bluuebunny/crossref_metadata_2025_split huggingface dataset:
A human monoclonal antibody neutralizing SARS-CoV-2 Omicron variants containing the L452R mutation
Authors: Stein Saskia C. , Hansen Guido , Ssebyatika George , Ströh Luisa J. , Ochulor Okechukwu , Herold Elisabeth , Schwarzloh Britta , Mutschall Doris , Zischke Jasmin , Cordes Anne K. , Schneider Talia , Hinrichs Imke , Blasczyk Rainer , Kleine-Weber Hannah , Hoffmann Markus , Klein Florian , Kaiser Franziska K. , Gonzalez-Hernandez Mariana , Armando Federico , Ciurkiewicz Malgorzata , Beythien Georg , Pöhlmann Stefan , Baumgärtner Wolfgang , Osterhaus Albert , Schulz Thomas F. , Krey Thomas 
Published: November 2024

ABSTRACT

The effectiveness of SARS-CoV-2 therapeutic antibodies targeting the spike (S) receptor-binding domain (RBD) has been hampered by the emergence of variants of concern (VOCs), which have acquired mutations to escape neutralizing antibodies (nAbs). These mutations are not evenly distributed on the RBD surface but cluster on several distinct surfaces, suggesting an influence of the targeted epitope on the capacity to neutralize a broad range of VOCs. Here, we identified a potent nAb from convalescent patients targeting the receptor-binding domain of a broad range of SARS-CoV-2 VOCs. Except for the Lambda and BA.2.86 variants, this nAb efficiently inhibited the entry of most tested VOCs, including Omicron subvariants BA.1, BA.2, XBB.1.5, and EG.5.1 and to a limited extent also BA.4/5, BA.4.6, and BQ.1.1. It bound recombinant S protein with picomolar affinity, reduced the viral load in the lung of infected hamsters, and prevented the severe lung pathology typical for SARS-CoV-2 infections. An X-ray structure of the nAb-RBD complex revealed an epitope that does not fall into any of the conventional classes and provided insights into its broad neutralization properties. Our findings highlight a conserved epitope within the SARS-CoV-2 RBD that should be preferably targeted by therapeutic antibodies and inform rational vaccine development.

IMPORTANCE
Therapeutic antibodies are effective in preventing severe disease from SARS-CoV-2 infection and constitute an important option in pandemic preparedness, but mutations within the S protein of virus variants (e.g., a mutation of L452) confer resistance to many of such antibodies. Here, we identify a human antibody targeting the S protein receptor-binding domain (RBD) with an elevated escape barrier and characterize its interaction with the RBD functionally and structurally at the atomic level. A direct comparison with reported antibodies targeting the same epitope illustrates important differences in the interface, providing insights into the breadth of antibody binding. These findings highlight the relevance of an extended neutralization profiling in combination with biochemical and structural characterization of the antibody-RBD interaction for the selection of future therapeutic antibodies, which may accelerate the control of potential future pandemics.
Lipid nanoparticles as adjuvant of norovirus VLP vaccine augment cellular and humoral immune responses in a TLR9- and type I IFN-dependent pathway
Authors: Dai Weiqian , Xing Man , Sun Lingjin , Lv Lihui , Wang Xiang , Wang Yihan , Pang Xueyang , Guo Yingying , Ren Jiling , Zhou Dongming 
Published: November 2024

ABSTRACT

Norovirus (NoV) virus-like particles (VLPs) adjuvanted with aluminum hydroxide (Alum) are common vaccine candidates in clinical studies. Alum adjuvants usually inefficiently assist recombinant proteins to induce cellular immune responses. Thus, novel adjuvants are required to develop NoV vaccines that could induce both efficient humoral and robust cellular immune responses. Lipid nanoparticles (LNPs) are well-known mRNA delivery vehicles. Increasing evidence suggests that LNPs may have intrinsic adjuvant activity and can be used as adjuvants for recombinant protein vaccines; however, the underlying mechanism remains poorly understood. In this study, we compared the adjuvant effect of LNPs and Alum for a bivalent GI.1/GII.4 NoV VLP vaccine. Compared with Alum, LNP-adjuvanted vaccines induced earlier production of binding, blocking, and neutralizing antibodies and promoted a more balanced IgG2a/IgG1 ratio. It is crucial that LNP-adjuvanted vaccines induced stronger Th1-type cytokine-producing CD4
+
T cell and CD8
+
T cell responses than Alum. The adjuvant activity of LNPs depended on the ionizable lipid components. Mechanistically, LNPs activated innate immune responses in a type I IFN-dependent manner and were partially dependent on Toll-like receptor (TLR) 9, thus affecting the adaptive immune responses of the vaccine. This conclusion was supported by RNA-seq analysis and
in vitro
cell experiments and by the deeply blunted T cell responses in IFNαR1
−/−
mice immunized with LNP-adjuvanted vaccines. This study not only identified LNPs as a high quality adjuvant for NoV VLP vaccines, but also clarified the underlying mechanism of LNPs as a potent immunostimulatory component for improving protein subunit vaccines.

IMPORTANCE

With the rapid development of mRNA vaccines, recurrent studies show that lipid nanoparticles (LNPs) have adjuvant activity. However, the mechanism of its adjuvant effect in protein vaccines remains unknown. In this study, we found that the LNP-adjuvanted norovirus bivalent virus-like particle vaccines led to durable antibody responses as well as Th1-type cytokine-producing CD4
+
T cell and CD8
+
T cell responses, which exceeded the efficiency of the conventional adjuvant aluminum hydroxide. Mechanistically, LNPs activated innate immune responses in a type I IFN-dependent manner and were partially dependent on Toll-like receptor 9, thus affecting the adaptive immune responses of the vaccine. This work unveils that LNPs as a potent immunostimulatory component may be ideal for generating CD8
+
T cell and B cell responses for recombinant protein vaccines.
Socioeconomic inequalities and dyslipidaemia in adult population of the Ravansar Non-Communicable Disease Cohort Study: the role of sex and age
Authors: Izadi Neda , Yari-Boroujeni Reza , Soofi Moslem , Niknam Mahdieh , Amiri Parisa , Najafi Farid 
Published: November 2024

ObjectivesThis study represents a pioneering attempt to quantify the contribution of age, sex and socioeconomic status (SES) to the observed inequalities in lipid profile components.DesignCross-sectional study.SettingThe data from the Ravansar Non-Communicable Disease (RaNCD) Cohort Study were used.Participants10 000 individuals aged 35–65 years.Main outcome measuresPrincipal component analysis was used to determine the SES of individuals. Using the concentration index (C-index) and curves, the study assessed socioeconomic inequalities in dyslipidaemia in different age groups and genders. Decomposition analysis was used to determine the contribution of sex, age and SES to the observed inequality in the prevalence of dyslipidaemia components between the wealthiest and poorest groups.ResultsThe prevalence of dyslipidaemia was 72.39% of the population and was significantly higher in women than in men (excluding hypertriglyceridaemia). Overall, no significant SES-based inequality in dyslipidaemia was observed (C-index=−0.045, p=0.116), but after adjustment for age and sex, individuals with high SES had increased odds of dyslipidaemia (OR=1.16, 95% CI: 1.03 to 1.31). Hypercholesterolaemia and hyper-low-density lipoprotein (LDL) were more common in individuals with lower SES (C-index=−0.117 and −0.105), while hypo-high-density lipoprotein (HDL) was more prevalent in individuals with higher SES (C-index=0.029), regardless of adjustment for age, sex and confounding factors. SES played a significant role in hypercholesterolaemia and hyper-LDL (322.11% and 400.14%), while sex dominated in hypertriglyceridaemia and hypo-HDL (814.05% and −615.26%) and contributed to the existing inequalities.ConclusionThe results highlight the existing inequalities in lipid profiles due to SES, sex and age. Consideration of these factors in interventions and policy decisions is critical to reduce abnormalities and inform future interventions.
Fasting plasma glucose trends in the elderly living with HIV/AIDS on combination antiretroviral therapy regimens
Authors: Shang Menglin , Zhang Jing , Chen Mingyu , Chen Xiuyuan , Liu Cong , Zhong Haidan , Du Peishan , Li Quanmin , Cai Weiping , Li Linghua , Gu Jing 
Published: November 2024

BackgroundWith the ageing of people living with HIV/AIDS (PLWHA), the prevalence of chronic comorbidities, especially hyperglycaemia, is increasing among elderly PLWHA. Antiretroviral therapy (ART) is associated with fasting plasma glucose (FPG) levels. This study aimed to investigate both short-term and long-term FPG characteristics and trends across different ART regimens in elderly Chinese PLWHA.MethodsThis retrospective cohort study, based on hospital treatment information, classified ART regimens as this retrospective cohort study used hospital treatment data. ART regimens are classified into three categories: non-nucleoside reverse transcriptase inhibitors (NNRTIs) based, protease inhibitors (PIs) based and integrase strand transfer inhibitor (INSTIs) based. Propensity score matching was applied to control for confounding factors. Follow-up FPG characteristics were then described, and a generalised linear mixed model was employed to estimate FPG trends under different regimens within 1-year and 5-year periods following ART initiation.ResultsParticipants had an average age of 58.28 years, with 75.02% male. FPG increased following ART initiation, with the most significant rise within 1 year of ART, followed by stabilisation. The FPG increase within 1 year was slower in the PIs-based group compared with the NNRTIs-based group (β=−0.08, 95% CI −0.15 to –0.01), while there was a higher prevalence of diabetes within 5 years of ART (31.55% vs 22.33%, standardised difference=0.357). The FPG increase within 1 year of ART did not differ between NNRTIs-based and INSTIs-based groups (β=−0.01, 95% CI −0.20, 0.18).ConclusionOur study highlights that elderly Chinese PLWHA experience an increase in FPG levels, particularly during the first year of ART, with variations observed across different ART regimens. The higher long-term prevalence of diabetes in the PIs-based regimen group emphasises the need for tailored glucose management strategies. Routine glucose monitoring and proactive management are crucial for preventing and controlling diabetes in this population, particularly given the long-term metabolic risks associated with ART.
Telehealth service use and quality of care among US adults with diabetes: A cross-sectional study of the 2022 health information national trends survey
Authors: Hong Young-Rock , Xie Zhigang , Nguyen Oliver T , Turner Kea , Walker Ashby F 
Published: November 2024

ObjectiveTo characterise telehealth use, reasons for using or not using telehealth and the factors associated with telehealth use among US adults with diabetes.DesignA cross-sectional study.SettingData were sourced from the 2022 Health Information National Trends Survey.ParticipantsUS adults aged 18 years or older with self-reported diagnosis of diabetes (both type 1 and type 2).Primary and secondary outcomesPast 12-month utilisation of telehealth services, modality (eg, video, voice only), overall perception of quality of care, perceived trust in healthcare system and patient-centred communication score.ResultsIn an analysis of 1116 US adults with diabetes, representing 33.6 million individuals, 48.1% reported telehealth use in the past year. Telehealth users were likely to be younger, women, with higher income, and urban dwellers. Older adults (≥65 years) were less likely to use telehealth compared with those aged 18–49 years (OR 0.43, 95% CI 0.20 to 0.90). Higher income and more frequent healthcare visits were predictors of telehealth usage, with no significant differences across race, education or location. Across respondents with telehealth usage, 39.3% reported having video-only, 35.0% having phone (voice)-only and 25.7% having both modalities. The main motivations included provider recommendation, convenience, COVID-19 avoidance and guidance on in-person care needs. Non-users cited preferences for in-person visits, privacy concerns and technology challenges. Patient-reported quality-of-care outcomes were comparable between telehealth users and non-users, with no significant differences observed by telehealth modality or area of residence (metro status).ConclusionsAround half of US adults with diabetes used telehealth services in the past year. Patient-reported care quality was similar for telehealth and in-person visits. However, further efforts are needed to address key barriers to telehealth adoption, including privacy concern, technology difficulties, and care coordination issues.
Long-term effects of pelvic floor training in male chronic pelvic pain, correlation between subjective and objective outcomes: a study protocol for a randomised controlled trial
Authors: Hallencreutz Grape Helena , Nordgren Birgitta , Renström Koskela Lotta 
Published: November 2024

IntroductionChronic primary pelvic pain syndrome (CPPPS) is a condition characterised by pain in the pelvic area together with lower urinary tract symptoms. Pathophysiology remains largely unclear. Common treatment modalities show unsatisfactory results. This randomised controlled trial aims to establish the long-term effect of pelvic floor re-education using biofeedback and home training for men with CPPPS evaluated with the National Institute of Health–Chronic Prostatitis Symptom Index (NIH-CPSI) and to explore if outcomes can be correlated to changes in objective urodynamic measures.Methods and analysisAfter inclusion all study participants will go through baseline testing consisting of urodynamic evaluation, assessment of the pelvic floor muscles and the NIH-CPSI questionnaire, thereafter, randomised to intervention or control group. Intervention consists of short daily session of pelvic floor muscle training, during 6 months. Parallelly with starting up, the intervention group will attend four bio-feedback sessions, to guide and facilitate the training. The training will initially aim on how to correctly activate and relax the pelvic floor muscles with functional enhancement further on. The control group will be offered to enter the intervention group after the 6-month assessment. The outcome will be assessed by repeating the baseline tests at 3, 6 and 12 months.To compare the primary outcome, the NIH-CPSI questionnaire between and within the two groups will be analysed. Secondary outcomes are the differences in sub-score reduction according to the domains in the NIH-CPSI questionnaire, the manual assessment of the pelvic floor muscles and numerical results from the urodynamic testing. The correlation between subjective and objective outcomes will be analysed.Ethics and disseminationThe study obtained ethical approval from the Swedish Ethical Review Authority (2023-00286-01). The study result will be published in a peer-reviewed medical journal and presented at an international conference.Trial registration numberThis trial is registered at Clinicaltrials.gov (NCT06115083).
Thresholds for the value judgement of health technologies in the United Arab Emirates: a consensus approach through voting sessions
Authors: Aldallal Sara , Farghaly Mohamed , Fahmy Sahar , Alnaqbi Khalid A , Al Naeem Wael , Alsaadi Mouza , Moukarzel Marleine , Nader Fasseeh Ahmad , Korra Nada , Abaza Sherif , Kaló Zoltán 
Published: November 2024

Background
In the evolving healthcare landscape of the United Arab Emirates (UAE), establishing cost-effectiveness thresholds (CETs) is pivotal to informing decision-makers about the value of health technologies.

Objective
This study aimed to establish CETs for the UAE that harmonise with international standards while reflecting the nation’s unique healthcare needs and economic context.

Setting
United Arab Emirates.

Methods
A multitiered methodology was employed, involving a literature review, a panel of national experts and workshops with key stakeholders, including healthcare providers, government health departments and healthcare payers. The panel and workshops were integral in assessing global CET practices and their applicability to the UAE providing a preliminary framework for CET in the UAE. Structured voting sessions were then conducted allowing voting on crucial aspects of CET to determine the baseline threshold, multipliers for severity, rarity and health gain, and methodologies for quantifying disease severity.

Results
CETs were linked to the economic status of the UAE, with a baseline threshold of 0.75 times the gross domestic product per capita for one quality-adjusted life year gained. A multiplier system was introduced to reflect societal views on disease severity, disease rarity and the relative health benefit of health technologies. Based on the voting results, disease rarity was deemed the most crucial factor, receiving a maximum multiplier of 3X, while severity and health gain were assigned a maximum of 2X. The multiplier values for both disease severity and relative health gain would be determined on a continuous scale. The proportional or relative shortfall method would be used to assess disease severity.

Conclusions
The proposed CET framework for the UAE will be dependent on local generation of cost-effectiveness evidence. Periodic review of CETs based on initial experiences ensures the responsiveness of policymakers to the changing healthcare and economic environment.
Closed-form solution for a mathematical extension of the multi-term fractional Bateman equations via Mikusiński operational method
Authors: Jornet Marc 
Published: November 2024

Abstract
We give a closed-form solution, in terms of multivariate Mittag–Leffler functions, for a lower triangular linear fractional system consisting of Riemann–Liouville derivatives. For such a task, we use Mikusiński algebraic calculus, while solving a certain difference equation. The system is motivated by an extension of the multi-order fractional Bateman model in nuclear physics. Thus, the paper contributes to the theory of operational analysis in physics.
Contemporary Management of Acute Ischemic Stroke
Authors: Ho James P. , Powers William J. 
Published: November 2024

In the past decade, adding mechanical thrombectomy (MT) of intracranial arterial occlusions to intravenous (IV) thrombolysis has revolutionized the treatment of acute ischemic stroke (AIS) by expanding the therapeutic window to 24 h. Treatment decisions require establishing a high probability of AIS; confirming time since last known well (LKW); assessing severity of the neurological deficit; determining any contraindications to IV thrombolysis; and performing neuroimaging, usually noncontrast computed tomography (NCCT), to exclude intracerebral hemorrhage. If time since LKW is less than 4.5 h, patients with disabling stroke without contraindications can proceed immediately to IV thrombolysis while the decision about MT is under way. For some patients, the MT decision can be made on the basis of clinical assessment, NCCT, and CT angiography showing a large vessel occlusion. Others may require additional neuroimaging. Patients who are not candidates for IV thrombolysis within 4.5 h or MT should be immediately evaluated for eligibility for extended-window IV thrombolysis or early antiplatelet treatment.
Laparoscopic Cholecystectomy for Gall Bladder Volvulus: A Report of an Original Case With Review of Literature
Authors: Mohammed Ayad Ahmad 
Published: November 2024

Background: Volvulus of gallbladder is defined as a rotation of the gallbladder on its mesentery along the axis of the cystic duct and cystic artery. Many factors are postulated to be the causes such as anatomical, mechanical, physiological, and hormonal risk factors but the presence of a distended gallbladder with a redundant mesentery is thought to be an important cause.Case presentation: A 68‐year‐old woman presented with right hypochondrial pain and vomiting for 2 days that was radiated to the interscapular region and associated with nausea and vomiting. The patient had no jaundice and the abdominal examination showed severe tenderness with guarding during palpation of the right upper abdomen with no palpable mass. The WBCs were elevated, with normal liver enzymes, bilirubin, and alkaline phosphatase. The ultrasound showed a single gallstone with increased wall thickness. There was no significant clinical improvement with antibiotics and analgesics. During laparoscopy, volvulus of the gallbladder was discovered causing gangrene of the gallbladder. Laparoscopic detorsion and successful laparoscopic cholecystectomy were performed. The patient was discharged on the third postoperative day with dramatic improvement with no postoperative complications.Conclusion: Gall bladder volvulus is an acute surgical emergency that is usually seen in the elderly population. It required a high index of suspicion especially in the absence of gallstones and must be differentiated from acalculous cholecystitis. Most cases are discovered at surgery. It must be managed with immediate detorsion and cholecystectomy, and the prognosis is excellent in most cases after an appropriate surgical intervention.
Preventing Allogeneic Stem Cell Transplant–Related Cardiovascular Dysfunction: ALLO-Active Trial
Authors: Dillon Hayley T. , Saner Nicholas J. , Ilsley Tegan , Kliman David S. , Foulkes Stephen J. , Brakenridge Christian J. , Spencer Andrew , Avery Sharon , Claus Piet , Dunstan David W. , Daly Robin M. , Fraser Steve F. , Owen Neville , Lynch Brigid M. , Kingwell Bronwyn A. , La Gerche Andre , Howden Erin J. 
Published: November 2024

BACKGROUND:
Allogeneic stem cell transplantation (allo-SCT) is an efficacious treatment for hematologic malignancies but can be complicated by cardiac dysfunction and exercise intolerance impacting quality of life and longevity. We conducted a randomized controlled trial testing whether a multicomponent activity intervention could attenuate reductions in cardiorespiratory fitness and exercise cardiac function (co-primary end points) in adults undergoing allo-SCT.

METHODS:

Sixty-two adults scheduled for allo-SCT were randomized to a 4-month activity program (activity; n=30) or usual care (UC; n=32). Activity comprised a multicomponent exercise training (3 days.week
-1
) and sedentary time reduction (≥30 minutes.day
-1
) program and was delivered throughout hospitalization (≈4 weeks) and for 12 weeks after discharge. Physiological assessments conducted before admission and at 12 weeks after discharge included cardiopulmonary exercise testing to quantify peak oxygen uptake (

V
˙

o

2
p
e
a
k

), exercise cardiac magnetic resonance imaging for peak cardiac (CI
peak
) and stroke volume (SVI
peak
) index, echocardiography-derived left ventricular ejection fraction and global longitudinal strain, and cardiac biomarkers (cTn-I [troponin-I] and BNP [B-type natriuretic peptide]).

RESULTS:

Fifty-two participants (84%) completed follow-up (25 activity and 27 UC); median (interquartile range [IQR]) adherence to the activity program was 74% (41%–96%). There was a marked decline in

V
˙

o

2
p
e
a
k

in the UC program (−3.4 mL‧kg
-1
‧min
-1
[95% CI, −4.9 to −1.8]) that was attenuated with activity (−0.9 mL‧kg
-1‧
min
-1
[95% CI, −2.5 to 0.8]; interaction
P
=0.029). Activity preserved exercise cardiac function, with preservation of CI
peak
(0.30 L‧min
-1
‧m
-2
[95% CI, −0.34 to 0.41]) and SVI
peak
(0.6 mL.m
-2
[95% CI, −1.3 to 2.5]), both of which declined with UC (CI
peak
, −0.68 L‧min
-1
‧m
-2
[95% CI, –1.3 to −0.32]; interaction
P
=0.008; SVI
peak
, −2.7 mL.m
-2
[95% CI, −4.6 to −0.9]; interaction
P=
0.014). There were no treatment effects of activity on cardiac biomarkers or echocardiographic indices.

CONCLUSIONS:
Intervening during and after allo-SCT with a multicomponent activity program during and after allo-SCT is beneficial for preserving a patient’s cardiorespiratory fitness and exercise cardiac function. These results may have important implications for cardiovascular morbidity and mortality after allo-SCT.

REGISTRATION:

URL:
https://anzctr.org.au/
; Unique identifier: ACTRN12619000741189.