bluuebunny/crossref_metadata_2025 huggingface dataset:
LINC00662 enhances cell progression and stemness in breast cancer by MiR-144-3p/SOX2 axis
Authors: An Congjing , Hu Zhigang , Li Yuehong , Zhao Pengxin , Liu Runtian , Zhang Qing , Zhu Peiling , Li Yanting , Wang Ying
Published: May 2022

Background

Breast cancer (BC) is one of the most prevalent malignancies among women globally. Emerging evidence indicates that long non-coding RNAs (lncRNAs) are associated with BC carcinogenesis. In the current study, we explored the mechanism by which LINC00662 regulates BC.

Methods

Quantitative real-time PCR (qRT-PCR) assessed RNA expressions while western blot for protein levels. Kaplan Meier analysis evaluated overall survival (OS). Cytoplasmic/nuclear fractionation, RNA binding protein immunoprecipitation (RIP) and luciferase reporter assays probed into the underlying molecular mechanism of LINC00662 in BC. Xenograft model was established to explore the influence of LINC00662 on BC progression in vivo. R square graphs were utilized to represent RNA relationships.

Results

LINC00662 is overtly overexpressed in BC tissues and cell lines. LINC00662 knockdown hampers cell proliferation, migration, invasion and stemness. LINC00662 expression is negatively correlated with OS of BC patients. LINC00662 up-regulates SOX2 expression by competitively binding to miR-144-3p, thereby modulating BC cell progression. Xenograft experiments verified that LINC00662 promotes BC tumor growth and cell stemness in vivo.

Conclusion

LINC00662 enhances cell proliferation, migration, invasion and stemness in BC by targeting miR-144-3p/SOX2 axis. The findings in the present study suggested that LINC00662 could be a potential therapeutic target for BC treatment.

Graphical Abstract
Boosting nutrient starvation-dominated cancer therapy through curcumin-augmented mitochondrial Ca2+ overload and obatoclax-mediated autophagy inhibition as supported by a novel nano-modulator GO-Alg@CaP/CO
Authors: Wang Xuan , Li Yunhao , Jia Fan , Cui Xinyue , Pan Zian , Wu Yan
Published: May 2022

Background

By hindering energy supply pathway for cancer cells, an alternative therapeutic strategy modality is put forward: tumor starvation therapy. And yet only in this blockade of glucose supply which is far from enough to result in sheer apoptosis of cancer cells.

Results

In an effort to boost nutrient starvation-dominated cancer therapy, here a novel mitochondrial Ca2+ modulator Alg@CaP were tailor-made for the immobilization of Glucose oxidase for depriving the intra-tumoral glucose, followed by the loading of Curcumin to augment mitochondrial Ca2+ overload to maximize the therapeutic efficiency of cancer starvation therapy via mitochondrial dysfunctions. Also, autophagy inhibitors Obatoclax were synchronously incorporated in this nano-modulator to highlight autophagy inhibition.

Conclusion

Here, a promising complementary modality for the trebling additive efficacy of starvation therapy was described for cutting off the existing energy sources in starvation therapy through Curcumin-augmented mitochondrial Ca2+ overload and Obatoclax-mediated autophagy inhibition.

Graphical Abstract
The cost-effectiveness of standalone HEPA filtration units for the prevention of airborne SARS CoV-2 transmission
Authors: Zafari Zafar , de Oliveira Pedro M. , Gkantonas Savvas , Ezeh Chinenye , Muennig Peter Alexander
Published: May 2022

Objective

Airborne infection from aerosolized SARS-CoV-2 poses an economic challenge for businesses without existing heating, ventilation, and air conditioning (HVAC) systems. The Environmental Protection Agency notes that standalone units may be used in areas without existing HVAC systems, but the cost and effectiveness of standalone units has not been evaluated.

Study design

Cost-effectiveness analysis with Monte Carlo simulation and aerosol transmission modeling.

Methods

We built a probabilistic decision-analytic model in a Monte Carlo simulation that examines aerosol transmission of SARS-CoV-2 in an indoor space. As a base case study, we built a model that simulated a poorly ventilated indoor 1000 square foot restaurant and the range of Covid-19 prevalence of actively infectious cases (best-case: 0.1%, base-case: 2%, and worst-case: 3%) and vaccination rates (best-case: 90%, base-case: 70%, and worst-case: 0%) in New York City. We evaluated the cost-effectiveness of improving ventilation rate to 12 air changes per hour (ACH), the equivalent of hospital-grade filtration systems used in emergency departments. We also provide a customizable online tool that allows the user to change model parameters.

Results

All 3 scenarios resulted in a net cost-savings and infections averted. For the base-case scenario, improving ventilation to 12 ACH was associated with 54 [95% Credible Interval (CrI): 29–86] aerosol infections averted over 1 year, producing an estimated cost savings of $152,701 (95% CrI: $80,663, $249,501) and 1.35 (95% CrI: 0.72, 2.24) quality-adjusted life years (QALYs) gained.

Conclusions

It is cost-effective to improve indoor ventilation in small businesses in older buildings that lack HVAC systems during the pandemic.
Strategies to reduce the energy content of foods pre-ordered for lunch in the workplace: a randomised controlled trial in an experimental online canteen
Authors: Breathnach Sarah , Lally Phillippa , Llewellyn Clare H. , Sutherland Alex , Koutoukidis Dimitrios A.
Published: May 2022

Background

Prompting employees to swap their usual lunches for lower-energy alternatives may help align energy intake with public health recommendations. We tested the effect of offering lower-energy swaps with and without physical activity calorie equivalent (PACE) information on the energy of lunches pre-ordered in an online hypothetical workplace canteen.

Methods

UK employed adults (n = 2,150) were invited to hypothetically pre-order their lunch from the canteen through a custom-made online platform. They were randomised 1:1:1 to: (i) control: no swaps offered; (ii) lower-energy swaps offered; or (iii) lower-energy swaps offered with PACE information. The primary outcome was the total energy ordered using analysis of covariance and controlling for the energy content of the initial items ordered. Secondary outcomes were swap acceptance rate and intervention acceptability.

Results

Participants were 54% female, had a mean age of 36.8 (SD = 11.6) and a BMI of 26.3 (SD = 5.6). Compared with an average 819 kcal energy ordered in the control, both the swaps and swaps + PACE interventions significantly reduced average energy ordered by 47 kcal (95% CI: -82 to -13, p = 0.003) and 66 kcal (95% CI: -100 to -31, p < 0.001), respectively. Compared with offering swaps only, the swaps + PACE intervention led to significantly higher swap acceptance (OR: 1.63, 95% CI: 1.27 to 2.09, p < 0.001) but did not significantly reduce energy ordered (-19 kcal, 95% CI: -53 to 16, p = 0.591). About 65% and 16% of intervention participants found the swap interventions acceptable and unacceptable, respectively, with the swaps + PACE intervention being considered more acceptable than swaps only (OR: 1.32, 95%CI: 1.09 to 1.60, p < 0.004).

Conclusion

Offering lower-energy swaps with or without PACE information reduced the energy of pre-ordered lunches experimentally. Both interventions hold promise for reducing the energy of purchased foods and drinks.

Trial Registration

As Predicted reference number: 56358, 22/01/21, https://aspredicted.org/pw2qr.pdf
Using the Kolb’s experiential learning cycle to explore the extent of application of one health competencies to solving global health challenges; a tracer study among AFROHUN-Uganda alumni
Authors: Ssekamatte Tonny , Isunju John Bosco , Nalugya Aisha , Mugambe Richard K. , Kalibala Patrick , Musewa Angella , Bikaako Winnie , Nattimba Milly , Tigaiza Arnold , Nakalembe Doreen , Osuret Jimmy , Wafula Solomon Tsebeni , Buregyeya Esther , Tsiouris Fatima , Michaels-Strasser Susan , Kabasa John David , Bazeyo William
Published: May 2022

Background

The Africa One Health University Network (AFROHUN) with support from the United States Agency for International Development (USAID), has since 2012 conducted pre and in-service One health (OH) trainings with the objective of improving global health security. These trainings aim to build competencies that, enhance a multidisciplinary approach to solving global health challenges. Despite the investment in OH trainings, there is limited documentation of the extent of acquisition and application of the OH competencies at workplaces. This tracer study explored the extent of acquisition and application of the OH competencies by the AFROHUN-Uganda alumni.

Methods

A cross-sectional study was conducted among a random sample of 182 AFROHUN-Uganda alumni of 2013–2018 cohorts. A blended approach of interviewer-administered and self-administered questionnaires was used. Virtual platforms such as Zoom, Microsoft teams, and Skype, and phone interviews were used to collect data when face-to-face interactions with alumni were not possible. Data were collected electronically, either through a link or with the aid of the KoboCollect mobile application, pre-installed on android enabled devices, and analysed using STATA14.0.

Results

The majority of respondents, 78.6% (143/182) had jobs that required application of OH knowledge and skills, 95.6% (174/182) had learned employable skills from OH activities and 89.6% (163/182) had applied such skills when searching for employment. About 21.7% (34/180) to a very high extent required OH field-specific theoretical knowledge at their workplaces, 27.4% (43/80) to a very high extent required OH field-specific practical knowledge/skills, 42.7% (67/180) to a high extent required a change in attitude and perceptions towards working with people from different disciplines, 49.0% (77/180) required collaboration and networking skills, and more than half, 51.0% (80/180) required team building skills.

Conclusions

The majority of OH alumni to a very high extent acquired and applied OH competences such as teamwork, effective communication, community entry and engagement, report writing and problem-solving skills. This study revealed the significant contribution of the AFROHUN Uganda OH activities towards supportive work environments, and highlights areas of improvement such as supporting the trainees to acquire people-management skills, innovation, and an entrepreneurial mind set.
Pressure pain thresholds in a real-world chiropractic setting: topography, changes after treatment, and clinical relevance?
Authors: Nim Casper G. , Aspinall Sasha L. , Weibel Rasmus , Steenfelt Martin G. , O’Neill Søren
Published: May 2022

Background

Changes in pain sensitivity are a commonly suggested mechanism for the clinical effect of spinal manipulative therapy (SMT). Most research has examined pressure pain thresholds (PPT) and has primarily been conducted in controlled experimental setups and on asymptomatic populations. Many important factors are likely to differ between research and clinical settings, which may affect PPT changes following SMT. Therefore, we planned to investigate PPT before and after clinical chiropractic care and investigate relationships with various potentially clinically-relevant factors.

Methods

We recruited participants from four Danish chiropractic clinics between May and August 2021. A total of 129 participants (72% of the invited) were included. We measured PPT at eight pre-determined test sites (six spinal and two extra-spinal) immediately before (pre-session) and immediately after (post-session) the chiropractic consultation.

We used regression analyses to investigate PPT changes, including the following factors: (i) vertebral distance to the nearest SMT site, (ii) rapid clinical response, (iii) baseline PPT, (iv) number of SMTs performed, (v) at the region of clinical pain compared to other regions, and (vi) if other non-SMT treatment was provided. We also performed topographic mapping of pre-session PPTs.

Results

After the consultation, there was a non-significant mean increase in PPT of 0.14 kg (95% CIs = − 0.01 to 0.29 kg). No significant associations were found with the distance between the PPT test site and nearest SMT site, the clinical response of participants to treatment, the pre-session PPT, the total number of SMTs performed, or the region/s of clinical pain. A small increase was observed if myofascial treatment was also provided. Topographic mapping found greater pre-session PPTs in a caudal direction, not affected by the region/s of clinical pain.

Conclusions

This study of real-world chiropractic patients failed to demonstrate a substantial local or generalized increase in PPT following a clinical encounter that included SMT. This runs counter to prior laboratory research and questions the generalizability of highly experimental setups investigating the effect of SMT on PPT to clinical practice.
Feasibility of postoperative spine stereotactic body radiation therapy in proximity of carbon and titanium hybrid implants using a robotic radiotherapy device
Authors: Henzen Dominik , Schmidhalter Daniel , Guyer Gian , Stenger-Weisser Anna , Ermiş Ekin , Poel Robert , Deml Moritz Caspar , Fix Michael Karl , Manser Peter , Aebersold Daniel Matthias , Hemmatazad Hossein
Published: May 2022

Background and purpose

To assess the feasibility of postoperative stereotactic body radiation therapy (SBRT) for patients with hybrid implants consisting of carbon fiber reinforced polyetheretherketone and titanium (CFP-T) using CyberKnife.

Materials and methods

All essential steps within a radiation therapy (RT) workflow were evaluated. First, the contouring process of target volumes and organs at risk (OAR) was done for patients with CFP-T implants. Second, after RT-planning, the accuracy of the calculated dose distributions was tested in a slab phantom and an anthropomorphic phantom using film dosimetry. As a third step, the accuracy of the mandatory image guided radiation therapy (IGRT) including automatic matching was assessed using the anthropomorphic phantom. For this goal, a standard quality assurance (QA) test was modified to carry out its IGRT part in presence of CFP-T implants.

Results

Using CFP-T implants, target volumes could precisely delineated. There was no need for compromising the contours to overcome artifact obstacles. Differences between measured and calculated dose values were below 11% for the slab phantom, and at least 95% of the voxels were within 5% dose difference. The comparisons for the anthropomorphic phantom showed a gamma-passing rate (5%, 1 mm) of at least 97%. Additionally the test results with and without CFP-T implants were comparable. No issues concerning the IGRT were detected. The modified machine QA test resulted in a targeting error of 0.71 mm, which corresponds to the results of the unmodified standard tests.

Conclusion

Dose calculation and delivery of postoperative spine SBRT is feasible in proximity of CFP-T implants using a CyberKnife system.
“Why them, why me, why us?” The experiences of parents of children with lysosomal acid lipase deficiency: an interpretative phenomenological analysis study
Authors: Hassall S. , Smith D. M. , Rust S. , Jones S. A. , Wittkowski A.
Published: May 2022

Background

Lysosomal acid lipase deficiency (LALD) is an ultra-rare, inherited metabolic disease within the category of lysosomal storage disorders, affecting an infant’s ability to metabolise cholesterol. Developments in treatment, including Enzyme Replacement Therapy, have proven successful, with some children living for a number of years with treatment, although the future still remains unknown. The aim of this study was to explore the lived experiences of parents of children with LALD.

Main text

Participants were recruited from across the United Kingdom between 2020 and 2021. Eight parents (five mothers and three fathers) whose child had a confirmed diagnosis of LALD were interviewed. Data collected from the semi-structured interviews were audio-record, transcribed and analysed using Interpretative Phenomenological Analysis (IPA). Three superordinate and nine subordinate themes emerged from the data: (1)Uncertainty—a double-edged sword(plunged into an uncertain world, living life with worry and walking the tightrope of stability), (2)Powerless against a shared battle with LALD(a helpless parent, a joint battle, protection against distress and a vulnerable parent needing help) and 3)Accepting a life with LALD(coming to terms with a diagnosis of LALD and a hidden condition).

Conclusions

The findings of this study highlight that the diagnosis of LALD proves to be a very challenging and emotionally distressing time in parents’ lives, with increased uncertainty about what the future will hold for their child. This study signified the importance of healthcare pathways and service provisions to support parents and their children throughout diagnosis and beyond.
Clinical and genetic spectrums of 413 North African families with inherited retinal dystrophies and optic neuropathies
Authors: Bouzidi Aymane , Charoute Hicham , Charif Majida , Amalou Ghita , Kandil Mostafa , Barakat Abdelhamid , Lenaers Guy
Published: May 2022

Background

Inherited retinal dystrophies (IRD) and optic neuropathies (ION) are the two major causes world-wide of early visual impairment, frequently leading to legal blindness. These two groups of pathologies are highly heterogeneous and require combined clinical and molecular diagnoses to be securely identified. Exact epidemiological studies are lacking in North Africa, and genetic studies of IRD and ION individuals are often limited to case reports or to some families that migrated to the rest of the world. In order to improve the knowledge of their clinical and genetic spectrums in North Africa, we reviewed published data, to illustrate the most prevalent pathologies, genes and mutations encountered in this geographical region, extending from Morocco to Egypt, comprising 200 million inhabitants.

Main body

We compiled data from 413 families with IRD or ION together with their available molecular diagnosis. The proportion of IRD represents 82.8% of index cases, while ION accounted for 17.8%. Non-syndromic IRD were more frequent than syndromic ones, with photoreceptor alterations being the main cause of non-syndromic IRD, represented by retinitis pigmentosa, Leber congenital amaurosis, and cone-rod dystrophies, while ciliopathies constitute the major part of syndromic-IRD, in which the Usher and Bardet Biedl syndromes occupy 41.2% and 31.1%, respectively. We identified 71 ION families, 84.5% with a syndromic presentation, while surprisingly, non-syndromic ION are scarcely reported, with only 11 families with autosomal recessive optic atrophies related toOPA7andOPA10variants, or with the mitochondrial related Leber ION. Overall, consanguinity is a major cause of these diseases within North African countries, as 76.1% of IRD and 78.8% of ION investigated families were consanguineous, explaining the high rate of autosomal recessive inheritance pattern compared to the dominant one. In addition, we identified many founder mutations in small endogamous communities.

Short conclusion

As both IRD and ION diseases constitute a real public health burden, their under-diagnosis in North Africa due to the absence of physicians trained to the identification of inherited ophthalmologic presentations, together with the scarcity of tools for the molecular diagnosis represent major political, economic and health challenges for the future, to first establish accurate clinical diagnoses and then treat patients with the emergent therapies.
Tumor organoids: applications in cancer modeling and potentials in precision medicine
Authors: Xu Hanxiao , Jiao Dechao , Liu Aiguo , Wu Kongming
Published: May 2022

Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity is associated with metastasis, relapse, and therapy resistance. These factors contribute to treatment failure and an unfavorable prognosis. Personalized tumor models faithfully capturing the tumor heterogeneity of individual patients are urgently needed for precision medicine. Advances in stem cell culture have given rise to powerful organoid technology for the generation of in vitro three-dimensional tissues that have been shown to more accurately recapitulate the structures, specific functions, molecular characteristics, genomic alterations, expression profiles, and tumor microenvironment of primary tumors. Tumoroids in vitro serve as an important component of the pipeline for the discovery of potential therapeutic targets and the identification of novel compounds. In this review, we will summarize recent advances in tumoroid cultures as an excellent tool for accurate cancer modeling. Additionally, vascularization and immune microenvironment modeling based on organoid technology will also be described. Furthermore, we will summarize the great potential of tumor organoids in predicting the therapeutic response, investigating resistance-related mechanisms, optimizing treatment strategies, and exploring potential therapies. In addition, the bottlenecks and challenges of current tumoroids will also be discussed in this review.
PIK3CA-related overgrowth with an uncommon phenotype: case report
Authors: Rotunno Roberta , Diociaiuti Andrea , Pisaneschi Elisa , Carnevale Claudia , Dentici Marialisa , El Hachem May
Published: May 2022

Background

Megalencephaly-capillary malformation syndrome is a rare multiple-malformation syndrome secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway. This is included in a heterogeneous group of disorders, now defined “PIK3CA-related overgrowth spectrum”.

Case presentation

We report a 22-months-old female presenting an uncommon phenotype associated with a genetic mosaicism in the PIK3CA gene, detected on DNA extracted from blood peripheral and tissue biopsy.

Conclusions

NGS is the preferred method for molecular diagnosis of PROS on affected skin and overgrown tissues as primary samples. The wide phenotypic variability is based on the distribution of mosaicism, in fact the same mutation can cause different PIK3CA related disorders. Continuous understanding of the clinical spectrum and of molecular basis of PROS and their overlap will lead to improve diagnosis, management and new treatment strategies.
Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial
Authors: Stahl Klaus , Wand Philipp , Seeliger Benjamin , Wendel-Garcia Pedro David , Schmidt Julius J. , Schmidt Bernhard M. W. , Sauer Andrea , Lehmann Felix , Budde Ulrich , Busch Markus , Wiesner Olaf , Welte Tobias , Haller Hermann , Wedemeyer Heiner , Putensen Christian , Hoeper Marius M. , Bode Christian , David Sascha
Published: May 2022

Background

Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy.

Methods

In the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE.

Results

A continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004).

Conclusions

Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints.

Trial registration Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994).
Globally elevated excitation–inhibition ratio in children with autism spectrum disorder and below-average intelligence
Authors: Manyukhina Viktoriya O. , Prokofyev Andrey O. , Galuta Ilia A. , Goiaeva Dzerassa E. , Obukhova Tatiana S. , Schneiderman Justin F. , Altukhov Dmitrii I. , Stroganova Tatiana A. , Orekhova Elena V.
Published: May 2022

Background

Altered neuronal excitation–inhibition (E–I) balance is strongly implicated in ASD. However, it is not known whether the direction and degree of changes in the E–I ratio in individuals with ASD correlates with intellectual disability often associated with this developmental disorder. The spectral slope of the aperiodic 1/f activity reflects the E–I balance at the scale of large neuronal populations and may uncover its putative alternations in individuals with ASD with and without intellectual disability.

Methods

Herein, we used magnetoencephalography (MEG) to test whether the 1/f slope would differentiate ASD children with average and below–average (< 85) IQ. MEG was recorded at rest with eyes open/closed in 49 boys with ASD aged 6–15 years with IQ ranging from 54 to 128, and in 49 age-matched typically developing (TD) boys. The cortical source activity was estimated using the beamformer approach and individual brain models. We then extracted the 1/f slope by fitting a linear function to the log–log-scale power spectra in the high-frequency range.

Results

The global 1/f slope averaged over all cortical sources demonstrated high rank-order stability between the two conditions. Consistent with previous research, it was steeper in the eyes-closed than in the eyes-open condition and flattened with age. Regardless of condition, children with ASD and below-average IQ had flatter slopes than either TD or ASD children with average or above-average IQ. These group differences could not be explained by differences in signal-to-noise ratio or periodic (alpha and beta) activity.

Limitations

Further research is needed to find out whether the observed changes in E–I ratios are characteristic of children with below-average IQ of other diagnostic groups.

Conclusions

The atypically flattened spectral slope of aperiodic activity in children with ASD and below-average IQ suggests a shift of the global E–I balance toward hyper-excitation. The spectral slope can provide an accessible noninvasive biomarker of the E–I ratio for making objective judgments about treatment effectiveness in people with ASD and comorbid intellectual disability.
Dried rhododendron flower ingestion presenting with bradycardia and hypotension: a case report
Authors: Baral Sushil , Baral Binaya Kumar , Sharma Pranit , Shrestha Surendra Lal
Published: May 2022

Background

Rhododendron toxicity can be a life-threatening situation when manifested; it results in bradycardia and hypotension. Treatment remains challenging when it is complicated with refractory hypotension involving the multiorgan system if not treated early.

Case presentation

A 33-year-old Magar male presented with history of ingestion of two handfuls of white rhododendron flower. He had ingested the flowers believing that it would help relieve the pain and remove the materials stuck in his food pipe. Symptoms presented included muscular discomfort, dizziness, nausea, palpitation, tingling sensation around the face and lips, difficulty breathing, chest tightness, and difficulty swallowing within 4–5 hours after the ingestion of the dried flower. High-flow oxygen, intravenous fluids, atropine, and other supportive measures were used during the emergency, followed later by transfer to the intensive care unit for further observation.

Conclusion

The patient was discharged with complete recovery after 2 days of hospital stay. Intentional or accidental ingestion of toxic plants can be severe or even life-threatening. Thus, clinicians should be familiar with local toxic plants with grayanotoxin action.
Epiregulin increases stemness-associated genes expression and promotes chemoresistance of non-small cell lung cancer via ERK signaling
Authors: Zhang Yujia , Qiu Fengjun , Ye Tingjie , Lee Sau Har , Xu Jiatuo , Jia Lingyan , Zeng Rui , Wang Xiaoling , Hu Xudong , Yan Xiaofeng , Li Hua , Lu Yanlin , Wang Xiaoling , Jiang Rilei , Xu Wei
Published: May 2022

Background

Chemoresistance often causes the failure of treatment and death of patients with advanced non-small-cell lung cancer. However, there is still no resistance genes signature and available enriched signaling derived from a comprehensive RNA-Seq data analysis of lung cancer patients that could act as a therapeutic target to re-sensitize the acquired resistant cancer cells to chemo-drugs. Hence, in this study, we aimed to identify the resistance signature for clinical lung cancer patients and explore the regulatory mechanism.

Method

Analysis of RNA-Seq data from clinical lung cancer patients was conducted in R studio to identify the resistance signature. The resistance signature was validated by survival time of lung cancer patients and qPCR in chemo-resistant cells. Cytokine application, small-interfering RNA and pharmacological inhibition approaches were applied to characterize the function and molecular mechanism of EREG and downstream signaling in chemoresistance regulation via stemness.

Results

The RTK and vitamin D signaling were enriched among resistance genes, where 6 genes were validated as resistance signature and associated with poor survival in patients. EREG/ERK signaling was activated by chemo-drugs in NSCLC cells. EREG protein promoted the NSCLC resistance to chemo-drugs by increasing stemness genes expression. Additionally, inhibition of EREG/ErbB had downregulated ERK signaling, resulting in decreased expression of stemness-associated genes and subsequently re-sensitized the resistant NSCLC cells and spheres to chemo-drugs.

Conclusions

These findings revealed 6 resistance genes signature and proved that EREG/ErbB regulated the stemness to maintain chemoresistance of NSCLC via ERK signaling. Therefore, targeting EREG/ErbB might significantly and effectively resolve the chemoresistance issue.
Therapeutic role of mesenchymal stem cell-derived exosomes in respiratory disease
Authors: Zargar Mehdi Jahedi , Kaviani Saeid , Vasei Mohammad , Soufi Zomorrod Mina , Heidari Keshel Saeed , Soleimani Masoud
Published: May 2022

Exosomes are extracellular vesicles found in various tissues, blood circulation, and tissue fluids, secreted into the extracellular environment by fusing a multivesicular body with a plasma membrane. Various cell types release these vesicles to contribute to many cellular functions, including intercellular communication, cell proliferation, differentiation, angiogenesis, response to stress, and immune system signaling. These natural nanoparticles have therapeutic effects in various diseases and exhibit a behavior similar to the cell from which they originated. In the meantime, exosomes derived from mesenchymal stem cells have attracted the attention of many researchers and physicians due to their unique ability to modulate the immune system, repair tissue and reduce inflammation. Numerous clinical and preclinical studies have examined the effect of MSC-derived exosomes in various diseases, and their results have been published in prestigious journals. This review article discusses the biogenesis and sources of exosomes, MSC-derived exosomes, the use of these exosomes in regenerative medicine, and treatments based on exosomes derived from stem cells in respiratory diseases.
Incidence of myocardial infarction in people with diabetes compared to those without diabetes: a systematic review protocol
Authors: Narres Maria , Kvitkina Tatjana , Claessen Heiner , Ubach Ellen , Wolff Georg , Metzendorf Maria-Inti , Richter Bernd , Icks Andrea
Published: May 2022

Background

Diabetes mellitus is an established risk factor for acute myocardial infarction (AMI). Incidence of AMI in people with diabetes remains significantly higher than in those without diabetes. However, published data are conflicting, and previous reviews in this field have some limitations regarding the definitions of AMI and source population (general population or people with diabetes as a population at risk) and concerning the statistical presentation of results.

Aims

To analyse the incidence of AMI in people with diabetes compared to those without diabetes and to investigate time trends.

Methods

We will perform a systematic literature search in MEDLINE, Embase and LILACS designed by an experienced information scientist. Two review authors will independently screen the abstracts and full texts of all references on the basis of inclusion criteria regarding types of study, types of population and the main outcome. Data extraction and assessment of risk of bias will be undertaken by two review authors working independently. We will assess incidence rate or cumulative incidence and relative risk of AMI comparing populations with and without diabetes.

Discussion

This review will summarise the available data concerning the incidence of AMI in people with and without diabetes and will thus contribute to the assessment and interpretation of the wide variations of incidence, relative risks and time trends of AMI in these populations.

Systematic review registration

PROSPERO CRD42020145562
A note on boundary point principles for partial differential inequalities of elliptic type
Authors: Meyer John Christopher
Published: May 2022

In this note we consider boundary point principles for partial differential inequalities of elliptic type. First, we highlight the difference between the conditions required to establish classical strong maximum principles and classical boundary point lemmas for second-order linear elliptic partial differential inequalities. We highlight this difference by introducing a singular set in the domain where the coefficients of the partial differential inequality need not be defined and, in a neighborhood of which, can blow-up. Secondly, as a consequence, we establish a comparison-type boundary point lemma for classical elliptic solutions to quasilinear partial differential inequalities. Thirdly, we consider tangency principles, for$C^{1}$C1elliptic weak solutions to quasilinear divergence structure partial differential inequalities. We highlight the necessity of certain hypotheses in the aforementioned results via simple examples.
Impact of socio-demographic and economic factors on intimate partner violence justification among women in union in Papua New Guinea
Authors: Adu Collins , Asare Bernard Yeboah-Asiamah , Agyemang-Duah Williams , Adomako Emmanuel Brenyah , Agyekum Amma Kyewaa , Peprah Prince
Published: May 2022

Background

Justification of intimate partner violence (IPV) has several implications, including reduced likelihood of help-seeking, increased experiences episodes of partner abuses, and poor health status and outcomes. However, in Papua New Guinea (PNG), where IPV is among the highest globally, little is known about factors influencing IPV justification among women in union. This study aimed at examining the prevalence of IPV justification and associated factors among women in union in PNG.

Methods

Data from the nationally representative cross-sectional demographic and health survey conducted among women aged 15–49 years during 2016–2018 in PNG were used. In all 9,943 women aged 15–49 years who were married or cohabiting during the survey were included. Bivariate and multivariate logistic regressions were performed and the results reported as crude odds ratios (cOR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI).

Results

Overall, almost 7 in 10 women (68.9%, 95%CI:68.0–69.9) justified IPV. Multiple regression analysis revealed that co-habitation (aOR: 1.33, 95%CI: 1.17–1.50, p < 0.001), polygyny (aOR: 1.36, 95%CI: 1.20–1.53, p < 0.001), exposure to television (aOR: 1.24, 95%CI: 1.08–1.42, p = 0.002) and richer wealth status (aOR: 1.19, 95%CI: 1.01–1.40, p = 0.035), significantly increased the odds of justifying IPV. We found significantly lower odds of IPV justification among women aged 45–49 years (aOR: 0.53, 95%CI: 0.37–0.77, p = 0.001) and those with higher level of education (aOR: 0.56, 95%CI: 0.42–0.74, p < 0.001).

Conclusion

The prevalence of IPV justification was high among women in union in PNG. Women’s justification of IPV was associated with socio-demographic and economic factors. Our findings call for appropriate strategies including public education and empowerment programmes that target IPV in PNG. Moreover, strategies and interventions to address IPV justification should target the women’s socio-economic and demographic contexts that influence IPV justification.
Prospective assessment of energy technologies: a comprehensive approach for sustainability assessment
Authors: Haase M. , Wulf C. , Baumann M. , Rösch C. , Weil M. , Zapp P. , Naegler T.
Published: May 2022

Background

A further increase in renewable energy supply is needed to substitute fossil fuels and combat climate change. Each energy source and respective technologies have specific techno-economic and environmental characteristics as well as social implications. This paper presents a comprehensive approach for prospective sustainability assessment of energy technologies developed within the Helmholtz Initiative “Energy System 2050” (ES2050).

Methods

The “ES2050 approach” comprises environmental, economic, and social assessment. It includes established life cycle based economic and environmental indicators, and social indicators derived from a normative concept of sustainable development. The elaborated social indicators, i.e. patent growth rate, acceptance, and domestic value added, address three different socio-technical areas, i.e. innovation (patents), public perception (acceptance), and public welfare (value added).

Results

The implementation of the “ES2050 approach” is presented exemplarily and different sustainability indicators and respective results are discussed based on three emerging technologies and corresponding case studies: (1) synthetic biofuels for mobility; (2) hydrogen from wind power for mobility; and (3) batteries for stationary energy storage. For synthetic biofuel, the environmental advantages over fossil gasoline are most apparent for the impact categories Climate Change and Ionizing Radiation—human health. Domestic value added accounts for 66% for synthetic biofuel compared to 13% for fossil gasoline. All hydrogen supply options can be considered to become near to economic competitiveness with fossil fuels in the long term. Survey participants regard Explosion Hazard as the most pressing concern about hydrogen fuel stations. For Li-ion batteries, the results for patent growth rate indicate that they enter their maturity phase.

Conclusions

The “ES2050 approach” enables a consistent prospective sustainability assessment of (emerging) energy technologies, supporting technology developers, decision-makers in politics, industry, and society with knowledge for further evaluation, steering, and governance. The approach presented is considered rather a starting point than a blueprint for the comprehensive assessment of renewable energy technologies though, especially for the suggested social indicators, their significance and their embedding in context scenarios for prospective assessments.
First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda
Authors: Kabahita Jupiter Marina , Kabugo Joel , Kakooza Francis , Adam Isa , Guido Ocung , Byabajungu Henry , Namutebi Joanitah , Namaganda Maria Magdalene , Lutaaya Pius , Otim James , Kakembo Fredrick Elishama , Kanyerezi Stephen , Nabisubi Patricia , Sserwadda Ivan , Kasule George William , Nakato Hasfah , Musisi Kenneth , Oola Denis , Joloba Moses L. , Mboowa Gerald
Published: May 2022

Background

Uganda remains one of the countries with the highest burden of TB/HIV. Drug-resistant TB remains a substantial challenge to TB control globally and requires new strategic effective control approaches. Drug resistance usually develops due to inadequate management of TB patients including improper treatment regimens and failure to complete the treatment course which may be due to an unstable supply or a lack of access to treatment, as well as patient noncompliance.

Methods

Two sputa samples were collected from Xpert MTB/RIF® assay-diagnosed multi-drug resistant tuberculosis (MDR-TB) patient at Lira regional referral hospital in northern Uganda between 2020 and 2021 for comprehensive routine mycobacterial species identification and drug susceptibility testing using culture-based methods. Detection of drug resistance-conferring genes was subsequently performed using whole-genome sequencing with Illumina MiSeq platform at the TB Supranational Reference Laboratory in Uganda.

Results

In both isolates, extensively drug-resistant TB (XDR-TB) was identified including resistance to Isoniazid (katG p.Ser315Thr), Rifampicin (rpoB p.Ser450Leu), Moxifloxacin (gyrA p.Asp94Gly), Bedaquiline (Rv0678 Glu49fs), Clofazimine (Rv0678 Glu49fs), Linezolid (rplC Cys154Arg), and Ethionamide (ethA c.477del). Further analysis of these two high quality genomes revealed that this 32 years-old patient was infected with the Latin American Mediterranean TB strain (LAM).

Conclusions

This is the first identification of extensively drug-resistant Mycobacterium tuberculosis clinical isolates with bedaquiline, linezolid and clofazimine resistance from Uganda. These acquired resistances were because of non-adherence as seen in the patient’s clinical history. Our study also strongly highlights the importance of combating DR-TB in Africa through implementing next generation sequencing that can test resistance to all drugs while providing a faster turnaround time. This can facilitate timely clinical decisions in managing MDR-TB patients with non-adherence or lost to follow-up.
A selected population study reveals the biochemical mechanism of intramuscular fat deposition in chicken meat
Authors: Cui Huanxian , Liu Lu , Liu Xiaojing , Wang Yongli , Luo Na , Tan Xiaodong , Zhu Yuting , Liu Ranran , Zhao Guiping , Wen Jie
Published: May 2022

Background

Increasing intramuscular fat (IMF) is an important strategy to improve meat quality, but the regulation mechanism of IMF deposition needs to be systematically clarified.

Results

A total of 520 chickens from a selected line with improved IMF content and a control line were used to investigate the biochemical mechanism of IMF deposition in chickens. The results showed that the increased IMF would improve the flavor and tenderness quality of chicken meat. IMF content was mainly determined both by measuring triglyceride (TG) and phospholipid (PLIP) in muscle tissue, but only TG content was found to be decisive for IMF deposition. Furthermore, the increase in major fatty acid (FA) components in IMF is mainly derived from TGs (including C16:0, C16:1, C18:1n9c, and C18:2n6c, etc.), and the inhibition of certain very-long-chain FAs would help to IMF/TG deposition.

Conclusions

Our study elucidated the underlying biochemical mechanism of IMF deposition in chicken: Prevalent accumulation of long-chain FAs and inhibitions of medium-chain FAs and very long chain FA would jointly result in the increase of TGs with the FA biosynthesis and cellular uptake ways. Our findings will guide the production of high-quality chicken meat.
An iron chelation-based combinatorial anticancer therapy comprising deferoxamine and a lactate excretion inhibitor inhibits the proliferation of cancer cells
Authors: Fujisawa Koichi , Takami Taro , Matsumoto Toshihiko , Yamamoto Naoki , Yamasaki Takahiro , Sakaida Isao
Published: May 2022

Background

Although iron chelation has garnered attention as a novel therapeutic strategy for cancer, higher levels of efficacy need to be achieved. In the present study, we examined the combinatorial effect of deferoxamine (DFO), an iron chelator, and α-cyano-4-hydroxy cinnamate (CHC), a suppressor of lactate excretion, on the proliferation of cancer cell lines.

Methods

We established a deferoxamine (DFO)-resistant cell line by culturing HeLa cells in media containing increasing concentrations of DFO. Metabolome and gene expression analyses were performed on these cells. Synergistic effect of the drugs on the cells was determined using an in vitro proliferation assay, and the combination index was estimated.

Results

DFO-resistant HeLa cells exhibited enhanced glycolysis, salvage cycle, and de novo nucleic acid synthesis and reduced mitochondrial metabolism. As DFO triggered a metabolic shift toward glycolysis and increased lactate production in cells, we treated the cancer cell lines with a combination of CHC and DFO. A synergistic effect of DFO and CHC was observed in HeLa cells; however, the same was not observed in the human liver cancer cell line Huh7. We hypothesized that the efficacy of the combination therapy in cancer cells depends on the degree of increase in lactate concentration upon DFO treatment.

Conclusion

Combination therapy involving administration of DFO and CHC is effective in cancer cells wherein DFO treatment results in an elevation in lactate levels. Our findings illustrate that the DFO-induced enhanced glycolysis provides specific targets for developing an efficient anticancer combinatorial therapy involving DFO. These findings will be beneficial for the development of novel cancer chemotherapeutics.