bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractDescription 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

Abstract
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

AbstractHigh-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