bluuebunny/crossref_metadata_2025 huggingface dataset:
Wind and Turbulence Observations With the Mars Microphone on Perseverance
Authors: Stott Alexander E. , Murdoch Naomi , Gillier Martin , Banfield Don , Bertrand Tanguy , Chide Baptiste , De la Torre Juarez Manuel , Hueso Ricardo , Lorenz Ralph , Martinez German , Munguira Asier , Mora Sotomayor Luis , Navarro Sara , Newman Claire , Pilleri Paolo , Pla‐Garcia Jorge , Rodriguez‐Manfredi Jose Antonio , Sanchez‐Lavega Agustin , Smith Michael , Viudez Moreiras Daniel , Williams Nathan , Maurice Sylvestre , Wiens Roger C. , Mimoun David
Published: May 2023

We utilize SuperCam's Mars microphone to provide information on wind speed and turbulence at high frequencies on Mars. To do so, we first demonstrate the sensitivity of the microphone signal level to wind speed, yielding a power law dependence. We then show the relationship between the microphone signal level and pressure, air and ground temperatures. A calibration function is constructed using Gaussian process regression (a machine learning technique) taking the microphone signal and air temperature as inputs to produce an estimate of the wind speed. This provides a high rate wind speed estimate on Mars, with a sample every 0.01 s. As a result, we determine the fast fluctuations of the wind at Jezero crater which highlights the nature of wind gusts over the Martian day. To analyze the turbulent behavior of this wind speed estimate, we calculate its normalized standard deviation, known as gustiness. To characterize the behavior of this high frequency turbulent intensity at Jezero crater, correlations are shown between the evaluated gustiness statistic and pressure drop rates/sizes, temperature and energy fluxes. This has implications for future atmospheric models on Mars, taking into account turbulence at the finest scales.
Autologous mesenchymal stem cells offer a new paradigm for salivary gland regeneration
Authors: Marinkovic Milos , Tran Olivia N. , Wang Hanzhou , Abdul-Azees Parveez , Dean David D. , Chen Xiao-Dong , Yeh Chih-Ko
Published: May 2023

Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the “immuno-privileged” status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient’s immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.
Genetic architecture of brain age and its causal relations with brain and mental disorders
Authors: Leonardsen Esten H. , Vidal-Piñeiro Didac , Roe James M. , Frei Oleksandr , Shadrin Alexey A. , Iakunchykova Olena , de Lange Ann-Marie G. , Kaufmann Tobias , Taschler Bernd , Smith Stephen M. , Andreassen Ole A. , Wolfers Thomas , Westlye Lars T. , Wang Yunpeng
Published: May 2023

The difference between chronological age and the apparent age of the brain estimated from brain imaging data—the brain age gap (BAG)—is widely considered a general indicator of brain health. Converging evidence supports that BAG is sensitive to an array of genetic and nongenetic traits and diseases, yet few studies have examined the genetic architecture and its corresponding causal relationships with common brain disorders. Here, we estimate BAG using state-of-the-art neural networks trained on brain scans from 53,542 individuals (age range 3–95 years). A genome-wide association analysis across 28,104 individuals (40–84 years) from the UK Biobank revealed eight independent genomic regions significantly associated with BAG (p < 5 × 10−8) implicating neurological, metabolic, and immunological pathways – among which seven are novel. No significant genetic correlations or causal relationships with BAG were found for Parkinson’s disease, major depressive disorder, or schizophrenia, but two-sample Mendelian randomization indicated a causal influence of AD (p = 7.9 × 10−4) and bipolar disorder (p = 1.35 × 10−2) on BAG. These results emphasize the polygenic architecture of brain age and provide insights into the causal relationship between selected neurological and neuropsychiatric disorders and BAG.
A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial to verify the efficacy and safety of ansofaxine (LY03005) for major depressive disorder
Authors: Mi Weifeng , Di Xiaolan , Wang Yiming , Li Huafang , Xu Xiufeng , Li Lehua , Wang Huaning , Wang Guoqiang , Zhang Kerang , Tian Feng , Luo Jiong , Yang Chanjuan , Zhou Yunfei , Xie Shiping , Zhong Hua , Wu Bin , Yang Dong , Chen Zhenhua , Li Yi , Chen Jindong , Lv Shuyun , Yi Qizhong , Jiang Zhiwei , Tian Jingwei , Zhang Hongyan
Published: May 2023

Major depressive disorder (MDD) is the most prevalent form of depression and is becoming a great challenge for public health and medical practice. Although first-line antidepressants offer therapeutic benefits, about 35% of depressed patients are not adequately treated, creating a substantial unmet medical need. A multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial was conducted in patients with MDD in China to assess the efficacy and safety of ansofaxine (LY03005), a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. Eligible 588 MDD patients were included and randomly assigned (1:1:1) to 8-week treatment with ansofaxine 80 mg/day(n = 187), ansofaxine 160 mg/day(n = 186), or placebo(n = 185). The primary efficacy endpoint was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score change from baseline to the end of the study. Safety indexes included adverse events, vital signs, physical examination, laboratory tests, 12-lead electrocardiogram (ECG), and evaluation of suicide tendency and sexual function. Significant differences were found in mean changes in MADRS total score at week 8 in the two ansofaxine groups (80 mg, −20.0; 160 mg, −19.9) vs. placebo (−14.6; p < 0.0001). All doses of ansofaxine were generally well-tolerated. Treatment-emergent adverse events (TEAEs) were reported by 137 (74.46%) patients in ansofaxine 80 mg group, 144 (78.26%) patients in ansofaxine 160 mg and 125 (67.93%) patients in the placebo group. The incidence of treatment-related adverse events (TRAEs) was 59.2% (109 patients), 65.22% (120 patients) in the 80, 160 mg ansofaxine groups, and 45.11% (83 patients) in the placebo group. The initial results of this trial indicate that ansofaxine at both the 80 mg/day and 160 mg/day was effective and safe in adult patients with MDD. ClinicalTrials.gov Identifier: NCT04853407.
Temporal dynamics in mental health symptoms and loneliness during the COVID-19 pandemic in a longitudinal probability sample: a network analysis
Authors: Odenthal Michael , Schlechter Pascal , Benke Christoph , Pané-Farré Christiane A.
Published: May 2023

Figuring out which symptoms are central for symptom escalation during the COVID-19 pandemic is important for targeting prevention and intervention. Previous studies have contributed to the understanding of the course of psychological distress during the pandemic, but less is known about key symptoms of psychological distress over time. Going beyond a pathogenetic pathway perspective, we applied the network approach to psychopathology to examine how psychological distress unfolds in a period of maximum stress (pre-pandemic to pandemic onset) and a period of repeated stress (pandemic peak to pandemic peak). We conducted secondary data analyses with the Understanding Society data (N = 17,761), a longitudinal probability study in the UK with data before (2019), at the onset of (April 2020), and during the COVID-19 pandemic (November 2020 & January 2021). Using the General Health Questionnaire and one loneliness item, we computed three temporal cross-lagged panel network models to analyze psychological distress over time. Specifically, we computed (1) a pre-COVID to first incidence peak network, (2) a first incidence peak to second incidence peak network, and (3) a second incidence peak to third incidence peak network. All networks were highly consistent over time. Loneliness and thinking of self as worthless displayed a high influence on other symptoms. Feeling depressed and not overcoming difficulties had many incoming connections, thus constituting an end-product of symptom cascades. Our findings highlight the importance of loneliness and self-worth for psychological distress during COVID-19, which may have important implications in therapy and prevention. Prevention and intervention measures are discussed, as single session interventions are available that specifically target loneliness and worthlessness to alleviate mental health problems.
Artificial Hsp104-mediated systems for re-localizing protein aggregates
Authors: Fischbach Arthur , Johns Angela , Schneider Kara L. , Hao Xinxin , Tessarz Peter , Nyström Thomas
Published: May 2023

Spatial Protein Quality Control (sPQC) sequesters misfolded proteins into specific, organelle-associated inclusions within the cell to control their toxicity. To approach the role of sPQC in cellular fitness, neurodegenerative diseases and aging, we report on the construction of Hsp100-based systems in budding yeast cells, which can artificially target protein aggregates to non-canonical locations. We demonstrate that aggregates of mutant huntingtin (mHtt), the disease-causing agent of Huntington’s disease can be artificially targeted to daughter cells as well as to eisosomes and endosomes with this approach. We find that the artificial removal of mHtt inclusions from mother cells protects them from cell death suggesting that even large mHtt inclusions may be cytotoxic, a trait that has been widely debated. In contrast, removing inclusions of endogenous age-associated misfolded proteins does not significantly affect the lifespan of mother cells. We demonstrate also that this approach is able to manipulate mHtt inclusion formation in human cells and has the potential to be useful as an alternative, complementary approach to study the role of sPQC, for example in aging and neurodegenerative disease.
Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting
Authors: Ruffo Elisa , Butchy Adam A. , Tivon Yaniv , So Victor , Kvorjak Michael , Parikh Avani , Adams Eric L. , Miskov-Zivanov Natasa , Finn Olivera J. , Deiters Alexander , Lohmueller Jason
Published: May 2023

Chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors are engineered cell-surface receptors that sense a target antigen and respond by activating T cell receptor signaling or a customized gene program, respectively. Here, to expand the targeting capabilities of these receptors, we develop “universal” receptor systems for which receptor specificity can be directed post-translationally via covalent attachment of a co-administered antibody bearing a benzylguanine (BG) motif. A SNAPtag self-labeling enzyme is genetically fused to the receptor and reacts with BG-conjugated antibodies for covalent assembly, programming antigen recognition. We demonstrate that activation of SNAP-CAR and SNAP-synNotch receptors can be successfully targeted by clinically relevant BG-conjugated antibodies, including anti-tumor activity of SNAP-CAR T cells in vivo in a human tumor xenograft mouse model. Finally, we develop a mathematical model to better define the parameters affecting universal receptor signaling. SNAP receptors provide a powerful strategy to post-translationally reprogram the targeting specificity of engineered cells.
Candida expansion in the gut of lung cancer patients associates with an ecological signature that supports growth under dysbiotic conditions
Authors: Seelbinder Bastian , Lohinai Zoltan , Vazquez-Uribe Ruben , Brunke Sascha , Chen Xiuqiang , Mirhakkak Mohammad , Lopez-Escalera Silvia , Dome Balazs , Megyesfalvi Zsolt , Berta Judit , Galffy Gabriella , Dulka Edit , Wellejus Anja , Weiss Glen J. , Bauer Michael , Hube Bernhard , Sommer Morten O. A. , Panagiotou Gianni
Published: May 2023

Candida species overgrowth in the human gut is considered a prerequisite for invasive candidiasis, but our understanding of gut bacteria promoting or restricting this overgrowth is still limited. By integrating cross-sectional mycobiome and shotgun metagenomics data from the stool of 75 male and female cancer patients at risk but without systemic candidiasis, bacterial communities in high Candida samples display higher metabolic flexibility yet lower contributional diversity than those in low Candida samples. We develop machine learning models that use only bacterial taxa or functional relative abundances to predict the levels of Candida genus and species in an external validation cohort with an AUC of 78.6–81.1%. We propose a mechanism for intestinal Candida overgrowth based on an increase in lactate-producing bacteria, which coincides with a decrease in bacteria that regulate short chain fatty acid and oxygen levels. Under these conditions, the ability of Candida to harness lactate as a nutrient source may enable Candida to outcompete other fungi in the gut.
Mastering morphology of non-fullerene acceptors towards long-term stable organic solar cells
Authors: An Kang , Zhong Wenkai , Peng Feng , Deng Wanyuan , Shang Ying , Quan Huilei , Qiu Hong , Wang Cheng , Liu Feng , Wu Hongbin , Li Ning , Huang Fei , Ying Lei
Published: May 2023

Despite the rapid progress of organic solar cells based on non-fullerene acceptors, simultaneously achieving high power conversion efficiency and long-term stability for commercialization requires sustainable research effort. Here, we demonstrate stable devices by integrating a wide bandgap electron-donating polymer (namely PTzBI-dF) and two acceptors (namely L8BO and Y6) that feature similar structures yet different thermal and morphological properties. The organic solar cell based on PTzBI-dF:L8BO:Y6 could achieve a promising efficiency of 18.26% in the conventional device structure. In the inverted structure, excellent long-term thermal stability over 1400 h under 85 °C continuous heating is obtained. The improved performance can be ascribed to suppressed charge recombination along with appropriate charge transport. We find that the morphological features in terms of crystalline coherence length of fresh and aged films can be gradually regulated by the weight ratio of L8BO:Y6. Additionally, the occurrence of melting point decrease and reduced enthalpy in PTzBI-dF:L8BO:Y6 films could prohibit the amorphous phase to cluster, and consequently overcome the energetic traps accumulation aroused by thermal stress, which is a critical issue in high efficiency non-fullerene acceptors-based devices. This work provides insight into understanding non-fullerene acceptors-based organic solar cells for improved efficiency and stability.
In situ continuous Dopa supply by responsive artificial enzyme for the treatment of Parkinson’s disease
Authors: Fang Xiao , Yuan Meng , Zhao Fang , Yu Aoling , Lin Qianying , Li Shiqing , Li Huichen , Wang Xinyang , Yu Yanbin , Wang Xin , Lin Qitian , Lu Chunhua , Yang Huanghao
Published: May 2023

Oral dihydroxyphenylalanine (Dopa) administration to replenish neuronal dopamine remains the most effective treatment for Parkinson’s disease (PD). However, unlike the continuous and steady dopamine signaling in normal neurons, oral Dopa induces dramatic fluctuations in plasma Dopa levels, leading to Dopa-induced dyskinesia. Herein, we report a functional nucleic acid-based responsive artificial enzyme (FNA-Fe3O4) for in situ continuous Dopa production. FNA-Fe3O4can cross the blood-brain barrier and target diseased neurons relying on transferrin receptor aptamer. Then, FNA-Fe3O4responds to overexpressed α-synuclein mRNA in diseased neurons for antisense oligonucleotide treatment and fluorescence imaging, while converting to tyrosine aptamer-based artificial enzyme (Apt-Fe3O4) that mimics tyrosine hydroxylase for in situ continuous Dopa production. In vivo FNA-Fe3O4treatment results in recovery of Dopa and dopamine levels and decrease of pathological overexpressed α-synuclein in PD mice model, thus ameliorating motor symptoms and memory deficits. The presented functional nucleic acid-based responsive artificial enzyme strategy provides a more neuron friendly approach for the diagnosis and treatment of PD.
Unified theoretical framework for black carbon mixing state allows greater accuracy of climate effect estimation
Authors: Wang Jiandong , Wang Jiaping , Cai Runlong , Liu Chao , Jiang Jingkun , Nie Wei , Wang Jinbo , Moteki Nobuhiro , Zaveri Rahul A. , Huang Xin , Ma Nan , Chen Ganzhen , Wang Zilin , Jin Yuzhi , Cai Jing , Zhang Yuxuan , Chi Xuguang , Holanda Bruna A. , Xing Jia , Liu Tengyu , Qi Ximeng , Wang Qiaoqiao , Pöhlker Christopher , Su Hang , Cheng Yafang , Wang Shuxiao , Hao Jiming , Andreae Meinrat O. , Ding Aijun
Published: May 2023

Black carbon (BC) plays an important role in the climate system because of its strong warming effect, yet the magnitude of this effect is highly uncertain owing to the complex mixing state of aerosols. Here we build a unified theoretical framework to describe BC’s mixing states, linking dynamic processes to BC coating thickness distribution, and show its self-similarity for sites in diverse environments. The size distribution of BC-containing particles is found to follow a universal law and is independent of BC core size. A new mixing state module is established based on this finding and successfully applied in global and regional models, which increases the accuracy of aerosol climate effect estimations. Our theoretical framework links observations with model simulations in both mixing state description and light absorption quantification.
Nearly 100% selective and visible-light-driven methane conversion to formaldehyde via. single-atom Cu and Wδ+
Authors: Luo Lei , Han Xiaoyu , Wang Keran , Xu Youxun , Xiong Lunqiao , Ma Jiani , Guo Zhengxiao , Tang Junwang
Published: May 2023

Direct solar-driven methane (CH4) reforming is highly desirable but challenging, particularly to achieve a value-added product with high selectivity. Here, we identify a synergistic ensemble effect of atomically dispersed copper (Cu) species and partially reduced tungsten (Wδ+), stabilised over an oxygen-vacancy-rich WO3, which enables exceptional photocatalytic CH4conversion to formaldehyde (HCHO) under visible light, leading to nearly 100% selectivity, a very high yield of 4979.0 μmol·g−1within 2 h, and the normalised mass activity of 8.5 × 106 μmol·g-1Cu·h−1of HCHO at ambient temperature. In-situ EPR and XPS analyses indicate that the Cu species serve as the electron acceptor, promoting the photo-induced electron transfer from the conduction band to O2, generating reactive •OOH radicals. In parallel, the adjacent Wδ+species act as the hole acceptor and the preferred adsorption and activation site of H2O to produce hydroxyl radicals (•OH), and thus activate CH4to methyl radicals (•CH3). The synergy of the adjacent dual active sites boosts the overall efficiency and selectivity of the conversion process.
Moist and warm conditions in Eurasia during the last glacial of the Middle Pleistocene Transition
Authors: Sánchez Goñi María Fernanda , Extier Thomas , Polanco-Martínez Josué M. , Zorzi Coralie , Rodrigues Teresa , Bahr André
Published: May 2023

The end of the Middle Pleistocene Transition (MPT, ~ 800-670 thousand years before present, ka) was characterised by the emergence of large glacial ice-sheets associated with anomalously warm North Atlantic sea surface temperatures enhancing moisture production. Still, the direction and intensity of moisture transport across Eurasia towards potential ice-sheets is poorly constrained. To reconstruct late MPT moisture production and dispersal, we combine records of upper ocean temperature and pollen-based Mediterranean forest cover, a tracer of westerlies and precipitation, from a subtropical drill-core collected off South-West Iberia, with records of East Asia summer monsoon (EASM) strength and West Pacific surface temperatures, and model simulations. Here we show that south-western European winter precipitation and EASM strength reached high levels during the Marine Isotope Stage 18 glacial. This anomalous situation was caused by nearly-continuous moisture supply from both oceans and its transport to higher latitudes through the westerlies, likely fuelling the accelerated expansion of northern hemisphere ice-sheets during the late MPT.
Confinement of unliganded EGFR by tetraspanin nanodomains gates EGFR ligand binding and signaling
Authors: Sugiyama Michael G. , Brown Aidan I. , Vega-Lugo Jesus , Borges Jazlyn P. , Scott Andrew M. , Jaqaman Khuloud , Fairn Gregory D. , Antonescu Costin N.
Published: May 2023

The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology. EGFR is activated by ligand binding, triggering receptor dimerization, activation of kinase activity, and intracellular signaling. EGFR is transiently confined within various plasma membrane nanodomains, yet how this may contribute to regulation of EGFR ligand binding is poorly understood. To resolve how EGFR nanoscale compartmentalization gates ligand binding, we developed single-particle tracking methods to track the mobility of ligand-bound and total EGFR, in combination with modeling of EGFR ligand binding. In comparison to unliganded EGFR, ligand-bound EGFR is more confined and distinctly regulated by clathrin and tetraspanin nanodomains. Ligand binding to unliganded EGFR occurs preferentially in tetraspanin nanodomains, and disruption of tetraspanin nanodomains impairs EGFR ligand binding and alters the conformation of the receptor’s ectodomain. We thus reveal a mechanism by which EGFR confinement within tetraspanin nanodomains regulates receptor signaling at the level of ligand binding.
Highly host-linked viromes in the built environment possess habitat-dependent diversity and functions for potential virus-host coevolution
Authors: Du Shicong , Tong Xinzhao , Lai Alvin C. K. , Chan Chak K. , Mason Christopher E. , Lee Patrick K. H.
Published: May 2023

Viruses in built environments (BEs) raise public health concerns, yet they are generally less studied than bacteria. To better understand viral dynamics in BEs, this study assesses viromes from 11 habitats across four types of BEs with low to high occupancy. The diversity, composition, metabolic functions, and lifestyles of the viromes are found to be habitat dependent. Caudoviricetes species are ubiquitous on surface habitats in the BEs, and some of them are distinct from those present in other environments. Antimicrobial resistance genes are identified in viruses inhabiting surfaces frequently touched by occupants and in viruses inhabiting occupants’ skin. Diverse CRISPR/Cas immunity systems and anti-CRISPR proteins are found in bacterial hosts and viruses, respectively, consistent with the strongly coupled virus–host links. Evidence of viruses potentially aiding host adaptation in a specific-habitat manner is identified through a unique gene insertion. This work illustrates that virus–host interactions occur frequently in BEs and that viruses are integral members of BE microbiomes.
Multiplatform molecular profiling uncovers two subgroups of malignant peripheral nerve sheath tumors with distinct therapeutic vulnerabilities
Authors: Suppiah Suganth , Mansouri Sheila , Mamatjan Yasin , Liu Jeffrey C. , Bhunia Minu M. , Patil Vikas , Rath Prisni , Mehani Bharati , Heir Pardeep , Bunda Severa , Velez-Reyes German L. , Singh Olivia , Ijad Nazanin , Pirouzmand Neda , Dalcourt Tatyana , Meng Ying , Karimi Shirin , Wei Qingxia , Nassiri Farshad , Pugh Trevor J. , Bader Gary D. , Aldape Kenneth D. , Largaespada David A. , Zadeh Gelareh
Published: May 2023

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive sarcoma, and a lethal neurofibromatosis type 1-related malignancy, with little progress made on treatment strategies. Here, we apply a multiplatform integrated molecular analysis on 108 tumors spanning the spectrum of peripheral nerve sheath tumors to identify candidate drivers of MPNST that can serve as therapeutic targets. Unsupervised analyses of methylome and transcriptome profiles identify two distinct subgroups of MPNSTs with unique targetable oncogenic programs. We establish two subgroups of MPNSTs: SHH pathway activation in MPNST-G1 and WNT/ß-catenin/CCND1 pathway activation in MPNST-G2. Single nuclei RNA sequencing characterizes the complex cellular architecture and demonstrate that malignant cells from MPNST-G1 and MPNST-G2 have neural crest-like and Schwann cell precursor-like cell characteristics, respectively. Further, in pre-clinical models of MPNST we confirm that inhibiting SHH pathway in MPNST-G1 prevent growth and malignant progression, providing the rational for investigating these treatments in clinical trials.
Gesticulation in individuals with at risk mental states for psychosis
Authors: Lopes-Rocha Ana Caroline , de Paula Ramos Willian Henrique , Argolo Felipe , Gondim João Medrado , Mota Natalia Bezerra , Andrade Julio Cesar , Jafet Andrea Fontes , de Medeiros Matheus Wanderley , Serpa Mauricio Henriques , Cecchi Guillermo , Ara Anderson , Gattaz Wagner Farid , Corcoran Cheryl Mary , Loch Alexandre Andrade
Published: May 2023

Nonverbal communication (NVC) is a complex behavior that involves different modalities that are impaired in the schizophrenia spectrum, including gesticulation. However, there are few studies that evaluate it in individuals with at-risk mental states (ARMS) for psychosis, mostly in developed countries. Given our prior findings of reduced movement during speech seen in Brazilian individuals with ARMS, we now aim to determine if this can be accounted for by reduced gesticulation behavior. Fifty-six medication-naïve ARMS and 64 healthy controls were filmed during speech tasks. The frequency of specifically coded gestures across four categories (and self-stimulatory behaviors) were compared between groups and tested for correlations with prodromal symptoms of the Structured Interview for Prodromal Syndromes (SIPS) and with the variables previously published. ARMS individuals showed a reduction in one gesture category, but it did not survive Bonferroni’s correction. Gesture frequency was negatively correlated with prodromal symptoms and positively correlated with the variables of the amount of movement previously analyzed. The lack of significant differences between ARMS and control contradicts literature findings in other cultural context, in which a reduction is usually seen in at-risk individuals. However, gesture frequency might be a visual proxy of prodromal symptoms, and of other movement abnormalities. Results show the importance of analyzing NVC in ARMS and of considering different cultural and sociodemographic contexts in the search for markers of these states.
Contralateral bone conducted sound wave propagation on the skull bones in fresh frozen cadaver
Authors: Lee Jihyeon , Cho Wan-Ho , Kong Tae Hoon , Jung Sung-Soo , Han Woojae , Park Sihun , Seo Young Joon
Published: May 2023

The study aimed to investigate the efficient pathway for BC sound transmission by measuring vibrations on the opposite side of the skull bone, referred to as the mastoid position. The realistic contralateral transmission pathway of bone conduction (BC) vibrations is investigated through each osseous structure in the midlines of the fresh-frozen whole head. BC stimulation is applied to the mastoid using a bone vibrator, and acceleration responses are observed on the contralateral mastoid bone and seven midline points of skull bones using triaxial accelerometers. The study finds that the range showing the highest contralateral transmission efficiency of bone vibration is the intermediate frequency range with contralateral direction. Within this range, a significant amplitude of acceleration response is measured at the face-side points and the back and upper parts of the head. The thesis suggests that signal transmission from the specific midline to the mastoid can be more efficient than the conventional configuration of BC from the mastoid to the mastoid.
Ketogenic diet enhances the effects of oxycodone in mice
Authors: Trinko R. , Diaz D. M. , Foscue E. , Thompson S. L. , Taylor J. R. , DiLeone R. J.
Published: May 2023

Opioids have been used to manage pain for thousands of years, but they have significant potential for abuse. Prescription opioids, like oxycodone, are associated with 32% of overdoses, that have reached a total of 75,673 deaths in 2021. A major challenge is maximizing their therapeutic potential while minimizing the negative side effects including opioid use disorder (OUD). The Ketogenic Diet (KD) has been reported to reduce pain and decrease the severity of alcohol use disorder, yet its effects on oxycodone responses remain unknown. KD mice displayed increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone, suggesting a dietary effect on opiate sensitivity. Male KD mice exposed to chronic oxycodone exhibited increased naloxone-induced jumps, suggesting a sex-specific effect of diet on opioid withdrawal. Consistent with this, male KD mice self-administered less oxycodone while female KD mice did not differ from controls. Finally, no effect of KD on motivation to obtain oxycodone was observed during a progressive ratio schedule. These data suggest sex-biased effects of KD on responses to opioids that should be considered and potentially leveraged in both clinical pain management and treatment of OUD.
An assessment of microvascular hemodynamics in human macula
Authors: Yu Dao-Yi , Mehnert Andrew , Balaratnasingam Chandrakumar , Yu Paula K. , Hein Martin , An Dong , Cringle Stephen J.
Published: May 2023

An adequate blood supply to meet the energy demands is essential for any tissue, particularly for high energy demand tissues such as the retina. A critical question is: How is the dynamic match between neuronal demands and blood supply achieved? We present a quantitative assessment of temporal and spatial variations in perfusion in the macular capillary network in 10 healthy human subjects using a non-invasive and label-free imaging technique. The assessment is based on the calculation of the coefficient of variation (CoV) of the perfusion signal from arterioles, venules and capillaries from a sequence of optical coherence tomography angiography images centred on the fovea. Significant heterogeneity of the spatial and temporal variation was found within arterioles, venules and capillary networks. The CoV values of the capillaries and smallest vessels were significantly higher than that in the larger vessels. Our results demonstrate the presence of significant heterogeneity of spatial and temporal variation within each element of the macular microvasculature, particularly in the capillaries and finer vessels. Our findings suggest that the dynamic match between neuronal demands and blood supply is achieved by frequent alteration of local blood flow evidenced by capillary perfusion variations both spatially and temporally in the macular region.
Morphological and morphometric study of the scapulae of Korean wild deer
Authors: Kang Myung-Cheon , Kwon Jun , Kim In-Shik , Park Byung-Yong , Tae Hyun-Jin , Jang Young-Jin , Sim Jeoungha , Ahn Dongchoon
Published: May 2023

Korean water deer (Hydropotes inermis argyropus; Heude, 1884) and Siberian roe deer (Capreolus pygargus; Pallas, 1771) are Korean wild deer classified in the tribe Capreolini. C. pygargus in Korea were previously considered a single species; however, it was recently suggested that roe deer living on Jeju Island (Jeju roe deer; Capreolus pygargus jejuensis) is a distinct subspecies from roe deer living on the Korean peninsula (mainland roe deer; Capreolus pygargus tianschanicus) based on several studies demonstrating genetic and morphological features. In this study, we suggests that the scapular morphology and osteometric data can be used for interspecies discrmination between Korean wild deer. To compare the morphological characteristics of scapula among the three groups of deer, we analyzed the features and nine osteomorphological measurements of 31 H. i. argyropus (14 males and 17 females), 18 C. p. jejuensis (4 males and 14 females), and 23 C. p. tianschanicus (16 females and 7 males). The estimated ages of the deer were over 32–35 months. Data were analyzed by one-way repeated measures analysis of variance with post hoc Duncan test and discriminant functional analysis (DFA). H. i. argyropus and C. p. tianschanicus had the smallest and largest scapulae, respectively. The scapulae of the three Korean wild deer had a similar triangular shape, which was obscured by the tuber of the scapular spine, pointed acromion, broad infraspinous fossa, narrow supraspinous fossa, and partial ossification of scapular cartilage in older deer. H. i. argyropus had certain distinctive features, including a caudally pointed acromion, a notch between the supraglenoid tubercle and glenoid cavity (NBSG), a glenoid notch, and no sexual dimorphism, except for the longest dorsal length (Ld) and the scapular index (SI). C. p. jejuensis had a larger scapular index (SI) (61.74 ± 0.74%), compared with the SIs of H. i. argyropus and C. p. tianschanicus. The unique features of the scapula in C. p. jejuensis include its S-shaped cranial border. The C. p. jejuensis had a cranially pointed acromion, less frequent presence of glenoid notch and NBSG, short length of supraglenoid tubercle, and no sexual dimorphism. The C. p. tianschanicus had elevated cranial margin of the glenoid cavity, and frequent presence of glenoid notch and NBSG, similar to the H. i. argyropus. Similar to C. p. jejuensis, C. p. tianschanicus had a cranially pointed acromion. However, sexual dimorphism was observed in C. p. tianschanicus. DFA using osteometric data showed 97.22% of specimens were classified correctly into their species, meaning the osteometric parameters can be used for interspecies discrimination of Korean wild deer. Our findings indicate that the scapular morphologies of the three Korean wild deer have certain similarities and differences, suggesting that C. p. jejuensis are distinct from C. p. tianschanicus.
The impact of surgical volume on hospital ranking using the standardized infection ratio
Authors: Ye Shangyuan , Li Daniel , Yu Tingting , Caroff Daniel A. , Guy Jeffrey , Poland Russell E. , Sands Kenneth E. , Septimus Edward J. , Huang Susan S. , Platt Richard , Wang Rui
Published: May 2023

The Centers for Medicare and Medicaid Services require hospitals to report on quality metrics which are used to financially penalize those that perform in the lowest quartile. Surgical site infections (SSIs) are a critical component of the quality metrics that target healthcare-associated infections. However, the accuracy of such hospital profiling is highly affected by small surgical volumes which lead to a large amount of uncertainty in estimating standardized hospital-specific infection rates. Currently, hospitals with less than one expected SSI are excluded from rankings, but the effectiveness of this exclusion criterion is unknown. Tools that can quantify the classification accuracy and can determine the minimal surgical volume required for a desired level of accuracy are lacking. We investigate the effect of surgical volume on the accuracy of identifying poorly performing hospitals based on the standardized infection ratio and develop simulation-based algorithms for quantifying the classification accuracy. We apply our proposed method to data from HCA Healthcare (2014–2016) on SSIs in colon surgery patients. We estimate that for a procedure like colon surgery with an overall SSI rate of 3%, to rank hospitals in the HCA colon SSI dataset, hospitals that perform less than 200 procedures have a greater than 10% chance of being incorrectly assigned to the worst performing quartile. Minimum surgical volumes and predicted events criteria are required to make evaluating hospitals reliable, and these criteria vary by overall prevalence and between-hospital variability.
Distinct oncogenic phenotypes in hematopoietic specific deletions of Trp53
Authors: Palanichamy Jayanth Kumar , Tran Tiffany M. , King Jennifer K. , Katzman Sol , Ritter Alexander J. , Sharma Gunjan , Tso Christine , Contreras Jorge R. , Fernando Thilini R. , Sanford Jeremy R. , Rao Dinesh S.
Published: May 2023

Loss of function in the tumor suppressor gene TP53 is the most common alteration seen in human cancer. In mice, P53 deletion in all cells leads predominantly to the development of T-cell lymphomas, followed by B-cell lymphomas, sarcomas and teratomas. In order to dissect the role of P53 in the hematopoietic system, we generated and analyzed two different mouse models deficient for P53. A pan-hematopoietic P53 deletion mouse was created using Vav1-Cre based deletion; and a B-cell-specific deletion mouse was created using a CD19-Cre based deletion. The Vav1-P53CKO mice predominantly developed T-cell malignancies in younger mice, and myeloid malignancies in older mice. In T-cell malignancies, there was accelerated thymic cell maturation with overexpression of Notch1 and its downstream effectors. CD19-P53CKO mice developed marginal zone expansion in the spleen, followed by marginal zone lymphoma, some of which progressed to diffuse large B-cell lymphomas. Interestingly, marginal zone and diffuse large B-cell lymphomas had a unique gene expression signature characterized by activation of the PI3K pathway, compared with wild type marginal zone or follicular cells of the spleen. This study demonstrates lineage specific P53 deletion leading to distinct phenotypes secondary to unique gene expression programs set in motion.
Label-free intraoperative nerve detection and visualization using ratiometric diffuse reflectance spectroscopy
Authors: Throckmorton Graham A. , Haugen Ezekiel , Thomas Giju , Willmon Parker , Baba Justin S. , Solórzano Carmen C. , Mahadevan-Jansen Anita
Published: May 2023

Iatrogenic nerve injuries contribute significantly to postoperative morbidity across various surgical disciplines and occur in approximately 500,000 cases annually in the US alone. Currently, there are no clinically adopted means to intraoperatively visualize nerves beyond the surgeon’s visual assessment. Here, we report a label-free method for nerve detection using diffuse reflectance spectroscopy (DRS). Starting with an in vivo rat model, fiber- and imaging-based DRS independently identified similar wavelengths that provided optimal contrast for nerve identification with an accuracy of 92%. Optical property measurements of rat and human cadaver tissues verify that the source of contrast between nerve and surrounding tissues is largely due to higher scattering in nerve and differences in oxygenated hemoglobin content. Clinical feasibility was demonstrated in patients undergoing thyroidectomies using both probe-based and imaging-based approaches where the nerve were identified with 91% accuracy. Based on our preliminary results, DRS has the potential to both provide surgeons with a label-free, intraoperative means of nerve visualization and reduce the incidence of iatrogenic nerve injuries along with its detrimental complications.
A topical rectal douche product containing Q-Griffithsin does not disrupt the epithelial border or alter CD4+ cell distribution in the human rectal mucosa
Authors: Franzén Boger Mathias , Benhach Nora , Hasselrot Tyra , Brand Rhonda M. , Rohan Lisa C. , Wang Lin , McGowan Ian , Edick Stacey , Ho Ken , Meyn Leslie , Matoba Nobuyuki , Palmer Kenneth E. , Broliden Kristina , Tjernlund Annelie
Published: May 2023

To reduce HIV transmission, locally applied pre-exposure prophylaxis (PrEP) products for anorectal use will be important complements to oral and injectable PrEP products already available. It is critical to preserve an intact rectal epithelium and avoid an influx of mucosal HIV target cells with such product use. In this phase 1 clinical trial, we evaluated application of a topical rectal douche product containing Q-Griffithsin (Q-GRFT). Colorectal tissue samples were obtained via sigmoidoscopy at baseline, 1 and 24 h after single-dose exposure in 15 healthy volunteers. In situ staining for epithelial junction markers and CD4+ cells were assessed as an exploratory endpoint. A high-throughput, digitalized in situ imaging analysis workflow was developed to visualize and quantify these HIV susceptibility markers. We observed no significant differences in epithelial distribution of E-cadherin, desmocollin-2, occludin, claudin-1, or zonula occludens-1 when comparing the three timepoints or Q-GRFT versus placebo. There were also no differences in %CD4+ cells within the epithelium or lamina propria in any of these comparisons. In conclusion, the rectal epithelium and CD4+ cell distribution remained unchanged following topical application of Q-GRFT. In situ visualization of HIV susceptibility markers at mucosal sites could be useful to complement standard product safety assessments.
The 15-year national trends of endocrine cancers incidence among Iranian men and women; 2005–2020
Authors: Balajam Narges Zargar , Mousavian Amir-Hossein , Sheidaei Ali , Gohari Kimiya , Tavangar Seyed Mohammad , Ghanbari-Motlagh Ali , Ostovar Afshin , Shafiee Gita , Heshmat Ramin
Published: May 2023

Cancer is one of the important health problems in Iran, which is considered as the third cause of death. Endocrine cancers are rare but mostly curable. Thyroid cancer, the most common endocrine tumors, includes about one percent of malignant cancer. In this study, we examined the 15-year national trend of endocrine cancer incidence in Iranian men and women. The data in each province were evaluated based on age, gender, and cancer type according to International Classification of Disease Codes version 10 (ICD-10) from 2005 to 2020 in Iran. All data were obtained from the reports of the Statistics Center of Iran (SCI), 6 phases of the step-by-step approach to monitoring the risk factors of chronic diseases over 18 years old (STEPs), and 3 periods of the CASPIAN study (survey of non-communicable diseases in childhood and adolescence). Statistical analyzes and graph generation were done using R statistical software. Poisson regression with mixed effects was used for data modeling and incidence rate estimation. The incidence of thyroid gland malignancy is higher in women than in men. On the other hand, the incidence of adrenal gland cancer is slightly higher in men than in women. The same pattern is observed for other endocrine neoplasms and related structures. The incidence rate of these types of cancers has generally increased from 2005 to 2020 in Iran. This increase is more in women than in men. In addition, in the middle of the country, there is a strong region in terms of the occurrence of these types of cancers. The incidence rate in these provinces is relatively higher for both sexes and all studied periods. We conducted a study to observe the changing trends for various types of endocrine cancers over 15 years in men and women. Considering the increasing trend of thyroid cancers in Iran, therefore, creating essential policies for the management of these types of cancers for prevention, rapid diagnosis, and, timely treatment is particularly important.
Anthropogenic change decouples a freshwater predator’s density feedback
Authors: Sinclair J. S. , Briland R. , Fraker M. E. , Hood J. M. , Frank K. T. , Faust M. D. , Knight C. , Ludsin S. A.
Published: May 2023

Intraspecific interactions within predator populations can affect predator–prey dynamics and community structure, highlighting the need to better understand how these interactions respond to anthropogenic change. To this end, we used a half-century (1969–2018) of abundance and size-at-age data from Lake Erie’s walleye (Sander vitreus) population to determine how anthropogenic alterations have influenced intraspecific interactions. Before the 1980s, the length-at-age of younger walleye (ages 1 and 2) negatively correlated with older (age 3 +) walleye abundance, signaling a ‘density feedback’ in which intraspecific competition limited growth. However, after the early 1980s this signal of intraspecific competition disappeared. This decoupling of the density feedback was related to multiple anthropogenic changes, including a larger walleye population resulting from better fisheries management, planned nutrient reductions to improve water quality and transparency, warmer water temperatures, and the proliferation of a non-native fish with novel traits (white perch,Morone americana). We argue that these changes may have reduced competitive interactions by reducing the spatial overlap between older and younger walleye and by introducing novel prey. Our findings illustrate the potential for anthropogenic change to diminish density dependent intraspecific interactions within top predator populations, which has important ramifications for predicting predator dynamics and managing natural resources.
Synthesis of L-methionine-loaded chitosan nanoparticles for controlled release and their in vitro and in vivo evaluation
Authors: Nuzaiba Pallath Muhammed , Gupta Subodh , Gupta Shobha , Jadhao Sanjay Balkrishna
Published: May 2023

Therapeutically popular controlled release-enabling technology has forayed into the nutrition sector. Polymer coated forms of L-methionine used in soy protein diets, and its intermediate metabolite, S-adenosyl-L-methionine, used in myriad of medical conditions have proved more efficacious over (highly catabolized) free forms. In this premier study, L-methionine-loaded chitosan nanoparticles (M-NPs) were synthesized using ionic gelation method and their efficacy was evaluated. Biophysical characterization of the NPs was done using a Nanopartica SZ 100 analyser, transmission electron microscopy, and Fourier transform infrared spectroscopy. The M-NPs were spherical and smooth and 218.9 ± 7.4 nm in size and in vitro testing confirmed the controlled release of methionine. A 60-days feeding trial in L. rohita fish fingerlings was conducted. A basal diet suboptimal (0.85%) in methionine was provided with one of the supplements as under: none (control), 0.8% chitosan NPs (0.8% NPs), 1.2% L-methionine (1.2% M) (crystalline free form), 0.6% M-NPs and 1.2% M-NPs. While the addition of 0.6% M-NPs to the basal diet complemented towards meeting the established dietary requirement and resulted in significantly highest (P < 0.05) growth and protein efficiency and sero-immunological test scores (serum total protein, serum globulin, serum albumin: globulin ratio, phagocytic respiratory burst/NBT reduction and lysozyme activity), 1.2% supplementation in either form (free or nano), for being 0.85% excess, was counterproductive. Liver transaminases and dehydrogenases corroborated enhanced growth. It was inferred that part of the methionine requirement in nano form (M-NPs) can confer intended performance and health benefits in animals relying on plant proteins-based diets limiting in this essential amino acid. The study also paves the way for exploring chitosan NPs-based sustained delivery of amino acids in human medical conditions.
Publisher Correction: An investigation of zinc isotope fractionation in cacao (Theobroma cacao L.) and comparison of zinc and cadmium isotope compositions in hydroponic plant systems under high cadmium stress
Authors: Barati Elnaz , Moore Rebekah E. T. , Ullah Ihsan , Kreissig Katharina , Coles Barry J. , Dunwell Jim M. , Rehkämper Mark
Published: May 2023

An amendment to this paper has been published and can be accessed via a link at the top of the paper.