bluuebunny/crossref_metadata_2025 huggingface dataset:
Human enteroids as a tool to study conventional and ultra-high dose rate radiation
Authors: Klett Katarina C , Martin-Villa Briana C , Villarreal Victoria S , Melemenidis Stavros , Viswanathan Vignesh , Manjappa Rakesh , Ashraf M Ramish , Soto Luis , Lau Brianna , Dutt Suparna , Rankin Erinn B , Loo Billy W , Heilshorn Sarah C
Published: October 2023

Radiation therapy, one of the most effective therapies to treat cancer, is highly toxic to healthy tissue. The delivery of radiation at ultra-high dose rates, FLASH radiation therapy (FLASH), has been shown to maintain therapeutic anti-tumor efficacy while sparing normal tissues compared to conventional dose rate irradiation (CONV). Though promising, these studies have been limited mainly to murine models. Here, we leveraged enteroids, three-dimensional cell clusters that mimic the intestine, to study human-specific tissue response to radiation. We observed enteroids have a greater colony growth potential following FLASH compared with CONV. In addition, the enteroids that reformed following FLASH more frequently exhibited proper intestinal polarity. While we did not observe differences in enteroid damage across groups, we did see distinct transcriptomic changes. Specifically, the FLASH enteroids upregulated the expression of genes associated with the WNT-family, cell-cell adhesion, and hypoxia response. These studies validate human enteroids as a model to investigate FLASH and provide further evidence supporting clinical study of this therapy.

Insight Box Promising work has been done to demonstrate the potential of ultra-high dose rate radiation (FLASH) to ablate cancerous tissue, while preserving healthy tissue. While encouraging, these findings have been primarily observed using pre-clinical murine and traditional two-dimensional cell culture. This study validates the use of human enteroids as a tool to investigate human-specific tissue response to FLASH. Specifically, the work described demonstrates the ability of enteroids to recapitulate previous in vivo findings, while also providing a lens through which to probe cellular and molecular-level responses to FLASH. The human enteroids described herein offer a powerful model that can be used to probe the underlying mechanisms of FLASH in future studies.
Dietary Betaine improves the intestinal health and growth performance of heat-stressed growing rabbits in summer
Authors: Chen Xiang , Li Zimei , Pu Junning , Cai Jingyi , Zhao Hua , Jia Gang , Liu Guangmang , Tian Gang
Published: October 2023

The main objective of this study is to explore how various amounts of Bet affect growth performance, nutritional digestibility, and intestinal health of growing rabbits under high-temperature environment in summer. A total of 150 healthy 35-d-old weaned QiXing meat rabbits (Germany White rabbit × Sichuan White rabbit) were individually assigned to five treatments, each with 30 replicates and one rabbit per replicate. The control group was fed with basal diet, while the experimental group received a basal diet supplemented with 0.75, 1.0, 1.5, and 2.0 g Bet/kg diet, respectively. During the whole experimental stage, all animals can eat and drink freely, and they were kept in the rabbit house with an average daily temperature of 30.11 ± 0.5 ℃ and a relative humidity of 71.02 ± 5.07%. The results showed that dietary supplementation with 1.5 g/kg Bet increased average daily gain and decreased feed to gain ratio from days 1 to 42 as compared to the control group (P < 0.05), adding 0.75, 1.0, 1.5, and 2.0 g/kg Bet increased average daily gain and average daily feed intake from days 22 to 42 (P < 0.05), and increased the nutritional digestibility of acid detergent fiber (P < 0.05). Furthermore, dietary supplementation with 1.0, 1.5, and 2.0 g/kg Bet reduced d-lactate content and diamine oxidase activity in the serum (P < 0.05). Compared to the control group, supplementation of 0.75 and 1.5 g/kg Bet improved glutathione peroxidase activities in the duodenum and ileum, adding 0.75, 1.0, 1.5, and 2.0 g/kg Bet decreased malonaldehyde content in the duodenum and jejunum (P < 0.05). Moreover, the supplement of 1.5 and 2.0 g/kg Bet upregulated JAM-2 and IL-10 levels in the jejunum (P < 0.05). In conclusion, supplementation with Bet in the diet improves the growth performance, nutrient digestibility, and intestinal health of growing rabbits under high-temperature environments, and the 1.5 g Bet/kg diet group has the best effect.
Motherhood and the Gender Productivity Gap
Authors: Gallen Yana
Published: October 2023

Using Danish matched employer–employee data, I compare the relative pay of men and women to their relative productivity as measured by production function estimation. I find that the gender “productivity gap” is 8%, implying that almost two thirds of the residual gender wage gap is due to productivity differences between men and women. Motherhood plays an important role, yet it also reveals a puzzle: The pay gap for mothers is entirely explained by productivity, whereas the gap for non-mothers is not. In addition, the decoupling of pay and productivity for women without children happens during their prime-child bearing years. These estimates are robust to a variety of specifications for the impact of observables on productivity, and robust to accounting for endogenous sorting of women into less productive firms using a control-function approach. This paper also provides estimates of the productivity gap across industries and occupations, finding the same general patterns for mothers compared to women without children within these subgroups.
UN Accountability Mandates in International Justice
Authors: D’Alessandra Federica
Published: October 2023

This article discusses an important international justice development, and specifically the rise of a new generation of ‘accountability mandates’ at the United Nations (UN). Often created in response to mass atrocities alleged in country situations falling outside of the International Criminal Court’s jurisdiction, UN accountability mandates are generally tasked to collect, consolidate, preserve, and analyse evidence of international law violations, prepare files, and preserve such evidence until it can be made available to support legal accountability proceedings, including as relevant of the criminal nature. Through such investigative and evidence preservation responsibilities, UN accountability mandates can help fill important impunity gaps by helping to collate information generated by a variety of sources, including civil society documenters, and by laying the groundwork for judicial authorities. Within this broad categorization, however, UN accountability mandates are not a monolith and exist along a spectrum based on the strength of any accountability requirements they contain — including whether they are explicitly mandated to follow criminal justice standards — and their general institutional and operational setup. The investigative mechanisms created for Syria, Myanmar and Daesh/ISIL are specifically tasked to fulfil ‘pre-prosecutorial’ functions and enjoy greater resources and independence than other, less resourced and more ‘hybrid’ mandates — expected to simultaneously fulfil the role of more traditional human rights investigations, while also supporting legal accountability. All, however, play a crucial role within the broader international justice ecosystem, while sharing common challenges that this article submits would be best addressed by permanently centralizing a variety of investigative support functions, to be administered by a dedicated, permanent, standing investigative entity. The article will first provide an overview of how and why UN accountability mandates have evolved over the past decade, and of the important role they have come to play. It will then turn to discussing the case and proposed models for a standing, permanent UN accountability mandate to support future investigations. After providing a comparative analysis of the possible alternatives, the article will conclude with some recommendations and ideas for the way forward.
Patient Expertise and Medical Authority: Epistemic Implications for the Provider–Patient Relationship
Authors: Watson Jamie Carlin
Published: October 2023

The provider–patient relationship is typically regarded as an expert-to-novice relationship, and with good reason. Providers have extensive education and experience that have developed in them the competence to treat conditions better and with fewer harms than anyone else. However, some researchers argue that many patients with long-term conditions (LTCs), such as arthritis and chronic pain, have become “experts” at managing their LTC. Unfortunately, there is no generally agreed-upon conception of “patient expertise” or what it implies for the provider–patient relationship. I review three prominent accounts of patient expertise and argue that all face serious objections. I contend, however, that a plausible account of patient expertise is available and that it provides a framework both for further empirical studies and for enhancing the provider–patient relationship.
Submucosal dissection to close wide cleft palate with folded mucoperiosteum for bilateral cleft lip and palate with popliteal pterygium syndrome
Authors: Kobayashi Shinji , Yabuki Yuichiro , Sugiyama Madoka , Hirakawa Takashi , Kurosawa Kenji
Published: October 2023

Characteristic features of popliteal pterygium syndrome (PPS) associated with the craniofacial region include cleft palate, syngnathia, and difficulty with reconstruction. We developed a new procedure of submucosal dissection with periosteotomy to close the folded mucosa in bilateral cleft lip and palate patients with PPS. This technique could be applicable for patients with wide cleft palate.
Intestinal obstruction, obturator hernia, and/or colonic neoplasms: a case study
Authors: Jin Zhaofang , Lai Jianjun
Published: October 2023

Occlusive hernias are rare and difficult to diagnose. We present an extraordinary case of simultaneous occurrence of an obturator hernia with colon cancer. An 86-year-old woman arrived at the hospital after ˃2 weeks of abdominal pain, nausea, vomiting, and constipation. The computed tomography axis map showed that part of the right lower abdominal small intestine had intruded into the femoral triangle through the obturator, which was diagnosed as an obturator hernia. When the abdominal cavity was opened for herniorrhaphy, a 4 × 4 cm colon mass was observed. Only herniorrhaphy was performed, without any complications. At present, there has been no report of the coexistence of occlusive hernia and colon cancer; the main symptoms are intestinal obstruction, nausea, vomiting, and constipation. The decision whether the tumor should be removed simultaneously with herniorrhaphy and/or a mesh patch.
Postorgasmic illness syndrome: one or several entities? A retrospective cohort study
Authors: Chea Maryane , Teng Maëlys , Chesnel Camille , Lagnau Philippe , Amarenco Gérard , Hentzen Claire
Published: October 2023

Background

Postorgasmic illness syndrome (POIS) is a rare syndrome in which patients experience various physical and cognitive symptoms after ejaculation, and its pathophysiology remains unknown.

Aim

The aim of this study was to characterize the clinical presentations, disease course, and treatment outcomes in outpatients, as well as to examine the validity of the preliminary criteria and symptom clusters of POIS.

Methods

This retrospective monocentric study was conducted in a neurourology department, with patients included from 2010 to 2023. The diagnostic criteria and symptom cluster descriptions were based on previous studies.

Outcomes

The study focused on the clinical features of POIS, the complementary tests performed, the treatments tried, and their effectiveness.

Results

Thirty-seven men were included in the study, with symptom onset occurring at a mean ± SD age of 23.6 ± 7.4 years. The mean time from ejaculation to symptom onset was 1 hour 22 minutes ± 3 hours 42 minutes. The mean duration of symptoms was 4.7 ± 3.4 days. Seventeen patients (46%) developed the symptoms primarily, whereas in 20 (54%) they appeared secondarily. All preliminary criteria were met in 19 patients (51%). The most common symptom clusters were “general” in all 37 patients (100%; eg, asthenia and concentration difficulties) and “head” in 35 patients (95%; mostly headache and a foggy feeling). In terms of treatments, antihistamines and nonsteroidal anti-inflammatory drugs were tried and partially improved symptoms for some patients.

Clinical Implications

This study helps to further characterize POIS by specifying the most frequent symptoms and comparing them with the initial criteria.

Strengths and Limitations

To our knowledge, this is one of the largest cohorts of patients consulting for symptoms suggestive of POIS. There are limitations due to the retrospective nature of the data collection, such as missing data and imprecision of treatment efficacy.

Conclusion

The majority of participants met at least 3 of the preliminary diagnostic criteria, with a majority of symptoms in the general and head clusters. However, the determination of predictive factors for treatment response based on the typology of the disorders remains to be established.
Neutrino signatures of 100 2D Axisymmetric Core-Collapse Supernova Simulations
Authors: Vartanyan David , Burrows Adam
Published: October 2023

We present in this paper a public data release of an unprecedentedly large set of core-collapse supernova (CCSN) neutrino emission models, comprising 100 detailed 2D axisymmetric radiation-hydrodynamic simulations evolved out to as late as ∼5 s post-bounce and spanning an extensive range of massive-star progenitors. The motivation for this paper is to provide a physically and numerically uniform benchmark data set to the broader neutrino detection community to help it characterize and optimize subsurface facilities for what is likely to be a once-in-a-lifetime galactic supernova burst event. With this release, we hope to (1) help the international experiment and modelling communities more efficiently optimize the retrieval of physical information about the next galactic CCSN, (2) facilitate the better understanding of core-collapse theory and modelling among interested experimentalists, and (3) help further integrate the broader supernova neutrino community.
Impact of orbiting satellites on star formation rate evolution and metallicity variations in Milky Way-like discs
Authors: Annem Bhargav , Khoperskov Sergey
Published: October 2023

At least one major merger is currently taking place in the Milky Way (MW). The Sagittarius (Sgr) dwarf galaxy is being tidally destroyed while orbiting around the MW, whose close passages perturb the disc externally. In this work, using hydrodynamical simulations, we investigate how massive dwarf galaxies on quasi-polar Sgr-like orbits impact the star formation (SF) inside the MW-like discs. First, we confirm that interactions with orbiting satellites enhance the SF rate in the host. However, prominent SF bursts are detected during the very close passages (<20 kpc) of massive (2 × 1010 M⊙) gas-poor satellites. For gas-rich satellites, while we observe substantial enhancement of the SF, we do not detect prominent peaks in the SF history of the host. This can be explained by the steady gas accretion from the satellite smoothening short-term variations in the SF. The impact of the satellite perturbations, especially its first encounters, is seen mainly in the outer (>10 kpc) disc. We also found that the close passages of satellites cause the formation of low-metallicity stars in the host, and the effect is the most prominent for gas infall from the satellites resulting in the dilution of the mean stellar metallicity. Our simulations are in favour of causality between the recent passages of the Sgr and the bursts of the SF in the solar neighbourhood (≈1 and ≈2 Gyr ago); however, to reproduce the SF burst at its first infall (≈6 Gyr), we require a very close passage (<20 kpc) with subsequent substantial mass-loss of the Sgr precursor.
Metric f(R) gravity with dynamical dark energy as a scenario for the Hubble tension
Authors: Montani Giovanni , De Angelis Mariaveronica , Bombacigno Flavio , Carlevaro Nakia
Published: October 2023

We introduce a theoretical framework to interpret the Hubble tension, based on the combination of a metric f(R) gravity with a dynamical dark energy contribution. The modified gravity provides the non-minimally coupled scalar field responsible for the proper scaling of the Hubble constant, in order to accommodate for the local SNIa pantheon+ data and Planck measurements. The dynamical dark energy source, which exhibits a phantom divide line separating the low redshift quintessence regime (−1 < w < −1/3) from the phantom contribution (w < −1) in the early Universe, guarantees the absence of tachyonic instabilities at low redshift. The resulting H0(z) profile rapidly approaches the Planck value, with a plateau behaviour for z ≳ 5. In this scenario, the Hubble tension emerges as a low redshift effect, which can be in principle tested by comparing SNIa predictions with far sources, like QUASARS and gamma ray bursts.
Map-based cosmology inference with weak lensing – information content and its dependence on the parameter space
Authors: Boruah Supranta S , Rozo Eduardo
Published: October 2023

Field-level inference is emerging as a promising technique for optimally extracting information from cosmological data sets. Previous analyses have shown field-based inference produces tighter parameter constraints than power spectrum analyses. However, estimates of the detailed quantitative gain in constraining power differ. Here, we demonstrate the gain in constraining power depends on the parameter space being constrained. As a specific example, we find that lognormal field-based analysis of an LSST Y1-like mock data set only marginally improves constraints relative to a 2-point function analysis in Lambda cold dark matter (ΛCDM), yet it more than doubles the constraining power of the data in the context of wCDM models. This effect reconciles some, but not all, of the discrepant results found in the literature. Our results suggest the importance of using a full systematics model when quantifying the information gain for realistic field-level analyses of future data sets.
CARD9 deficiency with allergic bronchopulmonary aspergillosis (ABPA)-like presentation: a case report
Authors: Fallahi Mazdak , Mahdaviani Seyed Alireza , Shafiei Mohammadreza , Ghadimi Soodeh , Rezaei Nima , Klein Christoph , Strobel Sophie , Jamee Mahnaz
Published: October 2023

Purpose: We present a patient with CARD9 deficiency and allergic bronchopulmonary aspergillosis (ABPA)-like presentation. Methods: Following medical history taking and routine laboratory investigations, an inborn error of immunity was suspected, and the responsible variant was identified using Whole Exome Sequencing and confirmed by Sanger sequencing. Results: A 14-year-old Iranian female presented with a history of chest pain, productive cough, dyspnea, malaise, and recurrent fever. Imaging by computed tomography (CT scan), chest X-ray (CXR), bronchoscopy, transbronchial lung biopsy (TBLB), and histopathology findings led to a diagnosis of ABPA-like presentation. The genetic study showed an autosomal recessive homozygous mutation in the CARD9 gene. Clinical remission was achieved following the administration of voriconazole, which was continued as prophylaxis. Conclusions: This is the first-time report of a patient with inherited CARD9 deficiency and ABPA-like presentation due to Aspergillus Terrus. This study paves the way to elucidate immunological mechanisms underlying CARD9 deficiency and aspergillosis.
Inadvertent inoculation of Apophysomyces following tetanus immunisation- a case report
Authors: Darlington Christopher , Cunningham Sophie , Asomah Francis , Norton Robert
Published: October 2023

Mucormycosis is a rare, life-threatening fungal infection. While typically affecting immunosuppressed individuals, cases in the immunocompetent have been reported, particularly secondary to trauma, and the subspecies Apophysomyces. These fungi are typically difficult to isolate. This case report describes cutaneous Mucormycosis caused by Apophysomyces complex at a vaccination site, given following a motor vehicle accident. This life-threatening infection occurred in an immunocompetent 17-year old girl, resulting in multiple hospital admissions and finally, radical surgical debridement of her left upper limb. This case highlights the aggressive nature of this infection and the importance of early clinical recognition as effective treatment requires aggressive debridement typically prior to microbiological confirmation.
Bilateral serous retinal detachment in pre-eclampsia a rare but favorable complication: case report
Authors: Benlghazi Abdelhamid , Bouhtouri Yassine , Belouad Moad , Brarou Houda , Messaoudi Hamza , Benali Saad , El Hassani Moulay Mehdi , Kouach Jaouad
Published: October 2023

Pre-eclampsia is a serious pregnancy-related condition that can cause damage to multiple organs, including the eyes. While pre-eclampsia is commonly associated with the narrowing of the retinal arteries, more severe complications such as cortical blindness, optic neuropathy, and serous retinal detachment (SRD) can occur in rare cases. This case report describes a 26-year-old primiparous woman who presented with headaches, bilateral visual fog, and tinnitus and was diagnosed with pre-eclampsia based on elevated blood pressure and proteinuria. Despite receiving antihypertensive treatment, the patient’s visual symptoms worsened, prompting an emergency cesarean section. An ophthalmological examination revealed bilateral macular SRD. SRD in pre-eclampsia is a rare complication that can occur even in the immediate post-partum period, with a favorable prognosis. It should be noted that any pre-eclamptic patient presenting with visual symptoms in the third trimester or post-partum should be considered for serous retinal detachment.
Peer review’s irremediable flaws: Scientists’ perspectives on grant evaluation in Germany
Authors: Barlösius Eva , Paruschke Laura , Philipps Axel
Published: October 2023

Peer review has developed over time to become the established procedure for assessing and assuring the scientific quality of research. Nevertheless, the procedure has also been variously criticized as conservative, biased, and unfair, among other things. Do scientists regard all these flaws as equally problematic? Do they have the same opinions on which problems are so serious that other selection procedures ought to be considered? The answers to these questions hints at what should be modified in peer review processes as a priority objective. The authors of this paper use survey data to examine how members of the scientific community weight different shortcomings of peer review processes. Which of those processes’ problems do they consider less relevant? Which problems, on the other hand, do they judge to be beyond remedy? Our investigation shows that certain defects of peer review processes are indeed deemed irreparable: (1) legitimate quandaries in the process of fine-tuning the choice between equally eligible research proposals and in the selection of daring ideas; and (2) illegitimate problems due to networks. Science-policy measures to improve peer review processes should therefore clarify the distinction between field-specific remediable and irremediable flaws than is currently the case.
Legal–institutional design and dynamic capabilities for mission-oriented innovation agencies: a new framework
Authors: Spanó Eduardo , Monnerat Rafael , Pacheco Carlos Américo , Bonacelli Maria Beatriz Machado
Published: October 2023

Recent scholarship emphasizes the need for mission-oriented innovation policies (MOIPs) to tackle grand challenges and the importance of dynamic capabilities in innovation agencies for their implementation. However, the development of dynamic capabilities in innovation agencies, especially in relation to the legal and institutional design of such agencies, remains understudied. We propose a framework integrating research on innovation policy, dynamic capabilities, and legal institutionalism, adapting the three high-order dynamic capabilities—sense, seize, and transform—into nine more concrete low-order capabilities for implementation of MOIPs. We also look at rules and institutional design related to five groups of routines affecting the development of dynamic capabilities: (1) governance, (2) organizational design, (3) budget and finance, (4) public procurement and partnerships, and (5) human resources. We conclude by outlining the analytical and policy implications for (re)designing innovation agencies to implement MOIPs.
Integration of simulation-based education in anaesthesiology specialist training
Authors: Savoldelli Georges L. , Burlacu Crina L. , Lazarovici Marc , Matos Francisco Maio , Østergaard Doris
Published: October 2023

BACKGROUND

Despite its importance in education and patient safety, simulation-based education and training (SBET) is only partially or poorly implemented in many countries, including most European countries. The provision of a roadmap may contribute to the development of SBET for the training of anaesthesiologists.

OBJECTIVE

To develop a global agenda for the integration of simulation into anaesthesiology specialist training; identify the learning domains and objectives that are best achieved through SBET; and to provide examples of simulation modalities and evaluation methods for these learning objectives.

DESIGN

Utstein-style meeting where an expert consensus was reached after a series of short plenary presentations followed by small group workshops, underpinned by Kern's six-step theoretical approach to curriculum development.

SETTING

Utstein-style collaborative meeting.

PARTICIPANTS

Twenty-five participants from 22 countries, including 23 international experts in simulation and two anaesthesia trainees.

RESULTS

We identified the following ten domains of expertise for which SBET should be used to achieve the desired training outcomes: boot camp/initial training, airway management, regional anaesthesia, point of care ultrasound, obstetrics anaesthesia, paediatric anaesthesia, trauma, intensive care, critical events in our specialty, and professionalism and difficult conversations. For each domain, we developed a course template that defines the learning objectives, instructional strategies (including simulation modalities and simulator types), and assessment methods. Aspects related to the practical implementation, barriers and facilitators of this program were also identified and discussed.

CONCLUSIONS

We successfully developed a comprehensive agenda to facilitate the integration of SBET into anaesthesiology specialist training. The combination of the six-step approach with the Utstein-style process proved to be extremely valuable in supporting content validity and representativeness. These results may facilitate the implementation and use of SBET in several countries.

TRIAL REGISTRATION

Not applicable.
RETRACTION OF CYSTOID MACULAR EDEMA FROM THE FOVEA AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR BIRDSHOT CHORIORETINOPATHY
Authors: Ba-Ali Shakoor , Fuchs Josefine , Larsen Michael
Published: October 2023

Purpose:

To report the effect of anti-vascular endothelial growth factor inhibitor on fovea-involving cystoid macular edema in a patient with Birdshot chorioretinopathy.

Methods:

A 42-year-old male patient presented to our hospital with bilateral posterior uveitis with retinal vasculitis, cystoid macular edema, and optic disk edema. He was diagnosed with birdshot chorioretinopathy based on clinical appearance and tissue type HLA-A29.

Results:

The patient underwent vitrectomy in the right eye without any change in visual acuity. Retinal leakage was reduced by oral prednisolone, which could not be tapered below 50 mg per day without relapse. Oral prednisolone, topical dexamethasone, and subtenon Kenalog were associated with intraocular pressure rise in both eyes. Hence, his uveitis responded to steroids, but there was no detectable effect of any steroid-sparing immunomodulatory drugs. The patient had been on oral prednisolone 50 mg for five years when it was decided to attempt intravitreal vascular endothelial growth factor inhibitor injection therapy. The anti-vascular endothelial growth factor therapy diminished cystoid macular edema in the fovea and improved the visual acuity.

Conclusion:

Here, we report for the first time the long-term outcomes of anti-vascular endothelial growth factor injections on fovea-involving cystoid macular edema in Birdshot chorioretinopathy to keep steroid at the minimal possible doses and preserve a satisfying visual acuity level.
A Case of Neuroleptic Malignant Syndrome in the Context of Lithium Toxicity and Aripiprazole Use
Authors: Schultz Autumn R. , Singh Sarina , Linek-Rajapaksha Carolyn E. , Goode Heather R. , Fusick Adam J.
Published: October 2023

Objective

Neuroleptic malignant syndrome (NMS) is a rare life-threatening condition that providers should be cognizant of when prescribing dopamine-receptor antagonists. Atypical antipsychotic agents were initially considered to have a lower risk of inducing the development of NMS compared with conventional antipsychotic. Considerable evidence, however, has suggested that atypical antipsychotics are associated with NMS, including the partial dopamine agonist, aripiprazole. There is growing evidence that other psychotropics, including lithium, cause this condition. Here, the authors present a case of a patient who developed NMS from lithium and aripiprazole and provide a literature review of reported NMS cases with either psychotropic.

Method and Results

The authors report the case of 60-year-old male patient who developed NMS over a hospital course during which both aripiprazole and lithium were prescribed. In addition, a literature review was performed and a summary of cases of NMS induced by either lithium and/or aripiprazole is provided.

Conclusions

This case adds to the growing body of literature of aripiprazole and lithium-induced NMS. Only 2 other cases are reported where concomitant aripiprazole and lithium use lead to NMS. Interestingly, our patient did develop lithium toxicity during hospitalization, but the NMS diagnosis occurred after lithium toxicity resolved. This varies from the other 2 cases where NMS developed despite lithium levels always being therapeutic. Unfortunately, there are more questions than answers surrounding this rare complication involving these 2 psychotropics and clinical vigilance is warranted when using these psychotropics especially in cases where aripiprazole and lithium are used in combination.
Ultrasensitive and multiplexed protein imaging with clickable and cleavable fluorophores
Authors: Pham Thai , Chen Yi , Labaer Joshua , Guo Jia
Published: October 2023

Single-cell spatial proteomic analysis holds great promise to advance our understanding of the composition, organization, interaction and function of the various cell types in complex biological systems. However, the current multiplexed protein imaging technologies suffer from low detection sensitivity, limited multiplexing capacity or technically demanding. To tackle these issues, here we report the development of a highly sensitive and multiplexed in situ protein profiling method using off-the-shelf antibodies. In this approach, the protein targets are stained with horseradish peroxidase (HRP) conjugated antibodies and cleavable fluorophores via click chemistry. Through reiterative cycles of target staining, fluorescence imaging, and fluoropohore cleavage, many proteins can be profiled in single cells in situ. Applying this approach, we successfully quantified 28 different proteins in a human formalin-fixed paraffin-embedded (FFPE) tonsil tissue, which represents the highest multiplexing capacity among the tyramide signal amplification (TSA) methods. Based on their unique protein expression patterns and their microenvironment, ∼820,000 cells in the tissue are classified into distinct cell clusters. We also explored the cell-cell interactions between these varied cell clusters and observed different subregions of the tissue are composed of cells from specific clusters.
Your body, my experience: A systematic review of embodiment illusions as a function of and method to improve body image disturbance
Authors: Portingale Jade , Krug Isabel , Liu Hermione , Kiropoulos Litza , Butler David
Published: October 2023

Embodiment illusions—which manipulate multisensory integration processes underlying self-perception—are increasingly used to understand and improve body image disturbance (BID): a core symptom of eating disorders (EDs) and body dysmorphic disorder (BDD). The current systematic review is the first to evaluate clinical and community-based evidence on whether (i) variations involving BID impact embodiment illusion susceptibility and (ii) embodiment illusions can improve BID. Thirty-two studies met inclusion criteria. Greater embodiment was generally observed among individuals with high (relative to low/no) BID (9 out of 14 studies; 64.29%). Embodiment produced an improvement in BID in most studies (20 out of 24; 83.33%). Effect sizes were generally medium to large across both findings. Although several issues exist within the literature (e.g., substantial methodological heterogeneity, non-validated measures), findings reiterate that disturbances in multisensory integration appear to underpin BID, although embodiment illusions offer opportunities to develop new therapeutic interventions for BID. Multiple factors are of particular interest for ensuring that embodiment illusion paradigms are best designed for future research and application (e.g., virtual reality versus real-world methods).
M1 Macrophage-Related Genes Model for NSCLC Immunotherapy Response Prediction
Authors: Wu Si-fan , Sheng Qi-qi , Liu Peng-jun , Jiao Zhe , Lv Jin-ru , Qiao Rong , Xie Dong-kun , Wang Zan-han , Ge Jia-mei , Li Peng-hui , Wei Tiao-xia , Lei Jie , Fan Jie-yi , Wang Liang
Published: October 2023

2.

Patients diagnosed with non-small cell lung cancer have a limited lifespan and exhibit poor immunotherapy outcomes. M1 macrophages have been found to be essential for anti-tumor immunity. This study aimed to develop an immunotherapy response evaluation model for NSCLC patients based on transcriptional expression. RNA sequencing profiles of 254 advanced-stage NSCLC patients treated with immunotherapy were downloaded from POPLAR and OAK projects. Immune cell infiltration in NSCLC patients has been examined, and thereafter different co-expressed genes were identified. Following that, the impact of M1 macrophage related genes on the prognosis of NSCLC patients was investigated. Six M1 macrophage co-expression genes, namelyNKX2-1,CD8A,SFTA3,IL2RB,IDO1, andCXCL9, exhibited a strong association with the prognosis of NSCLC and served as effective predictors for immunotherapy response. A response model was constructed using Cox regression model and Lasso Cox regression analysis. The M1 genes were validated on our previous TD- FOREKNOW NSCLC clinical trial by RT-qPCR. The response model showed excellent immunotherapy response predicting and prognosis evaluating value in advanced stage of NSCLC. The model can effectively predict advanced NSCLC prognosis and aid in identifying patients who could benefit from customized immunotherapy as well as sensitive drugs.
ATP-release pannexin channels are gated by lysophospholipids
Authors: Henze Erik , Burkhardt Russell N. , Fox Bennett W. , Schwertfeger Tyler J. , Gelsleichter Eric , Michalski Kevin , Kramer Lydia , Lenfest Margret , Boesch Jordyn M. , Lin Hening , Schroeder Frank C. , Kawate Toshimitsu
Published: October 2023

In addition to its role as cellular energy currency, adenosine triphosphate (ATP) serves as an extracellular messenger that mediates diverse cell-to-cell communication. Compelling evidence supports that ATP is released from cells through pannexins, a family of membrane proteins that form heptameric large-pore channels. However, the activation mechanisms that trigger ATP release by pannexins remain poorly understood. Here, we discover lysophospholipids as endogenous pannexin activators, using activity-guided fractionation of mouse tissue extracts combined with untargeted metabolomics and electrophysiology. We show that lysophospholipids directly and reversibly activate pannexins in the absence of other proteins. Secretomics experiments reveal that lysophospholipid-activated pannexin 1 leads to the release of not only ATP but also other signaling metabolites, such as 5’-methylthioadenosine, which is important for immunomodulation. We also demonstrate that lysophospholipids activate endogenous pannexin 1 in human monocytes, leading to the release of IL-1β through inflammasome activation. Our results provide a connection between lipid metabolism and purinergic signaling, both of which play major roles in immune responses.
Using long‐term data series to design adequate protected areas that ensure the conservation of inconspicuous small petrel species
Authors: De la Cruz Andrés , Pereira Jorge M. , Paiva Vitor H. , Ramos Jaime A. , Oliveira Nuno , Alonso Hany , Saavedra Camilo , Vázquez José Antonio , García‐Barón Isabel , Arcos José Manuel , Arroyo Gonzalo M.
Published: October 2023

Marine protected areas (MPAs) are widely used tools for conservation and management. Their correct delimitation is challenging, especially when the target species are small, elusive and inconspicuous, as little data are generally available to adequately assess their distribution at sea. Therefore, currently designated MPAs may not effectively cover key areas for small seabirds, particularly during migration and wintering seasons.

We used ensemble species distribution models (ESDMs) on a 15‐year time‐series data set of at‐sea census along the Atlantic Iberian arc to predict the potential distribution of the smallest European seabird, the European storm‐petrel (Hydrobates pelagicus), and compare it with official marine special protection areas (SPAs).

Occurrence of European storm‐petrel was related to shifts in sea surface temperature, and to small distances from the coast over the continental shelf.

Most relevant area for the species in the Atlantic Iberian arc was west‐central Portugal to north‐western coast of the Iberian Peninsula, with an additional key area in the Gulf of Cádiz. Both zones host significant SPAs, but they inadequately cover key areas for European storm‐petrels. Our findings support extending marine SPAs in the Atlantic Iberian arc to ensure their effective protection.

The distribution of the species expands over the years, varying in both size and location. These changes might be attributed to dynamic oceanographic variables, such as sea surface temperature and biomass of micronekton, which seem to play a significant role in their foraging behaviour.

Synthesis and applications. Our study highlights the importance of analysing long time series and ESDMs to design adequate protected areas, which ensure the conservation of small and highly mobile species such as storm petrels. Our results should be considered by decision‐makers to prioritise and update marine protected areas, while incorporating the dynamic nature of the ocean within an ecosystem‐based approach.
Effect of intradialytic weight resistance training exercise in sarcopenic hemodialysis patients: A randomized controlled trial
Authors: Chaovarin Chokchai , Chaiprasert Amnart , Satirapoj Bancha , Nata Naowanit , Kaewput Wisit , Tangwonglert Theerasak , Varothai Narittaya , Thimachai Paramat , Tasanavipas Pamila , Inkong Pitchamon , Siriwattanasit Narongrit , Khrongkab Natthaya , Supasyndh Ouppatham
Published: October 2023

Background

Sarcopenia has a high prevalence in end‐stage kidney disease (ESKD). However, there is limited evidence of resistance exercise in these patients.

Objective

The study investigated the effects of resistance exercise on muscle mass, strength, and physical functioning.

Method

Fifty‐three patients were randomly assigned to resistance training exercise (n = 26) and standard exercise (n = 27) groups. All of the patients were diagnosed with sarcopenia by the Asian Working Group for Sarcopenia 2019 criteria.

Results

After 12 weeks, an improvement in leg muscle strength was significantly greater in the resistant exercise group compared with standard exercise (12.19 vs. 2.83 kg, p < 0.001). Appendicular skeletal muscle mass had a mean difference (1.01 vs. 1.02 kg/m2, p = 0.96). Physical performance status had a mean difference (−2.3 vs. −18 s, p = 0.42). There were no serious adverse events.

Conclusion

Over a 12‐week follow‐up, resistance exercise improved muscle strength in sarcopenic ESKD patients. Muscle mass and physical performance showed no significant change, but there is still a trend demonstrating to improve.
Effects of different extraction methods on volatile profiles of flaxseed oils
Authors: Sun Xuelian , Wan Yilai , Liu Wenyu , Wei Changqing
Published: October 2023

To investigate the effects of different extraction methods on volatile compounds in flaxseed oil (FSO), we first carried out solvent extraction, cold pressing, and hot pressing treatments of flaxseed [Linum usitatissimum (L.)], then applied the headspace–gas chromatography–ion mobility spectrometry technology to identify the volatile substance compositions, and established flavor fingerprints of solvent‐extracted FSO, cold‐pressed FSO, and hot‐pressed FSO. In total, 81 volatile compounds were detected, including 27 aldehydes, 14 alcohols, 13 ketones, 9 heterocycles, 8 esters, 5 acids, 4 hydrocarbons, and 1 sulfur compound (dimethyl disulfide). Extraction methods had a great influence on the volatile profile of FSO. Solvent‐extracted FSO had more sweet, mild, floral, and sour volatile profiles, cold‐pressed FSO had stronger volatile profiles of winey, spicy, and fatty, and hot‐pressed FSO had green, grass, and plastic volatile profiles. Principal component analysis and Euclidean distance demonstrated that the volatile compounds of three FSO samples could be clearly distinguished. Of note, the cold‐pressed FSO and hot‐pressed FSO had similar volatile profiles, and they were different from solvent‐extracted FSO. This study could provide some guidance for improving the flavor quality of FSO and selecting the proper extraction method for FSO productions.

Practical Application

Practical Application: This study shows extraction methods significantly affect the formation of aroma characteristics in flaxseed oil (FSO), and it provides theoretical guidance for production to use the appropriate extraction methods for high‐quality FSO.
Effects of Tremella aurantialba on physical properties, in vitro glucose release, digesta rheology, and microstructure of bread
Authors: Feng Hui , Luo Lifei , Wang Liyan , Ding Yangyue , Sun Liping , Zhuang Yongliang
Published: October 2023

In this study, the functional properties of a mixture consisting of Tremella aurantialba powder (TAP) and wheat flour were investigated. Further, the effects of adding 0%, 1%, 3%, 5%, and 10% TAP on the physical properties of bread, as well as its glucose release, microstructure, and rheology during in vitro simulated digestion were studied. The water‐holding, oil‐holding, and swelling capacities of wheat flour were significantly enhanced (p < 0.05) with the increase of TAP. The addition of TAP increased the hardness, chewiness, gumminess, and moisture content and darkened the color of the bread. Sensory evaluation showed that adding the 3% of TAP could produce bread that satisfies the requirements of consumers. Furthermore, adding TAP could inhibit the release of glucose from the digesta into the dialysis solution, especially the addition of 10% TAP reduced the release of bread glucose by 23.81%. This phenomenon might be related to the increased viscosity of the digesta and the smooth physical barrier on the surface of starch granules during simulated in vitro digestion of bread. Therefore, as a natural food, T. aurantialba has great potential in improving the functional properties of bread and the application of starch matrix products.
Use of non‐canonical amino acids in genetic code expansion‐based therapeutics: Effects on mouse gut microbiota
Authors: Liang Manyu , Yang Yanhong , Zhang Jing , Sun Yingjie , Peng Haixia , Yi Huawei , Wang Qin , Gao Xiaowei
Published: October 2023

Vaccines and cell therapeutics based on genetic code expansion are emerging. A crucial step in these therapeutic technologies is the oral administration of non‐canonical amino acids (ncAAs) to control pathogen growth and therapeutic protein levels in vivo. Investigating the toxicity effects of ncAAs can help identify more suitable candidates for developing genetic code expansion‐based vaccines and cell therapeutics. In this study, we determined the effects of three ncAAs, namely, 4‐acetyl‐phenylalanine (pAcF), 4‐iodo‐phenylalanine (pIoF), and 4‐methoxy‐phenylalanine (pMeoF), commonly used in genetic code expansion‐based vaccines and cell therapeutics, on the main organs, serum biochemical parameters, and gut microbiota in mice. We observed that pIoF and pMeoF significantly altered serum biochemical parameters to some extent. Moreover, the alterations in the mouse gut microbial composition were considerably greater after the oral administration of pIoF and pMeoF than after that of pAcF, compared with that in the control mice. These findings suggest that pAcF is more suitable than pIoF and pMeoF for application in genetic code expansion‐based vaccines and cell therapeutics as it disturbs the physiological and gut microecological balance in mice to a lesser extent.
Safety and efficacy of amrubicin with primary prophylactic pegfilgrastim as second‐line chemotherapy in patients with small cell lung cancer
Authors: Sekikawa Motoki , Murakami Haruyasu , Morita Meiko , Doshita Kosei , Miura Keita , Kodama Hiroaki , Morikawa Noboru , Iida Yuko , Mamesaya Nobuaki , Kobayashi Haruki , Ko Ryo , Wakuda Kazushige , Ono Akira , Kenmotsu Hirotsugu , Naito Tateaki , Chiba Hirofumi , Takahashi Toshiaki
Published: October 2023

Background

Amrubicin (AMR) regimens have shown efficacy as second‐line treatment in patients with small cell lung cancer (SCLC); however, adverse events such as febrile neutropenia (FN) sometimes preclude their use. Further, the safety and efficacy of AMR with primary prophylactic pegfilgrastim (P‐PEG) have not been sufficiently evaluated. In this study, we evaluated the safety and efficacy of AMR with or without P‐PEG as second‐line chemotherapy for SCLC.

Methods

We retrospectively reviewed patients with SCLC who received AMR as second‐line chemotherapy at Shizuoka Cancer Center, between December 2014 and November 2021. Based on presence/absence of P‐PEG in their regimen, patients (n = 60) were divided into P‐PEG (n = 21) and non‐P‐PEG groups, and their clinical outcomes were evaluated.

Results

Median of AMR treatment cycles was five (range: 1–39 cycles) in P‐PEG group and four (range: 1–15 cycles) in non‐P‐PEG group. The incidence of FN (4.8% vs. 30.8%; p = 0.02) and AMR dose reduction because of adverse events (4.8% vs. 25.6%; p = 0.08) were lower in the P‐PEG group than in the non‐P‐PEG group. The objective response rates were 52.4% and 30.8%, and median progression‐free and overall survival were 4.7 and 3.0 months, and 9.6 and 6.8 months, in the P‐PEG and non‐P‐PEG groups, respectively.

Conclusions

AMR with P‐PEG as second‐line chemotherapy for SCLC reduced the incidence of FN at a maintained AMR dose intensity and was associated with favorable tumor responses and survival outcomes. P‐PEG should be considered for patients treated with AMR for SCLC including refractory relapsed SCLC.