bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study design and baseline characteristics for the reflect gene therapy trial ofm.11778g>A/ND4-LHON
Authors: Subramanian Prem S , Newman Nancy J , Moster Mark , Wang An-Guor , Yu-Wai-Man Patrick , Donahue Sean , Leroy Bart P , Carelli Valerio , Biousse Valerie , Vignal-Clermont Catherine , Sergott Robert C , Sadun Alfredo A , Rebolleda Gema , Chwalisz Bart K , Banik Rudrani , Bazin Fabienne , Cox Eric , Roux Michel , Taiel Magali , Sahel Jose-Alain 
Published: November 2022

ObjectiveREFLECT is the first randomised, double-masked, placebo-controlled multicentre phase 3 clinical trial that evaluated the efficacy and safety of bilateral intravitreal (IVT) injection of lenadogene nolparvovec in subjects with Leber hereditary optic neuropathy carrying the m.11778G>A mutation.Methods and analysisA total of 98 subjects were enrolled with vision loss of ≤12 months. The subjects were randomised to one of two treatment arms with all subjects receiving an intravitreal (IVT) injection of lenadogene nolparvovec in their first affected eye and the second-affected eye randomised to receive IVT of either lenadogene nolparvovec or placebo.ResultsThe majority of subjects were male with a mean duration of vision loss of 8.3 months. All but one subject experienced bilateral loss of vision at the time of injection. The mean best-corrected visual acuity of first-affected eyes was worse compared with second/not-yet-affected eyes. Analysis of retinal anatomical parameters showed increased thinning in the first-affected eyes when compared with the second/not-yet-affected eyes with both treatment arms showing significant changes compared with unaffected individuals.ConclusionThe REFLECT trial is the third and the largest phase 3 clinical study evaluating lenadogene nolparvovec in m.11778G>A Leber hereditary optic neuropathy (LHON) subjects. The observed demographics in REFLECT are consistent with previous reports in LHON subjects in the acute and dynamic phases of LHON disease. Combined with the visual function and anatomical parameters obtained in the previous RESCUE and REVERSE trials, REFLECT has provided a uniformly collected data set that should help direct future LHON clinical trials.
User interest in a new non-hormonal long-acting reversible contraceptive: what impact does mechanism of action have on past and future contraceptive decision-making?
Authors: Shankie-williams Kirsten Norma , Ratcliffe Sarah E , Dowland Samson N , Black Kirsten 
Published: November 2022

BackgroundWe are in the process of developing a new non-hormonal long-acting reversible method of contraception (LARC) in recognition of the fact that a significant minority of users are unhappy with their current method. Our method has a novel (post-fertilisation) mechanism of action (MOA), but little is known about the value users place on this.MethodsUsing in-depth interviews, we explored 30 Australian end-users’ experiences of contraception, recruited via social media. A thematic approach was taken to examine the influence the MOA has on choice and factors affecting willingness to try current methods and a novel non-hormonal LARC with a post-fertilisation effect.ResultsWe identified two themes that were the most salient across all interviews: that contraceptive decision-making involves a trade-off of priorities, influenced by contraceptive properties (including MOA) and the context in which contraception is used; and views on novel methods of contraception were influenced by willingness to trial new products and interest in non-hormonal options. Side effects, efficacy, and the financial burden of contraceptives were all considered more important than MOA during decision-making. Participants were willing to try a new method if endorsed by trusted sources, including friends and medical practitioners, and were enthusiastic to try a novel LARC with no hormones.ConclusionThis study found that the MOA had minimal impact on participants’ choice of contraception. Rather, avoidance of hormones and side effects influenced willingness to try a novel method over any unacceptable aspects of a post-fertilisation MOA.
Neighbourhood risk factors of recurrent tuberculosis in Cape Town: a cohort study using geocoded notification data
Authors: Molemans Marjan , van Leth Frank , McKelly David Henry , Wood Robin , Hermans Sabine 
Published: November 2022

BackgroundIndividuals with a history of tuberculosis (TB) disease are at higher risk of developing a subsequent episode than those without. Considering the role of social and environmental factors in tuberculosis, we assessed neighbourhood-level risk factors associated with recurrent tuberculosis in Cape Town, South Africa.MethodsThis cohort consisted of patients who completed treatment for their first drug-sensitive TB episode between 2003 and 2015. Addresses were geocoded at neighbourhood level. Data on neighbourhood-level factors were obtained from the Census 2011 (household size, population density) and the City of Cape Town (Socio-Economic Index). Neighbourhood-level TB burden was calculated annually by dividing the number of notified TB episodes by the population in that neighbourhood. Multilevel survival analysis was performed with the outcome recurrent TB, defined as a second episode of TB, and controlling for individual-level risk factors (age, gender and time since first episode in years). Follow-up ended at the second episode, or on 31 December 2015, whichever came first.ResultsThe study included 173 421 patients from 700 neighbourhoods. Higher Socio-Economic Index was associated with a lower risk of recurrence compared with average Socio-Economic Index. An increased risk was found for higher household size and TB burden, with an increase of 20% for every additional person in mean household size and 10% for every additional TB episode/100 inhabitants. No association was found with population density.ConclusionRecurrent TB was associated with increased household size and TB burden at neighbourhood level. These findings could be used to target TB screening activities.
Motor cortex functional connectivity is associated with underlying neurochemistry in ALS
Authors: Dey Avyarthana , Luk Collin C , Ishaque Abdullah , Ta Daniel , Srivastava Ojas , Krebs Dennell , Seres Peter , Hanstock Chris , Beaulieu Christian , Korngut Lawrence , Frayne Richard , Zinman Lorne , Graham Simon , Genge Angela , Briemberg Hannah , Kalra Sanjay 
Published: November 2022

ObjectiveTo identify structural and neurochemical properties that underlie functional connectivity impairments of the primary motor cortex (PMC) and how these relate to clinical findings in amyotrophic lateral sclerosis (ALS).Methods52 patients with ALS and 52 healthy controls, matched for age and sex, were enrolled from 5 centres across Canada for the Canadian ALS Neuroimaging Consortium study. Resting-state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy data were acquired. Functional connectivity maps, diffusion metrics and neurometabolite ratios were obtained from the analyses of the acquired multimodal data. A clinical assessment of foot tapping (frequency) was performed to examine upper motor neuron function in all participants.ResultsCompared with healthy controls, the primary motor cortex in ALS showed reduced functional connectivity with sensory (T=5.21), frontal (T=3.70), temporal (T=3.80), putaminal (T=4.03) and adjacent motor (T=4.60) regions. In the primary motor cortex, N-acetyl aspartate (NAA, a neuronal marker) ratios and diffusion metrics (mean, axial and radial diffusivity, fractional anisotropy (FA)) were altered. Within the ALS cohort, foot tapping frequency correlated with NAA (r=0.347) and white matter FA (r=0.537). NAA levels showed associations with disturbed functional connectivity of the motor cortex.ConclusionIn vivoneurochemistry may represent an effective imaging marker of impaired motor cortex functional connectivity in ALS.
Investigating physician leadership competencies in rural and remote areas of the province of Aceh, Indonesia
Authors: Maulina Fury , Hasanbasri Mubasysyir , Scheele Fedde , Busari Jamiu O 
Published: November 2022

BackgroundsGlobally, the most rural healthcare systems are lagging behind those of urban healthcare systems. Especially in rural and remote areas, the essential resources to provide principal health services are inadequate. It is purported that physicians have an important role in healthcare systems. Unfortunately, there is a paucity of studies on physician leadership development in Asia, especially on how to enhance physician leadership competencies in rural and remote low-resource settings. This study aimed to investigate doctors’ perceptions of existing and needed physician leadership competencies based on their experiences in primary care settings in low-resource rural and remote areas are in Indonesia.MethodsWe performed a qualitative study with a phenomenological approach. Eighteen primary care doctors, who worked in rural and remote areas of Aceh, Indonesia, purposively selected, were interviewed. Prior to the interview, participants were asked to select the top-five skills they deemed most essential for their work based on the five domains of the ‘Lead Self’, ‘Engage Others’, ‘Achieve Results’, ‘Develop Coalitions’ and ‘Systems Transformation’ (LEADS) framework. We then performed a thematic analysis of the interview transcripts.ResultsWe identified the following qualities a good physician leader in low-resource rural and remote settings should possess: (1) cultural sensitivity skills; (2) a strong character that includes courage and determination; and (3) creativity and flexibility skills.ConclusionsLocal cultural and infrastructural factors create a need for several different competencies within the LEADS framework. A profound amount of cultural sensitivity was considered the most important in addition to the ability to be resilient, versatile and ready for creative problem-solving.
Does time to surgery for traumatic hip fracture impact the efficacy of fascia iliaca blocks? A brief report
Authors: Akinola Kerrick , Salottolo Kristin , Meinig Richard , Fine Landon , Madayag Robert M , Ekengren Francie , Tanner Allen , Bar-Or David 
Published: November 2022

ObjectivesOutcomes after traumatic hip fracture have shown to be significantly improved with timely surgical management. This study determined whether there were differences in efficacy of fascia iliaca compartment block (FICB) on pain outcomes in patients with hip fracture, once stratified by time to surgery.MethodsTrauma patients (55–90 years) admitted to five Level I/II trauma centers within 12 hours of hip fracture were included. Patients with coagulopathy, significant multi-trauma (injury severity score >16), bilateral hip fractures, and postoperative FICBs were excluded. The primary exposure was analgesia modality: adjunctive FICB or systemic analgesics (no FICB). Study endpoints were incidence of delirium through 48 hours postoperatively (%), preoperative and postoperative oral morphine equivalents (OMEs), and preoperative and postoperative pain (0–10 scale). Adjusted regression models were used to examine the effect of FICB on outcomes; all models were stratified by time from arrival to surgery, ≤24 hours (earlier surgery; n=413) and >24 hours (later surgery; n=143).ResultsFICB use was similar with earlier and later surgery (70.2% vs 76.2%), and there were no demographic differences by utilization of FICB, by time to surgery. In the earlier surgery group, preoperative pain was lower for patients with FICB versus no FICB (3.6 vs 4.5, p<0.001), with no difference by FICB for delirium (OR 1.00, p>0.99) or OMEs (p=0.75 preoperative, p=0.91 postoperative). In the later surgery group, there was a nearly twofold reduction in preoperative OMEs with FICB than no FICB (25.5 mg vs 45.2 mg, p=0.04), with no differences for delirium (OR 4.21, p=0.18), pain scores (p=0.25 preoperative, p=0.27 postoperative), and postoperative OMEs (p=0.34).ConclusionsCompared with systemic analgesia, FICB resulted in improved pain scores at the preoperative assessment among patients with earlier surgery, whereas FICB reduced opioid consumption over the preoperative period only when surgery was later than 24 hours from arrival.Level of evidenceII, prospective, therapeutic.
Thin shell dynamics in Lovelock gravity
Authors: Guilleminot Pablo , Merino Nelson , Olea Rodrigo 
Published: November 2022

AbstractWe study matching conditions for a spherically symmetric thin shell in Lovelock gravity which can be read off from the variation of the corresponding first-order action. In point of fact, the addition of Myers’ boundary terms to the gravitational action eliminates the dependence on the acceleration in this functional and such that the canonical momentum appears in the surface term in the variation of the total action. This procedure leads to junction conditions given by the discontinuity of the canonical momentum defined for an evolution normal to the boundary.In particular, we correct existing results in the literature for the thin shell collapse in generic Lovelock theories, which were mistakenly drawn from an inaccurate analysis of the total derivative terms in the system.
Bottom quark mass with calibrated uncertainty
Authors: Erler Jens , Spiesberger Hubert , Masjuan Pere 
Published: November 2022

AbstractWe determine the bottom quark mass $${\hat{m}}_b$$

m
^

b

from QCD sum rules of moments of the vector current correlator calculated in perturbative QCD to $${{\mathcal {O}}} ({\hat{\alpha }}_s^3)$$

O
(

α
^

s
3

)

. Our approach is based on the mutual consistency across a set of moments where experimental data are required for the resonance contributions only. Additional experimental information from the continuum region can then be used for stability tests and to assess the theoretical uncertainty. We find $${\hat{m}}_b({\hat{m}}_b) = (4180.2 \pm 7.9)$$

m
^

b

(

m
^

b

)

=

(
4180.2
±
7.9
)

MeV for $${\hat{\alpha }}_s(M_Z) = 0.1182$$

α
^

s

(

M
Z

)

=
0.1182

.
The two-channel exotic charmonium-like resonances in the mass region (3900–4700) MeV
Authors: Badalian A. M. , Simonov Yu. A. 
Published: November 2022

AbstractNumerous resonances in the$$c{{\bar{c}}}$$cc¯and 4qsystems, containing$$c{{\bar{c}}}$$cc¯plus$$s{{\bar{s}}}$$ss¯quarks (or light$$q{{\bar{q}}}$$qq¯) were observed during last decades and recently the LHCb has found a remarkable narrow peak$$T_{cc}(3875)$$Tcc(3875)in the$$D D^*$$DD∗system. Besides there are several highly excited charmonium-like resonances, which can be treated as the shifted standard charmonium states. We analyze all these groups of the resonances in the mass region (3900–4700) MeV, using relativistic strong coupling theory with possible channel coupling phenomena. For the shifted charmonium states conventional charmonium spectrum is presented, being calculated with the relativistic string Hamiltonian, which does not contain fitting parameters, while for high excitations the universal flattened confining potential is used. It is shown thatX(4274), X(4500), X(4700) can be identified as$$3\,^3P_1, 4\,^3P_0, 5\,^3P_0$$33P1,43P0,53P0states. The group of exotic states are considered using the Extended Recoupling Model, where two mesons$$m_1,m_2$$m1,m2transfer into another pair of mesons$$m_3, m_4$$m3,m4and back (infinite number of times), creating the four-quark resonance. Within this approach the resonances –$$T_{cc}(3875), Z_c(3900), X(3915), Z_{cs}(3985), X(4014)$$Tcc(3875),Zc(3900),X(3915),Zcs(3985),X(4014), andX(4140) – can be explained as the exotic four-quark states in theS-wave decay channels.
Collider searches for heavy neutral leptons: beyond simplified scenarios
Authors: Abada Asmaa , Escribano Pablo , Marcano Xabier , Piazza Gioacchino 
Published: November 2022

AbstractWith very few exceptions, the large amount of available experimental bounds on heavy neutral leptons – HNL – have been derived relying on the assumption of the existence of a single (usually Majorana) sterile fermion state that mixes with only one lepton flavour. However, most of the extensions of the Standard Model involving sterile fermions predict the existence of several HNLs, with complex mixing patterns to all flavours. Consequently, most of the experimental bounds for HNLs need to be recast before being applied to a generic scenario. In this work, we focus on LHC searches of heavy neutral leptons and discuss how to reinterpret the available bounds when it comes to consider mixings to all active flavours, not only in the case with a single HNL, but also in the case when more heavy neutral leptons are involved. In the latter case, we also consider the possibility of interference effects and show how the bounds on the parameter space should be recast.
Efficient Simulation of Sparse Graphs of Point Processes
Authors: Mascart Cyrille , Hill David , Muzy Alexandre , Reynaud-Bouret Patricia 
Published: November 2022

We derive new discrete event simulation algorithms for marked time point processes. The main idea is to couple a special structure, namely the associated local independence graph, as defined by Didelez, with the activity tracking algorithm of Muzy for achieving high-performance asynchronous simulations. With respect to classical algorithms, this allows us to drastically reduce the computational complexity, especially when the graph is sparse.
Abstract B018: Eosinophils alter metastatic spread in pancreatic cancer
Authors: Hoffman Megan T. , Lenehan Patrick J. , Wang Jennifer , Ali Lestat , Qiang Li , Uchida Amiko , Vayrynen Sara , Costa Andressa Dias , Dougan Michael , Heckler Max , Nowak Jonathan , Wolpin Brian W. , Dougan Stephanie K. 
Published: November 2022

Abstract
Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the US with a 11% 5-year survival rate. A key contributor of this dismal prognosis is early and frequent metastatic spread with limited treatment options for patients. Metastasis in PDA is facilitated by a robust fibroinflammatory response in the primary tumor site, a large portion of which is composed of infiltrating immune cells, and survival during transit to establish in the secondary site. In the primary tumor reactive stroma, we found increased eosinophils in both human and mouse PDA compared to the normal pancreas. Eosinophils are an innate immune cell best known for their ability to control parasite responses and have been implicated in either pro- or anti-cancer roles in various solid tumors. We used the ΔdblGata mice, which lack eosinophils, to study the role of eosinophils during metastatic spread using a resectable model of PDA metastasis. This model of metastasis was developed to facilitate consistent seeding of lung metastasis in approximately 50 percent of mice from a transient subcutaneous tumor which undergoes subsequent surgical removal and harvest to evaluate metastasis at 4 weeks. We found that mice lacking eosinophils have increased metastasis to the lung in our resectable model of PDA metastasis but no difference in establishment of IV injected PDA tumor cells, suggesting eosinophil control at the primary tumor site. Single cell sequencing of the subcutaneous tumors finds differences in the angiogenic subtypes, tip and stalk cells, in mice lacking eosinophils. Sequencing of eosinophil populations in humans and mice find an increase in angiogenic signaling suggesting a regulatory role in tumor cell access to the circulation. We conclude that eosinophils in PDA inhibit the metastatic process through control of angiogenic signaling.
Citation Format: Megan T. Hoffman, Patrick J. Lenehan, Jennifer Wang, Lestat Ali, Li Qiang, Amiko Uchida, Sara Vayrynen, Andressa Dias Costa, Michael Dougan, Max Heckler, Jonathan Nowak, Brian W. Wolpin, Stephanie K. Dougan. Eosinophils alter metastatic spread in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B018.
Abstract B021: The axon guidance receptor UNC5B is a driver of pancreatic cancer metastasis
Authors: Harris Chris , Casabianca Anthony , Sechrist Zach , Shields Cory , Narrow Wade , Withers Tracy , Dudgeon Crissy , O'Dell Mike , Hezel Aram , Carpizo Darren 
Published: November 2022

Abstract
Axon guidance pathways have often been linked to tumorigenesis by informatics analyses, but their roles in tumorigenesis are not well understood at a functional level. Here we show that axon guidance receptor UNC5B and its ligand, NTN1, promote the metastasis of pancreatic ductal adenocarcinomas (PDACs) by reducing anoikis and by promoting a mesenchymal phenotype. In vivo, removal of two floxed UNC5B alleles eliminated PDAC metastasis in the genetically engineered KPC mouse model, and also reduced metastasis by xenografted PDAC cell lines. PDAC metastasis also decreased upon treatment of animals with NP137, an antibody that targets NTN1. In vitro, deletion of UNC5B from pancreatic adenocarcinoma cell lines reduced invasiveness, and was sufficient to convert PDAC cell lines from an epithelial to a mesenchymal state. UNC5B also increased YAP1 expression but decreased anoikis; anoikis could then be restored by treatment with the YAP1 inhibitor CA3. Clinically, UNC5B expression associated with poor outcomes in patients with pancreatic adenocarcinomas. UNC5B and NTN1 expression increased upon truncation of the SWI/SNF component ARID1A, which is recurrently mutated in PDACs. Highly focal amplifications of UNC5B were also observed in some patient samples, and were mutually exclusive with mutations in ARID1A or ARID1B. NP137 is currently in clinical trials for various cancers, and may benefit pancreatic adenocarcinoma patients, particularly those with UNC5B amplifications or with ARID1A/ARID1B mutations.
Citation Format: Chris Harris, Anthony Casabianca, Zach Sechrist, Cory Shields, Wade Narrow, Tracy Withers, Crissy Dudgeon, Mike O'Dell, Aram Hezel, Darren Carpizo. The axon guidance receptor UNC5B is a driver of pancreatic cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B021.