bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase II Study Evaluating the Interest to Combine UCPVax, a Telomerase CD4 TH1-Inducer Cancer Vaccine, and Atezolizumab for the Treatment of HPV Positive Cancers: VolATIL Study
Authors: Rebucci-Peixoto Magali , Vienot Angélique , Adotevi Olivier , Jacquin Marion , Ghiringhelli Francois , de la Fouchardière Christelle , You Benoit , Maurina Tristan , Kalbacher Elsa , Bazan Fernando , Meynard Guillaume , Clairet Anne-Laure , Fagnoni-Legat Christine , Spehner Laurie , Bouard Adeline , Vernerey Dewi , Meurisse Aurélia , Kim Stefano , Borg Christophe , Mansi Laura 
Published: July 2022

BackgroundThere is a strong rational of using anti–programmed cell death protein-1 and its ligand (anti–PD-1/L1) antibodies in human papillomavirus (HPV)–induced cancers. However, anti–PD-1/L1 as monotherapy induces a limited number of objective responses. The development of novel combinations in order to improve the clinical efficacy of an anti–PD-1/L1 is therefore of interest. Combining anti–PD-1/L1 therapy with an antitumor vaccine seems promising in HPV-positive (+) cancers. UCPVax is a therapeutic cancer vaccine composed of two separate peptides derived from telomerase (hTERT, human telomerase reverse transcriptase). UCPVax is being evaluated in a multicenter phase I/II study in NSCLC (non–small cell lung cancer) and has demonstrated to be safe and immunogenic. The aim of the VolATIL study is to evaluate the combination of atezolizumab (an anti-PD-L1) and UCPVax vaccine in a multicenter phase II study in patients with HPV+ cancers.MethodsPatients with HPV+ cancer (anal canal, head and neck, and cervical or vulvar), at locally advanced or metastatic stage, and refractory to at least one line of systemic chemotherapy are eligible. The primary end point is the objective response rate (ORR) at 4 months. Patients will receive atezolizumab every 3 weeks at a fixed dose of 1,200 mg in combination with the UCPVax vaccine at 1 mg subcutaneously.DiscussionAnti-cancer vaccines can restore cancer-immunity via the expansion and activation of tumor-specific T cells in patients lacking pre-existing anti-tumor responses. Moreover, preclinical data showed that specific TH1 CD4 T cells sustain the quality and homing of an antigen-specific CD8+ T-cell immunity. In previous clinical studies, the induction of anti-hTERT immunity was significantly correlated to survival in patients with advanced squamous anal cell carcinoma. Thus, there is a strong rational to combine an anti-cancer hTERT vaccine and an immune checkpoint inhibitor to activate and promote antitumor T-cell immunity. This pivotal proof of concept study will evaluate the efficacy and safety of the combination of a telomerase-based TH1 inducing vaccine (UCPVax) and an anti–PD-L1 (atezolizumab) immunotherapy in HPV+ cancers, as well as confirming their synergic mechanism, and settling the basis for a new combination for future clinical trials.Clinical Trial Registrationhttps://www.clinicaltrials.gov/, identifier NCT03946358.
Global trends in pediatric burn injuries and care capacity from the World Health Organization Global Burn Registry
Authors: Jordan Kelly C. , Di Gennaro Jane L. , von Saint André-von Arnim Amélie , Stewart Barclay T. 
Published: July 2022

BackgroundBurn injuries are a major cause of death and disability globally. The World Health Organization (WHO) launched the Global Burn Registry (GBR) to improve understanding of burn injuries worldwide, identify prevention targets, and benchmark acute care. We aimed to describe the epidemiology, risk factors, and outcomes of children with burns to demonstrate the GBR's utility and inform needs for pediatric burn prevention and treatment.MethodsWe performed descriptive analyses of children age ≤ 18 years in the WHO GBR. We also described facility-level capacity. Data were extracted in September of 2021.ResultsThere were 8,640 pediatric and adult entries from 20 countries. Of these, 3,649 (42%) were children (0–18 years old) from predominantly middle-income countries. The mean age was 5.3 years and 60% were boys. Children aged 1–5 years comprised 62% (n = 2,279) of the cohort and mainly presented with scald burns (80%), followed by flame burns (14%). Children &gt;5 years (n = 1,219) more frequently sustained flame burns (52%) followed by scald burns (29%). More than half of pediatric patients (52%) sustained a major burn (≥15% total body surface area) and 48% received surgery for wound closure during the index hospitalization. Older children had more severe injuries and required more surgery. Despite the frequency of severe injuries, critical care capacity was reported as “limited” for 23% of pediatric patients.ConclusionsChildren represent a large proportion of people with burn injuries globally and often sustain major injuries that require critical and surgical intervention. However, critical care capacity is limited at contributing centers and should be a priority for healthcare system development to avert preventable death and disability. This analysis demonstrates that the GBR has the potential to highlight key epidemiological characteristics and hospital capacity for pediatric burn patients. To improve global burn care, addressing barriers to GBR participation in low- and low-middle-income countries would allow for greater representation from a diversity of countries, regions, and burn care facilities.
Natural Phenylethanoid Supplementation Alleviates Metabolic Syndrome in Female Mice Induced by High-Fructose Diet
Authors: Zhan Xiujun , He Mingshuai , Pei Jierong , Fan Wenjing , Mwangi Charity Ngina , Zhang Peng , Chai Xin , Jiang Miaomiao 
Published: July 2022

Tyrosol (T), hydroxytyrosol (H), and salidroside (S) are typical phenylethanoids and also powerful dietary antioxidants. This study aimed at evaluating the influence of three natural phenylethanoids, which are dietary phenylethanoids of natural origins, on reversing gut dysbiosis and attenuating nonalcoholic fatty liver features of the liver induced by metabolic syndrome (MetS) mice. C57BL/6J female mice induced with high-fructose diet were established and administrated with salidroside, tyrosol, and hydroxytyrosol for 12 weeks, respectively. Biochemical analysis showed that S, T, and H significantly improved glucose metabolism and lipid metabolism, including reduced levels of total cholesterol insulin (INS), uric acid, low-density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (ALT). Histopathological observation of the liver confirmed the protective effects of S, T, and H against hepatic steatosis, which were demonstrated by the results of metabolomic analysis, such as the improvement in glycolysis, purine metabolism, bile acid, fatty acid metabolism, and choline metabolism. Additionally, 16S rRNA gene sequence data revealed that S, T, and H could enhance the diversity of gut microbiota. These findings suggested that S, T, and H probably suppress lipid accumulation and have hepatoprotective effects and improve intestinal microflora disorders to attenuate metabolic syndromes.
Comparative Pharmacokinetics and Local Tolerance of Tenofovir Alafenamide (TAF) From Subcutaneous Implant in Rabbits, Dogs, and Macaques
Authors: Gatto G. J. , Krovi A. , Li L. , Massud I. , Holder A. , Gary J. , Mills P. , Mitchell J. , Luecke E. , Demkovich Z. R. , Heneine W. , García-Lerma J. G. , Marzinke M. A. , Brand R. M. , Dobard C. W. , Johnson L. M. , Van Der Straten A. 
Published: July 2022

The administration of antiretrovirals (ARVs) for HIV pre-exposure prophylaxis (PrEP) is highly efficacious and may benefit from new long-acting (LA) drug delivery approaches. This paper describes a subcutaneous, reservoir-style implant for the LA delivery of tenofovir alafenamide (TAF) and documents the preclinical assessment of implant safety and pharmacokinetics (PK) in New Zealand White (NZW) rabbits (3 groups ofn= 5), beagle dogs (2 groups ofn= 6), and rhesus macaques (2 groups ofn= 3). Placebo implants were placed in rabbits (n= 10) and dogs (n= 12). Implant parameters, including selection of the TAF form, choice of excipient, and PCL formulation were tuned to achieve targeted concentrations of the active anabolite of TAF, tenofovir diphosphate (TFV-DP), within peripheral blood mononuclear cells (PBMCs) and mucosal tissues relevant to HIV transmission. Sustained concentrations of TFV-DP in PBMCs over 100 fmol/106cells were achieved in all animal species indicating that the implants effectively delivered TAF for 3–6 months. Unlike placebo implants without TAF, all active implants resulted in local adverse events (AEs) proximal to the implant ranging in severity from mild to moderate and included dermal inflammation and necrosis across all species. Despite these AEs, the implant performed as designed and achieved a constant drug release profile, supporting the continued development of this drug delivery platform.
Alteration of the Oligodendrocyte Lineage Varies According to the Systemic Inflammatory Stimulus in Animal Models That Mimic the Encephalopathy of Prematurity
Authors: Favrais Geraldine , Bokobza Cindy , Saliba Elie , Chalon Sylvie , Gressens Pierre 
Published: July 2022

Preterm birth before the gestational age of 32 weeks is associated with the occurrence of specific white matter damage (WMD) that can compromise the neurological outcome. These white matter abnormalities are embedded in more global brain damage defining the encephalopathy of prematurity (EoP). A global reduction in white matter volume that corresponds to chronic diffuse WMD is the most frequent form in contemporary cohorts of very preterm infants. This WMD partly results from alterations of the oligodendrocyte (OL) lineage during the vulnerability window preceding the beginning of brain myelination. The occurrence of prenatal, perinatal and postnatal events in addition to preterm birth is related to the intensity of WMD. Systemic inflammation is widely recognised as a risk factor of WMD in humans and in animal models. This review reports the OL lineage alterations associated with the WMD observed in infants suffering from EoP and emphasizes the role of systemic inflammation in inducing these alterations. This issue is addressed through data on human tissue and imaging, and through neonatal animal models that use systemic inflammation to induce WMD. Interestingly, the OL lineage damage varies according to the inflammatory stimulus, i.e., the liposaccharide portion of the E.Coli membrane (LPS) or the proinflammatory cytokine Interleukin-1β (IL-1β). This discrepancy reveals multiple cellular pathways inducible by inflammation that result in EoP. Variable long-term consequences on the white matter morphology and functioning may be speculated upon according to the intensity of the inflammatory challenge. This hypothesis emerges from this review and requires further exploration.
Acute effects of mixed circuit training on hemodynamic and cardiac autonomic control in chronic hemiparetic stroke patients: A randomized controlled crossover trial
Authors: Fonseca Guilherme F. , Midgley Adrian W. , Billinger Sandra A. , Michalski André C. , Costa Victor A. B. , Monteiro Walace , Farinatti Paulo , Cunha Felipe A. 
Published: July 2022

Objectives:To investigate whether a single bout of mixed circuit training (MCT) can elicit acute blood pressure (BP) reduction in chronic hemiparetic stroke patients, a phenomenon also known as post-exercise hypotension (PEH).Methods:Seven participants (58 ± 12 years) performed a non-exercise control session (CTL) and a single bout of MCT on separate days and in a randomized counterbalanced order. The MCT included 10 exercises with 3 sets of 15-repetition maximum per exercise, with each set interspersed with 45 s of walking. Systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP), cardiac output (Q), systemic vascular resistance (SVR), baroreflex sensitivity (BRS), and heart rate variability (HRV) were assessed 10 min before and 40 min after CTL and MCT. BP and HRV were also measured during an ambulatory 24-h recovery period.Results:Compared to CTL, SBP (∆-22%), DBP (∆-28%), SVR (∆-43%), BRS (∆-63%), and parasympathetic activity (HF; high-frequency component: ∆-63%) were reduced during 40 min post-MCT (p&lt; 0.05), while Q (∆35%), sympathetic activity (LF; low-frequency component: ∆139%) and sympathovagal balance (LF:HF ratio: ∆145%) were higher (p&lt; 0.001). In the first 10 h of ambulatory assessment, SBP (∆-7%), MAP (∆-6%), and HF (∆-26%) remained lowered, and LF (∆11%) and LF:HF ratio (∆13%) remained elevated post-MCTvs.CTL (p&lt; 0.05).Conclusion:A single bout of MCT elicited prolonged PEH in chronic hemiparetic stroke patients. This occurred concurrently with increased sympathovagal balance and lowered SVR, suggesting vasodilation capacity is a major determinant of PEH in these patients. This clinical trial was registered in the Brazilian Clinical Trials Registry (RBR-5dn5zd), available athttps://ensaiosclinicos.gov.br/rg/RBR-5dn5zd.Clinical Trial Registration:https://ensaiosclinicos.gov.br/rg/RBR-5dn5zd, identifier RBR-5dn5zd
Bioimpedance Body Measures and Serum Lipid Levels in Masculine Depression
Authors: von Zimmermann Claudia , Brückner Lena , Mühle Christiane , Weinland Christian , Kornhuber Johannes , Lenz Bernd 
Published: July 2022

BackgroundMajor depressive disorder (MDD) is a main reason for suicide, and serum lipids are involved in both affective disorders and related suicidal behavior. Moreover, masculine depression has been suggested as a subtype of depression with an increased risk for suicide. Here, we studied the relationship between body measures, serum lipids, suicidal thoughts, and masculine depression.MethodsDepressed patients (44% women) were divided by a sex-separated median-split into a group of 81 “patients with masculine depression” (mean age ± standard error: 36.4 ± 1.6 years) and a group of 82 “patients with non-masculine depression” (age 45.7 ± 1.6 years) according to the Male Depression Risk Scale. We compared body measures, serum lipid levels, and past suicidal ideation between these groups and explored differences between these groups and 176 healthy controls (51% women; age 37.2 ± 1.0 years).ResultsPatients with masculine depression did not significantly differ from patients with non-masculine depression in any of the body measures, lipid markers, or suicidal thoughts. Compared to healthy controls, both patient groups showed significantly higher body fat (B[masculine depression] = 0.041 and B[non–masculine depression] = 0.050), lower high-density lipoprotein (HDL) cholesterol (B = –0.045 and –0.044), and a higher risk for suicidal thoughts (B = 3.927 and 2.663) than healthy controls. Suicidal thoughts were significantly associated with lower low-density lipoprotein (LDL)/HDL ratios (B = –0.455) in patients with depression and with higher LDL cholesterol levels (B = 0.020) in healthy controls subjects.LimitationCorrelational study design and focus on in-patients.ConclusionIn the studied cohort, masculine depression was not significantly associated with the analyzed parameters of body measures, serum lipids, or suicidal thoughts in in-patients with depression.
Threshold effects of body mass index on cognitive function and heterogeneity by sex and cardiovascular risk factors
Authors: Kim Young-Joo , Yeom Hyun-E 
Published: July 2022

BackgroundDisclosing the underlying relationship between body mass index (BMI) and cognitive decline is imperative for cognitive impairment prevention and early detection. Empirical studies have indicated the risk of abnormal BMI leading to cognitive impairment. However, the relative risk of underweight or overweight on cognitive function is obscure. This study investigated the asymmetric causal effect of BMI on cognitive decline below and above an unknown threshold and the heterogeneity in the threshold level and the magnitude of the threshold effect due to sex and cardiovascular risk factors.MethodsThis study used 2010–2018 panel data from the Korean Longitudinal Study of Aging that assessed sociodemographic and health-related trends in Korean middle-aged to older population. A generalized method of moments estimator of the panel threshold model was applied to estimate the potential nonlinear pattern between BMI and cognitive function.ResultsThere was a threshold effect in the relationship between BMI and cognitive function. An increase in BMI below the threshold was associated with higher cognitive function, whereas a further increase in BMI above the threshold led to cognitive decline. The nonlinear pattern between BMI and cognitive function differed by sex and cardiovascular risk appearing more distinctively within men or the cardiovascular risk group.ConclusionsThe detrimental impact of being underweight or overweight on cognitive function is heterogeneous by sex or cardiovascular risk. For obese men or individuals with cardiovascular risk factors, maintaining adequate BMI should be highlighted to help prevent cognitive decline.
Spending and Hospital Stay for Melanoma in Hunan, China
Authors: Ke Xinchen , Lin Wenrui , Li Daishi , Zhao Shuang , Chen Mingliang , Xiao Yi , Chen Xiang , Shen Minxue , Su Juan 
Published: July 2022

ObjectiveThis study aimed to describe the economic burden of Chinese patients with melanoma in Hunan province of China, and to investigate the factors for hospitalization spending and length of stay (LOS) in patients undergoing melanoma surgery.MethodsData was extracted from the Chinese National Health Statistics Network Reporting System database in Hunan province during 2017–2019. Population and individual statistics were presented, and nonparametric tests and quantile regression were used to analyze the factors for spending and LOS.ResultA total of 2,644 hospitalized patients with melanoma in Hunan were identified. During 2017–2019, the total hospitalization spending was $5,247,972, and out-of-pocket payment (OOP) was $1,817,869, accounting for 34.6% of the total expenditure. The median spending was $1,123 [interquartile range (IQR): $555–2,411] per capita, and the median LOS was 10 days (IQR: 5–18). A total of 1,104 patients who underwent surgery were further analyzed. The non-parametric tests and quantile regression showed that women were associated with less spending and LOS than men. In general, patients aged 46–65 and those with lesions on the limbs had higher hospitalization costs and LOS than other subgroups.ConclusionMelanoma causes heavy economic burdens on patients in Hunan, such that the median spending is close to 60% of the averagely annual disposable income. Middle-aged men patients with melanoma on the limbs present the highest financial burden of melanoma.
Differences in HIV, STI and Other Risk Factors Among Younger and Older Male Sex Workers Who Have Sex With Men in Nairobi, Kenya
Authors: Muraguri Nicholas , Okal Jerry O. , Temmerman Marleen , Mukoko Dunstan , Musyoki Helgar K. , Gichangi Peter 
Published: July 2022

IntroductionPrevious surveys of male sex workers (MSW) in sub-Saharan Africa have not fully documented the HIV and sexually transmitted infections (STIs) rates and vulnerabilities by age category.MethodsThe bio-behavioral survey of MSW in Nairobi, Kenya, utilized respondent-driven sampling to recruit MSW. Structured interviews captured MSW's behavioral aspects, and biological tests for HIV and other STIs.ResultsAnalysis of the two age categories, 18–24 years (younger MSW) and 25 years and above (older MSW), shows that of all participants, a significantly higher proportion of younger MSW (59.6% crude, 69.6% RDS-adjusted) were recruited compared to older MSW (40.4% crude, 30.4% RDS-adjusted, P &lt; 0.001). Young male sex workers were more likely to report multiple sexual partnerships in the last 12 months and had multiple receptive anal intercourses (RAI) acts in the last 30 days than older MSW: 0–2 RAI acts (20.6 vs. 8.6%, P = 0.0300), 3–5 RAI acts (26.3 vs. 11.5, P &lt; 0.001), and &gt;5 RAI acts (26.3 vs. 11.5%, P &lt; 0.01). Furthermore, younger MSW were significantly more likely to have 3–5 insertive anal intercourse (IAI) with a regular male sex partner in the last 30 days than older MSW (24.3 vs. 8.0%, P &lt; 0.01). Younger MSW were also more likely to report other STIs [28.5% (95% CI: 19.1–40.4%)] than older MSW [19.0% (95% CI: 7.7–29.2%)]. However, older MSWs were more likely to be infected with HIV than younger MSW (32.3 vs. 9.9 %, P &lt; 0.01).ConclusionsOwing to the high risk sexual behaviors, HIV and STIs risks among younger and older MSW, intensified and targeted efforts are needed on risk reduction campaigns and expanded access to services.
Luteal phase support in fresh and frozen embryo transfers
Authors: Greenbaum Shirley , Athavale Ahlad , Hershko Klement Anat , Bentov Yaakov 
Published: July 2022

ContextLuteal phase support (LPS) has become an essential component of IVF protocols following both fresh and frozen embryo transfers, yet there is still controversy with regards to the optimal protocol of LPS to enhance treatment outcome.Search strategyA search via PubMed for all the selected topics was limited to publications from the past 10 years and to English language. We subsequently searched the reference lists of retrieved articles. Where available, RCTs were chosen over non-randomized studies. Here we provide an updated review of the current literature on various issues relating to LPS, in both fresh and frozen embryo transfers. The timing of LPS initiation as well as the route of administration and dosing are discussed for both fresh and frozen transfers. A separate discussion for frozen thawed embryo transfer in natural cycles and non-ovulatory cycles is presented.ConclusionsWe present data that supports the use of Progesterone LPS in fresh and frozen embryo transfers. No benefits were found to the addition of hCG or estradiol to progesterone LPS in fresh transfers, however GnRH agonist may have a role. IM Progesterone was not advantageous over vaginal progesterone in fresh transfers but was superior in frozen transfers. The timing of LPS introduction, the interval to embryo transfer, as well as the serum concentration of progesterone, have significant effects on the success of the treatment.
On Spectral Vectorial Differential Equation of Generalized Hermite Polynomials
Authors: Atia Mohamed Jalel , Benabdallah Majed 
Published: July 2022

In this paper, we first give some results on monic generalized Hermite polynomials (GHP) {Hn(μ)(x)}n≥0, orthogonal with respect to the positive weight |x|2μe−x2,μ>−12,x∈R, which will lead to the formulation of the second-order spectralvectorial differential equation (SVDE) that the GHP satisfies. This SVDE differs from the one given in G. Szego (problem 25. p. 380), which is a pseudo-spectral equation. Second, we give the SVDE, as conjecture, satisfied by the generalized Jacobi polynomials Jn(α,α+1)(x,μ), orthogonal with respect to the positive weight w(x,α;μ)=|x|−μ(1−x2)α(1−x), μ<1, α>−1 on [−1,1].