bluuebunny/crossref_metadata_2025_split huggingface dataset:
VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis
Authors: Nicholson Steve , Tovey Holly , Elliott Tony , Burnett Stephanie M. , Cruickshank Clare , Bahl Amit , Kirkbride Peter , Mitra Anita V. , Thomson Alastair H. , Vasudev Naveen , Venugopal Balaji , Slade Rachel , Tregellas Lucy , Morgan Bruno , Hassall Alison , Hall Emma , Pickering Lisa M. 
Published: October 2021

Abstract
Background
We investigated the first-line activity of vinflunine in patients with penis cancer. Cisplatin-based combinations are commonly used, but survival is not prolonged; many patients are unfit for such treatment or experience toxicity that outweighs clinical benefit.

Methods
Twenty-five patients with inoperable squamous carcinoma of the penis were recruited to a single-arm, Fleming–A’Hern exact phase II trial. Treatment comprised 4 cycles of vinflunine 320 mg/m2, given every 21 days. Primary endpoint was clinical benefit rate (CBR: objective responses plus stable disease) assessed after 4 cycles. Seven or more objective responses or disease stabilisations observed in 22 evaluable participants would exclude a CBR of <15%, with a true CBR of >40% being probable.

Results
Twenty-two participants were evaluable. Ten objective responses or disease stabilisations were confirmed. CBR was 45.5%, meeting the primary endpoint; partial response rate was 27.3%. Seven patients received >4 cycles of vinflunine. Dose reduction or treatment delay was required for 20% of cycles. In all, 68% of patients experienced at least one grade 3 adverse event. Two deaths on treatment were not caused by disease progression.

Conclusions
Pre-specified clinical activity threshold was exceeded. Toxicity was in keeping with experience in other tumours. Vinflunine merits further study in this disease.

Trial registration
NCT02057913.
The Variability in Potential Biomarkers for Cochlear Synaptopathy After Recreational Noise Exposure
Authors: Maele Tine Vande , Keshishzadeh Sarineh , Poortere Nele De , Dhooge Ingeborg , Keppler Hannah , Verhulst Sarah 
Published: October 2021

Purpose:
Speech-in-noise tests and suprathreshold auditory evoked potentials are promising biomarkers to diagnose cochlear synaptopathy (CS) in humans. This study investigated whether these biomarkers changed after recreational noise exposure.

Method:
The baseline auditory status of 19 normal-hearing young adults was analyzed using questionnaires, pure-tone audiometry, speech audiometry, and auditory evoked potentials. Nineteen subjects attended a music festival and completed the same tests again at Day 1, Day 3, and Day 5 after the music festival.

Results:
No significant relations were found between lifetime noise-exposure history and the hearing tests. Changes in biomarkers from the first session to the follow-up sessions were nonsignificant, except for speech audiometry, which showed a significant learning effect (performance improvement).

Conclusions:
Despite the individual variability in prefestival biomarkers, we did not observe changes related to the noise-exposure dose caused by the attended event. This can indicate the absence of noise exposure–driven CS in the study cohort, or reflect that biomarkers were not sensitive enough to detect mild CS. Future research should include a more diverse study cohort, dosimetry, and results from test–retest reliability studies to provide more insight into the relationship between recreational noise exposure and CS.

Supplemental Material

https://doi.org/10.23641/asha.16821283
Clinical relevance of intradermal test results in atopic dogs
Authors: Mallmann Stefanie , Klinger Christoph J. , Claßen Janine , Wagner Iris , Klima Andre , Castelletti Noemi , Müller Ralf S. 
Published: October 2021

Abstract
Topic and aims Canine atopic dermatitis (AD) is an inflammatory and pruritic skin disease and in most cases associated with IgE antibodies against environmental allergens. To date, the only causative therapeutic option is allergen immunotherapy (AIT). Offending allergens for AIT can be identified by intradermal testing (IDT) or serum allergen-specific IgE testing. The aim of the study was to evaluate positive IDT results considering the atopic dogs’ clinical history.
Material and methods An IDT was performed on 48 atopic dogs and their owners completed a detailed questionnaire about the seasonal course of their pruritus. Results of IDT were correlated with the seasonal occurrence of pruritus.
Results The most common positive IDT reactions were observed to mite allergens (33.3–62.5 %). Prevalence of positive reactions to individual tree, grass and weed pollen ranged between 8.3 % and 25 %. Moulds and epithelial allergens produced positive reactions in only 0–6.3 %. A correlation between positive IDT reactions and course of pruritus could neither be found for perennial nor for seasonal allergens.
Conclusion The evaluation of IDT reactions may not be an optimal method for identification of clinically relevant allergens in canine AD.
Clinical relevance The results of this study emphasise the importance of considering clinical history in addition to allergy test results in the formulation of an allergen extract for desensitisation.
Frequency of synchronous malignant liver lesions initially detected by ultrasound in patients with newly diagnosed underlying non-hematologic malignant disease: a retrospective study in 434 patients
Authors: Safai Zadeh Ehsan , Baumgarten Martin Axel , Dietrich Christoph F. , Görg Christian , Neesse Albrecht , Trenker Corinna , Alhyari Amjad 
Published: October 2021

Abstract
Introduction This study described the frequency of malignant synchronous focal liver lesions (FLLs) in patients with newly diagnosed non-hematologic malignant disease.
Methods From June 2013 to January 2017, 434 patients with synchronous FLLs and newly diagnosed underlying malignant disease were included in the study. The diagnosis of the FLLs was made by histology and/or contrast-enhanced imaging. The final medical report was used for analysis in the study.
Results Of the 434 liver lesions, 258 (59.4%) were malignant and 176 (40.6%) benign. All malignant lesions were metastases. The benign liver lesions were comprised of 93 cysts (21.4%), 52 hemangiomas (12.0%), 20 focal fatty sparing (4.6%), 4 focal nodular hyperplasia (0.9%), 3 unspecified benign lesions (0.7%), 2 regenerative nodules (0.5%), 1 calcification (0.2%), and 1 adenoma (0.2%). Diseases with the highest percentage frequency of synchronous malignant FLLs were cholangiocarcinoma with 86.7%, neuroendocrine tumor with 72.7%, and pancreatic carcinoma with 72.0%. Gastric carcinoma (33.3%), breast carcinoma (44.4%), and urothelial cell carcinoma (45.5%) were the diseases with the lowest percentage frequency of synchronous malignant FLLs.
Conclusion In total, the frequency of malignant synchronous FLLs in newly diagnosed non-hematologic malignant disease was 59.4%. In particular, cholangiocarcinoma, neuroendocrine tumor, and pancreatic carcinoma were the diseases with the highest rate of synchronous malignant FLLs.
Enantioselective Construction of Multi-Nitrogen-Containing Spirocycles: Asymmetric [3+2] Annulation of 4-Isothiocyanato­pyrazolones with Azodicarboxylates
Authors: Wang Baomin , Wei Shiqiang , Wang Wenyao , Xue Aiqi , Nawaz Shah , Qu Jingping 
Published: October 2021

AbstractThe 4-isothiocyanatopyrazolones were exploited as a class of efficient synthons for the construction of triazoline derivatives via asymmetric [3+2] annulation with azodicarboxylates, providing a wide range of structurally diverse multi-nitrogen-containing spirocycles in excellent yields (up to 97%) with excellent enantioselectivities (up to 97% ee).
Correlation and Prediction of Oxygen Index from Oxygen Saturation Index in Neonates with Acute Respiratory Failure
Authors: Maneenil Gunlawadee , Premprat Nutchana , Janjindamai Waricha , Dissaneevate Supaporn , Phatigomet Manapat , Thatrimontrichai Anucha 
Published: October 2021

Objective The aim of this article was to evaluate the correlation between the oxygen index (OI) and the oxygen saturation index (OSI, measured by pulse oximetry and noninvasively) in neonates with acute respiratory failure and to predict the OI from the OSI.
Study Design A retrospective cohort study was conducted in neonates requiring invasive mechanical ventilation who had arterial blood gas between 2018 and 2019 at a neonatal intensive care unit. The correlation between OI and OSI was analyzed by using the Pearson correlation coefficient.
Results A total of 636 measurements from 68 neonates (35 preterm and 33 terms) were recruited into the study. There was a strong correlation between the OI and the OSI (r = 0.90) in all neonates. The correlation between the OI and the OSI in persistent pulmonary hypertension of the newborn, congenital cyanotic heart disease, and other causes of respiratory failure also showed a strong correlation (r = 0.88, 0.93, and 0.88, respectively). The correlation was strong in neonates with an oxygen saturation less than 85% (r = 0.88), those with oxygen saturation ranging from 85 to 95% (r = 0.87), and also in preterm and term infants (gestational age < 28, 28 − 34, 34 − 36, and ≥37 weeks, r = 0.87, 0.92, 0.89, and 0.90, respectively). There were strong accuracy measures of the OI for OI cutoffs of 5, 10, 15, and 20 (area under the curve > 0.85). The equation relating the OI and OSI was represented by: OI = (2.3 × OSI) – 4.
Conclusion The OSI has a strong correlation with the OI, is a reliable assessor of the severity of respiratory failure in neonates without arterial sampling, and has high accuracy when the OI is less than 40.
Key Points
Prediction of Distance Running Performances of Female Runners Using
Nomograms
Authors: Lerebourg Lucie , Guignard Brice , Racil Ghazi , Jlid Mohamed Chedly , Held Eric , Coquart Jeremy Bernard 
Published: October 2021

AbstractThis study examined the validity, precision and accuracy of the predictions of
distance running performances in female runners from three nomograms. Official
rankings of French women for the 3000-m, 5000-m, and 10 000-m
track-running events from 2005 to 2019 were examined. Only female runners who
performed in the three distance events within the same year were included
(n=158). Each performance over any distance was predicted using the
three nomograms from the two other performances. The 3000-m, 5000-m and
10 000-m performances were 11min17 s±1min20 s, 19min29
s±2min20 s, 41min18 s±5min7 s, respectively. No difference was
found between the actual and predicted running performances regardless of the
nomogram (p>0.05). All predicted running performances were significantly
correlated with the actual ones, with a very high correlation coefficient
(p<0.001; r>0.90). Bias and 95% limits of agreement were
acceptable because, whatever the nomogram, they were less than or equal to
− 0.0±6.2% on the 3000-m,
0.0±3.7% on the 5000-m, and 0.1±9.3% on the
10 000-m. The study confirms the validity of the three nomograms to
predict track-running performance with a high level of accuracy. The predictions
from these nomograms are similar and may be used in training programs and
competitions.
Picosecond excited-state lifetimes of protonated indazole and benzimidazole: The role of the N–N bond
Authors: Marlton Samuel J. P. , McKinnon Benjamin I. , Greißel Phillip , Shiels Oisin J. , Ucur Boris , Trevitt Adam J. 
Published: October 2021

Certain chemical groups give rise to characteristic excited-state deactivation mechanisms. Here, we target the role of a protonated N–N chemical group in the excited-state deactivation of protonated indazole by comparison to its isomer that lacks this group, protonated benzimidazole. Gas-phase protonated indazole and protonated benzimidazole ions are investigated at room temperature using picosecond laser pump–probe photodissociation experiments in a linear ion-trap. Excited state lifetimes are measured across a range of pump energies (4.0–5.4 eV). The 1ππ* lifetimes of protonated indazole range from 390 ± 70 ps using 4.0 eV pump energy to ≤18 ps using 4.6 eV pump energy. The 1ππ* lifetimes of protonated benzimidazole are systematically longer, ranging from 3700 ± 1100 ps at 4.6 eV pump energy to 400 ± 200 ps at 5.4 eV. Based on these experimental results and accompanying quantum chemical calculations and potential energy surfaces, the shorter lifetimes of protonated indazole are attributed to πσ* state mediated elongation of the protonated N–N bond.
Best constants of Banach-Stone type theorems in subgroups of 𝐶(𝐾)
Authors: Dong Yunbai , Leung Denny , Li Lei , Wang Liguang 
Published: October 2021

Assume that

X
,
Y

X, Y

are compact Hausdorff spaces. Let

C
(
X

)
+

C(X)_+

,

C
(
Y

)
+

C(Y)_+

be the sets of all positive real functions on

X
,
Y

X,Y

respectively. Let

T
T

be a surjective map from a point separating multiplicative subgroup

G
⊂
C
(
X

)
+

G\subset C(X)_+

onto a point separating multiplicative subgroup

H
⊂
C
(
Y

)
+

H\subset C(Y)_+

satisfying

T
1
=
1

T1=1

and

1
M

‖
f
⋅

g

−
1

‖
≤
‖
T
f
⋅
(
T
g

)

−
1

‖
≤
M
‖
f
⋅

g

−
1

‖

\begin{equation*} \frac {1}{M}\|f\cdot g^{-1}\|\leq \|Tf\cdot (Tg)^{-1}\|\leq M \|f\cdot g^{-1}\| \end{equation*}

for all

f
,
g
∈
G

f, g\in G

and for some constant

M
≥
1

M\geq 1

. Then there exists a homeomorphism

τ
\tau

from the Šilov boundary

∂
H

\partial H

of

H
H

onto the Šilov boundary

∂
G

\partial G

of

G
G

such that

f
(
τ
(
y
)
)

M
2

≤
(
T
f
)
(
y
)
≤

M
2

⋅
f
(
τ
(
y
)
)

\begin{equation*} \frac {f(\tau (y))}{M^2}\leq (Tf)(y)\leq M^2\cdot f(\tau (y)) \end{equation*}

for all

f
∈
G

f\in G

and all

y
∈
∂
H

y\in \partial H

. The constant

M
2

M^2

in the inequality above is optimal.

A similar argument yields a generalization of the classical Banach-Stone Theorem to isometries defined from an additive subgroup of

C
0

(
X
)

C_0(X)

into

C
0

(
Y
)

C_0(Y)

for locally compact Hausdorff spaces

X
X

and

Y
Y

.
Reducing Your Risk of Alzheimer’s Dementia: Building a Better Brain as We Age
Authors: Bennett David A 
Published: October 2021

Abstract
Alzheimer’ dementia is a large and growing public health problem. Of utmost importance for limiting the impact of the disease on society is the prevention of dementia, that is, delay onset either by years whereby death ensues prior to dementia onset. The Religious Orders Study and the Rush Memory and Aging Project are two harmonized cohort studies of aging and dementia that include organ donation at death. Ongoing since 1994 and 1997, respectively, we published on the association of numerous experiential, psychological, and medical risk factors for dementia, many of which are potentially modifiable. Here, selected findings are reviewed based on a presentation at the 2020 National Academy of Neuropsychology given virtually in Chicago in October of 2020.
Cloning of the cycloisomaltotetraose-forming enzymes using whole genome sequence analyses of Agreia sp. D1110 and Microbacterium trichothecenolyticum D2006
Authors: Fujita Akihiro , Kawashima Akira , Noguchi Yuji , Hirose Shuichi , Kitagawa Noriaki , Watanabe Hikaru , Mori Tetsuya , Nishimoto Tomoyuki , Aga Hajime , Ushio Shimpei , Yamamoto Koryu 
Published: October 2021

ABSTRACT
We performed whole genome sequence analyses of Agreia sp. D1110 and Microbacterium trichothecenolyticum D2006 that secrete enzymes to produce cyclo-{→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→6)-α-d-Glcp-(1→} (CI4) from dextran. Full-length amino acid sequences of CI4-forming enzymes were identified by matching known N-terminal amino acid sequences with products of the draft genome. Domain searches revealed that the CI4-forming enzymes are composed of Glycoside Hydrolase family 66 (GH66) domain, Carbohydrate Binding Module family 35 (CBM35) domain, and CBM13 domain, categorizing the CI4-forming enzymes in the GH66. Furthermore, the amino acid sequences of the two CI4-forming enzymes were 71% similar to each other and up to 51% similar to cycloisomaltooligosaccharide glucanotransferases (CITases) categorized in GH66. Differences in sequence between the CI4-forming enzymes and the CITases suggest mechanisms to produce specific cycloisomaltooligosaccharides, and whole genome sequence analyses identified a gene cluster whose gene products likely work in concert with the CI4-forming enzymes.
MoNET: an R package for multi-omic network analysis
Authors: Li Jin , Chen Feng , Liang Hong , Yan Jingwen 
Published: October 2021

AbstractMotivationThe increasing availability of multi-omic data has enabled the discovery of disease biomarkers in different scales. Understanding the functional interaction between multi-omic biomarkers is becoming increasingly important due to its great potential for providing insights of the underlying molecular mechanism.ResultsLeveraging multiple biological network databases, we integrated the relationship between single nucleotide polymorphisms (SNPs), genes/proteins and metabolites, and developed an R package Multi-omic Network Explorer Tool (MoNET) for multi-omic network analysis. This new tool enables users to not only track down the interaction of SNPs/genes with metabolome level, but also trace back for the potential risk variants/regulators given altered genes/metabolites. MoNET is expected to advance our understanding of the multi-omic findings by unveiling their transomic interactions and is likely to generate new hypotheses for further validation.Availability and implementationThe MoNET package is freely available on https://github.com/JW-Yan/MONET.Supplementary informationSupplementary data are available at Bioinformatics online.
Prospective evaluation of the learning curve and electrical characteristics of left bundle branch area pacing
Authors: Heckman L I B , Luermans J G L M , Jastrzebski M , Stipdonk A M W , Westra S , Weijs B , Den Uijl D , Linz D , Mafi-Rad M , Prinzen F W , Vernooy K 
Published: October 2021

Abstract

Background
Left bundle branch area pacing (LBBAP) has recently been introduced as a physiological pacing technique with a synchronous ventricular activation.

Objective
To prospectively evaluate the feasibility and learning curve, as well as the electrical characteristics of LBBAP.

Methods
In 80 consecutive LBBAP pacemaker patients, ECG characteristics during intrinsic rhythm, RV septum pacing (RVSP) and LBBAP were evaluated. From the ECG's QRS duration and LVAT (stimulus to V6 R-wave peak time, RWPT) were measured. Also, the left bundle branch potential (LBBpot) to V6 RWPT interval was measured and compared to the LVAT. After conversion of the ECG into VCG (Kors conversion matrix), QRS area, as measurement for electrical dyssynchrony, was calculated.

Results
Permanent lead implantation was successful in 77/80 patients (96%) undergoing an attempt at LBBAP. LBBAP lead implantation time as well as fluoroscopy time were significantly shorter during last 25% of implantation compared to first 25% of implantations (17±5 min vs. 33±16 min and 12±7 min vs. 21±13 min, respectively, panel A and B). LBB capture was obtained in 54/80 patients (68%). In 36/45 patients (80%) with intact AV conduction and narrow QRS an LBBpot was present. The mean interval between the LBBpot and the onset of QRS was 22±6 ms.
In the patients with narrow QRS (n=45), QRS duration increased significantly during both RVSP (139±24 ms) and LBBAP (123±21 ms), compared to intrinsic rhythm (95±13 ms).
QRS area on the other hand, increased during both RVSP (73±20 μVs) but decreased during LBBAP (41±15 μVs), to values close to intrinsic rhythm (32±16 μVs, panel C). For all patients, QRS area was significantly lower in patients with LBB capture compared to patients without capture (43±18 μVs vs 54±21 μVs, respectively).
In patients with LBB capture (n=54), LVAT was significantly shorter compared to patients without LBB capture (75±14 vs. 88±9 ms, respectively). In the patients with LBB capture, there was a significant correlation between the LBBpot – V6 RWPT and S – V6 RWPT intervals (Pearson correlation 0.739, P&lt;0.001).

Conclusion
LBBAP is a safe and feasible technique, with a clear learning curve that seems obtained after ± 40–60 implantations. LBB capture is obtained in two-thirds of patients. Although QRS duration remains prolonged, LBBAP largely restores ventricular electrical synchrony to values close to intrinsic (narrow QRS) rhythm.

Funding Acknowledgement
Type of funding sources: None.
Characteristics of patients with atrial high rate episodes detected by implanted defibrillator and resynchronisation devices
Authors: Miyazawa K , Pastori D , Martin D , Choucair W , Halperin J , Lip G 
Published: October 2021

Abstract

Aims
Atrial high rate episodes (AHRE) are associated with increased risks of thromboembolism and cardiovascular mortality. However, the clinical characteristics of patients developing AHRE of various durations are not well studied.

Methods
This was an ancillary analysis of the multicenter, randomized IMPACT trial. In the present analysis, we classified patients according to duration of AHRE ≤6 minutes, &gt;6 minutes to ≤6 hours, &gt;6 hours to ≤24 hours and &gt;24 hours, and investigated the association between clinical factors and the development of each duration of AHRE.

Results
Of 2,718 patients included in the trial, 945 (34.8%) developed AHRE. The incidence rates of each AHRE duration category were 10.7, 24.0, 0.14, and 0.07%, respectively. Using Cox regression analysis, heart failure was inversely associated with AHRE &lt;6 minutes (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.40–0.85, p=0.005), while age ≥65 years and history of atrial fibrillation (AF) and/or atrial flutter (AFL) were risk factors for AHRE &gt;6 minutes. Female gender was inversely associated with AHRE &gt;6 minutes to ≤6 hours (HR 0.72, 95% CI 0.54–0.96, p=0.027) and &gt;6 hours to ≤24 hours (HR 0.70, 95% CI 0.49–1.02, p=0.061). Hypertension was associated with AHRE &gt;24 hours (HR 2.13, 95% CI 1.24–3.65, p=0.006).

Conclusion
AHRE &gt;6 minutes to ≤6 hours were most prevalent among all AHRE duration categories. Age and history of AF/AFL were risk factors for AHRE &gt;6 minutes. Women were at lower risk for AHRE &gt;6 minutes to ≤24 hours, while hypertension was associated with AHRE &gt;24 hours.

Funding Acknowledgement
Type of funding sources: None. Cumulative incidence of each AHRE burden