bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and experimental treatment of type 1 diabetes
Authors: Long S Alice , Buckner Jane H
Published: August 2022

Type 1 diabetes (T1D) is an autoimmune disease resulting in the destruction of the insulin-producing pancreatic beta cells. Disease progression occurs along a trajectory from genetic risk, the development of islet autoantibodies, and autoreactive T cells ultimately progressing to clinical disease. Natural history studies and mechanistic studies linked to clinical trials have provided insight into the role of the immune system in disease pathogenesis. Here, we review our current understanding of the underlying etiology of T1D, focusing on the immune cell types that have been implicated in progression from pre-symptomatic T1D to clinical diagnosis and established disease. This knowledge has been foundational for the development of immunotherapies aimed at the prevention and treatment of T1D.
Gallup Democracy in Exercising the NATO Membership Option: The Cases of Finland and Sweden
Authors: Kanniainen Vesa
Published: August 2022

The article asks whether the exercising of the NATO membership option is justified for Finland and Sweden in the light of their geopolitical state after Russia’s attack on Ukraine. It was the Gallup democracy, which launched the political moves toward the membership. In both countries, the majority of people turned to favor the membership within 2–3 months. Finland activated first. Sweden was fast in catching up with the Finnish process. The theory of option pricing is employed to analyze the optimal timing of exercising the option when the uncertainty regarding the value of the membership is rapidly diluting. The Turkish intervention in the membership process after the membership applications of Finland and Sweden were delivered suggests a bargaining phase once the application is delivered. Finally, the effects of the Gallup surveys on the political equilibrium are analyzed in a voter–politician model (JEL codes: D72, D74, and H56).
Periodontal ligament cells derived small extracellular vesicles are involved in orthodontic tooth movement
Authors: Zhang Yimei , Zhang Ting , Zhang Ziqian , Su Junxiang , Wu Xiaowen , Chen Liyuan , Ge Xuejun , Wang Xiujing , Jiang Nan
Published: August 2022

Objectives

Small extracellular vesicles (EVs) from human periodontal ligament cells (hPDLCs) are closely associated with periodontal homeostasis. Far less is known about EVs association with orthodontic tooth movement (OTM). This study aimed to explore the role of small EVs originated from hPDLCs during OTM.

Materials and methods

Adult C57BL/6 mice were used. Springs were bonded to the upper first molars of mice for 7 days to induce OTM in vivo. To block small EVs release, GW4869 was intraperitoneally injected and the efficacy of small EVs inhibition in periodontal ligament was verified by transmission electron microscope (TEM). Tooth movement distance and osteoclastic activity were studied. In vitro, hPDLCs were isolated and administered compressive force in the EV-free culture media. The cell morphologies and CD63 expression of hPDLCs were studied. Small EVs were purified and characterized using a scanning electron microscope, TEM, western blot, and nanoparticle tracking analysis. The expression of proteins in the small EVs was further processed and validated using a human immuno-regulated cytokines array and an enzyme-linked immunosorbent assay (ELISA).

Results

The small EV depletion significantly decreased the distance and osteoclastic activity of OTM in the mice. The hPDLCs displayed different morphologies under force compression and CD63 expression level decreased verified by western blot and immunofluorescence staining. Small EVs purified from supernatants of the hPDLCs showed features with <200 nm diameter, the positive EVs marker CD63, and the negative Golgi body marker GM130. The number of small EVs particles increased in hPDLCs suffering force stimuli. According to the proteome array, the level of soluble intercellular adhesion molecule-1 (sICAM-1) displayed the most significant fold change in small EVs under compressive force and this was further confirmed using an ELISA.

Limitations

Further mechanism studies are warranted to validate the hPDLC-originated small EVs function in OTM through proteins delivery.

Conclusions

The notable decrease in the OTM distance after small EV blocking and the significant alteration of the sICAM-1 level in the hPDLC-originated small EVs under compression provide a new vista into small EV-related OTM biology.
A polygenic risk score predicts atrial fibrillation in cardiovascular disease
Authors: Marston Nicholas A , Garfinkel Amanda C , Kamanu Frederick K , Melloni Giorgio M , Roselli Carolina , Jarolim Petr , Berg David D , Bhatt Deepak L , Bonaca Marc P , Cannon Christopher P , Giugliano Robert P , O’Donoghue Michelle L , Raz Itamar , Scirica Benjamin M , Braunwald Eugene , Morrow David A , Ellinor Patrick T , Lubitz Steven A , Sabatine Marc S , Ruff Christian T
Published: August 2022

Aims

Interest in targeted screening programmes for atrial fibrillation (AF) has increased, yet the role of genetics in identifying patients at highest risk of developing AF is unclear.

Methods and results

A total of 36,662 subjects without prior AF were analyzed from four TIMI trials. Subjects were divided into quintiles using a validated polygenic risk score (PRS) for AF. Clinical risk for AF was calculated using the CHARGE-AF model. Kaplan–Meier event rates, adjusted hazard ratios (HRs), C-indices, and net reclassification improvement were used to determine if the addition of the PRS improved prediction compared with clinical risk and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Over 2.3 years, 1018 new AF cases developed. AF PRS predicted a significant risk gradient for AF with a 40% increased risk per 1-SD increase in PRS [HR: 1.40 (1.32–1.49); P < 0.001]. Those with high AF PRS (top 20%) were more than two-fold more likely to develop AF [HR 2.45 (1.99–3.03), P < 0.001] compared with low PRS (bottom 20%). Furthermore, PRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, ranging from a 3-year incidence of 1.3% in patients with low clinical and genetic risk to 8.7% in patients with high clinical and genetic risk. The subgroup of patients with high clinical risk, high PRS, and elevated NT-proBNP had an AF risk of 16.7% over 3 years. The C-index with the CHARGE-AF clinical risk score alone was 0.65, which improved to 0.67 (P < 0.001) with the addition of NT-proBNP, and increased further to 0.70 (P < 0.001) with the addition of the PRS.

Conclusion

In patients with cardiovascular conditions, AF PRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score and NT-proBNP.
Effects of low phosphorus availability on root cambial activity, biomass production and root morphological pattern in two clones of Chinese fir
Authors: Rashid Muhammad Haroon U , Guo Haolan , Zheng Shanshan , Li Linxin , Ma Xiangqing , Farooq Taimoor Hassan , Nawaz Muhammad Farrakh , Gautam Narayan Prasad , Wu Pengfei
Published: August 2022

Phosphorous (P) is a crucial limiting nutrient for plant growth and development in terrestrial ecosystems. As one of the most important subtropical coniferous tree species, Chinese fir (Cunninghamia lanceolata) plays a major role in timber supply, climate mitigation and forest recreation. In this study, two Chinese fir clones (020 and 061) with a high growth rate were subjected to two levels of P supply in a greenhouse pot experiment: P-deficient P0 (no P supply) and P-replete P1 (1.0 mmol L−1 KH2PO4). Our objectives were to study the differences in morphology and growth patterns, cambial development mechanism and secondary root growth. Root sampling was performed at 40, 80 and 120 days after treatment initiation. Results indicated that the P-replete condition produced more root cambial cells (RCCs) in third class (larger) roots of clone-061 than in those of clone-020; concomitantly, clone-061 showed significantly greater stem height (42.87 ± 1.33 cm), root collar diameter (5.45 ± 0.126 mm), root average diameter (RAD, third class = 1.27 ± 0.04 mm) in different root classes and whole-plant biomass (7.55 ± 0.69 g) compared with clone-020 under the P-replete condition. Root diameter and biomass increase due to higher cambial activity resulted in greater seedling quality. In addition, a significant positive correlation was observed between the number of RCCs and root morphological traits (root length, root surface area, RAD and root volume). Root development was significantly promoted by cambium activity in the P-replete environment, thereby enhancing plant secondary growth. Based on these outcomes, we suggest that clone-061 would be more useful for enhancing production. Regarding commercial purposes, these findings will contribute to the improvement of P fertilization efficiency.
Plasma Biomarkers of Alzheimer’s Disease Are Associated with Physical Functioning Outcomes Among Cognitively Normal Adults in the Multiethnic HABS-HD Cohort
Authors: O’Bryant Sid E , Petersen Melissa , Hall James R , Large Stephanie , Johnson Leigh A ,   HABS-HD Study Team, O’Bryant Sid E , Yaffe Kristine , Toga Arthur , Rissman Robert , Johnson Leigh , Braskie Meredith , King Kevin , Borzage Matthew , Hall James R , Petersen Melissa , Palmer Raymond , Barber Robert , Shi Yonggang , Zhang Fan , Nandy Rajesh , McColl Roderick , Mason David , Christian Bradley , Philips Nicole , Large Stephanie
Published: August 2022

In this study, we examined the link between plasma Alzheimer’s disease (AD) biomarkers and physical functioning outcomes within a community-dwelling, multiethnic cohort. Data from 1 328 cognitively unimpaired participants (n = 659 Mexican American and n = 669 non-Hispanic White) from the ongoing Health & Aging Brain Study—Health Disparities (HABS-HD) cohort were examined. Plasma AD biomarkers (amyloid beta [Aβ]40, Aβ42, total tau [t-tau], and neurofilament light chain [NfL]) were assayed using the ultra-sensitive Simoa platform. Physical functioning measures were the Timed Up and Go (TUG) and the Short Physical Performance Battery (SPPB). Cross-sectional linear regression analyses revealed that plasma Aβ 40 (p < .001), Aβ 42 (p = .003), and NfL (p < .001) were each significantly associated with TUG time in seconds. Plasma Aβ 40 (p < .001), Aβ 42 (p < .001), t-tau (p = .002), and NfL (p < .001) were each significantly associated with SPPB Total Score. Additional analyses demonstrate that the link between plasma AD biomarkers and physical functioning outcomes were strongest among Mexican Americans. Plasma AD biomarkers are receiving a great deal of attention in the literature and are now available clinically including use in clinical trials. The examination of AD biomarkers and physical functioning may allow for the development of risk profiles, which could stratify a person’s risk for neurodegenerative diseases, such as AD, based on plasma AD biomarkers, physical functioning, ethnicity, or a combination of these measures prior to the onset of cognitive impairment.
Genomic features of renal cell carcinoma developed during end-stage renal disease and dialysis
Authors: Johnson Todd A , Maekawa Shigekatsu , Fujita Masashi , An Jisong , Ju Young-Seok , Maejima Kazuhiro , Kanazashi Yuki , Jikuya Ryosuke , Okawa Yuki , Sasagawa Shota , Yagi Ken , Okazaki Yasushi , Kuroda Naoto , Takata Ryo , Obara Wataru , Nakagawa Hidewaki
Published: August 2022

Patients with end-stage renal disease (ESRD) or receiving dialysis have a much higher risk for renal cell carcinoma (RCC), but carcinogenic mechanisms and genomic features remain little explored and undefined. This study’s goal was to identify the genomic features of ESRD RCC and characterize them for associations with tumor histology and dialysis exposure. In this study, we obtained 33 RCCs, with various histological subtypes, that developed in ESRD patients receiving dialysis and performed whole-genome sequencing and transcriptome analyses. Driver events, copy-number alteration (CNA) analysis and mutational signature profiling were performed using an analysis pipeline that integrated data from germline and somatic SNVs, Indels and structural variants as well as CNAs, while transcriptome data were analyzed for differentially expressed genes and through gene set enrichment analysis. ESRD related clear cell RCCs’ driver genes and mutations mirrored those in sporadic ccRCCs. Longer dialysis periods significantly correlated with a rare mutational signature SBS23, whose etiology is unknown, and increased mitochondrial copy number. All acquired cystic disease (ACD)-RCCs, which developed specifically in ESRD patients, showed chromosome 16q amplification. Gene expression analysis suggests similarity between certain ACD-RCCs and papillary RCCs and in TCGA papillary RCCs with chromosome 16 gain identified enrichment for genes related to DNA repair, as well as pathways related to reactive oxygen species, oxidative phosphorylation and targets of Myc. This analysis suggests that ESRD or dialysis could induce types of cellular stress that impact some specific types of genomic damage leading to oncogenesis.
Enhancement of Humoral and Cellular Immunity Against Severe Acute Respiratory Syndrome Coronavirus 2 by a Third Dose of BNT162b2 Vaccine in Japanese Healthcare Workers
Authors: Miyakawa Kei , Kato Hideaki , Ohtake Norihisa , Jeremiah Sundararaj Stanleyraj , Ryo Akihide
Published: August 2022

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised concerns regarding vaccine effectiveness. We investigated humoral and cellular immune responses against SARS-CoV-2 in healthcare workers before and after a third (booster) dose of the BNT162b2 messenger RNA vaccine. It significantly enhanced both humoral and cellular immunity in previously uninfected individuals. However, cellular immunity was not enhanced in previously infected persons, suggesting that 3 antigenic stimuli by vaccination or natural infection reached a plateau of cellular immunity. Even with reinforced immunity to SARS-CoV-2, we confirmed several postbooster breakthrough cases caused by the Omicron variant.
Biomarkers for monitoring the equine large intestinal inflammatory response to stress-induced dysbiosis and probiotic supplementation
Authors: Collinet Axelle , Grimm Pauline , Jacotot Emmanuel , Julliand Véronique
Published: August 2022

Large intestine barrier disturbances can have serious consequences for the health of horses. The loss of mucosal integrity that leads to increased intestinal permeability may result from a local inflammatory immune response following alterations of the microbiota, known as dysbiosis. Therefore, our research aimed to identify noninvasive biomarkers for studying the intestinal permeability and the local inflammatory immune response in horses. Regarding the biomarkers used in other mammalian species, we measured the concentrations of lipopolysaccharides (LPS), reflected by 3-OH C14, C16, and C18 fatty acids, in blood, and fecal secretory immunoglobulin-A (SIgA). These biomarkers were evaluated in two trials including 9 and 12 healthy horses, which developed large intestinal dysbiosis experimentally induced by 5 d of antibiotic administration (trimethoprim sulfadiazine [TMS]) or 5 d of abrupt introduction of high starch levels (barley) into the diet. Horses were either control or supplemented with Lactobacillus acidophilus, Ligilactobacillus salivarius, and Bifidobacterium lactis. Correlations were performed between biomarkers and fecal bacterial diversity, composition, and function. No significant interaction between day and supplementation, or supplementation effect were observed for each biomarker. However, with the dietary stressor, a significant increase in blood concentrations of 3-OH C16 (P = 0.0125) and C14 (P = 0.0252) fatty acids was measured 2 d after the cessation of barley administration. Furthermore, with the antibiotic stressor, blood levels of 3-OH C16 progressively increased (P = 0.0114) from the first day to 2 d after the end of TMS administration. No significant day effect was observed for fecal SIgA concentrations for both stressors. These results indicate that both antibiotic- and diet-induced dysbiosis resulted in a local translocation of LPS 2 d after the cessation of the stressor treatments, suggesting an impairment of intestinal permeability, without detectable local inflammation. Blood LPS and fecal SIgA concentrations were significantly correlated with several bacterial variations in the large intestine, which are features of antibiotic- and diet-induced dysbiosis. These findings support the hypothesis that a relationship exists between dysbiosis and the loss of mucosal integrity in the large intestine of horses.
Apparent digestibility of energy and nutrients and efficiency of microbial phytase is influenced by body weight of pigs
Authors: Lagos L Vanessa , Bedford Mike R , Stein Hans H
Published: August 2022

An experiment was conducted to test the hypothesis that regardless of pig body weight (BW), increasing dietary phytase results in increased phytate degradation and improved digestibility of minerals, amino acids (AA), and gross energy (GE). Eighteen pigs were equipped with a T-cannula in the distal ileum and allotted to a triplicated 6 × 3 Youden square design with six diets and three collection periods of 7 d, for a total of nine replicate pigs per diet. This design was repeated four times to simulate four production phases, and there was a 7-d resting period before each collection phase started (BW at start of collections: 29.3, 53.6, 85.1, and 114.4 kg for phases 1, 2, 3, and 4, respectively). Six corn-soybean meal diets were formulated by including 0, 250, 500, 1,000, 2,000, or 4,000 phytase units/kg feed (FTU). The six diets were used throughout the experiment. Samples of feces and ileal digesta were collected in each period. Results indicated that regardless of pig BW, increasing inclusion of phytase increased (quadratic; P < 0.05) apparent ileal digestibility (AID) of crude protein (CP) and most AA, increased apparent total tract digestibility (ATTD) of Ca, P, K, Mg (linear and quadratic; P < 0.05), and Na (linear; P < 0.05), but decreased (linear and quadratic; P < 0.05) AID and ATTD of GE. In all phases, ileal concentrations of inositol phosphate (IP) 6, IP5, IP4, and IP3 decreased (linear and quadratic; P < 0.05), whereas ileal inositol increased (linear and quadratic; P < 0.05) with increasing dietary phytase. However, as pig BW increased, AID of GE, CP, and AA increased (linear, P < 0.05), and the AID of a few AA (Met, Phe, Thr, Trp, Ala, Asp, Gly, and Ser) also increased quadratically (P < 0.05). The ATTD of GE, K, and Mg increased (linear and quadratic; P < 0.05), but ATTD of Ca and Na (linear; P < 0.05) and of P (linear and quadratic; P < 0.05) decreased as pig BW increased. Ileal IP6 and IP3 (linear and quadratic; P < 0.05) and ileal IP5 and IP4 (linear; P < 0.05) increased, whereas ileal inositol decreased (linear; P < 0.05) as pig BW increased. In conclusion, regardless of pig BW, increasing dietary phytase increased phytate degradation and inositol release in the small intestine, and consequently increased mineral and AA digestibility. Older pigs have reduced Ca, P, and Na digestibility, but increased K, Mg, AA, and GE digestibility compared with younger pigs. The efficiency of dietary phytase to degrade phytate appears to decrease as pigs get older.
AI agency vs. human agency: understanding human–AI interactions on TikTok and their implications for user engagement
Authors: Kang Hyunjin , Lou Chen
Published: August 2022

Artificial intelligence (AI) technology has vastly reshaped user experiences on social media. AI-powered social media use and its outcomes largely depend on how users collaborate with AI that exercises agency. Through in-depth interviews with TikTok users, this study investigates how users collaborate with AI when using AI-powered social media and how such dynamics shape user engagement. We found that TikTok users are receptive to personalized experiences enabled by machine agency. However, by influencing each other, user agency and machine agency also led to user–AI synergy. Users deliberately influence content curation algorithms to make them cater more precisely to their needs; AI also facilitates users’ content creation and networking. Such AI–user collaboration on TikTok significantly influences medium engagement and social-interactive engagement. These findings advance our understanding of the dynamics between human agency and machine agency and, thus, how AI transforms user experiences on social media.
Identification and Bioassays of Sex-Specific Compounds From a Nuisance Net-Spinning Caddisfly Smicridea fasciatella (Trichoptera: Hydropsychidae)
Authors: Cavallaro Michael C , Medeiros Matthew J , Halloran Sean , Millar Jocelyn G
Published: August 2022

Municipalities in Arizona and Nevada along the Colorado River are subject to seasonal mass emergences of a nuisance net-spinning caddisfly, Smicridea fasciatella McLachlan (Trichoptera: Hydropsychidae). Here, we describe the characterization and field testing of S. fasciatella extracts to evaluate their potential as lures in baited traps. Solvent extracts of external (i.e., full body—cuticular hydrocarbon, abdominal hexane washes) and internal (i.e., crushed abdomen) parts of adult S. fasciatella were prepared from both sexes, and analyzed by coupled gas chromatography-mass spectrometry (GCMS). Several sex-specific compounds were identified, including (6Z,9Z)-6,9-nonadecadiene and (3Z,6Z,9Z)-3,6,9-nonadecatriene from males, and 2-undecanone, 2-tridecanone, and a heptadecene isomer from females. Extracts from both sexes were also analyzed by coupled gas chromatography-electroantennographic detection (EAD) using antennae of males for detection. Antennae of males weakly responded to 2-undecanone and 2-tridecanone, and to their corresponding alcohols, 2-undecanol and 2-tridecanol, which were included in field tests. Extracts of adult males did not elicit a response from male antennae, suggesting that males do not produce aggregation pheromones attractive to other males. The synchronized, dense populations of lekking males and other possible mating signals (e.g., visual recognition) may have contributed to the minimal attraction seen to test lures deployed in PHEROCON 1C traps. Overall, our results suggest that for this species, attractant pheromones have minimal or no role in bringing the sexes together for mating.
The Genus Haemaphysalis (Acari: Ixodidae) in Laos: An Update of Species Records and a Review of Taxonomic Challenges
Authors: Vongphayloth Khamsing , Apanaskevich Dmitry A , Lakeomany Khaithong , Phommavanh Nothasine , Sinh Nam Vu , Fiorenzano Jodi M , Hertz Jeffrey C , Sutherland Ian W , Brey Paul T , Robbins Richard G
Published: August 2022

Haemaphysalis Koch, 1844, is the largest genus of ticks in Southeast Asia, but little information is available concerning the species present in Laos. Recent research has yielded records for 10 Haemaphysalis species in Laos, including 5 new records, as well as 3 morphological entities of uncertain status. Further morphological and molecular studies are needed to clarify our taxonomic understanding of this genus in Southeast Asia.
Fluralaner Baits Reduce the Infestation of Peromyscus spp. Mice (Rodentia: Cricetidae) by Ixodes scapularis (Acari: Ixodidae) Larvae and Nymphs in a Natural Environment
Authors: Pelletier Jérôme , Rocheleau Jean-Philippe , Aenishaenslin Cécile , Dimitri Masson Gabrielle , Lindsay L Robbin , Ogden Nicholas H , Bouchard Catherine , Leighton Patrick A
Published: August 2022

The development of interventions that reduce Lyme disease incidence remains a challenge. Reservoir-targeted approaches aiming to reduce tick densities or tick infection prevalence with Borrelia burgdorferi have emerged as promising ways to reduce the density of infected ticks. Acaricides of the isoxazoline family offer high potential for reducing infestation of ticks on small mammals as they have high efficacy at killing feeding ticks for a long period. Fluralaner baits were recently demonstrated as effective, in the laboratory, at killing Ixodes scapularis larvae infesting Peromyscus mice, the main reservoir for B. burgdorferi in northeastern North America. Here, effectiveness of this approach for reducing the infestation of small mammals by immature stages of I. scapularis was tested in a natural environment. Two densities of fluralaner baits (2.1 baits/1,000 m2 and 4.4 baits/1,000 m2) were used during three years in forest plots. The number of I. scapularis larvae and nymphs per mouse from treated and control plots were compared. Fluralaner baiting reduced the number of larvae per mouse by 68% (CI95: 51–79%) at 2.1 baits/1,000 m2 and by 86% (CI95: 77–92%) at 4.4 baits/1,000 m2. The number of nymphs per mouse was reduced by 72% (CI95: 22–90%) at 4.4 baits/1,000 m2 but was not significantly reduced at 2.1 baits/1,000 m2. Reduction of Peromyscus mouse infestation by immature stages of I. scapularis supports the hypothesis that an approach targeting reservoirs of B. burgdorferi with isoxazolines has the potential to reduce tick-borne disease risk by decreasing the density of infected ticks in the environment.
Unclosure: The international law of seabed mining and the systemic cycles of capital accumulation
Authors: Tedeschini Michele
Published: August 2022

The growing electric vehicle industry is heavily reliant on minerals like lithium, cobalt, nickel, and copper. As corporations scramble to access vast deposits of those minerals lying in the ocean floor, the international law of seabed mining has come under scrutiny. This article situates negotiations concerning that law, which took place between 1973 and 1994, within Giovanni Arrighi’s historiographical framework of the systemic cycles of capital accumulation. It argues that the legal regime in question was shaped by the Reagan administration, as part of a strategy to solve a profitability crisis affecting US nationals. While temporarily diverting wealth towards American financial markets, however, the legal arrangements that the United States imposed could not affect the dynamics of capital accumulation on a global scale.
ON GESTATION AND MOTHERHOOD
Authors: Mahmoud Zaina , Romanis Elizabeth Chloe
Published: August 2022

In English law, legal motherhood is allocated to the person who gestated. However, we argue that gestation—legally denoted as the “natural” source of parenting obligations—is often constructed as mothering, rather than the precursor to it. This means that women and pregnant people are treated as mothers prior to birth in legal and medical contexts. Since legal motherhood is an important status, defining the role an individual plays in a child’s life, the conflation of gestation and motherhood does not reflect that, legally, a fetus does not have personhood. This blurring between gestation and motherhood is metaphysically incoherent, as a fetus is not an entity that can be parented. This conflation poses a real harm to pregnant people’s autonomy, specifically those who do not intend to parent or who do not identify as women. More broadly, the medico-legal conflation of gestation and mothering is autonomy-limiting for all pregnant people as, resultantly, they may be coerced into obstetric intervention through legal processes. We argue for a better recognition of the differences between gestation and mothering, to promote autonomy and reflect the very different ways families may be formed.
Very-high-energy flat spectral radio quasar candidates
Authors: Malik Zahoor , Sahayanathan Sunder , Shah Zahir , Iqbal Naseer , Manzoor Aaqib
Published: August 2022

The attenuation of very-high-energy (VHE) photons by the extragalactic background light (EBL) prevents the observation of high-redshift flat spectrum radio quasars (FSRQs). However, the correlation of the VHE spectral index with source redshift suggests that the EBL intensity may be less than what is predicted. This deviation can draw new constraints on the opacity of the Universe to VHE gamma-rays. Therefore, more FSRQs may fall above the sensitivity of the forthcoming VHE telescopes than the ones predicted by the existing EBL models. In order to account for the lower EBL intensity predicted by the index–redshift correlation, we introduce a redshift-dependent correction factor to the opacity, estimated from a commonly used cosmological EBL model. Considering this modified opacity, we identify the plausible VHE FSRQ candidates by linearly extrapolating the Fermi gamma-ray spectrum at 10 GeV to the VHE regime. Our study suggests that among 744 FSRQs reported in the Fermi Fourth Catalogue Data Release 2, 32 FSRQs will be detectable by the Cherenkov Telescope Array Observatory (CTAO). Because FSRQs are proven to be highly variable, we assume a scenario where the average Fermi gamma-ray flux increases by a factor of 10, and this predicts an additional 90 FSRQs that can be detected by the CTAO.
Photohadronic interpretations of the different incarnations of 1ES 2344+514
Authors: Sahu Sarira , Valadez Polanco Isabel Abigail , Rajpoot Subhash
Published: August 2022

Since its discovery in 1995, the high-energy peaked blazar 1ES 2344+514 has undergone several episodes of GeV–TeV flaring and has been observed in the multiwavelength by several telescopes. The observed X-ray spectrum of 1996 and the flaring event of 2016 establish that 1ES 2344+514 has a temporary behaviour like that of an extremely high-energy peaked BL Lacertae object (EHBL). Such behaviour has also been observed in several nearby high-energy peaked blazars. We use the photohadronic model to account for the GeV–TeV flaring observed events of 1995 and 2007. Also, a recently proposed two-zone photohadronic model, which is successful in explaining the multi-TeV flaring events of many transient EHBL-like sources, is employed to explain the GeV–TeV flaring spectra of MJD 57611 and MJD 57612. We find that the zone-2 parameters of the two-zone photohadronic model play a central role in explaining these spectra. This is probably an indication of a new type of transient EHBL-like source. We find that our fits to the observed spectra are comparable or better than the other leptonic and hadronic models employed in the literature to address the same issue.
Regulation of nuclear DNA damage response by mitochondrial morphofunctional pathway
Authors: Oanh Nguyen Thi Kim , Lee Ho-Soo , Kim Yong-Hyun , Min Sunwoo , Park Yeon-Ji , Heo June , Park Yong-Yea , Lim Won-Chung , Cho Hyeseong
Published: August 2022

Cells are constantly challenged by genotoxic stresses that can lead to genome instability. The integrity of the nuclear genome is preserved by the DNA damage response (DDR) and repair. Additionally, these stresses can induce mitochondria to transiently hyperfuse; however, it remains unclear whether canonical DDR is linked to these mitochondrial morphological changes. Here, we report that the abolition of mitochondrial fusion causes a substantial defect in the ATM-mediated DDR signaling. This deficiency is overcome by the restoration of mitochondria fusion. In cells with fragmented mitochondria, genotoxic stress-induced activation of JNK and its translocation to DNA lesion are lost. Importantly, the mitochondrial fusion machinery of MFN1/MFN2 associates with Sab (SH3BP5) and JNK, and these interactions are indispensable for the Sab-mediated activation of JNK and the ATM-mediated DDR signaling. Accordingly, the formation of BRCA1 and 53BP1 foci, as well as homology and end-joining repair are impaired in cells with fragmented mitochondria. Together, these data show that mitochondrial fusion-dependent JNK signaling is essential for the DDR, providing vital insight into the integration of nuclear and cytoplasmic stress signals.
Structural basis of 3′-end poly(A) RNA recognition by LARP1
Authors: Kozlov Guennadi , Mattijssen Sandy , Jiang Jianning , Nyandwi Samuel , Sprules Tara , Iben James R , Coon Steven L , Gaidamakov Sergei , Noronha Anne M , Wilds Christopher J , Maraia Richard J , Gehring Kalle
Published: August 2022

La-related proteins (LARPs) comprise a family of RNA-binding proteins involved in a wide range of posttranscriptional regulatory activities. LARPs share a unique tandem of two RNA-binding domains, La motif (LaM) and RNA recognition motif (RRM), together referred to as a La-module, but vary in member-specific regions. Prior structural studies of La-modules reveal they are pliable platforms for RNA recognition in diverse contexts. Here, we characterize the La-module of LARP1, which plays an important role in regulating synthesis of ribosomal proteins in response to mTOR signaling and mRNA stabilization. LARP1 has been well characterized functionally but no structural information exists for its La-module. We show that unlike other LARPs, the La-module in LARP1 does not contain an RRM domain. The LaM alone is sufficient for binding poly(A) RNA with submicromolar affinity and specificity. Multiple high-resolution crystal structures of the LARP1 LaM domain in complex with poly(A) show that it is highly specific for the RNA 3′-end, and identify LaM residues Q333, Y336 and F348 as the most critical for binding. Use of a quantitative mRNA stabilization assay and poly(A) tail-sequencing demonstrate functional relevance of LARP1 RNA binding in cells and provide novel insight into its poly(A) 3′ protection activity.
Efficacy of Cabozantinib in Metastatic MiT Family Translocation Renal Cell Carcinomas
Authors: Thouvenin Jonathan , Alhalabi Omar , Carlo Maria , Carril-Ajuria Lucia , Hirsch Laure , Martinez-Chanza Nieves , Négrier Sylvie , Campedel Luca , Martini Dylan , Borchiellini Delphine , Chahoud Jad , Lodi Massimo , Barthélémy Philippe , Hasanov Elshad , Hahn Andrew W , Gil Thierry , Viswanathan Srinivas R , Bakouny Ziad , Msaouel Pavlos , Asim Bilen Mehmet , Choueiri Toni K , Albiges Laurence , Tannir Nizar M , Malouf Gabriel G
Published: August 2022

Background

MiT family translocation renal cell carcinoma (TRCC) is a rare and aggressive subgroup of renal cell carcinoma harboring high expression of c-MET. While TRCC response rates to VEGF receptor tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors are limited, efficacy of cabozantinib (a VEGFR, MET, and AXL inhibitor) in this subgroup is unclear.

Methods

We performed a multicenter, retrospective, international cohort study of patients with TRCC treated with cabozantinib. The main objectives were to estimate response rate according to RECIST 1.1 and to analyze progression-free survival (PFS) and overall survival (OS).

Results

Fifty-two patients with metastatic TRCC treated in the participating centers and evaluable for response were included. Median age at metastatic diagnosis was 40 years (IQR 28.5-53). Patients’ IMDC risk groups at diagnosis were favorable (9/52), intermediate (35/52), and poor (8/52). Eleven (21.2%) patients received cabozantinib as frontline therapy, 15 (28.8%) at second line, and 26 (50%) at third line and beyond. The proportion of patients who achieved an objective response was 17.3%, including 2 complete responses and 7 partial responses. For 26 (50%) patients, stable disease was the best response. With a median follow-up of 25.1 months (IQR 12.6-39), median PFS was 6.8 months (95%CI 4.6-16.3) and median OS was 18.3 months (95%CI 17.0-30.6). No difference of response was identified according to fusion transcript features.

Conclusion

This real-world study provides evidence of the activity of cabozantinib in TRCC, with more durable responses than those observed historically with other VEGFR-TKIs or ICIs.
Alginate hydrogel cross-linked by Ca2+ to promote spinal cord neural stem/progenitor cell differentiation and functional recovery after a spinal cord injuryhh
Authors: Zhou Jun , Wu Yaqi , Tang Zhijian , Zou Kaipeng , Chen Juan , Lei Zuowei , Wan Xueyan , Liu Yanchao , Zhang Huaqiu , Wang Yu , Blesch Armin , Lei Ting , Liu Shengwen
Published: August 2022

Alginate capillary hydrogels seeded with differentiated cells can fill the lesion cavity and promote axonal regeneration after grafting into the injured spinal cord. Neural stem/progenitor cells (NSPCs) can potentially repair the spinal cord; however, effects of alginate hydrogels (AHs) on NSPCs remain unknown. In this study, we fabricated AHs cross-linked by Ca2+ and seeded hydrogels with rat embryonic day 14 NSPCs. Immunocytochemistry and electron microscopy show that NSPCs survive, proliferate and differentiate into neurons in vitro within the capillaries. After transplantation into an acute T8 complete spinal cord transection site in adult rats, approximately one-third (38.3%) of grafted cells survive and differentiate into neurons (40.7%), astrocytes (26.6%) and oligodendrocytes (28.4%) at 8 weeks post-grafting. NSPCs promote the growth of host axons within the capillaries in a time-dependent manner. Host axons make synapse-like contacts with NSPC-derived neurons within the hydrogel channels, and graft-derived axons extend into the host white and gray matter making putative synapses. This is paralleled by improved electrophysiological conductivity across the lesion and partial hindlimb locomotor recovery.
‘The Last Shot’—the shared and distinct brain regions involved in processing unexpectedness of success and failure in the context of social cooperation
Authors: Li Peng , Wang Jing , Liu Yi
Published: August 2022

Individual success and failure in social cooperation matter not only to oneself but also to teammates. However, the common and distinct neural activities underlying salient success and failure in social cooperation are unclear. In this functional magnetic resonance imaging (fMRI) study, participants in the social group (Experiment one) cooperated with two human beings during a dice-gambling task, whereas those in the nonsocial group (Experiment two) cooperated with two computers. The social group reported more pride in success and more guilt in failure. The fMRI results in Experiment one demonstrate that left temporoparietal junction (LTPJ) activation increased exclusively with linearly changing unexpected success, whereas increasing anterior cingulate cortex (ACC) activation was only coupled with increasing unexpectedness of failure. Moreover, the dorsal medial prefrontal cortex (dMPFC) and left anterior insula were recruited in both success and failure feedback conditions. Dynamic causality model analysis suggested that the dMPFC first received information from the LTPJ and ACC separately and then returned information to these regions. The between-experiment comparison showed more dMPFC activity in social vs nonsocial contexts irrespective of success and failure feedback. Our findings shed light on the common and distinct neural substrates involved in processing success and failure feedback in social cooperation.
Measuring the response to visually presented faces in the human lateral prefrontal cortex
Authors: Nikel Lara , Sliwinska Magdalena W , Kucuk Emel , Ungerleider Leslie G , Pitcher David
Published: August 2022

Neuroimaging studies identify multiple face-selective areas in the human brain. In the current study, we compared the functional response of the face area in the lateral prefrontal cortex to that of other face-selective areas. In Experiment 1, participants (n = 32) were scanned viewing videos containing faces, bodies, scenes, objects, and scrambled objects. We identified a face-selective area in the right inferior frontal gyrus (rIFG). In Experiment 2, participants (n = 24) viewed the same videos or static images. Results showed that the rIFG, right posterior superior temporal sulcus (rpSTS), and right occipital face area (rOFA) exhibited a greater response to moving than static faces. In Experiment 3, participants (n = 18) viewed face videos in the contralateral and ipsilateral visual fields. Results showed that the rIFG and rpSTS showed no visual field bias, while the rOFA and right fusiform face area (rFFA) showed a contralateral bias. These experiments suggest two conclusions; firstly, in all three experiments, the face area in the IFG was not as reliably identified as face areas in the occipitotemporal cortex. Secondly, the similarity of the response profiles in the IFG and pSTS suggests the areas may perform similar cognitive functions, a conclusion consistent with prior neuroanatomical and functional connectivity evidence.
Review of Contrast-Enhanced Mammography
Authors: Lorente-Ramos Rosa M. , Armán Javier Azpeitia
Published: August 2022

Contrast-enhanced mammography (CEM) is a new breast imaging technique. CEM provides morphologic (mammography) and functional information obtained after the injection of iodinated contrast material. We review the basics and state-of-the-art CEM, highlighting the potential challenges to implement CEM in a breast imaging department. We also provide an update in CEM technique and interpretation; the performance of this modality versus conventional breast imaging modalities (mammography, ultrasound, and MRI); existing clinical applications; potential challenges; and pitfalls.
Physical Activity and Nutrition-Related Beliefs, Behaviors, and Challenges in Individuals Living With Cancer and Their Caregivers
Authors: Packel Lora , Dychtwald Dan , Pontiggia Laura , Deutsch Jonathan , Milliron Brandy-Joe
Published: August 2022

Background and Purpose:

This study explored physical activity and nutrition beliefs, behaviors, and challenges; examined dyadic interactions; and explored lifestyle programming preferences to inform future interventions to improve the physical and mental health of patients with cancer and their caregivers.

Methods:

A convergent mixed-methods design with structured surveys and interviews. Descriptive statistics and quantitative comparisons were performed using SAS. Interviews were analyzed using inductive and deductive thematic analysis.

Setting:

Hope Lodge Cheltenham, Pennsylvania.

Participants:

Caregivers (n = 52) and patients (n = 50).

Intervention and Measurements:

The Godin Leisure Time Questionnaire, theory of planned behavior, and the National Cancer Institute's Food Attitudes and Behaviors Survey were embedded in structured surveys.

Results:

The sample was physically active with no significant changes postdiagnosis. Physical activity was lower in patients with higher fatigue, while it was higher in those with stronger intention and perceived behavioral control. Most participants believed that dietary intake was linked to health; however, there was confusion toward national recommendations. Higher levels of nutrition self-efficacy were associated with lower perceived barriers to nutrition in both groups. Participants wanted information tailored to cancer type provided in a variety of mediums by health care providers, researchers, and cancer centers.

Limitations:

Physically active sample of convenience, recall bias with questionnaires.

Conclusions:

Perceived behavioral control, intention to exercise, and education about using exercise for fatigue management and mental health should be emphasized. Nutrition interventions should focus on addressing barriers, clarifying guidelines, and operationalizing recommendations. Information should be specific to cancer type and include support for caregivers.
Rehabilitation Course and Management of Intravascular Lymphoma Presenting as Recurrent Strokes: A Case Report
Authors: Thomas Jade , Britton-Carpenter Amanda , Rucker Jason
Published: August 2022

Background and Purpose:

Intravascular lymphoma (IVL) is characterized by the proliferation of lymphoma cells within small blood vessels. Diagnosis of IVL is difficult, and neurologic manifestations of the disease are common. Currently, there is little information related to the clinical course and rehabilitation of patients with IVL. This case report describes the presentation and treatment of an individual with IVL presenting as recurrent strokes.

Case Description:

A 53-year-old man was admitted for treatment of bilateral multifocal infarcts in cerebral watershed areas. Initial assessments indicated that he required minimal assistance for functional activities, and he was discharged home with outpatient services. He was readmitted 7 days later with worsening confusion, left hemiparesis, and deteriorating functional mobility. Rehabilitation team concerns related to the patient's progressive functional decline led to additional testing, resulting in a diagnosis of IVL.

Outcomes:

The patient initially required relatively little assistance with most functional activities, scoring 23 to 24/24 and 21/24 on the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility and Daily Activity Scales, respectively, 46/56 on the Berg Balance Scale (BBS), and 19/30 on the Montreal Cognitive Assessment (MoCA). He was subsequently readmitted and demonstrated a rapid functional decline, as evidenced by AM-PAC and BBS scores of 7/24 and 6/56, respectively.

Discussion:

This patient presented with neurological deficits and an initial diagnosis of bilateral multifocal infarcts. Documentation of his progressive functional decline and decreasing AM-PAC and BBS scores facilitated interdisciplinary communication and led to additional diagnostic testing, resulting in a final diagnosis of IVL and appropriate medical intervention.
Clinical Outcomes of Combined Anterior Cruciate Ligament Reconstruction and Lateral Extra-articular Tenodesis Procedures in Skeletally Immature Patients: A Systematic Review From the SANTI Study Group
Authors: Carrozzo Alessandro , Monaco Edoardo , Saithna Adnan , Annibaldi Alessandro , Guy Sylvain , Ferreira Alexandre , Vieira Thais Dutra , Ferretti Andrea , Sonnery-Cottet Bertrand
Published: August 2022

Background:

The treatment of anterior cruciate ligament (ACL) tears in the pediatric population has changed significantly in the past few decades. Pediatric patients who underwent ACL reconstruction (ACLR) have a high risk of rerupture of up to 32%. The addition of lateral extra-articular procedures [lateral extra-articular tenodesis (LET)], already shown to be effective in reducing the risk of rerupture in adults, may also be effective in pediatric patients. The purpose of this study was to systematically review the clinical outcomes of ACLR+LET tenodesis in pediatric patients.

Methods:

Data were collected from Pubmed, MEDLINE, Cochrane, and Scopus Databases according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Studies reporting the clinical outcomes of ACLR+LET in the pediatric population using autograft, return to play, growth disturbances, failure rate, and surgical complications were included.

Results:

A total of 5 studies comprising 381 pediatric patients were included. Three main surgical techniques with common features were used. The mean age of all pediatric patients in the included studies was 11.73 years (range, 5.6 to 16) with a mean follow-up of 50.1 months. The overall graft failure rate of the included studies was 4.65%. The return to play was 95.11%. The mean Lysholm score was 94.51 and the mean Pediatric International Knee Documentation Committee (Pedi-IKDC) was 93.39. In all, 1.9% of the patients had a coronal plane deformity and 0.8% had a limb length discrepancy. 4.6% of the patients had a contralateral ACL tear.

Conclusions:

A combined ACLR+LET in pediatric patients showed a graft failure ranging from 0% to 13.6% at a mean follow-up of 50.1 months. This low graft failure rate is consistent with ACLR+LET in adults. Further investigations are needed to validate these findings and the potential role of LET in reducing graft rupture rates in this population.

Level of Evidence:

Level IV—systematic review of level IV studies.
Engaging the Front Line
Authors: Laux Lori , McGonigal Michelle , Yaglowski Jason , Vietmeier Shawn
Published: August 2022

Employee engagement is a key driver in achieving successful quality improvement initiatives. An important aspect of engagement is enabling the nursing staff to have a role in problem solving at the front line, thus improving productivity. Finding an appropriate methodology that resonates with the frontline staff can be challenging. This article discusses the use of the Lean Methodology to prevent central line–associated bloodstream infections in a large urban hospital. The case study provided will review an initial attempt at frontline problem solving using the Lean Methodology and a more successful strategy with the development of a nurse champion program.