bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xpert MTB/RIF Ultra Is Highly Sensitive for the Diagnosis of Tuberculosis Lymphadenitis in a High-HIV Setting
Authors: Minnies Stephanie , Reeve Byron W. P. , Rockman Loren , Nyawo Georgina , Naidoo Charissa C. , Kitchin Natasha , Rautenbach Cornelia , Wright Colleen A. , Whitelaw Andrew , Schubert Pawel , Warren Robin M. , Theron Grant 
Published: September 2021

Tuberculosis lymphadenitis (TBL) is the most common extrapulmonary tuberculosis (EPTB) manifestation. Xpert MTB/RIF Ultra (Ultra) is a World Health Organization-endorsed diagnostic test, but performance data for TBL, including on noninvasive specimens, are limited. Fine-needle aspiration biopsy specimens (FNABs) from outpatients (≥18 years) with presumptive TBL (
n
= 135) underwent (i) routine Xpert MTB/RIF testing (later with Ultra once programmatically available), (ii) an MGIT 960 culture (if Xpert or Ultra negative or rifampin resistant), and (iii) study Ultra testing. Concentrated paired urine specimens underwent Ultra testing.
The Acceleration of Outer-Belt Electrons by Localized Electric Fields
Authors: Kropotkin A. P. 
Published: September 2021

Abstract
To explain the populations of the outer-belt energetic electrons, including relativistic electrons, that sporadically appear in the magnetosphere, a mechanism was proposed long ago for the acceleration of those electrons by short-term bursts of the electric field, which appear on the night side during substorm disturbances (Kropotkin, 1996). This mechanism can be substantially specified if the modern concepts of bursty bulk flows in the geomagnetic tail, the occurrence of dipolarization fronts, and the excitation of localized field-aligned-resonant poloidal Alfvén oscillations involving a strong component of the electric field in the dawn-dusk direction are taken into account.
Pharmaceutical industry payments and assisted reproduction in Australia: a retrospective observational study
Authors: Karanges Emily Aspasia , Nangla Conrad , Parker Lisa , Fabbri Alice , Farquhar Cynthia , Bero Lisa 
Published: September 2021

ObjectivesTo investigate the extent and nature of pharmaceutical industry payments related to fertility and assisted reproduction in Australia.Design and settingThis retrospective observational study employed four databases compiled from publicly available pharmaceutical industry transparency reports on educational event sponsorship (October 2011–April 2018), payments to healthcare professionals (October 2015–April 2018) and patient group support (January 2013–December 2017). Analyses were restricted to fertility-related payments by two major manufacturers of fertility medicines in Australia: Merck Serono and Merck, Sharp and Dohme (MSD).Primary and secondary outcome measuresDescriptive statistics on fertility-related payments and other transfers of value (counts, total and median costs in Australian dollars) for educational events and to healthcare professionals and patient groups.ResultsBetween October 2011 and April 2018, Merck Serono and MSD spent $A4 522 263 on 970 fertility-related events for healthcare professionals, including doctors, nurses and fertility scientists. 56.8% (551/970) events were held by fertility clinics and 29.3% (284/970) by professional medical associations. Between October 2015 and April 2018, Merck Serono spent $A403 800 across 177 payments to 118 fertility healthcare professionals, predominantly for educational event attendance. Recipients included obstetricians and gynaecologists (76.3% of payments, 135/177), nurses (11.3%, 20/177) and embryologists/fertility scientists (9.6%, 17/117). The highest paid healthcare professionals held leadership positions in major fertility clinics. Merck Serono provided $A662 850 to fertility-related patient groups for advocacy and education (January 2013–December 2017).ConclusionsThe pharmaceutical industry sponsored a broad range of fertility clinicians and organisations, including doctors, nurses, embryologists, professional medical organisations, fertility clinics and patient groups. This sponsorship may contribute to the overuse of fertility services.
Association of residual stenosis after balloon angioplasty with vessel wall geometries in intracranial atherosclerosis
Authors: Hou Zhikai , Zhang Zhe , Yan Long , You Jidong , Wan Min , Song Jia , Pan Yuesong , Hui Ferdinand , Miao Zhongrong , Lou Xin , Wang Yongjun , Jing Jing , Ma Ning 
Published: September 2021

BackgroundPercutaneous transluminal balloon angioplasty (PTBA) may be an alternative treatment for patients with symptomatic intracranial atherosclerotic disease (ICAD) refractory to medical treatment. This study aimed to investigate the association of vessel wall geometric characteristics on high-resolution magnetic resonance vessel wall imaging (MR-VWI) with low residual stenosis in patients with ICAD after PTBA.MethodsPatients with symptomatic ICAD who underwent PTBA were prospectively and consecutively enrolled. High-resolution MR-VWI was performed before the PTBA. Vessel wall geometries of the target artery, including normalized wall index (NWI: wall area/vessel area × 100%), normalized wall thickness index (NWTI: mean wall thickness/vessel radius × 100%), and remodeling index (RI) were evaluated. Low residual stenosis was defined as postprocedural stenosis degree ≤50%. Perioperative complications including symptomatic ischemic stroke/intracranial hemorrhage, death, and arterial dissection were recorded. The baseline characteristics, vessel wall geometries, and perioperative complications were compared between the patients with low residual stenosis and high residual stenosis.ResultsAmong 60 patients prospectively enrolled, low residual stenosis was achieved in 46 participants (77%). Three patients (5%) suffered from symptomatic ischemic stroke within 30 days. Multivariable logistic regression showed that a lower NWI and lower NWTI were associated with low residual stenosis after PTBA (adjusted OR 0.57, 95% CI 0.35 to 0.94, p=0.027; and adjusted OR 0.88, 95% CI 0.80 to 0.98, p=0.015).ConclusionsLower NWI and NWTI of the target artery on high-resolution MR-VWI were associated with low residual stenosis in patients with ICAD after PTBA.
Variants of Homomorphism Polynomials Complete for Algebraic Complexity Classes
Authors: Chaugule Prasad , Limaye Nutan , Varre Aditya 
Published: September 2021

We present polynomial families complete for the well-studied algebraic complexity classes VF, VBP, VP, and VNP. The polynomial families are based on the homomorphism polynomials studied in the recent works of Durand et al. (2014) and Mahajan et al. (2018). We consider three different variants of graph homomorphisms, namely
injective homomorphisms
,
directed homomorphisms
, and
injective directed homomorphisms
, and obtain polynomial families complete for VF, VBP, VP, and VNP under each one of these. The polynomial families have the following properties:

•
The polynomial families complete for VF, VBP, and VP are model independent, i.e., they do not use a particular instance of a formula, algebraic branching programs, or circuit for characterising VF, VBP, or VP, respectively.

•

All the polynomial families are hard under
p
-projections.
Algorithms and Lower Bounds for De Morgan Formulas of Low-Communication Leaf Gates
Authors: Kabanets Valentine , Koroth Sajin , Lu Zhenjian , Myrisiotis Dimitrios , Oliveira Igor C. 
Published: September 2021

The class FORMULA[s]∘G consists of Boolean functions computable by size-sDe Morgan formulas whose leaves are any Boolean functions from a class G. We givelower boundsand (SAT, Learning, andpseudorandom generators(PRGs))algorithmsfor FORMULA[n1.99]∘G, for classes G of functions withlow communication complexity. Let R(k)G be the maximumk-party number-on-forehead randomized communication complexity of a function in G. Among other results, we show the following:•The Generalized Inner Product function GIPkncannot be computed in FORMULA[s]° G on more than 1/2+ε fraction of inputs fors=o(n2/k⋅4k⋅R(k)(G)⋅log⁡(n/ε)⋅log⁡(1/ε))2).This significantly extends the lower bounds against bipartite formulas obtained by [62]. As a corollary, we get an average-case lower bound for GIPknagainst FORMULA[n1.99]∘PTFk−1, i.e., sub-quadratic-size De Morgan formulas with degree-k-1)PTF(polynomial threshold function) gates at the bottom. Previously, it was open whether a super-linear lower bound holds for AND of PTFs.•There is a PRG of seed length n/2+O(s⋅R(2)(G)⋅log⁡(s/ε)⋅log⁡(1/ε)) that ε-fools FORMULA[s]∘G. For the special case of FORMULA[s]∘LTF, i.e., size-sformulas withLTF(linear threshold function) gates at the bottom, we get the better seed length O(n1/2⋅s1/4⋅log⁡(n)⋅log⁡(n/ε)). In particular, this provides the first non-trivial PRG (with seed length o(n)) for intersections ofnhalfspaces in the regime where ε≤1/n, complementing a recent result of [45].•There exists a randomized 2n-t#SAT algorithm for FORMULA[s]∘G, wheret=Ω(n\√s⋅log2⁡(s)⋅R(2)(G))/1/2.In particular, this implies a nontrivial #SAT algorithm for FORMULA[n1.99]∘LTF.•The Minimum Circuit Size Problem is not in FORMULA[n1.99]∘XOR; thereby making progress on hardness magnification, in connection with results from [14, 46]. On the algorithmic side, we show that the concept class FORMULA[n1.99]∘XOR can be PAC-learned in time 2O(n/log n).
The Role of mRNA Translational Control in Tumor Immune Escape and Immunotherapy Resistance
Authors: Cerezo Michaël , Robert Caroline , Liu Lunxu , Shen Shensi 
Published: September 2021

Abstract
Tremendous advances have been made in cancer immunotherapy over the last decade. Among the different steps of gene expression, translation of mRNA is emerging as an essential player in both cancer and immunity. Changes in mRNA translation are both rapid and adaptive, and translational reprogramming is known to be necessary for sustaining cancer cell proliferation. However, the role of mRNA translation in shaping an immune microenvironment permissive to tumors has not been extensively studied. Recent studies on immunotherapy approaches have indicated critical roles of mRNA translation in regulating the expression of immune checkpoint proteins, tuning the secretion of inflammation-associated factors, modulating the differentiation of immune cells in the tumor microenvironment, and promoting cancer resistance to immunotherapies. Careful consideration of the role of mRNA translation in the tumor-immune ecosystem could suggest more effective therapeutic strategies and may eventually change the current paradigm of cancer immunotherapy. In this review, we discuss recent advances in understanding the relationship between mRNA translation and tumor-associated immunity, the potential mechanisms of immunotherapy resistance in cancers linked to translational reprogramming, and therapeutic perspectives and potential challenges of modulating translational regulation in cancer immunotherapy.
The Landmark Discovery That Paved the Way to a Mechanistic Understanding of P53 Gain of Function and Personalized Medicine
Authors: Napoli Marco , Deshpande Avani A. , Flores Elsa R. 
Published: September 2021

Abstract
In 1990, Baker and colleagues reported their seminal findings in Cancer Research focusing on the transition from adenoma to carcinoma of the colon. By sequencing the TP53 locus in 58 colorectal tumors (25 adenomas and 33 carcinomas) and measuring its allelic deletions, they discovered that this transition requires the loss of one TP53 allele and the mutation of the other one. Here, we discuss how this landmark discovery shed a new light on p53 mutations, prompting the generation of novel mouse models that definitively proved the mutant p53 gain-of-function hypothesis suggested by these results. Finally, we evaluate the implications that the Vogelstein model of cancer progression had on numerous aspects of cancer biology and cancer care, including the characterization of tumor evolution and the response to therapy, and how it ultimately contributed to the wider adoption of early detection screenings and personalized medicine.
See related article by Baker and colleagues, Cancer Res 1990;50:7717–22
Lowering mTORC1 Drives CAR T-Cells Home in Acute Myeloid Leukemia
Authors: Maiti Abhishek , Daver Naval G. 
Published: September 2021

Abstract
Cellular therapies have demonstrated limited efficacy thus far in acute myeloid leukemia (AML). A recent study shows that mTOR complex 1 activation downregulated CXCR4 reducing marrow infiltration of EpCAM-targeting chimeric antigen receptor (CAR) T-cells in AML. Abrogating mTOR signaling by cotreatment with mTOR inhibitors during IL2-mediated ex vivo expansion upregulated CXCR4 and bolstered bone marrow migration and AML elimination by CAR T-cells.
See related article by Nian et al., p. 6026
Contemporary Patients With Congenital Heart Disease
Authors: Brouwer Charlotte , Hebe Joachim , Lukac Peter , Nürnberg Jan-Hendrik , Cosedis Nielsen Jens , de Riva Silva Marta , Blom Nico , Hazekamp Mark , Zeppenfeld Katja 
Published: September 2021

Background:
Poor outcome after atrial tachycardia (AT) radiofrequency catheter ablation (RFCA) in repaired congenital heart disease (CHD) has been attributed to CHD complexity. This may not apply to contemporary patients. The objective of our study was to assess outcome after RFCA for AT in contemporary patients with CHD according to prior atrial surgery and predefined procedural endpoints.

Methods:
Patients with CHD referred for AT RFCA to 3 European centers were classified as no atrial surgery/cannulation only, limited or extensive prior atrial surgery. Procedural success was predefined as termination and nonreinducibility for focal AT and bidirectional block across ablation lines for intra-atrial reentrant tachycardia and after empirical substrate ablation for noninducible patients. Patients were followed for AT recurrence and mortality.

Results:
Ablation was performed in 290 patients (41±17 years, 59% male; 3-dimensional mapping 89%, irrigated tip catheters 90%, transbaffle access 15%). In 197, 233 AT were targeted (196 intra-atrial reentrant tachycardia [64% cavotricuspid (mitral) isthmus–dependent, 33% systemic-venous incision–dependent] and 37 focal AT). In 93 noninducible patients, empirical substrate ablation was performed. Procedural success was achieved in 209 (84%) patients. AT recurred in 148 (54%) 10 (interquartile range, 0–25) months after RFCA. AT-free survival was significantly better in patients with no atrial repair/cannulation only and in patients with complete procedural success independently of CHD complexity. From 94 patients undergoing reablation, the initially targeted substrate had recovered in 64%.

Conclusions:
In contemporary patients with CHD, outcome after AT ablation is associated with presence of prior atrial surgery and achievement of predefined procedural endpoints rather than CHD complexity. Techniques to improve lesion durability are likely to further improve long-term outcome.
Human RyR2 (Ryanodine Receptor 2) Loss-of-Function Mutations
Authors: Li Yanhui , Wei Jinhong , Guo Wenting , Sun Bo , Estillore John Paul , Wang Ruiwu , Yoruk Ayhan , Roston Thomas M. , Sanatani Shubhayan , Wilde Arthur A.M. , Gollob Michael H. , Roberts Jason D. , Tseng Zian H. , Jensen Henrik K. , Chen S.R. Wayne 
Published: September 2021

Background:

The overall objective of the present study is to extend our understanding of the clinical phenotype and underlying mechanism of a newly discovered cardiac arrhythmia syndrome through a multicenter study. Gain-of-function mutations in the cardiac Ca
2+
release channel (RyR2 [ryanodine receptor 2]) cause catecholaminergic polymorphic ventricular tachycardia, whereas loss-of-function RyR2 mutations are linked to a new cardiac arrhythmia disorder termed Ca
2+
-release deficiency syndrome (CRDS). Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmia disorder characterized by stress-induced bidirectional and polymorphic ventricular tachyarrhythmias and is routinely diagnosed by using exercise stress testing. Conversely, RyR2-CRDS is characterized by ventricular arrhythmias and sudden cardiac death but a negative exercise stress testing for catecholaminergic polymorphic ventricular tachycardia. There are currently no clinical diagnostic tests for CRDS and affected patients may manifest with sudden cardiac death as their first symptom. In the absence of effective clinical diagnostic tools, in vitro functional characterization of associated RyR2 mutations provides an alternative means to identify potential cases of CRDS.

Methods:
We searched for patients presenting with phenotypes compatible with CRDS that have RyR2 mutations and performed in vitro functional characterization.

Results:

We found that 3 novel (G570D, R4147K, and A4203V) and 2 previously reported (M4109R and A4204V) RyR2 mutations associated with CRDS phenotypes markedly reduced caffeine-induced Ca
2+
release and store overload-induced Ca
2+
release. We also characterized 2 additional loss-of-function RyR2 mutations previously reported (Q3925E and L4769S) that are located in the central and channel pore-forming domains critical for Ca
2+
activation and channel gating. Q3925E was identified through postmortem genetic testing in an individual who died suddenly, while L4769S is a variant of uncertain significance reported in ClinVar, suggesting that RyR2 CRDS may be under detected.

Conclusions:
These findings provide further support for the existence of an emerging RyR2 loss-of-function associated arrhythmia syndrome (CRDS) and shed new insights into the disease mechanism.
Atrial Fibrillation in Spontaneous Intracerebral Hemorrhage, Dijon Stroke Registry (2006–2017)
Authors: Gabet Amélie , Olié Valérie , Béjot Yannick 
Published: September 2021

Background
Atrial fibrillation (AF) represents a major indication for oral anticoagulants (OAC) that contribute to spontaneous intracerebral hemorrhage (ICH). This study evaluated AF prevalence among patients with ICH, temporal trends, and early functional outcomes and death of patients.

Methods and Results

Patients with first‐ever ICH were prospectively recorded in the population‐based stroke registry of Dijon, France, (2006–2017). Association between AF and early outcome of patients with ICH (ordinal modified Rankin Scale score and death at discharge) were analyzed using ordinal and logistic regressions. Among 444 patients with ICH, 97 (21.9%) had AF, including 65 (14.6%) with previously known AF treated with OAC, and 13 (2.9%) with newly diagnosed AF. AF prevalence rose from 17.2% (2006–2011) to 25.8% (2012–2017) (
P
‐trend=0.05). An increase in the proportion of AF treated with OAC (11.3% to 17.5%,
P
‐trend=0.09) and newly diagnosed AF (1.5% to 4.2%,
P
‐trend=0.11) was observed. In multivariable analyses, after adjustment for premorbid OAC, AF was not significantly associated with ordinal modified Rankin Scale score (odds ratio [OR], 1.29; 95% CI, 0.69–2.42) or death (OR, 0.89; 95% CI, 0.40–1.96) in patients with ICH. Nevertheless, adjusted premorbid OAC use remained highly associated with a higher probability of death (OR, 2.53; 95% CI, 1.11–5.78).

Conclusions
AF prevalence and use of OAC among patients with ICH increased over time. Premorbid use of OAC was associated with poor outcome after ICH, thus suggesting a need to better identify ICH risk before initiating or pursuing OAC therapy in patients with AF, and to develop acute treatment and secondary prevention strategies after ICH in patients with AF.
Investigating Rurality as a Risk Factor for State and Trait Hopelessness in Hospitalized Patients With Ischemic Heart Disease
Authors: Bomgaars Deb , Jensen Gwenneth A. , White Lynn L. , Van De Griend Kristin M. , Visser Angela K. , Goodyke Madison P. , Luong Anna , Tintle Nathan L. , Dunn Susan L. 
Published: September 2021

Background
Rurality and hopelessness are each associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining rurality as a risk factor for hopelessness in patients with IHD. This study evaluated rurality as a risk factor for state and trait hopelessness in adults hospitalized with IHD in samples drawn from the Great Lakes and Great Plains regions of the United States.

Methods and Results

A descriptive cross‐sectional design was used. Data were collected from 628 patients hospitalized for IHD in the Great Lakes (n=516) and Great Plains (n=112). Rural–Urban Commuting Area codes were used to stratify study participants by level of rurality. Levels of state hopelessness (measured by the State‐Trait Hopelessness Scale) were higher in rural patients (58.8% versus 48.8%; odds ratio [OR], 1.50; 95% CI, 1.03–2.18), a difference that remained statistically significant after adjusting for demographics, depression severity (measured by the Patient Health Questionnaire–8), and physical functioning (measured by the Duke Activity Status Index; OR, 1.59; 95% CI, 1.06–2.40;
P
=0.026). There was evidence of an interaction between marital status and rurality on state hopelessness after accounting for covariates (
P
=0.02). Nonmarried individuals had an increased prevalence of state hopelessness (nonmarried 72.0% versus married 52.0%) in rural areas (
P
=0.03).

Conclusions
Rural patients with IHD, particularly those who are nonmarried, may be at higher risk for state hopelessness compared with patients with IHD living in urban settings. Understanding rurality differences is important in identifying subgroups most at risk for hopelessness.

Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT04498975.