bluuebunny/crossref_metadata_2025 huggingface dataset:
A distributed parameter model of the Janus–Helmholtz transducer
Authors: Liu Wenzhao , Mo Xiping , Chai Yong , Wu Tong , Pan Rui
Published: January 2024

The Janus–Helmholtz (JH) transducer is a low-frequency, high-power, broadband underwater transducer type. Numerous studies have shown the effectiveness of the finite element method (FEM) in designing JH transducers and predicting their electroacoustic performance. However, a precise theoretical model for JH transducers has not yet been proposed, and the modal identification problem of JH transducers remains unsolved. In this paper, a distributed parameter model (DPM) of the JH transducer is proposed, which consists of the DPM of a Janus transducer and the DPM of a cylindrical liquid cavity under elastic wall conditions. By comparing the DPM with FEM, it is confirmed that the DPM can accurately calculate the resonant frequencies, admittance, amplitude, and phase of vibration velocity of the JH transducer. Additionally, a physical analogy is introduced to reveal the relationships between the transducer's resonances. Two JH transducers with different liquid cavities are fabricated and tested, and the results from the DPM, FEM, and experiments exhibit good agreement. The DPM can not only provide valuable theoretical support but also significantly reduce much time in designing JH transducers. Furthermore, it may inspire further advancements in adjusting the resonant frequencies or expanding the working bandwidth of JH transducers.
Identification of region-specific gene isoforms in the human brain using long-read transcriptome sequencing
Authors: Shimada Mihoko , Omae Yosuke , Kakita Akiyoshi , Gabdulkhaev Ramil , Hitomi Yuki , Miyagawa Taku , Honda Makoto , Fujimoto Akihiro , Tokunaga Katsushi
Published: January 2024

In neurological and neuropsychiatric diseases, different brain regions are affected, and differences in gene expression patterns could potentially explain this mechanism. However, limited studies have precisely explored gene expression in different regions of the human brain. In this study, we performed long-read RNA sequencing on three different brain regions of the same individuals: the cerebellum, hypothalamus, and temporal cortex. Despite stringent filtering criteria excluding isoforms predicted to be artifacts, over half of the isoforms expressed in multiple samples across multiple regions were found to be unregistered in the GENCODE reference. We then especially focused on genes with different major isoforms in each brain region, even with similar overall expression levels, and identified that many of such genes including
GAS7
might have distinct roles in dendritic spine and neuronal formation in each region. We also found that DNA methylation might, in part, drive different isoform expressions in different regions. These findings highlight the significance of analyzing isoforms expressed in disease-relevant sites.
The multilevel extensive diversity across the cynomolgus macaque captured by ultra-deep adaptive immune receptor repertoire sequencing
Authors: Zhu Yan , Tang Haipei , Xie Wenxi , Chen Sen , Zeng Huikun , Lan Chunhong , Guan Junjie , Ma Cuiyu , Yang Xiujia , Wang Qilong , Wei Lai , Zhang Zhenhai , Yu Xueqing
Published: January 2024

The extent to which AIRRs differ among and within individuals remains elusive. Via ultra-deep repertoire sequencing of 22 and 25 tissues in three cynomolgus macaques, respectively, we identified 84 and 114 novel IGHV and TRBV alleles, confirming 72 (85.71%) and 100 (87.72%) of them. The heterogeneous V gene usage patterns were influenced, in turn, by genetics, isotype (for BCRs only), tissue group, and tissue. A higher proportion of intragroup shared clones in the intestinal tissues than those in other tissues suggests a close intra-intestinal adaptive immunity network. Significantly higher mutation burdens in the public clones and the inter-tissue shared IgM and IgD clones indicate that they might target the shared antigens. This study reveals the extensive heterogeneity of the AIRRs at various levels and has broad fundamental and clinical implications. The data generated here will serve as an invaluable resource for future studies on adaptive immunity in health and diseases.
Changing fitness effects of mutations through long-term bacterial evolution
Authors: Couce Alejandro , Limdi Anurag , Magnan Melanie , Owen Siân V. , Herren Cristina M. , Lenski Richard E. , Tenaillon Olivier , Baym Michael
Published: January 2024

The distribution of fitness effects of new mutations shapes evolution, but it is challenging to observe how it changes as organisms adapt. Using
Escherichia coli
lineages spanning 50,000 generations of evolution, we quantify the fitness effects of insertion mutations in every gene. Macroscopically, the fraction of deleterious mutations changed little over time whereas the beneficial tail declined sharply, approaching an exponential distribution. Microscopically, changes in individual gene essentiality and deleterious effects often occurred in parallel; altered essentiality is only partly explained by structural variation. The identity and effect sizes of beneficial mutations changed rapidly over time, but many targets of selection remained predictable because of the importance of loss-of-function mutations. Taken together, these results reveal the dynamic—but statistically predictable—nature of mutational fitness effects.
Material conflicts
The War Below
Ernest Scheyder
One Signal Publishers/Atria, 2024. 384 pp.
Authors: Ali Saleem H.
Published: January 2024

A journalist probes tensions surrounding two minerals that are key to green technologies
A very energetic Galactic particle accelerator
Authors: Bosch-Ramon Valentí
Published: January 2024

The most powerful plasma jets in the Milky Way emit very-high-energy gamma rays
Toward the eradication of medical diagnostic errors
Authors: Topol Eric J.
Published: January 2024

The medical community does not broadcast the problem, but there are many studies that have reinforced a serious issue with diagnostic errors.
A recent study
concluded: “We estimate that nearly 800,000 Americans die or are permanently disabled by diagnostic errors each year.” Diagnostic errors are inaccurate assessments of a patient’s root cause of illness, such as
missing a heart attack
or infection or assigning the wrong diagnosis of pneumonia when the correct one is pulmonary embolism. Despite
ever-increasing use of medical imaging
and
laboratory tests
intended to promote diagnostic accuracy, there is nothing to suggest improvement since the
report by the National Academies of Sciences, Engineering and Medicine in 2015
, which provided a conservative estimate that 5% of adults experience a diagnostic error each year, and that most people will experience at least one in their lifetime.
iCub3 avatar system: Enabling remote fully immersive embodiment of humanoid robots
Authors: Dafarra Stefano , Pattacini Ugo , Romualdi Giulio , Rapetti Lorenzo , Grieco Riccardo , Darvish Kourosh , Milani Gianluca , Valli Enrico , Sorrentino Ines , Viceconte Paolo Maria , Scalzo Alessandro , Traversaro Silvio , Sartore Carlotta , Elobaid Mohamed , Guedelha Nuno , Herron Connor , Leonessa Alexander , Draicchio Francesco , Metta Giorgio , Maggiali Marco , Pucci Daniele
Published: January 2024

We present an avatar system designed to facilitate the embodiment of humanoid robots by human operators, validated through iCub3, a humanoid developed at the Istituto Italiano di Tecnologia. More precisely, the paper makes two contributions: First, we present the humanoid iCub3 as a robotic avatar that integrates the latest significant improvements after about 15 years of development of the iCub series. Second, we present a versatile avatar system enabling humans to embody humanoid robots encompassing aspects such as locomotion, manipulation, voice, and facial expressions with comprehensive sensory feedback including visual, auditory, haptic, weight, and touch modalities. We validated the system by implementing several avatar architecture instances, each tailored to specific requirements. First, we evaluated the optimized architecture for verbal, nonverbal, and physical interactions with a remote recipient. This testing involved the operator in Genoa and the avatar in the Biennale di Venezia, Venice—about 290 kilometers away—thus allowing the operator to visit the Italian art exhibition remotely. Second, we evaluated the optimized architecture for recipient physical collaboration and public engagement on stage, live, at the We Make Future show, a prominent world digital innovation festival. In this instance, the operator was situated in Genoa while the avatar operated in Rimini—about 300 kilometers away—interacting with a recipient who entrusted the avatar with a payload to carry on stage before an audience of approximately 2000 spectators. Third, we present the architecture implemented by the iCub Team for the All Nippon Airways (ANA) Avatar XPrize competition.
Human metapneumovirus infection of organoid-derived human bronchial epithelium represents cell tropism and cytopathology as observed in
in vivo
models
Authors: Ribó-Molina Pau , van Nieuwkoop Stefan , Mykytyn Anna Z. , van Run Peter , Lamers Mart M. , Haagmans Bart L. , Fouchier Ron A. M. , van den Hoogen Bernadette G.
Published: January 2024

Human metapneumovirus (HMPV), a member of the
Pneumoviridae
family, causes upper and lower respiratory tract infections in humans.
In vitro
studies with HMPV have mostly been performed in monolayers of undifferentiated epithelial cells.
In vivo
studies in cynomolgus macaques and cotton rats have shown that ciliated epithelial cells are the main target of HMPV infection, but these observations cannot be studied in monolayer systems. Here, we established an organoid-derived bronchial culture model that allows physiologically relevant studies on HMPV. Inoculation with multiple prototype HMPV viruses and recent clinical virus isolates led to differences in replication among HMPV isolates. Prolific HMPV replication in this model caused damage to the ciliary layer, including cilia loss at advanced stages post-infection. These cytopathic effects correlated with those observed in previous
in vivo
studies with cynomolgus macaques. The assessment of the innate immune responses in three donors upon HMPV and RSV inoculation highlighted the importance of incorporating multiple donors to account for donor-dependent variation. In conclusion, these data indicate that the organoid-derived bronchial cell culture model resembles
in vivo
findings and is therefore a suitable and robust model for future HMPV studies.

IMPORTANCE

Human metapneumovirus (HMPV) is one of the leading causative agents of respiratory disease in humans, with no treatment or vaccine available yet. The use of primary epithelial cultures that recapitulate the tissue morphology and biochemistry of the human airways could aid in defining more relevant targets to prevent HMPV infection. For this purpose, this study established the first primary organoid-derived bronchial culture model suitable for a broad range of HMPV isolates. These bronchial cultures were assessed for HMPV replication, cellular tropism, cytopathology, and innate immune responses, where the observations were linked to previous
in vivo
studies with HMPV. This study exposed an important gap in the HMPV field since extensively cell-passaged prototype HMPV B viruses did not replicate in the bronchial cultures, underpinning the need to use recently isolated viruses with a controlled passage history. These results were reproducible in three different donors, supporting this model to be suitable to study HMPV infection.
Dietary supplementation with probiotics promotes weight loss by reshaping the gut microbiome and energy metabolism in obese dogs
Authors: Kang Anna , Kwak Min-Jin , Lee Daniel Junpyo , Lee Jeong Jae , Kim Min Kyu , Song Minho , Lee Minjee , Yang Jungwoo , Oh Sangnam , Kim Younghoon
Published: January 2024

Obesity and overweight among companion animals are significant concerns, paralleling the issues observed in human populations. Recent research has highlighted the potential benefits of various probiotics in addressing weight-related changes, obesity, and associated pathologies. In this study, we delved into the beneficial probiotic mechanisms in high-fat-induced obese canines, revealing that
Enterococcus faecium
IDCC 2102 (IDCC 2102) and
Bifidobacterium lactis
IDCC 4301 (IDCC 4301) have the capacity to mitigate the increase in body weight and lipid accumulation in obese canines subjected to a high-fat diet and hyperlipidemic
Caenorhabditis elegans
(
C. elegans
) strain VS29. Both IDCC 2102 and IDCC 4301 demonstrated the ability to reduce systemic inflammation and hormonal disruptions induced by obesity. Notably, these probiotics induced modifications in the microbiota by promoting lactic acid bacteria, including
Lactobacillaceae
,
Ruminococcaceae
, and
S24-7
, with concomitant activation of pyruvate metabolism. IDCC 4301, through the generation of bacterial short-chain fatty acids and carboxylic acids, facilitated glycolysis and contributed to ATP synthesis. Meanwhile, IDCC 2102 produced bacterial metabolites such as acetic acid and butyric acid, exhibiting a particular ability to stimulate dopamine synthesis in a canine model. This stimulation led to the restoration of eating behavior and improvements in glucose and insulin tolerance. In summary, we propose novel probiotics for the treatment of obese animals based on the modifications induced by IDCC 2102 and IDCC 4301. These probiotics enhanced systemic energy utilization in response to high caloric intake, thereby preventing lipid accumulation and restoring stability to the fecal microbiota. Consequently, this intervention resulted in a reduction in systemic inflammation caused by the high-fat diet.

IMPORTANCE

Probiotic supplementation affected commensal bacterial proliferation, and administering probiotics increased glycolysis and activated pyruvate metabolism in the body, which is related to propanate metabolism as a result of pyruvate metabolism activation boosting bacterial fatty acid production via dopamine and carboxylic acid specialized pathways, hence contributing to increased ATP synthesis and energy metabolism activity.
Erratum to: Mustela strandi (Mustelidae, Carnivora) from the Early Pleistocene of Crimea
Authors: Gimranov D. O. , Jiangzuo Q. , Lavrov A. V. , Lopatin A. V.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0012496623050010
Erratum to: Infection with Trematodes in Littorina obtusata Snails (Gastropoda: Littorinidae) with Different Shell Color Genotypes
Authors: Kozminsky E. V.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0012496623050046
Erratum to: Content of 13 С and 15 N Isotopes in Bone Collagen of Geographical, Age, and Sex Groups of the Ural Cave Bear (Mammalia, Carnivora, Ursidae, Ursus (Spelaearctos) kanivetz Verestchagin, 1973)
Authors: Kosintsev P. A. , Konovalova K. Yu. , Simonova G. V.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0012496623050095
Erratum to: Fatty Acid Composition of Total Lipids in Atlantic Salmon Salmo salar L. Parr and Smolts Reared in Aquaculture at Various Lighting Regimes
Authors: Provotorov D. S. , Murzina S. A. , Voronin V. P. , Kuritsyn A.E. , Nemova N. N.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0012496623050113
Erratum to: Autumn Migration of Greater Noctule Bat (Nyctalus Lasiopterus): through Countries and over Mountains to a New Migration Flight Record in Bats
Authors: Vasenkov D. A. , Vasiliev N. S. , Sidorchuk N. V. , Rozhnov V. V.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S0012496623050125
Bound States of a Short-Range Defect on the Surface of an Intrinsic Antiferromagnetic Topological Insulator in a Noncollinear Phase
Authors: Men’shov V. N. , Chulkov E. V.
Published: January 2024

The features of electronic states on the surface of an intrinsic antiferromagnetic topological insulator (AFM TI) containing defects are theoretically investigated. Our approach takes into account the role of the electrostatic potential and the variation in the orientation of magnetic moments in the near-surface layers. A change in the spectral characteristics of the surface states under the transformation of magnetization from an equilibrium AFM phase of A-type to a ferromagnetic phase through a noncollinear texture is described. It is shown that in AFM TI with uniaxial anisotropy, an external magnetic field applied along the easy axis can cause a significant modulation of the exchange gap size in the spectrum of surface states and even invert the gap sign. Modeling the single defect effect as a surface potential perturbation over a finite scale, we analytically investigate the formation of a bound state and its behavior depending on the strength of potential and exchange scattering by the defect and the exchange gap size. The energy level of the bound state is demonstrated to experience a sharp shift in the vicinity of the spin-flop transition. The theoretical results obtained allow us to provide a consistent explanation of recent experimental data on scanning tunneling spectroscopy of antisite defects on the surface of the prototype AFM TI MnBi2Te4 in an external magnetic field.
Erratum to: Basalts of a Seamount on the Eastern Flank of the Charlie Gibbs Transform Fracture Zone, North Atlantic: Petrochemical and Isotopic Evidence of a Microplume-Affected Formation in the Axial Zone of the Mid-Atlantic Ridge
Authors: Skolotnev S. G. , Peyve A. A. , Dokashenko S. A. , Dobrolyubov V. N. , Okina O. I. , Ermolaev B. V.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S1028334X23060016
Erratum to: Rare Earth Element Resource Potential of Super-Large Deposits in Eastern Fennoscandia
Authors: Kogarko L. N.
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S1028334X23060028
Erratum to: Comment on Rogozin et al., (2023), Morphology of Lakes of the Central Tunguska Plateau (Krasnoyarsk krai, Evenkiya): New Data on the Problem of the Tunguska Event of 1908
Authors: Gasperini Luca , Bellucci Luca Giorgio , Stanghellini Carlo , Stanghellini Giuseppe , Polonia Alina
Published: January 2024

An Erratum to this paper has been published: https://doi.org/10.1134/S1028334X23060119
Ovarian mass Presenting as Paraneoplastic cerebellar degeneration with peripheral neuropathy and anti-Yo antibody
Authors: Sahoo Debananda , Dey Anupam , Dash Anil , Dash Arpita
Published: January 2024

Paraneoplastic neurological syndromes (PNS) are a group of disorders with diverse neurological manifestations that are observed in patients with various types of cancer. Any portion of the nervous system can be affected by these syndromes, which are brought on by processes other than metastasis, direct tumour spread or chemotherapy side effects. An immune-mediated attack on the cerebellar Purkinje cells and consequent cerebellar symptoms define paraneoplastic cerebellar degeneration(PCD), a subtype of the PNS. Axonal or demyelinating paraneoplastic peripheral neuropathies are both possible. Here, we describe the case of a middle-aged woman who presented with subacute-onset cerebellar symptoms and peripheral neuropathy, was discovered to have a positive anti-Yo antibody, and was later detected to have an ovarian mass. This case illustrates the significance of considering a paraneoplastic aetiology in patients with otherwise unexplained neurological manifestations and initiating an appropriate workup and early treatment for the primary malignancy.
Methotrexate treatment for peritoneal trophoblastic implants after laparoscopic salpingectomy and secondary laparoscopic excision of ectopic pregnancy
Authors: Maher Mohamed A , Fairley Helen , Khatri Pinky , Khunda Aethele
Published: January 2024

Ectopic pregnancy is a one of the primary causes of maternal mortality in first trimester. The most common site of ectopic pregnancy is the fallopian tube. Surgical management of tubal ectopic pregnancy includes salpingotomy or salpingectomy. Persistent ectopic pregnancy can happen after salpingotomy due to incomplete removal of ectopic tissue. However, it is very rare after salpingectomy. In our case, the patient had right-sided salpingectomy and histology confirmed right-sided tubal ectopic pregnancy. She presented 19 days’ later with abdominal pain, haemoperitoneum and persistent high beta-HCG (B-HCG). A second laparoscopy was done and tissue implants were removed from the surface of the right ovary and the omentum, which were confirmed to be products of conception on histology. The pain settled postoperative. However, B-HCG remained high postoperative. Subsequently, methotrexate treatment was given leading to full resolution of the pregnancy with one dose.
Voriconazole-induced periostitis in a patient with HIV treated for coccidioidomycosis meningitis
Authors: Nguyen Quynh P , Wooten Darcy
Published: January 2024

Voriconazole-induced periostitis is a rare adverse effect in patients on long-term therapy, characterised by periosteal inflammation and associated bony pain. The accompanying lab abnormalities (elevated serum alkaline phosphatase and fluoride) and characteristic imaging findings (uptake of radionuclide tracer on nuclear bone scan) are critical for diagnosis. The disease process is thought to be secondary to excess fluoride from voriconazole which stimulates bone formation and decreases osteoclast bone resorption. Management includes stopping voriconazole and switching to another agent.
Evaluating workforce needs: an investigation of healthcare professionals’ attitudes, beliefs and preparedness towards the management of Para athlete mental health at the Tokyo 2020 and Beijing 2022 Paralympic Games
Authors: Runciman Phoebe , Eken Maaike , van der Hoven Helene , Badenhorst Marelise , Blauwet Cheri , Gouttebarge Vincent , Swartz Leslie , Derman Wayne
Published: January 2024

Objectives

To examine healthcare professionals (HCPs) attitudes, beliefs and preparedness towards the management of Para athlete mental health during the Tokyo 2020 and Beijing 2022 Paralympic Games.

Methods

A cross-sectional observational study was conducted. National Paralympic Committee’s HCPs (n=857) working at the Tokyo 2020 and Beijing 2022 Paralympic Games were invited to respond to an anonymous online survey regarding the management of Para athlete mental health in their team. Data were analysed using descriptive frequency statistics.

Results

The survey was completed by 256 HCPs (30% of respondents). Most HCPs agreed that mental health was a concern in Para athletes (n=210; 82%). However, half (n=122; 48%) agreed that they did not screen Para athletes for mental health symptoms, and half (n=130; 51%) agreed that there was increased stigma around disclosure of mental health symptoms among Para athletes, compared with athletes without disability. Most HCPs (n=221; 86%) agreed they wanted to improve their knowledge and skills surrounding athlete mental healthcare. Culturally sensitivite, non-discriminatory and contextual factors were highlighted as desired areas of education for HCPs and active information dissemination for Para athletes.

Conclusion

HCPs working at the Paralympic Games considered Para athlete mental healthcare important and reported perceived stigma, yet indicated low rates of mental health screening. Most respondents expressed the need for mental health education. Culturally sensitive training and active education strategies should be implemented to optimally manage Para athlete mental health.
Effectiveness of SARS-CoV-2 primary vaccines and boosters in patients with type 2 diabetes mellitus in Hungary (HUN-VE 4 Study)
Authors: Molnár Gergő A , Vokó Zoltán , Sütő Gábor , Rokszin György , Nagy Dávid , Surján György , Surján Orsolya , Nagy Péter , Kenessey István , Wéber András , Pálosi Mihály , Müller Cecília , Kásler Miklós , Wittmann István , Kiss Zoltan
Published: January 2024

Introduction

Type 2 diabetes mellitus is a risk factor for severe COVID-19 infection and is associated with increased risk of complications. The present study aimed to investigate effectiveness and persistence of different COVID vaccines in persons with or without diabetes during the Delta wave in Hungary.

Research design and methods

Data sources were the national COVID-19 registry data from the National Public Health Center and the National Health Insurance Fund on the total Hungarian population. The adjusted incidence rate ratios and corresponding 95% CIs were derived from a mixed-effect negative binomial regression model.

Results

A population of 672 240 cases with type 2 diabetes and a control group of 2 974 102 non-diabetic persons free from chronic diseases participated. Unvaccinated elderly persons with diabetes had 2.68 (95% CI 2.47 to 2.91) times higher COVID-19-related mortality rate as the ‘healthy’ controls. Primary immunization effectively equalized the risk of COVID-19 mortality between the two groups. Vaccine effectiveness declined over time, but the booster restored the effectiveness against mortality to over 90%. The adjusted vaccine effectiveness of the primary Pfizer-BioNTech against infection in the 14–120 days of postvaccination period was 71.6 (95% CI 66.3 to 76.1)% in patients aged 65–100 years with type 2 diabetes and 64.52 (95% CI 59.2 to 69.2)% in the controls. Overall, the effectiveness tended to be higher in individuals with diabetes than in controls. The booster vaccines could restore vaccine effectiveness to over 80% concerning risk of infection (eg, patients with diabetes aged 65–100 years: 89.1 (88.1–89.9)% with Pfizer-on-Pfizer, controls 65–100 years old: 86.9 (85.8–88.0)% with Pfizer-on-Pfizer, or patients with diabetes aged 65–100 years: 88.3 (87.2–89.2)% with Pfizer-on-Sinopharm, controls 65–100 years old: 87.8 (86.8–88.7)% with Pfizer-on-Sinopharm).

Conclusions

Our data suggest that people with type 2 diabetes may have even higher health gain when getting vaccinated as compared with non-diabetic persons, eliminating the marked, COVID-19-related excess risk of this population. Boosters could restore protection.
Proton pump inhibitors alter gut microbiota by promoting oral microbiota translocation: a prospective interventional study
Authors: Xiao Xue , Zhang Xian , Wang Jin , Liu Yuqiang , Yan Hailin , Xing Xiaocun , Yang Jinlin
Published: January 2024

Background

The mechanism by which proton pump inhibitors (PPIs) alter gut microbiota remains to be elucidated. We aimed to learn whether PPI induced gut microbiota alterations by promoting oral microbial translocation.

Methods

Healthy adult volunteers were randomly assigned: PP group (n=8, 40 mg esomeprazole daily for seven days) and PM group (n=8, 40 mg esomeprazole along with chlorhexidine mouthwash after each meal for seven days). Fecal and saliva samples were analysed using 16S ribosomal RNA sequencing. Mouse models were introduced to confirm the findings in vivo, while the effect of pH on oral bacteria proliferation activity was investigated in vitro.

Results

Taxon-based analysis indicated that PPI administration increased Streptococcus abundance in gut microbiota (P<0.001), and the increased species of Streptococcus were found to be from the oral site or oral/nasal sites, in which Streptococcus anginosus was identified as the significantly changed species (P<0.004). Microbial source tracker revealed that PPI significantly increased the contribution of oral bacteria to gut microbiota (P=0.026), and no significant difference was found in PM group (P=0.467). Compared to the baseline, there was a 42-fold increase in gut abundance of Streptococcus anginosus in PP group (P=0.002), and the times decreased to 16-fold in PM group (P=0.029). Mouse models showed that combination of PPI and Streptococcus anginosus significantly increased the gut abundance of Streptococcus anginosus compared with using PPI or Streptococcus anginosus only. Furthermore, Streptococcus anginosus cannot survive in vitro at a pH lower than 5.

Conclusions

PPIs altered gut microbiota by promoting oral-originated Streptococcus translocation into gut.
Dematiaceous fungal infections: clinical and pathologic conundrums
Authors: Hartsough Emily Mae , Foreman Ruth K. , Martinez-Lage Maria , Branda John , Sohani Aliyah R. , Zukerberg Lawerence
Published: January 2024

Dematiaceous fungi are defined by pigment within their cell walls. They are increasingly recognised human pathogens, causing a wide range of clinical presentations, from localised subcutaneous infections to disseminated disease in rare cases. We report our institutional experience with diagnosis of dematiaceous fungal infections from 2005 to 2022 and highlight four instructive cases that clinically and pathologically mimicked other diseases for which the diagnosis was confirmed by fungal culture (one case) or supported by PCR with 28S rRNA and internal transcribed spacer primers (three cases). Two patients were immunocompromised and two had presumed exposure to the organism. In each highlighted case, fungal infection was not clinically suspected, and the pathologist was critical in making the diagnosis and ensuring appropriate clinical management, which was supplemented by fungal stains and novel molecular methods.
Development of therapeutic monoclonal antibodies against DKK1 peptide-HLA-A2 complex to treat human cancers
Authors: Qian Jianfei , Wang Qiang , Xiao Liuling , Xiong Wei , Xian Miao , Su Pan , Yang Maojie , Zhang Chuanchao , Li Yabo , Zhong Ling , Ganguly Siddhartha , Zu Youli , Yi Qing
Published: January 2024

Background

Targeted immunotherapy with monoclonal antibodies (mAbs) is an effective and safe method for the treatment of malignancies. Development of mAbs with improved cytotoxicity, targeting new and known tumor-associated antigens, therefore continues to be an active research area. We reported that Dickkopf-1 (DKK1) is a good target for immunotherapy of human cancers based on its wide expression in different cancers but not in normal tissues. As DKK1 is a secreted protein, mAbs binding directly to DKK1 have limited effects on cancer cells in vivo.

Methods

The specificity and antibody-binding capacity of DKK1-A2 mAbs were determined using indirect ELISA, confocal imaging, QIFIKIT antibody-binding capacity and cell surface binding assays. The affinity of mAbs was determined using a surface plasmon resonance biosensor. A flow cytometry-based cell death was performed to detect tumor cell apoptosis. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays were used to evaluate the ability of DKK1-A2 mAbs to mediate ADCC and CDC activities against tumor cells in vitro. Flow cytometry data were collected with an FACSymphony A3 cell analyzer and analyzed with FlowJo V.10.1 software. Human cancer xenograft mouse models were used to determine the in vivo therapeutic efficacy and the potential safety and toxicity of DKK1-A2 mAbs. In situ TUNEL assay was performed to detect apoptosis in tumors and mouse organs.

Results

We generated novel DKK1-A2 mAbs that recognize the DKK1 P20 peptide presented by human HLA-A*0201 (HLA-A2) molecules (DKK1-A2 complexes) that are naturally expressed by HLA-A2+DKK1+cancer cells. These mAbs directly induced apoptosis in HLA-A2+DKK1+hematologic and solid cancer cells by activating the caspase-9 cascade, effectively lysed the cancer cells in vitro by mediating CDC and ADCC and were therapeutic against established cancers in their xenograft mouse models. As DKK1 is not detected in most human tissues, DKK1-A2 mAbs neither bound to or killed HLA-A2+blood cells in vitro nor caused tissue damage in tumor-free or tumor-bearing HLA-A2-transgenic mice.

Conclusion

Our study suggests that DKK1-A2 mAbs may be a promising therapeutic agent to treat human cancers.
Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders
Authors: Huffman Brandon M , Singh Harshabad , Ali Lestat R , Horick Nora , Wang S Jennifer , Hoffman Megan T , Metayer Katherine A , Murray Shayla , Bird Alexandra , Abrams Thomas A , Biller Leah H , Chan Jennifer A , Meyerhardt Jeffrey A , McCleary Nadine J , Goessling Wolfram , Patel Anuj K , Wisch Jeffrey S , Yurgelun Matthew B , Mouw Kent , Reardon Brendan , Van Allen Eliezer M , Zerillo Jessica A , Clark Jeffrey W , Parikh Aparna , Mayer Robert J , Schlechter Benjamin , Ng Kimmie , Kumar Sunil , Del Vecchio Fitz Catherine , Kuperwasser Charlotte , Hanna Glenn J , Coveler Andrew L , Rubinson Douglas A , Welsh Emma L , Pfaff Kathleen , Rodig Scott , Dougan Stephanie K , Cleary James M
Published: January 2024

Background

Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed.

Methods

This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint of the trial was objective response rate (ORR). Exploratory objectives included analysis of potential predictive biomarkers including assessment of tumor-associated immune cell populations with multichannel immunofluorescence and analysis of circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18).

Results

In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. Despite the high level of HPV positivity observed with circulating TTMV-HPV DNA testing, the majority of patients had low levels of tumor-associated CD8+PD-1+ T cells on pretreatment biopsy. Patients who benefited from pembrolizumab had decreasing TTMV-HPV DNA scores and a complete responder’s TTMV-HPV DNA became undetectable. Long-term pembrolizumab responses were observed in one patient from the trial (5.3 years) and three patients (2.5, 6, and 8 years) from the retrospective cohort. Long-term responders had HPV-positive tumors, lacked liver metastases, and achieved a radiological complete response.

Conclusions

Pembrolizumab has durable efficacy in a rare subset of anal cancers. However, despite persistence of HPV infection, indicated by circulating HPV DNA, most advanced anal cancers have low numbers of tumor-associated CD8+PD-1+ T cells and are resistant to pembrolizumab.
A “neat” synthesis of substituted 2-hydroxy-pyrido[1,2-a]pyrimidin-4-ones
Authors: Gaube Gregory , Mutter James , Leitch David C.
Published: January 2024

We report the synthesis of a series of substituted 2-hydroxy-pyrido[1,2-a]pyrimidin-4-ones through a condensation of 2-aminopyridines and diethyl malonate. This method is contrasted with three reported general procedures for the preparation of these compounds, revealing that simple, “neat” synthesis conditions are suitable for a number of derivatives, including halogenated compounds suitable for further functionalization. Environmental, safety, and economic factors were considered in exploring this effective and robust synthetic method.
The influence of estrogen on myocardial post-translational modifications and cardiac function in women
Authors: Shorthill Samantha K. , Jones Timothy L.M. , Woulfe Kathleen C. , Cherrington Brian D. , Bruns Danielle R.
Published: January 2024

The lifetime risk of heart failure (HF) is comparable in men and women; nevertheless, disparities exist in our understanding of how HF differs between sexes. Several differences in cardiac physiology exist between men and women including the propensity to develop specific HF phenotypes. Men are more likely to be diagnosed with HF failure with reduced ejection fraction, while women have a greater propensity to develop HF with preserved ejection fraction. The mechanisms responsible for these differences remain unclear. Post-translational modifications (PTMs) of myofilament proteins likely contribute to these sex-specific propensities. The role of PTMs in heart disease is an expanding field with immense potential therapeutic targets. However, numerous PTMs remain underexplored, particularly in the context of the female heart. Estrogen, a key gonadal hormone, cardioprotective in pre-menopausal women and its loss with menopause likely contributes to disease in aging women. However, how estrogen regulates PTMs to contribute to HF development is not fully clear. This review outlines key sex differences in HF along with characterizing the contributions of novel myocardial PTMs in cardiac physiology and their regulation by estrogen. Collectively, we highlight the necessity for further investigation into women’s heart health and the distinctive mechanisms distinguishing women from men.
Vesicle condensation induced by synapsin: condensate size, geometry, and vesicle shape deformations
Authors: Alfken Jette , Neuhaus Charlotte , Major András , Taskina Alyona , Hoffmann Christian , Ganzella Marcelo , Petrovic Arsen , Zwicker David , Fernández-Busnadiego Rubén , Jahn Reinhard , Milovanovic Dragomir , Salditt Tim
Published: January 2024

We study the formation of vesicle condensates induced by the protein synapsin, as a cell-free model system mimicking vesicle pool formation in the synapse. The system can be considered as an example of liquid–liquid phase separation (LLPS) in biomolecular fluids, where one phase is a complex fluid itself consisting of vesicles and a protein network. We address the pertinent question why the LLPS is self-limiting and stops at a certain size, i.e., why macroscopic phase separation is prevented. Using fluorescence light microscopy, we observe different morphologies of the condensates (aggregates) depending on the protein-to-lipid ratio. Cryogenic electron microscopy then allows us to resolve individual vesicle positions and shapes in a condensate and notably the size and geometry of adhesion zones between vesicles. We hypothesize that the membrane tension induced by already formed adhesion zones then in turn limits the capability of vesicles to bind additional vesicles, resulting in a finite condensate size. In a simple numerical toy model we show that this effect can be accounted for by redistribution of effective binding particles on the vesicle surface, accounting for the synapsin-induced adhesion zone.

Graphic abstract
The Quantum Technology Open Master: widening access to the quantum industry
Authors: Goorney Simon , Sarantinou Matoula , Sherson Jacob
Published: January 2024

In this article we conceive of the Open Master, a new form of Transnational Education, as a means of enhancing accessibility to specialist expertise in Quantum Technology. Through participatory action research conducted during the setup and operation of a pan-European pilot project, the QTEdu Open Master (QTOM), we examine the viability of this educational model to offer flexible learning opportunities to STEM Master’s students through the setup and year-long operation of an online course exchange platform. A crucial lynchpin in the Open Master model are the mechanisms of local accreditation available for the awarding of credit, which we divide into distinct course types varying in formality and applicability. Furthermore, we have elucidated the strategies taken by staff to successfully implement the Open Master and benefit from its transformative value, building long-lasting communities within and between faculty, and scaling up educational offerings across Europe. With this research, we reflect on a possible future for QT Education.
Evaluation of the Quality of Sustainable Entrepreneurship Education in Universities Based on the Grey Correlation Algorithm
Authors: Li Chen , Sun Zhiyuan
Published: January 2024

In order to strengthen the evaluation of the quality of sustainable entrepreneurship education in universities, a study was conducted to calculate the correlation degree of the quality of sustainable entrepreneurship education in universities based on the grey correlation algorithm. The study also constructs an evaluation index system and evaluation model from three aspects: the foundation of the entrepreneurship education environment, the allocation of entrepreneurship education resources and the performance of starting an undertaking education result. The result that the evaluation model is more similar to the actual situation indicates that the evaluation indexes have a certain degree of scientificity. The evaluation method of starting an undertaking sustainable education in C&U based on the grey correlation degree algorithm has higher accuracy, recall, and F1 value compared with the traditional way. Therefore, the method has a better evaluation effect for the quality evaluation of entrepreneurship sustainable education in C&U.
Revisiting Ediacaran to early Cambrian depositional history of western North China: did it remain passive until the mid-Paleozoic?
Authors: Sun Jiaopeng , Dong Yunpeng , Chen Qiang , Ma Yao
Published: January 2024

Whether the North China Block (NCB) remained in extension from its cratonization to the mid-Paleozoic is questionable. Here, we conduct a synthesis of zircon U–Pb data of Statherian–Ordovician sandstones to provide a historical review of provenance changes in the western NCB through time. In contrast to typical NCB basement sources characterized by
c.
2.7–1.8 Ga ages with spectral peaks at
c.
2.5 and 1.9 Ga during much of
c.
1.8–0.45 Ga, Ediacaran to Cambrian Stage 3 succussions contain abundant zircons with Meso- to Neoproterozoic ages. The exotic provenance, further verified by southeastward palaeo-flow, implies sources from the western Bainaimiao arc terrane (BAT), where basement rocks with suitable ages exist. Hence, the BAT should have evolved at the NCB margin before
c.
0.56 Ga, but after rifting of the NCB (until
c.
773 Ma). This event led to a craton-wide stratigraphic break during the Mesoproterozoic–Ediacaran. The presence of 521–515 Ma detrital zircons in Cambrian Stage 3 strata indicates subduction onset of the Palaeo-Asian Ocean before
c.
515 Ma, coincident with the Precambrian–Cambrian boundary paraconformity. A sequence of depositional shifts triggered by the tectonic activities of the BAT unveils a complicated plate reorganization history of the northern NCB, contesting the view that the NCB remained passive from the Statherian.

Supplementary material
: Figures S1, S2 and Tables S1 and S2 are available at
https://doi.org/10.6084/m9.figshare.c.7040743
Energy and Emissions of Machine Learning on Smartphones vs. the Cloud
Authors: Patterson David , Gilbert Jeffrey M. , Gruteser Marco , Robles Efren , Sekar Krishna , Wei Yong , Zhu Tenghui
Published: January 2024

A Google case study finds ML training in the cloud can reduce CO
2
e emissions up to 100×.
Synthesized Image Training Techniques: On Improving Model Performance Using Confusion
Authors: Idris Azeez , Khaleel Mohammed , Tavanapong Wallapak , De Groen Piet C.
Published: January 2024

The performance of supervised deep learning image classifiers has significantly improved with large, labeled datasets and increased computing power. However, obtaining large, labeled image datasets in areas like medicine is expensive. This study seeks to improve model performance on limited labeled datasets by reducing confusion. We observed that misclassification (or confusion) between classes is usually more prevalent between specific classes. Thus, we developed a synthesized image training technique (SIT2), a novel confusion-based training framework that identifies pairs of classes with high confusion and synthesizes not-sure images from these pairs. The not-sure images are utilized in three new training strategies as follows: (1) the not-sure training strategy pretrains a model using not-sure images and the original training images, (2) the sure-or-not strategy pretrains with synthesized sure or not-sure images, and (3) the multi-label strategy pretrains with synthesized images but predicts the original class(es) of the synthesized images. Finally, the pretrained model is fine-tuned on the original dataset. An extensive evaluation was conducted on five medical and nonmedical datasets. Several improvements are statistically significant, which shows the promising future of our confusion-based training framework.
Multiply Complementary Priors for Image Compressive Sensing Reconstruction in Impulsive Noise
Authors: Li Yunyi , Xiao Fu , Liang Wei , Gui Linqing
Published: January 2024

Impulsive noise is always present in real-world image Compressive Sensing (CS) acquisition systems, where existing CS reconstruction performance may seriously deteriorate. In this article, we propose a robust CS formulation for image reconstruction to suppress outliers in the presence of impulsive noise. To address this issue, we consider a novel truncated-Cauchy loss function as the metric of residual error to elevate the reconstruction robustness. Specifically, we design a complementary priors model to incorporate nonconvex nonlocal low-rank prior and deep denoiser prior for high-accuracy image reconstruction. By means of the half-quadratic optimization theory and generalized soft-thresholding technique, we also develop an alternative optimization algorithm for solving the induced nonconvex optimization problem. Numerical simulations demonstrate the robustness and accuracy of the proposed robust CS method compared to some recent CS methods for image reconstruction in impulsive noise.
The Intestinal Microbiota and Therapeutic Responses to Immunotherapy
Authors: Herrera Pamela S. , van den Brink Marcel
Published: January 2024

The intestinal microbiota, a complex ecosystem of microorganisms, has emerged as an important player in modulating various aspects of human health and disease. The microbiota is in a state of constant cross talk with itself and its host, and these interactions regulate several aspects of host homeostasis, including immune responses. Studies have demonstrated a relationship between the microbiota and outcomes of several cancer immunotherapies. This review explores the different roles of intestinal microbiota in shaping the efficacy and safety of cancer immunotherapies, including allogeneic hematopoietic cell transplantation, immune checkpoint blockade, and CAR T cell therapy.
Social Ecological Systems in Flux
Authors: Lejano Raul P. , Stokols Daniel
Published: January 2024

A world in flux confronts the present generation, raising fears of systems gone awry. Whether it is the prospect of runaway climate change or the dangers of unbridled artificial intelligence, these dilemmas suggest that scientific and technological remedies have not been matched by progress in harnessing social and political capacities for collective action. Part of this impasse stems from a gap between the multidimensional nature of contemporary global crises and unidimensional modes of understanding and managing them. In this article, we describe an integrative approach rooted in the paradigm of social ecology that might enable us to tackle these challenges more comprehensively. We discuss, for example, how a social ecological perspective focuses attention not only on the carbon footprint of society but also on the social footprint of carbon. We review the tenets of social ecology and reflect on its promise for spurring new modes of collaborative research and collective action, including more effective strategies for planetary governance.