bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of brain response in operators subject to recoil force from firing long-range rifles
Authors: Seeburrun Tanvi , Bustamante Michael C. , Hartlen Devon C. , Azar Austin , Ouellet Simon , Cronin Duane S.
Published: February 2024

Mild traumatic brain injury (mTBI) may be caused by occupational hazards military personnel encounter, such as falls, shocks, exposure to blast overpressure events, and recoil from weapon firing. While it is important to protect against injurious head impacts, the repeated exposure of Canadian Armed Forces (CAF) service members to sub-concussive events during the course of their service may lead to a significant reduction in quality of life. Symptoms may include headaches, difficulty concentrating, and noise sensitivity, impacting how personnel complete their duties and causing chronic health issues. This study investigates how the exposure to the recoil force of long-range rifles results in head motion and brain deformation. Direct measurements of head kinematics of a controlled population of military personnel during firing events were obtained using instrumented mouthguards. The experimentally measured head kinematics were then used as inputs to a finite element (FE) head model to quantify the brain strains observed during each firing event. The efficacy of a concept recoil mitigation system (RMS), designed to mitigate loads applied to the operators was quantified, and the RMS resulted in lower loading to the operators. The outcomes of this study provide valuable insights into the magnitudes of head kinematics observed when firing long-range rifles, and a methodology to quantify effects, which in turn will help craft exposure guidelines, guide training to mitigate the risk of injury, and improve the quality of lives of current and future CAF service members and veterans.
Robust optimal damper placement based on robustness index simultaneously considering variation of elastoplastic design criteria and input level
Authors: Hosoda Mizuki , Fujita Kohei
Published: February 2024

Dampers should be installed at appropriate quantities and locations to control building vibrations against excitations such as earthquakes and wind loads. One of the objectives of the structural optimization problem for damper placement is to minimize the initial cost of damper installation to satisfy various structural constraints under a set of input levels and target performance values. However, it is arbitrary what input levels should be used in the design, and it is also necessary to account for various uncertainties in the inputs and structural properties. This study presents a new method for assessing the robustness of building structures with design variables while simultaneously considering various phases of structural performance criteria and input amplitudes. The proposed robustness index is a multidimensional function that can take into account the influence of different input levels on the structural performance. In this paper, the proposed new robustness index is applied to the robust optimal design of the damper placement, where the damping coefficient of the linear oil damper added to the building is uncertain. The worst resonant seismic motion for the building is investigated based on the critical double impulse method and its equivalent one-cycle sine wave, which is used as the input seismic motion. By applying the equivalent one-cycle sine wave to the structural response analysis with variations in the input velocity amplitude, the proposed robustness index is effective in comprehensively assessing the relationships between the input velocity amplitude of the seismic motion and the upper response limit of the structure under the variation of the damping coefficient of the oil damper. The comprehensive and efficient evaluation of these relationships enables a more detailed assessment of the influence of uncertainties in design variables on structural performance. In the numerical examples, the optimal damper placement for a 12-story building model is discussed based on the robustness and structural performance of both acceleration and story ductility distribution.
Unveiling the contemporary progress of graphene-based nanomaterials with a particular focus on the removal of contaminants from water: a comprehensive review
Authors: Assad Humira , Lone Imtiyaz Ahmad , Kumar Alok , Kumar Ashish
Published: February 2024

Water scarcity and pollution pose significant challenges to global environmental sustainability and public health. As these concerns intensify, the quest for innovative and efficient water treatment technologies becomes paramount. In recent years, graphene-based nanomaterials have emerged as frontrunners in this pursuit, showcasing exceptional properties that hold immense promise for addressing water contamination issues. Graphene, a single layer of carbon atoms arranged in a hexagonal lattice, exhibits extraordinary mechanical, electrical, and chemical properties. These inherent characteristics have led to a surge of interest in leveraging graphene derivatives, such as graphene oxide (GO), reduced graphene oxide and functionalized graphene, for water treatment applications. The ability of graphene-based nanomaterials to adsorb, catalyze, and photocatalyze contaminants makes them highly versatile in addressing diverse pollutants present in water sources. This review will delve into the synthesis methods employed for graphene-based nanomaterials and explore the structural modifications and functionalization strategies implemented to increase their pollutant removal performance in water treatment. By offering a critical analysis of existing literature and highlighting recent innovations, it will guide future research toward the rational design and optimization of graphene-based nanomaterials for water decontamination. The exploration of interdisciplinary approaches and cutting-edge technologies underscores the evolving landscape of graphene-based water treatment, fostering a path toward sustainable and scalable solutions. Overall, the authors believe that this review will serve as a valuable resource for researchers, engineers, and policymakers working toward sustainable and effective solutions for water purification.
Privately protected areas in Mexico, a 2012–2023 update
Authors: Bezaury-Creel Juan E.
Published: February 2024

In 2002, the first privately protected area (PPA) was legally “certified” by the Mexican government. The last PPA country review used data from 2012, so a decadal update is considered to be timely. By June 2023, 546 land parcels within 27 states held valid certificates as PPAs or ICCAs, for a total of 718,526 ha. PPAs include 175,006 ha of private lands plus 9,860 ha of public property, which jointly represent a 44% increase from their 2012 coverage of 128,369 ha, while community lands or “territories and areas conserved by indigenous peoples and local communities” (ICCAs) now comprise 486,082 ha. No new uncertified PPA inventory has been developed to date, but their number and territorial coverage have increased. After more than 20 years of use of the certified “voluntary conservation use areas” (ADVCs) mechanism, this review gives us a clearer and more mature picture of the benefits and limitations of using this legal tool. For example, no 10-year—the initial minimum required by law—certificates remain. Meanwhile, the Kunming-Montreal Global Biodiversity Framework’s 30x30 target, with emphasis on effectively conserved and managed areas, has resulted in the development of an ADVC assessment tool, while advances toward the establishment of a legal “easement in gross” mechanism, through contractual means, have been developed for one Mexican state, which will serve as a proof-of-concept precedent for other states. Overall, certification of ADVCs has proved to be a useful tool for conservation of biodiversity and environmental services, which certainly needs to evolve to become more effective and efficient, in order to be a more widely used tool and increase its contribution for achieving Target 3 of the Kunming-Montreal Global Biodiversity Framework for Mexico.
A study of clinical and serological correlation of early myocardial injury in elderly patients infected with the Omicron variant
Authors: Yu Xueying , Li Xiaoguang , Xia Shuai , Lu Lu , Fan Jiahui , Wang Ying , Fu Yan , Suo Chen , Man Qiuhong , Xiong Lize
Published: February 2024

Introduction

Myocardial injury in elderly Omicron variant patients is a leading cause of severe disease and death. This study focuses on elucidating the clinical characteristics and potential risk factors associated with myocardial injury in elderly patients infected with the Omicron variant.

Methods

Myocardial injury was defined based on elevated cardiac troponin concentrations exceeding the 99th percentile upper reference limit. Among 772 elderly Omicron-infected patients, categorized into myocardial injury (n = 263) and non-myocardial injury (n = 509) groups. The stratified log-rank statistic was used to compare the probability of patients developing intensive care. Receiver operating characteristic curves were used to determine the best cut-off values of clinical and laboratory data for predicting myocardial injury. Univariate and multivariate logistic regression was adopted to analyze the risk factors for myocardial injury.

Results

The occurrence of myocardial injury in Omicron variant-infected geriatric patients was up to 34.07% and these patients may have a higher rate of requiring intensive care (P < 0.05). By comparing myocardial injury patients with non-myocardial injury patients, notable differences were observed in age, pre-existing medical conditions (e.g., hypertension, coronary heart disease, cerebrovascular disease, arrhythmia, chronic kidney disease, and heart failure), and various laboratory biomarkers, including cycle threshold-ORF1ab gene (Ct-ORF1ab), cycle threshold-N gene (Ct-N), white blood cell count, neutrophil (NEUT) count, NEUT%, lymphocyte (LYM) count, LYM%, and D-dimer, interleukin-6, procalcitonin, C-reactive protein, serum amyloid A, total protein, lactate dehydrogenase, aspartate aminotransferase, glomerular filtration rate, blood urea nitrogen, and serum creatinine (sCr) levels (P < 0.05). Furthermore, in the multivariable logistic regression, we identified potential risk factors for myocardial injury in Omicron variant–infected elderly patients, including advanced age, pre-existing coronary artery disease, interleukin-6 > 22.69 pg/ml, procalcitonin > 0.0435 ng/ml, D-dimer > 0.615 mg/L, and sCr > 81.30 μmol/L.

Conclusion

This study revealed the clinical characteristics and potential risk factors associated with myocardial injury that enable early diagnosis of myocardial injury in Omicron variant-infected elderly patients, providing important reference indicators for early diagnosis and timely clinical intervention.
Case Report: Giant left atrial cystic tumor: myxoma or intracardiac blood cyst?
Authors: Xiao Weizhang , Qin Jing , Feng Jia , Jiang Feng , Chen Xinming , Cao Xiang , Xue Qun , Shi Jiahai
Published: February 2024

Background

Primary cardiac tumors are uncommon, with the majority being benign myxomas. Cystic myxoma, a particularly rare type of benign cardiac tumor, demands cautious differential diagnosis from other cardiac tumors.

Case summary

A 43-year-old male patient presenting with intermittent dyspnea was referred to our department for surgical evaluation. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) unveiled an intra-left atrial cyst, which was subsequently found to be blood-filled during a video-assisted microinvasive heart surgery. Pathological examination depicted a cyst wall filled with small stellate and fat spindle cells, along with a mucoid matrix, indicating a diagnosis of cystic myxoma.

Conclusions

We herein presented a rare case of an adult patient with cystic myxoma, initially misdiagnosed as an intracardiac blood cyst (CBC) prior to surgery, and ultimately verified via pathological findings.
Anti-hypertensive effect of a novel angiotensin II receptor neprilysin inhibitor (ARNi) -S086 in DSS rat model
Authors: Sun Jingchao , Xiao Ying , Xu Wenjie , Xing Wei , Du Frank , Tian Maozhi , Xu Danqi , Ren Yihua , Fang Xin
Published: February 2024

Introduction

Angiotensin receptor-neprilysin inhibitor (ARNi), comprised of an angiotensin receptor blocker (ARB) and a neprilysin inhibitor (NEPi), has established itself as a safe and effective intervention for hypertension. S086 is a novel ARNi cocrystal developed by Salubris for the treatment of heart failure and hypertension.

Methods

Dahl Salt Sensitive (DSS) hypertensive rat model and telemetry system were employed in this study to investigate the anti-hypertensive efficacy of S086 and compare it with the first ARNi-LCZ696.

Results and discussion

The study showed that oral administration of S086 dose-dependently lowered blood pressure (P < 0.001). The middle dosage of S086 (23 mg/kg) exhibited efficacy comparable to LCZ696 (68 mg/kg), while also demonstrating superiority at specific time points (P < 0.05). Notably, water consumption slightly decreased post-treatment compared to the vehicle group. Furthermore, there were significant increases in natriuresis and diuresis observed on the first day of treatment with 23 mg/kg and 68 mg/kg S086 (P < 0.001). However, over the course of treatment, the effects in all treatment groups gradually diminished. This study demonstrates the anti-hypertensive efficacy of S086 in DSS hypertensive rat model, offering promising avenues for the clinical development of S086 as a hypertension treatment.
Ion channel trafficking implications in heart failure
Authors: Reisqs Jean-Baptiste , Qu Yongxia Sarah , Boutjdir Mohamed
Published: February 2024

Heart failure (HF) is recognized as an epidemic in the contemporary world, impacting around 1%–2% of the adult population and affecting around 6 million Americans. HF remains a major cause of mortality, morbidity, and poor quality of life. Several therapies are used to treat HF and improve the survival of patients; however, despite these substantial improvements in treating HF, the incidence of HF is increasing rapidly, posing a significant burden to human health. The total cost of care for HF is USD 69.8 billion in 2023, warranting a better understanding of the mechanisms involved in HF. Among the most serious manifestations associated with HF is arrhythmia due to the electrophysiological changes within the cardiomyocyte. Among these electrophysiological changes, disruptions in sodium and potassium currents’ function and trafficking, as well as calcium handling, all of which impact arrhythmia in HF. The mechanisms responsible for the trafficking, anchoring, organization, and recycling of ion channels at the plasma membrane seem to be significant contributors to ion channels dysfunction in HF. Variants, microtubule alterations, or disturbances of anchoring proteins lead to ion channel trafficking defects and the alteration of the cardiomyocyte's electrophysiology. Understanding the mechanisms of ion channels trafficking could provide new therapeutic approaches for the treatment of HF. This review provides an overview of the recent advances in ion channel trafficking in HF.
An integrative approach to ancient agricultural terraces and forms of dependency: the case of Cutamalla in the prehispanic Andes
Authors: Mader Christian , Godde Philipp , Behl Martin , Binder Christoph , Hägele Elena , Isla Johny , Leceta Fernando , Lyons Mike , Marsh Erik , Odenthal Rachel , Fernengel Emilia , Stryjski Paul , Weber Ann-Kristin , Reindel Markus , Meister Julia
Published: February 2024

This paper presents an integrative and interdisciplinary approach to the study of ancient agricultural terraces and food production systems. Our approach consists of (1) a resource dependency theoretical framework and (2) the application of a variety of archaeological and geoscientific methods, including archaeological and geomorphological surveys, archaeological excavations, drone surveys, mapping based on satellite imagery and high-resolution digital elevation models (DEMs), geographic information system (GIS) applications, soil testing, phytolith analysis, radiocarbon dating, and calculations of food supply capacity and labor requirements. We apply these to the prehispanic site of Cutamalla (3,300 m asl) in the southern Peruvian Andes, which serves as an ideal and pioneering case study. Previous research has focused primarily on the settlement of Cutamalla, particularly through large-scale archaeological excavations, but less attention has been paid to the extensive farming terraces surrounding the settlement and the close relationship between agricultural and settlement activities. By analyzing both the terrace and settlement levels, we take a new perspective and introduce the term agricultural terrace-settlement system for such complexes. Our results show that the residential occupation of Cutamalla and the use of the surrounding farming terraces coincided: the agricultural terrace-settlement system was intensively used for a relatively short period of about 200 years (~250–40 BCE) during the Formative Late Paracas and transitional Initial Nasca periods, long before the famous Inka terrace agricultural systems. There is no evidence of reoccupation of the site and subsequent reuse of the agricultural system. Our data also document the large extent of agricultural terraces around Cutamalla (221 ha) and that maize was likely a major crop grown there. Finally, we place these findings in their broader socio-economic and ecological context. Cutamalla was an important regional center and economic hub during a very dynamic period characterized by significant population growth and increased violence. Not only a more humid climate, but probably also forced collective labor were cornerstones of substantial agricultural production in Cutamalla and the region.
Teaching comprehensive sexuality education in a traumatized society: recognizing teachers as sexual, reproductive, and mental health frontline workers
Authors: Macleod Catriona Ida , du Plessis Ulandi
Published: February 2024

Introduction

Research on school-based sexuality education in South Africa, taught within Life Orientation (LO), has mainly focused on learners’ responses, how teachers approach the subject, and the curriculum content. Critiques have included heteronormative biases, an emphasis on danger, disease and damage, a reinforcement of gendered binaries, and the lack of pleasure or well-being discourses. In contrast, our research focused on the unexpected moments teachers experience, i.e., the ethical, emotional or psychological challenges they encounter in their interactions with learners.

Methods

We interviewed 49 teachers across a range of schools in three provinces. Data were analyzed using narrative thematic analysis.

Results

Teachers’ narratives referred to an alarming array of traumas and psychosocial problems experienced by learners, including sexual abuse, substance abuse, neglect, HIV diagnosis, unsafe abortion, witnessing murders, and attempted suicide. Teaching particular topics, they indicated, triggered learner distress, although, sometimes, distress was triggered by innocuous topics. Teachers felt insufficiently skilled to teach certain topics sensitively to promote the well-being of learners who experienced current or past trauma. They also felt ill-equipped to deal with learners reporting trauma or psychosocial problems to them. Strategies narrated included allowing learners to skip relevant classes, building trust, understanding learners’ needs, being a learner’s advocate, and drawing on learners’ grounded expertise. Teachers spoke of experiencing burnout and secondary trauma themselves.

Discussion

We argue that LO teachers are, in effect, sexual, reproductive and mental health frontline workers. They need in-depth training in learner-centered and dialogical approaches to build trust within the classroom sensitively and in basic screening, containment, referral and lay counselling skills to assist distressed learners outside the class. A wellbeing approach to sexuality education requires providing LO teachers with ongoing support and consultation with peers and mental health professionals to avoid burnout and promote well-being.
Behind the screen: drug discovery using the big data of phenotypic analysis
Authors: Froney Merrill M. , Jarstfer Michael B. , Pattenden Samantha G. , Solem Amanda C. , Aina Olubunmi O. , Eslinger Melissa R. , Thomas Aeisha , Alexander Courtney M.
Published: February 2024

Technological advances in drug discovery are exciting to students, but it is challenging for faculty to maintain the pace with these developments, particularly within undergraduate courses. In recent years, a High-throughput Discovery Science and Inquiry-based Case Studies for Today’s Students (HITS) Research Coordination Network has been assembled to address the mechanism of how faculty can, on-pace, introduce these advancements. As a part of HITS, our team has developed “Behind the Screen: Drug Discovery using the Big Data of Phenotypic Analysis” to introduce students and faculty to phenotypic screening as a tool to identify inhibitors of diseases that do not have known cellular targets. This case guides faculty and students though current screening methods using statistics and can be applied at undergraduate and graduate levels. Tested across 70 students at three universities and a variety of courses, our case utilizes datasets modeled on a real phenotypic screening method as an accessible way to teach students about current methods in drug discovery. Students will learn how to identify hit compounds from a dataset they have analyzed and understand the biological significance of the results they generate. They are guided through practical statistical procedures, like those of researchers engaging in a novel drug discovery strategy. Student survey data demonstrated that the case was successful in improving student attitudes in their ability to discuss key topics, with both undergraduate and graduate students having a significant increase in confidence. Together, we present a case that uses big data to examine the utility of a novel phenotypic screening strategy, a pedagogical tool that can be customized for a wide variety of courses.
The characteristics of soil salinization effects on nitrogen mineralization and nitrification in upland fields
Authors: Tao Yinglu , Xie Wenjun , Xu Lei , Zhang Lichang , Wang Guangmei , Wang Xiaoning , Shi Cailing
Published: February 2024

The influence of soil salinization on nitrogen (N) transformation is largely unknown, which impedes the reasonable management of N in saline fields. A comprehensive meta-analysis was thus conducted to evaluate the effects of salinity and relative soil physicochemical properties on net N mineralization and nitrification in upland soils. Results showed that effects of salinity on the net-N mineralization rate (Min) and nitrification rate (Nit) changed with the salinity level and incubation time. Generally, the inhibitory effect of salt on Min and Nit decreased gradually with incubation time. At 14–16 days of soil incubation, significant stimulatory effects on Min were observed in middle-level (ECe: 12–16 dS m-1) and high-level (ECe >16 dS m-1) saline soils, and on Nit in low-level (ECe: 4–12 dS m-1) saline soils. Regression analysis revealed that the effects of soil organic carbon (SOC), total N (TN), C/N, pH, and clay content on Min and Nit were closely related to salinity levels. Nit at 5–7 days of soil incubation first enhanced and then decreased with C/N increase, and the threshold value was 34.7. The effect of pH on Nit changed with salinity levels, and shifted from stimulation to inhibition with increasing pH. Min at 5–7 days of soil incubation in middle-level group first increased with increasing pH, and decreased when pH was higher than 8.1. Salinization deeply affected soil properties, which further influenced N turnover via alteration of the availability of substrates and microbial biomass and activities. Our findings suggest that the influence of salinity on soil N turnover closely related with salinity level, and salinity level should be considered fully when optimizing N management in saline upland fields.
COVID-19, deforestation, and green economy
Authors: Singhal Vibha , Jinger Dinesh , Rathore Avinash Chandra , Pal Rama , Samal Ipsita , Bhoi Tanmaya Kumar , Paramesh Venkatesh , Fahad Shah , Jaremko Lukasz , Abdelsalam Nader R. , Jaremko Mariusz
Published: February 2024

Corona has severely impacted many sectors in the past 2. 5 years, and forests are one of the major hits among all sectors affected by the pandemic. This study presents the consolidated data on deforestation patterns across the globe during COVID and also analyzes in depth the region-specific contributing factors. Exacerbated deforestation during COVID alarms biodiversity conservation concerns and pushes back the long-term efforts to combat pollution and climate change mitigation. Deforestation also increases the risk of the emergence of new zoonotic diseases in future, as deforestation and COVID are intricately related to each other. Therefore, there is a need to check deforestation and inculcation of conservation measures in building back better policies adopted post-COVID. This review is novel in specifically providing insight into the implications of COVID-19 on forests in tropical as well as temperate global regions, causal factors, green policies given by different nations, and recommendations that will help in designing nature-based recovery strategies for combating deforestation and augmenting afforestation, thus providing better livelihood, biodiversity conservation, climate change mitigation, and better environmental quality.
Loss of NSD2 causes dysregulation of synaptic genes and altered H3K36 dimethylation in mice
Authors: Kinoshita Shiori , Kojima Kazuaki , Ohnishi Eriko , Takayama Yuka , Kikuchi Hiroki , Takada Shuji , Nakabayashi Kazuhiko , Kawai Tomoko , Hata Kenichiro
Published: February 2024

Background: Epigenetic disruptions have been implicated in neurodevelopmental disorders. NSD2 is associated with developmental delay/intellectual disability; however, its role in brain development and function remains unclear.

Methods: We performed transcriptomic and epigenetic analyses using Nsd2 knockout mice to better understand the role of NSD2 in the brain.

Results and discussion: Transcriptomic analysis revealed that the loss of NSD2 caused dysregulation of genes related to synaptic transmission and formation. By analyzing changes in H3 lysine 36 dimethylation (H3K36me2), NSD2-mediated H3K36me2 mainly marked quiescent state regions and the redistribution of H3K36me2 occurred at transcribed genes and enhancers. By integrating transcriptomic and epigenetic data, we observed that H3K36me2 changes in a subset of dysregulated genes related to synaptic transmission and formation. These results suggest that NSD2 is involved in the regulation of genes important for neural function through H3K36me2. Our findings provide insights into the role of NSD2 and improve our understanding of epigenetic regulation in the brain.
No bidirectional relationship between inflammatory bowel disease and diverticular disease: a genetic correlation and Mendelian randomization study
Authors: Aierken Ailikamu , Atabieke Falide , Aierken Munire , Li Jian , Xia Yu , Aizezi Yierzhati , Li Shui-Xue
Published: February 2024

Background: Although previous studies found that inflammatory bowel disease (IBD) and diverticular disease (DD) usually co-exist clinically, studies examining the relationship are spare.

Aim: Our study aspires to investigate the causal correlation between the IBD [including ulcerative colitis (UC) and Crohn’s disease (CD)] and DD using the Mendelian randomization (MR) analysis.

Methods: We conducted a two-sample bidirectional MR analysis using publicly available genome-wide association studies (GWAS) summary data. The single nucleotide polymorphism (SNP) data associated with DD and IBD were obtained from the Finnish Biobank and UK Biobank, respectively. Through secondary data analysis of all GWAS summary data, we systematically screened genetic instrumental variables. To address the impact of horizontal pleiotropy, several methods were employed, including the inverse variance-weighted method (IVW), maximum likelihood method, Egger regression method, weighted median method, and simple median method. These approaches aimed to detect and correct for the potential bias caused by horizontal pleiotropy.

Results: Genetically predicted DD did not have a causal effect on IBD (OR 1.06, 95% CI 0.98–1.17, p = 0.15), and had no causal effect on UC (OR 1.10, 95% CI 0.94–1.20, p = 0.36) and CD (OR 1.03, 95% CI 0.92–1.16, p = 0.62) either. Furthermore, in the reverse MR analysis, we did not observe any significant causal effect of IBD on DD. Results of complementary methods showed consistent results with those of the IVW method.

Conclusion: This study’s findings do not provide evidence for a causal relationship between IBD and DD, which contradicts the majority of observational studies.
Ehf and Fezf2 regulate late medullary thymic epithelial cell and thymic tuft cell development
Authors: Lammers Sören , Barrera Victor , Brennecke Philip , Miller Corey , Yoon Joon , Balolong Jared , Anderson Mark S. , Ho Sui Shannan , Steinmetz Lars M. , von Andrian Ulrich H. , Rattay Kristin
Published: February 2024

Thymic epithelial cells are indispensable for T cell maturation and selection and the induction of central immune tolerance. The self-peptide repertoire expressed by medullary thymic epithelial cells is in part regulated by the transcriptional regulator Aire (Autoimmune regulator) and the transcription factor Fezf2. Due to the high complexity of mTEC maturation stages (i.e., post-Aire, Krt10+ mTECs, and Dclk1+ Tuft mTECs) and the heterogeneity in their gene expression profiles (i.e., mosaic expression patterns), it has been challenging to identify the additional factors complementing the transcriptional regulation. We aimed to identify the transcriptional regulators involved in the regulation of mTEC development and self-peptide expression in an unbiased and genome-wide manner. We used ATAC footprinting analysis as an indirect approach to identify transcription factors involved in the gene expression regulation in mTECs, which we validated by ChIP sequencing. This study identifies Fezf2 as a regulator of the recently described thymic Tuft cells (i.e., Tuft mTECs). Furthermore, we identify that transcriptional regulators of the ELF, ESE, ERF, and PEA3 subfamily of the ETS transcription factor family and members of the Krüppel-like family of transcription factors play a role in the transcriptional regulation of genes involved in late mTEC development and promiscuous gene expression.
A case report of multicentric reticulohistiocytosis with atypical cutaneous presentation
Authors: Chen Xiangru , An Lin , Jiang Zhongmin , Jia Yuxi
Published: February 2024

Multicentric reticulohistiocytosis (MRH) is a rare systemic disorder characterized by histiocytic hyperplasia that mainly involves the skin, mucous membranes, and joints. The typical clinical features include papules, nodules, and arthritis. MRH lesions are relatively extensive but small and scattered. Joint inflammation is characterized by diffuse symmetric polyarthritis as the first symptom, which can be severe and disabling due to destructive joint changes. MRH is easily misdiagnosed in clinical practice. Here, we report the case of an elderly male patient who presented with polyarticular pain in the hip and interphalangeal joints as the first manifestation, followed by the development of large, isolated, bulging skin nodules, which are atypical MRH lesions. This is rare in all MRH case reports, and we made the correct diagnosis by combining skin histopathology, immunohistochemistry, and other clinical examinations. We performed surgical treatment on the local skin lesions of this patient. This case suggests that clinicians should actively correlate the condition and accurately diagnose MRH when encountering atypical skin changes or other diseases as the first symptom and explore the mechanisms of MRH and other clinical manifestations.
Insights into midgut cell types and their crucial role in antiviral immunity in the lepidopteran model Bombyx mori
Authors: Awais Mian Muhammad , Fei Shigang , Xia Junming , Feng Min , Sun Jingchen
Published: February 2024

The midgut, a vital component of the digestive system in arthropods, serves as an interface between ingested food and the insect’s physiology, playing a pivotal role in nutrient absorption and immune defense mechanisms. Distinct cell types, including columnar, enteroendocrine, goblet and regenerative cells, comprise the midgut in insects and contribute to its robust immune response. Enterocytes/columnar cells, the primary absorptive cells, facilitate the immune response through enzyme secretions, while regenerative cells play a crucial role in maintaining midgut integrity by continuously replenishing damaged cells and maintaining the continuity of the immune defense. The peritrophic membrane is vital to the insect’s innate immunity, shielding the midgut from pathogens and abrasive food particles. Midgut juice, a mixture of digestive enzymes and antimicrobial factors, further contributes to the insect’s immune defense, helping the insect to combat invading pathogens and regulate the midgut microbial community. The cutting-edge single-cell transcriptomics also unveiled previously unrecognized subpopulations within the insect midgut cells and elucidated the striking similarities between the gastrointestinal tracts of insects and higher mammals. Understanding the intricate interplay between midgut cell types provides valuable insights into insect immunity. This review provides a solid foundation for unraveling the complex roles of the midgut, not only in digestion but also in immunity. Moreover, this review will discuss the novel immune strategies led by the midgut employed by insects to combat invading pathogens, ultimately contributing to the broader understanding of insect physiology and defense mechanisms.
Transcriptomics of early responses to purified Piscine orthoreovirus-1 in Atlantic salmon (Salmo salar L.) red blood cells compared to non-susceptible cell lines
Authors: Tsoulia Thomais , Sundaram Arvind Y. M. , Braaen Stine , Jørgensen Jorunn B. , Rimstad Espen , Wessel Øystein , Dahle Maria K.
Published: February 2024

Piscine red blood cells (RBC) are nucleated and have been characterized as mediators of immune responses in addition to their role in gas exchange. Salmonid RBC are major target cells of Piscine orthoreovirus-1 (PRV-1), the etiological agent of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar). PRV-1 replicates in RBC ex vivo, but no viral amplification has been possible in available A. salmon cell lines. To compare RBC basal transcripts and transcriptional responses to PRV-1 in the early phase of infection with non-susceptible cells, we exposed A. salmon RBC, Atlantic salmon kidney cells (ASK) and Salmon head kidney cells (SHK-1) to PRV-1 for 24 h. The RNA-seq analysis of RBC supported their previous characterization as pluripotent cells, as they expressed a wide repertoire of genes encoding pattern recognition receptors (PRRs), cytokine receptors, and genes implicated in antiviral activities. The comparison of RBC to ASK and SHK-1 revealed immune cell features exclusively expressed in RBC, such as genes involved in chemotactic activity in response to inflammation. Differential expression analysis of RBC exposed to PRV-1 showed 46 significantly induced genes (≥ 2-fold upregulation) linked to the antiviral response pathway, including RNA-specific PRRs and interferon (IFN) response factors. In SHK-1, PRV induced a more potent or faster antiviral response (213 genes induced). ASK cells showed a differential response pattern (12 genes induced, 18 suppressed) less characterized by the dsRNA-induced antiviral pathway. Despite these differences, the RIG-I-like receptor 3 (RLR3) in the family of cytosolic dsRNA receptors was significantly induced in all PRV-1 exposed cells. IFN regulatory factor 1 (IRF1) was significantly induced in RBC only, in contrast to IRF3/IRF7 induced in SHK-1. Differences in IRF expression and activity may potentially affect viral propagation.
Addressing health care disruption in rural Mozambique due to extreme climate events: mobile units tackling cyclones, vaccine-preventable diseases, and beyond
Authors: Rossi Benedetta , Formenti Beatrice , Cerini Carlo , Tique Nerisia , da Celma Cossa Rafaela , Boniotti Federica , Comini Bruno , Tomasoni Lina Rachele , Castelli Francesco
Published: February 2024

Floods, and cyclones are occurring with increasing frequency and intensity worldwide due to global warming. Mozambique is very susceptible to these extreme events due to its geographical location. In the last ten years, four of the most severe extreme climatic events have been observed in this country, leading to widespread destruction of infrastructure and the displacement of inhabitants. Cyclones Dineo in 2017, Idai and Kenneth in 2019 and recently Freddy in 2023 affected in total over two million people impacting food and water security, causing cholera outbreaks and damage to health facilities. The mobile health units, known as Brigadas Móveis (BM), are crucial to the Mozambican health system as they provide people in the most remote areas with vaccinations, and antimalarials, and other interventions. The BM activities in five districts of Inhambane province in the south of Mozambique are run by the NGO Medicus Mundi Italia in collaboration with the local health authorities. Cyclone Freddy flooded the province of Inhambane, affecting road accessibility and the BM’s planned operations in all five districts with a loss of 37.8% of BM outreach activities. The temporary absence of the BM service resulted in rural communities having no access to health care, including routine vaccine administration. Adaptation strategies need to be implemented to address the healthcare challenges associated with extreme climate events. As described in our experience in Inhambane, BM restored outreach activities immediately after the cyclone, improving access to care after challenging situations.
Microplastics pollution in genetically connected populations of Holothuria forskali from south Bay of Biscay
Authors: Menéndez Daniel , Álvarez Almudena , Garcia-Vazquez Eva , Ardura Alba
Published: February 2024

Introductio

Sea cucumbers are increasingly demanded as seafood in different cultures around the world. Holothurians could be potentially exploited in southern Bay of Biscay (Iberian Cantabrian coast) where they are not fished yet. Recent studies show relatively high pollution by emerging pollutants like microplastics (MPs) in the region; perhaps the exposure of holothurians to those MPs may put them at risk.

Material and methods

Here we analysed 60 samples of Holothuria forskali taken from the west and east of the Cape Peñas transition zone in different seasons. MPs were quantified from body wall tissue, and mitochondrial DNA sequences (16S and COI genes) were employed to determine population connectivity and infer replenishment capacity.

Results

Much higher MPs content in holothurian tissue than in water and sediments confirmed bioconcentration in this species. Significant differences between sampling locations were found, holothurian pollution being consistent with the occurrence of MPs sources like rivers, fishing ports and aquaculture. Genetic connectivity and no signals of diversity reduction in the most polluted samples suggest population replenishment capacity in H. forskali in the studied region. Results for a few samples of H. mammata from the same sampling points confirmed a higher MPs pollution at the west of Cape Peñas.

Discussion

According to these exploratory results, sea cucumbers seem to accumulate MPs especially in the western Cantabrian Sea. Further studies are recommended to understand the possible MPs threat for these holothurian species.
Case report: Treatment of Wilson’s disease by human amniotic fluid administration
Authors: Liang Libin , Xin Hong , Shen Xueyan , Xu Yanping , Zhang Lansen , Liu Dehui , Zhao Liling , Tong Xinglong
Published: February 2024

Background

Wilson’s disease (WD) is not an uncommon genetic disease in clinical practice. However, the current WD therapies have limitations. The effectiveness of stem cell therapy in treating WD has yet to be verified, although a few animal studies have shown that stem cell transplantation could partially correct the abnormal metabolic phenotype of WD. In this case report, we present the therapeutic effect of human amniotic fluid containing stem cells in one WD patient.

Case presentation

A 22-year-old Chinese woman was diagnosed with WD 1 year ago in 2019. The available drugs were not effective in managing the progressive neuropsychiatric symptoms. We treated the patient with pre-cultured human amniotic fluid containing stem cells. Amniotic fluid was collected from pregnant women who underwent induced labor at a gestational age of 19–26 weeks, and then, the fluid was cultured for 2 h to allow stem cell expansion. Cultured amniotic fluid that contained amniotic fluid derived stem cells (AFSC) in the range of approximately 2.8–5.5 × 104/ml was administrated by IV infusion at a rate of 50–70 drops per minute after filtration with a 300-mu nylon mesh. Before the infusion of amniotic fluid, low-molecular-weight heparin and dexamethasone were successively administrated. The patient received a total of 12 applications of amniotic fluid from different pregnant women, and the treatment interval depended on the availability of amniotic fluid. The neuropsychiatric symptoms gradually improved after the stem cell treatment. Dystonia, which included tremor, chorea, dysphagia, dysarthria, and drooling, almost disappeared after 1.5 years of follow-up. The Unified Wilson’s Disease Rating Scale score of the patient decreased from 72 to 10. Brain magnetic resonance imaging (MRI) showed a reduction in the lesion area and alleviation of damage in the central nervous system, along with a partial recovery of the lesion to the normal condition. The serum ceruloplasmin level was elevated from undetectable to 30.8 mg/L, and the 24-h urinary copper excretion decreased from 171 to 37 μg. In addition, amniotic fluid transplantation also alleviates hematopoietic disorders. There were no adverse reactions during or after amniotic fluid administration.

Conclusion

Amniotic fluid administration, through which stem cells were infused, significantly improves the clinical outcomes in the WD patient, and the finding may provide a novel approach for managing WD effectively.
Inflammation mechanism and anti-inflammatory therapy of dry eye
Authors: Chu Liyuan , Wang Caiming , Zhou Hongyan
Published: February 2024

Dry eye is a widespread chronic inflammatory disease that causes fatigue, tingling, burning, and other symptoms. Dry eye is attributed to rheumatic diseases, diabetes, hormone disorders, and contact lenses, which activate inflammatory pathways: mitogen-activated protein kinases (MAPK) and nuclear factor-B (NF-κB), promote macrophage inflammatory cell and T cell activation, and inflammation factors. Clinicians use a combination of anti-inflammatory drugs to manage different symptoms of dry eye; some of these anti-inflammatory drugs are being developed. This review introduces the dry eye inflammation mechanisms and the involved inflammatory factors. We also elucidate the anti-inflammatory drug mechanism and the detection limits.
Efficacy of erector spine plane block in two different approaches to lumbar spinal fusion surgery: a retrospective pilot study
Authors: Birnbaums Jānis Verners , Ozoliņa Agnese , Solovjovs Leonids , Glāzniece-Kagane Zane , Nemme Jānis , Logina Ināra
Published: February 2024

Background

Erector spine plane block (ESPB) has been widely used in spinal surgery, although there are variable data about its efficacy.

Objectives

This study aimed to evaluate the efficacy of ESPB in elective lumbar spinal fusion surgery patients with two different surgical approaches.

Materials and methods

Retrospectively, 45 elective lumbar transpedicular fusion (TPF) surgery patients undergoing open surgery with different approaches [posterior transforaminal fusion approach (TLIF) or combined posterior and anterior approach (TLIF+ALIF)] were divided into 2 groups: general anesthesia (GA, n = 24) and general anesthesia combined with ESPB (GA + ESPB, n = 21). The primary outcome was to analyze the efficacy of ESPB in two different surgical approaches in terms of pain intensity in the first 48 h. Secondary: Fentanyl-free patients and opioid consumption in the first 24 h postoperatively. Comparative analysis was performed (SPSS® v. 28.0) (p < 0.05).

Results

Out of 45 patients (27 female), 21 received GA + ESPB and 24 received GA. The average age was 60.3 ± 14.3 years. Chronic back pain before the operation was registered in 56% of patients. ESPB was performed in 17 TLIF and in 4 TLIF+ALIF patients. ESPB significantly reduced pain intensity at rest in both surgical approaches 48 h after surgery (p < 0.05). The need for postoperative fentanyl infusion was significantly lower in the group treated with GA + ESPB in both surgical approaches than in those who only received GA (29% vs. 77% in TLIF and 0% vs. 80% in TLIF+ALIF); p = 0.01 and p = 0.004. Additionally, we observed that ESPB provides a good analgesic effect for up to 6.8 ± 3.2 h in the TLIF and 8.9 ± 7.6 h in the TLIF+ALIF approaches. Consequently, ESPB reduced the initiation of the fentanyl compared to GA alone, with a mean difference of 3.2 ± 4.2 h in the TLIF subgroup (p = 0.045) and 6.7 ± 5.3 h in TLIF +ALIF (p = 0.028). Only in the TLIF+ALIF approach, ESPB reduced the total fentanyl consumption compared to those with GA (1.43 ± 0.45 mg/24 h vs. 0.93 ± 0.68 mg/24 h; p = 0.015).

Conclusion

ESPB significantly reduced pain at rest after surgery, the number of patients requiring immediate postoperative fentanyl analgesia, and total fentanyl consumption in both surgical approaches, particularly in TLIF+ALIF. However, the application of ESPB does not always provide completely sufficient analgesia.