bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive single-KIR+NKG2C+NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia
Authors: Haroun-Izquierdo Alvaro , Vincenti Marianna , Netskar Herman , van Ooijen Hanna , Zhang Bin , Bendzick Laura , Kanaya Minoru , Momayyezi Pouria , Li Shuo , Wiiger Merete Thune , Hoel Hanna Julie , Krokeide Silje Zandstra , Kremer Veronika , Tjonnfjord Geir , Berggren Stéphanie , Wikström Kristina , Blomberg Pontus , Alici Evren , Felices Martin , Önfelt Björn , Höglund Petter , Valamehr Bahram , Ljunggren Hans-Gustaf , Björklund Andreas , Hammer Quirin , Kveberg Lise , Cichocki Frank , Miller Jeffrey S , Malmberg Karl-Johan , Sohlberg Ebba 
Published: November 2022

BackgroundNatural killer (NK) cells hold great promise as a source for allogeneic cell therapy against hematological malignancies, including acute myeloid leukemia (AML). Current treatments are hampered by variability in NK cell subset responses, a limitation which could be circumvented by specific expansion of highly potent single killer immunoglobulin-like receptor (KIR)+NKG2C+adaptive NK cells to maximize missing-self reactivity.MethodsWe developed a GMP-compliant protocol to expand adaptive NK cells from cryopreserved cells derived from select third-party superdonors, that is, donors harboring large adaptive NK cell subsets with desired KIR specificities at baseline. We studied the adaptive state of the cell product (ADAPT-NK) by flow cytometry and mass cytometry as well as cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq). We investigated the functional responses of ADAPT-NK cells against a wide range of tumor target cell lines and primary AML samples using flow cytometry and IncuCyte as well as in a mouse model of AML.ResultsADAPT-NK cells were >90% pure with a homogeneous expression of a single self-HLA specific KIR and expanded a median of 470-fold. The ADAPT-NK cells largely retained their adaptive transcriptional signature with activation of effector programs without signs of exhaustion. ADAPT-NK cells showed high degranulation capacity and efficient killing of HLA-C/KIR mismatched tumor cell lines as well as primary leukemic blasts from AML patients. Finally, the expanded adaptive NK cells had preserved robust antibody-dependent cellular cytotoxicity potential and combination of ADAPT-NK cells with an anti-CD16/IL-15/anti-CD33 tri-specific engager led to near-complete killing of resistant CD45dimblast subtypes.ConclusionsThese preclinical data demonstrate the feasibility of off-the-shelf therapy with a non-engineered, yet highly specific, NK cell population with full missing-self recognition capability.
Highly excited and exotic fully-strange tetraquark states
Authors: Dong Rui-Rui , Su Niu , Chen Hua-Xing 
Published: November 2022

AbstractSome hadrons have the exotic quantum numbers that the traditional $$\bar{q} q$$

q

¯

q

mesons and qqq baryons can not reach, such as $$J^{PC} = 0^{--}/0^{+-}/1^{-+}/2^{+-}/3^{-+}/4^{+-}$$

J

PC

=

0

-
-

/

0

+
-

/

1

-
+

/

2

+
-

/

3

-
+

/

4

+
-

, etc. We investigate for the first time the exotic quantum number $$J^{PC}=4^{+-}$$

J

PC

=

4

+
-

, and study the fully-strange tetraquark states with such an exotic quantum number. We systematically construct all the diquark–antidiquark interpolating currents, and apply the method of QCD sum rules to calculate both the diagonal and off-diagonal correlation functions. The obtained results are used to construct three mixing currents that are nearly non-correlated, and we use one of them to extract the mass of the lowest-lying state to be $$2.85^{+0.19}_{-0.22}$$

2
.

85

-
0.22

+
0.19

GeV. We apply the Fierz rearrangement to transform this mixing current to be the combination of three meson–meson currents, and the obtained Fierz identity suggests that this state dominantly decays into the P-wave $$\phi (1020) f_2^\prime (1525)$$

ϕ

(
1020
)

f
2
′

(
1525
)

channel. This fully-strange tetraquark state of $$J^{PC}=4^{+-}$$

J

PC

=

4

+
-

is a purely exotic hadron to be potentially observed in future particle experiments.
Constraints on ultralight axions, vector gauge bosons, and unparticles from geodetic and frame-dragging measurements
Authors: Poddar Tanmay Kumar 
Published: November 2022

AbstractThe geodetic and frame-dragging effects are the direct consequences of the spacetime curvature near Earth which can be probed from the Gravity probe B (GP-B) satellite. The satellite result matches quite well with Einstein’s general relativistic result. The gyroscope of the satellite which measures the spacetime curvature near Earth contains lots of electrons and nucleons. Ultralight axions, vector gauge bosons, and unparticles can interact with these electrons and nucleons through different spin-dependent and spin-independent operators and change the drift rate of the gyroscope. Some of these ultralight particles can either behave as a long range force between some dark sector or Earth and the gyroscope or they can behave as a background oscillating dark matter fields or both. These ultralight particles can contribute an additional precession of the gyroscopes, limited to be no larger than the uncertainty in the GP-B measurements. Compared with the experimental results, we obtain bounds on different operator couplings.
European mineral intelligence – collecting, harmonizing and sharing data on European raw materials
Authors: Jørgensen Lisbeth Flindt , Wittenberg Antje , Deady Eimear , Kumelj Špela , Tulstrup Jørgen 
Published: November 2022

Abstract
The major share of raw materials needed to sustain our present lifestyle and even more importantly, required for the crucial green transition, are sourced outside Europe. The European Commission aims to enhance Europe's resilience and strengthen domestic sourcing. Although Europe has a long tradition of mining and extractive activities, it is acknowledged that there are several challenges to achieve European sourcing of certain raw materials such as the critical raw materials. A basic prerequisite to enable access to domestic raw materials is information on raw material occurrences, current and past mining activities, resources and reserves. The Geological Survey organizations (GSOs) of Europe play a key role in generating, compiling, gathering and storing the most up-to-date information as well as long-term data series on raw materials at national and regional levels. Over the last decade, the GSOs have joined forces and taken essential steps to harmonize and share data on raw materials. The results of this co-operation are illustrated as interactive maps on the European Geological Data Infrastructure (EGDI). This paper describes the data compiled in co-operation between the GSOs, and analyses the strengths and weaknesses of, as well as opportunities for and threats towards, the data.
Brittle tectonic evolution of Gondwana: implications for shale-gas and groundwater exploration
Authors: Linol Bastien , Dhansay Taufeeq 
Published: November 2022

Abstract

Brittle structures are crucial for enabling several key natural processes in the Earth's upper crust. In addition, understanding the 3D characteristics and geological evolution of these features is equally important to support various developmental objectives, such as those,
inter alia
, linked to natural gas, groundwater, hydrothermal minerals and seismicity. In this study, we map various fractures of Gondwana based on the available geological information, satellite imagery and digital elevation data. The lengths and orientations of more than 10 000 fractures in their present-day position reveal four clearly defined patterns, with those striking NW being predominant. Archean–Paleoproterozoic domains are defined by fractures oriented north and NE, whereas the Mesoproterozoic has dominant NNW-striking fractures. In contrast, the Neoproterozoic has mostly NE-striking fractures and the Phanerozoic sequences are defined by a predominant NW and a subordinate west fracture pattern. The style and geometry of these structures can be linked to major geodynamic events that led to the formation of Gondwana building blocks during the Eburnean (
c.
2.2–1.8 Ga), Kibaran (
c.
1.4–1.0 Ga) and Pan African–Brasiliano (
c.
800–550 Ma) orogens, and amalgamation of Pangaea (
c.
350–250 Ma). Many structures were reactivated and new faults formed during opening of the Atlantic and Indian oceans (
c.
180–120 Ma), the India–Asia collision and rifting across East Africa since about 40 Ma. Although the changes in palaeogeography remain difficult to model with accuracy, major structural orientations are corroborated by the occurrence of major mineral deposits and seismicity. The spatial distribution of mapped patterns across the different continents also correlates well with large shale gas prospects and increased groundwater yields. Thus, Gondwana fractures need to be considered in more detail for informing future development related to water and energy use, especially across regions of Africa.
Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer
Authors: McKenzie Duncan R. , Graham Rosalind , Lechmere Thomas , Domingo-Vila Clara , Alaguthurai Thanussuyah , Arman Celeste , Pollock Emily , Gousis Charalampos , Kakkassery Helen , Carpenter Esme , Kurshan Ashwini , Vidler Jennifer , Kulasekararaj Austin , Patten Piers , North Bernard V. , Tree Timothy , Doores Katie J. , Hayday Adrian C. , Irshad Sheeba 
Published: November 2022

This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer.Significance:Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with cancer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses; (ii) evaluated the immune response among patients with cancer to a third dose of COVID-19 vaccine; and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer.
Hippo-Yap Signaling Maintains Sinoatrial Node Homeostasis
Authors: Zheng Mingjie , Li Rich G. , Song Jia , Zhao Xiaolei , Tang Li , Erhardt Shannon , Chen Wen , Nguyen Bao H. , Li Xiao , Li Min , Wang Jianxin , Evans Sylvia M. , Christoffels Vincent M. , Li Na , Wang Jun 
Published: November 2022

Background:
The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entities because of its small size and complex composition and function. The Hippo signaling pathway is a molecular signaling pathway fundamental to heart development and regeneration. Although abnormalities of the Hippo pathway are associated with cardiac arrhythmias in human patients, the role of this pathway in the SAN is unknown.

Methods:

We investigated key regulators of the Hippo pathway in SAN pacemaker cells by conditionally inactivating the Hippo signaling kinases
Lats1
and
Lats2
using the tamoxifen-inducible, cardiac conduction system–specific Cre driver

Hcn4
CreERT2

with
Lats1
and
Lats2
conditional knockout alleles. In addition, the Hippo-signaling effectors
Yap
and
Taz
were conditionally inactivated in the SAN. To determine the function of Hippo signaling in the SAN and other cardiac conduction system components, we conducted a series of physiological and molecular experiments, including telemetry ECG recording, echocardiography, Masson Trichrome staining, calcium imaging, immunostaining, RNAscope, cleavage under targets and tagmentation sequencing using antibodies against Yap1 or H3K4me3, quantitative real-time polymerase chain reaction, and Western blotting. We also performed comprehensive bioinformatics analyses of various datasets.

Results:

We found that
Lats1/2
inactivation caused severe sinus node dysfunction. Compared with the controls,
Lats1/2
conditional knockout mutants exhibited dysregulated calcium handling and increased fibrosis in the SAN, indicating that
Lats1/2
function through both cell-autonomous and non–cell-autonomous mechanisms. It is notable that the
Lats1/2
conditional knockout phenotype was rescued by genetic deletion of
Yap
and
Taz
in the cardiac conduction system. These rescued mice had normal sinus rhythm and reduced fibrosis of the SAN, indicating that
Lats1/2
function through
Yap
and
Taz.
Cleavage Under Targets and Tagmentation sequencing data showed that Yap potentially regulates genes critical for calcium homeostasis such as
Ryr2
and genes encoding paracrine factors important in intercellular communication and fibrosis induction such as
Tgfb1
and
Tgfb3
. Consistent with this,
Lats1/2
conditional knockout mutants had decreased
Ryr2
expression and increased
Tgfb1
and
Tgfb3
expression compared with control mice.

Conclusions:
We reveal, for the first time to our knowledge, that the canonical Hippo-Yap pathway plays a pivotal role in maintaining SAN homeostasis.
Changes in Blood Pressure Outcomes Among Hypertensive Individuals During the COVID-19 Pandemic: A Time Series Analysis in Three US Healthcare Organizations
Authors: Gotanda Hiroshi , Liyanage-Don Nadia , Moran Andrew E. , Krousel-Wood Marie , Green Jonas B. , Zhang Yiyi , Nuckols Teryl K. 
Published: November 2022

Background:
The COVID-19 pandemic may have negatively affected medical care for and self-management of chronic hypertension. We sought to examine the impact of the pandemic on blood pressure (BP) among individuals with hypertension.

Methods:
Using an interrupted time series analysis, we compared the level and trend (slope) of BP outcomes before the public health emergency declaration (prepandemic period: August 2018 through January 2020) versus after the stay-at-home orders (pandemic period: April 2020 through November 2020) among adults with hypertension followed at 3 large health systems (n=137 593). Outcomes include systolic and diastolic BP recorded in electronic health records and the proportion of individuals with BP <140/90 mm Hg.

Results:

The number of BP measurements substantially dropped early in the pandemic and then gradually increased. During the pandemic period, systolic and diastolic BP increased by 1.79 mm Hg (95% CI, 1.57–2.01;
P
<0.001) and 1.30 mm Hg (95% CI, 1.18–1.42;
P
<0.001), respectively, compared with the prepandemic period. Similarly, the proportion of patients with controlled BP decreased by 3.43 percentage points (95% CI, −3.97 to −2.90;
P
<0.001). A trend showing increasing control in the prepandemic period (+3.19 percentage points per year [95% CI, +2.96 to +3.42];
P
<0.001) flattened during the pandemic period (+0.27 percentage points per year [95% CI, −0.81 to −1.37];
P
=0.62).

Conclusions:
The first 8 months of the pandemic were associated with worsening BP outcomes among individuals with hypertension. Opportunities to ensure ongoing access to health care with telemedicine and home BP monitoring may mitigate adverse impacts on BP control for future disasters/emergencies.
Tacitus on the Visit of Germanicus to Egypt
Authors: Woods David 
Published: November 2022

Abstract
This paper investigates why, when Tacitus describes the visit of Germanicus to the East in AD 17-19, he chooses to describe his visit to Egypt in particular (Ann. 2.59-61) at such length in contrast to his cursory descriptions of his other much more significant achievements during the same period. It is argued that he did this for two main reasons, partly to emphasize his implication that this was the event that finally persuaded Tiberius to order the death of Germanicus and partly to complete his characterization of Germanicus as a man of wondrous comitas.
A 30-Year Climatology of Northeastern U.S. Atmospheric Rivers
Authors: Kaminski Anna N. , Cordeira Jason M. , Metz Nicholas D. , Bachli Katie , Duncan Megan , Ericksen Michaela , Glade Ivy , Roberts Cassandra , Evans Clark 
Published: November 2022

Abstract
Atmospheric rivers (ARs) are a frequently studied phenomenon along the West Coast of the United States, where they are typically associated with the heaviest local flooding events and almost one-half of the annual precipitation totals. By contrast, ARs in the northeastern United States have received considerably less attention. The purpose of this study is to utilize a unique visual inspection methodology to create a 30-yr (1988–2017) climatology of ARs in the northeastern United States. Consistent with its formal definition, ARs are defined as corridors with integrated vapor transport (IVT) values greater than 250 kg m−1 s−1 over an area at least 2000 km long but less than 1000 km wide in association with an extratropical cyclone. Using MERRA2 reanalysis data, this AR definition is used to determine the frequency, duration, and spatial distribution of ARs across the northeastern United States. Approximately 100 ARs occur in the northeastern United States per year, with these ARs being quasi-uniformly distributed throughout the year. On average, northeastern U.S. ARs have a peak IVT magnitude between 750 and 999 kg m−1 s−1, last less than 48 h, and arrive in the region from the west to southwest. Average AR durations are longer in summer and shorter in winter. Further, ARs are typically associated with lower IVT in winter and higher IVT in summer. Spatially, ARs more frequently occur over the Atlantic Ocean coastline and adjacent Gulf Stream waters; however, the frequency with which large IVT values are associated with ARs is highest over interior New England.
A Case Study of a West Sumatra Squall Line Using Satellite Observations
Authors: Lopez-Bravo Clemente , Vincent Claire L. , Huang Yi , Lane Todd P. 
Published: November 2022

Abstract
A West Sumatra squall line occurred on 10 January 2016, with a clear offshore propagation of convection. Satellite-derived products from Himawari-8 Advanced Himawari Imager and the Geostationary Cloud Algorithm Testbed Geocat are used to investigate the westward propagation of cloudiness from Sumatra to the Indian Ocean with a lifetime of 1.5 days. A convective mask based on deep convective cell detection and a cell-tracking algorithm are used to estimate the propagation speed of the cloud system. Two distinct mesoscale convective responses are identified: 1) a rapid development in South Sumatra is influenced by the convective environment over the Indian Ocean. The propagation speed is estimated to be ∼5 m s−1 within the first 200 km from the coast. This speed is consistent with density currents. In contrast, 2) the coupling to the inertia–gravity wave is only evident for the northwest of Sumatra with speeds of ∼12 m s−1. The analysis of brightness temperature from the 10.4-μm spectral band and cloud-top temperature showed that the lifetime of the squall line is approximately 30 h with a propagating distance of ∼1000 km. Retrieved cloud properties and tracking of the offshore propagation indicated that the cloud structure consisted of multiple types of cells, propagating as envelopes of convection, and revealed the influence of large-scale variability of the Indian Ocean. Filtered OLR anomalies, satellite-derived rainfall, moisture flux convergence, and background winds flow around Sumatra are used to explore the effects of Kelvin wave activity that likely influenced the lifetime of the squall line.
Perioperative Lidocaine Infusion Reduces Opioid Use in Enhanced Recovery After Surgery Patients Undergoing Laparoscopic Colectomy
Authors: Thomas Gregory J. , Bauman John C. , Bergeron Shelli , Wasvary Harry J. , Ziegler Matthew A. 
Published: November 2022

Background Enhanced Recovery After Surgery (ERAS) programs have become a mainstay of modern surgical care, and efforts to decrease postoperative opioid consumption have been increasingly employed. A previous study from our institution demonstrated that ERAS protocols decreased opioid use in the first 48 hours after surgery by 61%. In the present study, a lidocaine infusion was added for postoperative pain control. The aim was to analyze the differences in opioid requirements with and without this infusion in the first 48 hours after laparoscopic colectomy in ERAS patients. Methods Retrospective review of patients was conducted at an academically affiliated tertiary care hospital. The population included patients undergoing elective laparoscopic colon surgery enrolled in the ERAS program with the implementation of a lidocaine drip from June 2019 to October 2019, and compared to a previous patient cohort of ERAS patients evaluated without the lidocaine drip from September 2015 to May 2018. Results The primary endpoint was postoperative opioid use in the first 48 hours based on IV morphine milligram equivalents (MME). Secondary measures included type of surgery, age, BMI, prior abdominal surgery, and prior opioid use. Median MMEs were 6.0 in the lidocaine infusion group and 12.5 in the group without lidocaine, representing a 52% reduction (p < 0.001). Discussion This study demonstrates a significant reduction in post-op opioid use in ERAS patients who receive a lidocaine infusion after laparoscopic colectomy. Further studies should focus on measures to limit the treatment side effects in order to maximize the opioid-sparing benefits of this intervention.