bluuebunny/crossref_metadata_2025 huggingface dataset:
Wild populations of Pacific oysters (Magallana gigas) emerge during the blob heatwave in south Puget Sound, Washington USA
Authors: Beck Emma Lee , Ruesink Jennifer , Troyer Stena , Behrens Michael
Published: March 2024

Marine heatwaves have altered ecosystems globally, including changing community composition and facilitating the spread of invasive species. In south Puget Sound, Washington (USA), non-native Pacific oysters (Magallana gigas) have been farmed extensively for almost a century and grown in enhancement sites, however, they have only recently recruited in the wild. This study explores how the appearance of Pacific oysters was related spatially (eight sites) and temporally (decade) to warmer summer water temperatures in south Puget Sound and compares oyster persistence across five sites where recruitment occurred. The largest recruitment event from 2012-2020 was in the summer of 2015, in the middle of the east Pacific Blob marine heatwave which led to warm water temperatures off the west coast of North America. Throughout the study period, the number of oyster recruits each year was positively correlated with warmer water temperatures. Oyster population densities differed across the five sites where recruitment occurred and generally declined after 2015, but showed no site by year interactions, which is consistent with spatially-variable recruitment and similar post-recruitment survival. Mean oyster shell heights also differed among sites, which could reflect different growth trajectories or recreational harvest patterns. This study supports the claim that warming sea surface temperatures may interact with species introductions to change modern biogeography.
Seagrasses produce most of the soil blue carbon in three Maldivian islands
Authors: Macreadie Peter I. , Wartman Melissa , Roe Philippa , Hodge Jessica M. , Helber Stephanie B. , Waryszak Pawel , Raoult Vincent
Published: March 2024

Blue carbon is fast garnering international interest for its disproportionate contribution to global carbon stocks. However, our understanding of the size of these blue carbon stocks, as well as the provenance of carbon that is stored within them, is still poor. This is especially pertinent for many small-island nations that may have substantial blue carbon ecosystems that are poorly studied. Here, we present a preliminary assessment of blue carbon from three islands in the Maldives. The higher purpose of this research was to assess the feasibility of using blue carbon to help offset carbon emissions associated with Maldivian tourism, the largest Maldivian industry with one of the highest destination-based carbon footprints, globally. We used stable isotope mixing models to identify how habitats contributed to carbon found in sediments, and Loss on Ignition (LoI) to determine carbon content. We found that for the three surveyed islands, seagrasses (Thalassia hemprichii, Thalassodendron ciliatum, Halodule pinofilia, Syringodium isoetifolium, and Cymodocea rotundata) were the main contributors to sediment blue carbon (55 – 72%) while mangroves had the lowest contribution (9 – 44%). Surprisingly, screw pine (Pandanus spp.), a relative of palm trees found across many of these islands, contributed over a quarter of the carbon found in sediments. Organic carbon content (‘blue carbon’) was 6.8 ± 0.3 SE % and 393 ± 29 tonnes ha-1 for mangrove soils, and 2.5 ± 0.2% and 167 ± 20 tonnes ha-1 for seagrasses, which is slightly higher than global averages. While preliminary, our results highlight the importance of seagrasses as carbon sources in Maldivian blue carbon ecosystems, and the possible role that palms such as screw pines may have in supplementing this. Further research on Maldivian blue carbon ecosystems is needed to: 1) map current ecosystem extent and opportunities for additionality through conservation and restoration; 2) determine carbon sequestration rates; and 3) investigate options and feasibility for tourism-related blue carbon crediting. Overall, the opportunity for blue carbon in the Maldives is promising, but the state of knowledge is very limited.
The protective effect of tumor necrosis factor-alpha inhibitors in COVID-19 in patients with inflammatory rheumatic diseases compared to the general population—A comparison of two German registries
Authors: Hasseli Rebecca , Hanses Frank , Stecher Melanie , Specker Christof , Weise Tobias , Borgmann Stefan , Hasselberger Martina , Hertenstein Bernd , Hower Martin , Hoyer Bimba F. , Koll Carolin , Krause Andreas , von Lilienfeld-Toal Marie , Lorenz Hanns-Martin , Merle Uta , Nunes de Miranda Susana M. , Pletz Mathias W. , Regierer Anne C. , Richter Jutta G. , Rieg Siegbert , Roemmele Christoph , Ruethrich Maria M. , Schmeiser Tim , Schulze-Koops Hendrik , Strangfeld Anja , Vehreschild Maria J.G.T. , Voit Florian , Voll Reinhard E. , Vehreschild Jörg Janne , Müller-Ladner Ulf , Pfeil Alexander
Published: March 2024

Objectives

To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared.

Methods

4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total.

Results

Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19.

Conclusion

Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease.
Development and clinical validation of a dual ddPCR assay for detecting carbapenem-resistant Acinetobacter baumannii in bloodstream infections
Authors: Kou Xiaoxia , Zhu Detu , Zhang Yandong , Huang Liyan , Liang Jiawei , Wu Ziman , Liu Ze , Guan Chushi , Yu Lin
Published: March 2024

Objective

Acinetobacter baumannii (A. baumannii, AB) represents a major species of Gram-negative bacteria involved in bloodstream infections (BSIs) and shows a high capability of developing antibiotic resistance. Especially, carbapenem-resistant Acinetobacter baumannii (CRAB) becomes more and more prevalent in BSIs. Hence, a rapid and sensitive CRAB detection method is of urgent need to reduce the morbidity and mortality due to CRAB-associated BSIs.

Methods

A dual droplet digital PCR (ddPCR) reaction system was designed for detecting the antibiotic resistance gene OXA-23 and AB-specific gene gltA. Then, the specificity of the primers and probes, limit of detection (LOD), linear range, and accuracy of the assay were evaluated. Furthermore, the established assay approach was validated on 37 clinical isolates and compared with blood culture and drug sensitivity tests.

Results

The dual ddPCR method established in this study demonstrated strong primer and probe specificity, distinguishing CRAB among 21 common clinical pathogens. The method showed excellent precision (3 × 10−4 ng/μL, CV < 25%) and linearity (OXA-23: y = 1.4558x + 4.0981, R2 = 0.9976; gltA: y = 1.2716x + 3.6092, R2 = 0.9949). While the dual qPCR LOD is 3 × 10−3 ng/μL, the dual ddPCR’s LOD stands at 3 × 10−4 ng/μL, indicating a higher sensitivity in the latter. When applied to detect 35 patients with BSIs of AB, the results were consistent with clinical blood culture identification and drug sensitivity tests.

Conclusion

The dual ddPCR detection method for OXA-23 and gltA developed in this study exhibits good specificity, excellent linearity, and a higher LOD than qPCR. It demonstrates reproducibility even for minute samples, making it suitable for rapid diagnosis and precision treatment of CRAB in BSIs.
Prevalence and risk factors of seafood-borne Vibrio vulnificus in Asia: a systematic review with meta-analysis and meta-regression
Authors: Tanveer Maryum , Ntakiyisumba Eurade , Won Gayeon
Published: March 2024

Vibrio vulnificus is a free-living marine bacterium associated with the contamination of fish and shellfish—the most consumed seafood in Asia. Owing to its potentially lethal clinical consequences, the consumption of seafood contaminated with V. vulnificus has become a growing public health concern. This systematic review with meta-analysis and meta-regression aimed to integrate data on the prevalence of seafood-borne V. vulnificus specifically in Asia and assess the potential risk factors that can influence the outcomes. A comprehensive literature search of four electronic databases yielded 279 relevant studies, among which 38 fulfilled the inclusion criteria. These selected studies were subjected to risk-of-bias assessment and data extraction by three independent researchers. A meta-analysis of the eligible studies estimated the overall prevalence of seafood-borne V. vulnificus in Asia to be 10.47% [95% confidence interval (CI): 6.8–15.8%], with bivalve shellfish, such as oysters, mussels, clams, and cockles being the most contaminated seafood. The highest prevalence was reported in Japan, where 47.6% of the seafood samples tested positive for V. vulnificus. The subgroup and meta-regression analyses identified three potential covariates—detection method, publication year, and country—associated with between-study heterogeneity. Furthermore, data visualization displayed the variations in V. vulnificus prevalence across the studies, associated with differences in sample type, sample size, and sampling stage. This study provides valuable insights into the prevalence of V. vulnificus in fish and shellfish across the entire Asian continent and highlights the potential factors that cause variation in the prevalence rates among the studies. These findings underscore the importance of enhancing hygiene measures throughout the seafood supply chain to mitigate V. vulnificus infection risks and ensure the safety of consumers.
Engagement of α3β1 and α2β1 integrins by hypervirulent Streptococcus agalactiae in invasion of polarized enterocytes
Authors: De Gaetano Giuseppe Valerio , Lentini Germana , Coppolino Francesco , Famà Agata , Pietrocola Giampiero , Beninati Concetta
Published: March 2024

The gut represents an important site of colonization of the commensal bacterium Streptococcus agalactiae (group B Streptococcus or GBS), which can also behave as a deadly pathogen in neonates and adults. Invasion of the intestinal epithelial barrier is likely a crucial step in the pathogenesis of neonatal infections caused by GBS belonging to clonal complex 17 (CC17). We have previously shown that the prototypical CC17 BM110 strain invades polarized enterocyte-like cells through their lateral surfaces using an endocytic pathway. By analyzing the cellular distribution of putative GBS receptors in human enterocyte-like Caco-2 cells, we find here that the alpha 3 (α3) and alpha 2 (α2) integrin subunits are selectively expressed on lateral enterocyte surfaces at equatorial and parabasal levels along the vertical axis of polarized cells, in an area corresponding to GBS entry sites. The α3β1 and α2β1 integrins were not readily accessible in fully differentiated Caco-2 monolayers but could be exposed to specific antibodies after weakening of intercellular junctions in calcium-free media. Under these conditions, anti-α3β1 and anti-α2β1 antibodies significantly reduced GBS adhesion to and invasion of enterocytes. After endocytosis, α3β1 and α2β1 integrins localized to areas of actin remodeling around GBS containing vacuoles. Taken together, these data indicate that GBS can invade enterocytes by binding to α3β1 and α2β1 integrins on the lateral membrane of polarized enterocytes, resulting in cytoskeletal remodeling and bacterial internalization. Blocking integrins might represent a viable strategy to prevent GBS invasion of gut epithelial tissues.
Growth dynamic of biofilm-associated Naegleria fowleri in freshwater on various materials
Authors: Goudot Sébastien , Mathieu Laurence , Herbelin Pascaline , Soreau Sylvie , Jorand Frédéric P. A.
Published: March 2024

In industrial water systems, the occurrence of biofilm-associated pathogenic free-living amoebae (FLA) such as Naegleria fowleri is a potential hygienic problem, and factors associated with its occurrence remain poorly understood. This study aimed to evaluate the impact of four cooling circuit materials on the growth of N. fowleri in a freshwater biofilm formed at 42°C and under a hydrodynamic shear rate of 17 s−1 (laminar flow): polyvinyl chloride, stainless steel, brass, and titanium. Colonization of the freshwater biofilms by N. fowleri was found to be effective on polyvinyl chloride, stainless steel, and titanium. For these three materials, the ratio of (bacterial prey)/(amoeba) was found to control the growth of N. fowleri. All materials taken together, a maximum specific growth rate of 0.18 ± 0.07 h−1 was associated with a generation time of ~4 h. In contrast, no significant colonization of N. fowleri was found on brass. Therefore, the contribution of copper is strongly suspected.
The horizontal ladder test (HLT) protocol: a novel, optimized, and reliable means of assessing motor coordination in Sus scrofa domesticus
Authors: Liu Xiaobo , Gutierrez Ana G. , Vega Arlette , Willms Joshua O. , Driskill Jackson , Panthagani Praneetha , Sanchez Jordan , Aguilera Monica , Backus Brittany , Bailoo Jeremy D. , Bergeson Susan E.
Published: March 2024

Pigs can be an important model for preclinical biological research, including neurological diseases such as Alcohol Use Disorder. Such research often involves longitudinal assessment of changes in motor coordination as the disease or disorder progresses. Current motor coordination tests in pigs are derived from behavioral assessments in rodents and lack critical aspects of face and construct validity. While such tests may permit for the comparison of experimental results to rodents, a lack of validation studies of such tests in the pig itself may preclude the drawing of meaningful conclusions. To address this knowledge gap, an apparatus modeled after a horizontally placed ladder and where the height of the rungs could be adjusted was developed. The protocol that was employed within the apparatus mimicked the walk and turn test of the human standardized field sobriety test. Here, five Sinclair miniature pigs were trained to cross the horizontally placed ladder, starting at a rung height of six inches and decreasing to three inches in one-inch increments. It was demonstrated that pigs can reliably learn to cross the ladder, with few errors, under baseline/unimpaired conditions. These animals were then involved in a voluntary consumption of ethanol study where animals were longitudinally evaluated for motor coordination changes at baseline, 2.5, 5, 7.5, and 10% ethanol concentrations subsequently to consuming ethanol. Consistent with our predictions, relative to baseline performance, motor incoordination increased as voluntary consumption of escalating concentrations of ethanol increased. Together these data highlight that the horizontal ladder test (HLT) test protocol is a novel, optimized and reliable test for evaluating motor coordination as well as changes in motor coordination in pigs.
Delipid extracorporeal lipoprotein filter from plasma system: a new intensive lipid lowering therapy for patients with acute ischemic stroke
Authors: Jiao Yuqiong , Yang Qi , Ye Ting , Zhu Jun , Li Qunyi , Han Xiang , Dong Qiang
Published: March 2024

Objectives

To investigate the safety and efficacy of the delipid extracorporeal lipoprotein filter from plasma (DELP) system, a new low-density lipoprotein cholesterol (LDL-C) adsorption system, in acute ischemic stroke (AIS) patients.

Patients and methods

In the present study, a total of 180 AIS patients were enrolled during March 2019 to February 2021. They were divided into DELP group (n1 = 90) and the control group (n2 = 90). The treatment protocol and vascular access of DELP treatment was established and evaluated. For the DELP group, clinical data and laboratory results including plasma lipid and safety parameters before and after the apheresis were collected and analyzed. For all participants, neurological scores were assessed and recorded.

Results

For the DELP group, 90 patients including 70 males and 20 females were included. The mean LDL-C was significantly decreased from 3.15 ± 0.80 mmol/L to 2.18 ± 0.63 mmol/L (30.79%, p < 0.001) during a single DELP treatment, and decreased from 3.42 ± 0.87 mmol/L to 1.87 ± 0.48 mmol/L (45.32%, p < 0.001) after two DELP treatments. No clinically relevant changes were observed in hematologic safety parameters and blood pressure levels except for hematocrit and total protein throughout the whole period of DELP treatment. The DELP group showed improvement relative to the control group in National Institute of Health stroke scale scores (NIHSS) on the 14th and 90th day after stroke. Moreover, the DELP group had a significantly higher ratio of mRS 0 to 1 on the 90th day after stroke.

Conclusion

The new LDL-C adsorption system, the DELP system, may provide a new option for intensive lipid lowering therapy in AIS patients in view of its safety, efficacy, and operation feasibility.
Habituation disorders in auditory middle latency response of persistent postural-perceptual dizziness patients
Authors: Murofushi Toshihisa , Goto Fumiyuki , Ushio Munetaka
Published: March 2024

Objectives

To study habituation disorders in auditory middle latency response (AMLR) to repetitive stimuli of persistent postural-perceptual dizziness (PPPD) patients.

Subjects

Twenty-eight PPPD (10 men and 18 women, mean 59.5 years of age, 26–81 years of age) were enrolled. For comparison, data of 13 definite vestibular migraine (VM) patients (3 men, 10 women, mean age 45.5), 13 definite unilateral Meniere’s disease (MD) patients (2 men, 11 women, mean age 50.6), and 8 healthy control (HC) subjects (2 men, 6 women, mean age 37.1) in the previous study were utilized.

Methods

The electrodes were placed on the vertex and the spinal process of the fifth cervical vertebra. Clicks (0.1 msec, 70 dB nHL) were binaurally presented and averaged (800 times). Averaged responses were divided into 4 sets (S1 to S4) according to the temporal order. As peaks, Na, and Pa were identified, and relative Na-Pa amplitudes in S2–S4 to S1 were analyzed.

Results

The mean relative amplitude of PPPD patients showed lack of habituation (potentiation) as shown in VM patients, although the extent of potentiation was weaker than VM. Comparison of relative S4 amplitudes showed significant differences among the 4 groups (p = 0.0013 one-way ANOVA), Multiple comparison revealed significant differences between PPPD and MD (p = 0.0337 Dunnet’s test).

Conclusion

PPPD patients showed lack of habituation (potentiation) of Na-Pa amplitude in AMLR to repetitive stimuli. Lack of habituation (potentiation) might be associated with sensory processing disorders in PPPD.
Recurrence timing and patterns incorporating lymph node status after neoadjuvant chemoradiotherapy plus esophagectomy for esophageal squamous cell carcinoma
Authors: Liu Guihong , Hu Binbin , Chen Tao , Zhang Xin , Tang Yu , Chen Qian , Shi Huashan
Published: March 2024

Purpose

About 40% of esophageal squamous cell carcinoma (ESCC) patients experienced recurrence after neoadjuvant chemoradiotherapy (nCRT) plus esophagectomy. While limited information was available on recurrence risk stratification in ESCC after neoadjuvant treatment. Our previous study showed ypN status was a reliable tool to differentiate and predict the prognosis in the recurrent population. Here, we evaluated recurrence timing and patterns in ESCC patients, taking into consideration lymph node status after nCRT.

Materials and methods

A total of 309 ESCC patients treated with nCRT plus esophagectomy between 2018 and 2021 were enrolled in this observational cohort study. Lymph node status was recorded by the pathologist according to the surgical specimens. We retrospectively investigated the timing and patterns of recurrence and the prognoses in ESCC patients, taking into consideration lymph node status after nCRT.

Results

After nCRT plus surgery in ESCC patients, lymph node metastasis was associated with unfavorable clinicopathological factors and high risks of recurrence. In the recurrent subgroup, ypN+ patients experienced earlier recurrence, especially for locoregional recurrence within the first year. Moreover, ypN+ patients had poorer prognosis. However, the recurrence patterns in the ypN- and ypN+ groups were similar. Besides, there were no significant differences in surgery to recurrence, recurrence to death, or overall survival among patients with locoregional or distant recurrence for overall patients and within ypN- or ypN+ groups.

Conclusions

Lymph node metastasis was correlated with unfavorable clinicopathological factors and high risks of recurrence. Despite a similar recurrence pattern in the recurrent subgroup between the ypN- and ypN+ groups, ypN+ patients exhibited earlier recurrence and a worse prognosis.
Dark horse target Claudin18.2 opens new battlefield for pancreatic cancer
Authors: Xu Qian , Jia Caiyan , Ou Yan , Zeng Chuanxiu , Jia Yingjie
Published: March 2024

Pancreatic cancer is one of the deadliest malignant tumors, which is a serious threat to human health and life, and it is expected that pancreatic cancer may be the second leading cause of cancer death in developed countries by 2030. Claudin18.2 is a tight junction protein expressed in normal gastric mucosal tissues, which is involved in the formation of tight junctions between cells and affects the permeability of paracellular cells. Claudin18.2 is highly expressed in pancreatic cancer and is associated with the initiation, progression, metastasis and prognosis of cancer, so it is considered a potential therapeutic target. Up to now, a number of clinical trials for Claudin18.2 are underway, including solid tumors such as pancreatic cancers and gastric cancers, and the results of these trials have not yet been officially announced. This manuscript briefly describes the Claudia protein, the dual roles of Cluadin18 in cancers, and summarizes the ongoing clinical trials targeting Claudin18.2 with a view to integrating the research progress of Claudin18.2 targeted therapy. In addition, this manuscript introduces the clinical research progress of Claudin18.2 positive pancreatic cancer, including monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, CAR-T cell therapy, and hope to provide feasible ideas for the clinical treatment of Claudin18.2 positive pancreatic cancer.
Tumor integrin targeted theranostic iron oxide nanoparticles for delivery of caffeic acid phenethyl ester: preparation, characterization, and anti-myeloma activities
Authors: Smith Barkley , Li Yuancheng , Fields Travis , Tucker Michael , Staskiewicz Anna , Wong Erica , Ma Handong , Mao Hui , Wang Xinyu
Published: March 2024

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells preferentially in the bone marrow. Currently, emerging chemotherapy drugs with improved biosafety profiles, such as immunomodulatory agents and protease inhibitors, have been used in clinics to treat MM in both initial therapy or maintenance therapy post autologous hematopoietic stem cell transplantation (ASCT). We previously discovered that caffeic acid phenethyl ester (CAPE), a water-insoluble natural compound, inhibited the growth of MM cells by inducing oxidative stress. As part of our continuous effort to pursue a less toxic yet more effective therapeutic approach for MM, the objective of this study is to investigate the potential of CAPE for in vivo applications by using magnetic resonance imaging (MRI)-capable superparamagnetic iron oxide nanoparticles (IONP) as carriers. Cyclo (Arg-Gly-Asp-D-Phe-Cys) (RGD) is conjugated to IONP (RGD-IONP/CAPE) to target the overexpressed αvβ3 integrin on MM cells for receptor-mediated internalization and intracellular delivery of CAPE. A stable loading of CAPE on IONP can be achieved with a loading efficiency of 48.7% ± 3.3% (wt%). The drug-release studies indicate RGD-IONP/CAPE is stable at physiological (pH 7.4) and basic pH (pH 9.5) and subject to release of CAPE at acidic pH (pH 5.5) mimicking the tumor and lysosomal condition. RGD-IONP/CAPE causes cytotoxicity specific to human MM RPMI8226, U266, and NCI-H929 cells, but not to normal peripheral blood mononuclear cells (PBMCs), with IC50s of 7.97 ± 1.39, 16.75 ± 1.62, and 24.38 ± 1.71 μM after 72-h treatment, respectively. Apoptosis assays indicate RGD-IONP/CAPE induces apoptosis of RPMI8226 cells through a caspase-9 mediated intrinsic pathway, the same as applying CAPE alone. The apoptogenic effect of RGD-IONP/CAPE was also confirmed on the RPMI8226 cells co-cultured with human bone marrow stromal cells HS-5 in a Transwell model to mimic the MM microenvironment in the bone marrow. In conclusion, we demonstrate that water-insoluble CAPE can be loaded to RGD-IONP to greatly improve the biocompatibility and significantly inhibit the growth of MM cells in vitro through the induction of apoptosis. This study paves the way for investigating the MRI-trackable delivery of CAPE for MM treatment in animal models in the future.
Breaking genetic shackles: The advance of base editing in genetic disorder treatment
Authors: Xu Fang , Zheng Caiyan , Xu Weihui , Zhang Shiyao , Liu Shanshan , Chen Xiaopeng , Yao Kai
Published: March 2024

The rapid evolution of gene editing technology has markedly improved the outlook for treating genetic diseases. Base editing, recognized as an exceptionally precise genetic modification tool, is emerging as a focus in the realm of genetic disease therapy. We provide a comprehensive overview of the fundamental principles and delivery methods of cytosine base editors (CBE), adenine base editors (ABE), and RNA base editors, with a particular focus on their applications and recent research advances in the treatment of genetic diseases. We have also explored the potential challenges faced by base editing technology in treatment, including aspects such as targeting specificity, safety, and efficacy, and have enumerated a series of possible solutions to propel the clinical translation of base editing technology. In conclusion, this article not only underscores the present state of base editing technology but also envisions its tremendous potential in the future, providing a novel perspective on the treatment of genetic diseases. It underscores the vast potential of base editing technology in the realm of genetic medicine, providing support for the progression of gene medicine and the development of innovative approaches to genetic disease therapy.
Safety of midodrine in patients with heart failure with reduced ejection fraction: a retrospective cohort study
Authors: Wu Ming-Ju , Chen Cheng-Hsu , Tsai Shang-Feng
Published: March 2024

Background: Heart failure with reduced ejection fraction (HFrEF) poses significant health risks. Midodrine for maintaining blood pressure in HFrEF, requires further safety investigation. This study explores midodrine’s safety in HFrEF through extensive matched analysis.

Methods: Patients with HFrEF (LVEF <50%) without malignancy, non-dialysis dependence, or non-orthostatic hypotension, were enrolled between 28 August 2013, and 27 August 2023. Propensity score matching (PSM) created 1:1 matched groups. Outcomes included mortality, stage 4 and 5 chronic kidney disease (CKD), emergency room (ER) visits, intensive care unit (ICU) admissions, hospitalizations, and respiratory failure. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated for each outcome, and Kaplan-Meier survival analysis was performed. Subgroup analyses were conducted based on gender, age (20-<65 vs. ≥65), medication refill frequency, and baseline LVEF.

Results: After 1:1 PSM, 5813 cases were included in each group. The midodrine group had higher risks of respiratory failure (HR: 1.16, 95% CI: 1.08–1.25), ICU admissions (HR: 1.14, 95% CI: 1.06–1.23), hospitalizations (HR: 1.21, 95% CI: 1.12–1.31), and mortality (HR: 1.090, 95% CI: 1.01–1.17). Interestingly, midodrine use reduced ER visits (HR: 0.77, 95% CI: 0.71–0.83). Similar patterns of lower ER visit risk and higher risks for ICU admissions, respiratory failure, and overall hospitalizations were observed in most subgroups.

Conclusion: In this large-scale study, midodrine use was associated with reduced ER visits but increased risks of respiratory failure, prolonged ICU stays, higher hospitalizations, and elevated mortality in HFrEF patients. Further research is needed to clarify midodrine’s role in hemodynamic support and strengthen existing evidence.
Japanese quails (Coturnix Japonica) show keel bone damage during the laying period—a radiography study
Authors: Hildebrand Lisa , Gerloff Christoph , Winkler Birthe , Eusemann Beryl Katharina , Kemper Nicole , Petow Stefanie
Published: March 2024

Keel bone damage is an important welfare issue in laying hens and can occur with a high prevalence of up to 100% of hens within one flock. Affected hens suffer from pain. Although multiple factors contribute to the prevalence and severity of keel bone damage, selection for high laying performance appears to play a key role. With up to 300 eggs/year, Japanese quails show a high laying performance, too, and, thus, may also show keel bone damage. However, to our knowledge, there are no scientific results on keel bone damage in Japanese quails to date. Therefore, the aim of this study was to assess whether keel bone fractures and deviations occur in Japanese quails and to obtain more detailed information about the development of their keel bone during the production cycle. A group of 51 female quails were radiographed at 8, 10, 15, 19, and 23 weeks of age. The X-rays were used to detect fractures and deviations and to measure the lateral surface area, length, and radiographic density of the keel bone. In addition, the length of the caudal cartilaginous part of the keel bone was measured to learn more about the progress of ossification. At 23 weeks of age, quails were euthanized and their macerated keel bones assessed for fractures and deviations. Both keel bone deviations and keel bone fractures were detected in the Japanese quails. In the 23rd week of age, 82% of the quails had a deviated keel bone as assessed after maceration. Furthermore, there was a decrease in radiographic density, lateral surface area, and length of the keel bone between weeks of age 8 and 19. This could indicate a general loss of bone substance and/or demineralization of the keel bone. Our study shows that keel bone damage is not only a problem in laying hens but also affects female Japanese quails.
High-throughput sequencing reveals the structure and metabolic resilience of desert microbiome confronting climate change
Authors: Mousa Walaa K. , Abu-Izneid Tareq , Salah-Tantawy Ahmed
Published: March 2024

Introduction

Desert ecosystems harbor a unique microbial diversity that is crucial for ecological stability and biogeochemical cycles. An in-depth understanding of the biodiversity, compositions, and functions of these microbial communities is imperative to navigate global changes and confront potential threats and opportunities applicable to agricultural ecosystems amid climate change.

Methods

This study explores microbial communities in the rhizosphere and endosphere of desert plants native to the Arabian Peninsula using next-generation sequencing of the 16S rRNA gene (V3-V4 hypervariable region).

Results

Our results reveal that each microbial community has a diverse and unique microbial composition. Based on alpha and beta diversity indices, the rhizosphere microbiome is significantly diverse and richer in microbial taxa compared to the endosphere. The data reveals a shift towards fast-growing microbes with active metabolism, involvement in nutrient cycling, nitrogen fixation, and defense pathways. Our data reveals the presence of habitat-specific microbial communities in the desert, highlighting their remarkable resilience and adaptability to extreme environmental conditions. Notably, we observed the existence of radiation-resistant microbes such as Deinococcus radiotolerans, Kocuria sp., and Rubrobacter radiotolerans which can tolerate high levels of ionizing radiation. Additionally, examples of microbes exhibiting tolerance to challenging conditions include Nocardioides halotolerans, thriving in high-salinity environments, and hyperthermophilic microbes such as Quasibacillus thermotolerans. Moreover, functional analysis reveals enrichment in chaperon biosynthesis pathways associated with correct protein folding under heat stress conditions.

Discussion

Our research sheds light on the unique diversity of desert microbes and underscores their potential applications to increase the resilience of agriculture ecosystems, offering a promising strategy to fortify crops against the challenges posed by climate change, ultimately supporting sustainable food production for our ever-expanding global population.
A decade of advances in the study of buckwheat for organic farming and agroecology (2013-2023)
Authors: Vieites-Álvarez Yedra , Reigosa Manuel J. , Sánchez-Moreiras Adela M.
Published: March 2024

During the last decade, research has shown the environment and human health benefits of growing buckwheat (Fagopyrumspp.). This comprehensive review aims to summarize the major advancements made in the study of buckwheat from 2013 to 2023, focusing on its agronomic characteristics, nutritional value, and potential applications in sustainable agriculture. The review examines the diverse applications of buckwheat in organic and agroecological farming systems, and discusses the ability of buckwheat to control weeds through allelopathy, competition, and other sustainable farming methods, such as crop rotation, intercropping and green manure, while improving soil health and biodiversity. The review also explores the nutritional value of buckwheat. It delves into the composition of buckwheat grains, emphasizing their high protein content, and the presence of essential amino acids and valuable micronutrients, which is linked to health benefits such as lowering cholesterol levels, controlling diabetes and acting against different types of cancer, among others. Finally, the review concludes by highlighting the gaps in current knowledge, and proposing future research directions to further optimize buckwheat production in organic or agroecological farming systems. It emphasizes the need for interdisciplinary collaboration, and the integration of traditional knowledge with modern scientific approaches to unlock the full potential of buckwheat as a sustainable crop.
Addressing psychosocial needs in patients with Long-COVID (PsyLoCo-Study): study protocol of a pilot-study of a specialized modular intervention
Authors: Allwang Christine , Frank Tamara , Bruckmann Paul , Dinkel Andreas , Binneboese Marius , Wallis Hannah , Elgner Melanie , Giel Katrin E. , Schurr Marisa , Gündel Harald , Wedekind Lisa , Kuhn Julia , Lahmann Claas , Müller Anne-Maria , Beckmann Pauline , Massag Janka , Mikolajczyk Rafael , Junne Florian
Published: March 2024

Introduction

After an acute infection with the corona virus 10-20% of those affected suffer from ongoing or new symptoms. A causal therapy for the phenomenon known as Long/Post-COVID is still lacking and specific therapies addressing psychosocial needs of these patients are imperatively needed. The aim of the PsyLoCo-study is developing and piloting a psychotherapeutic manual, which addresses Long/Post-COVID-related psychosocial needs and supports in coping with persistent bodily symptoms as well as depressive or anxiety symptoms.

Methods and analysis

This pilot trial implements a multi-centre, 2-arm (N=120; allocation ratio: 1:1), parallel group, randomised controlled design. The pilot trial is designed to test the feasibility and estimate the effect of 1) a 12-session psychotherapeutic intervention compared to 2) a wait-list control condition on psychosocial needs as well as bodily and affective symptoms in patients suffering from Long/Post-COVID. The intervention uses an integrative, manualized, psychotherapeutic approach. The primary study outcome is health-related quality of life. Outcome variables will be assessed at three timepoints, pre-intervention (t1), post-intervention (t2) and three months after completed intervention (t3). To determine the primary outcome, changes from t1 to t2 are examined. The analysis will be used for the planning of the RCT to test the efficacy of the developed intervention.

Discussion

The pilot study will evaluate a 12-session treatment manual for Long/Post-COVID sufferers and the therapy components it contains. The analysis will provide insights into the extent to which psychotherapeutic treatment approaches improve the symptoms of Long/Post-COVID sufferers. The treatment manual is designed to be carried out by psychotherapists as well as people with basic training in psychotherapeutic techniques. This approach was chosen to enable a larger number of practitioners to provide therapeutic support for Long/Post-COVID patients. After completion of the pilot study, it is planned to follow up with a randomized controlled study and to develop a treatment guideline for general practitioners and interested specialists.

Trial registration

The pilot trial has been registered with the German Clinical Trials Register (Deutsches Register Klinischer Studien; Trial-ID: DRKS00030866; URL: https://drks.de/search/de/trial/DRKS00030866) on March 7, 2023.
Tracing the paths: a systematic review of mediators of complex trauma and complex post-traumatic stress disorder
Authors: Harris Joseph , Loth Eva , Sethna Vaheshta
Published: March 2024

Complex trauma is associated with complex-posttraumatic stress disorder (CPTSD). While dissociative processes, developmental factors and systemic factors are implicated in the development of CPTSD, there are no existing systematic reviews examining the underlying pathways linking complex trauma and CPTSD. This study aims to systematically review evidence of mediating factors linking complex trauma exposure in childhood (birth to eighteen years of age) and subsequent development of CPTSD (via self-reports and diagnostic assessments). All clinical, at-risk and community-sampled articles on three online databases (PsycINFO, MedLine and Embase) were systematically searched, along with grey literature from ProQuest. Fifteen articles were eligible for inclusion according to pre-determined eligibility criteria and a search strategy. Five categories of mediating processes were identified: 1) dissociative processes; 2) relationship with self; 3) emotional developmental processes; 4) social developmental processes; and 5) systemic and contextual factors. Further research is required to examine the extent to which targeting these mediators may act as mechanisms for change in supporting individuals to heal from complex trauma.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022346152.
Reduced body-image disturbance by body-image interventions is associated with neural-response changes in visual and social processing regions: a preliminary study
Authors: Hamamoto Yumi , Oba Kentaro , Ishibashi Ryo , Ding Yi , Nouchi Rui , Sugiura Motoaki
Published: March 2024

Introduction

Body-image disturbance is a major factor in the development of eating disorders, especially among young women. There are two main components: perceptual disturbance, characterized by a discrepancy between perceived and actual body size, and affective disturbance, characterized by a discrepancy between perceived and ideal body size. Interventions targeting body-image disturbance ask individuals to describe their own body without using negative expressions when either viewing it in a mirror or imagining it. Despite the importance of reducing body-image disturbance, its neural mechanisms remain unclear. Here we investigated the changes in neural responses before and after an intervention. We hypothesized that neural responses correlated with the degree of body-image disturbance would also be related to its reduction, i.e., a reduction in perceptual and affective disturbances would be related to changes in attentional and socio-cognitive processing, respectively.

Methods

Twenty-eight young adult women without known psychiatric disorders underwent a single 40-min intervention. Participants completed tasks before and after the intervention, in which they estimated their perceived and ideal body sizes using distorted silhouette images to measure body-image disturbance. We analyzed the behavioral and neural responses of participants during the tasks.

Results

The intervention did not significantly reduce body-image disturbance. Analysis of individual differences showed distinct changes in neural responses for each type of disturbance. A decrease in perceptual disturbance was associated with bodily visuospatial processing: increased activation in the left superior parietal lobule, bilateral occipital gyri, and right cuneus. Reduced affective disturbance was associated with socio-cognitive processing; decreased activation in the right temporoparietal junction, and increased functional connectivity between the left extrastriate body area and the right precuneus.

Discussion

We identified distinct neural mechanisms (bodily visuospatial and socio-cognitive processing) associated with the reduction in each component of body-image disturbance. Our results imply that different neural mechanisms are related to reduced perceptual disturbance and the expression thereof, whereas similar neural mechanisms are related to the reduction and expression of affective disturbance. Considering the small sample size of this study, our results should be regarded as preliminary.
Deployment of attention to facial expressions varies as a function of emotional quality—but not in alexithymic individuals
Authors: Surber Chiara , Hoepfel Dennis , Günther Vivien , Kersting Anette , Rufer Michael , Suslow Thomas , Bodenschatz Charlott Maria
Published: March 2024

Background

Alexithymia is a risk factor for emotional disorders and is characterized by differences in automatic and controlled emotion processing. The multi-stimulus free-viewing task has been used to detect increased negative and reduced positive attentional biases in depression and anxiety. In the present eye-tracking study, we examined whether lexical emotional priming directs attention toward emotion-congruent facial expressions and whether alexithymia is related to impairments in lexical priming and spontaneous attention deployment during multiple face perception.

Materials and methods

A free-viewing task with happy, fearful, angry, and neutral faces shown simultaneously was administered to 32 alexithymic and 46 non-alexithymic individuals along with measures of negative affect and intelligence. Face presentation was preceded by masked emotion words. Indices of initial orienting and maintenance of attention were analyzed as a function of prime or target category and study group.

Results

Time to first fixation was not affected by prime category or study group. Analysis of fixation duration yielded a three-way interaction. Alexithymic individuals exhibited no prime or target category effect, whereas non-alexithymic individuals showed a main effect of target condition, fixating happy faces longer than neutral and angry faces and fearful faces longer than angry faces.

Discussion

Our results show evidence of attentional biases for positive and fearful social information in non-alexithymic individuals, but not in alexithymic individuals. The lack of spontaneous attentional preference for these social stimuli in alexithymia might contribute to a vulnerability for developing emotional disorders. Our data also suggest that briefly presented emotion words may not facilitate gaze orientation toward emotion-congruent stimuli.
Development and implementation of a municipal outdoor play policy for children and youth in Nova Scotia, Canada: a community case study
Authors: Caldwell Hilary A. T. , Arthur Mike , Simms Ashley , Mawhinney Hannah , Hancock Friesen Camille L. , Kirk Sara F. L.
Published: March 2024

Background: Children and youth benefit from outdoor play; however, environments and policies to support outdoor play are often limited. The purpose of this paper is to describe a case study of the development of a municipal outdoor play policy in Nova Scotia, Canada. The outdoor play policy was developed by the Town of Truro with support from the UpLift Partnership, a School-Community-University Partnership in Nova Scotia, Canada. UpLift supports the health and well-being of school-aged children and youth using a Health Promoting Schools approach which identifies the important role of municipal government in creating healthy school communities. The UpLift Partnership and the municipality hosted online workshops for municipal staff, community leaders and partners that included content about the importance of outdoor play, barriers and facilitators to outdoor play, best practices for youth engagement, the policy development process, and how policy actions can support outdoor play. Workshop participants developed policy actions for their community of Truro, Nova Scotia to increase opportunities for outdoor play for children and youth. Following the workshops, a small team from the municipality and UpLift drafted an outdoor play policy and submitted it to Truro town council for approval. The outdoor play policy was adopted in Fall 2021 and has since informed recreation and municipal planning decisions. By presenting a case study of the development of this outdoor play policy, we hope other communities may be inspired to develop and adopt their own outdoor play policies to benefit children and youth in their communities.
Case report: A patient with ALK-positive large B-cell lymphoma benefited from myeloma-like treatment combined with the ALK inhibitor lorlatinib
Authors: Liu Dan , Xing Lijie , Wang Hui , Li Ping , Wei Haichen , Li Zengjun
Published: March 2024

Introduction

Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL). Patients with ALK+ LBCLs have poor response and survival outcomes when treated with traditional chemotherapy regiments. The efficacy of second- and third-generation ALK inhibitors has been reported in treating ALK+ LBCLs. Additionally, owing to the plasmablastic morphology and immune features observed in ALK+ LBCLs, plasma cell tumor therapies may be effective for this patient population. In this case report, we utilized a myeloma-like therapy combined with a third-generation ALK inhibitor for a newly diagnosed ALK+ LBCL patient.

Case presentation

We reported a 32-year-old male patient diagnosed with ALK+ LBCL. Immunohistochemistry (IHC) analysis revealed a plasma cell immunophenotype characterized by CD138 positivity but negativity for mature B lymphocyte markers. The patient received six cycles of VRD (bortezomib 1.3 mg/m2 d1, 4, 8, and 11; lenalidomide 25 mg qd d1–14; dexamethasone 20 mg d1–2, d4–5, d8–9, and d11–12) and cyclophosphamide (1.0 g q3w) treatment. Lorlatinib (100 mg once daily) was added starting from the second cycle of treatment onwards. After four cycles of treatment, the patient achieved complete remission, which was maintained for more than 6 months after completing chemotherapy, without any significant safety concerns.

Conclusion

VRD and cyclophosphamide combined with a third-generation ALK inhibitor resulted in durable complete remission for an individual with ALK+ LBCL, suggesting it as a therapeutic option for patients with this subtype.