bluuebunny/crossref_metadata_2025 huggingface dataset:
Metagenomics analysis reveals the performance of homo- and heterofermentative lactic acid bacteria in alfalfa silage fermentation, bacterial community, and functional profiles
Authors: Okoye Charles Obinwanne , Wei Zhenwu , Jiang Huifang , Wu Yanfang , Wang Yongli , Gao Lu , Li Xia , Jiang Jianxiong
Published: June 2023

Alfalfa (Medicago sativa L.) is a kind of roughage frequently utilized as an animal feed but challenging to be ensiled due to its low water-soluble carbohydrate (WSC), high water content, and elevated buffering capacity, thus requiring the application of lactic acid bacteria (LAB) to improve its fermentation. This study employed high-throughput metagenomic sequence technology to reveal the effects of homofermentative LAB, Lactobacillus plantarum (Lp), or Pediococcus pentosaceus (Pp), and heterofermentative LAB, L. buchneri (Lb), or their combinations (LbLp or LbPp) (applied at 1.0 × 109 colony forming units (cfu) per kilogram of alfalfa biomass fresh material) on the fermentation, microbial community, and functional profiles of alfalfa silage after 7, 14, 30, and 60 ensiling days. The results indicated a reduction (P < 0.05) in glucose and pH and higher (P < 0.05) beneficial organic acid contents, xylose, crude protein, ammonia nitrogen, and aerobic stability in Lb-, LbPp-, and LbLp-inoculated alfalfa silages after 30 and 60 d. Also, higher (P < 0.05) WSC contents were recorded in LbLp-inoculated alfalfa silages after 30 d (10.84 g/kg dry matter [DM]) and 60 d (10.92 g/kg DM). Besides, LbLp-inoculated alfalfa silages recorded higher (P < 0.05) LAB count (9.92 log10 cfu/g) after 60 d. Furthermore, a positive correlation was found between the combined LAB inoculants in LbLp-inoculated alfalfa silages and dominant LAB genera, Lactobacillus and Pediococcus, with fermentation properties after 30 and 60 d. In addition, the 16S rRNA gene-predicted functional analyses further showed that the L. buchneri PC-C1 and L. plantarum YC1-1-4B combination improved carbohydrate metabolism and facilitated further degradation of polysaccharides in alfalfa after 60 d of ensiling. These findings reveal the significant performance of L. buchneri and L. plantarum in combination with dominant LAB species in suppressing the growth of Clostridia, molds, and yeasts and improving the fermentation characteristics and functional carbohydrate metabolism of alfalfa after 60 d ensiling, thus suggesting the need for further studies to uncover the diverse performance of the LAB combination and their consortium with other natural and artificial inoculants in various kinds of silages.
miR-130b duplex (miR-130b-3p/miR-130b-5p) negatively regulates goat intramuscular preadipocyte lipid droplets accumulation by inhibiting Krüppel-like factor 3 expression
Authors: Li Yanyan , He Changsheng , Ran Li , Wang Yong , Xiong Yan , Wang Youli , Zhu Jiangjiang , Lin Yaqiu
Published: June 2023

Intramuscular lipid deposition is important for meat quality improvement. microRNAs and their target mRNAs provide a new approach for studying the mechanism of fat deposition. The present study aimed to investigate the effect of miR-130b duplex (miR-130b-5p, miR-130b-3p) and its target gene KLF3 in regulating goat intramuscular adipocyte differentiation. Goat intramuscular preadipocytes were isolated from 7-d-old male Jianzhou big-ear goats and identified by Oil red O staining after differentiation induction. miR-130b-5p and miR-130b-3p mimics or inhibitors and their corresponding controls were transfected into goat intramuscular preadipocytes, respectively, and differentiation was induced by 50μM oleic acid for 48 h. Oil red O and Bodipy staining indicated that both miR-130b-5p and miR-130b-3p can reduce lipid droplets accumulation and triglyceride (TG) content (P < 0.01). Differentiation markers C/EBPα, C/EBPβ, PPARγ, pref1, fatty acids synthesis markers ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, AP2, SREBP1, and TG markers LPL, ATGL, HSL were assessed by qPCR. All the markers measured were downregulated by miR-130b-5p and miR-130b-3p analog (P < 0.01), suggesting that miR-130b inhibits goat intramuscular adipocyte adipogenic differentiation, fatty acids synthesis, and lipid lipolysis. To examine the mechanism of miR-130b duplex inhibition of lipid deposition, TargetScan, miRDB, and starBase were used to predict the potential targets, KLF3 was found to be the only one intersection. Furthermore, the 3ʹUTR of KLF3 was cloned, qPCR analysis and dual luciferase activity assay showed that both miR-130b-5p and miR-130b-3p could directly regulate KLF3 expression (P < 0.01). In addition, overexpression and interference of KLF3 were conducted, it was found that KLF3 positively regulated lipid droplets accumulation by Oil red O, Bodipy staining, and TG content detection (P < 0.01). Quantitative PCR result indicated that KLF3 overexpression promoted lipid droplets accumulation relative genes C/EBPβ, PPARγ, pref1, ACC, FASN, DGAT1, DGAT2, AGPAT6, TIP47, GPAM, ADRP, SREBP1, LPL, and ATGL expression (P < 0.01). Downregulation of KLF3 inhibited the expression of genes such as C/EBPα, C/EBPβ, PPARγ, pref1, TIP47, GPAM, ADRP, AP2, LPL, and ATGL expression (P < 0.01). Taken together, these results indicate that miR-130b duplex could directly inhibit KLF3 expression, then attenuated adipogenic and TG synthesis genes expression, thus leading to its anti-adipogenic effect.
Effects of a Saccharomyces cerevisiae fermentation product on fecal characteristics, metabolite concentrations, and microbiota populations of dogs undergoing transport stress
Authors: Oba Patrícia M , Carroll Meredith Q , Sieja Kelly M , Yang Xiaojing , Epp Tammi Y , Warzecha Christine M , Varney Jessica L , Fowler Jason W , Coon Craig N , Swanson Kelly S
Published: June 2023

Previously, a Saccharomyces cerevisiae fermentation product (SCFP) positively altered fecal microbiota, fecal metabolites, and immune cell function of adult dogs. Our objective was to determine the fecal characteristics, microbiota, and metabolites of SCFP-supplemented dogs subjected to transport stress. All procedures were approved by the Four Rivers Kennel IACUC prior to experimentation. Thirty-six adult dogs (18 male, 18 female; age: 7.1 ± 0.77 y; body weight: 28.97 ± 3.67 kg) were randomly assigned to be controls or receive SCFP supplementation (250 mg/dog/d) (n=18/group) for 11 wk. At that time, fresh fecal samples were collected before and after transport in a hunting dog trailer with individual kennels. The trailer was driven 40 miles round trip for about 45 min. Fecal microbiota data were evaluated using Quantitative Insights Into Microbial Ecology 2, while all other data were analyzed using the Mixed Models procedure of Statistical Analysis System. Effects of treatment, transport, and treatment*transport were tested, with P<0.05 being considered significant. Transport stress increased fecal indole concentrations and relative abundances of fecal Actinobacteria, Collinsella, Slackia, Ruminococcus, and Eubacterium. In contrast, relative abundances of fecal Fusobacteria, Streptococcus, and Fusobacterium were reduced by transport. Fecal characteristics, metabolites, and bacterial alpha and beta diversity measures were not affected by diet alone. Several diet*transport interactions were significant, however. Following transport, relative abundance of fecal Turicibacter increased in SCFP-supplemented dogs, but decreased in controls. Following transport, relative abundances of fecal Proteobacteria, Bacteroidetes, Prevotella, and Sutterella increased in controls, but not in SCFP-supplemented dogs. In contrast, relative abundances of fecal Firmicutes, Clostridium, Faecalibacterium, and Allobaculum increased and fecal Parabacteroides and Phascolarctobacterium decreased after transport stress in SCFP-supplemented dogs, but not in controls. Our data demonstrate that both transport stress and SCFP alter fecal microbiota in dogs, with transport being the primary cause for shifts. SCFP supplementation may provide benefits to dogs undergoing transport stress, but more research is necessary to determine proper dosages. More research is also necessary to determine if and how transport stress impacts gastrointestinal microbiota and other indicators of health.
The impact of selenium on insects
Authors: So John , Choe Dong-Hwan , Rust Michael K , Trumble John T , Lee Chow-Yang
Published: June 2023

Selenium, a naturally occurring metalloid, is an essential trace element for many higher organisms, including humans. Humans primarily become exposed to selenium by ingesting food products containing trace amounts of selenium compounds. Although essential in these small amounts, selenium exhibits toxic effects at higher doses. Previous studies investigating the effects on insects of order Blattodea, Coleoptera, Diptera, Ephemeroptera, Hemiptera, Hymenoptera, Lepidoptera, Odonata, and Orthoptera revealed impacts on mortality, growth, development, and behavior. Nearly every study examining selenium toxicity has shown that insects are negatively affected by exposure to selenium in their food. However, there were no clear patterns of toxicity between insect orders or similarities between insect species within families. At this time, the potential for control will need to be determined on a species-by-species basis. We suspect that the multiple modes of action, including mutation-inducing modification of important amino acids as well as impacts on microbiome composition, influence this variability. There are relatively few studies that have examined the potential effects of selenium on beneficial insects, and the results have ranged from increased predation (a strong positive effect) to toxicity resulting in reduced population growth or even the effective elimination of the natural enemies (more common negative effects). As a result, in those pest systems where selenium use is contemplated, additional research may be necessary to ascertain if selenium use is compatible with key biological control agents. This review explores selenium as a potential insecticide and possible future directions for research.
Potential insecticidal extracts from Artocarpus lacucha against Spodoptera litura (Lepidoptera: Noctuidae) larvae
Authors: Ruttanaphan Torranis , Songoen Weerasak , Pluempanupat Wanchai , Bullangpoti Vasakorn
Published: June 2023

Artocarpus lacucha, a plant in the Moraceae family, has traditionally been used in Southeast Asian medicine to treat various ailments. This study investigated the insecticidal potential against Spodoptera litura of several compounds extracted from A. lacucha using a topical application method. A sequential extraction method was employed with A. lacucha stems to identify the most toxic crude extract by using hexane, dichloromethane, ethyl acetate, and methanol solvents. Subsequently, the most toxic crude extract was analyzed for chemical composition by HPLC, followed by the isolation process. Among these crude extracts, the ethyl acetate crude extract was the most toxic to second-instar S. litura larvae (24-h LD50 value of ~9.07 µg/larva). Our results showed that the catechin isolated from the ethyl acetate crude extract exhibited the highest toxicity against this insect (24-h LD50 value of ~8.37 µg/larva). Additionally, catechin significantly decreased the activities of acetylcholinesterase, carboxylesterases, and glutathione S-transferase in the larvae. These findings suggest that catechin isolated from A. lacucha could be a potential insecticidal agent against S. litura. However, the toxicity and persistence of catechin under field conditions need to be further investigated to develop this novel insecticide.
Impact of renal and hepatic function on first opioid prescriptions in cancer patients: an acute care hospital database study linked to medical claims data and laboratory data
Authors: Takahashi Richi , Miyashita Mitsunori , Oba Mari S , Murakami Yoshitaka
Published: June 2023

Background

Cancer patients often have impaired renal and hepatic function. Opioids are essential to relieve painful symptoms in cancer patients. However, it is unknown which opioids are first prescribed for cancer patients with renal and hepatic impairment. The objective is to investigate the association between the type of first prescribed opioids and the renal/hepatic function of cancer patients.

Methods

We used a multicenter database from 2010 to 2019. The number of days from the first opioid prescription to the death was defined as the prognostic period. This period was divided into six categories. The prevalence of opioid prescriptions was calculated for each assessment of renal and hepatic function, divided into prognostic periods. Multinomial logistic regression analysis was used to explore the influence of renal and hepatic function on the first opioid choice.

Results

The study included 11 945 patients who died of cancer. In all prognostic period categories, the patients with worse renal function received fewer morphine prescriptions. No trend was observed in hepatic function. The odds ratio of oxycodone to morphine with reference to estimated glomerular filtration rate (eGFR) ≥90 was 1.707 (95% confidence interval: 1.433–2.034) for estimated glomerular filtration rate <30. The odds ratio of fentanyl to morphine with reference to estimated glomerular filtration rate ≥90 was 1.785 (95% confidence interval: 1.492–2.134) for estimated glomerular filtration rate <30. No association was identified between hepatic function and the choice of prescribed opioids.

Conclusion

Cancer patients with renal impairment tended to avoid morphine prescriptions, and no specific trend was observed in cancer patients with hepatic impairment.
Respiratory Syncytial Virus Infection Among Hospitalized Infants in Four Middle-Income Countries
Authors: Biggs Holly M , Simões Eric A F , Abu Khader Ilham , Thompson Mark G , Gordon Aubree , Hunt Danielle R , DeGroote Nicholas P , Porter Rachael M , Bino Silvia , Marar Basima I , Gresh Lionel , de Jesus-Cornejo Joanne , Langley Gayle , Thornburg Natalie J , Peret Teresa C T , Whitaker Brett , Zhang Yange , Wang Lijuan , Patel Mira C , McMorrow Meredith , Campbell William , Hasibra Iris , Duka Enkeleda , Al-Gazo Mahmoud , Kubale John , Sanchez Felix , Lucero Marilla G , Tallo Veronica L , Azziz-Baumgartner Eduardo , Simaku Artan , Gerber Susan I ,   IRIS Network, Levine Min Z , Edwards Laura , Balmaseda Angel , Kuan Guillermina , Sanchez Nery , Ojeda Sergio , Al-Sanouri Tareq M , Arbaji Ali , Mendoza-Dancel Lei Lanna , Iana Cruz Karen , Sanvictores Diozele M
Published: June 2023

Background

Understanding respiratory syncytial virus (RSV) global epidemiology is important to inform future prevention strategies.

Methods

Hospitalized infants <1-year-old with acute illness were enrolled prospectively in Albania, Jordan, Nicaragua, and Philippines during respiratory seasons in 2015–2017. Medical chart review, parental interview, and post-discharge follow up were conducted. Respiratory specimens were tested using real-time RT-PCR for RSV. Infant characteristics associated with very severe illness (intensive care unit [ICU] admission or receipt of supplemental oxygen) were assessed using logistic regression to adjust for potential confounders (age, sex, study site, and preterm birth).

Results

Of 3634 enrolled hospitalized infants, 1129 (31%) tested positive for RSV. The median age of RSV-positive infants was 2.7 (IQR: 1.4–6.1) months and 665 (59%) were male. Very severe illness in 583 (52%) RSV-positive infants was associated with younger age (aOR 4.1, 95% CI: 2.6–6.5 for 0–2 compared to 9–11-months; P < .01), low weight-for-age z-score (aOR 1.9, 95% CI: 1.2–2.8; P < .01), ICU care after birth (aOR 1.6, 95% CI: 1.0–2.5; P = .048), and cesarean delivery (aOR 1.4, 95% CI: 1.0–1.8; P = .03). RSV subgroups A and B co-circulated at all sites with alternating predominance by year; subgroup was not associated with severity (aOR 1.0, 95% CI: 0.8–1.4). Nine (0.8%) RSV-positive infants died during admission or within ≤30 days of discharge, of which 7 (78%) were <6-months-old.

Conclusions

RSV was associated with nearly a third of infant acute illness hospitalizations in four middle-income countries during the respiratory season, where, in addition to young age, factors including low weight-for-age might be important predictors of severity. RSV prevention strategies targeting young infants could substantially reduce RSV-associated hospitalizations in middle-income countries.
Salvage high-dose rate brachytherapy for myxofibrosarcoma of the brachium: a technical report
Authors: Murakami Naoya , Nakatani Fumihiko , Takahashi Kana , Nakamura Satoshi , Igaki Hiroshi , Shikama Naoto
Published: June 2023

An 80-year-old male presented with T1N0M0 myxofibrosarcoma in or next to the humeral canal, which is located between the biceps and triceps of the right upper arm. Because the tumor was close to critical anatomical structures such as the brachial artery, median nerve and ulnar nerve, it was deemed impossible to perform limb-sparing surgery with an adequate resection margin. Therefore, preoperative external beam radiation therapy (EBRT) followed by limb-sparing surgery was offered. Magnetic resonance imaging taken after 40 Gy/20 fractions of EBRT showed an inadequate response, and limb-sparing surgery was not deemed possible at this point. Amputation of the right arm was offered, but the patient refused. Therefore, salvage high-dose-rate interstitial brachytherapy (HDR-ISBT) was offered. Under local anesthesia and sedation, 14 plastic needles were inserted, and 36 Gy in 6 fractions of HDR-ISBT was performed. Although radiation-induced incomplete paralysis of the median nerve was noted, no local progression or distant metastasis was found on the CT that was taken 2 years after the treatment.
A giant chylolymphatic cyst of the retroperitoneum: a case report
Authors: Alafandi Bana Zuhair , Al Aliwy Marwan , Hakim Raghad , Merjaneh Laura , Balid Mohamed Muhanad , Markaby Joud , Shehade Linda , Agha Sarab , Ayoub Kusay
Published: June 2023

Chylolymphatic cysts are an extremely rare variant of mesenteric cysts and account for 7.3% of all abdominal cysts. They can develop anywhere along the mesentery of the gastrointestinal tract and present in a wide range of symptoms. A 46-year-old male presented with mild abdominal pain and intermittent claudication in his right leg for the last 2 months and a history of a retroperitoneal resection of a simple abdominal cyst 5 years ago. Abdominal ultrasound and computerized tomography showed a fluid-filled cystic lesion measuring 17 × 11 × 10 cm in the right retroperitoneum. The cyst was surgically excised, and the histopathological examination was consistent with the chylolymphatic cyst. On a 1-year follow-up, the patient is recovered with no recurrence observed. Our report presents a case of a giant retroperitoneal chylolymphatic cyst with uncommon presenting symptoms and a rare etiology.
Partner responses to low desire among couples coping with male hypoactive sexual desire disorder and associations with sexual well-being
Authors: Belu Charlene F , Corsini-Munt Serena , Dubé Justin P , Wang Grace A , Rosen Natalie O
Published: June 2023

Background

Hypoactive sexual desire disorder (HSDD) is characterized by persistently low desire and associated distress. Low desire is one of the most common sexual complaints among men and is associated with poor well-being. Interpersonal factors are key to understanding low desire, yet there are few dyadic studies of HSDD in men. Previous work on genito-pelvic pain and low desire in women has established that greater facilitative (eg, affectionate) partner responses are associated with greater sexual satisfaction and function and that more negative (eg, critical) or solicitous (eg, sympathetic, avoidant) partner responses are associated with lower sexual satisfaction and function. Examining how partner responses are associated with adjustment to HSDD may shed light on the interpersonal dynamics of this understudied sexual dysfunction.

Aim

In a cross-sectional study, we examined whether partner responses to low desire in men were associated with sexual desire, sexual satisfaction, and sexual distress for both members of the couple.

Methods

Men with HSDD and their partners (N  =  67 couples) completed measures of facilitative, negative, and avoidant partner responses to men’s low sexual desire—as perceived by the man with HSDD and self-reported by their partner—and sexual desire, sexual satisfaction, and sexual distress. Data were analyzed using multilevel modeling guided by the actor–partner interdependence model.

Outcomes

Outcomes included the partner-focused subscale of the Sexual Desire Inventory–2, Global Measure of Sexual Satisfaction, and Sexual Distress Scale–Revised.

Results

When men with HSDD perceived more facilitative partner responses to their low desire, they and their partners reported greater sexual satisfaction. When men with HSDD perceived and their partners self-reported more negative partner responses, they each reported lower sexual satisfaction. In addition, when men with HSDD perceived more avoidant partner responses, their partners reported greater sexual distress. Partner responses were not associated with sexual desire for either member of the couple.

Clinical Implications

Findings support the importance of the interpersonal context for HSDD in men and suggest potential future targets of treatment when working with affected couples.

Strengths and Limitations

This study is one of the only dyadic studies of HSDD in men, as assessed via clinical interview or self-report symptoms reviewed by the clinical team. Despite our best efforts to recruit this sample over 6 years, the small size limited power to detect all predicted effects.

Conclusion

More facilitative and fewer negative or avoidant partner responses to low desire are associated with greater sexual well-being in couples coping with HSDD.
Constraint propagation on GPU: A case study for the AllDifferent constraint
Authors: Tardivo Fabio , Dovier Agostino , Formisano Andrea , Michel Laurent , Pontelli Enrico
Published: June 2023

The AllDifferent constraint is a fundamental tool in Constraint Programming. It naturally arises in many problems, from puzzles to scheduling and routing applications. Such popularity has prompted an extensive literature on filtering and propagation for this constraint. This paper investigates the use of General Processing Units (GPUs) to accelerate filtering and propagation. In particular, the paper presents an efficient parallelization of the AllDifferent constraint on GPU, along with an analysis of different design and implementation choices and evaluation of the performance of the resulting system on several benchmarks.
How Fast is Your Detector? The Effect of Temporal Response on Image Quality
Authors: Mullarkey Tiarnan , Geever Matthew , Peters Jonathan J P , Griffiths Ian , Nellist Peter D , Jones Lewys
Published: June 2023

With increasing interest in high-speed imaging, there should be an increased interest in the response times of our scanning transmission electron microscope detectors. Previous works have highlighted and contrasted the performance of various detectors for quantitative compositional or structural studies, but here, we shift the focus to detector temporal response, and the effect this has on captured images. The rise and decay times of eight detectors' single-electron response are reported, as well as measurements of their flatness, roundness, smoothness, and ellipticity. We develop and apply a methodology for incorporating the temporal detector response into simulations, showing that a loss of resolution is apparent in both the images and their Fourier transforms. We conclude that the solid-state detector outperforms the photomultiplier tube–based detectors in all areas bar a slightly less elliptical central hole and is likely the best detector to use for the majority of applications. However, using the tools introduced here, we encourage users to effectively evaluate which detector is most suitable for their experimental needs.
The Effect of Body Armor on Pulmonary Function Using Plethysmography
Authors: Dunnick Dustin , Kins Keoni , Bhammar Dharini M , Schilling Brian K
Published: June 2023

Military tactical athletes face the unique task of performing physically demanding occupational duties, often while wearing body armor. Forced vital capacity and forced expiratory volume measured using spirometry have been shown to decrease, while wearing plate-carrier style body armor, little is known about the comprehensive effects of wearing body armor on pulmonary function, including lung capacities. Further, the effects of loaded body armor vs. unloaded on pulmonary function are also unknown. Therefore, this study examined how loaded and unloaded body armor affects pulmonary function. Twelve college-aged males performed spirometry and plethysmography under three conditions (basic athletic attire [CNTL], unloaded plate carrier [UNL], and loaded plate carrier [LOAD]). Compared to CNTL, LOAD and UNL conditions significantly reduced functional residual capacity by 14% and 17%, respectively. Compared with CNTL, LOAD condition also showed a small but statistically significant lowered forced vital capacity (P = .02, d = 0.3), a 6% lower total lung capacity (P < .01, d = 0.5), and lowered maximal voluntary ventilation (P = .04, d = 0.4). A loaded plate-carrier style body armor exerts a restrictive effect on total lung capacity, and both loaded and unloaded body armor affects functional residual capacity, which could impact breathing mechanics during exercise. Resulting endurance performance decreases may need to be factored based on the style and loading of body armor, especially for longer-duration operations.
Borrowing from the Past: Scarlattian Phrase Structure, Type 2 Sonatas, and Phrygian Tonality in Isaac Albéniz’s Works
Authors: Martín Entrialgo Alberto
Published: June 2023

The importance of Domenico Scarlatti in nineteenth-century Spanish music has frequently been acknowledged. Likewise, comparisons between Isaac Albéniz’s and Scarlatti’s writing have been recurrent in Albéniz scholarship. Most of this literature, while referring to biographical circumstances, has mentioned their emulation of the guitar, their recourse to Spanish folklore, certain harmonic effects, and the use of the Phrygian mode and the so-called cadencia andaluza. However, phrase structural and formal procedures common to both composers have remained unnoticed, as, for instance, Albéniz’s use of the ‘type 2’ sonata as a way of emulating Scarlatti. The aim of this article is to offer some much-needed justification for such comparisons between Albéniz’s and Scarlatti’s music, devoting particular attention to Albéniz’s Iberia. The article also serves to put Albéniz at the centre of ongoing debates in the field of music theory, such as the application of ‘galant’ schemata to later music and in particular disputes about the interpretation of nineteenth-century sonata form from the perspective of eighteenth-century practice.
Radiative hydrodynamical simulations of super-Eddington accretion flow in tidal disruption event: the accretion flow and wind
Authors: Bu De-Fu , Qiao Erlin , Yang Xiao-Hong
Published: June 2023

One key question in tidal disruption events theory is how much of the fallback debris can be accreted to the black hole. Based on radiative hydrodynamic simulations, we study this issue for efficiently ‘circularized’ debris accretion flow. We find that for a black hole disrupting a solar-type star, $15{{\, \rm per\, cent}}$ of the debris can be accreted for a 107 M⊙ black hole. While for a 106 M⊙ black hole, the value is $43{{\, \rm per\, cent}}$. We find that wind can be launched in the super-Eddington accretion phase regardless of the black hole mass. The maximum velocity of the wind can reach 0.7c (with c being the speed of light). The kinetic power of wind is well above 1044 erg s−1. The results can be used to study the interaction of wind and the circumnuclear medium around quiescent supermassive black holes.
Investigating the OH-H2 relation in diffuse Galactic clouds
Authors: Rawlins Katherine , Mookerjea Bhaswati
Published: June 2023

We investigate the correlation between OH and H2 column densities in diffuse Galactic clouds, in order to identify potential molecular tracers of interstellar H2. For this, we analyse near-UV spectra extracted from the ESO/VLT archives towards seventeen sightlines (five of them new) with known N(H2), along with nine sightlines with no H2 information. N(OH) shows only marginal correlation with N(H2) (1020 to 2 × 1021 cm−2), at the 95 per cent confidence level. We use orthogonal distance regression analysis to obtain N(OH) /N(H2) = (1.32±0.15) × 10−7, which is ∼ 33 per cent higher than the previous estimates based on near-UV data. We also obtain N(CH) /N(H2) = (3.83±0.23) × 10−8 and a significant correlation between N(OH) and N(CH), with N(OH) = (2.61±0.19) × N(CH), both of which are consistent with previous results. Comparison with predictions of numerical models indicate that OH absorption arises from diffuse gas (nH ∼ 50 cm−3) illuminated by radiation fields ∼ 0.5–5 G0, while CH is associated with higher density of 500 cm−3. We posit that the apparent dichotomy in the properties of the diffuse clouds giving rise to OH and CH absorption could be due to either (a) the presence of multiple spectroscopically unresolved clouds along the line-of-sight, or, (b) density gradients along the line-of-sight within a single cloud.
A Quantitative Theory for Genomic Offset Statistics
Authors: Gain Clément , Rhoné Bénédicte , Cubry Philippe , Salazar Israfel , Forbes Florence , Vigouroux Yves , Jay Flora , François Olivier
Published: June 2023

Genomic offset statistics predict the maladaptation of populations to rapid habitat alteration based on association of genotypes with environmental variation. Despite substantial evidence for empirical validity, genomic offset statistics have well-identified limitations, and lack a theory that would facilitate interpretations of predicted values. Here, we clarified the theoretical relationships between genomic offset statistics and unobserved fitness traits controlled by environmentally selected loci and proposed a geometric measure to predict fitness after rapid change in local environment. The predictions of our theory were verified in computer simulations and in empirical data on African pearl millet (Cenchrus americanus) obtained from a common garden experiment. Our results proposed a unified perspective on genomic offset statistics and provided a theoretical foundation necessary when considering their potential application in conservation management in the face of environmental change.
Dendritic cell vaccine trials in gliomas: Untangling the lines
Authors: Hotchkiss Kelly M , Batich Kristen A , Mohan Aditya , Rahman Rifaquat , Piantadosi Steven , Khasraw Mustafa
Published: June 2023

Glioblastoma is a deadly brain tumor without any significantly successful treatments to date. Tumor antigen-targeted immunotherapy platforms including peptide and dendritic cell (DC) vaccines, have extended survival in hematologic malignancies. The relatively “cold” tumor immune microenvironment and heterogenous nature of glioblastoma have proven to be major limitations to translational application and efficacy of DC vaccines. Furthermore, many DC vaccine trials in glioblastoma are difficult to interpret due to a lack of contemporaneous controls, absence of any control comparison, or inconsistent patient populations. Here we review glioblastoma immunobiology aspects that are relevant to DC vaccines, review the clinical experience with DC vaccines targeting glioblastoma, discuss challenges in clinical trial design, and summarize conclusions and directions for future research for the development of effective DC vaccines for patients.
Sialic acid metabolism orchestrates transcellular connectivity and signaling in glioblastoma
Authors: Kuliesiute Ugne , Joseph Kevin , Straehle Jakob , Madapusi Ravi Vidhya , Kueckelhaus Jan , Kada Benotmane Jasim , Zhang Junyi , Vlachos Andreas , Beck Juergen , Schnell Oliver , Neniskyte Urte , Heiland Dieter Henrik
Published: June 2023

Background

In glioblastoma (GBM), the effects of altered glycocalyx are largely unexplored. The terminal moiety of cell coating glycans, sialic acid, is of paramount importance for cell-cell contacts. However, sialic acid turnover in gliomas and its impact on tumor networks remain unknown.

Methods

We streamlined an experimental setup using organotypic human brain slice cultures as a framework for exploring brain glycobiology, including metabolic labeling of sialic acid moieties and quantification of glycocalyx changes. By live, 2-photon and high-resolution microscopy we have examined morphological and functional effects of altered sialic acid metabolism in GBM. By calcium imaging we investigated the effects of the altered glycocalyx on a functional level of GBM networks.

Results

The visualization and quantitative analysis of newly synthesized sialic acids revealed a high rate of de novo sialylation in GBM cells. Sialyltrasferases and sialidases were highly expressed in GBM, indicating that significant turnover of sialic acids is involved in GBM pathology. Inhibition of either sialic acid biosynthesis or desialylation affected the pattern of tumor growth and lead to the alterations in the connectivity of glioblastoma cells network.

Conclusions

Our results indicate that sialic acid is essential for the establishment of GBM tumor and its cellular network. They highlight the importance of sialic acid for glioblastoma pathology and suggest that dynamics of sialylation have the potential to be targeted therapeutically.
The effects of carbohydrate-restricted diet on psychological outcomes: a systematic review of randomized controlled trials
Authors: Sindler Dominik , Kastovska Barbora , Dostal Tomas , Cipryan Lukas , Elavsky Steriani
Published: June 2023

Context

Carbohydrate-restricted diets are widely used as an effective treatment tool for many chronic diseases. The impact of these diets on physical health is well known, but their impact on psychological health is less well described in the scientific literature. This is an important aspect to focus on, especially if the diets are to be sustainable in the long term.

Objective

The objective of this study was to systematically review the scientific literature describing the effect of carbohydrate-restricted diets and ketogenic diets on psychological outcomes, as observed in randomized controlled trials. Additionally, the potential synergistic effect of carbohydrate-restricted diets and exercise or social factors on these outcomes was researched.

Data Sources

Five databases (Web of Science, PubMed, Scopus, ScienceDirect, and MEDLINE Complete) were searched without restriction of publication date.

Data Extraction

The first data extraction was made in October 2020 and the second in May 2022. Abstract screening was performed by 3 independent reviewers. The quality of studies was assessed using the Jadad scale.

Data Analysis

Sixteen randomized controlled studies were included in the analysis. Five studies focused on clinical populations, 9 on obese/overweight populations, and 2 on healthy populations; all studies examined adult people. Four psychological outcomes were identified (quality of life, mental health, mood, and fatigue), and they were examined in connection with a very low-carbohydrate or ketogenic diet.

Conclusion

Daily low-carbohydrate intake may not negatively affect psychological well-being, and low-carbohydrate diets and ketogenic diets are no worse than other diets in this respect. An intervention of 12 weeks or longer can bring benefits in psychological well-being. The synergistic effect of diet and exercise or social factors was not reviewed due to lack of evidence.
Olanzapine With or Without Fosaprepitant for Preventing Chemotherapy Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial (ALLIANCE A221602)
Authors: Navari Rudolph M , Le-Rademacher Jennifer , Smieliauskas Fabrice , Ruddy Kathryn J , James Saphner Thomas , Liu Heshan , Harlos Elizabeth , Onitilo Adedayo A , Giridhar Karthik , Paul Singh Preet , Reddy Pavan S , Chow Selina , Kruter Flavio , Raptis George , Loprinzi Charles L
Published: June 2023

Purpose

A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used.

Materials and Methods

A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 ­olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%.

Results

A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist.

Conclusion

This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy (ClinicalTrials.gov Identifier: NCT03578081).
Pre-Diagnosis Pain in Patients With Pancreatic Cancer Signals the Need for Aggressive Symptom Management
Authors: McNearney Terry A , Digbeu Biai Dominique Elmir , Baillargeon Jacques G , Ladnier Dennis , Rahib Lola , Matrisian Lynn M
Published: June 2023

Objective

This study assessed the impact of pancreatic cancer (PC) pain on associated symptoms, activities, and resource utilization from 2016 to 2020 in an online patient registry.

Patients and Methods

Responses from PC patient volunteers (N = 1978) were analyzed from online surveys in a cross-sectional study. Comparisons were performed between PC patient groups reporting, (1) the presence vs. absence of pre-diagnosis PC pain, (2) high (4-8) vs. low (0-3) pain intensity scores on an 11-point numerical rating scale (NRS), and (3) year of PC diagnosis (2010-2020). Descriptive statistics and all bivariate analyses were performed using Chi-square or Fisher’s Exact tests.

Results

PC pain was the most frequently reported pre-diagnosis symptom (62%). Pre-diagnostic PC pain was reported more frequently by women, those with a younger age at diagnosis, and those with PC that spread to the liver and peritoneum. Those with pre-diagnostic PC pain vs. those without reported higher pain intensities (2.64 ± 2.54 vs.1.56 ± 2.01 NRS mean ± SD, respectively, P = .0039); increased frequencies of post-diagnosis symptoms of cramping after meals, feelings of indigestion, and weight loss (P = .02-.0001); and increased resource utilization in PC pain management: (ER visits N = 86 vs. N = 6, P = .018 and analgesic prescriptions, P < .03). The frequency of high pain intensity scores was not decreased over a recent 11-year span.

Conclusions

PC pain continues to be a prominent PC symptom. Patients reporting pre-diagnosis PC pain experience increased GI metastasis, symptoms burden, and are often undertreated. Its mitigation may require novel treatments, more resources dedicated to ongoing pain management and surveillance to improve outcomes.
Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors
Authors: Sanda Gregory E , Shabto Julie M , Goyal Subir , Liu Yuan , Martini Dylan J , Nazha Bassel , Brown Jacqueline T , Yantorni Lauren B , Anne Russler Greta , Caulfield Sarah , Joshi Shreyas S , Narayan Vikram M , Kissick Haydn , Ogan Kenneth , Master Viraj A , Carthon Bradley C , Kucuk Omer , Bilen Mehmet Asim
Published: June 2023

Background

In advanced urothelial cancers (UC), immune checkpoint inhibitors (ICI) show promise as a durable therapy. Immune-related adverse events (irAEs), a side effect of ICIs, may serve as an indicator of beneficial response. We investigated the relationship between irAEs and clinical outcomes in patients with advanced UC who received ICI.

Materials and Methods

In this retrospective study, we investigated 70 patients with advanced UC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on patients were collected through chart review. Cox’s proportional hazard model and logistic regression were applied to estimate the association with overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). The possible lead-time bias was handled in extended Cox regression models.

Results

The median age of the cohort was 68. Over one-third (35%) of patients experienced an irAE, with skin being the most frequent organ involved (12.9%). Patients that experienced at least one irAE had significantly enhanced OS (HR: 0.38, 95% CI, 0.18-0.79, P = .009), PFS (HR: 0.27, 95% CI, 0.14-0.53, P < .001), and CB (OR: 4.20, 95% CI, 1.35-13.06, P = .013). Patients who experienced dermatologic irAEs also had significantly greater OS, PFS, and CB.

Conclusion

Of patients with advanced UC that had undergone ICI therapy, those who had irAEs, especially dermatologic irAEs, had significantly greater OS, PFS, and CB. These results may suggest that irAE’s may serve as an important marker of durable response to ICI therapy in urothelial cancer. The findings of this study need to be validated with larger cohort studies in the future.
Mogamulizumab-Associated Myositis With and Without Myasthenia Gravis and/or Myocarditis in Patients With T-Cell Lymphoma
Authors: Virgen Cesar A , Sparks Jeffrey A , Nohria Anju , O’Hare Meabh J , Goyal Amrita , Said Jordan T , Tawa Marianne , LeBoeuf Nicole R , Kupper Thomas S , Fisher David C , Larocca Cecilia
Published: June 2023

Mogamulizumab is being increasingly prescribed for the treatment of T-cell lymphomas (MF/SS/ATLL). We conducted a retrospective cohort study to identify muscular immune-related adverse events (irAEs) associated with mogamulizumab in patients with T-cell lymphoma followed at Dana-Farber Cancer Institute from January 2015 to June 2022. We identified 5 cases of mogamulizumab-associated myositis and/or myocarditis (MAM/Mc), 2 additionally affected by myasthenia gravis, among 42 patients with T-cell lymphoma. Three cases experienced ­mogamulizumab-associated rash (MAR) prior to developing MAM/Mc. The incidence (n = 5/42, 11.9%) of muscular mogamulizumab-associated irAEs may be higher than has been previously reported in clinical trials and may be of late onset (a median of 5 cycles and as late as 100 days from the last infusion). We highlight the utility of IVIG, together with systemic corticosteroids, for the treatment of these potentially fatal side effects associated with mogamulizumab therapy.
Reflections on the Financial Toxicity of Cancer: 10 Years Later
Authors: Zafar S Yousuf , Peppercorn Jeffrey
Published: June 2023

This commentary reflects on the decade since the publication of an article on the financial toxicity of cancer treatment and the international recognition of the scope and depth of the problem, in the hope that the coming decade is characterized by evaluation and demonstration of optimal solutions to the problem.
Multilayered regulation of developmentally programmed pre-anthesis tip degeneration of the barley inflorescence
Authors: Shanmugaraj Nandhakumar , Rajaraman Jeyaraman , Kale Sandip , Kamal Roop , Huang Yongyu , Thirulogachandar Venkatasubbu , Garibay-Hernández Adriana , Budhagatapalli Nagaveni , Tandron Moya Yudelsy Antonia , Hajirezaei Mohammed R , Rutten Twan , Hensel Götz , Melzer Michael , Kumlehn Jochen , von Wirén Nicolaus , Mock Hans-Peter , Schnurbusch Thorsten
Published: June 2023

Leaf and floral tissue degeneration is a common feature in plants. In cereal crops such as barley (Hordeum vulgare L.), pre-anthesis tip degeneration (PTD) starts with growth arrest of the inflorescence meristem dome, which is followed basipetally by the degeneration of floral primordia and the central axis. Due to its quantitative nature and environmental sensitivity, inflorescence PTD constitutes a complex, multilayered trait affecting final grain number. This trait appears to be highly predictable and heritable under standardized growth conditions, consistent with a developmentally programmed mechanism. To elucidate the molecular underpinnings of inflorescence PTD, we combined metabolomic, transcriptomic, and genetic approaches to show that barley inflorescence PTD is accompanied by sugar depletion, amino acid degradation, and abscisic acid responses involving transcriptional regulators of senescence, defense, and light signaling. Based on transcriptome analyses, we identified GRASSY TILLERS1 (HvGT1), encoding an HD-ZIP transcription factor, as an important modulator of inflorescence PTD. A gene-edited knockout mutant of HvGT1 delayed PTD and increased differentiated apical spikelets and final spikelet number, suggesting a possible strategy to increase grain number in cereals. We propose a molecular framework that leads to barley PTD, the manipulation of which may increase yield potential in barley and other related cereals.
BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period
Authors: Li Zhenmeiyu , Liu Guoping , Yang Lin , Sun Mengge , Zhang Zhuangzhi , Xu Zhejun , Gao Yanjing , Jiang Xin , Su Zihao , Li Xiaosu , Yang Zhengang
Published: June 2023

The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.