bluuebunny/crossref_metadata_2025 huggingface dataset:
Respecting, protecting and fulfilling the human right to health
Authors: Nampewo Zahara , Mike Jennifer Heaven , Wolff Jonathan
Published: March 2022

Background

Human rights are best protected, promoted and guaranteed when they can compel binding and enforceability duty. One prominent criticism of category of human rights which includes the human right to health is that it is difficult, to assign the duties that correspond to these rights, because of stark disparity in how the main duty bearers approach their duties.

Methods

This paper adopts a doctrinal approach to examine and evaluate the duties to the right to health. The method in this study entails a detailed literature search to systematically evaluate the legal implications, regulations, arguments and policy regarding the nature of the obligation to the right to health. This study also engages with normative and philosophical aspects of human rights.

Results

This paper posits that human rights protect against common, serious, and remediable threats and risks, and ensure that there are remedies from governments and third parties. However, it is difficult to compel duties especially in regard to the right to health. First it is not easy to achieve a uniform standard for duty bearers implied by the words ‘highest attainable physical and mental health.’ Theorists discussed in the paper outline views of what this could mean, from serious to common health concerns. Second, the right to health is not a legally established right in many jurisdictions, making it difficult to enforce. This paper outlines different layers of state and non-state legal duty bearers to enforce the right to health.

Conclusion

The duty to respect, protect, fulfil and even remedy the right to health, will often be meaningless in practice without a clear identification of the necessary duty bearers to enforce them. The law is the starting point for this to not only enshrine this right as a legally enforceable one but also to clearly identify duty bearers. Without this, the human right to health as outlined under international and regional human rights law generates an implausible, or even impossible, profusion of duties. There remains much work still to be done especially on the moral and legal fronts in order to fully guarantee this right.

Trial Registration

Not applicable

Our work does not report results of a health care intervention on human participants. Registration is therefore not applicable.
Clear cell carcinoma arising from abdominal wall endometriosis—a report on two cases and literature review
Authors: Bahall Vishal , De Barry Lance , Rampersad Arlene
Published: March 2022

Background

Malignant transformation of abdominal wall endometriosis is extremely rare. Clear cell carcinoma and endometrioid carcinoma are the two most prevalent histological subtypes of malignant endometriosis. To date, approximately, thirty cases of clear cell carcinoma arising from abdominal wall endometriosis have been described worldwide.

Case presentation

We report two cases of clear cell carcinoma developing postoperatively in the anterior abdominal wall in women with a history of extensive endometriosis. Histopathology of the resected abdominal wall tumor demonstrated benign endometriosis contiguous with features of clear cell carcinoma. These histological features satisfied Sampson’s criteria which are required for diagnosing malignant endometriosis. Both patients were successfully managed with platinum-based adjuvant chemotherapy following cytoreductive surgery.

Conclusion

Clear cell carcinoma arising from the abdominal wall endometriosis is a rare, highly aggressive cancer with a propensity to recur or metastasize. Due to the limited publications on this clinical entity, there are no clearly established protocols regarding adjuvant treatment, and an evaluation of prognostic factors is lacking. Clinicians must have a high index of suspicion for malignant endometriosis of the abdominal wall, particularly in patients with an abdominal wall mass, prior abdominal surgery, and long-standing endometriosis. By presenting our case, we expect to raise awareness and study of this rare endometriosis-related neoplasm.
CYP1B1-catalyzed 4-OHE2 promotes the castration resistance of prostate cancer stem cells by estrogen receptor α-mediated IL6 activation
Authors: Lin Qimei , Cao Jiasong , Du Xiaoling , Yang Kuo , Yang Xu , Liang Zhixian , Shi Jiandang , Zhang Ju
Published: March 2022

Background

Resistance to androgen deprivation therapy remains a major challenge for the clinical treatment of patients with castration-resistant prostate cancer (CRPC). CYP1B1, a critical enzyme that catalyzes the conversion of estradiol to 4-Hydroxy-17β-estradiol (4-OHE2), has been reported to promote the development and progression of hormone-related cancer, but its role in CRPC is unclear.

Methods

To explore the underlying mechanism which CYP1B1 promotes the prostate cancer stem cells (PCSCs) characteristics, bioinformatics analyses of human clinical prostate cancer (PCa) datasets were performed. CYP1B1, IL6, and estrogen receptor-α (ERα) expression levels were evaluated in PCa and CRPC tissues via immunohistochemistry. The high-performance liquid chromatography-mass spectrometry assay was carried out to examine intracellular 4-OHE2 levels. Serum-free suspension culture and flow cytometry assays were performed to evaluate PCSCs. Chromatin immunoprecipitation was used to validate that 4-OHE2 recruited ERα to the IL6 promoter.

Results

CYP1B1 expression was significantly increased in CRPC tissues and androgen-independent PCa cell lines. CYP1B1+ PCa cells were significantly enriched in bicalutamide-treated LNCaP cells, and CYP1B1 knockdown reduced the cell viability under bicalutamide treatment. In addition, CYP1B1 knockdown decreased the intracellular 4-OHE2 concentration, accompanied by reduced PCSC characteristics. In PCa cells, 4-OHE2 stimulated ERα transcriptional activity and upregulated the expression of IL6 and downstream genes of the IL6-STAT3 signaling. 4-OHE2 increased cell viability under bicalutamide treatment and promoted PCSC characteristics, while IL6 neutralizing antibody reversed these effects. Mechanistically, siERα and the ER antagonist ICI182780 significantly attenuated 4-OHE2-induced IL6 expression, and 4-OHE2 promoted the binding of ERα to the estrogen response element of the IL6 promoter.

Conclusions

Our findings indicate that CYP1B1-catalyzed 4-OHE2 enhanced PCSC characteristics and attenuated bicalutamide sensitivity by ERα-mediated the IL6-STAT3 pathway activation. Our study further emphasizes the role of CYP1B1 in castration resistance and illustrates a novel mechanism of CRPC development.

Graphical Abstract
Family-focused contextual factors associated with lifestyle patterns in young children from two mother-offspring cohorts: GUSTO and EDEN
Authors: Chia Airu , Descarpentrie Alexandra , Cheong Rene N. , Toh Jia Ying , Natarajan Padmapriya , Sugianto Ray , Cai Shirong , Saldanha-Gomes Cécilia , Dargent-Molina Patricia , de Lauzon-Guillain Blandine , Plancoulaine Sabine , Lança Carla , Saw Seang Mei , Godfrey Keith M. , Shek Lynette P. , Tan Kok Hian , Charles Marie-Aline , Chong Yap Seng , Heude Barbara , Eriksson Johan G. , Müller-Riemenschneider Falk , Lioret Sandrine , Chong Mary F.-F. , Bernard Jonathan Y.
Published: March 2022

Background

Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses.

Purpose

Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors.

Methods

Ten behavioural variables related to child’s diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5–6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression.

Results

Three broadly similar lifestyle patterns were identified in both cohorts: “discretionary consumption and high screen time”, “fruit, vegetables, and low screen time” and “high outdoor playtime and walking”. The latter two patterns showed small differences between cohorts and sexes. The “discretionary consumption and high screen time” pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating.

Conclusions

Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health.
Overground robotic training effects on walking and secondary health conditions in individuals with spinal cord injury: systematic review
Authors: Tamburella Federica , Lorusso Matteo , Tramontano Marco , Fadlun Silvia , Masciullo Marcella , Scivoletto Giorgio
Published: March 2022

Overground powered lower limb exoskeletons (EXOs) have proven to be valid devices in gait rehabilitation in individuals with spinal cord injury (SCI). Although several articles have reported the effects of EXOs in these individuals, the few reviews available focused on specific domains, mainly walking. The aim of this systematic review is to provide a general overview of the effects of commercial EXOs (i.e. not EXOs used in military and industry applications) for medical purposes in individuals with SCI. This systematic review was conducted following the PRISMA guidelines and it referred to MED-LINE, EMBASE, SCOPUS, Web of Science and Cochrane library databases. The studies included were Randomized Clinical Trials (RCTs) and non-RCT based on EXOs intervention on individuals with SCI. Out of 1296 studies screened, 41 met inclusion criteria. Among all the EXO studies, the Ekso device was the most discussed, followed by ReWalk, Indego, HAL and Rex devices. Since 14 different domains were considered, the outcome measures were heterogeneous. The most investigated domain was walking, followed by cardiorespiratory/metabolic responses, spasticity, balance, quality of life, human–robot interaction, robot data, bowel functionality, strength, daily living activity, neurophysiology, sensory function, bladder functionality and body composition/bone density domains. There were no reports of negative effects due to EXOs trainings and most of the significant positive effects were noted in the walking domain for Ekso, ReWalk, HAL and Indego devices. Ekso studies reported significant effects due to training in almost all domains, while this was not the case with the Rex device. Not a single study carried out on sensory functions or bladder functionality reached significance for any EXO. It is not possible to draw general conclusions about the effects of EXOs usage due to the lack of high-quality studies as addressed by the Downs and Black tool, the heterogeneity of the outcome measures, of the protocols and of the SCI epidemiological/neurological features. However, the strengths and weaknesses of EXOs are starting to be defined, even considering the different types of adverse events that EXO training brought about. EXO training showed to bring significant improvements over time, but whether its effectiveness is greater or less than conventional therapy or other treatments is still mostly unknown. High-quality RCTs are necessary to better define the pros and cons of the EXOs available today. Studies of this kind could help clinicians to better choose the appropriate training for individuals with SCI.
Ethnobotanical study on wild edible plants traditionally used by Messiwa people, Morocco
Authors: Ghanimi Ridwane , Ouhammou Ahmed , Ahouach Abdellah , Cherkaoui Mohamed
Published: March 2022

Background

The traditional knowledge on wild edible plants has been shown in many studies a worrying decline throughout the last few decades. Therefore, the first aim of this study was to document the population knowledge on wild edible plants among the Messiwa people. The second objective was to assess the traditional knowledge of our informants according to their socio-economic status.

Methods

The survey was conducted among 149 informants through a semi-structured questionnaire. The relative importance of the plants was obtained by calculating the relative frequency of citation (RFC) for each species. To compare means, we used Student'sttest for two-group comparisons and Snedecor'sF-test for multi-group comparisons. The multi-range Duncan test was used for multiple mean comparisons. The correspondence factor analysis (CFA) was also used.

Results

A set of 64 species belonging to 56 genera from 34 families has been collected and identified. The species used for nutritional and medicinal purposes represent 56%, while 44% were used exclusively as nutritional plants. The most used parts are, respectively, the aerial parts (58%), the fruits (17%), the underground parts (13%), the seeds (8%), and finally the flowers (5%). On the other hand, the higher level of knowledge on wild edible plants was found among women, the elderly, illiterate, married people, and those engaged in agricultural occupations.

Conclusion

This work could be a basis to be reproduced on other regions in Morocco and to be widened through pharmacological and nutritional studies in order to promote and valorize these wild edible plants.
A study of the plant folk nomenclature of the Yi people in Xiaoliangshan, Yunnan Province, China, and the implications for protecting biodiversity
Authors: Addi Yi-Won , Zhang Yu , Ding Xiao-Yong , Guo Chang-An , Wang Yu-Hua
Published: March 2022

Background

Folk plant nomenclature is a part of knowledge of indigenous people often used to distinguish plant species. This study aimed to document the folk botanical nomenclature of the Yi people in Xiaoliangshan, Yunnan Province, which has not been systematically investigated to date. The results of this study will assist in conserving biodiversity and the language of the Yi people and will promote the transmission of ethnobotanical knowledge.

Methods

An ethnobotanical survey of plants used by the Yi people in Xiaoliangshan, Yunnan Province, was conducted from September 2019 to August 2021. Semi-structured interviews and key informant interviews were conducted to collect and document ethnobotanical information, which was then used to analyse the folk botanical nomenclature of the Yi people. In addition, the folk names of plants used by the Xiaoliangshan Yi community were compared with those of the Yi people living in the Daliangshan, where the environment is considerably different.

Results

In this study, 266 informants were interviewed, and the names of 228 indigenous plants were extracted from 3088 use reports. The nomenclature used by the local Yi people is based on plant characteristics, plant habitat, plant use, and the local culture. By comparing the folk plant names of the Yi people in Xiaoliangshan with those of the Yi people in Daliangshan, we found that the plant names of the two places have some similarities and also with their own unique characters. The important folk plant names of the Yi people in Xiaoliangshan usually have a monosyllable non-binomial structure or have

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and "divine attributes" in their names.

Conclusions

The Yi people in Xiaoliangshan have a rich and diverse knowledge of plant naming determined by cultural, and environmental factors. The botanical nomenclature of the Yi people has distinct rules and characteristics, and the plant naming directly includes important plants that they believe to be used and protected, which is of great significance to the protection of biodiversity.
Predicting yellow rust in wheat breeding trials by proximal phenotyping and machine learning
Authors: Koc Alexander , Odilbekov Firuz , Alamrani Marwan , Henriksson Tina , Chawade Aakash
Published: March 2022

Background

High-throughput plant phenotyping (HTPP) methods have the potential to speed up the crop breeding process through the development of cost-effective, rapid and scalable phenotyping methods amenable to automation. Crop disease resistance breeding stands to benefit from successful implementation of HTPP methods, as bypassing the bottleneck posed by traditional visual phenotyping of disease, enables the screening of larger and more diverse populations for novel sources of resistance. The aim of this study was to use HTPP data obtained through proximal phenotyping to predict yellow rust scores in a large winter wheat field trial.

Results

The results show that 40–42 spectral vegetation indices (SVIs) derived from spectroradiometer data are sufficient to predict yellow rust scores using Random Forest (RF) modelling. The SVIs were selected through RF-based recursive feature elimination (RFE), and the predicted scores in the resulting models had a prediction accuracy of rs = 0.50–0.61 when measuring the correlation between predicted and observed scores. Some of the most important spectral features for prediction were the Plant Senescence Reflectance Index (PSRI), Photochemical Reflectance Index (PRI), Red-Green Pigment Index (RGI), and Greenness Index (GI).

Conclusions

The proposed HTPP method of combining SVI data from spectral sensors in RF models, has the potential to be deployed in wheat breeding trials to score yellow rust.
Plasma levels of receptor-interacting protein kinase 3 is associated with postoperative acute kidney injury in acute DeBakey type I aortic dissection
Authors: Wang Lei , Zhong Guodong , Zhou Hao , Lv Xiaochai , Dong Yi , Wang Xiaoli , Dai Xiaofu , Xu Yanfang , Chen Liangwan
Published: March 2022

Background

Postoperative acute kidney injury (AKI) in acute DeBakey type I aortic dissection (ADIAD) is common but has unclear pathogeneses and limited treatments. Receptor-interacting protein kinase 3 (RIP3), a mediator of necroptosis, is associated with human sepsis-induced and posttraumatic AKI, but its role in human postoperative AKI in ADIAD remains unclear. We assumed that RIP3 levels is associated with postoperative AKI in ADIAD.

Methods

Plasma samples and the clinical data of continuous patients with ADIAD were collected prospectively. The patients were divided into three groups according to AKI stage postoperatively. The plasma RIP3 levels were compared among the groups, and the relationship between RIP3 and serum creatinine (sCr), inflammatory cytokines as well as clinical results were analyzed.

Results

Eighty patients were enrolled. The postoperative and elevated RIP3 levels among the three groups were significantly different (P < 0.0001), both with a positive trend across the AKI stage (Pfor trend < 0.001), and they were also independent risk factors for postoperative AKI in ADIAD (OR = 1.018 and 1.026,P < 0.05). The postoperative RIP3 levels were positively correlated with the aortic crossclamp time (R = 0.253,P < 0.05); the peak values of sCr, procalcitonin, interleukin-6 and lactate postoperatively; the mechanical ventilation time; and the ICU stay time (R = 0.66, 0.369, 0.409, 0.397, 0.474 and 0.435, respectively; allP < 0.001). Plasma RIP3 level and sCr were comparable in diagnosing postoperative AKI in ADIAD (P = 0.898), and higher postoperative RIP3 level was associated with lower survival rate.

Conclusion

The plasma RIP3 levels are associated with postoperative AKI, inflammatory response and clinical outcomes in ADIAD.
The school environment and bullying victimization among seventh graders with autism spectrum disorder: a cohort study
Authors: Lu Hsin-Hui , Chen Duan-Rung , Chou An-Kuo
Published: March 2022

Background

There is strong evidence to support the association between bullying and the onset of mental health conditions in students with ASD (autism spectrum disorder). In Taiwan, the seventh grade marks the first year of middle school, following elementary school. This period is also when peers tend to perform bullying behaviours to establish status among the peer group. Therefore, seventh grade is considered one of the most challenging times for students with ASD due to several changes within the school environment and the developmental changes that arise at this age. This study aims to assess the association between the school environment and bullying victimization among students with autism spectrum disorder (ASD) enrolled in regular classes in their first year of middle school.

Methods

Data were obtained from the Special Needs Education Longitudinal Study database located in the Survey Research Data Archive of Academia Sinica. The analysis included one hundred eighty-four seventh graders with ASD who were in regular classes across Taiwan. The primary variables under study were whether the participants had experienced social exclusion, insults or teasing, extortion, or sexual harassment over the past semester.

Results

Participants with a higher positive friendship quality (P = 0.027) and who had received more peer support upon encountering difficulties in school (P = 0.041) were less likely to experience social exclusion. Participants with a higher positive friendship quality (P = 0.001) and a more positive classroom learning environment (P = 0.031) were less likely to have experienced insults or teasing. However, participants with more friends were more likely to be extorted (P = 0.015) and sexually harassed (P = 0.001) than those with fewer friends. Furthermore, participants in regular classes on a part-time basis were 2.59 times more likely to report sexual harassment than those in regular classes on a full-time basis (P = 0.021).

Conclusions

This study suggests that a supportive school environment reduces the likelihood that seventh-graders with ASD will be bullied. Clinicians should consider the association between the school environment and bullying victimization among adolescents with ASD in regular classes during their first year of middle school.
Radiomics predicts the prognosis of patients with locally advanced breast cancer by reflecting the heterogeneity of tumor cells and the tumor microenvironment
Authors: Wang Xuanyi , Xie Tiansong , Luo Jurui , Zhou Zhengrong , Yu Xiaoli , Guo Xiaomao
Published: March 2022

Background

This study investigated the efficacy of radiomics to predict survival outcome for locally advanced breast cancer (LABC) patients and the association of radiomics with tumor heterogeneity and microenvironment.

Methods

Patients with LABC from 2010 to 2015 were retrospectively reviewed. Radiomics features were extracted from enhanced MRI. We constructed the radiomics score using lasso and assessed its prognostic value. An external validation cohort from The Cancer Imaging Archive was used to assess phenotype reproducibility. Sequencing data from TCGA and our center were applied to reveal genomic landscape of different radiomics score groups. Tumor infiltrating lymphocytes map and bioinformatics methods were applied to evaluate the heterogeneity of tumor microenvironment. Computational histopathology was also applied.

Results

A total of 278 patients were divided into training cohort and validation cohort. Radiomics score was constructed and significantly associated with disease-free survival (DFS) of the patients in training cohort, validation cohort and external validation cohort (p < 0.001, p = 0.014 and p = 0.041, respectively). The radiomics-based nomogram showed better predictive performance of DFS compared with TNM model. Distinct gene expression patterns were identified. Immunophenotype and immune cell composition was different in each radiomics score group. The link between radiomics and computational histopathology was revealed.

Conclusions

The radiomics score could effectively predict prognosis of LABC after neoadjuvant chemotherapy and radiotherapy. Radiomics revealed heterogeneity of tumor cell and tumor microenvironment and holds great potential to facilitate individualized DFS estimation and guide personalized care.
Developmental transcriptomics throughout the embryonic developmental process of Rhipicephalus turanicus reveals stage-specific gene expression profiles
Authors: Ruiling Zhang , Wenjuan Liu , Kexin Zhang , Xuejun Wang , Zhong Zhang
Published: March 2022

Background

Ticks are important vectors and transmit diverse pathogens, including protozoa, viruses, and bacteria. Tick-borne diseases can cause damage to both human health and the livestock industries. The control and prevention of ticks and tick-borne diseases has relied heavily on acaricides.

Methods

In the present study, using a high-throughput RNA sequencing (RNA-Seq) technique, we performed a comprehensive time-series transcriptomic analysis throughout the embryogenesis period of Rhipicephalus turanicus.

Results

Altogether, 127,157 unigenes were assembled and clustered. Gene expression differences among the embryonic stages demonstrated that the most differentially expressed genes (DEGs) were observed in the comparisons of early embryonic stages (RTE5 vs. RTE10, 9726 genes), and there were far fewer DEGs in later stages (RTE25 vs. RTE30, 2751 genes). Furthermore, 16 distinct gene modules were identified according to weighted gene co-expression network analysis (WGCNA), and genes in different modules displayed stage-specific characteristics. Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment suggested that some genes involved in organ and tissue formation were significantly upregulated in the early embryonic developmental stages, whereas metabolism-related pathways were more enriched in the later embryonic developmental stages.

Conclusions

These transcriptome studies revealed gene expression profiles at different stages of embryonic development, which would be useful for interrupting the embryonic development of ticks and disrupting the transmission of tick-borne diseases.

Graphical Abstract
Determinants of apprehension to return to sport after reconstruction of the anterior cruciate ligament: an exploratory observational retrospective study
Authors: Martini Alexandre , Ayala Anne , Lechable Marc , Rannou François , Lefèvre-Colau Marie-Martine , Nguyen Christelle
Published: March 2022

Background

Only 65% of people return to a level of sport equivalent to that before after anterior cruciate ligament (ACL) surgery. Persisting apprehension may in part explain this observation. We aimed to describe characteristics of people with ACL-Return to Sport after Injury (RSI) scores ≥ 60/100 (low apprehension) at 6 months after injury and to identify variables independently associated with low apprehension at 6 months.

Methods

We conducted a single-center retrospective study. People who had surgery for an ACL rupture and who participated in an outpatient post-operative rehabilitation program were included consecutively. The ACL-RSI questionnaire was self-administered at 6 months after injury. Baseline characteristics of people with ACL-RSI scores ≥ 60/100 and < 60/100 were described. Multiple logistic regression was performed to identify baseline variables associated with low apprehension at 6 months.

Results

We included 37 participants: 13/37 (35.1%) were women and mean age was 27.2 (9.2) years. At 6 months, 21/37 (56.8%) had an ACL-RSI score ≥ 60/100. Participants who had an ACL-RSI score ≥ 60/100 more often received a preoperative rehabilitation (16/21 [76.2%] vs 5/16 [31.2%]), and had less often knee pain (7/21 [33.3%] vs 7/16 [43.7%]) and effusion (5/21 [23.8%] vs 8/16 [50.0%]) at 1 month after surgery, than participants who had an ACL-RSI score < 60/100. In the multivariate analysis, preoperative rehabilitation was associated with low apprehension at 6 months (OR [95% CI] = 0.107 [0.023 to 0.488], p = 0.002).

Conclusions

Preoperative rehabilitation was independently associated with low apprehension at 6 months.

Trial registration. Not applicable.
Pancoast tumor presenting with multiple joint pains: a case report
Authors: Mohamud Safia , Oyawusi Mosunmola , Weir Roger L. , Halbert Etuajie O. , Millis Richard M. , Gebremedhin Teddy , Dehkordi Ozra
Published: March 2022

Background

Pancoast tumors represent a unique subset of lung cancers wherein a primary neoplasm arises in the lung’s apex and invades the surrounding soft tissues. One of the main challenges in the diagnosis and treatment of these apical lung cancers is that they are usually not visualized on initial chest x-ray and, by the time the patient presents with symptoms, the tumor has almost always invaded nearby structures.

Case presentation

Herein we report a case of a 58-year-old nonsmoking African American male who presented to the neurology clinic with a history of multiple chronic joint pains. The patient complained of shoulder pain that traveled into his right arm and right finger and had worsened over the past 9 months. The patient also reported decreased right proximal strength and swelling of his right hand. Magnetic resonance imaging of the shoulder and cervical region showed mild cervical spondylosis and a questionable right apical mass. A subsequent high-resolution computed tomography scan of the chest revealed a large right apical lung mass, with chest wall invasion and erosion of the adjacent ribs. Biopsy of the mass confirmed poorly differentiated non-small cell lung cancer. Radiation therapy was initiated, and the patient’s pain improved significantly. Given the size of the tumor, chemotherapy was recommended by the oncology team. The patient decided against chemotherapy.

Conclusion

This case highlights the importance of early diagnosis by expanding the differential diagnosis in patients presenting with weakness, sensory loss, and shoulder pain beyond radiculopathy or joint-related diseases. A comprehensive history and careful examination may lead to an earlier diagnosis, more appropriate treatment, and better outcome in cases of Pancoast tumor presenting with neuropathic or musculoskeletal pain.
Rapid and robust derivation of mesenchymal stem cells from human pluripotent stem cells via temporal induction of neuralized ectoderm
Authors: Jin Wei , He Yi , Li Tuo , Long Fei , Qin Xin , Yuan Yuan , Gao Ge , Shakhawat Hosen Md , Liu Xinguang , Jin Guoxiang , Zhou Zhongjun
Published: March 2022

Background

Mesenchymal stem cells (MSCs) are emerging as the mainstay of regenerative medicine because of their ability to differentiate into multiple cell lineages. The infinite proliferative potential of human pluripotent stem cells (PSCs) grants an unlimited supply of MSCs. Despite their great potential in therapeutic applications, several drawbacks have hindered its clinical translation, including limited number of replication, compromised potential and altered function in late passages. The aim of this study is to establish an efficient method for the production of MSCs from pluripotent stem cells for potential clinical application in rare human disease Hutchinson-Gilford progeria syndrome.

Results

We established a robust method allowing rapid derivation of MSCs from both human iPSCs and ESCs via a temporal induction of neural ectoderm in chemically defined media. The iPSC- and ESC-derived MSCs satisfy the standard criteria of surface markers. They exhibited a high tri-lineage differentiation potential with over 90% transcriptional similarity to the primary MSCs derived from bone marrow. To evaluate the potential application of this method in disease modeling, MSCs were generated from iPSCs derived from a patient with Hutchinson-Gilford progeria syndrome (HGPS-MSCs) and from mutation-rectified HGPS-iPSCs (cHGPS-MSCs). HGPS-MSCs manifested accelerated senescence whereas mutation rectification rescued cellular senescence in HGPS-MSCs.

Conclusions

The robust method of MSC derivation from ESCs and iPSCs provides an efficient approach to rapidly generate sufficient MSCs for in vitro disease modeling and clinical applications.
TSLP regulates mitochondrial ROS-induced mitophagy via histone modification in human monocytes
Authors: Lin Yi-Ching , Lin Yu-Chih , Tsai Mei-Lan , Liao Wei-Ting , Hung Chih-Hsing
Published: March 2022

Background

Thymic stromal lymphopoietin (TSLP) is a Th2-like cytokine involved in asthma pathogenesis. Excessive reactive oxygen species (ROS) production can lead to airway inflammation, hyperresponsiveness and remodeling. Mitophagy, followed by ROS production, is the selective degradation of mitochondria by autophagy and often occurs in defective mitochondria. In the present study, we aimed to examine the effects of TSLP on ROS production and mitophagy in human monocytes and to investigate the underlying mechanisms, including epigenetic regulation.

Results

TSLP induced ROS generation, and the effects were reversed by the antioxidant N-acetylcysteine (NAC) in THP-1 cells. Transmission electron microscopy images showed donut-shaped mitochondria that lost the cristae ultrastructure after TSLP stimulation. A decrease in mitochondrial membrane potential, decreased MTCO2 expression, and increased mitochondrial DNA release after TSLP stimulation were found. TSLP enhanced mitochondrial complex I and complex II/III activity and increased mitochondrial copy numbers and the expression of the complex II SHDA gene. TSLP-induced SHDA expression was inhibited by the histone acetyltransferase inhibitor anacardic acid (AA) and the histone methyltransferase inhibitor methylthioadenosine (MTA), and chromatin immunoprecipitation assays revealed that TSLP enhanced H3 acetylation, H4 acetylation, and H3K4 and H3K36 trimethylation in the SHDA promoter. Confocal laser microscopy showed that TSLP treatment increased the signals of the mitophagy-related proteins PINK1, LC3, phospho-parkin and phospho-ubiquitin, and pretreatment with AA and MTA reduced TSLP-induced PINK1 and LC3 accumulation in mitochondria. Western blot analysis showed that TSLP significantly increased phosphor-AMPK signal intensity, and the effects were inhibited by the antioxidant NAC. The increased signal intensities of the mitophagy-related proteins PINK1, Parkin and LC3 I/II were decreased by dorsomorphin, an AMPK inhibitor. TSLP decreased M1-related cytokine CXCL-10 production and increased M2-related cytokine CCL-1 and CCL-22 production, which was suppressed by the mitophagy inhibitor Mdivi-1 and PINK1 gene knockdown.

Conclusions

Epithelial-derived TSLP regulates ROS production and mitophagy through AMPK activation and histone modification and alters M1/M2 chemokine expression in human monocytes.

Graphical Abstract
Clinical impact of ventilator-associated pneumonia in patients with the acute respiratory distress syndrome: a retrospective cohort study
Authors: Le Pape Marc , Besnard Céline , Acatrinei Camelia , Guinard Jérôme , Boutrot Maxime , Genève Claire , Boulain Thierry , Barbier François
Published: March 2022

Background

The clinical impact and outcomes of ventilator-associated pneumonia (VAP) have been scarcely investigated in patients with the acute respiratory distress syndrome (ARDS).

Methods

Patients admitted over an 18-month period in two intensive care units (ICU) of a university-affiliated hospital and meeting the Berlin criteria for ARDS were retrospectively included. The association between VAP and the probability of death at day 90 (primary endpoint) was appraised through a Cox proportional hazards model handling VAP as a delay entry variable. Secondary endpoints included (i) potential changes in the PaO2/FiO2 ratio and SOFA score values around VAP (linear mixed modelling), and (ii) mechanical ventilation (MV) duration, numbers of ventilator- and vasopressor-free days at day 28, and length of stay (LOS) in patients with and without VAP (median or absolute risk difference calculation). Subgroup analyses were performed in patients with COVID-19-related ARDS and those with ARDS from other causes.

Results

Among the 336 included patients (101 with COVID-19 and 235 with other ARDS), 176 (52.4%) experienced a first VAP. VAP induced a transient and moderate decline in the PaO2/FiO2 ratio without increase in SOFA score values. VAP was associated with less ventilator-free days (median difference and 95% CI, − 19 [− 20; − 13.5] days) and vasopressor-free days (− 5 [− 9; − 2] days) at day 28, and longer ICU (+ 13 [+ 9; + 15] days) and hospital (+ 11.5 [+ 7.5; + 17.5] days) LOS. These effects were observed in both subgroups. Overall day-90 mortality rates were 35.8% and 30.0% in patients with and without VAP, respectively (P = 0.30). In the whole cohort, VAP (adjusted HR 3.16, 95% CI 2.04–4.89, P < 0.0001), the SAPS-2 value at admission, chronic renal disease and an admission for cardiac arrest predicted death at day 90, while the COVID-19 status had no independent impact. When analysed separately, VAP predicted death in non-COVID-19 patients (aHR 3.43, 95% CI 2.11–5.58, P < 0.0001) but not in those with COVID-19 (aHR 1.19, 95% CI 0.32–4.49, P = 0.80).

Conclusions

VAP is an independent predictor of 90-day mortality in ARDS patients. This condition exerts a limited impact on oxygenation but correlates with extended MV duration, vasoactive support, and LOS.
MetaPop: a pipeline for macro- and microdiversity analyses and visualization of microbial and viral metagenome-derived populations
Authors: Gregory Ann C. , Gerhardt Kenji , Zhong Zhi-Ping , Bolduc Benjamin , Temperton Ben , Konstantinidis Konstantinos T. , Sullivan Matthew B.
Published: March 2022

Background

Microbes and their viruses are hidden engines driving Earth’s ecosystems from the oceans and soils to humans and bioreactors. Though gene marker approaches can now be complemented by genome-resolved studies of inter-(macrodiversity) and intra-(microdiversity) population variation, analytical tools to do so remain scattered or under-developed.

Results

Here, we introduce MetaPop, an open-source bioinformatic pipeline that provides a single interface to analyze and visualize microbial and viral community metagenomes at both the macro- and microdiversity levels. Macrodiversity estimates include population abundances and α- and β-diversity. Microdiversity calculations include identification of single nucleotide polymorphisms, novel codon-constrained linkage of SNPs, nucleotide diversity (π and θ), and selective pressures (pN/pS and Tajima’s D) within and fixation indices (FST) between populations. MetaPop will also identify genes with distinct codon usage. Following rigorous validation, we applied MetaPop to the gut viromes of autistic children that underwent fecal microbiota transfers and their neurotypical peers. The macrodiversity results confirmed our prior findings for viral populations (microbial shotgun metagenomes were not available) that diversity did not significantly differ between autistic and neurotypical children. However, by also quantifying microdiversity, MetaPop revealed lower average viral nucleotide diversity (π) in autistic children. Analysis of the percentage of genomes detected under positive selection was also lower among autistic children, suggesting that higher viral π in neurotypical children may be beneficial because it allows populations to better “bet hedge” in changing environments. Further, comparisons of microdiversity pre- and post-FMT in autistic children revealed that the delivery FMT method (oral versus rectal) may influence viral activity and engraftment of microdiverse viral populations, with children who received their FMT rectally having higher microdiversity post-FMT. Overall, these results show that analyses at the macro level alone can miss important biological differences.

Conclusions

These findings suggest that standardized population and genetic variation analyses will be invaluable for maximizing biological inference, and MetaPop provides a convenient tool package to explore the dual impact of macro- and microdiversity across microbial communities.
Socioeconomic disadvantage and ethnicity are associated with large differences in children’s working memory ability: analysis of a prospective birth cohort study following 13,500 children
Authors: Mooney Kate E. , Pickett Kate E. , Shire Katy , Allen Richard J. , Waterman Amanda H.
Published: March 2022

Working memory is a limited capacity system that stores and processes information over short time periods and is essential for learning new information. Some studies have investigated the associations between socioeconomic position and working memory, however none have examined this across potentially dissociable aspects of working memory. Further, there are very few studies about children’s working memory differences across and within different ethnic groups. Therefore, there is a need to understand the potential associations between socioeconomic position, ethnicity, and different aspects of children’s working memory. We investigated children’s working memory (n = 15,154) by socioeconomic group, using a latent class measure of family socioeconomic position, and then by ethnic group. To account for potential problems in applying socioeconomic measures across different ethnic groups, we then examined associations using an ethnic-specific socioeconomic measure within the ethnic majority group (White British) and the largest ethnic minority group (Pakistani). We found a strong association between socioeconomic group at birth and working memory at age 7–10 years, where the difference between the least and most deprived socioeconomic groups was equivalent to at least a 1-year age difference. We also found substantial differences in working memory between nine ethnic groups that varied by working memory task, where the difference between groups was equivalent to an age difference of between 6 and 24 months. Finally, we found evidence for a socioeconomic gradient in working memory for White British children, but this was considerably reduced in Pakistani children. These findings show the importance of separating out different ethnic groups when investigating associations between socioeconomic position and cognitive function, and that researchers need to be mindful when applying socioeconomic measures across ethnic groups. Where possible, ethnic-specific measures of socioeconomic position should be developed and applied for studies like these. Future research considering the possible mechanisms behind associations between ethnicity and working memory, and mechanisms by which socioeconomic position differentially influences working memory performance for different ethnic groups would shed further light on this important topic.
Are pro-inflammatory markers associated with psychological distress in a cross-sectional study of healthy adolescents 15–17 years of age? The Fit Futures study
Authors: Linkas Jonas , Ahmed Luai Awad , Csifcsak Gabor , Emaus Nina , Furberg Anne-Sofie , Grimnes Guri , Pettersen Gunn , Rognmo Kamilla , Christoffersen Tore
Published: March 2022

Background

Inflammatory markers have been associated with depression and anxiety disorder in adolescents. Less is known about the association between inflammation and subclinical symptoms in the form of psychological distress. We investigated prevalence of psychological distress and examined the associations between common pro-inflammatory markers and psychological distress in an adolescent population sample.

Methods

The study was based on data from 458 girls and 473 boys aged 15–17 years from the Fit Futures Study, a large-scale study on adolescent health, conducted in Northern Norway. Psychological distress was measured with the Hopkins Symptom Checklist (HSCL-10). Serum-levels of the following low-grade inflammatory markers were measured: C-reactive protein (CRP), interleukin 6 (IL-6), transforming growth factor-alpha (TGF-α), tumor necrosis factor alpha variant 1 (TRANCE) and tumor necrosis factor alpha variant 2 (TWEAK). Associations between quartiles of inflammatory markers and HSCL-10 were examined by logistic regression and adjusted for potential confounders in sex-stratified analyses.

Results

The proportion of psychological distress above cutoff were 26.9% and 10.8% among girls and boys, respectively. In both girls and boys, crude analysis showed positive associations between all inflammatory markers and HSCL-10, except for TWEAK and TRANCE in boys. However, none of these associations were statistically significant. Further, there were no significant findings in the adjusted analyses.

Conclusion

There was a higher prevalence of psychological distress in girls compared to boys. Pro-inflammatory markers were not significantly associated with psychological distress in data from healthy adolescents aged 15–17 years.
Differential impacts of e-portfolio assessment on language learners’ engagement modes and genre-based writing improvement
Authors: Pourdana Natasha , Tavassoli Kobra
Published: March 2022

Portfolio assessment (PA) as an assessmentforlearning (AfL) alternative has been under-represented in second/foreign language acquisition (SLA) research literature. This study examined the potential impacts of electronic PA (e-PA) on English-as-a-Foreign-Language (EFL) learners’ engagement modes in descriptive and narrative genres of writing on Moodle™. To do so, 56 university students were non-randomly selected and assigned into two intermediate-level EFL cohorts. In a pretest-mediation-posttest study, descriptive and narrative writing tasks completed by two groups were subjected to teacher feedback, student reflection logs, and subsequent revision every week. Results of repeated measures ANOVA indicated significant progress in lower-level skills (sentence structure, word choice/grammar, mechanics), and moderate progress in higher-level skills (organization, development) in both groups’ genre-based writing. Results of one-way ANCOVA reported the notable pretest-to-posttest achievement by both groups with no intergroup statistical differences. The content of students’ reflection logs was inductively analyzed for their behavioral, emotional, and cognitive modes of engagement in e-PA. Qualitative data analysis indicated similar writing time intervals and recurrence of revisions as the behavioral mode of both groups. Participants also expressed novelty, low anxiety, and enjoyment as their emotional experiences. In terms of their cognitive experience, the majority agreed upon the applicability of teacher feedback and positive perception of writing improvement in e-PA. Yet, they were critical to regular mismatches between the scopes of teacher assessment and self-assessment, as well as teacher linguistic bias towards certain writing features. Several pedagogical implications of the study promote the facilitating role of e-PA in genre-based academic writing and e-learning contexts.