bluuebunny/crossref_metadata_2025 huggingface dataset:
The variability of the broad-line Balmer decrement for quasars from the Sloan Digital Sky Survey reverberation mapping
Authors: Ma Yan-Song , Li Shao-Jun , Gu Chen-Sheng , Jiang Jian-Xia , Hou Kai-Li , Qin Shu-Hao , Bian Wei-Hao
Published: May 2023

Based on the spectral decomposition through a code of PrepSpec, the light curves (spanning 6.5 yr in the observed frame) of the broad-line Balmer decrement, i.e. the flux ratio of the broad Hα to the broad Hβ line, are calculated for a sample of 44 Sloan Digital Sky Survey reverberation-mapped quasars (z < 0.53). It is found that the logarithm of the mean broad-line Balmer decrement is 0.62 with a standard deviation of 0.15 dex. The relations between the mean Balmer decrement and the supermassive black hole accretion properties (the luminosity, black hole mass, Eddington ratio, and accretion rate) are investigated and no obvious correlations are found. It is found that there are 27 quasars ($61{{\ \rm per\ cent}}$ ) showing strong negative correlations between the Balmer decrement variance and the continuum variance, i.e. the Balmer decrement would be smaller with larger continuum flux. Assuming that the dust obscuration leads to the variance in the Balmer decrement and the continuum, an expected slope is −1/3, which is not consistent with most of measured slopes. Using the interpolated cross-correlation function, the time delays between the inverse Balmer decrement and the continuum are measured for 14 quasars with the maximum correlation coefficient larger than 0.6. It suggests that the size corresponding to the Balmer decrement lag extends from the broad-line region size to the torus size.
Selenium deficiency causes oxidative stress and activates inflammation, apoptosis, and necroptosis in the intestine of weaned calves
Authors: Lei Lei , Jing Mu , Yingce Zheng , Pei Zhang , Yun Liu
Published: May 2023

Selenium performs a variety of biological functions in organisms, including antioxidant and anti-inflammatory effects. This study investigated how selenium deficiency affects weaned calves' intestines. According to Inductively coupled plasma mass spectrometry (ICP-MS) analysis of intestinal selenium concentrations in calves, the Se-D group had a significantly lower concentration of selenium. Hematoxylin-eosin staining showed that the intestinal epithelial cells were detached, the goblet cells were lost, and the intestinal villi were fragmented and loosely arranged in the Se-D group, along with hyperemia and inflammatory infiltration. Of the 22 selenoprotein genes, 9 were downregulated in response to selenium deficiency in Reverse transcription-PCR (RT-PCR), whereas 6 genes were upregulated. In the Se-D group, oxidative stress was detected by measuring redox levels in the intestines. Furthermore, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, RT-PCR, and Western blotting (WB) results indicated that both intrinsic and extrinsic apoptosis pathways are activated in the intestine during selenium deficiency. Selenium deficiency also induced necroptosis in the intestine through upregulation of MLKL, RIPK1, and RIPK3 mRNA levels. In addition, according to hematoxylin-eosin staining and ELISA, selenium-deficient calves had severe inflammation in their intestines. As a result of RT-PCR and WB analyses, we found that selenium deficiency was associated with nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Our study suggested that weaned calves' intestines are affected by selenium deficiency, which causes oxidative stress, inflammation, apoptosis, and necroptosis.
The connection of α- and β-domains in mammalian metallothionein-2 differentiates Zn(II) binding affinities, affects folding, and determines zinc buffering properties
Authors: Singh Avinash Kumar , Pomorski Adam , Wu Sylwia , Peris-Díaz Manuel D , Czepczyńska-Krężel Hanna , Krężel Artur
Published: May 2023

Mammalian metallothioneins (MTs) are small Cys-rich proteins involved in Zn(II) and Cu(I) homeostasis. They bind seven Zn(II) ions in two distinct β- and α-domains, forming Zn3Cys9 and Zn4Cys11 clusters, respectively. After six decades of research, their role in cellular buffering of Zn(II) ions has begun to be understood recently. This is because of different affinities of bound ions and the proteins’ coexistence in variously Zn(II)-loaded Zn4-7MT species in the cell. To date, it has remained unclear how these mechanisms of action occur and how the affinities are differentiated despite the Zn(S-Cys)4 coordination environment being the same. Here, we dissect the molecular basis of these phenomena by using several MT2 mutants, hybrid protein, and isolated domains. Through a combination of spectroscopic and stability studies, thiol(ate) reactivity, and steered molecular dynamics, we demonstrate that both protein folding and thermodynamics of Zn(II) ion (un)binding significantly differ between isolated domains and the whole protein. Close proximity reduces the degrees of freedom of separated domains, making them less dynamic. It is caused by the formation of intra- and interdomain electrostatic interactions. The energetic consequence of domains connection has a critical impact on the role of MTs in the cellular environment, where they function not only as a zinc sponge but also as a zinc buffering system keeping free Zn(II) in the right concentrations. Any change of that subtle system affects the folding mechanism, zinc site stabilities, and cellular zinc buffer components.
Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma
Authors: Burger Michael C , Forster Marie-Therese , Romanski Annette , Straßheimer Florian , Macas Jadranka , Zeiner Pia S , Steidl Eike , Herkt Stefanie , Weber Katharina J , Schupp Jonathan , Lun Jennifer H , Strecker Maja I , Wlotzka Karolin , Cakmak Pinar , Opitz Corinna , George Rosemol , Mildenberger Iris C , Nowakowska Paulina , Zhang Congcong , Röder Jasmin , Müller Elvira , Ihrig Kristina , Langen Karl-Josef , Rieger Michael A , Herrmann Eva , Bonig Halvard , Harter Patrick N , Reiss Yvonne , Hattingen Elke , Rödel Franz , Plate Karl H , Tonn Torsten , Senft Christian , Steinbach Joachim P , Wels Winfried S
Published: May 2023

Background

Glioblastoma (GB) is incurable at present without established treatment options for recurrent disease. In this phase I first-in-human clinical trial we investigated safety and feasibility of adoptive transfer of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2, which is expressed at elevated levels by a subset of glioblastomas.

Methods

Nine patients with recurrent HER2-positive GB were treated with single doses of 1 × 107, 3 × 107, or 1 × 108 irradiated CAR-NK cells injected into the margins of the surgical cavity during relapse surgery. Imaging at baseline and follow-up, peripheral blood lymphocyte phenotyping and analyses of the immune architecture by multiplex immunohistochemistry and spatial digital profiling were performed.

Results

There were no dose-limiting toxicities, and none of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Five patients showed stable disease after relapse surgery and CAR-NK injection that lasted 7 to 37 weeks. Four patients had progressive disease. Pseudoprogression was found at injection sites in 2 patients, suggestive of a treatment-induced immune response. For all patients, median progression-free survival was 7 weeks, and median overall survival was 31 weeks. Furthermore, the level of CD8+ T-cell infiltration in recurrent tumor tissue prior to CAR-NK cell injection positively correlated with time to progression.

Conclusions

Intracranial injection of HER2-targeted CAR-NK cells is feasible and safe in patients with recurrent GB. 1 × 108 NK-92/5.28.z cells was determined as the maximum feasible dose for a subsequent expansion cohort with repetitive local injections of CAR-NK cells.
Direct observation of spreading precursor liquids in a corner
Authors: Miao Weining , Tian Shihao , Yuan Quanzi , Tian Ye , Jiang Lei
Published: May 2023

Precursor liquid is a nanoscale liquid creeping ahead of the macroscopic edge of spreading liquids, whose behaviors tightly correlate with the three-phase reaction efficiency and patterning accuracy. However, the important spatial–temporal characteristic of the precursor liquid still remains obscure because its real-time spreading process has not been directly observed. Here, we report that the spreading ionic liquid precursors in a silicon corner can be directly captured on video using in situ scanning electron microscopy. In situ spreading videos show that the precursor liquid spreads linearly over time (${\rm{\Delta }}L\ \sim\ {\rm{\Delta }}T$) rather than obeying the classic Lucas–Washburn law ($l\ \sim\ {t}^{1/2}$) and possesses a characteristic width of ∼250–310 nm. Theoretical analyses and molecular dynamics simulations demonstrate that the unique behaviors of precursor liquids originate from the competing effect of van der Waals force and surface energy. These findings provide avenues for directly observing liquid/solid interfacial phenomena on a microscopic level.
CSI acquisition in RIS-assisted mobile communication systems
Authors: Han Yu , Tang Wankai , Li Xiao , Matthaiou Michail , Jin Shi
Published: May 2023

Reconfigurable intelligent surface- (RIS) assisted mobile communication is a promising technological paradigm thanks to the attractive advantages of low cost and flexible control of electromagnetic waves. However, the low-cost features of RISs entail some fundamental challenges to the acquisition of channel state information (CSI), which is essential for the optimal RIS design. To tackle this problem, there have been extensive studies on CSI acquisition in RIS-assisted mobile communication systems, from the perspective of architectural improvement as well as specific mathematical solutions. This article aims to overview the existing works on CSI acquisition in RIS-assisted mobile communication systems.
MYB30 Regulates Submergence Tolerance by Repressing Ethylene Biosynthesis via ACS7 in Arabidopsis
Authors: Zhang Yiyi , Xie Yuanfu , Shi Haifan , Zhuang Yufen , Zheng Yuan , Lin Honghui , Zhou Huapeng
Published: May 2023

Floods impose detrimental effects on natural and agro-ecosystems, leading to a significant loss of worldwide crop production. Global climate change has even worsened this situation. Flooding is a continuous process including two stages of submergence and re-oxygenation, and both are harmful to plant growth and development, resulting in a serious decline in crop yield. Therefore, the understanding of plant flooding tolerance and developing flooding-resistant crops are of great significance. Here, we report that the Arabidopsis thaliana (Arabidopsis) R2R3-MYB transcription factor MYB30 participates in plant submergence response through 1-aminocyclopropane-1-carboxylic acid synthase 7 (ACS7) by repressing ethylene (ET) biosynthesis. The MYB30 loss-of-function mutant exhibits reduced submergence tolerance with a higher level of ET production, whereas the MYB30-overexpressing plant displays enhanced submergence tolerance and repressed ET production. The coding gene of ACS7 might be a direct target of MYB30 during the submergence response. MYB30 binds to the promoter of ACS7 and represses its transcription. The ACS7 loss-of-function mutant with defect in ET biosynthesis displays enhanced submergence tolerance, whereas plants overexpressing ACS7 exhibit a submergence-sensitive phenotype. Genetic analysis shows that ACS7 functions downstream of MYB30 in both ET biosynthesis and submergence response. Taken together, our work revealed a novel transcriptional regulation that modulates submergence response in plants.
Integrated genetic and metabolic characterization of Latin American cassava (Manihot esculenta) germplasm
Authors: Perez-Fons Laura , Ovalle Tatiana Maria , Drapal Margit , Ospina Maria Alejandra , Gkanogiannis Anestis , Bohorquez-Chaux Adriana , Becerra Lopez-Lavalle Luis Augusto , Fraser Paul David
Published: May 2023

Cassava (Manihot esculenta Crantz) is an important staple crop for food security in Africa and South America. The present study describes an integrated genomic and metabolomic approach to the characterization of Latin American cassava germplasm. Classification based on genotyping correlated with the leaf metabolome and indicated a key finding of adaption to specific eco-geographical environments. In contrast, the root metabolome did not relate to genotypic clustering, suggesting the different spatial regulation of this tissue's metabolome. The data were used to generate pan-metabolomes for specific tissues, and the inclusion of phenotypic data enabled the identification of metabolic sectors underlying traits of interest. For example, tolerance to whiteflies (Aleurotrachelus socialis) was not linked directly to cyanide content but to cell wall–related phenylpropanoid or apocarotenoid content. Collectively, these data advance the community resources and provide valuable insight into new candidate parental breeding materials with traits of interest directly related to combating food security.
The effect of IHAPIM program on health perceptions and health responsibilities of immigrant men: a randomized controlled trial
Authors: Korkmaz Mehmet , Avcı Iknur Aydın
Published: May 2023

Background

Health promotion interventions for immigrant health are generally directed toward women and youth. There is no program specific to migrant male in the global and national literature to protect, improve and promote their health. The aim of this study was to examine the effect of the Increasing Health Awareness of Immigrant Men (IHAPIM) program on health perceptions, health responsibilities, perceived stress level, attitudes toward utilizing health care services and the types of coping strategies of immigrant male.

Methods

Researchers applied the short-term IHAPIM program experimental group for 5 weeks. This study was held in the two districts where predominantly immigrants live. The immigrant male’s health perceptions, health responsibilities, perceived stress level, attitudes toward utilizing health care services and the types of coping strategies measured before and after 3 months of the IHAPIM program was performed.

Results

The study results showed that the levels of health perceptions, health responsibilities and the types of coping strategies of immigrant male were significantly different between the two study groups.

Conclusions

At the end of the study, the experimental group showed improvement in measures of the health perceptions, health responsibilities, attitudes toward utilizing health care services, the types of coping strategies and perceived stress level of male decreased. Nursing interventions specific to immigrant male and sensitive to their language have led to positive changes in the health variables of immigrant male.
Effect of psychological factors on COVID-19 vaccine hesitancy
Authors: Kim Hee Jin , Kim Eun , Han Doug Hyun
Published: May 2023

Background

Vaccine hesitancy can prevent full immunization against coronavirus infectious disease-19 (COVID-19). We hypothesized that multiple factors, including an individual’s personality and psychological factors, are associated with vaccine hesitancy.

Methods

A total of 275 non-vaccinated individuals were recruited for this study. Participants completed a self-report questionnaire including sociodemographic factors, health status, COVID-19 literacy and psychological factors (depressive symptoms, generalized anxiety, somatization, illness anxiety, temperament and character). In a hierarchical logistic regression analysis, a discrete set of hierarchical variables with vaccine acceptance or hesitancy as the dependent variable was added to the demographic factors for Model 1; Model 1 + health status for Model 2; Model 2 + COVID-19 literacy for Model 3 and Model 3 + psychological factors for Model 4.

Results

Models 3 and 4 could predict vaccine hesitancy. High scores on the Generalized Anxiety Disorder-7 and the Illness Attitude Scale, low confidence, low collective responsibility and low reward dependence were risk factors for vaccine hesitancy.

Conclusions

The present study demonstrates that psychological factors play critical roles in vaccine hesitancy. In addition to conventional policies that emphasize COVID-19 vaccines’ safety and efficacy and the collective benefits of vaccination, a more individualized approach that considers an individual’s emotions and personality is necessary.
ASSESSING BODY DOSE RATE CONSTANT AND EFFECTIVE BODY ABSORPTION FACTOR IN TAIWANESE REFERENCE PHANTOMS
Authors: Hung Shih-Yen , Luzhbin Dmytro , Chang Shu-Jun , Chao Max Min , Wu Jay
Published: May 2023

The self-attenuation of a patient’s body is an important factor in nuclear medicine for designing radiation shielding. Taiwanese reference man (TRM) and Taiwanese reference woman (TRW) were constructed to simulate the body dose rate constant and the effective body absorption factor for 18F-FDG, 131I-NaI and 99mTc-MIBI using the Monte Carlo technique. For TRM, the maximum body dose rate constants for 18F-FDG, 131I-NaI and 99mTc-MIBI were 1.26 × 10−1, 4.89 × 10−2 and 1.76 × 10−2 mSv-m2/GBq-h, respectively, at heights of 110, 110 and 100 cm. For TRW, the results were 1.23 × 10−1, 4.75 × 10−2 and 1.68 × 10−2 mSv-m2/GBq-h at heights of 100, 100 and 90 cm. The effective body absorption factors were 32.6, 36.7 and 46.2% for TRM and 34.2, 38.5 and 48.6% for TRW. Regional reference phantoms along with the derived body dose rate constant and effective body absorption factor should be used for determining regulatory secondary standards in nuclear medicine.
Antisocial behavior is associated with reduced frontoparietal network efficiency in youth
Authors: Tillem Scott , Dotterer Hailey L , Goetschius Leigh G , Lopez-Duran Nestor , Mitchell Colter , Monk Christopher S , Hyde Luke W
Published: May 2023

Youth antisocial behavior (AB) is associated with deficits in socioemotional processing, reward and threat processing and executive functioning. These deficits are thought to emerge from differences in neural structure, functioning and connectivity, particularly within the default, salience and frontoparietal networks. However, the relationship between AB and the organization of these networks remains unclear. To address this gap, the current study applied unweighted, undirected graph analyses to resting-state functional magnetic resonance imaging data in a cohort of 161 adolescents (95 female) enriched for exposure to poverty, a risk factor for AB. As prior work indicates that callous-unemotional (CU) traits may moderate the neurocognitive profile of youth AB, we examined CU traits as a moderator. Using multi-informant latent factors, AB was found to be associated with less efficient frontoparietal network topology, a network associated with executive functioning. However, this effect was limited to youth at low or mean levels of CU traits, indicating that these neural differences were specific to those high on AB but not CU traits. Neither AB, CU traits nor their interaction was significantly related to default or salience network topologies. Results suggest that AB, specifically, may be linked with shifts in the architecture of the frontoparietal network.
Neurocognitive functioning in comorbid insomnia and sleep apnea patients is better after positive airway pressure therapy, but worse after cognitive behavioral therapy for insomnia: exploratory analysis of cognitive outcomes from the Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea study
Authors: Turner Arlener D , Ong Jason C , Jones Alex L , Tu Alice , Salanitro Matthew , Crawford Megan R
Published: May 2023

Study Objectives

Neurocognitive impairments in comorbid insomnia and sleep apnea (COMISA) are not well documented. We explored neurocognitive functioning and treatment effects in individuals with COMISA as an ancillary study to a randomized clinical trial.

Methods

Participants with COMISA (n = 45; 51.1% female; mean age = 52.07 ± 13.29 years), from a 3-arm randomized clinical trial combining cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) concurrently (CBT-I+PAP) or sequentially, completed neurocognitive testing at baseline, and post-treatment. Using Bayesian linear mixed models, we estimated effects of CBT-I, PAP, or CBT-I+PAP, compared to baseline, and CBT-I+PAP compared to PAP on 12 metrics across five cognitive domains.

Results

This COMISA sample had worse neurocognitive performance at baseline than reported for insomnia, sleep apnea, and controls in the literature, though short-term memory and psychomotor speed performance appears intact. When comparing PAP to baseline, performance on all measures was better after treatment. Performance after CBT-I was worse compared to baseline, and only performance in attention/vigilance, executive functioning via Stroop interference and verbal memory was better with moderate–high effect sizes and moderate probability of superiority (61–83). Comparisons of CBT-I+PAP to baseline generated results similar to PAP and comparing CBT-I+PAP to PAP revealed superior performance in only attention/vigilance via psychomotor vigilance task lapses and verbal memory for PAP.

Conclusions

Treatment combinations involving CBT-I were associated with poorer neurocognitive performance. These potentially temporary effects may stem from sleep restriction, a component of CBT-I often accompanied by initially reduced total sleep time. Future studies should examine long-term effects of individual and combined COMISA treatment pathways to inform treatment recommendations.

Clinical trial

This was an ancillary study from a clinical trial (Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS), which was preregistered at www.clinicaltrials.gov (NCT01785303)).
Effects of Host and Weather Factors on the Growth Rate of Septoria nodorum Blotch Lesions on Winter Wheat
Authors: Adhikari Urmila , Brown James , Ojiambo Peter S. , Cowger Christina
Published: May 2023

Septoria nodorum blotch (SNB), caused by Parastagonospora nodorum, is a major disease of winter wheat that occurs frequently in the central and southeastern United States. Quantitative resistance to SNB in wheat is determined by various disease resistance components and their interaction with environmental factors. A study was conducted in North Carolina from 2018 to 2020 to characterize SNB lesion size and growth rate and to quantify the effects of temperature and relative humidity on lesion expansion in winter wheat cultivars with different levels of resistance. Disease was initiated in the field by spreading P. nodorum-infected wheat straw in experimental plots. Cohorts (groups of foliar lesions arbitrarily selected and tagged as an observational unit) were sequentially selected and monitored throughout each season. Lesion area was measured at regular intervals, and weather data were collected using in-field data loggers and the nearest weather stations. Final mean lesion area was approximately seven times greater on susceptible than on moderately resistant cultivars, and lesion growth rate was approximately four times higher on susceptible than on moderately resistant cultivars. Across trials and cultivars, temperature had a strong effect of increasing lesion growth rates ( P < 0.001), while relative humidity had no significant effect ( P = 0.34). Lesion growth rate declined slightly and steadily over the duration of cohort assessment. Our results demonstrate that restricting lesion growth is an important component of SNB resistance in the field and suggest that the ability to limit lesion size may be a useful breeding goal.
Telemedicine and remote monitoring in cystic fibrosis
Authors: Edmondson Claire , Lechtzin Noah
Published: May 2023

Purpose of review

Guidelines for cystic fibrosis (CF) care recommend multidisciplinary teams see patients at least quarterly with frequent measurement of spirometry and collection of respiratory cultures. This can be burdensome for people with CF, particularly if they live far from a specialized care center. This has led to an interest in telehealth coupled with remote monitoring. We review the recent literature on these topics for people with CF.

Recent findings

The COVID-19 pandemic accelerated a move toward remote delivery of CF care and multiple recent publications have reported on the feasibility of telehealth, remote spirometry, remote collection of respiratory cultures, adherence monitoring, cough assessment, symptom monitoring and activity tracking. Useful data can be obtained and both clinicians and patients have favorable opinions about remote delivery of healthcare, though the impact on clinical outcomes is not yet known.

Telehealth and remote monitoring for people with CF is feasible and has grown in use, though it is too early to know how prominently these approaches will fit into routine care for CF.
Role of inguinal and pelvic lymph node dissection for primary urethral carcinoma: a systematic review
Authors: Kochergin Maxim , Fahmy Omar , Asimakopoulos Anastasios D. , Gakis Georgios
Published: May 2023

Purpose of review

Primary urethral carcinoma (PUC) is a rare urologic tumor. There is limited evidence on this entity. This review summarizes the existing evidence on lymph node dissection (LND) in patients with PUC.

Recent findings

We performed a systematic search of the PubMed, EMBASE, and Web of Science databases to evaluate the impact of inguinal and pelvic LND on the oncological outcomes of PUC and to identify indications for this procedure.

Results

Three studies met the inclusion criteria. The cancer detection rate in clinically nonpalpable inguinal lymph node (cN0) was 9% in men and 25% in women. In clinically palpable lymph node (cN+), the malignancy rate was 84% and 50% in men and women, respectively. Overall cancer detection rate in pelvic lymph nodes in patients with cN0 was 29%. Based on tumor stage, the detection rate was 11% in cT1–2 N0 and 37% in cT3–4 N0. Nodal disease was associated with higher recurrence and worse survival. Pelvic LND seems to improve overall survival for patients with LND regardless of the location or stage of lymph nodes. Inguinal LND improved overall survival only in patients with palpable lymph nodes. Inguinal LND had no survival benefit in patients with nonpalpable lymph nodes.

The available, albeit scarce, data suggest that inguinal LND derives the highest benefit in women and in patients with palpable inguinal nodes, whereas the benefit of pelvic LND seems to be more pronounced across all stages of invasive PUC. Prospective studies are urgently needed to further address the prognostic benefit of locoregional LND in PUC.
Profile of injuries in recent warfare
Authors: Chiniard Thomas , Boutonnet Mathieu , Duron Sandrine , Bertho Kilian , Travers Stéphane , Pasquier Pierre
Published: May 2023

BACKGROUND

The epidemiology of French military severe trauma patients injured during recent military operations remains poorly described, even if French operations, casualties sustained, and care rendered in a different trauma system are distinct from others. This study aimed at describing the characteristics of these patients upon arrival at hospital in France and during hospital stay.

METHODS

This 5-year retrospective cohort study included all French military servicemen injured during military operations and admitted to the intensive care unit. Data on the characteristics upon arrival at the Percy hospital in France and during hospital stay were obtained from a national civilian trauma registry.

RESULTS

Of 1,990 military trauma patients injured in military operations, 39 were finally admitted to the intensive care unit of the Percy hospital and included in the analysis. Traumas were related to battle injuries and nonbattle injuries in 27 and 12 patients, respectively. Ninety-eight wounds were described: torso (n = 32), limbs (n = 32), head and neck (n = 25), and spine (n = 9). The mechanism of injury was explosion in 19 patients, gunshot wound in 8 patients, motor vehicular crash in 7 patients, or other mechanisms in 5 patients. The median Injury Severity Score was 25.5 (interquartile range, 14–34).

CONCLUSION

This study highlights the small number of military severe trauma patients injured in recent warfare and their characteristics. The use of dedicated systemic military trauma registries could improve the specific epidemiological knowledge on recent warfare and help better prepare for future conflicts that may include major engagements and large-scale combat operations.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level V.
Sleep is required for neural network plasticity in the jellyfishCassiopea
Authors: Abrams Michael J. , Zhang Lilian , Emster Konnor von , Lee Brandon H. , Zeigler Hannah , Jain Tanya , Jafri Ali , Chen Zhiqin , Harland Richard M.
Published: May 2023

Sleep in animals plays roles that appear specific to the brain, including synaptic homeostasis [1], neurotransmitter regulation [2], cellular repair [3], memory consolidation [4], and neural plasticity [5,6]. Would any of these functions of sleep be relevant to an animal without a brain? The upside-down jellyfishCassiopea xamachana, like other cnidarians, lacks a centralized nervous system, yet the animal sleeps [7]. By tracking the propensity of the radially spaced ganglia to initiate muscle contractions over several days we determined how neural activity changes between sleep and wake in a decentralized nervous system. Ganglia-network sleep/ wake activity patterns range from being highly specialized to a few ganglia, to being completely unspecialized. Ganglia specialization also changes over time, indicating a high degree of plasticity in the neural network. The ganglia that lead activity can persist or switch between sleep/wake transitions, signifying a level of local control of the behavioral state in a decentralized nervous system. Following sleep deprivation, ganglia usage becomes far more sleep specialized, demonstrating reduced network plasticity. Together, these findings identify a novel behavioral control system that is decentralized and yet displays temporal specialization and centralization, and show a role for sleep in maintaining neural network plasticity, revealing a conserved function of sleep in this brain-less animal.
Protein interactome homeostasis through an N-recognin E3 ligase is a vulnerability in aneuploid cancer
Authors: Kathiresan Meena , Animesh Sambhavi , Morris Robert , Kreuzer Johannes , Patra Krushna C. , Shi Lei , Merritt Joshua , Yin Xunqin , Benes Cyril H. , Bardeesy Nabeel , Haas Wilhelm
Published: May 2023

Aneuploidy and resulting gene copy number alterations (CNAs) are important hallmarks of human cancers. Since CNAs are not associated with dosage compensation in mRNA expression, cancer cells with a high CNA burden must harbor mechanisms to mitigate proteotoxic stress resulting from stoichiometric imbalance and accumulation of unfolded proteins (1). Here, we show that aneuploid human cancer cells exhibit discordance between CNAs and protein levels due to compensation at the proteome level, mainly concerning multi-protein complexes. Moreover, we identify the N-recognin ubiquitin ligase UBR4 as a critical mediator of protein interactome homeostasis that is essential for viability, specifically in highly aneuploid cancersin vitroandin vivo. UBR4 prunes the proteome to ensure the balanced expression of protein complex members. Inactivation of UBR4 in highly aneuploid cancer cells causes a convergence of copy number and protein levels and induces proteotoxic stress pathways. UBR4 inhibition may present a broadly applicable therapeutic strategy for cancer and other diseases driven by aneuploidy.

One-Sentence Summary

The N-recognin ubiquitin ligase UBR4 as a critical mediator of protein interactome homeostasis that is essential for viability in aneuploid cancers.
Ribosomal dysregulation: A conserved pathophysiological mechanism in human depression and mouse chronic stress
Authors: Zhang Xiaolu , Eladawi Mahmoud Ali , Ryan William George , Fan Xiaoming , Prevoznik Stephen , Devale Trupti , Ramnani Barkha , Malathi Krishnamurthy , Sibille Etienne , Mccullumsmith Robert , Tomoda Toshifumi , Shukla Rammohan
Published: May 2023

The underlying biological mechanisms that contribute to the heterogeneity of major depressive disorder (MDD) presentation remain poorly understood, highlighting the need for a conceptual framework that can explain this variability and bridge the gap between animal models and clinical endpoints. Here, we hypothesize that comparative analysis of molecular data from different experimental systems of chronic stress and MDD has the potential to provide insight into these mechanisms and address this gap. Thus, we compared transcriptomic profiles of brain tissue from postmortem MDD subjects and from mice exposed to chronic variable stress (CVS) to identify orthologous genes. Ribosomal protein genes (RPGs) were downregulated, and associated RP-pseudogenes were upregulated in both conditions. Analysis across independent cohorts confirmed that this dysregulation was specific to the prefrontal cortex of both species. A seeded gene co-expression analysis using altered RPGs common between the MDD and CVS groups revealed that downregulated RPGs homeostatically regulated the synaptic changes in both groups through a RP-pseudogene-driven mechanism.In-vitroandin-silicoanalysis further demonstrated that the inverse RPG/RP-pseudogene association was a glucocorticoid-driven endocrine response to stress that was reversed during remission from MDD. This study provides the first evidence that ribosomal dysregulation during stress is a conserved phenotype in human MDD and CVS exposed mouse. Our results establish a foundation for the hypothesis that stress-induced alterations in RPGs and, consequently, ribosomes contribute to the synaptic dysregulation underlying MDD and chronic stress-related mood disorders. We discuss a ribosome-dependent mechanism for the variable presentations of depression and other mood disorders.

Significance Statement

The presented study highlights the pressing need for a connection between animal models of depression and clinical endpoints. The lack of concordance between these two areas has hindered our understanding of MDD’s biological underpinnings. The study’s hypothesis that orthologous gene from experimental systems of chronic stress and MDD can bridge this gap is a major advance in this field. The study indicates that dysregulation of ribosomes in the synapse is a common feature in both human MDD and mice exposed to CVS. This dysregulation is a response to endocrine disturbances and is driven by mechanisms that involve pseudogenes. These findings support the hypothesis that stress-induced alterations in RPGs and, consequently, ribosomes may contribute to the variable presentations of depression.
Adsorption of respiratory syncytial virus (RSV), rhinovirus, SARS-CoV-2, and F+ bacteriophage MS2 RNA onto wastewater solids from raw wastewater
Authors: Roldan-Hernandez Laura , Boehm Alexandria B.
Published: May 2023

Despite the wide adoption of wastewater surveillance, more research is needed to understand the fate and transport of viral genetic markers in wastewater. This information is essential for the interpretation of wastewater surveillance data and the development of mechanistic models that link wastewater measurements to the number of individuals shedding virus. In this study, we examined the solid-liquid partitioning behavior of four viruses in wastewater: SARS-CoV-2, respiratory syncytial virus (RSV), rhinovirus (RV), and F+ coliphage/MS2. We used two approaches to achieve this: we (1) conducted laboratory partitioning experiments using lab-grown viruses and (2) examined the distribution of endogenous viruses in wastewater. Partition experiments were conducted at 4°C and 22°C; wastewater samples were spiked with varying concentrations of each virus and stored for three hours to allow the system to equilibrate. Solids and liquids were separated via centrifugation and viral RNA concentrations were quantified using reverse-transcription-digital droplet PCR (RT-ddPCR). For the distribution experiment, wastewater samples were collected from six wastewater treatment plants and processed without spiking exogenous viruses; viral RNA concentrations were measured in wastewater solids and liquid. Overall, RNA concentrations were higher in solids than the liquid fraction of wastewater by approximately 3–4 orders of magnitude. Partition coefficients (KF) from laboratory experiments were determined using the Freundlich model and ranged from 2,000–270,000 ml·g-1across viruses and temperature conditions. Distribution coefficients (Kd) determined from endogenous wastewater viruses were consistent with results from laboratory experiments.Further research is needed to understand how virus and wastewater characteristics might influence the partition of viral genetic markers in wastewater.

Synopsis

We examined the solid-liquid partitioning behavior of SARS-CoV-2, RSV, RV, and F+coliphage/MS2 RNA in wastewater influent. Overall, partition/distribution coefficients were similar across viruses and temperature conditions.
Dimensional clinical phenotyping using post-mortem brain donor medical records: Association with neuropathology
Authors: Vogelgsang Jonathan S. , Dan Shu , Lally Anna P. , Chatigny Michael , Vempati Sangeetha , Abston Joshua , Durning Peter T. , Oakley Derek H. , McCoy Thomas H. , Klengel Torsten , Berretta Sabina
Published: May 2023

INTRODUCTION

Transdiagnostic dimensional phenotypes are essential to investigate the relationship between continuous symptom dimensions and pathological changes. This is a fundamental challenge to postmortem work, as assessment of newly developed phenotypic concepts needs to rely on existing records.

METHODS

We adapted well-validated methodologies to compute NIMH research domain criteria (RDoC) scores using natural language processing (NLP) from electronic health records (EHRs) obtained from post-mortem brain donors and tested whether RDoC cognitive domain scores were associated with hallmark Alzheimer’s disease (AD) neuropathological measures.

RESULTS

Our results confirm an association of EHR-derived cognitive scores with hallmark neuropathological findings. Notably, higher neuropathological load, particularly neuritic plaques, was associated with higher cognitive burden scores in the frontal (ß=0.38, p=0.0004), parietal (ß=0.35, p=0.0008), temporal (ß=0.37, p=0. 0004) and occipital (ß=0.37, p=0.0003) lobes.

DISCUSSION

This proof of concept study supports the validity of NLP-based methodologies to obtain quantitative measures of RDoC clinical domains from postmortem EHR.
Shigella O-specific polysaccharide functional IgA responses mediate protection against shigella infection in an endemic high-burden setting
Authors: Bernshtein Biana , Kelly Meagan , Cizmeci Deniz , Zhiteneva Julia A. , Macvicar Ryan , Kamruzzaman Mohammad , Bhuiyan Taufiqur R. , Chowdhury Fahima , Khan Ashraful Islam , Qadri Firdausi , Charles Richelle C. , Xu Peng , Kováč Pavol , Kaminski Robert W. , Alter Galit , Ryan Edward T.
Published: May 2023

Shigella is the second leading cause of diarrheal disease-related death in young children in low and middle income countries. The mechanism of protection against shigella infection and disease in endemic areas is uncertain. While historically LPS-specific IgG titers have been associated with protection in endemic settings, emerging deeper immune approaches have recently elucidated a protective role for IpaB-specific antibody responses in a controlled human challenge model in North American volunteers. To deeply interrogate potential correlates of immunity in areas endemic for shigellosis, here we applied a systems approach to analyze the serological response to shigella across endemic and non-endemic populations. Additionally, we analyzed shigella-specific antibody responses over time in the context of endemic resistance or breakthrough infections in a high shigella burden location. Individuals with endemic exposure to shigella possessed broad and functional antibody responses across both glycolipid and protein antigens compared to individuals from non-endemic regions. In high shigella burden settings, elevated levels of OSP-specific FcαR binding antibodies were associated with resistance to shigellosis. OSP-specific FcαR binding IgA found in resistant individuals activated bactericidal neutrophil functions including phagocytosis, degranulation and reactive oxygen species production. Moreover, IgA depletion from resistant serum significantly reduced binding of OSP-specific antibodies to FcαR and antibody mediated activation of neutrophils and monocytes. Overall, our findings suggest that OSP-specific functional IgA responses contribute to protective immunity against shigella infection in high-burden settings. These findings will assist in the development and evaluation of shigella vaccines.
An inimitable proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site VFAQ on Spike protein along with furin cleavage site makes SARS-CoV-2 unique
Authors: Pandya Medha , shukla Dhruvam , Shah Sejal , Das Kajari , Dave Sushma , Das Jayashankar
Published: May 2023

A novel coronavirus (2019-nCoV) or Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) that affects humans has been discovered in Wuhan, China, in 2019. Its genome has been sequenced, and the genetic data was quickly made public. We discovered a novel proprotein convertase subtilisin kexin-9 (PCSK9) cleavage site in the Spike protein of the 2019-nCoV. The recent research also demonstrates that the previously found proprotein convertase 3 (PC3) or furin cleavage site, which was assumed to be unique, is already present in animal corona viruses. In this article, we suggest that the combination of the both proprotein convertase PC3 cleavage site and the PCSK9 site renders SARS-CoV-2 unique in terms of the pathogenicity, potential functional effects, and implications for the development of antiviral drugs.
Brain cell type specific proteomics approach to discover pathological mechanisms in the childhood CNS disorder mucolipidosis type IV
Authors: Sangster Madison , Shahriar Sanjid , Niziolek Zachary , Carisi Maria Carla , Lewandowski Michael , Budnik Bogdan , Grishchuk Yulia
Published: May 2023

1 Mucolipidosis IV (MLIV) is an ultra-rare, recessively inherited lysosomal disorder resulting from inactivating mutations inMCOLN1, the gene encoding the lysosomal cation channel TRPML1. The disease primarily affects the central nervous system (CNS) and manifests in the first year with cognitive and motor developmental delay, followed by a gradual decline in neurological function across the second decade of life, blindness, and premature death in third or fourth decades. Brain pathology manifestations in MLIV are consistent with hypomyelinating leukodystrophy with brain iron accumulation. Presently, there are no approved or investigational therapies for MLIV, and pathogenic mechanisms remain largely unknown. The MLIV mouse model,Mcoln1-/-mice, recapitulates all major manifestations of the human disease. Here, to better understand the pathological mechanisms in the MLIV brain, we performed cell type specific LC-MS/MS proteomics analysis in the MLIV mouse model and reconstituted molecular signatures of the disease in either freshly isolated populations of neurons, astrocytes, oligodendrocytes, and neural stem cells, or whole tissue cortical homogenates from young adult symptomaticMcoln1-/-mice. Our analysis confirmed on the molecular level major histopathological hallmarks of MLIV universally present inMcoln1-/-tissue and brain cells, such as hypomyelination, lysosomal dysregulation, and impaired metabolism of lipids and polysaccharides. Importantly, pathway analysis in brain cells revealed mitochondria-related alterations in allMcoln1-/-brain cells, except oligodendrocytes, that was not possible to resolve in whole tissue. We also report unique proteome signatures and dysregulated pathways for each brain cell population used in this study. These data shed new light on cell-intrinsic mechanisms of MLIV and provide new insights for biomarker discovery and validation to advance translational studies for this disease.
Integrative multi-dimensional characterization of striatal projection neuron heterogeneity in adult brain
Authors: Gayden Jenesis , Puig Stephanie , Srinivasan Chaitanya , Phan BaDoi N. , Abdelhady Ghada , Buck Silas A. , Gamble Mackenzie C. , Tejeda Hugo A. , Dong Yan , Pfenning Andreas R. , Logan Ryan W. , Freyberg Zachary
Published: May 2023

Striatal projection neurons (SPNs) are traditionally segregated into two subpopulations expressing dopamine (DA) D1-like or D2-like receptors. However, this dichotomy is challenged by recent evidence. Functional and expression studies raise important questions: do SPNs co-express different DA receptors, and do these differences reflect unique striatal spatial distributions and expression profiles? Using RNAscope in mouse striatum, we report heterogenous SPN subpopulations distributed across dorsal-ventral and rostral-caudal axes. SPN subpopulations co-express multiple DA receptors, including D1and D2(D1/2R) and D1and D3. Our integrative approach using single-nuclei multi-omics analyses provides a simple consensus to describe SPNs across diverse datasets, connecting it to complementary spatial mapping. Combining RNAscope and multi-omics shows D1/2R SPNs further separate into distinct subtypes according to spatial organization and conserved marker genes. Each SPN cell type contributes uniquely to genetic risk for neuropsychiatric diseases. Our results bridge anatomy and transcriptomics to offer new understandings of striatal neuron heterogeneity.
Prophage rates in the human microbiome vary by body site and host health
Authors: Inglis Laura K. , Roach Michael J. , Edwards Robert A.
Published: May 2023

Phages integrated into a bacterial genome–called prophages–continuously monitor the health of the host bacteria to determine when to escape the genome, protect their host from other phage infections, and may provide genes that promote bacterial growth. Prophages are essential to almost all microbiomes, including the human microbiome. However, most human microbiome studies focus on bacteria, ignoring free and integrated phages, so we know little about how these prophages affect the human microbiome. We compared the prophages identified in 11,513 bacterial genomes isolated from human body sites to characterise prophage DNA in the human microbiome. Here, we show that prophage DNA comprised an average of 1-5% of each bacterial genome. The prophage content per genome varies with the isolation site on the human body, the health of the human, and whether the disease was symptomatic. The presence of prophages promotes bacterial growth and sculpts the microbiome. However, the disparities caused by prophages vary throughout the body.