bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarkers of mitochondrial origin: a futuristic cancer diagnostic
Authors: Gayan Sukanya , Joshi Gargee , Dey Tuli 
Published: July 2022

AbstractCancer is a highly fatal disease without effective early-stage diagnosis and proper treatment. Along with the oncoproteins and oncometabolites, several organelles from cancerous cells are also emerging as potential biomarkers. Mitochondria isolated from cancer cells are one such biomarker candidates. Cancerous mitochondria exhibit different profiles compared with normal ones in morphology, genomic, transcriptomic, proteomic and metabolic landscape. Here, the possibilities of exploring such characteristics as potential biomarkers through single-cell omics and Artificial Intelligence (AI) are discussed. Furthermore, the prospects of exploiting the biomarker-based diagnosis and its futuristic utilization through circulatory tumor cell technology are analyzed. A successful alliance of circulatory tumor cell isolation protocols and a single-cell omics platform can emerge as a next-generation diagnosis and personalized treatment procedure.
Early biomolecular changes in brain microvascular endothelial cells under Epstein–Barr virus influence: a Raman microspectroscopic investigation
Authors: Indari Omkar , Tiwari Deeksha , Tanwar Manushree , Kumar Rajesh , Jha Hem Chandra 
Published: July 2022

Abstract
The brain microvascular endothelial cells (ECs) play an important role in protecting the brain from hazardous pathogens. However, some viral pathogens can smartly modulate the endothelial pathways to gain entry inside the brain. Further, these viruses can cause endothelial dysfunction which could develop serious neurological ailments. Epstein–Barr virus (EBV), an oncogenic virus, has also been linked to various neurological disorders. The virus primarily infects epithelial and B cells, however, it also has a tendency to infect ECs and cause endothelial activation. However, the impact of EBV influence on ECs is still underexplored. Studying the early events of virus-mediated cellular modulation could help in understanding the virus’ infection strategy or aftermath. Raman microspectroscopy has been widely utilized in biomedical sciences to decipher cellular changes. To understand the EBV-influenced EC modulation by studying intracellular biomolecular changes at early time points, we utilized the Raman microspectroscopy tool. We treated the ECs with EBV and acquired the Raman spectra at different time points (2, 4, 6, 12, 24 and 36 h) and different sites (nucleus and periphery) to check changes in Raman intensities associated with specific biomolecules. In the EBV-treated cells, the status of various biomolecules in terms of Raman intensities was observed to be altered compared with uninfected cells. Specifically, the cholesterol, polysaccharide, nucleotides, nucleic acid and proline moieties were altered at different time points. We also investigated the possible correlation between these molecules using molecular network analysis and observed various associated factors. These factors could be influenced by EBV to alter the associated biomolecular levels. Our study paves the pathway to study EBV infection in human brain microvascular ECs and highlights specific biomolecular alterations, which can be focused for further mechanistic investigations.
Liver cirrhosis and immune dysfunction
Authors: Hasa Elda , Hartmann Phillipp , Schnabl Bernd 
Published: July 2022

Abstract
Cirrhosis is end-stage liver disease resulting from various etiologies and is a common cause of death worldwide. The progression from compensated to decompensated cirrhosis to acute-on-chronic liver failure (ACLF) is due to multiple factors, including continuation of alcohol use or continued exposure to other toxins, an imbalance of the gut microbiota (dysbiosis), increased gut permeability and a disrupted immune response. This disrupted immune response is also named cirrhosis-associated immune dysfunction, which is characterized by worsening systemic inflammation with concomitant immune paralysis, as liver disease deteriorates. This review highlights central immunologic events during the exacerbation of cirrhosis and characterizes the different immune cell populations involved therein.
An Outsider’s Perspective on Why We Climb Mountains and Why Projects Like the i5k Matter
Authors: Molik David C 
Published: July 2022

Abstract
Initiatives like the i5k are creating evermore genome assemblies. These initiatives are resource heavy, and their justifications and economics deserve attention. Scientifically, these initiatives are important, paving the way for cross-species analysis, requiring the building of new computational analysis and tools, and creating other new resources. However, an open question remains of how we quantitively measure the impact of genomes, and by extension these initiatives. This forum article discusses one such method which is to look at the publications about a species over time, however, this method does not show any signal from a published genome, leaving an open question of how to measure impact.
Therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
Authors: Yoshino Maki , Ishihara Hiroki , Nemoto Yuki , Nakamura Kazutaka , Nishimura Koichi , Tachibana Hidekazu , Fukuda Hironori , Toki Daisuke , Yoshida Kazuhiko , Kobayashi Hirohito , Iizuka Junpei , Shimmura Hiroaki , Hashimoto Yasunobu , Tanabe Kazunari , Kondo Tsunenori , Takagi Toshio 
Published: July 2022

Abstract

Objectives
To explore the therapeutic role of deferred cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with nivolumab plus ipilimumab.

Patients and methods
Forty-one patients with synchronous metastatic renal cell carcinoma who received nivolumab plus ipilimumab as first-line systemic therapy at our affiliated institutions were retrospectively evaluated. We focused on the prognosis, including tumor responses in primary kidney and metastatic lesions in patients treated with deferred cytoreductive nephrectomy. In addition, the overall survival according to nephrectomy status (i.e. deferred cytoreductive nephrectomy vs. upfront cytoreductive nephrectomy vs. without cytoreductive nephrectomy) was compared.

Results
During a median follow-up period of 12.0 months, seven (30%) patients received deferred cytoreductive nephrectomy at a median time of 10.4 months after nivolumab plus ipilimumab initiation. All the patients showed tumor shrinkage in their primary kidney lesions, including six (86%) patients with ≥30% of shrinkage. Metastatic lesions were also shrunk by ≥30% in six (86%) patients, including two (29%) obtaining complete response. At the last time of follow-up, three (43%) patients were disease-free. The overall survival rate after nivolumab plus ipilimumab initiation tended to be higher in patients with deferred cytoreductive nephrectomy compared with those with upfront cytoreductive nephrectomy (1-year survival rate: 100% vs. 72.4%, P = 0.0587) and those without cytoreductive nephrectomy (vs. 58.2%, P = 0.0613).

Conclusions
The present retrospective data showed that deferred cytoreductive nephrectomy had the potential to exert a therapeutic effect in a subset of patients who obtained favorable tumor responses to nivolumab plus ipilimumab for a certain period. Prospective randomized clinical trials are needed to confirm the prognostic impact of deferred cytoreductive nephrectomy after frontline immunotherapy in synchronous metastatic renal cell carcinoma.
Shrub encroachment threatens persistence of an endemic insular wetland rodent
Authors: Boone Wesley W , Albrecht Audrey A , Conrad Jeremy R , Lechowicz Chris J , Hellgren Eric C , McCleery Robert A 
Published: July 2022

AbstractShrub encroachment is altering the structure and species composition of natural communities across the globe. However, little research has focused on how shrub encroachment influences wetland vertebrates, including small mammals. We sought to determine how vegetative structure and shrub cover influenced the occurrence of a threatened semiaquatic mammalian subspecies, the Sanibel Island rice rat (Oryzomys palustris sanibeli). We evaluated the influence of vegetation and metrics of inundation on probability of occurrence and localized seasonal colonization and extinction rates of the Sanibel Island rice rat over a 3-year period. We found Sanibel Island rice rats on 18 (33.3%) of our 54 sites. Their occurrence was positively associated with greater sand cordgrass (Spartina bakeri) cover and increased elevation, but negatively associated with greater shrub cover. Their probability of localized colonization was negatively associated with greater shrub cover. Localized extinction probabilities for Sanibel Island rice rats were positively associated with increased rainfall totals in the preceding 3 months and greater shrub cover. Using aerial photography from across the Sanibel Island rice rat’s range, we found 5.5-fold greater shrub cover in 2015 than in 1944. We suggest that increases in shrub cover and reduced cordgrass cover may be driving the decline of this once ubiquitous endemic species and that the encroachment of freshwater wetlands requires greater attention due to its potential to imperil wetland-dependent wildlife.
Winter torpor and activity patterns of a fishing bat (Myotis macropus) in a mild climate
Authors: Barratt Alice E , Gonsalves Leroy , Turbill Christopher 
Published: July 2022

AbstractSmall insectivorous bats often enter a state of torpor, a controlled, reversible decrease in body temperature and metabolic rate. Torpor provides substantial energy savings and is used more extensively during periods of low temperature and reduced prey availability. We studied torpor use and activity of a small (10.1 ± 0.4 g) fishing bat, Myotis macropus, during winter in a mild climate in Australia. We predicted that the thermal stability of water would make foraging opportunities in winter more productive and consistent in a riparian habitat compared to a woodland habitat, and therefore, fishing bats would use torpor less than expected during winter compared to other bats. Using temperature-sensitive radio transmitters, we recorded the skin temperature of 12 adult (6 M, 6 F) bats over 161 bat-days (13.4 ± 5.4 days per bat) during Austral winter (late May to August), when daily air temperature averaged 6.2–18.2°C. Bats used torpor every day, with bouts lasting a median of 21.3 h and up to 144.6 h. Multiday torpor bouts were more common in females than males. Arousals occurred just after sunset and lasted 3.5 ± 2.9 h. Arousals tended to be longer in males than females and to occur on warmer evenings, suggesting some winter foraging and perhaps male harem territoriality or other mating-related activity was occurring. The extensive use of torpor by M. macropus during relatively mild winter conditions when food is likely available suggests torpor might function to minimize the risks of mortality caused by activity and to increase body condition for the upcoming breeding season.
Carpel-specific down-regulation of GhCKXs in cotton significantly enhances seed and fiber yield
Authors: Zeng Jianyan , Yan Xingying , Bai Wenqin , Zhang Mi , Chen Yang , Li Xianbi , Hou Lei , Zhao Juan , Ding Xiaoyan , Liu Ruochen , Wang Fanlong , Ren Hui , Zhang Jingyi , Ding Bo , Liu Haoru , Xiao Yuehua , Pei Yan 
Published: July 2022

Abstract
Cytokinin is considered to be an important driver of seed yield. To increase the yield of cotton while avoiding the negative consequences caused by constitutive overproduction of cytokinin, we down-regulated specifically the carpel genes for cytokinin oxidase/dehydrogenase (CKX), a key negative regulator of cytokinin levels, in transgenic cotton. The carpel-specific down-regulation of CKXs significantly enhanced cytokinin levels in the carpels. The elevated cytokinin promoted the expression of carpel- and ovule-development-associated genes, GhSTK2, GhAG1, and GhSHP, boosting ovule formation and thus producing more seeds in the ovary. Field experiments showed that the carpel-specific increase of cytokinin significantly increased both seed yield and fiber yield of cotton, without resulting in detrimental phenotypes. Our study details the regulatory mechanism of cytokinin signaling for seed development, and provides an effective and feasible strategy for yield improvement of seed crops.
Cold-mode and hot-mode accretion in galaxy formation: an entropy approach
Authors: Tollet E , Cattaneo A , Macciò A V , Kang X 
Published: July 2022

ABSTRACT
We have analysed two cosmological zoom simulations with $M_{\rm vir}\sim 10^{12}{\rm \, M}_\odot$ from the Numerical Investigation of a Hundred Astrophysical Objects (NIHAO) series, both with and without feedback. We show that an entropy criterion based on the equation of state of the intergalactic medium can successfully separate cold- and hot-mode accretion. The shock-heated gas has non-negligible turbulent support and cools inefficiently. In the simulations without feedback, only a small fraction (≲20 per cent) of the stellar mass comes from baryons that have been in the hot circumgalactic medium, although quantitative conclusions should be taken with caution due to our small-number statistics. With feedback, the fraction is larger because of the reaccretion of gas heated by supernovae, which has lower entropies and shorter cooling times than the gas heated by accretion shocks. We have compared the results of NIHAO to predictions of the GalICS 2.1 semi-analytic model of galaxy formation. The shock-stability criterion implemented in GalICS 2.1 successfully reproduces the transition from cold- to hot-mode accretion.
High-energy γ-ray detection of supernova remnants in the Large Magellanic Cloud
Authors: Campana R , Massaro E , Bocchino F , Miceli M , Orlando S , Tramacere A 
Published: July 2022

ABSTRACT
We present the results of a cluster search in the γ-ray sky images of the Large Magellanic Cloud (LMC) region by means of the Minimum Spanning Tree (MST) and DBSCAN algorithms, at energies higher than 6 and 10 GeV, using 12 yr of Fermi-LAT data. Several significant clusters were found, the majority of which associated with previously known γ-ray sources. We confirm our previous detection of the supernova remnants N 49B and N 63A and found new significant clusters associated with the SNRs N 49, N 186D, and N 44. These sources are among the brightest X-ray remnants in the LMC and corresponds to core-collapse supernovae interacting with dense H ii regions, indicating that a hadronic origin of high-energy photons is the most likely process.
Tobacco Retail Outlets, Neighborhood Deprivation and the Risk of Prenatal Smoke Exposure
Authors: Wheeler David C , Boyle Joseph , Jeremy Barsell D , Maguire Rachel L , Zhang Junfeng (Jim) , Oliver Jason A , Jones Shaun , Dahman Bassam , Murphy Susan K , Hoyo Cathrine , Baggett Chris D , McClernon Joseph , Fuemmeler Bernard F 
Published: July 2022

Abstract

Introduction
Smoking and smoke exposure among pregnant women remain persistent public health issues. Recent estimates suggest that approximately one out of four nonsmokers have measurable levels of cotinine, a marker indicating regular exposure to secondhand smoke. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy. However, most of these studies have relied upon self-reported measures of smoking.

Aims and Methods
To more accurately assess smoke exposure resulting from both smoking and secondhand exposure in mothers during pregnancy, we used Bayesian regression models to estimate the association of cotinine levels with tobacco retail outlet (TRO) exposure and a neighborhood deprivation index (NDI) in six counties in North Carolina centered on Durham County.

Results
Results showed a significant positive association between TRO exposure (β = 0.008, 95% credible interval (CI) = [0.003, 0.013]) and log cotinine after adjusting for individual covariates (eg, age, race/ethnicity, education, marital status). TRO exposure was not significant after including the NDI, which was significantly associated with log cotinine (β = 0.143, 95% CI = [0.030, 0.267]). However, in a low cotinine stratum (indicating secondhand smoke exposure), TRO exposure was significantly associated with log cotinine (β = 0.005, 95% CI = [0.001, 0.009]), while in a high cotinine stratum (indicating active smoking), the NDI was significantly associated with log cotinine (β = 0.176, 95% CI = [0.005, 0.372]).

Conclusions
In summary, our findings add to the evidence that contextual factors are important for active smoking during pregnancy.

Implications
In this study, we found several significant associations that suggest a more nuanced understanding of the potential influence of environmental- and individual-level factors for levels of prenatal smoke exposure. Results suggested a significant positive association between TRO exposure and cotinine levels, after adjusting for the individual factors such as race, education, and marital status. Individually, NDI was similarly positively associated with cotinine levels as well. However, when combining TRO exposure alongside NDI in the same model, TROs were no longer significantly associated with overall cotinine levels.
Isoniazid Adherence Reduces Mortality and Incident Tuberculosis at 96 Weeks Among Adults Initiating Antiretroviral Therapy With Advanced Human Immunodeficiency Virus in Multiple High-Burden Settings
Authors: Gupta Amita , Sun Xin , Krishnan Sonya , Matoga Mitch , Pierre Samuel , McIntire Katherine , Koech Lucy , Faesen Sharlaa , Kityo Cissy , Dadabhai Sufia S , Naidoo Kogieleum , Samaneka Wadzanai P , Lama Javier R , Veloso Valdilea G , Mave Vidya , Lalloo Umesh , Langat Deborah , Hogg Evelyn , Bisson Gregory P , Kumwenda Johnstone , Hosseinipour Mina C ,   for the ACTG A5274/REMEMBER Study Team
Published: July 2022

Abstract

Background
People with human immunodeficiency virus (HIV) and advanced immunosuppression initiating antiretroviral therapy (ART) remain vulnerable to tuberculosis (TB) and early mortality. To improve early survival, isoniazid preventive therapy (IPT) or empiric TB treatment have been evaluated; however, their benefit on longer-term outcomes warrants investigation.

Methods
We present a 96-week preplanned secondary analysis among 850 ART-naive outpatients (≥13 years) enrolled in a multicountry, randomized trial of efavirenz-containing ART plus either 6-month IPT (n = 426) or empiric 4-drug TB treatment (n = 424). Inclusion criteria were CD4 count &lt;50 cells/mm3 and no confirmed or probable TB. Death and incident TB were compared by strategy arm using the Kaplan-Meier method. The impact of self-reported adherence (calculated as the proportion of 100% adherence) was assessed using Cox-proportional hazards models.

Results
By 96 weeks, 85 deaths and 63 TB events occurred. Kaplan-Meier estimated mortality (10.1% vs 10.5%; P = .86) and time-to-death (P = .77) did not differ by arm. Empiric had higher TB risk (6.1% vs 2.7%; risk difference, −3.4% [95% confidence interval, −6.2% to −0.6%]; P = .02) and shorter time to TB (P = .02) than IPT. Tuberculosis medication adherence lowered the hazards of death by ≥23% (P &lt; .0001) in empiric and ≥20% (P &lt; .035) in IPT and incident TB by ≥17% (P ≤ .0324) only in IPT.

Conclusions
Empiric TB treatment offered no longer-term advantage over IPT in our population with advanced immunosuppression initiating ART. High IPT adherence significantly lowered death and TB incidence through 96 weeks, emphasizing the benefit of ART plus IPT initiation and completion, in persons with advanced HIV living in high TB-burden, resource-limited settings.
Quantitative Analysis of Florigen for the Variability of Floral Induction in Cabbage/Radish Inter-generic Grafting
Authors: Motoki Ko , Kinoshita Yu , Nakano Ryohei , Hosokawa Munetaka , Nakazaki Tetsuya 
Published: July 2022

Abstract
Grafting-induced flowering is a key phenomenon to understand systemic floral induction caused by florigen. It can also be used as a breeding technique enabling rapid seed production of crops with long generation times. However, the degree of floral induction in grafted plants is often variable. Moreover, it is difficult in some crop species. Here, we explored the factors promoting variability in the grafting-induced flowering of cabbage (Brassica oleracea L. var. capitata), an important vegetable crop with a long generation time, via the quantitative analysis of florigen accumulation. Significant variability in the flowering response of grafted cabbage was observed when rootstocks of different genotypes were used. As reported previously, B. oleracea rootstocks did not induce the flowering of grafted cabbage plants, but radish (Raphanus sativus L.) rootstocks unstably did, depending on the accessions used. Immunoblotting analysis of the FLOWERING LOCUS T (FT) protein, a main component of florigen, revealed that floral induction was quantitatively correlated with the level of accumulated FT protein in the grafted scion. To identify rootstock factors that cause variability in the floral induction of the grafted scion, we investigated FT protein accumulation and flowering response in grafted scions when the transcription levels of FT and the leaf area of rootstocks were altered by vernalization, daylength and leaf trimming treatments. We concluded that increasing the total amount of FT protein produced in the rootstock is important for the stable floral induction of the grafted cabbage, and this can be accomplished by increasing FT transcription and the leaf area of the rootstock.
Test–Retest Reliability of a Static and Dynamic Motor Fatigability Protocol Using Grip and Pinch Strength in Children With Cerebral Palsy
Authors: Brauers Lieke , Smeets Rob , Feys Peter , Gordon Andrew M , van der Leij-Roelofsen Bertie , Bastiaenen Caroline , Rameckers Eugene , Klingels Katrijn 
Published: July 2022

AbstractObjectiveThe purpose of this study was to investigate the test–retest reliability, measurement error, and interpretability of new motor fatigability outcomes of grip and pinch strength for children with unilateral cerebral palsy (UCP).MethodsMotor fatigability during grip and pinch strength was measured twice (within 48 hours) in both hands of 50 children (mean age = 11 years 2 months; 14, 31, and 5 children with Manual Ability Classification System levels I, II, and III, respectively) using a 30-second static and dynamic maximum exertion protocol. For static motor fatigability, the Static Fatigue Index (SFI) and mean force (Fmean) in the first (Fmean1) and last (Fmean3) 10 seconds were calculated. For dynamic motor fatigability, Fmean1, Fmean3, and the number of peaks in the first and last 10 seconds were calculated.ResultsFor static motor fatigability, the intraclass correlation coefficients (ICCs) were moderate to high for Fmean1 and Fmean3 (0.56–0.88), and the SFI showed low to moderate reliability (ICC = 0.32–0.72). For dynamic motor fatigability, the ICCs were moderate to high for all outcomes (0.54–0.91). The standard error of measurement agreement and the smallest detectable difference agreement were large in all outcomes, except for the SFI in static motor fatigability. Details per age group are provided. In general, younger children (6–11 years old) showed lower reliability than older children (12–18 years old).ConclusionMost outcome measures for static and dynamic motor fatigability of grip and pinch strength show moderate to high reliability in children with UCP, indicating that these tests can be used reliably to investigate the presence of motor fatigability in UCP, especially in older children. Standard error of measurement agreement and smallest detectable difference agreement indicated that these outcome measures should be interpreted with caution when evaluating change.ImpactMost of the proposed outcome measures for static and dynamic motor fatigability of grip and pinch are reliable in children with UCP and can be used for discriminative purposes.