/week).

Results

Annually, the Brazilian SUS expended Int$ 4.5 billion in direct costs related to cancer treatment, of which Int$ 553 million due to colon and breast cancers. Direct costs related to colon and breast cancers attributable to lack of physical activity were Int$ 23.4 million and Int$ 26.9 million, respectively. Achieving at least the physical activity guidelines would save Int$ 10.3 mi (colon, Int$ 6.4 mi; breast, Int$ 3.9 mi).

Conclusions

Lack of physical activity accounts for Int$ 50.3 million annually in direct costs related to colon and post-menopausal breast cancers. Population-wide interventions aiming to promote physical activity are needed to reduce the economic burden of cancer in Brazil.
Burnout profiles among French workers in health units for inmates: results of the EHCAU study
Authors: Boulier Stéphanie , Baumann Cédric , Rousseau Hélène , Horrach Pierre , Bourion-Bédès Stéphanie
Published: June 2021

Background

Health care personnel who work in penitentiary environments are at risk of burnout due to a variety of factors. Latest research have brought forward a classification system consisting of five burnout profiles on a continuum between engagement and burnout. The objective of this study was to measure the prevalence of these profiles among professionals working in French health units providing health services for inmates according to the three levels of care and to investigate their characteristics to propose appropriate management and prevention approaches.

Methods

This study involved a cross-sectional analysis of data from the Evaluation of Health CAre in Units for inmates (EHCAU) study, a multicentric cohort study of professionals practising in health units for inmates in eastern France. Burnout was assessed by the Maslach Burnout Inventory (MBI) at the levels of emotional exhaustion, depersonalization and personal accomplishment. Job conditions and characteristics were measured using the Karasek Job Content Questionnaire and the Effort-Reward Imbalance Questionnaire. Data on sociodemographic characteristics and self-reported health status were also collected. Differences between MBI profiles were identified using Fisher’s exact test and the Wilcoxon test.

Results

Of the 350 professionals surveyed, 150 responded (42.9%). The most frequent profiles were ineffective (36.9%) and engagement (34.8%). The burnout (7.8%), overextended (15.6%) and disengaged (5.0%) profiles made up the remaining quarter. Significant differences in the burnout profiles were observed in regard to professional occupation (p = 0.01), irregular eating hours (p = 0.04), history of complaint procedures (p = 0.05), anxiety (p < 0.0001), depression (p < 0.0001) and the mental component of self-reported quality of life (p < 0.0001).

Conclusions

These results confirm that special attention should be given to professionals working in these challenging settings. The results have important implications for theory and research and for more customized approach interventions.

Trial registration

ID RCB: 2018-A03029–46.
Experiences and lessons learned from the real-world implementation of an HIV recent infection testing algorithm in three routine service-delivery settings in Kenya and Zimbabwe
Authors: de Wit Mariken M. , Rice Brian , Risher Kathryn , Welty Susie , Waruiru Wanjiru , Magutshwa Sitholubuhle , Motoku John , Kwaro Daniel , Ochieng Benard , Reniers Georges , Cowan Frances , Rutherford George , Hargreaves James R. , Murphy Gary
Published: June 2021

Introduction

Testing for recent HIV infection can distinguish recently acquired infection from long-standing infections. Given current interest in the implementation of recent infection testing algorithms (RITA), we report our experiences in implementing a RITA in three pilot studies and highlight important issues to consider when conducting recency testing in routine settings.

Methods

We applied a RITA, incorporating a limited antigen (LAg) avidity assay, in different routine HIV service-delivery settings in 2018: antenatal care clinics in Siaya County, Kenya, HIV testing and counselling facilities in Nairobi, Kenya, and female sex workers clinics in Zimbabwe. Discussions were conducted with study coordinators, laboratory leads, and facility-based stakeholders to evaluate experiences and lessons learned in relation to implementing recency testing.

Results

In Siaya County 10/426 (2.3%) of women testing HIV positive were classified as recent, compared to 46/530 (8.7%) of women and men in Nairobi and 33/313 (10.5%) of female sex workers in Zimbabwe. Across the study setting, we observed differences in acceptance, transport and storage of dried blood spot (DBS) or venous blood samples. For example, the acceptance rate when testing venous blood was 11% lower than when using DBS. Integrating our study into existing services ensured a quick start of the study and kept the amount of additional resources required low. From a laboratory perspective, the LAg avidity assay was initially difficult to operationalise, but developing a network of laboratories and experts to work together helped to improve this. A challenge that was not overcome was the returning of RITA test results to clients. This was due to delays in laboratory testing, the need for multiple test results to satisfy the RITA, difficulties in aligning clinic visits, and participants opting not to return for test results.

Conclusion

We completed three pilot studies using HIV recency testing based on a RITA in Kenya and Zimbabwe. The main lessons we learned were related to sample collection and handling, LAg avidity assay performance, integration into existing services and returning of test results to participants. Our real-world experience could provide helpful guidance to people currently working on the implementation of HIV recency testing in sub-Saharan Africa.
Methyltransferase-directed orthogonal tagging and sequencing of miRNAs and bacterial small RNAs
Authors: Mickutė Milda , Kvederavičiūtė Kotryna , Osipenko Aleksandr , Mineikaitė Raminta , Klimašauskas Saulius , Vilkaitis Giedrius
Published: June 2021

Background

Targeted installation of designer chemical moieties on biopolymers provides an orthogonal means for their visualisation, manipulation and sequence analysis. Although high-throughput RNA sequencing is a widely used method for transcriptome analysis, certain steps, such as 3′ adapter ligation in strand-specific RNA sequencing, remain challenging due to structure- and sequence-related biases introduced by RNA ligases, leading to misrepresentation of particular RNA species. Here, we remedy this limitation by adapting two RNA 2′-O-methyltransferases from the Hen1 family for orthogonal chemo-enzymatic click tethering of a 3′ sequencing adapter that supports cDNA production by reverse transcription of the tagged RNA.

Results

We showed that the ssRNA-specific DmHen1 and dsRNA-specific AtHEN1 can be used to efficiently append an oligonucleotide adapter to the 3′ end of target RNA for sequencing library preparation. Using this new chemo-enzymatic approach, we identified miRNAs and prokaryotic small non-coding sRNAs in probiotic Lactobacillus casei BL23. We found that compared to a reference conventional RNA library preparation, methyltransferase-Directed Orthogonal Tagging and RNA sequencing, mDOT-seq, avoids misdetection of unspecific highly-structured RNA species, thus providing better accuracy in identifying the groups of transcripts analysed. Our results suggest that mDOT-seq has the potential to advance analysis of eukaryotic and prokaryotic ssRNAs.

Conclusions

Our findings provide a valuable resource for studies of the RNA-centred regulatory networks in Lactobacilli and pave the way to developing novel transcriptome and epitranscriptome profiling approaches in vitro and inside living cells. As RNA methyltransferases share the structure of the AdoMet-binding domain and several specific cofactor binding features, the basic principles of our approach could be easily translated to other AdoMet-dependent enzymes for the development of modification-specific RNA-seq techniques.
α2β1 integrins spatially restrict Cdc42 activity to stabilise adherens junctions
Authors: Howden Jake D. , Michael Magdalene , Hight-Warburton Willow , Parsons Maddy
Published: June 2021

Background

Keratinocytes form the main protective barrier in the skin to separate the underlying tissue from the external environment. In order to maintain this barrier, keratinocytes form robust junctions between neighbouring cells as well as with the underlying extracellular matrix. Cell–cell adhesions are mediated primarily through cadherin receptors, whereas the integrin family of transmembrane receptors is predominantly associated with assembly of matrix adhesions. Integrins have been shown to also localise to cell–cell adhesions, but their role at these sites remains unclear.

Results

Here we show that α2β1 integrins are enriched at mature keratinocyte cell–cell adhesions, where they play a crucial role in organising cytoskeletal networks to stabilize adherens junctions. Loss of α2β1 integrin has significant functional phenotypes associated with cell–cell adhesion destabilisation, including increased proliferation, reduced migration and impaired barrier function. Mechanistically, we show that α2β1 integrins suppress activity of Src and Shp2 at cell–cell adhesions leading to enhanced Cdc42–GDI interactions and stabilisation of junctions between neighbouring epithelial cells.

Conclusion

Our data reveals a new role for α2β1 integrins in controlling integrity of epithelial cell–cell adhesions.
The adaptive benefit of evolved increases in hemoglobin-O2 affinity is contingent on tissue O2 diffusing capacity in high-altitude deer mice
Authors: Wearing Oliver H. , Ivy Catherine M. , Gutiérrez-Pinto Natalia , Velotta Jonathan P. , Campbell-Staton Shane C. , Natarajan Chandrasekhar , Cheviron Zachary A. , Storz Jay F. , Scott Graham R.
Published: June 2021

Background

Complex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O2consumption,V̇O2max, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F2inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O2affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O2transport pathway to examine the links between cardiorespiratory traits andV̇O2max.

Results

Physiological experiments revealed that increases in Hb-O2affinity of red blood cells improved blood oxygenation in hypoxia but were not associated with an enhancement inV̇O2max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O2affinity onV̇O2max in hypoxia was contingent on the capacity for O2diffusion in active tissues.

Conclusions

These results suggest that increases in Hb-O2affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O2diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O2affinity is contingent on the capacity to extract O2from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.
Accomplishing Career Transitions 2019: facilitating success towards the professoriate
Authors: Segarra Verónica A. , Vigoreaux Jim , Zavala Maria Elena , Edwards Ashanti
Published: June 2021

The Minorities Affairs Committee of the American Society for Cell Biology through its Accomplishing Career Transitions (ACT) program aims to ease critical transitions for postdocs and junior faculty from underrepresented backgrounds in STEM or from minority-serving institutions as they work towards promotion and tenure at a wide range of academic institutions. The ACT program is a 2-year cohort-based professional and skills development program that kicks off with a summer workshop and continues with additional online training sessions on selected topics, forging the creation of a permanent mentoring community for the participants. In this BMC Proceedings Supplement, we highlight selected content from the first ACT summer workshop held in 2019 at the Rizzo Center in Chapel Hill, NC. The goal of this BMC Proceedings Supplement is to amplify impact of ACT programming in a way that transcends the ACT Fellow community to benefit an increased number of scientists.
Machine-learning-based children’s pathological gait classification with low-cost gait-recognition system
Authors: Xu Linghui , Chen Jiansong , Wang Fei , Chen Yuting , Yang Wei , Yang Canjun
Published: June 2021

Background

Pathological gaits of children may lead to terrible diseases, such as osteoarthritis or scoliosis. By monitoring the gait pattern of a child, proper therapeutic measures can be recommended to avoid the terrible consequence. However, low-cost systems for pathological gait recognition of children automatically have not been on market yet. Our goal was to design a low-cost gait-recognition system for children with only pressure information.

Methods

In this study, we design a pathological gait-recognition system (PGRS) with an 8 × 8 pressure-sensor array. An intelligent gait-recognition method (IGRM) based on machine learning and pure plantar pressure information is also proposed in static and dynamic sections to realize high accuracy and good real-time performance. To verifying the recognition effect, a total of 17 children were recruited in the experiments wearing PGRS to recognize three pathological gaits (toe-in, toe-out, and flat) and normal gait. Children are asked to walk naturally on level ground in the dynamic section or stand naturally and comfortably in the static section. The evaluation of the performance of recognition results included stratified tenfold cross-validation with recall, precision, and a time cost as metrics.

Results

The experimental results show that all of the IGRMs have been identified with a practically applicable degree of average accuracy either in the dynamic or static section. Experimental results indicate that the IGRM has 92.41% and 97.79% intra-subject recognition accuracy, and 85.78% and 78.81% inter-subject recognition accuracy, respectively, in the static and dynamic sections. And we find methods in the static section have less recognition accuracy due to the unnatural gesture of children when standing.

Conclusions

In this study, a low-cost PGRS has been verified and realize feasibility, highly average precision, and good real-time performance of gait recognition. The experimental results reveal the potential for the computer supervision of non-pathological and pathological gaits in the plantar-pressure patterns of children and for providing feedback in the application of gait-abnormality rectification.
Hukou-based rural–urban disparities in maternal health service utilization and delivery modes in two Chinese cities in Guangdong Province
Authors: Shen Menghan , Wu Yushan , Xiang Xin
Published: June 2021

Background

Most existing research on rural–urban health inequalities focuses on disparities in service access and health outcomes based on region. This paper examines rural–urban disparities in maternal healthcare utilization and delivery modes based on household registration (hukou) status to understand the role of state institutions in producing healthcare disparities in China.

Methods

Utilizing administrative data from the Public Maternal Health Insurance scheme, we analyzed 54,733 live births in City A (2015–2019) and 25,849 live births in City B (2018–2019) in Guangdong Province in China. We constructed regression models using hukou status (rural versus urban) as the explanatory variable.

Results

While there is no statistically significant difference in rural and urban mothers’ probability of obtaining the minimum recommended number of prenatal care checkups in City A (OR = 0.990 [0.950, 1.032]), mothers with rural hukou status have a lower probability of obtaining the minimum recommended number of visits in City B than their counterparts with urban hukou (OR = 0.781 [0.740, 0.825]). The probability of delivering in tertiary hospital is lower among mothers with rural hukou than among those with urban hukou in both cities (City A: OR = 0.734 [0.701, 0.769]; City B: OR = 0.336 [0.319, 0.354]). Mothers with rural hukou are more likely to have a Cesarean section than those with urban hukou in both cities (City A: OR = 1.065 [1.027, 1.104]; City B: OR = 1.127 [1.069, 1.189]). Compared with mothers with urban hukou, mothers with rural hukou incurred 4 % (95 % CI [-0.046, -0.033]) and 9.4 % (95 % CI [-0.120, -0.068]) less in total medical costs for those who delivered via Cesarean section and 7.8 % (95 % CI [-0.085, -0.071]) and 19.9 % (95 % CI [-0.221, -0.177]) less for those who delivered via natural delivery in City A and City B, respectively.

Conclusions

Rural hukou status is associated with younger age, no difference or lower probability of having a minimum number of prenatal checkups, higher likelihood of delivering in nontertiary hospitals, increased Cesarean delivery rates, and lower medical cost for delivery in these two Chinese cities. Evaluating how hukou status influences maternal healthcare in Chinese cities is important for devising targeted public policies to promote more equitable maternal health services.
False-negative frozen section of sentinel nodes in early breast cancer (cT1-2N0) patients
Authors: Loh Zhu-Jun , Lee Kuo-Ting , Chen Ya-Ping , Kuo Yao-Lung , Chung Wei-Pang , Hsu Ya-Ting , Huang Chien-Chang , Hsu Hui-Ping
Published: June 2021

Background

Sentinel lymph node biopsy (SLNB) is the standard approach for the axillary region in early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes in intraoperative frozen sections (FNSN) using real-world data.

Methods

A case–control study with a 1:3 ratio was conducted. FNSN was determined when sentinel nodes (SNs) were negative in frozen sections but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) sections. The control was defined as having no metastasis of SNs in both frozen and FFPE sections.

Results

A total of 20 FNSN cases and 60 matched controls from 333 SLNB patients were enrolled between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between the FNSN and control groups. The FNSN patients had larger tumor sizes on preoperative mammography (P = 0.033) and more lymphatic tumor emboli on core biopsy (P < 0.001). Four FNSN patients had metastasis in nonrelevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in nonrelevant SNs were recognized in two patients. All FNSN patients underwent a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed breast cancer recurrence. The disease-free survival, breast cancer-specific survival, and overall survival in FNSN were not inferior to those in controls.

Conclusions

Patients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, the outcomes of FNSN patients after completing ALND were noninferior to those without SN metastasis. ALND provides a correct staging for patients with metastasis in nonsentinel axillary lymph nodes.
Review article inferior vena cava thrombosis: a case series of patients observed in Taiwan and literature review
Authors: Lin Hsuan-Yu , Lin Ching-Yeh , Shen Ming-Ching
Published: June 2021

Inferior vena cava thrombosis (IVCT) is rare and can be under-recognized. However, the associated complications and mortality may be severe. We report the first case series of IVCT observed in Taiwan with a brief literature review. Eight Taiwanese patients with IVCT between May 2012 and December 2019 were enrolled in this study. Deep venous thrombosis (DVT, 8/8) and pulmonary embolism (5/8) were reported. Various risk factors were identified, including an unretrieved inferior vena cava (IVC) filter, pregnancy, surgery, presence of lupus of anticoagulants, essential thrombocythemia, antithrombin deficiency, and hemoglobin H disease. Of note, four of our patients experienced complete IVC thrombosis with bilateral lower extremity swelling (due to DVT) and abdominal wall superficial venous dilatation, while four other patients presented with partial IVCT and unilateral DVT. The etiology, clinical characteristics, presentations, diagnosis, and treatment of IVCT were reviewed.
TPM, FPKM, or Normalized Counts? A Comparative Study of Quantification Measures for the Analysis of RNA-seq Data from the NCI Patient-Derived Models Repository
Authors: Zhao Yingdong , Li Ming-Chung , Konaté Mariam M. , Chen Li , Das Biswajit , Karlovich Chris , Williams P. Mickey , Evrard Yvonne A. , Doroshow James H. , McShane Lisa M.
Published: June 2021

Background

In order to correctly decode phenotypic information from RNA-sequencing (RNA-seq) data, careful selection of the RNA-seq quantification measure is critical for inter-sample comparisons and for downstream analyses, such as differential gene expression between two or more conditions. Several methods have been proposed and continue to be used. However, a consensus has not been reached regarding the best gene expression quantification method for RNA-seq data analysis.

Methods

In the present study, we used replicate samples from each of 20 patient-derived xenograft (PDX) models spanning 15 tumor types, for a total of 61 human tumor xenograft samples available through the NCI patient-derived model repository (PDMR). We compared the reproducibility across replicate samples based on TPM (transcripts per million), FPKM (fragments per kilobase of transcript per million fragments mapped), and normalized counts using coefficient of variation, intraclass correlation coefficient, and cluster analysis.

Results

Our results revealed that hierarchical clustering on normalized count data tended to group replicate samples from the same PDX model together more accurately than TPM and FPKM data. Furthermore, normalized count data were observed to have the lowest median coefficient of variation (CV), and highest intraclass correlation (ICC) values across all replicate samples from the same model and for the same gene across all PDX models compared to TPM and FPKM data.

Conclusion

We provided compelling evidence for a preferred quantification measure to conduct downstream analyses of PDX RNA-seq data. To our knowledge, this is the first comparative study of RNA-seq data quantification measures conducted on PDX models, which are known to be inherently more variable than cell line models. Our findings are consistent with what others have shown for human tumors and cell lines and add further support to the thesis that normalized counts are the best choice for the analysis of RNA-seq data across samples.
Schizophrenia, the gut microbiota, and new opportunities from optogenetic manipulations of the gut-brain axis
Authors: Patrono Enrico , Svoboda Jan , Stuchlík Aleš
Published: June 2021

Schizophrenia research arose in the twentieth century and is currently rapidly developing, focusing on many parallel research pathways and evaluating various concepts of disease etiology. Today, we have relatively good knowledge about the generation of positive and negative symptoms in patients with schizophrenia. However, the neural basis and pathophysiology of schizophrenia, especially cognitive symptoms, are still poorly understood. Finding new methods to uncover the physiological basis of the mental inabilities related to schizophrenia is an urgent task for modern neuroscience because of the lack of specific therapies for cognitive deficits in the disease. Researchers have begun investigating functional crosstalk between NMDARs and GABAergic neurons associated with schizophrenia at different resolutions. In another direction, the gut microbiota is getting increasing interest from neuroscientists. Recent findings have highlighted the role of a gut-brain axis, with the gut microbiota playing a crucial role in several psychopathologies, including schizophrenia and autism.

There have also been investigations into potential therapies aimed at normalizing altered microbiota signaling to the enteric nervous system (ENS) and the central nervous system (CNS). Probiotics diets and fecal microbiota transplantation (FMT) are currently the most common therapies. Interestingly, in rodent models of binge feeding, optogenetic applications have been shown to affect gut colony sensitivity, thus increasing colonic transit. Here, we review recent findings on the gut microbiota–schizophrenia relationship using in vivo optogenetics. Moreover, we evaluate if manipulating actors in either the brain or the gut might improve potential treatment research. Such research and techniques will increase our knowledge of how the gut microbiota can manipulate GABA production, and therefore accompany changes in CNS GABAergic activity.
Application of a targeted and quantificational foraminoplasty device in percutaneous transforaminal endoscopic discectomy for L5–S1 disc herniation: preliminary clinical outcomes
Authors: Liu Jinlong , Wu Junlong , Zhang Honglei , Zuo Rui , Liu Jiabin , Zhang Chao
Published: June 2021

Objective

Percutaneous transforaminal endoscopic discectomy (PTED) is minimally invasive and has been widely used to treat patients with lumbar disc herniation (LDH) due to its safety and efficiency. However, due to the unique anatomy of the L5–S1 level, the PTED procedure is often difficult to perform in the region. ZESSYS, a targeted and quantificational foraminoplasty device, may help to overcome these anatomical limitations. In this study, we assessed the efficiency and the short-term effects of PTED with ZESSYS at the L5–S1 level.

Methods

Between January and August of 2018, fifty-six patients with lumbar disc herniation at the single level of L5–S1 and who underwent percutaneous transforaminal endoscopic discectomy were enrolled in this retrospective cohort study. They were segregated into the transforaminal endoscopic surgical system (TESSYS) group and the ZESSYS group. The puncture time, foraminoplasty time, decompression time, and fluoroscopy time were evaluated for operation efficiency. Clinical outcomes were assessed by the visual analog scale (VAS) score and Oswestry Disability Index (ODI) score. The MacNab criteria were used to evaluate patient subjective satisfaction at 12-month follow-up postoperatively.

Results

The average puncture time (5.29 ± 2.05 min), foraminoplasty time (12.82 ± 2.52 min), and fluoroscopy time (26.29 ± 5.96 s) were all significantly shorter in the ZESSYS group than in the TESSYS group (average puncture time 8.07 ± 3.13 min, p < 0.01; foraminoplasty time, 17.18 ± 2.92 min, p < 0.01; fluoroscopy time, 34.73 ± 6.86 s; p < 0.01). No significant differences were observed between the 2 groups in the decompression time (p = 0.057). The VAS score of low back pain and leg pain, as well as the ODI score, improved at all time points postoperatively compared with preoperative, in both the TESSYS group and the ZESSYS group (P < 0.05). There were no significant differences in the VAS score of low back pain, VAS score of leg pain, and ODI score between the TESSYS group and the ZESSYS group at the same time points (P > 0.05). According to the MacNab criteria, the excellent and good rate at 12-month follow-up postoperatively was 85.7% in the TESSYS group and 89.3% in the ZESSYS group (P > 0.05).

Conclusion

The targeted and quantificational foraminoplasty device named ZESSYS was more efficient in the puncture and foraminoplasty procedures, effectively protecting the exiting nerve and minimizing the level of radiation exposure. The device is efficient and safe for PTED in treating lumbar disc herniation at the L5–S1 level.
Transmission of infectious laryngotracheitis virus vaccine and field strains: the role of degree of contact and transmission by whole blood, plasma and poultry dust
Authors: Yegoraw Addisu A. , Assen Awol M. , Gerber Priscilla F. , Walkden-Brown Stephen W.
Published: June 2021

Understanding the mechanisms of transmission of infectious laryngotracheitis virus (ILTV) is critical to proper control as both vaccine and wild-type strains circulate within chicken flocks with potential adverse consequences. The relative efficiency of transmission by direct contact between chickens and airborne transmission has not been investigated. Furthermore, relatively high levels of ILTV DNA have been detected in poultry dust and blood but the infectivity of these is unknown. In this study, comparison of in-contact and airborne transmission of two vaccine and one field strain of ILTV revealed that all transmitted to 100% of in-contact birds by 6 days post-exposure (dpe). Airborne transmission without contact resulted in 100% transmission by 14 and 17 dpe for the wild-type and Serva vaccine virus but only 27% transmission by 21 dpe for the A20 vaccine virus. The infectivity of dust or extracts of dust and blood or plasma from infected chickens at various stages of infection was assessed by inoculation into susceptible chickens. There was no transmission by any of these materials. In conclusion, direct contact facilitated efficient ILTV transmission but the virus was unable to be transmitted by dust from infected chickens suggestive of a limited role in the epidemiology of ILTV.
Typhlitis induced by Histomonas meleagridis affects relative but not the absolute Escherichia coli counts and invasion in the gut in turkeys
Authors: Abdelhamid Mohamed Kamal , Rychlik Ivan , Hess Claudia , Hatfaludi Tamas , Crhanova Magdalena , Karasova Daniela , Lagler Julia , Liebhart Dieter , Hess Michael , Paudel Surya
Published: June 2021

Unlike in chickens, dynamics of the gut microbiome in turkeys is limitedly understood and no data were yet published in context of pathological changes following experimental infection. Thus, the impact of Histomonas meleagridis-associated inflammatory changes in the caecal microbiome, especially the Escherichia coli population and their caecal wall invasion in turkeys was investigated. Birds experimentally inoculated with attenuated and/or virulent H. meleagridis and non-inoculated negative controls were divided based on the severity of macroscopic caecal lesions. The high throughput amplicon sequencing of 16SrRNA showed that the species richness and diversity of microbial community significantly decreased in severely affected caeca. The relative abundances of operational taxonomic units belonging to Anaerotignum lactatifermentans, E. coli, and Faecalibacterium prausnitzii were higher and paralleled with a decreased abundances of those belonging to Alistipes putredinis, Streptococcusalactolyticus, Lactobacillus salivarius and Lactobacillus reuteri in birds with the highest lesion scores. Although the relative abundance of E. coli was higher, the absolute count was not affected by the severity of pathological lesions. Immunohistochemistry showed that E. coli was only present in the luminal content of caecum and did not penetrate even severely inflamed and necrotized caecal wall. Overall, it was demonstrated that the fundamental shift in caecal microbiota of turkeys infected with H. meleagridis was attributed to the pathology induced by the parasite, which only led to relative but not absolute changes in E. coli population. Furthermore, E. coli cells did not show tendency to penetrate the caecal tissue even when the intestinal mucosal barriers were severely compromised.
Do Patients With Atypical Parathyroid Adenoma Need Close Follow-up?
Authors: Saponaro Federica , Pardi Elena , Mazoni Laura , Borsari Simona , Torregrossa Liborio , Apicella Matteo , Frustaci Gianluca , Materazzi Gabriele , Miccoli Paolo , Basolo Fulvio , Marcocci Claudio , Cetani Filomena
Published: June 2021

Context

Atypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy.

Objective

This work aims to retrospectively evaluate the clinical and biochemical profiles of patients with APA, the outcome after parathyroidectomy (PTX), and the presence of CDC73 germline and somatic mutations.

Methods

This monocentric study was conducted on consecutive patients undergoing PTX for primary hyperparathyroidism (PHPT) between June 2000 and December 2020. Fifty-eight patients with a confirmed histopathological diagnosis of APA, and age- and sex-matched controls with parathyroid adenoma (PA) were also included.

Results

Fifty-four patients had sporadic PHPT and 4 had familial isolated hyperparathyroidism (FIHP). Thirty-four patients (59%) had symptomatic disease. Serum calcium and parathyroid hormone (PTH) levels were significantly higher in symptomatic compared to asymptomatic patients (P = .048 and .008, respectively). FIHP patients were younger than their sporadic counterparts (30 ± 17 years vs 55 ± 13 years). APA patients had significantly higher serum calcium and PTH levels and lower 25-hydroxyvitamin D concentration, bone mineral density, and T score at one-third distal radius compared to those with PA. Four of 56 APA patients displayed a CDC73 germline mutation. No somatic CDC73 mutation was identified in 24 tumor specimens. The mean follow-up after surgery was 60 ± 56.4 months. All but 6 patients (90%), 5 with apparently sporadic PHPT and 1 with FIHP, were cured after surgery.

Conclusion

The large majority of patients with APA, despite a moderate/severe phenotype, have a good prognosis. Germline CDC73 mutation–positive patients had a higher rate of persistent/recurrent disease. CDC73 gene alterations do not seem to have a relevant role in the tumorigenesis of sporadic APA.
Failing Gender, Failing the West
Authors: Uhlig Tija
Published: June 2021

Although nonbinary sex/gender has seen some attention in recent years in academia and popular culture, it is mostly seen through the lens of modernity, which views trans as a straight movement from one “gender identity” to another. This article aims to tell a story that is different from this narrative of modern trans identity. It is, therefore, written as an autoethnodrama rooted in the author's own embodied experience of (un)becoming genderqueer in a postsocialist borderland. The main theoretical threads are border epistemologies and the monstrous process of (un)becoming self/other, specified through the figuration of the genderqueer clown. The first scene of this drama is about orientation and clowning in a post-Soviet space in the 1990s. The second scene is about failing gender and failing the West/East divide in front of a public bathroom in 2019. The research-drama ends with drifting, drowning, and getting lost in a stream of body liquids. This opens up possibilities for affection and compassion in failing together with all the creatures who are filling that stream.
DNA binding alters ARv7 dimer interactions
Authors: Özgün Fatma , Kaya Zeynep , Morova Tunç , Geverts Bart , Abraham Tsion E. , Houtsmuller Adriaan B. , van Royen Martin E. , Lack Nathan A.
Published: June 2021

Androgen receptor (AR) splice variants are proposed to be a potential driver of lethal castration-resistant prostate cancer. AR splice variant 7 (ARv7) is the most commonly observed isoform and strongly correlates with resistance to second-generation anti-androgens. Despite this clinical evidence, the interplay between ARv7 and the highly expressed full-length AR (ARfl) remains unclear. In this work, we show that ARfl/ARv7 heterodimers readily form in the nucleus via an intermolecular N/C interaction that brings the four termini of the proteins in close proximity. Combining fluorescence resonance energy transfer and fluorescence recovery after photobleaching, we demonstrate that these heterodimers undergo conformational changes following DNA binding, indicating dynamic nuclear receptor interaction. Although transcriptionally active, ARv7 can only form short-term interactions with DNA at highly accessible high-occupancy ARfl binding sites. Dimerization with ARfl does not affect ARv7 binding dynamics, suggesting that DNA binding occupancy is determined by the individual protein monomers and not the homodimer or heterodimer complex. Overall, these biophysical studies reveal detailed properties of ARv7 dynamics as both a homodimer or heterodimer with ARfl.
Genetic compensation for cilia defects in cep290 mutants by upregulation of cilia-associated small GTPases
Authors: Cardenas-Rodriguez Magdalena , Austin-Tse Christina , Bergboer Judith G. M. , Molinari Elisa , Sugano Yuya , Bachmann-Gagescu Ruxandra , Sayer John A. , Drummond Iain A.
Published: June 2021

Mutations in CEP290 (also known as NPHP6), a large multidomain coiled coil protein, are associated with multiple cilia-associated syndromes. Over 130 CEP290 mutations have been linked to a wide spectrum of human ciliopathies, raising the question of how mutations in a single gene cause different disease syndromes. In zebrafish, the expressivity of cep290 deficiencies were linked to the type of genetic ablation: acute cep290 morpholino knockdown caused severe cilia-related phenotypes, whereas deficiencies in a CRISPR/Cas9 genetic mutant were restricted to photoreceptor defects. Here, we show that milder phenotypes in genetic mutants were associated with the upregulation of genes encoding the cilia-associated small GTPases arl3, arl13b and unc119b. Upregulation of UNC119b was also observed in urine-derived renal epithelial cells from human Joubert syndrome CEP290 patients. Ectopic expression of arl3, arl13b and unc119b in cep290 morphant zebrafish embryos rescued Kupffer's vesicle cilia and partially rescued photoreceptor outer segment defects. The results suggest that genetic compensation by upregulation of genes involved in a common subcellular process, lipidated protein trafficking to cilia, may be a conserved mechanism contributing to genotype-phenotype variations observed in CEP290 deficiencies.

This article has an associated First Person interview with the first author of the paper.
... und was davon übrig bleibt
Authors: Brombacher Christoph , Helmig Guido , Hüster-Plogmann Heidemarie , Klee Marlies , Rentzel Philippe , Rodel Sylvia , Veszeli Marcel
Published: June 2021

Im Mittelpunkt des Artikels steht der ins Mittelalter datierende Latrinenschacht, der in der Südwestecke der Parzelle zum Vorschein kam. Die interdisziplinäre Aufarbeitung dieses Befundes umfasst die mikromorphologische Untersuchung von Bodenproben zur lokalen Charakterisierung der Sedimente, die Interpretation des osteologischen Materials und der botanischen Makroreste hinsichtlich Ernährungsgewohnheiten und landwirtschaftlicher Aktivitäten sowie die Datierung des Befundes anhand der geborgenen archäologischen Funde.
Baugeschichtliche Untersuchungen im Jahre 1999
Authors: Jaggi Bernard , Reicke Daniel , Ritzmann Hans
Published: June 2021

Die Abteilung Bauforschung der Basler Denkmalpflege befasste sich im Berichtsjahr 1999 wieder mit sehr unterschiedlich gelagerten Fällen. Es wurden insgesamt 31 Objekte bearbeitet. Im vorliegenden Bericht werden 24 abgeschlossene Arbeiten näher erläutert.
Die Beth-El-Steine von Riehen
Authors: Moosbrugger-Leu Rudolf
Published: June 2021

Hinter der Riehener Dorfkirche wurde 1973 ein kleiner mittelalterlicher Friedhof entdeckt. Die Gräber waren beigabenlos. In den Grabgruben konnten keine Spuren von Särgen oder hölzernen Ausschachtungen festgestellt werden. Die Toten wurden wahrscheinlich in einem Leichentuch beigesetzt. In einigen Gruben fiel ein Stein auf, der unmittelbar hinter dem Schädelscheitel anstand. Diese Steine waren in der Erde verborgen und hatten keine erkennbare konstruktive Funktion.

Der Autor bringt sie in Beziehung zu einer Stelle im Alten Testament (1. Moses, 28, 10-19: Jakob weiht nach seinem Traum von der Himmelsleiter den Stein, den er als Kopfkissen benutzt hat, indem er Öl darüber giesst und nennt den Ort Beth-El, Haus Gottes). Der Akt der Steinsetzung im Grab wird als Glaubensbekenntnis der damaligen Bevölkerung gedeutet.
Auf den Spuren des alten Basler Buchgewerbes
Authors: Tschudin Peter F.
Published: June 2021

In der Verfüllung des alten Kellers des Hauses St. Alban-Vorstadt 28 sind eine Druckletter, Reste von Letternmetall und Buchbeschlägen sowie Werkzeuge des Buchgewerbes und einer Buntmetall verarbeitenden Werkstatt gefunden worden. Sie gehören zu den frühesten Belegstücken der Drucktechnik der Inkunabelzeit und erhellen die Frühgeschichte des Buchdrucks.