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(A) The combined sleeve of LCL-biceps femoris-PFL (blue arrowhead) with locking Krackow sutures in place (yellow arrow) which are passed through the fibular head. (B) The biceps femoris tendon (white arrow) repositioned onto the fibular head. LCL, lateral collateral ligament; PFL, popliteofibular ligament.
PMC9663643
10.1177_23259671221131817-fig2.jpg
0.437065
9a7db4be76734bd48517c7d1eeedf08e
(A) Krackow sutures (blue arrow) are placed through the anterior tunnel of the fibular head. The sutures are not yet tensioned or tied. (B) Krackow sutures that have been tensioned and tied over the anteromedial tibial cortex. Double black arrow indicates the course of the LCL, the thin green arrow indicates the peroneal nerve, and the yellow arrowhead indicates the biceps femoris tendon. LCL, lateral collateral ligament.
PMC9663643
10.1177_23259671221131817-fig3.jpg
0.431081
9ec640aef5d94a518d8999db37618816
(A) MRI showing PLC avulsion injury with biceps femoris tendon (yellow arrowhead) attached to the avulsed fibular styloid fracture fragment (red arrow). (B) MRI at 3 months after repair demonstrating the healed biceps femoris tendon and fibular styloid (orange arrowhead). The white arrow represents the drill hole path through the fibular head and heading toward the anteromedial tibia. MRI, magnetic resonance imaging; PLC, posterolateral corner.
PMC9663643
10.1177_23259671221131817-fig4.jpg
0.406803
28344267eb3d44dab9711dc53623f8b1
(A) The location of injury to the LCL was observed in the following frequencies: 18% (n = 5) of injuries were femoral-sided injuries, 0% were a midsubstance tear, and 82% (n = 23) were an avulsion off of the fibular head. (B) The location of injury to the biceps femoris was observed in the following frequencies: 100% (n = 14) of injuries were an avulsion off of the fibular head and 0% were an injury at the myotendinous junction. (C) The location of injury to the popliteus tendon was observed in the following frequencies: 69% (n = 9) were femoral-sided injuries, 0% were midsubstance, and 31% (n = 4) were at the myotendinous junction. (D) The location of injury to the popliteofibular ligament was observed in the following frequencies: 100% (n = 12) of injuries were an avulsion off of the fibular head. Image adapted from Kahan JB, Li D, Schneble CA, et al. The pathoanatomy of posterolateral corner ligamentous disruption in multiligament knee injuries is predictive of peroneal nerve injury. Am J Sports Med. 2020;48(14):3541-3548. LCL, lateral collateral ligament.
PMC9663643
10.1177_23259671221131817-fig5.jpg
0.437658
0d089f4c92e94434a0089b6b26823c09
Posterolateral corner injury classification system according to Kahan et al. 7 The injuries were classified into 3 main classes based on location to the LCL: class P (proximal) femoral avulsion (n = 5, 18%), class M midsubstance tear (n = 0), and class D (distal) fibular avulsion (n = 23, 82%). Class D injuries were subclassified based on the number of structures avulsed from the fibular head: class D1 (n = 0), class D2 (n = 15, 65%), and class D3 (n = 8, 35%). Image adapted from Kahan JB, Li D, Schneble CA, et al. The pathoanatomy of posterolateral corner ligamentous disruption in multiligament knee injuries is predictive of peroneal nerve injury. Am J Sports Med. 2020;48(14):3541-3548.
PMC9663643
10.1177_23259671221131817-fig6.jpg
0.431082
dcb9d962bc084196a055552e2cf18b3a
Flowchart diagram representing children lost to follow-up and included in the final analysis and the reasons for a drop-out.
PMC9663913
fped-10-959643-g001.jpg
0.403089
cafa626b3d5148ceaddbcdb5e85d12b9
Cytotoxic effects of different concentrations of standard (drug) and isolated colchicine after 24-hours of treatment. A. On MCF-7 cells, B. On 4T1 cells, and C. On fibroblast cells. Data are given as mean ± SE for each point of three separate experiments, *; P<0.05, **; P<0.001 vs. control.
PMC9663959
Cell-J-24-647-g01.jpg
0.432107
f18662b5b66949a79708aba620a29dfd
The growth inhibitory effect of different concentrations of isolated and standard colchicine (drug) after 48 hours. A. On MCF-7 cells, B. 4T1 cells, and C. Fibroblast cells. Data are given as mean ± SE for each point of three separate experiments, *; P<0.05 and **; P<0.001 vs. control.
PMC9663959
Cell-J-24-647-g02.jpg
0.402422
4f5de4ff4a6543b9b847dabcbb5bbbca
mRNA expression of pro-apoptotic and anti-apoptotic genes. A. P53, BAX, BCL-2 in MCF-7 cells, B. p53, Bax, Bcl-2 in 4T1 cells. The expression of pro-apoptotic and anti-apoptotic genes in both cell lines was determined by measuring mRNA levels using real-time polymerase chain reaction (PCR). Data are given as mean ± SE for each point of three separate experiments, *; P<0.01, **; P<0.05, ***; P<0.001, between equal concentrations of colchicine and $; P<0.01, $$; P<0.05, $$$; P<0.001, between different concentrations of colchicine. C. Colchicine effects on the expression of BAX/BCL-2 in MCF-7 and 4T1 cells. Data are given as mean ± SE for each point of three separate experiments. *; P<0.01, **; P<0.05, ***; P<0.001 vs. control and $; P<0.01, $$; P<0.05, $$$; P<0.001 vs. equal concentrations of isolated and standard colchicine (drug).
PMC9663959
Cell-J-24-647-g03.jpg
0.458085
7dab9b4c8a354a54ab761cbb15bc6e83
Expression of pro-apoptotic and anti-apoptotic proteins and densitometric analysis. A. The effects of colchicine on the expression of pro-apoptotic and anti-apoptotic proteins in MCF-7 and 4T1 cells. Cells were exposed to the isolated and standard colchicine (drug) at 0.5 and 1 µg/ml and 200 and 400 µg/ml, respectively for 24 hours. The protein expression of P53, Bax, Bcl-2, caspase-3 and -9 was determined by Western blotting against controls, B. Densitometricy analysis of P53, Bax, Bcl-2, Caspase-3 and -9 proteins in MCF-7 cell line, and C. Densitometricy analysis in 4T1 cell line. Data are given as mean ± SE for each point of three separate experiments. Different letters indicate a significant difference (P<0.05) and the same characters indicate a non-significant difference between the treatments (P>0.05). I; Isolated and D; Drug.
PMC9663959
Cell-J-24-647-g04.jpg
0.428085
34fed1d206184d7ca560590897fbadcb
Results of Fluorescence Microscope image and early and late apoptos of MCF-7 cells. A. Untreated cells as the control group, B. Treated cells with 0.5 µg/ml of standard colchicine (drug), C. Treated cells with 1 µg/ml of standard colchicine (drug), D. Treated cells with 0.5 µg/ml of isolated colchicine, E. Treated cells with 1 µg/ml of isolated colchicine (scale bar: 50 µm), and F. The results of early and late apoptosis in MCF-7 cells determined by Annexin V-PI method. **; P<0.001 vs. control, and $$; P<0.001 vs. equal concentrations of isolated and standard colchicine (drug).
PMC9663959
Cell-J-24-647-g05.jpg
0.427629
52d0fa73a7574835b4bde92c4de05d14
Results of Fluorescence Microscope image and early and late apoptos of 4T1 cells. A. Untreated cells as control group, B. Treated cells with 200 µg/ml of standard colchicine, C. Treated cells with 400 µg/ml of standard colchicine (drug), D. Treated cells with 200 µg/ml of isolated colchicine, E. Treated cells with 400 µg/ml of standard colchicine (drug) (scale bar: 50 µm), and F. Results of early and late apoptosis in 4T1 cells determined by Annexin V-PI method. **; P<0.001 vs. control and $$; P<0.001 vs. same concentration of isolated and standard colchicine (drug).
PMC9663959
Cell-J-24-647-g06.jpg
0.403894
935bf95848634bfe8dae264eeb26f75e
Workstreams (WS) in the Life After Prostate Cancer Diagnosis (LAPCD) study.
PMC9664269
bmjopen-2022-060861f01.jpg
0.450818
15cac6bffaa34af99e24106a59977696
Theory of change model.
PMC9664269
bmjopen-2022-060861f02.jpg
0.437532
0cecfcb720ae407e97d7db1971c09d41
Summary of results. UAG, User Advisory Group.
PMC9664269
bmjopen-2022-060861f03.jpg
0.493705
7f14a01025f34ee2891e8c8f5934efc9
General schematic diagram of common environmental factors associated with Alzheimer's disease.
PMC9664454
d2ra05384e-f1.jpg
0.434728
98a2b799e1354ea6bb3aaa27328320ce
Fabrication of optical chemosensors using (A) metal organic frameworks (MOFs) and (B) mesoporous silica (MSNs).
PMC9664454
d2ra05384e-f2.jpg
0.439021
5f10055843824db9b61e647aec405bb1
Preparation of mesoporous silica as nanoporous carrier. Briefly, TEOS (tetraethoxysilane) is reacted with a cationic surfactant (e.g., CTAB) in water/acetone/diethyl ether solvent to form mesoporous silica nanospheres (MSNs). Filtration is then carried out followed by calcination at 550 °C.
PMC9664454
d2ra05384e-f3.jpg
0.409105
b4c7d43065624cf8bf70eb1b0317d8ff
General schematic representation for fabrication of metal organic frameworks (MOFs) with different dimensions.
PMC9664454
d2ra05384e-f4.jpg
0.464596
0990057639434b6d9865a16ad6e99e2b
Preparation, properties and applications of metal organic frameworks.
PMC9664454
d2ra05384e-f5.jpg
0.437616
7cd796a793404fe6b979f87575dc558e
General schematic diagram of different immobilization approaches of organic probes on different carriers.
PMC9664454
d2ra05384e-f6.jpg
0.428815
1c8a6e89472c4090af85ccfa3e00d8f1
(A) Schematic diagram for sensing Hg2+ ions using bis(diethylamino)-3oxospiro[isoindoline-1,9′-xanthen]-2ylcarbamothioyl)-4-butylbenzamide (BOICB) probe.94 (B) Schematic representation of fabrication of nanorod TAM optical chemosensors and interactions with Hg2+ ions under optimum conditions.95 (C) Representative design of the Nin-NH-MIL-101(Al) sensor applied for purification of water polluted with Hg(ii) ions and the reversible process by using 0.1 M thiourea solution (which can be repeated several times).96 Reproduced with permission from ref. 94–96.
PMC9664454
d2ra05384e-f7.jpg
0.525061
e34c468a782049c4a2cd987ee45eddf9
(A) General schematic presentation of optical chemosensors based on aluminosilica network platforms via direct functionalization with δ-tetrakis(1-methylpyridinium-4-yl)porphine ρ-toluenesulfonate for Cd(ii) ions detection.76 (B) Chelating ligand immobilized mesostructures Ia 3d aluminosilica for visualization and removal of Cd(ii).97 (C) The Zr-based metal–organic frameworks (UiO-66) with its micropore geometry for the visual detection, determination and removal of ultra-trace of some toxic metal ions such as Cd2+.98 (D) General steps of fabricating Cd2+ ion optical chemosensors built on mesoporous nanosphere silica for naked-eye determination of ultra-traces of Cd2+ ions.99 Reproduced with permission from ref. 69,97–99.
PMC9664454
d2ra05384e-f8.jpg
0.390804
37f9976fab7f4019b9d6555c4e57c81d
(A) General representation of fluorescent probe prepared based on amino-functionalized metal–organic frameworks (MOF-5-NH2) for the detection of Pb2+.100 (B) Ratiometric fluorescent (RF) probe CDs/QDs@ZIF-8 by encapsulating carbon dots (CDs) and thioglycolic acid modified CdTe quantum dots (QDs) into porous metal–organic frameworks (MOFs) for detection of Pb2+.101 (C) Phosphorescent sensor to monitor Pb2+ using metal–organic framework-5.102 Reproduced with permission from ref. 100–102.
PMC9664454
d2ra05384e-f9.jpg
0.451864
ba0efa500ed24e5388f46d63db0f401f
XRD pattern of calcium titanate nanoparticles showing peaks at theta angles of 32.7º, 47.1°, 58.9°, and 69°
PMC9664598
12935_2022_2780_Fig1_HTML.jpg
0.465351
42bb31c4e82a4419b5b9422438e8ef97
Zeta Potential and Size distribution of calcium titanate nanoparticles
PMC9664598
12935_2022_2780_Fig2_HTML.jpg
0.467546
a29991f9b278458b916b79997760da59
TEM image of calcium titanate nanoparticles
PMC9664598
12935_2022_2780_Fig3_HTML.jpg
0.448761
40f8886f846d4b8b96741d7c415d2962
Viability of cancer MCF-7 cells after exposure to five different concentrations of calcium titanate nanoparticles (0.01, 0.1, 1, 10 and 100 µg/ml) for 24 h or (0.1, 1, 10, 100 and 1000 µg/ml) for 72 h
PMC9664598
12935_2022_2780_Fig4_HTML.jpg
0.416001
46d43a4659b44e598cac8300159ec086
Examples for the scored Comet nuclei in MCF-7 cells showing nuclei with intact DNA (In) and other nuclei with different degree of damaged DNA damage (200 × magnification)
PMC9664598
12935_2022_2780_Fig5_HTML.jpg
0.505523
061feb1d10d64590a7471a25fc6c8bf0
Level of ROS within the control and treated MCF-7 cells with IC50/72 of calcium titanate nanoparticles ((200 × magnification)
PMC9664598
12935_2022_2780_Fig6_HTML.jpg
0.435871
e6bf7f7fbaa747beaa09072f00977516
Expression levels of p53, Bax and Bcl2 genes in the control and treated MCF-7 cells with IC50/72 h of Calcium Titanate nanoparticles. Results are expressed as mean ± SD. *: Indicates statistical significant difference from the compared control at p < 0.05 using student t-test
PMC9664598
12935_2022_2780_Fig7_HTML.jpg
0.472081
55e4c94262b14c5ab65edaf863b39fa6
Cell cycle distribution of the control and treated MCF-7 cells with IC50/72 of calcium titanate nanoparticles
PMC9664598
12935_2022_2780_Fig8_HTML.jpg
0.461868
6426cd9cd3d948cdb3ec27b2370a347f
Apoptosis induction in the control and treated MCF-7 cells with IC50/72 of calcium titanate nanoparticles. Q2-1 denotes necrosis phase; Q2-2 denotes late apoptosis phase, Q2-3 denotes normal viable cells and Q2-4 denotes early apoptosis phase
PMC9664598
12935_2022_2780_Fig9_HTML.jpg
0.371581
cc87953380f643a4bce6afe83c36e649
Age at diagnosis of HbSS of the participants.
PMC9665090
IANN_A_2129090_F0001_C.jpg
0.532838
8f322e18204b40b2ad16563ec0a74657
Steady state packed cell volume of participants.
PMC9665090
IANN_A_2129090_F0002_C.jpg
0.430643
9e709b75c1b44299b9474ef3dd9de1da
Number of hospital admission in a year in the participants.
PMC9665090
IANN_A_2129090_F0003_C.jpg
0.447228
49682dc27dac4047b5c8c46e3d40546e
Number of bone pain crisis per year in the participants.
PMC9665090
IANN_A_2129090_F0004_C.jpg
0.363162
4058607ce7b94e518d837d2045f956a8
Complications of sickle cell anaemia in the participants.
PMC9665090
IANN_A_2129090_F0005_C.jpg
0.431122
ced94c176860473ea9791db7c8525efb
Expanded SEIR model flowchart.Each compartment represents a distinct state of infection, with arrows indicating flows between compartments.
PMC9665358
pone.0277521.g001.jpg
0.461504
7c6e8e8e941f4a44942d5e8c9ede2209
Model fits and long-term predictions.a) Median model fits to the 7-day moving average of daily confirmed case data, along with short-term predictions, assuming long-term immunity. The cases due to the alpha, delta, and other variants are given in red, green, and blue, respectively. b) Long-term forecasts of daily confirmed cases until February 2023. The 7-day moving average of confirmed case data is given in red. The median model predictions given estimates of social distancing measures and vaccination rate as of Sept. 24th 2021 are given by the black curve, while the model predictions given a full release of social distancing measures are given by the blue curve. The yellow and blue shading represent the 90% confidence intervals for these two scenarios. If the vaccination rate is increased by 1.5x, the median model prediction given social distancing measures estimated on Sept. 24th 2021 is given by the green dashed curve, while in the case of full release of social measures, it is given in magenta. The blue dashed line represents a full release of social measures on Mar. 1st 2021, when the fraction of immunity was much lower than present, which produces a peak of 250,000 daily confirmed cases (assuming social measures are not modified). c) Total proportion susceptible (blue), and total immune (black) over time. The proportion immune given estimates of social measures and vaccination as of Sept. 24th 2021 is given by the solid black line, while a full release of social measures is shown as a dashed black line. If the vaccination rate is increased by 1.5x, the proportion immune is represented by the red dashed line. The 90% confidence interval is shown as a yellow band. As of Sept. 24th 2021, 9% of the population were susceptible, while 90% were immune. d) Proportion of the population with natural immunity (red) along with the proportion of the population with vaccine-conferred immunity (blue). As of Sept. 24th 2021, the fraction of the population with natural immunity is 34%, while the fraction with vaccine-induced immunity is 56%.
PMC9665358
pone.0277521.g002.jpg
0.403261
3d3d2408c43546038d28a4845e29261f
Model predictions of hospitalizations and deaths.Median predictions of a) total hospitalizations and b) daily deaths over time. Several scenarios are shown. Median model predictions given estimates of social distancing measures and daily vaccination rate as of Sept. 24th 2021 are shown by the solid black curve, while the median model predictions given a full release of social measures is shown in blue. The 90% confidence interval for these two scenarios (social measures estimated on Sept. 24th 2021, and full release of social measures) are given by the yellow and blue bands, respectively. If vaccination rate is increased by a factor of 1.5x, the median model predictions are shown by the green curve when applying estimates of social measures as of Sept. 24th 2021 and shown in magenta under a full release of social measures. The daily hospitalization and death data is shown by the red circles.
PMC9665358
pone.0277521.g003.jpg
0.442687
ab8de1c9bbce42f5887ebc521c240af5
Scenarios of waning immunity.(Top row) Scenarios of waning immunity, given waning intervals of 1 year, 2.5 years, and 5 years. The median model predictions of confirmed cases given estimated social distancing measures as of Sept. 24th 2021 and release of social measures are given by the black and blue curves, respectively. The 90% confidence interval for the median case is given by the orange shading, while the confirmed case data is given in red. (Bottom row) Forecasts for total proportion susceptible (blue), and total immune (black) are shown over time. Solid curves represent the impact of maintaining social measures and vaccination rates as of Sept. 24th 2021, while the dashed curve denotes the effects for a full release of social measures.
PMC9665358
pone.0277521.g004.jpg
0.429622
900f7d0decda45ed82873a7d2fa62e8e
Model ensemble and probability of elimination over time, given long-term immunity.Ensemble of predictions of daily confirmed cases, and probability of elimination over time, assuming long-term immunity, given a) estimated social measures as of Sept. 24th, 2021 and b) after the full release of social measures. The predictions of the model ensemble (250 in total, see Methods) are represented by the thin curves in the background of the figure. Given the estimated social measures and vaccination rate as of Sept. 24th, 2021, the probability of fadeout is given by the blue curves, whereas increasing vaccination to 1.5x is presented by the green curves, respectively. If estimated social measures are continued along with the vaccination rate as of Sept. 24th 2021, 99% probability of elimination will be achieved on Nov. 13th 2021, while if social measures are fully released, 99% probability of elimination will be achieved on Nov. 22nd 2021. With a 1.5x increase in vaccination, the corresponding 99% probability of pandemic fadeout will be achieved on Nov. 8th 2021 and Nov. 19th 2021 for continuing with estimated social measures and given a release of social measures, respectively. Even though there is a significant probability of resurgence given a full release of social measures, the size of the wave is likely to be very small.
PMC9665358
pone.0277521.g005.jpg
0.434613
c571df17ebe04300b1ab8a83ab3028a9
Model ensemble and probability of elimination over time, given waning of immunity.Ensemble of predictions of daily confirmed cases, and probability of elimination over time, assuming waning of natural immunity over 2.5 years, given a) estimates of social measures as of Sept. 24th 2021 and b) after the full release of social measures. The predictions of the model ensemble (250 in total, see Methods) are represented by the thin curves in the background of the figure. For the estimated social measures and vaccination rate, the probability of fadeout is given by the blue curves. For these scenarios, the probability of elimination does not reach 50% until 2023.
PMC9665358
pone.0277521.g006.jpg
0.425746
0b54c7aa266747ecb92eaeb4a508e83f
Simulations of emerging variants.a) Median model predictions (black) fit to the 7-day moving average of daily confirmed cases in Florida to Sept. 24th 2021 (blue), given waning of immunity over 2.5 years. Confirmed case data from Sept. 24th to Feb. 14th 2022 is shown by the gray curve. Four scenarios of the emergence of a 4th variant are shown: 2x transmissibility of the original variants, emerging on November 1st (red, solid line), 1.5x transmissibility, emerging on November 1st (blue, solid line), 2x transmissibility, emerging on December 1st (red, dashed line), and 1.5x transmissibility, emerging on December 1st (blue, dashed line). b) Simulations of a 5th variant, emerging on Mar. 1st 2022 (blue), May 1st 2022 (red), July 1st 2022 (green), and Sept. 1st 2022 (magenta). Solid lines represent the case of a 5x increase in transmissibility compared to the original variant, while the dashed lines represent a 3.5x increase in transmissibility.
PMC9665358
pone.0277521.g007.jpg
0.563099
87e248128b6f4aee9d497acead67ef53
Responders and countries.
PMC9666278
can-16-1443fig1.jpg
0.367238
f932d710f77e4611974eb142ecd1944e
Availability of National Health Care System.
PMC9666278
can-16-1443fig2.jpg
0.499532
251c233a9c034d5da96303f38a7a4861
Availability of National Cancer Registry.
PMC9666278
can-16-1443fig3.jpg
0.423544
addd75dd4bd34c5abd67c7496219f112
Availability of National Breast Screening Programme.
PMC9666278
can-16-1443fig4.jpg
0.493542
4af72a52f952412388a0ebdc98591bcf
Breast cancer management in dedicated or accredited breast centres with multidisciplinary care team.
PMC9666278
can-16-1443fig5.jpg
0.423566
395328c131c9469b9a0d3de508d88c06
Frequency of breast screening.
PMC9666278
can-16-1443fig6.jpg
0.449687
c913e15143a84804b0193c150b509267
Proportion of patient undergoing breast conservation surgery.
PMC9666278
can-16-1443fig7.jpg
0.476222
d480aed4a00049d5b45bf2b5fb575999
Most important hurdles in offering breast reconstruction, if any.
PMC9666278
can-16-1443fig8.jpg
0.447587
49e98924245c466c8f1feeb761638dd0
Mode of training in oncoplastic procedures.
PMC9666278
can-16-1443fig9.jpg
0.408785
dce8ad065ce949c7894786b3fcc0c5ba
Knockdown of STING post-Golgi cofactors activates tonic IFN signaling.a A spatiotemporal map of selected STING cofactor candidates identified in the primary proteomic screen. Open, half-filled and filled circles indicate cofactors identified at 0.5 h, 4 h and 8 h after STING activation, respectively. b lfnb1 mRNA expression in ligand activation assay and tonic activation assay c. Wild-type MEFs were transfected with specific siRNA against each of the 31 selected candidate cofactors. Then, knockdown cells were either simulated with HT-DNA (1 µg/mL, 4 h) then qRT-PCR for Ifnb1 expression b or directly measured Ifnb1 expression without stimulation c. Fold-changes were determined by normalizing to control siRNA in either assay. Primary data are shown in Supplementary Fig. 1. d qRT-PCR analysis of resting-state lfnb1 and Ccl4 (an ISG) mRNA expression after control, Sec24c or Gcc2 siRNA knockdown in wild-type MEFs. n = 4. e ELISA analysis of mouse IFN-β in the supernatant after control, Sec24c or Gcc2 siRNA knockdown followed by DXMAA stimulation (50 µM, 8 h). n = 3. f Confocal microscopy images of STING colocalization with Golgi. StingKO MEFs stably expressing HA-STING were transfected with control, Sec24c or Gcc2 siRNA followed by mock or HTDNA stimulation (1 µg/mL, 1.5 h). HA-STING in green, GM130 (a Golgi marker) in red and DAPI in blue. Scale bar, 20 µm. Data are representative of at least three independent experiments. Data (d and e) are shown as mean ± s.e.m. P values were determined by One-way ANOVA.
PMC9666523
41467_2022_33765_Fig1_HTML.jpg
0.432338
d4f06718f2eb43b99aae69c0b61e7e92
GCC2 is required for STING Golgi-exit.a A diagram of Golgin family members at the trans-Golgi network (TGN). b qRT-PCR analysis of tonic (left) or ligand-activated (right) lfnb1 mRNA expression after mock knockdown (siCtrl) or specific siRNA knockdown of Gcc1, Gcc2, Golga1, or Golga4 in wild-type MEFs. n = 3. c A heatmap showing expression of indicated ISGs (right) at the resting-state in Gcc2WT and Gcc2KO MEFs after control, Sting, Mavs siRNA knockdown. d Western blot analysis of STING signaling kinetics. Gcc2WT and Gcc2KO MEFs were stimulated with HTDNA (1 µg/mL) for indicated times (top). Quantification of relative Sting protein abundance (normalized to Tubulin, then set 0 h value to 1) are shown on the right. p-Sting, p-Tbk1, and p-Irf3 are key phosphorylation events of the STING signaling pathway. e ELISA analysis of mIFN-β in the supernatant in Gcc2WT and Gcc2KO MEFs 24 h after HSV-GFP infection (m.o.i. = 1). n = 4. f HSV-1-GFP infection in Gcc2WT and Gcc2KO MEFs. Top, representative FACS plot of GFP expression 24 h after HSV-1-GFP infection (m.o.i. = 1). Lower panels, percentage of GFP+ cells (lower left), GFP MFI (Mean fluorescence intensity, lower middle) and HSV-1 titers in the supernatant (lower right) in Gcc2WT and Gcc2KO MEFs. g–i Confocal microscopy analysis of endogenous STING trafficking and signaling. Gcc2WT or Gcc2KO MEFs were stimulated with HT-DNA (1 µg/mL) for indicated times (top). Cells were then stained for endogenous STING (green) and Golgi marker GM130 (red) (g, top). Quantification of fluorescence intensity of endogenous STING in the Golgi (GM130+ area) using Fiji (g, bottom). A similar set of cells were stained for p-Tbk1 and p-Irf3 (images in Supplementary Fig. 3e, f). Quantification of fluorescence intensity of endogenous p-TBK1 (h) and p-IRF3 (i) in Gcc2WT and Gcc2KO MEFs are shown. The colored area corresponds to Golgi-dwell time. n = 3. Data are representative of at least three independent experiments. At least 14 cells in two different views were analyzed (g–i). Data (b, e and g–i) are shown as mean ± s.e.m. P values were determined by one-way ANOVA (b and e) or by two-way ANOVA (g–i).
PMC9666523
41467_2022_33765_Fig2_HTML.jpg
0.426776
d1e1a40f0b6b403bbe1013eeb5e79ffc
Temperature-mediated slowdown of trafficking at the Golgi enhances STING signaling.a A diagram of expected STING trafficking at 37 °C and 20 °C. Top, at normal cell culture temperature (37 °C), STING activation triggers trafficking from the ER to Golgi then to endolysosomes. Bottom, lowering the temperature to 20 °C slows down post-Golgi vesicle trafficking, leading to STING accumulation on the Golgi. b Western blot analysis of STING signaling kinetics. Wild-type MEFs were first acclimated in 37 °C or 20 °C then stimulated with HT-DNA (1 µg/mL) for indicated times (top) while remaining at the same temperature. Control experiments with DMXAA or poly(I:C) stimulation are shown in Supplementary Fig. 5. c and d Confocal microscopy analysis of endogenous STING trafficking and signaling. Wild-type MEFs were stimulated with HT-DNA (1 µg/mL) while incubated at 37 °C or 20 °C. Endogenous STING trafficking (c, images on top, quantifications at the bottom) and signaling activation (d, p-TBK1 quantification on top, images at the bottom) were analyzed as in Fig. 2g, h. Scale bar, 20 µm. n = 3. Data are representative of at least three independent experiments. At least 17 cells in two different views were analyzed (c, d). Data (c, d) are shown as mean ± s.e.m. P values were determined by Two-way ANOVA (c, d).
PMC9666523
41467_2022_33765_Fig3_HTML.jpg
0.410378
db02e6e00c404b8bb2405e651954a902
Both cGAS and STING are required for tonic IFN signaling in Gcc2-KO cells.a, b Western Blot (a) and qRT-PCR (b) analysis of tonic IFN signaling in Gcc2WT, Gcc2KO, Gcc2KOSTINGKO, and Gcc2KOcGASKO MEFs. Two independent CRISPR/Cas9 knockout clones of each genotype are included. p-Sting, p-Tbk1, and p-Stat1 are key phosphorylation events of the STING signaling pathway (a). Expression of IFN genes and ISGs are shown in a heatmap (b, left) and representative bar graphs (b, right). n = 3. c, d Western Blot (c) and qRT-PCR (d) analysis of tonic IFN signaling in Gcc2WT, Gcc2KO, Gcc2KOcGASKO MEFs reconstituted with vector control, wild-type cGAS, E225A/D227A cGAS (enzymatic-dead mutant), K407A/K411A cGAS (DNA-binding mutant). Cells were analyzed as in a, b. n = 3. e, f Western Blot (e) and qRT-PCR (f) analysis of tonic IFN signaling in Gcc2WT, Gcc2KO, Gcc2KOSTINGKO MEFs reconstituted with vector control, wild-type STING, R238A/Y240A STING (ligand-binding mutant), S366A STING (IFN signaling mutant). Cells were analyzed as in a, b. n = 3. g, h qPCR analysis of mtDNA content (g) and qRT-PCR analysis of tonic IFN signaling (h) in two independent clones of Gcc2WT, Gcc2KO with or without mtDNA depletion by EtBr. n = 3. i Intracellular cGAMP level in Gcc2WT and Gcc2KO cells mock treated or stimulated with HT-DNA. n = 8. j qPCR analysis of indicated cytoplasmic DNA species in Gcc2WT and Gcc2KO cells. n = 5. Data are representative of at least three independent experiments. Data (b, d, f, and g–j) are shown as mean ± s.e.m. P values were determined by one-way ANOVA (b, d, f, and g–j).
PMC9666523
41467_2022_33765_Fig4_HTML.jpg
0.413495
7c9520a1cba24fd290db92e230e4a605
cGAS drives STING signaling to maintain a basal state of immune defense.a, b qRT-PCR analysis of baseline immune gene expression in cGASWT and cGASKO mouse heart or BMDMs (n = 3). Heatmaps of multiple ISGs are shown in a. Representative bar graphs are shown in b. c, d Western Blot (c) and qRT-PCR (d) analysis of tonic IFN signaling in cGASWT and cGASKO MEFs. Two independent clones of cGASWT and cGASKO MEFs were shown. p-Sting, p-Tbk1 and p-Stat1 are key phosphorylation events of the STING signaling pathway (c). Expression of ISGs are shown in a heatmap (d, left) and representative bar graphs (d, right). n = 3. e, f Western blot (c) and qRT-PCR (d) analysis of tonic IFN signaling in cGASWT and cGASKO MEFs reconstituted with vector control, wild-type cGAS, E225A/D227A cGAS (enzymatic-dead mutant), K407A/K411A cGAS (DNA-binding mutant). Cells were analyzed as in c, d. n = 3. Data are representative of at least three independent experiments. Data (b, d, and f) are shown as mean ± s.e.m. P values were determined by one-way ANOVA (b, d, and f).
PMC9666523
41467_2022_33765_Fig5_HTML.jpg
0.44125
add7cba20c824ee0a097b4ea6a3c6d99
RAB14 and other Rabs mediate STING post-Golgi trafficking.a qRT-PCR analysis of tonic Ifnb1 mRNA expression in StingWT or StingKO MEFs after siRNA knockdown of indicated Rab GTPases (bottom). Solid red bars indicate siRNAs that induce STING-dependent IFN signaling. n = 3. b Co-immunoprecipitation analysis of STING:Rab interaction. HEK293T cells were transfected with FLAG-Sting and various HA-Rab GTPases (as indicated on top), IP with the FLAG antibody and blotted with indicated antibody on the right. Percentages of IP/Input are shown on the bottom. Note the expression level of Rab14 plasmid is low in whole cell lysate but IP/Input% is high. c A heatmap showing expression of ISGs in Rab14WT, Rab14KO, Rab14KOStingKO-pool, and Rab14KOMavsKO-pool MEFs. Bar graphs are shown in Supplementary Fig. 7g. d Western blot analysis of STING signaling kinetics in Rab14WT and Rab14KO MEFs. Cells were stimulated with DMXAA (10 µg/mL) for indicated times (top) and blotted for total- and phosphor-proteins as indicated on the right. Quantification of relative Sting protein abundance (normalized to Tubulin, then set 0 h value to 1) are shown on the right. e Confocal microscopy analysis of endogenous STING trafficking in Rab14WT and Rab14KO MEFs. Cells were stimulated with DMXAA (10 µg/mL) and analyzed as in Fig. 2g. Endogenous STING in green and GM130 (a Golgi marker) in red. Scale bar, 20 µm. n = 3. Data are representative of at least three independent experiments. At least 37 cells in two different views were analyzed (e). Data (a and e) are shown as mean ± s.e.m. P values are determined by One-way ANOVA (a) or by Two-way ANOVA (e).
PMC9666523
41467_2022_33765_Fig6_HTML.jpg
0.384811
c5760c5a805142878e4e1984ec27c5d1
Gcc2−/− mice develop STING-dependent serologic autoimmunity.a A heatmap showing IgM autoantibody array analysis of Gcc2+/+, Gcc2−/−, and Gcc2−/−Sting−/− mouse serum (6-month-old). n = 5. b Representative bar graphs of elevated IgM autoantibodies in Gcc2+/+, Gcc2−/− and Gcc2−/−Sting−/− mouse serum (6-month-old). n = 5. Data are shown as mean ± s.e.m. P values are determined by one-way ANOVA, ns, not significant.
PMC9666523
41467_2022_33765_Fig7_HTML.jpg
0.498617
26962e3d20784c6393b5666a9faef2c7
Gcc2-KO and Rab14-KO induce anti-tumor immunity.a B16 tumor growth in wild-type mice. Left, Western blot analysis of CRISPR/Cas9 knockout pooled B16 cells. Right, tumor volumes of wild-typepool, Sec24KO-pool, Gcc2KO-pool, Rab14KO-pool, or Npc1KO-pool B16 melanoma cells after subcutaneous injection in wild-type mice. b Wild-type, Gcc2KO and Rab14KO B16 cell proliferation analysis by IncuCyte. Representative single-cell CRISPR/Cas9 knockout clones are shown. c Wild-type, Gcc2KO and Rab14KO B16 tumor growth in wild-type mice. Left, mean tumor volume. Middle, individual mouse tumor growth curve. Right, Kaplan–Meier survival curve. d, e Wild-type, Gcc2KO and Rab14KO B16 tumor growth in Rag1−/− mice (d) and Ifnar1−/− mice (e). Left, mean tumor volume, Right, Kaplan–Meier survival curve. Data in b, c are representative of two independent experiments and in d, e are pooled from two independent experiments. Data (a–e) are shown as mean ± s.e.m. P values are determined by two-way ANOVA in (a–e). ns, not significant. Mantel-Cox tests were used for survival studies.
PMC9666523
41467_2022_33765_Fig8_HTML.jpg
0.417534
56beca3e90a74fb0a36a83d13e17b5f7
An overall model.Homeostatic cGAS activity drives STING trafficking that supports the basal level of immune defense and maintains a healthy state. cGas−/− cells and mice have lowered basal immune defense, leading to infection risk. Interruption of STING post-Golgi trafficking by Gcc2−/− and Rab14−/− leads to tonic IFN activation, increased autoimmunity and anti-tumor immunity.
PMC9666523
41467_2022_33765_Fig9_HTML.jpg
0.425968
8036accf4dd54967a3b3412348574d8f
Nature-based thinking as a theoretical lens for participatory assessment of urban NBS.The photo was taken by Arjen Buijs
PMC9666616
13280_2022_1772_Fig1_HTML.jpg
0.453238
d15606ca56264775ae7e8ff59857b4a0
The continuum of evidence by DeMeo et al. (2015) (authors’ interpretation)
PMC9666616
13280_2022_1772_Fig2_HTML.jpg
0.486268
077334b6affc42d890143f556057f1c3
Stages in participatory monitoring and assessment
PMC9666616
13280_2022_1772_Fig3_HTML.jpg
0.444251
055cc2eec4504862a59afd5a1dd3c0a9
Criteria for politicised and contextualised assessment applied at the level of the full set of indicators (Step 5 of the action framework)
PMC9666616
13280_2022_1772_Fig4_HTML.jpg
0.487771
d8f175f1eef3471182c75767c227e42c
Functional scheme. The study consists of several steps: from data collection to various tests to evaluate the model
PMC9667561
12859_2022_5038_Fig1_HTML.jpg
0.387049
8ab787082bc04f7c902052cf0dff63dc
Session 1 survey. The figure represents the boxes of session 1 in which one is asked to list the characteristics of the patient and the disease and comment on them
PMC9667561
12859_2022_5038_Fig2_HTML.jpg
0.44369
8876b793963f4f6c88c4db930b679217
Session 2 survey. The figure depicts the questions in session 2 for each category of surgical techniques and comments on them
PMC9667561
12859_2022_5038_Fig3_HTML.jpg
0.386121
e5eeecc3d46d48788e7862983bbe8dcc
Session 3 survey. The figure shows the demands of session 3. It represents the opportunity to list the estimated results in daily clinical practice and to comment on them
PMC9667561
12859_2022_5038_Fig4_HTML.jpg
0.470015
ef3469fe725f46e591af1fcc933c0b20
Model architectures. The CBOW architecture predicts the current word based on the context and the Skip-gram predicts surrounding words given the current word
PMC9667561
12859_2022_5038_Fig5_HTML.jpg
0.444006
cfb04bd3a4264785ae7af3ffba595912
Web Graphic User Interface of ETHOS. This figure represents the GUI of ETHOS, which allows the execution of various analyses. In the center of the figure, the available analyses. On the left-hand side at the bottom of the figure is the table showing the analysis results
PMC9667561
12859_2022_5038_Fig6_HTML.jpg
0.502963
e36f48a690f84aeda73712cec252065d
Infiltrative basal cell carcinoma in the supra-alar region of the nose. As seen, the lesion is widespread and crusted
PMC9667695
tao-60-155-g1.jpg
0.49986
f07fd4e3efcf46b5af87bdec73521a83
Preparing the flap: The midline of both eyebrows was marked and an approximately a 2-cm area was identified as the estimated pedicle region starting from 2 (1.7–2.2) cm laterally
PMC9667695
tao-60-155-g2.jpg
0.446075
dbf801a2b2814d8db49d5d287ae468f0
(a-b) Creating template from the intact side using suture foil, (c) modifying template according to the defect area, (d) using template for designing the flap
PMC9667695
tao-60-155-g3.jpg
0.434337
84a99f8751a54e3c8a6ee27f2cc466b3
(a) Using the conchal cartilage to reconstruct the alar cartilage, (bd) shaping the conchal cartilage as an alar cartilage (e) applying the shaped cartilage to the defect area, (f) final status of the flap
PMC9667695
tao-60-155-g4.jpg
0.450796
2185b35a94e54e13a305d79067a6e806
View of the patient eight weeks after pedicle cutting and 13 weeks after the first operation
PMC9667695
tao-60-155-g5.jpg
0.493004
0773837680de43ce99411b83fd6252ae
Daily rainfall (mm), temperature (°C), and incident radiation (MJ m-2 day-1) during the summer season of maize and soybean in 2018, 2019, and 2020.
PMC9667818
fpls-13-1006720-g001.jpg
0.427899
ccf337817dcf45d0b35cc10adb489fa3
Field demonstration of maize/soybean strip intercropping system. (A) Intercrops were at the vegetative growth stage, and (B) Intercrops were at the reproductive growth stage (Photos: Muhammad Ali Raza). Location: Punjab Province, Pakistan.
PMC9667818
fpls-13-1006720-g002.jpg
0.444601
3627606ef98d465e8e17858395efdcf2
Leaf area index of maize (A–C) and soybean (D–F) in response to different maize planting densities (6 maize plants m-2, low, D1; 8 maize plants m-2, medium, D2; and 10 maize plants m-2, high, D3) under maize/soybean strip intercropping. Bars show ± standard errors (n = 3). The different lowercase letters within a bar show a significant difference (p < 0.05) among treatments. The M and S represent the sole maize and soybean, respectively.
PMC9667818
fpls-13-1006720-g003.jpg
0.404003
7a8f19115eeb4a1fb95e65e77204091b
Dry matter of maize (A–C) and soybean (D–F) in response to different maize planting densities (6 maize plants m-2, low, D1; 8 maize plants m-2, medium, D2; and 10 maize plants m-2, high, D3) under maize/soybean strip intercropping. Bars show ± standard errors (n = 3). The different lowercase letters within a bar show a significant difference (p < 0.05) among treatments. The M and S represent the sole maize and soybean, respectively.
PMC9667818
fpls-13-1006720-g004.jpg
0.397827
0d8c15f16fc342cd892029e63d245524
Three years average grain yield of maize (A), soybean (B), total grain yield (C) in response to different maize planting densities (6 maize plants m-2, low, D1; 8 maize plants m-2, medium, D2; and 10 maize plants m-2, high, D3) under maize/soybean strip intercropping. Bars show ± standard errors (n = 3). The different lowercase letters within a bar show a significant difference (p < 0.05) among treatments. The M and S represent the sole maize and soybean, respectively.
PMC9667818
fpls-13-1006720-g005.jpg
0.484871
bcfa861ae75142869f523f027e7cde1e
Geographic location and odds of National Comprehensive Cancer Network (NCCN) treatment nonadherence for women diagnosed with early-stage ovarian cancer (OC). The fully adjusted effect of geographic location on the odds of receiving care that did not adhere to the NCCN treatment guidelines among women with early-staged OC (stages I and II) is shown. Models are adjusted for insurance status, age, race and ethnicity, socioeconomic status, marital status, tumor characteristics, Charlson Comorbidity Score, year of diagnosis, treatment at a high-volume hospital, proximity of closest high-volume hospital, and distance traveled to receive care. Statistically significant locations are outlined by contour lines.
PMC9667974
pkac067f1.jpg
0.428351
ef4ac97595504a668c09777ddf6ebcb7
Geographic location and odds of National Comprehensive Cancer Network (NCCN) treatment nonadherence for women diagnosed with advanced-staged ovarian cancer (OC). The fully adjusted effect of geographic location on the odds of receiving care that did not adhere to the NCCN treatment guidelines among women with advanced-staged OC (stages III and IV) is shown. Models are adjusted for insurance status, age, race and ethnicity, socioeconomic status, marital status, tumor characteristics, Charlson Comorbidity Score, year of diagnosis, treatment at a high-volume hospital, proximity of closest high-volume hospital, and distance traveled to receive care. Statistically significant locations are outlined by contour lines.
PMC9667974
pkac067f2.jpg
0.422421
af3e03d517e74b6aa63c7dc413283660
Time series of geographic risk of National Comprehensive Cancer Network (NCCN) treatment nonadherence for women diagnosed with ovarian cancer in California. The fully adjusted effect of geographic location on women’s risk of receiving care that did not adhere to the NCCN treatment guidelines over time and by early (stages I and II) vs advanced stages (stages III and IV) is shown. We examined 7 periods that overlapped by 2 years over a 22-year period. The last period, 2014-2017, is consistent with the implementation of all the Affordable Care Act initiatives. Models are adjusted for insurance status, age, race and ethnicity, socioeconomic status, marital status, tumor characteristics, Charlson Comorbidity Score, year of diagnosis, treatment at a high-volume hospital, proximity of closest high volume hospital, and distance traveled to receive care. Statistically significant locations are outlined by contour lines.
PMC9667974
pkac067f3.jpg
0.443048
8293d6e4b727427fbb6777329866f685
Participant flow diagram.
PMC9668014
bmjopen-2022-066511f01.jpg
0.413411
d4c5fa897dc84d3c9a73119caa47b066
Bounding boxes as visual warnings used in XP3
PMC9668227
42979_2022_1455_Fig10_HTML.jpg
0.441795
daf18de644884655a2b095b844f85944
Mean TLX scores per type of modality
PMC9668227
42979_2022_1455_Fig11_HTML.jpg
0.482304
232c00c767354f63855aaf6292882740
The experimental procedure
PMC9668227
42979_2022_1455_Fig1_HTML.jpg
0.390583
8fe92392844445f5b716b35f73420bb0
The lab setup used in experiment 1
PMC9668227
42979_2022_1455_Fig2_HTML.jpg
0.367212
1f3bcd05afd147b3b2a73aff1ee22297
Self-reported attitude toward AVs
PMC9668227
42979_2022_1455_Fig3_HTML.jpg
0.421384
49c1d6a0d3184c9799927a5e7269d412
Visual warnings used in XP1
PMC9668227
42979_2022_1455_Fig4_HTML.jpg
0.410713
a85053f8821b43e2912b15fc01db4e4a
Visual warnings used in XP2
PMC9668227
42979_2022_1455_Fig5_HTML.jpg
0.434157
8d9d5b2428404bcf9b7e13ecab1db53a
Mean UEQ scores between XP1, XP2, and XP3
PMC9668227
42979_2022_1455_Fig6_HTML.jpg
0.437229
60ecf21ebf074126889b56b96f8e6cc1
Comparison of SUS scores between XP1 and XP2
PMC9668227
42979_2022_1455_Fig7_HTML.jpg
0.481223
20b2e4e74e90437095d6fa33b7b8e843
Correlation coefficient charts per condition between TLX scores and SUS scores in XP2
PMC9668227
42979_2022_1455_Fig8_HTML.jpg
0.449854
f951406735484f07b3c1ce84bad826dd
TTS dashboard for the wizard used in XP3
PMC9668227
42979_2022_1455_Fig9_HTML.jpg
0.404782
b3c043c33cc147f39d684c5212b328c4
(a) CD spectra of HT-200 °C l-lysine in water at four different pHs (2.5, 7.3, 9.7 and 13) as a function of the temperature between 80 and 96 °C (measuring steps, 2 °C in heating and cooling). (b) Selected smoothed spectra from the figure a overlapped to a CD spectrum (reduced by 10 folds) of a protein with a secondary structures formed by 16% of α-Helix, 33% β-Strand, 21% Turn, and 30% Unordered. The simulation (grey dashed line) has been performed using a CONTINN algorithm11,23,24 of B23 CDApps10 and Leucyl–Leucine (Leu–Leu) (dashed red). (c) CD spectra of Leucyl–Leucine in ethanediol/H2O (2:1) at − 110 °C (blue), 26 °C (grey) 80 °C (red) and l-lysine at pH 7.3 at 20 °C in H2O (dashed grey)9.
PMC9668811
41598_2022_24109_Fig10_HTML.jpg
0.430765
6a2325d73e6048619626d352ea130da7
Size distribution by intensity of Dynamic Light Scattering of HTT-130 °C PLL (a) and HTT-200 °C (b) using as precursors the l-lysine aqueous solutions at pH 2.5, 7.3, 9.7 and 13.
PMC9668811
41598_2022_24109_Fig11_HTML.jpg