bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproductive health status of adolescent mothers in an Iranian setting: a cross-sectional study
Authors: Zare Maryam , Mardi Afrouz , Gaffari-moggadam Mozhgan , Nezhad-dadgar Nazila , Abazari Malek , Shadman Atefeh , Ziapour Arash
Published: April 2022

Background

In low and middle-income countries (LMICs), where millions of women give birth before the age of 18, the reproductive health status of married adolescent mothers, including family planning, sexual, psychosocial, and maternal health, remains a significant and recurring phenomenon. As a result, the purpose of this study was to assess the reproductive health status of married adolescent mothers who sought treatment at Ardabil health care centers in 2019.

Methods

A cross-sectional study was carried out in five health centers in Ardabil, Iran. This research included 312 married adolescent mothers who were under 19 years old. Health workers who asked questions of each participant completed a demographic questionnaire and the Reproductive Health Assessment Scale for Married Adolescent Women, and all data were self-reported. Univariate and multivariate linear regressions were used to determine risk factors associated with reproductive health scores. The data was examined using statistical software (SPSS version 20).

Results

The mean age (years) of the respondents was 16.41 ± 0.85, the mean age of their husbands was 24.18 ± 2.29, and the mean age of their marriage was 15.06 ± 1.15. In this study, adolescent mothers had an average reproductive health score of 63.78 ± 11.06. There was a significant association between reproductive health status and age, education, husband’s age and education, and contraceptive methods among married adolescent mothers (p < 0.05).

Conclusion

The research findings indicated that adolescent mothers had an average level of reproductive health. Several socio-demographic characteristics, including age, education, gravida, and contraception, were linked to reproductive health scores. Programmers and policymakers should prioritize improving the reproductive health of adolescent mothers through education and increasing women’s and spouses’ knowledge and awareness.
Prevalence and factors associated with adverse drug events among patients on dolutegravir-based regimen at the Immune Suppression Syndrome Clinic of Mbarara Regional Referral Hospital, Uganda: a mixed design study
Authors: Namulindwa Angella , Wasswa John Hans , Muyindike Winnie , Tamukong Robert , Oloro Joseph
Published: April 2022

Background

In low income countries such as Uganda progress has been made towards achieving the United Nations AIDS programme 95-95-95 target however efforts are still impeded by pretreatment drug resistance and adverse drug events (ADEs) hence introduction of dolutegravir-based antiretroviral therapy as first-line treatment due to a higher genetic barrier to resistance, better tolerability and safety profile. However, recent studies have raised concerns regarding its safety in real-clinical settings due to ADEs and being a recently introduced drug there is need to actively monitor for ADEs, hence this study aimed to establish the prevalence and factors associated with ADEs among patients on dolutegravir-based regimen at the Immune Suppression Syndrome (ISS) Clinic- Mbarara Regional Referral Hospital (MRRH).

Methods

A mixed design study was conducted at ISS Clinic-MRRH among 375 randomly selected patients who had been exposed to DTG-based regimen for at-least 12 weeks. These were interviewed to obtain data on socio-demographics, dietary habits and their files reviewed for ADEs. Data entry was done using Epi-data 3.0 and exported to SPSS 25.0 for analysis. Prevalence was determined as a percentage, and ADE associated factors assessed using bivariate analysis, those found significant were further subjected to multivariate analysis and considered significant at P < 0.05.

Results

The prevalence of ADEs among patients on DTG-based regimen was found to be 33.1% (124/375) with 5.6% (7/124) participants discontinued from treatment due ADEs, 4 due to hyperglycemia and 3 liver toxicity. The commonly experienced ADE was allergy at 36.3%. Male sex (AOR 1.571, 95% CI 1.433–1.984), WHO stage one at entry to care (AOR 4.586, 95% CI 1.649–12.754), stage two (AOR 4.536, 95% CI 1.611–12.776), stage three (AOR 3.638, 95% CI 1.262–10.488), were significantly associated with ADEs. Patients with undetectable viral load at initiation of DTG-based regimen were 67.6% less likely to experience ADEs (AOR = 0.324, 95% CI 0.1167–0.629).

Conclusion

This study reports a prevalence of 33.1% of ADEs among patients on DTG-based regimen. The most commonly experienced ADE was allergy. Male sex, early HIV disease stage at entry into care and detectable viral load at initiation of DTG-based regimen were significantly associated with ADEs. It is crucial to actively monitor patients with these characteristics for ADEs.
Individual and community-level determinants of non-use of contraceptive among women with no fertility desire in Ethiopia: a multilevel mixed-effect analysis
Authors: Mare Kusse Urmale , Aychiluhm Setognal Birara , Tadesse Abay Woday , Mohammed Osman Ahmed
Published: April 2022

Background

In Ethiopia, about two-third of women in the reproductive-age do not use any method of contraception. Moreover, evidence on non-use of contraceptives among women who do not have future fertility desires are limited. Therefore, this study intended to identify both individual and community-level determinants of non-use of contraceptives among this group in Ethiopia using a multilevel mixed effect analysis.

Methods

Data retrieved from the demographic and health survey program official database website (http://dhsprogram.com) were used in this study. The suvey was conducting using a multistage cluster sampling technique and a weighted sample of 4398 reproductive-age women with no fertility desire was used in this study. Four models were fitted using a multilevel multivariable logistic regression to identify determinants of non-use of contraceptives and model with the lowest Akaike’s Information Criterion was selected as a best fitted model. Adjusted odds ratio with its corresponding 95% confidence interval was used to declare the statistical significance of the independent variables.

Results

Overall, 65.3% [95% CI (63.9%, 66.7%)] of women with no fertility desire were not using any contraceptive method. Living in large central [AOR (95% CI)  0.45 (0.31, 0.67)] and metropolitan regions [AOR (95% CI) 0.39 (0.22, 0.68)] and being from household with middle [AOR (95% CI)  0.65 (0.42, 0.93)] and rich wealth index [AOR (95% CI)  0.67 (0.44, 0.98)] were negatively associated with non-use of contraceptives. Besides, being from a community with high women illiteracy [AOR (95% CI)  1.38 (1.15, 1.67)], being Muslim [AOR (95% CI)  1.86 (1.22, 2.85)], having history of pregnancy termination [AOR (95% CI) 1.59 (1.10, 2.31)], having a husband who desire to have more children [AOR (95% CI)  1.46 (1.02, 2.09)] were the positive determinants of non-utilization of contraceptives.

Conclusion

Nearly two-third of reproductive-age women with no fertility desire in Ethiopia do not use any contraceptive method. Awareness creation interventions on the benefits of contraceptives targeting Muslim religion followers and improving women education and their economic empowerment at household level may decrease the proportion of non-use of contraceptives at a national level.
A survey on the influence of CYBATHLON on the development and acceptance of advanced assistive technologies
Authors: Meyer Jan T. , Weber Selina , Jäger Lukas , Sigrist Roland , Gassert Roger , Lambercy Olivier
Published: April 2022

Background

Advanced assistive technologies (AAT) aim to exploit the vast potential of technological developments made in the past decades to improve the quality of life of people with disabilities. Combining complex robotic technologies with the unique needs of people with disabilities requires a strong focus on user-centered design to ensure that the AAT appropriately addresses the daily life struggles of target users. The CYBATHLON aims to promote this mindset by empowering the AAT target users (“pilots”) to compete on race tracks that represent approximations of daily life obstacles. The objective of this work was to investigate the AAT technology development, usability, and user involvement (i.e., application of user-centered design) in the context of the CYBATHLON.

Methods

With an online survey targeting the pilots and technical leads of teams preparing for the CYBATHLON 2020 Global Edition, we investigated to what extent the pilots were involved in device development and how this influences the perceived usability of the showcased AAT. Furthermore, the effects of user-centered design variables on the individual race performances were analyzed.

Results

A total of 81 responses from 35 pilots and 46 technical leads were collected in the two weeks prior to the event. Of all teams partaking in the included disciplines of the CYBATHLON 2020 Global Edition, 81.8% (36 of 44) were included in the study. User-centered design appeared to be a prevalent practice among the teams, as 85.7% of all pilots reported a certain level of involvement. However, only 25.5% of the pilots reported daily life usage, despite QUEST usability scores of both respondent groups showing moderate to high satisfaction with the respected AAT across all investigated disciplines. An explorative linear mixed model indicated that daily life usage (p < 0.05) and prolonged user involvement (e.g., more than 2 years, p < 0.001) have a significant positive effect on the race performance at the competition.

Conclusions

We conclude that the CYBATHLON positively fulfills its conceptual goals of promoting active participation and inclusion of people with disabilities in the design and evaluation of AAT, thereby stimulating the development of promising novel technological solutions. Also, our data could underline the value of the competition as a benchmark, highlighting remaining usability limitations or technology adoption hurdles.
Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome
Authors: Johri Amer M. , Hétu Marie-France , Heyland Daren K. , Herr Julia E. , Korol Jennifer , Froese Shawna , Norman Patrick A. , Day Andrew G. , Matangi Murray F. , Michos Erin D. , LaHaye Stephen A. , Saunders Fraser W. , Spence J. David
Published: April 2022

Background

L-carnitine (L-C), a ubiquitous nutritional supplement, has been investigated as a potential therapy for cardiovascular disease, but its effects on human atherosclerosis are unknown. Clinical studies suggest improvement of some cardiovascular risk factors, whereas others show increased plasma levels of pro-atherogenic trimethylamine N-oxide. The primary aim was to determine whether L-C therapy led to progression or regression of carotid total plaque volume (TPV) in participants with metabolic syndrome (MetS).

Methods

This was a phase 2, prospective, double blinded, randomized, placebo-controlled, two-center trial. MetS was defined as ≥ 3/5 cardiac risk factors: elevated waist circumference; elevated triglycerides; reduced HDL-cholesterol; elevated blood pressure; elevated glucose or HbA1c; or on treatment. Participants with a baseline TPV ≥ 50 mm3 were randomized to placebo or 2 g L-C daily for 6 months.

Results

The primary outcome was the percent change in TPV over 6 months. In 157 participants (L-C N = 76, placebo N = 81), no difference in TPV change between arms was found. The L-C group had a greater increase in carotid atherosclerotic stenosis of 9.3% (p = 0.02) than the placebo group. There was a greater increase in total cholesterol and LDL-C levels in the L-C arm.

Conclusions

Though total carotid plaque volume did not change in MetS participants taking L-C over 6-months, there was a concerning progression of carotid plaque stenosis. The potential harm of L-C in MetS and its association with pro-atherogenic metabolites raises concerns for its further use as a potential therapy and its widespread availability as a nutritional supplement.

Trial registration: ClinicalTrials.gov, NCT02117661, Registered April 21, 2014, https://clinicaltrials.gov/ct2/show/NCT02117661.
Safety of stereotactic body radiation therapy for localized prostate cancer without treatment planning MRI
Authors: Amarell Katherine , Jaysing Anna , Mendez Christopher , Haas Jonathan A. , Blacksburg Seth R. , Katz Aaron E. , Sanchez Astrid , Tong Angela , Carpenter Todd , Witten Matthew , Collins Sean P. , Lischalk Jonathan W.
Published: April 2022

Background

The use of treatment planning prostate MRI for Stereotactic Body Radiation Therapy (SBRT) is largely a standard, yet not all patients can receive MRI for a variety of clinical reasons. Thus, we aim to investigate the safety of patients who received CT alone based SBRT planning for the definitive treatment of localized prostate cancer.

Methods

Our study analyzed 3410 patients with localized prostate cancer who were treated with SBRT at a single academic institution between 2006 and 2020. Acute and late toxicity was evaluated using the Common Terminology Criteria for Adverse Events version 5.0. Expanded Prostate Cancer Index Composite (EPIC) questionnaires evaluated QOL and PSA nadir was evaluated to detect biochemical failures.

Results

A total of 162 patients (4.75%) received CT alone for treatment planning. The CT alone group was older relative to the MRI group (69.9 vs 67.2, p < 0.001) and had higher risk and grade disease (p < 0.001). Additionally, the CT group exhibited a trend in larger CTVs (82.56 cc vs 76.90 cc; p = 0.055), lower total radiation doses (p = 0.048), and more frequent pelvic nodal radiation versus the MRI group (p < 0.001). There were only two reported cases of Grade 3 + toxicity within the CT alone group. Quality of life data within the CT alone group revealed declines in urinary and bowel scores at one month with return to baseline at subsequent follow up. Early biochemical failure data at median time of 2.3 years revealed five failures by Phoenix definition.

Conclusions

While clinical differences existed between the MRI and CT alone group, we observed tolerable toxicity profiles in the CT alone cohort, which was further supported by EPIC questionnaire data. The overall clinical outcomes appear comparable in patients unable to receive MRI for their SBRT treatment plan with early clinical follow up.
Technical aspects and early results of uniportal video-assisted thoracoscopic complex segmentectomy: a 30 case-series study
Authors: Kong Xiang-Long , Lu Jun , Li Peng-Ju , Ni Bo-Xiong , Zhu Kai-Bin , Xu Hai , Xu Shi-Dong
Published: April 2022

Background

With the advantages of better cosmetic incision and faster recovery, uniportal video-assisted thoracoscopic surgery (UP-VATS) has developed rapidly worldwide in recent decades, and indications for UP-VATS have been further expanded to those for conventional VATS. Complex segmentectomy that makes several or intricate intersegmental planes, with more complex procedures, continues to be difficult in minimally invasive techniques. However, there are few reports on UP-VATS complex segmentectomy. In this report, we describe the perioperative clinical data and operative techniques and present our early results of UP-VATS complex segmentectomy in our hospital.

Methods

The records of a total of 30 patients who underwent UP-VATS complex segmentectomy by a single surgeon between January 2021 and June 2021 were retrospectively reviewed. We defined cases as complex segmentectomy if they required resection of segments 9 and 10, combined segmentectomy, segmentectomy + subsegmentectomy, subsegmentectomy, or combined subsegmentectomy.

Results

The mean age was 52.8 ± 9.9 years old; the mean nodule size was 0.84 ± 0.36 cm; the mean margin width was 2.307 ± 0.309 cm; the median operative time was 229.0 ± 58.06 min; the mean operative hemorrhage was 56.60 ± 17.95 mL; 5.58 ± 1.74 lymph nodes dissected had not metastasized; the mean duration of postoperative chest tube drainage was 4.7 ± 1.4 days; and the mean postoperative hospital stay was 6.5 ± 3.0 days. Although 1 patient experienced a prolonged air leak, the other 29 recovered uneventfully. Another patient failed to reach the 2-cm safe margins and subsequently underwent completion lobectomy.

Conclusions

UP-VATS complex segmentectomy is a safe and effective procedure in the treatment of lung cancers, sparing more pulmonary parenchyma and ensuring safe margins, with the disadvantage being the lengthy operative times during early skill acquisition.
Differential responses to immune checkpoint inhibitor dictated by pre-existing differential immune profiles in squamous cell carcinomas caused by same initial oncogenic drivers
Authors: Chen Samantha M. Y. , Popolizio Vince , Woolaver Rachel A. , Ge Huaibin , Krinsky Alexandra L. , John Jessy , Danis Etienne , Ke Yao , Kramer Yonatan , Bian Li , Nicklawsky Andrew G. , Gao Dexiang , Liu Silvia , Chen Zhangguo , Wang Xiao-jing , Wang Jing H.
Published: April 2022

Background

While immune checkpoint inhibitors (ICI) were approved for head and neck squamous cell carcinomas (HNSCCs), the response rate remains relatively low. Mechanisms underlying ICI unresponsiveness versus sensitivity are not fully understood.

Method

To better delineate differential responses to ICI treatment, we employed mouse SCC models, termed KPPA tumors that were caused by deleting p53 and hyperactivating PIK3CA, two most frequently mutated genes in human HNSCCs. We transplanted two KPPA tumor lines (TAb2 versus TCh3) into C57BL/6 recipients and examined the immune tumor microenvironment using flow cytometry. Furthermore, we employed single-cell RNA sequencing to identify the difference in tumor infiltrating lymphocytes (TILs).

Results

We found that different KPPA tumors exhibited heterogeneous immune profiles pre-existing treatment that dictated their sensitivity or unresponsiveness to anti-PD-L1. Unresponsive TAb2 tumors were highly enriched with functional tumor-associated macrophages (TAMs), especially M2-TAMs. In contrast, sensitive TCh3 tumors contained more CD8 TILs with better effector functions. TAb2 tumor cells drastically expanded F4/80+ TAMs from bone marrow precursors, requiring CSF1 and VEGF. Consistently, a higher combined expression of VEGF-C and CSF1 predicts worse survival in PIK3CAAmp/TP53Mutated HNSCC patients. Unresponsive TAb2 tumors upregulated distinct signaling pathways that correlate with aggressive tumor phenotypes. While anti-PD-L1 did not affect the TME of TAb2 tumors, it significantly increased the number of CD8 TILs in TCh3 tumors.

Conclusions

We uncovered tumor-intrinsic differences that may underlie the differential responses to ICI by establishing and employing two SCC tumor lines, TAb2 vs. TCh3, both of which harbor TP53 deletion and PIK3CA hyperactivation. Our study indicates the limitation of stratifying cancers according to their genetic alterations and suggests that evaluating HNSCC tumor-intrinsic cues along with immune profiles in the TME may help better predict ICI responses. Our experimental models may provide a platform for pinpointing tumor-intrinsic differences underlying an immunosuppressive TME in HNSCCs and for testing combined immunotherapies targeting either tumor-specific or TAM-specific players to improve ICI efficacy.
Inhibition of carbonic anhydrases IX/XII by SLC-0111 boosts cisplatin effects in hampering head and neck squamous carcinoma cell growth and invasion
Authors: Sarnella Annachiara , Ferrara Ylenia , Auletta Luigi , Albanese Sandra , Cerchia Laura , Alterio Vincenzo , De Simone Giuseppina , Supuran Claudiu T. , Zannetti Antonella
Published: April 2022

Background

Hypoxic tumor microenvironment (TME) contributes to the onset of many aspects of the cancer biology associated to the resistance to conventional therapies. Hypoxia is a common characteristic and negative prognostic factor in the head and neck squamous carcinomas (HNSCC) and is correlated with aggressive and invasive phenotype as well as with failure to chemo- and radio-therapies. The carbonic anhydrase isoenzymes IX and XII (CA IX/XII), regulators of extra and intracellular pH, are overexpressed in TME and are involved in adaptative changes occurring in cancer cells to survive at low O2. In this study, we aim to investigate in HNSCC cells and murine models the possibility to target CA IX/XII by the specific inhibitor SLC-0111 to potentiate the effects of cisplatin in hampering cell growth, migration and invasion. Furthermore, we analyzed the signal pathways cooperating in acquisition of a more aggressive phenotype including stemness, epithelial-mesenchymal transition and apoptotic markers.

Methods

The effects of cisplatin, CA IX/XII specific inhibitor SLC-0111, and the combinatorial treatment were tested on proliferation, migration, invasion of HNSCC cells grown in 2D and 3D models. Main signal pathways and the expression of stemness, mesenchymal and apoptotic markers were analyzed by western blotting. Molecular imaging using NIR-Annexin V and NIR-Prosense was performed in HNSCC xenografts to detect tumor growth and metastatic spread.

Results

HNSCC cells grown in 2D and 3D models under hypoxic conditions showed increased levels of CA IX/XII and greater resistance to cisplatin than cells grown under normoxic conditions. The addition of CA IX/XII inhibitor SLC-0111 to cisplatin sensitized HNSCC cells to the chemotherapeutic agent and caused a reduction of proliferation, migration and invasiveness. Furthermore, the combination therapy hampered activation of STAT3, AKT, ERK, and EMT program, whereas it induced apoptosis. In HNSCC xenografts the treatment with cisplatin plus SLC-0111 caused an inhibition of tumor growth and an induction of apoptosis as well as a reduction of metastatic spread at a higher extent than single agents.

Conclusion

Our results highlight the ability of SLC-0111 to sensitize HNSCC to cisplatin by hindering hypoxia-induced signaling network that are shared among mechanisms involved in therapy resistance and metastasis.
Very late intubation in COVID-19 patients: a forgotten prognosis factor?
Authors: Camous Laurent , Pommier Jean-David , Martino Frederic , Tressieres Benoît , Demoule Alexandre , Valette Marc
Published: April 2022

Description of all consecutive critically ill COVID 19 patients hospitalized in ICU in University Hospital of Guadeloupe and outcome according to delay between steroid therapy initiation and mechanical ventilation onset. Very late mechanical ventilation defined as intubation after day 7 of dexamethasone therapy was associated with grim prognosis and a high mortality rate of 87%.
Overlapping rheumatoid arthritis and antisynthetase syndrome with secondary Sjögren’s syndrome: a case report and review of the literature
Authors: Weerasinghe W. S. , Jayasinghe Chandrika
Published: April 2022

Background

Overlap syndromes account for about 25% of autoimmune diseases. They are many possible combinations of known autoimmune diseases increasingly diagnosed with the identification of of a large number of autoantibodies. In this case report, we present a patient with rare overlapping rheumatoid arthritis–antisynthetase syndrome with associated secondary Sjögren’s syndrome atypically presenting without interstitial lung disease.

Case presentation

A 52-year-old Sinhalese female, a known patient with type 2 diabetes mellitus, presented with a history of symmetrical inflammatory-type polyarthritis with significant morning stiffness, proximal muscle weakness, pain, and roughening of the fingertips with associated sicca symptoms of 5 months duration. Examination revealed features of active joint inflammation, mechanic’s hand, xerostomia, and left-sided breast lump. Investigations confirmed the presence of rheumatoid arthritis with strongly positive rheumatoid factor (202 U/ml) and anti-cyclic citrullinated peptide antibody (717 U/ml). Antisynthetase syndrome was also diagnosed with borderline-positive anti-aminoacyl-tRNA antibodies but without interstitial lung disease. Sjögren’s syndrome was confirmed by the clinical history and histology and considered a secondary disorder. As her breast lump proved to be benign, no further interventions were done. She was started on sulfasalazine and methotrexate with steroid bridging therapy and achieved remission and had good control of the disease without any joint deformity or flare-up on 6-month clinic follow-up.

Discussion

Overlapping rheumatoid arthritis–antisynthetase syndrome is a very rare disease with disabling complications. Early identification of the atypical presentations of the overlap syndromes, by thorough investigations, helps physicians to prescribe proper disease-modifying antirheumatoid drugs and biological drugs. It also helps predict the prognosis of the patients before they develop complications.
Metabolites and novel compounds with anti-microbial or antiaging activities from Cordyceps fumosorosea
Authors: Wei Jie , Zhou Xue , Dong Mei , Yang Lufan , Zhao Cheng , Lu Ruili , Bao Guanhu , Hu Fenglin
Published: April 2022

High-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) analysis revealed that there are 20 main components in spores and mycelia extract of Cordyceps fumosorosea strain RCEF 6672 including mannitol (1), uridine (2), adenine (3). N6-(2-hydroxyethyl)-adenosine (4). N6-(2-hydroxyethylacetate)-adenosine (5), fumosoroseanoside A (6) and B (7), ovalicin-4α-alcohol (8), 1-linoleoyl-sn-glycero-3-phosphocholine (9) and its isomer (10), fumosoroseain A (11) and its isomer (12), 5 non-ribosomal peptides (13 to 17) and 3 fatty acids (18 to 20). The compounds 5, 6, 7, 9 and 11 were prepared with preparative and semi-preparative HPLC and identified with 1D and 2D NMR. Compounds 4 and 5 were the first time identified from C. fumosorosea. Compounds 6, 7 and 11 are novel compounds. Compounds 6 and 7 showed antibacterial and antifungal activities, and 11 showed antiaging activity. All the secondary metabolites (4 to 8 and 11 to 17) have strong bioactivities indicating that the metabolites have pharmaceutical development potentiality.

Graphical Abstract
Are there bubbles in the vanilla price?
Authors: Khan Khalid , Su Chi-Wei , Khurshid Adnan , Umar Muhammad
Published: April 2022

This paper investigates the presence of the bubbles that are experienced in the global vanilla (VNL) price, using the GSADF approach. The results show that there are five bubbles in the VNL price that are driven by specific reasons. Also, in this regard, the opening and ending points of each bubble coincide with specific events that contribute toward the formation, as well as the rupture of the bubbles. It has also been noted that the cyclone Hudah and the monopoly of the cartels trigger the first bubble, while the regulation and export taxation policy drive the second bubble. However, market-oriented policies, the abolition of cartels, and the exchange rate adjustments are the leading factors that form the third bubble. Furthermore, political instability, hurricanes and bad weather are the key factors driving the fourth bubble. And finally, the rising global demand and decreasing supply, price speculation, poor quality, and cyclone Enawo create the last bubble. It needs the VNL market to be more stable in order to continue supply, which can then control the price fluctuations. The minimum role of the cartels and middlemen is vital for VNL price stability. Therefore, the governments should ideally facilitate the big companies to directly negotiate with farmers which may be beneficial for both companies and the farmers alike.
Recent advances in carbon quantum dots for virus detection, as well as inhibition and treatment of viral infection
Authors: Xue Yuxiang , Liu Chenchen , Andrews Gavin , Wang Jinyan , Ge Yi
Published: April 2022

In the last decade, carbon quantum dots (CQDs), as a novel class of carbon-based nanomaterials, have received increasing attention due to their distinct properties. CQDs are ultimately small nanoparticles with an average size below 10 nm, possessing high water solubility, alluring photoluminescence, photostability, excellent biocompatibility, low/none toxicity, environmental friendliness, and high sustainability, etc. In history, there are intermittent threats from viruses to humans, animals and plants worldwide, resulting in enormous crises and impacts on our life, environment, economy and society. Some recent studies have unveiled that certain types of CQDs exhibited high and potent antiviral activities against various viruses such as human coronavirus, arterivirus, norovirus and herpesvirus. Moreover, they have been successfully explored and developed for different virus detections including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This article exclusively overviews and discusses the recent progress of designing, synthesizing, modifying/functionalizing and developing CQDs towards effective virus detection as well as the inhibition and treatment of viral infection. Their mechanisms and applications against various pathogenic viruses are addressed. The latest outcomes for combating the coronavirus disease 2019 (COVID-19) utilizing CQDs are also highlighted. It can be envisaged that CQDs could further benefit the development of virus detectors and antiviral agents with added broad-spectrum activity and cost-effective production.
One or two pups - optimal reproduction strategies of common noctule females
Authors: Zukalova Katerina , Seidlova Veronika , Piacek Vladimir , Nemcova Monika , Pribyl Michal , Pikula Jiri , Zukal Jan
Published: April 2022

Background

The success of animal reproduction is impacted by a trade-off between energetic costs and mortality associated with immediate vs. future reproductive attempts. The reproductive strategies of European insectivorous bats differ from common mammalian standards due to the use of delayed fertilisation. Phenology of bat reproduction, including length of pregnancy, which may vary in the same species at different latitudes, between years at the same site or between individuals within a colony, is influenced by ecological conditions. To assess factors influencing the course of pregnancy, we evaluated levels of blood progesterone in 20 female common noctule bats Nyctalus noctula. The bats were individually tagged and randomly divided into two groups with different hibernation ending points (i.e. a control group vs. a treatment group with one-week longer hibernation). Following emergence from hibernation, the bats were kept in a wooden box at a stable temperature of 22 °C.

Results

The majority of females gave birth to a single neonate (65%), but one female aborted her pups 2 days before the first successful births of other females. Based on development of progesterone concentration, we were able to define a number of different reproduction strategies, i.e. females with single offspring or twins, and females with supposed resorption of one embryo (embryonic mortality after implantation of the developing fertilised egg). Progesterone levels were much higher in females with two embryos during the first part of gestation and after birth. Progesterone levels were at their highest mid-gestation, with no difference between females carrying one or two foetuses. Length of gestation differed significantly between the two groups, with the longer hibernation (treatment) group having a roughly two-day shorter gestation period.

Conclusions

Female N. noctula are able to manipulate their litter size to balance immediate and future reproduction success. The estimated gestation length of approx. 49-days appears to be standard for N. noctula, with females optimising their thermoregulatory behaviour to keep the length of gestation as close to the standard as possible.
Pharmacokinetic and pharmacodynamic analyses of terlipressin in patients with hepatorenal syndrome
Authors: Wang Xiaofeng , Jamil Khurram
Published: April 2022

The objective of this population pharmacokinetics (PK) analysis was to characterize the PK of terlipressin and its active metabolite, lysine-vasopressin (L-VP), in patients with hepatorenal syndrome (HRS), following intravenous administration of terlipressin 1 mg to 2 mg every 6 h. Sparse PK samples from 69 patients with HRS who participated in terlipressin phase 3 clinical studies were used for model development. In addition, mean arterial pressure (MAP) and heart rate (HR) from 40 patients with HRS were available to explore the relationship between terlipressin and L-VP plasma concentrations and pharmacodynamic (PD) response. A two-compartment model with first-order elimination adequately described the PK of terlipressin. L-VP was well characterized as the active metabolite of terlipressin by a one-compartment model with first-order elimination. The population PK modeling results showed that the estimated clearances for terlipressin and L-VP are 27.4 L/h and 318 L/h, respectively, for a typical patient with a body weight of 86 kg. Body weight was identified as the only covariate for the clearance of terlipressin. However, simulation suggested that body weight had no clinically meaningful effects on the exposure of L-VP through terlipressin. Therefore, no weight-based dose is needed for terlipressin to treat HRS patients. PD response, change in MAP, and HR were well correlated to L-VP concentrations; compared with baseline values, the estimated maximum decrease in HR would be 10.6 bpm and the estimated maximum increase in MAP would be 16.2 mm Hg.
The roles and mechanisms of senescence-associated secretory phenotype (SASP): can it be controlled by senolysis?
Authors: Ohtani Naoko
Published: April 2022

Cellular senescence is a state of irreversible cell cycle arrest that can be induced by a variety of potentially oncogenic stimuli, including DNA damage. Hence, senescence has long been considered to suppress tumorigenesis, acting as a guardian of homeostasis. However, recent studies have revealed that senescent cells exhibit the secretion of a series of inflammatory cytokines, chemokines, growth factors, and matrix remodeling factors that alter the local tissue environment and contribute to chronic inflammation and cancer. This senescence phenotype is termed as senescence-associated secretory phenotype (SASP) and is observed not only in cultured cells in vitro but also in vivo. Recently, the physiological and pathological roles of SASP have been increasingly clarified. Notably, several studies have reported that the intrinsic mechanism of SASP factor production is predominantly mediated through the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) pathway by aberrantly accumulated DNA fragments from the nucleus of senescent cells. In contrast, various extrinsic triggers of SASP also exist in vivo, for example, the SASP induction in hepatic stellate cells in the tumor microenvironment of obesity-associated liver cancer by the translocated gut microbial metabolites. Recently, the strategy for the elimination of senescent cells (senolysis) has attracted increasing attention. Thus, the role of SASP and the effects and outcomes of senolysis in vivo will be also discussed in this review.
Shedding light on the phenotypic–genotypic correlation of rare treatable and potentially treatable pediatric movement disorders
Authors: Saleh Dina Amin , Attia Azza Abd El Moneim
Published: April 2022

Background

Advances in genetic science have led to the identification of many rare treatable pediatric movements disorders (MDs). We explored the phenotypic–genotypic spectrum of pediatric patients presenting with MDs. By this, we aimed at raising awareness about such rare disorders, especially in our region. Over the past 3 years, we reviewed the demographic data, clinical profile, molecular genetics and other diagnostic workups of pediatric patients presenting with MDs.

Results

Twelve patients were identified; however, only six patients were genetically confirmed. The phenomenology of MDs ranged from paroxysmal kinesigenic choreoathetosis (1 patient), exercise-induced dyskinesia (2 patients), ataxia (2 patients) and dystonia (2 patients). Whole-exome sequencing in addition to the functional studies for some patients revealed a specific genetic diagnosis being responsible for their MDs. The genetic diagnosis of our patients included infantile convulsions and paroxysmal choreoathetosis syndrome and episodic ataxia due to “pathogenic homozygous mutation of PRRT2 gene,” glucose transporter type 1 deficiency-exercise induced dyskinesia due to “De Novo pathogenic heterozygous missense mutation of exon 4 of SLC2A1 gene,” aromatic L amino acid decarboxylase deficiency due to “pathogenic homozygous mutation of the DDC gene,” myopathy with extrapyramidal signs due to “likely pathogenic homozygous mutations of the MICU1 gene,” mitochondrial trifunctional protein deficiency due to “homozygous variant of uncertain significance (VUS) of HADHB gene” and glutaric aciduria II with serine deficiency due to “homozygous VUS for both ETFDH and PHGDH genes.” After receiving the treatment as per recognized treatment protocols, two patients showed complete resolution of symptoms and the rest showed variable responses.

Conclusion

Identifying the genetic etiology of our patients guided us to provide either disease-specific treatment or redirected our management plan. Hence, highlighting the value of molecular genetic analysis to avoid the diagnostic odyssey and identify treatable MDs.
Appraising the Effect of Potential Risk Factors on Thyroid Cancer: A Mendelian Randomization Study
Authors: Huang Lulu , Feng Xiuming , Yang Wenjun , Li Xiangzhi , Zhang Kang , Feng Shuzhen , Wang Fei , Yang Xiaobo
Published: April 2022

Context

Various risk factors have been associated with the risk of thyroid cancer in observational studies. However, the causality of the risk factors is not clear given the susceptibility of confounding and reverse causation.

Objective

A 2-sample Mendelian randomization approach was used to estimate the effect of potential risk factors on thyroid cancer risk.

Methods

Genetic instruments to proxy 55 risk factors were identified by genome-wide association studies (GWAS). Associations of these genetic variants with thyroid cancer risk were estimated in GWAS of the FinnGen Study (989 cases and 217 803 controls). A Bonferroni-corrected threshold of P = 9.09 × 10-4 was considered significant, and P < 0.05 was considered to be suggestive of an association.

Results

Telomere length was significantly associated with increased thyroid cancer risk after correction for multiple testing (OR 4.68; 95% CI, 2.35-9.31; P = 1.12 × 10-5). Suggestive associations with increased risk were noted for waist-to-hip ratio (OR 1.85; 95% CI, 1.02-3.35; P = 0.042) and diastolic blood pressure (OR 1.60; 95% CI, 1.08-2.38; P = 0.019). Suggestive associations were noted between hemoglobin A1c (HbA1c) (OR 0.20; 95% CI, 0.05-0.82; P = 0.025) and decreased risk of thyroid cancer. Risk of thyroid cancer was not associated with sex hormones and reproduction, developmental and growth, lipids, diet and lifestyle, or inflammatory factors (All P > 0.05).

Conclusion

Our study identified several potential targets for primary prevention of thyroid cancer, including central obesity, diastolic blood pressure, HbA1c, and telomere length, which should inform public health policy.
Plasma Levels of Triglycerides and IL-6 Are Associated With Weight Regain and Fat Mass Expansion
Authors: Qiao Qi , Bouwman Freek G , van Baak Marleen A , Roumans Nadia J T , Vink Roel G , Mariman Edwin C M
Published: April 2022

Context

Long-term weight loss (WL) maintenance is the biggest challenge for overweight and obesity because of the almost unavoidable phenomenon of partial or even total weight regain (WR) after WL.

Objective

In the present study we investigated the relations of (the changes of) adipocyte size and other risk biomarkers with WR during the follow-up of the Yoyo dietary intervention.

Methods

In this randomized controlled study, 48 overweight/obese participants underwent a very-low-calorie diet to lose weight, followed by a weight-stable period of 4 weeks and a follow-up period of 9 months. Anthropometric measurements, adipocyte volume of abdominal subcutaneous adipose tissue, and plasma metabolic parameters (free fatty acids [FFAs], triglycerides [TGs], total cholesterol, glucose, insulin, homeostasis model assessment of insulin resistance [HOMA-IR], interleukin 6 [IL-6], angiotensin-converting enzyme [ACE] activity, retinol binding protein 4 [RBP4]) at the beginning and the end of follow-up were analyzed.

Results

Our results show that changes of TGs, IL-6, HOMA-IR, and ACE are significantly positively correlated with WR. Multiple linear regression analysis shows that only TG and IL-6 changes remained significantly correlated with WR and increased body fat mass. Moreover, the change in HOMA-IR was tightly correlated with the change in TGs. Surprisingly, change in adipocyte volume during follow-up was not correlated with WR nor with other factors, but positive correlations between adipocyte volume and HOMA-IR were found at the beginning and end of the follow-up.

Conclusion

These results suggest that TGs and IL-6 are independently linked to WR via separate mechanisms, and that HOMA-IR and adipocyte volume may indirectly link to WR through the change of plasma TGs.
Al-MPS Obstructs EMT in Breast Cancer by Inhibiting Lipid Metabolism via miR-215-5p/SREBP1
Authors: Wu Chenlu L , Xu Lili L , Peng Jing , Zhang Danhua H
Published: April 2022

Alkali-extractable mycelial polysaccharide (Al-MPS) is a natural macromolecular polymer that has shown anti-hyperlipidemic and antitumor abilities. This study investigates the mechanism by which Al-MPS inhibits lipid metabolism and epithelial-mesenchymal transition (EMT) in breast cancer (BC). BC cells (MCF-7 and MDA-MB-231) were transfected and/or treated with Al-MPS. CCK-8, Transwell, and scratch assays were used to evaluate the tumorigenic behaviors of BC cells. The expression levels of SREBP1, E-cadherin, N-cadherin, Snail, vimentin, FASN, ACLY, and ACECS1 in BC cells were detected by Western blotting. Dual-luciferase reporter and RNA pull-down assays were performed to verify the binding between miR-215-5p and SREBP1 mRNA. Nude mice were injected with MDA-MB-231 cells and treated with Al-MPS. The changes in tumor volume and protein expression were monitored. miR-215-5p was downregulated and SREBP1 was upregulated in BC. Al-MPS increased miR-215-5p expression and inhibited SREBP1 expression, lipid metabolism, and EMT in BC. Inhibition of miR-215-5p or overexpression of SREBP1 promoted the tumorigenic behaviors of BC cells by stimulating lipid metabolism and counteracted the antitumor effect of Al-MPS. SREBP1 was a downstream target of miR-215-5p. In conclusion, Al-MPS inhibits lipid metabolism and EMT in BC via the miR-215-5p/SREBP1 axis. This study supports the application of polysaccharides in cancer treatment and the molecules regulated by Al-MPS may be used as biomarkers or therapeutic targets for BC.
Children and young people with lymphoedema: a project to assess the education needs of healthcare professionals
Authors: Noble-Jones Rhian , Hocking Karl , Thomas Melanie J
Published: April 2022

Healthcare professionals need adequate preparatory education to treat children and young people with lymphoedema confidently and competently. This collaborative international project, based on existing literature and expert focus groups, seeks to identify the nature of that education need and in what format it could be addressed.
British Lymphology Society's position paper for management of people with lymphoedema in presence of deep vein thrombosis: a summary
Authors: O'Neill Catriona , Elwell Rebecca
Published: April 2022

There is some confusion surrounding the management of people with lymphoedema in the presence of deep vein thrombosis (DVT). This may be in relation to the suitability of commencing compression therapy or regarding the continuation of compression therapy in those who develop DVT. The purpose of this British Lymphology Society position paper is to support evidence-based practice and debunk the myths surrounding the management of DVT and lymphoedema.
Conservative management of massive localised lymphoedema using compression wraps: a case study
Authors: Longhurst Sarah
Published: April 2022

Massive localised lymphoedema (MLL) is an issue that affects patients with obesity. Much of the literature surrounding MLL focuses upon surgical management. This case study will explore the conservative management of a patient with MLL of the distal thighs. MLL of the legs negatively impacts patients' mobility, which, in turn, affects their ability to undertake physical activity. Encouraging exercise and activity forms part of conventional lymphoedema treatment, as well as compression garments (in this case, compression wraps), good skin care and weight management. The impact of the COVID-19 pandemic on this patient's lymphoedema treatment will also be considered. The treatment of not just MLL, but lymphoedema in general, requires commitment from patients, their carers and staff. This case study illustrates what can be achieved, despite a pandemic, when a patient, their carers and lymphoedema therapists fully commit to a treatment regimen that is manageable and well-supported. The patient's MLL has shrunk significantly, and her weight continues to reduce. Informed consent was gained from the patient concerned in this case study.
Dipping your toes into research: experiencing the transition from pure clinical work to combining clinical and research roles
Authors: Chalmers Sophie
Published: April 2022

Sophie Chalmers is a clinical academic and registered allied health professional working in collaboration with an NHS Trust and Higher Education Institution to enhance research capacity building across alied health professional teams in Bolton NHS Foundation Trust, with support from the University of Central Lancashire. Sophie describes her experience of transitioning from a full-time clinician to dipping her toes into research through a 2-year research secondment.
Admission to delivery suites: the importance of antenatal education
Authors: Saime Syafiqah H , Abdul-Mumin Khadizah H , Hashim Sarena
Published: April 2022

This article discusses the challenges in ensuring women have appropriate education to guide their decision on when to present to hospital during labour. Unnecessary admission to the delivery suite can cause overcrowding, which may affect the services provided to women in active labour. Pregnancy is a demanding and sometimes overwhelming experience and women's fears can be compounded if they do not know what to expect from labour. Antenatal education to inform women on the signs and symptoms of the first stage of labour, and how to recognise deviations from normal, is vital in encapsulating holistic antenatal care. Therefore, antenatal education is integral to positive pregnancy outcomes, enhancing women's ability to take control of their pregnancy by undertaking self-management at home prior to the onset of active labour and their confidence in coming to the delivery suite at the appropriate time.
Academics' experiences of online interprofessional education in response to COVID-19
Authors: Power Alison , Park Vikki , Owens Melissa , Palapal Sy Michael
Published: April 2022

This is the fourth article in a series exploring experiences of engaging with interprofessional education during the COVID-19 pandemic. Alongside students and practitioners, academics have had significant learning opportunities during the pandemic through reflecting on experiences of developing and delivering interprofessional education using emergency remote teaching. This article presents reflective accounts from academics across the UK, revealing their authentic experiences of maintaining interprofessional education within health and social care programmes during the pandemic. Personal reflective accounts provide case studies that lead to shared learning and suggestions for future interprofessional education provision.