bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual and reproductive health in Britain during the first year of the COVID-19 pandemic: cross-sectional population survey (Natsal-COVID-Wave 2) and national surveillance data
Authors: Mitchell Kirstin R , Willis Malachi , Dema Emily , Baxter Andrew J , Connolly Anne , Riddell Julie , Bosó Pérez Raquel , Clifton Soazig , Gibbs Jo , Tanton Clare , Geary Rebecca , Ratna Natasha , Mohammed Hamish , Unemo Magnus , Bonell Christopher , Copas Andrew , Sonnenberg Pam , Mercer Catherine H , Field Nigel 
Published: March 2023

ObjectivesTo assess sexual behaviour, and sexual and reproductive health (SRH) outcomes, after 1 year of the COVID-19 pandemic in Britain.Methods6658 participants aged 18–59 and resident in Britain completed a cross-sectional web-panel survey (Natsal-COVID-Wave 2, March-April 2021), 1 year after the first lockdown. Natsal-COVID-2 follows the Natsal-COVID-Wave 1 survey (July-August 2020) which captured impacts in the initial months. Quota-based sampling and weighting resulted in a quasi-representative population sample. Data were contextualised with reference to the most recent probability sample population data (Natsal-3; collected 2010–12; 15 162 participants aged 16–74) and national surveillance data on recorded sexually transmitted infection (STI) testing, conceptions, and abortions in England/Wales (2010–2020). The main outcomes were: sexual behaviour; SRH service use; pregnancy, abortion and fertility management; sexual dissatisfaction, distress and difficulties.ResultsIn the year from the first lockdown, over two-thirds of participants reported one or more sexual partners (women 71.8%; men 69.9%), while fewer than 20.0% reported a new partner (women 10.4%; men 16.8%). Median occasions of sex per month was two. Compared with 2010–12 (Natsal-3), we found less sexual risk behaviour (lower reporting of multiple partners, new partners, and new condomless partners), including among younger participants and those reporting same-sex behaviour. One in 10 women reported a pregnancy; pregnancies were fewer than in 2010–12 and less likely to be scored as unplanned. 19.3% of women and 22.8% of men were distressed or worried about their sex life, significantly more than in 2010–12. Compared with surveillance trends from 2010 to 2019, we found lower than expected use of STI-related services and HIV testing, lower levels of chlamydia testing, and fewer conceptions and abortions.ConclusionsOur findings are consistent with significant changes in sexual behaviour, SRH, and service uptake in the year following the first lockdown in Britain. These data are foundational to SRH recovery and policy planning.
Bottom quark and tau lepton masses in a toy $$\textrm{SU}(6)$$ model
Authors: Chen Ning , Mao Ying-nan , Teng Zhaolong 
Published: March 2023

AbstractWe study a toy $$\textrm{SU}(6)$$

SU
(
6
)

model with the symmetry breaking pattern of the extended 331 symmetry of $$\textrm{SU}(3)_c \otimes \textrm{SU}(3)_W \otimes \textrm{U}(1)_X$$

SU

(
3
)

c

⊗
SU

(
3
)

W

⊗
U

(
1
)

X

. A “fermion-Higgs mismatching” symmetry breaking pattern is proposed for more realistic model building. Within such symmetry breaking pattern, only one Higgs doublet develops vacuum expectation value for the spontaneous electroweak symmetry breaking, and gives tree-level top quark mass. A natural VEV splittings in the 331 breaking Higgs fields gives tree-level masses to both bottom quark and tau lepton. The $$125\,\textrm{GeV}$$

125

GeV

SM-like Higgs boson discovered at the LHC can have Yukawa couplings to bottom quark and tau lepton as in the SM prediction, and this suggests the 331 symmetry breaking scale to be $$\sim {{{\mathcal {O}}}}(10)\,\textrm{TeV}$$

∼
O
(
10
)

TeV

.
f(Q, T) gravity, its covariant formulation, energy conservation and phase-space analysis
Authors: Loo Tee-How , Solanki Raja , De Avik , Sahoo P. K. 
Published: March 2023

AbstractIn the present article we analyze the matter-geometry coupled f(Q, T) theory of gravity. We offer the fully covariant formulation of the theory, with which we construct the correct energy balance equation and employ it to conduct a dynamical system analysis in a spatially flat Friedmann–Lemaître–Robertson–Walker spacetime. We consider three different functional forms of the f(Q, T) function, specifically, $$f(Q,T)=\alpha Q+ \beta T$$

f
(
Q
,
T
)
=
α
Q
+
β
T

, $$f(Q,T)=\alpha Q+ \beta T^2$$

f

(
Q
,
T
)

=
α
Q
+
β

T
2

, and $$f(Q,T)=Q+ \alpha Q^2+ \beta T$$

f

(
Q
,
T
)

=
Q
+
α

Q
2

+
β
T

. We attempt to investigate the physical capabilities of these models to describe various cosmological epochs. We calculate Friedmann-like equations in each case and introduce some phase space variables to simplify the equations in more concise forms. We observe that the linear model $$f(Q,T)=\alpha Q+ \beta T$$

f
(
Q
,
T
)
=
α
Q
+
β
T

with $$\beta =0$$

β
=
0

is completely equivalent to the GR case without cosmological constant $$\Lambda $$
Λ
. Further, we find that the model $$f(Q,T)=\alpha Q+ \beta T^2$$

f

(
Q
,
T
)

=
α
Q
+
β

T
2

with $$\beta \ne 0$$

β
≠
0

successfully depicts the observed transition from decelerated phase to an accelerated phase of the universe. Lastly, we find that the model $$f(Q,T)= Q+ \alpha Q^2+ \beta T$$

f

(
Q
,
T
)

=
Q
+
α

Q
2

+
β
T

with $$\alpha \ne 0$$

α
≠
0

represents an accelerated de-Sitter epoch for the constraints $$\beta < -1$$

β
<
-
1

or $$ \beta \ge 0$$

β
≥
0

.
Spherically symmetric distributions with an invariant and vanishing complexity factor by means of the extended geometric deformation
Authors: León P. , Las Heras C. 
Published: March 2023

AbstractIn this work, we will analyze the complexity factor, proposed by L. Herrera, of spherically symmetric static distribution through the gravitational decoupling method. Specifically, we will consider both spatial and temporal deformations of the metric function, and we will impose conditions over the complexity factor to close the system of equations. In particular, we found that the regularity at the center of both the seed and final solutions led to important restrictions on the deformation of the spatial metric components. These are particularly restrictive for the MGD method. In this case, we show that if the seed solution is regular at $$r=0,$$

r
=
0
,

the final solution with invariant complexity factor will be singular at this point unless $$f=0.$$

f
=
0
.

We also show that solutions with the same temporal components will, in general, lead to the same solutions with vanishing complexity factor in the MGD approach. Finally, we will construct realistic models using different seed solutions such as Tolman IV and FS (Finch–Skeas).
Individualized Tracking of Neurocognitive-State-Dependent Eye-Movement Features Using Mobile Devices
Authors: Lai Hsin-Yu , Sodini Charles G. , Sze Vivienne , Heldt Thomas 
Published: March 2023

With current clinical techniques, it is difficult to assess a patient's neurodegenerative disease (e.g., Alzheimer's) state accurately and frequently. The most widely used tests are qualitative or only performed intermittently, motivating the need for quantitative, accurate, and unobtrusive metrics to track disease progression. Clinical studies have shown that saccade latency (an eye movement measure of reaction time) and error rate (the proportion of eye movements in the wrong direction) may be significantly affected by neurocognitive diseases. Nevertheless, how these features change over time as a disease progresses is underdeveloped due to the constrained recording setup.
In this work, our goal is to first understand how these features change over time in healthy individuals. To do so, we used a mobile app to frequently and accurately measure these features outside of the clinical environment from 80 healthy participants. We analyzed their longitudinal characteristics and designed an individualized longitudinal model using a Gaussian process. With a system that can measure eye-movement features on a much finer timescale in a broader population, we acquired a better understanding of eye-movement features from healthy individuals and provided research directions in understanding whether eye-movement features can be used to track neurocognitive states.
Co-Clinical Study of [fam-] Trastuzumab Deruxtecan (DS8201a) in Patient-Derived Xenograft Models of Uterine Carcinosarcoma and Its Association with Clinical Efficacy
Authors: Yagishita Shigehiro , Nishikawa Tadaaki , Yoshida Hiroshi , Shintani Daisuke , Sato Sho , Miwa Maiko , Suzuki Mikiko , Yasuda Masanori , Ogitani Yusuke , Jikoh Takahiro , Yonemori Kan , Hasegawa Kosei , Hamada Akinobu 
Published: March 2023

Abstract

Purpose:
Uterine carcinosarcoma (UCS), a subtype of endometrial carcinoma, is a rare and aggressive cancer with a poor prognosis. High clinical efficacy of trastuzumab deruxtecan (T-DXd) in HER2-expressing UCS was recently reported in a phase II trial (STATICE trial). We performed a co-clinical study of T-DXd using patient-derived xenograft (PDX) models of participants in the STATICE trial.

Experimental Design:
Tumor specimens were resected during primary surgery or biopsied at recurrence from patients with UCS and transplanted into immunodeficient mice. Seven UCS-PDXs from six patients were established and HER2, estrogen receptor (ER), and p53 expression in PDX and the original tumor was assessed. Drug efficacy tests were performed using six of the seven PDXs. Of the six UCS-PDXs tested, two were derived from patients enrolled in the STATICE trial.

Results:
The histopathological characteristics of the six PDXs were well-conserved from the original tumors. HER2 expression was 1+ in all PDXs, and ER and p53 expression was almost similar to that in the original tumors. Remarkable tumor shrinkage after T-DXd administration was observed in four of the six PDXs (67%), comparable with the response rate (70%) of HER2 1+ patients in the STATICE trial. Two patients enrolled in the STATICE trial showed partial response as the best response, and the clinical effect was well-replicated with marked tumor shrinkage.

Conclusions:
We successfully performed a co-clinical study of T-DXd in HER2-expressing UCS, along with the STATICE trial. Our PDX models can predict clinical efficacy and serve as an effective preclinical evaluation platform.
BLEACH&STAIN 15-marker Multiplexed Imaging in 3,098 Human Carcinomas Reveals Six Major PD-L1–driven Immune Phenotypes with Distinct Spatial Orchestration
Authors: Bady Elena , Möller Katharina , Mandelkow Tim , Raedler Jonas B. , Yang Cheng , Ebner Julia , Lurati Magalie C.J. , Simon Ronald , Vettorazzi Eik , Büscheck Franziska , Luebke Andreas M. , Dum David , Menz Anne , Sauter Guido , Höflmayer Doris , Weidemann Sören , Fraune Christoph , Uhlig Ria , Bernreuther Christian , Jacobsen Frank , Clauditz Till S. , Wilczak Waldemar , Burandt Eike , Steurer Stefan , Minner Sarah , Lennartz Maximilian , Blessin Niclas C. 
Published: March 2023

Abstract

Multiplex fluorescence IHC (mfIHC) approaches were yet either limited to six markers or limited to a small tissue size that hampers translational studies on large tissue microarray cohorts. Here we have developed a BLEACH&STAIN mfIHC method that enabled the simultaneous analysis of 15 biomarkers (PD-L1, PD-1, CTLA-4, panCK, CD68, CD163, CD11c, iNOS, CD3, CD8, CD4, FOXP3, CD20, Ki67, and CD31) in 3,098 tumor samples from 44 different carcinoma entities within one week. To facilitate automated immune checkpoint quantification on tumor and immune cells and study its spatial interplay an artificial intelligence–based framework incorporating 17 different deep-learning systems was established. Unsupervised clustering showed that the three PD-L1 phenotypes (PD-L1+ tumor and immune cells, PD-L1+ immune cells, PD-L1−) were either inflamed or noninflamed. In inflamed PD-L1+patients, spatial analysis revealed that an elevated level of intratumoral M2 macrophages as well as CD11c+ dendritic cell (DC) infiltration (P &lt; 0.001 each) was associated with a high CD3+ CD4± CD8± FOXP3± T-cell exclusion and a high PD-1 expression on T cells (P &lt; 0.001 each). In breast cancer, the PD-L1 fluorescence intensity on tumor cells showed a significantly higher predictive performance for overall survival (OS; AUC, 0.72, P &lt; 0.001) compared with the commonly used percentage of PD-L1+ tumor cells (AUC, 0.54). In conclusion, our deep-learning–based BLEACH&STAIN framework facilitates rapid and comprehensive assessment of more than 60 spatially orchestrated immune cell subpopulations and its prognostic relevance.

Implications:
The development of an easy-to-use high-throughput 15+1 multiplex fluorescence approach facilitates the in-depth understanding of the immune tumor microenvironment (TME) and enables to study the prognostic relevance of more than 130 immune cell subpopulations.
Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways
Authors: Spain Lavinia , Coulton Alexander , Lobon Irene , Rowan Andrew , Schnidrig Desiree , Shepherd Scott T.C. , Shum Benjamin , Byrne Fiona , Goicoechea Maria , Piperni Elisa , Au Lewis , Edmonds Kim , Carlyle Eleanor , Hunter Nikki , Renn Alexandra , Messiou Christina , Hughes Peta , Nobbs Jaime , Foijer Floris , van den Bos Hilda , Wardenaar Rene , Spierings Diana C.J. , Spencer Charlotte , Schmitt Andreas M. , Tippu Zayd , Lingard Karla , Grostate Lauren , Peat Kema , Kelly Kayleigh , Sarker Sarah , Vaughan Sarah , Mangwende Mary , Terry Lauren , Kelly Denise , Biano Jennifer , Murra Aida , Korteweg Justine , Lewis Charlotte , O'Flaherty Molly , Cattin Anne-Laure , Emmerich Max , Gerard Camille L. , Pallikonda Husayn Ahmed , Lynch Joanna , Mason Robert , Rogiers Aljosja , Xu Hang , Huebner Ariana , McGranahan Nicholas , Al Bakir Maise , Murai Jun , Naceur-Lombardelli Cristina , Borg Elaine , Mitchison Miriam , Moore David A. , Falzon Mary , Proctor Ian , Stamp Gordon W.H. , Nye Emma L. , Young Kate , Furness Andrew J.S. , Pickering Lisa , Stewart Ruby , Mahadeva Ula , Green Anna , Larkin James , Litchfield Kevin , Swanton Charles , Jamal-Hanjani Mariam ,   for the PEACE Consortium, Turajlic Samra 
Published: March 2023

Abstract

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.

Significance:
Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA.
See related commentary by Shain, p. 1294.
This article is highlighted in the In This Issue feature, p. 1275
Sleep Irregularity Is Associated With Hypertension: Findings From Over 2 Million Nights With a Large Global Population Sample
Authors: Scott Hannah , Lechat Bastien , Guyett Alisha , Reynolds Amy C. , Lovato Nicole , Naik Ganesh , Appleton Sarah , Adams Robert , Escourrou Pierre , Catcheside Peter , Eckert Danny J. 
Published: March 2023

Background:
Irregularities in sleep duration and sleep timing have emerged as potential risk factors for hypertension. This study examined associations between irregularity in sleep duration and timing with hypertension in a large, global sample over multiple months.

Methods:
Data from 12 287 adults, who used an under-mattress device to monitor sleep duration and timing and also provided blood pressure recordings on ≥5 separate occasions, were analyzed. Sleep duration irregularity was assessed as the SD in total sleep time across the ≈9-month recording period. Sleep timing irregularity was assessed as SDs in sleep onset time, sleep midpoint, and sleep offset time. Logistic regressions were conducted to investigate associations between sleep irregularity and hypertension, defined as median systolic blood pressure ≥140 mm Hg or median diastolic blood pressure ≥90 mm Hg.

Results:

Participants were middle-aged (mean±SD, 50±12 years), mostly men (88%) and overweight (body mass index, 28±6 kg/m
−2
). Sleep duration irregularity was consistently associated with an ≈9% to 17% increase in hypertension independently of the total sleep time. A ≈34-minute increase in sleep onset time irregularity was associated with a 32% increase in hypertension (1.32 [1.20–1.45]). A 32-minute increase in sleep midpoint irregularity was associated with an 18% increase in hypertension (1.18 [1.09–1.29]), while a 43-minute increase in sleep offset time irregularity was associated with an 8.9% increase in hypertension (1.09 [1.001–1.18]).

Conclusions:
These findings support that sleep irregularity, both in duration and timing, is a risk marker for poor cardiovascular health. Further mechanistic investigations of temporal relationships between day-to-day fluctuations in sleep duration and timing, next-day blood pressure, and other cardiovascular outcomes are warranted.
Intrarenal Renin-Angiotensin System Activation Alters Relationship Between Systolic Blood Pressure and Progression of Chronic Kidney Disease
Authors: Park Cheol Ho , Kim Hyung Woo , Park Jung Tak , Chang Tae Ik , Yoo Tae-Hyun , Lee Joongyub , Sung Suah , Jung Ji Yong , Hyun Young Youl , Oh Kook-Hwan , Kang Shin-Wook , Han Seung Hyeok ,   on the behalf of the KNOW-CKD (Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease) Investigators
Published: March 2023

Background:
Elevated blood pressure and intrarenal renin-angiotensin system activity are closely related to chronic kidney disease (CKD) progression. However, interrelationship between blood pressure and intrarenal renin-angiotensin system activity on the risk of CKD progression is unknown.

Methods:
We analyzed 2076 participants from the Korean Cohort Study for Outcomes in Patients With CKD. The main exposure was systolic blood pressure (SBP). The urinary angiotensinogen-to-creatinine ratio was stratified according to the median value (3.65 μg/gCr). The primary outcome was a composite kidney outcome of a ≥50% decline in estimated glomerular filtration rate from baseline measurement or initiation of kidney replacement therapy.

Results:

During 10 550 person-years of follow-up (median, 5.2 years), the composite outcome occurred in 800 (38.5%) participants. In the multivariable cause-specific hazard model, higher SBP was associated with an increased risk of CKD progression. There was a significant interaction between SBP and urinary angiotensinogen-to-creatinine ratio on the risk of the primary outcome (
P
value for interaction=0.019). In patients with urinary angiotensinogen-to-creatinine <3.65 μg/gCr, the hazard ratios (95% CIs) for SBP 120 to 129, 130 to 139, and ≥140 mmHg were 1.46 (1.07–1.99), 1.71 (1.25–2.35), and 2.40 (1.73–3.32), respectively, compared with SBP <120 mmHg. However, these associations were not observed in patients with urinary angiotensinogen-to-creatinine ≥3.65 μg/gCr.

Conclusions:
In this prospective CKD cohort, higher SBP was associated with CKD progression when urinary angiotensinogen levels were low, while this association was not seen when urinary angiotensinogen levels were high. This finding suggests that intrarenal renin-angiotensin system activity may modify the relationship between SBP and adverse kidney outcome.
Prognostic Value of Machine‐Learning‐Based PRAISE Score for Ischemic and Bleeding Events in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Shi Boqun , Wang Hao‐Yu , Liu Jinpeng , Cai Zhongxing , Song Chenxi , Yin Dong , Wang Hongjian , Dong Qiuting , Song Weihua , Dou Ke‐Fei 
Published: March 2023

Background
The PRAISE (Prediction of Adverse Events Following an Acute Coronary Syndrome) score is a machine‐learning‐based model for predicting 1‐year all‐cause death, myocardial infarction, and Bleeding Academic Research Consortium (BARC) type 3/5 bleeding. Its utility in an unselected Asian population undergoing percutaneous coronary intervention for acute coronary syndrome remains unknown. We aimed to validate the PRAISE score in a real‐world Asian population.

Methods and Results
A total of 6412 consecutive patients undergoing percutaneous coronary intervention for acute coronary syndrome were prospectively included. The PRAISE scores were compared with established scoring systems (GRACE [Global Registry of Acute Coronary Events] 2.0, PRECISE‐DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy), and PARIS [Patterns of Non‐Adherence to Anti‐Platelet Regimen in Stented Patients]) to evaluate their discrimination, calibration, and reclassification. The risk of all‐cause mortality (hazard ratio [HR], 12.24 [95% CI, 5.32–28.15]) and recurrent acute myocardial infarction (HR, 3.92 [95% CI, 1.76–8.73]) was greater in the high‐risk group than in the low‐risk group. The C‐statistics for death, myocardial infarction, and major bleeding were 0.75 (0.67–0.83), 0.61 (0.52–0.69), and 0.62 (0.46–0.77), respectively. The observed to expected ratio of death, myocardial infarction, and major bleeding was 0.427, 0.260, and 0.106, respectively. Based on the decision curve analysis, the PRAISE score displayed a slightly greater net benefit for the 1‐year risk of death (5%–10%) than the GRACE score did.

Conclusions
The PRAISE score showed limited potential for risk prediction in our validation cohort with acute coronary syndrome. As a result, new prediction models or model refitting are required with improved discrimination and accuracy in risk prediction.