bluuebunny/crossref_metadata_2025 huggingface dataset:
A case of massive hemoptysis caused by immunoglobulin G4-related respiratory disease in adults: case report and review of literature
Authors: Mei Chun-xia , Yue Guo-long , Feng Xia , Wu Hai-qiao , Li Jiong
Published: December 2024

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated chronic fibro-inflammatory condition, that can involve multiple systems. Immunoglobulin G4-related respiratory disease (IgG4-RRD) is relatively rare, with non-specific clinical symptoms. Hemoptysis is a rare clinical symptom of IgG4-RRD, and cases of massive hemoptysis in adults have not been reported. We present here a rare case of massive hemoptysis caused by IgG4-RRD in adults and review relevant literature. An 84-year-old female presented with recurrent cough and blood-streaked sputum, progressing to massive hemoptysis. Her chest CT showed patchy lesions in the lungs, initially misdiagnosed as a tumor. Ultimately, a biopsy confirmed the diagnosis of IgG4-RRD. The patient was treated with prednisone combined with leflunomide, which controlled her condition and maintained remission. However, after 13 months without hemoptysis, she experienced intermittent hemoptysis followed by a massive episode. Increasing the prednisone dose and continuing leflunomide treatment controlled the condition once again, with no recurrence in the subsequent year of follow-up. In patients with IgG4-RRD, particularly those with hemoptysis, it is essential to remain vigilant for massive hemoptysis. Similarly, in patients with lung patch lesions and no evidence of a tumor on biopsy, IgG4-RRD should not be overlooked. Early diagnosis and timely treatment can improve the patient’s clinical prognosis.
Association of the immunogenicity of intramuscular SARS-CoV-2 mRNA vaccination with computed tomography muscle images in patients with muscular disorders
Authors: Naka Tomoaki , Funato Michinori , Yasuda Kunihiko , Nakayama Takahiro , Kuru Satoshi
Published: December 2024

Backgrounds

Intramuscular mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have a low intensity and latency of antibody response in patients with muscular disorders (MDs). However, the mechanisms involved in this phenomenon remain unknown. This study aimed to clarify the mechanism of the low immunogenicity of intramuscular SARS-CoV-2 mRNA vaccination in patients with MDs.

Methods

We evaluated 44 individuals, including 23 patients with MDs and 21 patients without MDs. The median age of the patients was 39 years (range 20–63 years). The anti-SARS-CoV-2 spike protein receptor-binding domain (S-RBD) IgG levels from a previous study were reused. Mean computed tomography (CT) values and areas of the deltoid muscle from CT images were measured, and they were compared with the anti-SARS-CoV-2 S-RBD IgG levels.

Results

One month following the second vaccination, the antibody response among patients with MDs showed a low tendency compared with that among patients without MDs. Surprisingly, a similar pattern was observed when comparing mean CT values. Patients with mean CT values of zero HU and lower had a lower tendency of antibody response after the intramuscular administration of SARS-CoV-2 mRNA vaccines.

Conclusion

The low immunogenicity of intramuscular SARS-CoV-2 mRNA vaccination against MDs may be mainly affected by disease type and MD pathogenesis. However, SARS-CoV-2 immunization in patients with MDs warrants further investigation.
Development of a two-component recombinant vaccine for COVID-19
Authors: Sun Yi-Sheng , Xu Fang , Zhu Han-Ping , Xia Yong , Li Qiao-Min , Luo Yuan-Yuan , Lu Hang-Jing , Wu Bei-Bei , Wang Zhen , Yao Ping-Ping , Zhou Zhan
Published: December 2024

Introduction

Though COVID-19 as a public health emergency of international concern (PHEIC) was declared to be ended by the WHO, it continues to pose a significant threat to human society. Vaccination remains one of the most effective methods for preventing COVID-19. While most of the antigenic regions are found in the receptor binding domain (RBD), the N-terminal domain (NTD) of the S protein is another crucial region for inducing neutralizing antibodies (nAbs) against COVID-19.

Methods

In the two-dose immunization experiment, female BALB/c mice were intramuscularly immunized with different ratios of RBD-Fc and NTD-Fc proteins, with a total protein dose of 8 μg per mouse. Mice were immunized on day 0 and boosted on day 7. In the sequential immunization experiment, groups of female BALB/c mice were immunized with two doses of the inactivated SARS-CoV-2 vaccine (prototype strain) on day 0 and 7. On day 28, mice were boosted with RBD-Fc, NTD-Fc, RBD-Fc/NTD-Fc (9:1), RBD-Fc/NTD-Fc (3:1), inactivated SARS-CoV-2 vaccine (protoype strain), inactivated SARS-CoV-2 vaccine (omicron strain), individually. The IgG antibodies were detected using ELISA, while the neutralizing antibodies were measured through a microneutralization assay utilizing both the prototype and omicron strains. The ELISPOT assays were performed to measure the secretion of IL-4 and IFN-γ, and the concentrations of secreted IL-2 and IL-10 in the supernatants were measured by ELISA.

Results

We have first developed a two-component recombinant vaccine for COVID-19 based on RBD-Fc and NTD-Fc proteins, with an optimal RBD-Fc/NTD-Fc ratio of 3:1. This novel two-component vaccine demonstrated the ability to induce durable and potent IgG antibodies, as well as the neutralizing antibodies in both the two-dose homologous and sequential vaccinations. Heterologous booster with this two-component vaccine could induce higher neutralizing antibody titers than the homologous group. Additionally, the vaccine elicited relatively balanced Th1- and Th2-cell immune responses.

Conclusion

This novel two-component recombinant vaccine exhibits high immunogenicity and offers a potential booster strategy for COVID-19 vaccine development.
Recent advances in the role of mesenchymal stem cells as modulators in autoinflammatory diseases
Authors: Chen Baiyu , Chen Zhilei , He Mengfei , Zhang Lijie , Yang Longyan , Wei Lingling
Published: December 2024

Mesenchymal stem cells (MSCs), recognized for their self-renewal and multi-lineage differentiation capabilities, have garnered considerable wide attention since their discovery in bone marrow. Recent studies have underscored the potential of MSCs in immune regulation, particularly in the context of autoimmune diseases, which arise from immune system imbalances and necessitate long-term treatment. Traditional immunosuppressive drugs, while effective, can lead to drug tolerance and adverse effects, including a heightened risk of infections and malignancies. Consequently, adjuvant therapy incorporating MSCs has emerged as a promising new treatment strategy, leveraging their immunomodulatory properties. This paper reviews the immunomodulatory mechanisms of MSCs and their application in autoimmune diseases, highlighting their potential to regulate immune responses and reduce inflammation. The immunomodulatory mechanisms of MSCs are primarily mediated through direct cell contact and paracrine activity with immune cells. This review lays the groundwork for the broader clinical application of MSCs in the future and underscores their significant scientific value and application prospects. Further research is expected to enhance the efficacy and safety of MSCs-based treatments for autoimmune diseases.
Very low doses of rituximab in autoimmune hemolytic anemia—an open-label, phase II pilot trial
Authors: Moser Miriam M. , Thalhammer Renate , Sillaber Christian , Derhaschnig Ulla , Firbas Christa , Jäger Ulrich , Jilma Bernd , Schoergenhofer Christian
Published: December 2024

Introduction

Although rituximab is approved for several autoimmune diseases, no formal dose finding studies have been conducted. The amount of CD20+ cells differs significantly between autoimmune diseases and B-cell malignancies. Hence, dose requirements of anti-CD20 therapies may differ accordingly.

Methods

We conducted a phase II pilot trial investigating the effects and safety of very low doses of rituximab, i.e., 5 mg/m2 every 3 weeks, 20 mg every 4 weeks, 50 mg every 3 months (n = 3 each) and 100 mg every 3 months (n = 1) in patients with autoimmune hemolytic anemia (AIHA) to effectively suppress CD20+ cell counts. Doses were increased if circulating CD20+ cell depletion was insufficient (i.e., <95% reduction from baseline) in a dose group. Plasma rituximab concentrations were quantified by enzyme-linked immunosorbent assay, CD20+ cell counts were determined by flow cytometry.

Results

Ten patients were included in the final analysis (7 with cold agglutinin disease, 2 with warm AIHA, 1 with mixed-type AIHA). The first infusion depleted ≥95% of CD20+ cells in all but one of the included patients. However, the dosing regimens were found ineffective, because a sustained CD20+ cell depletion was not achieved, and CD20+ cells recovered with a high interindividual variability. CD20+ lymphocytes were below the detection limit if rituximab plasma concentrations exceeded 0.4 μg/mL. One endokarditis occured.

Conclusion

Rituximab doses as low as 5 mg/m2 transiently depleted CD20+ cells in almost all patients, but the tested low-dose regimens failed to permanently suppress CD20+ cells. The empirically identified EC95% of 0.4 μg/mL rituximab may guide future studies using low-doses of rituximab.

Clinical trial registration

https://clinicaltrials.gov/, identifier [EudraCT 2016-002478-11].
Identification and treatment of Enterococcus avium-induced diabetic foot ulcer: a case report and microbiome analysis
Authors: Jin Yuanling , Zhu Tao , Cai Xiao , Fu Zheng , Pan QiangLong , Tu HaiXia , Wang ShouXing , Li Yan
Published: December 2024

Diabetic foot ulcer (DFU) is a severe complication of diabetes. Due to conservative or delayed treatment, the majority of DFU patients frequently miss the optimal treatment window, thereby leading to amputation. Despite being a rare pathogen with low virulence, Enterococcus avium (E. avium) exhibits some antibiotic resistance and can be fatal for immunocompromised patients. This report describes a DFU case, caused by E. avium infection due to exposure to poultry. Wound microbiota was dynamically monitored using bacterial culture followed by 16S rRNA gene sequencing throughout the illness. Combination of antibiotics was administered to control the secondary infection.

Case report

A 56-year-old man presented with a two-week history of redness, swelling, heat, pain, and pus discharge from a ruptured wound on his left heel. The patient was diagnosed with osteomyelitis and a Wagner grade 3 diabetic foot ulcer infection, complicated by the soft tissue infection in the left heel. Strain identification and antibiotic susceptibility tests were immediately performed after admission. The patient underwent three debridement procedures at the DFU site. However, we observed recurrent bacterial infections, based on the clinical progression. Second-generation sequencing detected various pathogens. After targeted treatment with Vacuum sealing drainage (VSD) combined with antibiotic bone cement, the patient’s condition stabilised. A skin graft was subsequently performed. Antibiotics were used to control the infection and blood glucose level was controlled throughout the treatment.

Conclusion

Thus, this report provides a comprehensive description of a DFU case, caused by E. avium. Antibiotics and surgical measures should be adjusted according to the pathogens responsible for wound infections in DFU patients. It is important to reduce the mortality and prevent irreversible amputations.
Mapping the current trends and hotspots of extracellular vesicles in Alzheimer's disease: a bibliometric analysis
Authors: Xing Xiaolian , Liu Hongwei , Zhang Minheng , Li Yang
Published: December 2024

Background

Extracellular vesicles (EVs) have garnered significant attention in Alzheimer's disease (AD) research over the past decade, largely due to their potential in diagnostics and therapeutics. Although the investigation of EVs in AD is a relatively recent endeavor, a comprehensive bibliometric analysis of this rapidly growing field has yet to be conducted.

Methods

This study aims to elucidate and synthesize the relationship between EVs and AD, offering critical insights to guide future research and expand therapeutic possibilities. Over the past 10–15 years, substantial progress has been made in this domain. Through bibliometric techniques, this analysis assesses research performance by examining scientific publications and metrics, including productivity indicators, impact measurements, data mining, and visualization tools.

Results

A total of 602 publications were analyzed using various online platforms for bibliometric analysis. Notably, the number of publications began to increase rapidly in 2018, with China and the United States emerging as leaders in this research area. The National Institute on Aging produced the highest number of publications among institutions. The Journal of Molecular Sciences and the Journal of Biological Chemistry were the most prolific and most frequently cited journals, respectively. Among individual contributors, Dimitrios Kapogiannis was identified as the most productive author, while Edward J. Goetzl was the most co-cited. The most prevalent keywords included “neurodegenerative diseases,” “exosomes,” “blood biomarkers,” “amyloid beta,” “microglia,” and “tau protein.” Current research hotspots involve microRNA dysregulation, oxidative stress, carboxyl-terminal fragments, small EVs, and mesenchymal stem cell-derived EVs, indicating key areas for future research.

Conclusion

Research on microRNA dysregulation, oxidative stress, carboxyl-terminal fragments, small EVs, and mesenchymal stem cell-derived EVs represents a critical frontier in the study of Alzheimer's disease. The role of EV-mediated neuroinflammation in AD is a focal point of ongoing investigation and will likely shape future developments in the field.
Association between metallic implants and stroke in US adults from NHANES 2015–2023 a cross-sectional study
Authors: Wu Kai , Pang Liang , Su Pingping , Lv Cunxian
Published: December 2024

Objective

Metal implants play a vital role in orthopedic treatment and are widely used in fracture repair, joint replacement and spinal surgery. Although these implants often contain key elements such as chromium (Cr), their potential health effects, particularly their association with stroke risk, have not been fully elucidated. This study aimed to evaluate the association between metallic implants and stroke.

Methods

Using data from the 2015 to 2023 National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional analysis of 12,337 US adults, in which 3,699 participants reported having metal implants and 8,638 without. Implant-like.

Results

Through logistic regression analysis, we revealed a significant positive association between metallic implants and stroke risk (adjusted OR = 1.458, 95%CI (1.130, 1.881), p = 0.004). Further stratified analysis found that this positive association was more significant among older and less physically active participants.

Conclusion

Findings suggest that metallic implants may be associated with an increased risk of stroke, but given the inherent limitations of cross-sectional studies, this study cannot establish causality.
Dynamic fluctuations in brain iron content during migraine attacks: insights from relaxometry and diffusion tensor imaging
Authors: Birkl Christoph , Filippi Vera , Steiger Ruth , Frank Florian , Magnesius Stephanie , Gizewski Elke R. , Broessner Gregor
Published: December 2024

Background

There is evidence that iron metabolism may play a role in the underlying pathophysiological mechanism of migraine. Studies using R2∗ (=1/T2∗) relaxometry, a common MRI-based iron mapping technique, have reported increased R2∗ values in various brain structures of migraineurs, indicating iron accumulation compared to healthy controls.

Purpose

To investigate whether there are short-term changes in R2∗ during a migraine attack.

Population

26-year-old male patient diagnosed with episodic migraine with aura according to ICHD-3 criteria.

Sequence

3 T, 64-channel head coil, for quantification of R2∗ relaxation a multi-echo gradient echo (GRE) sequence with TE = 4.92, 9.84, 14.7, 19.6, 24.6 and 29.51 ms, TR = 35 ms, flip angle = 15°, and 0.9 × 0.9 × 0.9 mm3 isotropic resolution was used.

Assessment

Quantitative MRI, including R2∗ relaxometry and diffusion tensor imaging (DTI), was acquired from a migraine patient on 21 consecutive days, including migraine-free days and days with a migraine attack.

Statistical test

Statistical analysis was performed using R, the Shapiro–Wilk test, the t-test and Mann Whitney U test, analysis of variance (ANOVA) or Kruskal–Wallis test, depending on the distribution of the data. p-value <0.05 was considered significant.

Results

Significant difference in R2∗ was found between the left and right hemispheres during a migraine attack. An increase in R2∗ was observed in the left hemisphere, whereas in the right hemisphere R2∗ was found to decrease. In the left cerebral white matter, R2∗ increased by 1.8% (p = 0.021), in the right cerebral white matter, R2∗ anisotropy decreased by 17% (p = 0.011) during a migraine attack.

Data conclusion

Our study showed a decrease and increase in iron content during the migraine cycle. Furthermore, during a migraine attack, white matter iron content increased, accompanied by a decrease in anisotropic tissue components, suggesting additional changes in vascular components.
Exploring the effect of a sweltering environment on the risk of death from cardiovascular diseases
Authors: Chen Zhaocong , Li Wangchao , Zhu Zhengjie , Miao Xueliang , Jiang Shuai , Li Caiming
Published: December 2024

Background

A substantial body of research has demonstrated a notable impact of hot temperatures on mortality from cardiovascular diseases (CVDs). However, a paucity of studies has addressed the influence of sweltering conditions on CVD mortality.

Objective

To investigate the effect of sweltering conditions on mortality from CVD among permanent residents of Huizhou City, using the temperature-humidity index (THI) as an indicator.

Methods

This study employs descriptive statistics, distributed lag non-linear model (DLNM) and general algebraic modeling system (GAMs) with the THI as an indicator in order to examine the impact of sweltering conditions on the mortality of CVD among permanent residents of Huizhou City.

Results

Sweltering conditions increase the risk of death from CVDs and have a cumulative lag effect. The greater the THI, the more pronounced the increase in mortality, and after a certain range, the mortality rate from CVDs increases significantly, and the effect is gender-specific. The lag effect generally peaks in 2–3 days, and the lag effect of stroke mortality is longer and deeper than that of coronary heart disease (CAD) mortality.

Conclusion

Sweltering increased the mortality of cardiovascular diseases in Huizhou city, so we should pay attention to public health intervention strategies under sweltering.
Analysis of the pathogenicity and pathological characteristics of NOTCH3 gene-sparing cysteine mutations in vitro and in vivo models
Authors: Gong Zhenping , Wang Wan , Zhao Ying , Wang Yadan , Sun Ruihua , Zhang Haohan , Wang Fengyu , Lu Yaru , Zhang Jiewen
Published: December 2024

Background

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common inherited cerebral small vessel diseases caused by the NOTCH3 gene mutation. This mutation leads to the accumulation of NOTCH3 extracellular domain protein (NOTCH3ECD) into the cerebral arterioles, causing recurrent stroke, white matter lesions, and cognitive impairment. With the development of gene sequencing technology, cysteine-sparing mutations can also cause CADASIL disease, however, the pathogenicity and pathogenic mechanisms of cysteine-sparing mutations remain controversial.

Objective

To analyze the pathogenicity and pathological features of cysteine-sparing mutations in both in vitro and in vivo mouse models.

Methods

A cysteine-sparing mutant of NOTCH3ECD R75Q was constructed by lentiviral transfection in vitro, and the NOTCH3 R75Q knock-in mouse model was constructed by CRISPR/Cas-mediated genome engineering in vivo. A cycloheximide pulse-chase experiment was used to analyze the degradation of NOTCH3 extracellular domain proteins, and the deposition characteristics of NOTCH3ECD were quantitatively analyzed by immunohistochemical staining. The characteristics of the smooth muscle cells and granular osmiophilic materials were observed using electron microscopy.

Results

We elucidated that the NOTCH3 R75Q mutation is pathogenic. NOTCH3ECD R75Q was found to be resistant to protein degradation and more likely to cause abnormal aggregation of NOTCH3ECD, resulting in reduced cell activity in vitro. The NOTCH3 R75Q mouse model showed pathological characteristics of CADASIL, with age-dependent NOTCH3ECD, granular osmiophilic material, and degenerated smooth muscle cells detected in the brain.

Conclusion

To our knowledge, this is the first study to analyze the pathogenicity of NOTCH3 R75Q cysteine-sparing mutations in both in vitro and in vivo models. We demonstrate that NOTCH3ECD induced by NOTCH3 R75Q mutation has toxic effects on cells and reveal the deposition characteristics of NOTCH3ECD in the brain. This provides a feasible model and lays the foundation for further studies on the pathogenesis and therapeutic strategies of NOTCH3 cysteine-sparing mutations.
Impact of a glutamine-enriched peptide formula on gastrointestinal toxicity and on the interruption of oncologic treatment in patients with adenocarcinoma of the rectum
Authors: Salas-Salas Bárbara Gabriela , Ferrera-Alayón Laura , Calleja-Fernández Alicia , Chicas-Sett Rodolfo , Nogués-Ramia Eva , Zafra-Martín Juan , Lloret Marta
Published: December 2024

Background

Patients with rectal cancer may develop gastrointestinal toxicity associated with chemo-radiotherapeutic treatment that conditions their clinical, functional, and nutritional evolution. The aim of the study was to evaluate the efficacy of nutritional supplementation with a glutamine-enriched peptide diet (PD) compared to exclusive dietary advice (DA) on gastrointestinal toxicity, interruption of oncologic treatment, and nutritional evolution in patients with rectal cancer undergoing neoadjuvant treatment.

Methods

Prospective cohort study with two groups. Patients with rectal cancer in treatment with neoadjuvant chemo-radiotherapy were recruited. One group of patients received nutritional supplementation with PD, and another group received DA exclusively, from the beginning of radiotherapy until the time of surgery. Intestinal toxicity was evaluated with the CTCAE 5.0 scale, functionality with the ECOG scale and nutritional status with GLIM criteria.

Results

Fifty-four patients were initially selected, although 51 were finally enrolled: 25 in the PD group and 26 in the DA group. There was a reduction in the risk of diarrhea in the PD group midway through radiotherapy treatment [RR of 0.218 (95% CI = 0.052–0.923)] and at the end of treatment [RR of 0.103 (95% CI = 0.020–0.537)], as well as a reduction in the risk of developing mucositis at the end of treatment [RR of 0.405 (95% CI = 0.280–0.584)]. The use of a PD also decreased treatment interruptions with radiotherapy in stage III patients (0 vs. 15.8%, p = 0.049) and in malnourished patients (0 vs. 18.2%, p = 0.040).

Conclusion

The glutamine-enriched peptide diet had a protective effect on the development of diarrhea and mucositis associated with chemo-radiotherapeutic treatment in patients with colorectal cancer under neoadjuvant treatment, as well as the interruption of radiotherapeutic treatment.
Melanin-concentrating hormone attenuates the hedonic feeding induced by orexin-A in the ventral tegmental area of high-fat diet male mice
Authors: Liu Xiaoning , Yang Helin , Xu Wenguang , Wang Xuezhe , Tang Wenhui , Wang Xiaoxuan , Jiao Yang , Luan Xinchi , Li Pengmeng , Guo Feifei
Published: December 2024

Objective

The ventral tegmental area (VTA), a pivotal hub in the brain’s reward circuitry, receives inputs from the lateral hypothalamic area (LHA). However, it remains unclear whether melanin-concentrating hormone (MCH) and orexin-A (OX-A) neurons in the LHA exert individual or cooperative influence on palatable food consumption in the VTA. This study aims to investigate the modulatory role of MCH and OX-A in hedonic feeding within the VTA of high-fat diet (HFD) mice.

Methods

Male mice were subjected to an 8-week high-fat diet. To visualize the projections from the LHA to VTA, we employed fluorescent gold retrograde tracing combined with immunofluorescence staining. Immunofluorescence staining or enzyme-linked immunosorbent assay was used to detect the activity of the VTA neurons, expression of OX-A or MCH in the LHA, as well as the activity of their receptors (OXR1 and MCHR1) in the VTA following a sucrose preference test. Single-unit extracellular electrical discharge recordings were conducted to assess the effects of OX-A and MCH on VTA neurons in HFD mice. Additionally, chemogenetic inhibition of MCH neurons and immunofluorescence staining were utilized to observe the regulatory roles of MCH in changes of hedonic feeding induced by OX-A in HFD mice.

Results

Sucrose intake resulted in lower activation of VTA neurons in the HFD mice compared to CON mice, while OX-Aergic and MCHergic neurons project from the LHA to the VTA. Although sucrose intake increased the expression of OX-A and MCH in HFD mice, it led to diminished activation of OXR1-positive and MCHR1-positive VTA neurons compared to CON mice. Extracellular single-unit recording revealed that MCH significantly suppressed the firing rate of OX-A-responsive neurons in the VTA. MCH attenuated the hedonic feeding response induced by OX-A in HFD mice, and administration of MCHR1 antagonist (SNAP94847) significantly potentiated the effect of OX-A. Chemogenetic inhibition of MCH neurons improved the activity of OXR1-expressing neurons, which could be reversed by pretreatment with an OXR1 antagonist (SB334867). Furthermore, chemogenetic inhibition of MCH enhanced hedonic feeding behavior, which was counteracted by SB334867 treatment in HFD mice.

Conclusion

Melanin-concentrating hormone could attenuate the hedonic feeding behavior induced by orexin-A in the VTA of HFD mice.
10 years of BiTE immunotherapy: an overview with a focus on pancreatic cancer
Authors: Paredes-Moscosso Solange R. , Nathwani Amit C.
Published: December 2024

Various therapeutic strategies have been developed to treat Pancreatic Cancer (PaCa). Unfortunately, most efforts have proved unfruitful, as the poor prognosis observed in this disease has only attained little improvement in the past 40 years. Recently, deeper understanding of the immune system and its interaction with malignant tumors have allowed significant advances in immunotherapy. Consistent with this, some of the most promising approaches are those that involve T-cell redirection to the tumor site, such as bispecific T-cell engagers (BiTEs). These recombinant antibodies bridge cytotoxic T-cells to tumor cells, inducing target cell-dependent polyclonal T-cell activation/proliferation, which in turn results in elimination of bound tumor cells. Blinatumomab, an anti-CD19 BiTE, received FDA approval in 2014 for Precursor B-cell Acute Lymphoblastic Leukemia. In the past decade, it has demonstrated impressive clinical benefit in patients with B-cell leukemias; and other T-cell engagers have been FDA-approved for hematological malignancies and other diseases, yet limited effect has been observed with other BiTEs against solid cancers, including PaCa. Nevertheless, on May 2024, Tarlatamab, an anti-DLL3 BiTE was approved by the FDA for extensive small cell lung cancer, becoming the first BiTE for solid tumors. In this review, the generation of BiTEs, therapeutic features, manufacturing issues as well as the remaining challenges and novel strategies of BiTE therapy in the context of PaCa, including the lessons we can learn from the use of BiTEs on other types of cancer will be explored.
Frost tolerance improvement in pea and white lupin by a high-throughput phenotyping platform
Authors: Franguelli Nicolò , Cavalli Daniele , Notario Tommaso , Pecetti Luciano , Annicchiarico Paolo
Published: December 2024

The changing climate could expand northwards in Europe the autumn sowing of cool-season grain legumes to take advantage of milder winters and to escape the increasing risk of terminal drought. Greater frost tolerance is a key breeding target because sudden frosts following mild-temperature periods may produce high winter mortality of insufficiently acclimated plants. The increasing year-to-year climate variation hinders the field-based selection for frost tolerance. This study focused on pea and white lupin with the objectives of (i) optimizing an easy-to-build, high-throughput phenotyping platform for frost tolerance assessment with respect to optimal freezing temperatures, and (ii) verifying the consistency of genotype plant mortality responses across platform and field conditions. The platform was a 13.6 m2 freezing chamber with programmable temperature in the range of −15°C to 25°C. The study included 11 genotypes per species with substantial variation for field-based winter plant survival. Plant seedlings were evaluated under four freezing temperature treatments, i.e., −7°C, −9°C, −11°C, and −13°C, after a 15-day acclimation period at 4°C. Genotype plant mortality and lethal temperature corresponding to 50% mortality (LT50) were assessed at the end of a regrowth period, whereas biomass injury was observed through a 10-level visual score based on the amount of necrosis and mortality after recovery and regrowth. On average, pea displayed higher frost tolerance than white lupin (mean LT50 of −12.8 versus −11.0°C). The genotype LT50 values ranged from −11.6°C to −14.5°C for pea and from −10.0°C to −12.0°C for lupin. The freezing temperature that maximized the genotype mortality variation was −13°C for pea and −11°C for lupin. The genotype mortality at these temperatures exhibited high correlations with LT50 values (0.91 for pea and 0.94 for lupin) and the biomass injury score (0.98 for pea and 0.97 for lupin). The frost tolerance responses in the platform showed a good consistency with the field-based winter survival of the genotypes. Our study indicates the reliability of genotype frost tolerance assessment under artificial conditions for two cool-season grain legumes, offering a platform that could be valuable for crop improvement as well as for genomics and ecophysiological research.
Quantitative relationship model between soil profile salinity and soil depth in cotton fields based on data assimilation algorithm: forecasting cotton field yields and profits
Authors: Gao Yang , Chang Lin , Zeng Mei , Hu Quanze , Hui Jiaojiao , Jiang Qingsong
Published: December 2024

Soil salinization seriously affects the efficiency of crops in absorbing soil nutrients, and the cotton production in southern Xinjiang accounts for more than 60% of China’s total. Therefore, it is crucial to monitor the dynamic changes in the salinity of the soil profile in cotton fields in southern Xinjiang, understand the status of soil salinization, and implement effective prevention and control measures. The drip-irrigated cotton fields in Alaer Reclamation Area were taken as the research objects. The multivariate linear regression model was used to study the relationship between soil salinity and soil depth in different periods, and the Kalman filter algorithm was used to improve the model accuracy. The results showed that the month with the highest improvement in model accuracy was July, with the model accuracy R2 increasing by 0.26 before and after calibration; followed by June and October, with the model accuracy R2 increasing by 0.19 and 0.18 respectively; the lowest improvement was in March, which was only 0.01. After the model was calibrated by the Kalman filter algorithm, the fitting accuracy (R2) between the predicted value and the actual value was as high as 0.79, and the corresponding RMSE was only 96.17 μS cm-1, and the measured value of soil salinity was consistent with the predicted value. Combined with the predicted conductivity data of each soil layer, the total yield of the study area was predicted to be 5,203-5,551 kg hm-2, and the income was about 4,953-7,441 RMB hm-2. It can be seen that Kalman filtering can improve the prediction accuracy of the model and provide a theoretical basis for studying the mechanism of soil salt migration in drip-irrigated cotton fields at different stages. It is of great significance for evaluating the potential relationship between cotton yield and deep soil salinity and guiding the efficient prevention and control of saline soil in cotton fields.
Resilience promotes self-esteem in children and adolescents with hearing impairment: the mediating role of positive coping strategy
Authors: Qi Ling , Zhang Hongling , Nie Rong , Du Yukai
Published: December 2024

Background

The level of self-esteem in adolescents appears to be contingent upon their satisfaction across various domains of life, exerting a notable influence on their mental wellbeing. The purposes of this study were to further validate the influence of resilience and positive coping strategy on their self-esteem and to explore the mediating effect of positive coping strategy in the relationship between resilience and self-esteem.

Methods

A total of 657 children and adolescents with a hearing impairment from 14 deaf/special schools in Hubei province completed measures of self-esteem, resilience, and positive coping.

Results

(1) Self-esteem is positively correlated with resilience and positive coping, (2) resilience is a significant predictor of self-esteem, and (3) the association between resilience and self-esteem was partly mediated by a positive coping strategy.

Conclusion

This study indicated the partly mediating effects of positive coping strategy on the association between resilience and self-esteem among Chinese children and adolescents with hearing impairment. These results also highlighted that intervention to promote resilience and coping strategies might be helpful to improve their self-esteem.
Stimulant medications effects in heat-related illness in ADHD patients: a large database study
Authors: Zinabu Samrawit , Gasmelseed Huda , Wheaton Noah , Girma Fikirte , Wong Christian , Tabraiz Sair Ahmad , Mubasher Ayesha , Mack Aaron , Lexima Patrice , Qazi Ozair , Mohammed Ahmad , Sood Aseem , Michael Miriam
Published: December 2024

Introduction

Attention Deficit Hyperactivity Disorder (ADHD), a prevalent neurodevelopmental disorder affecting a significant portion of the population, is commonly managed with stimulant medications. These medications, while effective, have been associated with thermoregulatory dysfunction and an increased risk of heat-related adverse events. The current study sought to compare the incidence of such events in ADHD patients receiving stimulant medications with those not on these treatments.

Methods

A retrospective cohort study was conducted utilizing de-identified electronic medical records from a Global Research Network. The study population comprised ADHD patients on stimulant medication aged 6-24 years, with a comparison group of ADHD patients not receiving stimulant medications. Patients were followed from the date of first cohort inclusion (index event) for one year to track heat-related illnesses, including dehydration, hyperthermia, heat stroke, and other heat-related conditions. Propensity score matching was employed to balance baseline characteristics (age, gender) between cohorts. Risk ratios, odds ratios, and hazard ratios were calculated to assess the incidence of heat-related illnesses between groups. Statistical analysis was performed on the TriNetX platform, with survival analysis conducted via Kaplan-Meier estimates.

Results

Analysis revealed a decreased risk of heat-related illnesses in the stimulant medication group, with a risk ratio of 0.559(95% CI: 0.485, 0.644). The mean number of events was also lower in the stimulants medication group (p=0.028). Additionally, Kaplan-Meier survival analysis indicated a higher probability of remaining free from heat-related illnesses in the stimulant group over a one-year period, with a statistically significant difference (log-rank test, χ² = 93.035, p < 0.0001).

Discussion

These results suggest that stimulant medications may be associated with a reduced risk of heat-related illnesses in ADHD patients, potentially contributing to better overall outcomes in this population. Further research is warranted to explore the underlying mechanisms and to confirm these findings across larger and more varied patient populations.
The relationship between problematic internet use and psychological distress in older Chinese teachers (40+) during different stages of the COVID-19 pandemic: three cross-sectional studies
Authors: Chen Xiu-Mei , Wang Li-Feng , Liao Xiao-Ling , Wang Shuai , Yang Lan , Chen I-Hua
Published: December 2024

Background

Despite a consensus on the negative implications of problematic internet use (PIU) for mental health, there is a notable gap in research concerning older demographics, particularly older teachers. This study aimed to investigate the prevalence of PIU and its impact on the mental wellbeing of this population.

Methods

Three sub-studies were conducted: Study 1 (2020) investigated how fear induced by COVID-19 influenced PIU and psychological distress among 3,929 older teachers. Study 2 (2021) examined the effects of PIU on psychological needs thwarting (the frustration of basic psychological needs) and psychological distress, involving 3,502 participants. Study 3 (2022) explored the impact of PIU on occupational burnout and psychological distress, with 1,276 participants. The Generalized Linear Model in Jamovi 2.3.23 was used to evaluate the three mediation models.

Results

The three sub-studies revealed a high prevalence of PIU among older teachers (27.4% in Study 1, 27.4% in Study 2, and 24.5% in Study 3). High levels of PIU were associated with elevated psychological distress during the 3 years of the COVID-19 pandemic. In Study 1, fear of COVID-19 indirectly influenced psychological distress through PIU as a mediator. In Studies 2 and 3, respectively, psychological needs thwarting and occupational burnout mediated the relationship between PIU and psychological distress.

Conclusion

This study confirmed the high prevalence of PIU among older school teachers and the detrimental effect of PIU on psychological needs thwarting, occupational burnout, and psychological distress. Given these findings, education authorities and school management should take proactive steps to mitigate PIU and ensure the health and wellbeing of older teachers.
Association of physical activity, sedentary behavior and stroke in older adults
Authors: Bai Long , Wen Zongliang , Yan Xuebing , Wu Shenqin , Chen Jialin
Published: December 2024

Objective

The aim of this study was to investigate the relationship between physical activity, sedentary behavior and stroke in people aged 60 years and older.

Methods

The study included 3,010 participants aged 60 and older from the National Health and Nutrition Examination Survey (NHANES). Data on sedentary behavior, physical activity and stroke were obtained through questionnaires. Statistical analyses were performed using a complex multistage sampling design and weighted multivariate logistic regression. Smoothed curve fitting and threshold effects analyses were used to explore non-linear relationships between physical activity, sedentary behavior and stroke.

Results

There were 244 (7.53%) participants aged 60 years and older who had experienced a stroke. After adjusting for all covariates, physical activity, sedentary behavior and stroke were significantly associated [OR (95% CI) for physical activity: 0.622 (0.443, 0.875), p = 0.009; OR (95% CI) for sedentary behavior: 2.602 (1.557, 4.348), p = 0.003]. C-reactive protein mediated the association between sedentary behavior and stroke among older adults, with a mediation of 3.64%.

Conclusion

In people aged 60 years and older, sedentary behavior was positively associated with stroke, whereas physical activity was negatively associated with stroke, and C-reactive protein mediated the relationship between sedentary behavior and stroke.
Advancements and challenges in microfluidic paper-based analytical devices: design, manufacturing, sustainability, and field applications
Authors: Aryal Prakash , Henry Charles S.
Published: December 2024

Microfluidic paper-based analytical devices (µPADs) have gained significant attention in analytical science and technology due to their numerous advantages over traditional analytical techniques, including cost-effectiveness, miniaturization, and sustainability. µPADs are widely used in point-of-care diagnostics, health monitoring, environmental detection, food safety, forensics, and security. Since the first report in 2007, there have been substantial advancements in their fabrication techniques, detection methods, and applications. Over the years, significant efforts and advancements have been made to improve the cost-effectiveness, manufacturing scalability, user-friendliness, and sustainability of µPADs. In this review, we explore the general trends and advancements in the fabrication, sensing methods, and applications of µPADs, highlighting key improvements and innovations. We also examine the eco-friendliness of µPADs and present real-world success stories from field studies and citizen science initiatives. Additionally, we address the challenges associated with transitioning µPADs from the lab to the field. Finally, we examine the outlook for µPADs and propose strategies to improve their usefulness in various fields.
Positive airway pressure delivery: overcoming old hurdles, exploring new frontiers
Authors: Messineo Ludovico , White David P. , Noah William H.
Published: December 2024

Despite being the gold-standard treatment for obstructive sleep apnea (OSA), continuous positive airway pressure (CPAP) faces important challenges, particularly with patient adherence. Many individuals find CPAP difficult to tolerate due to noise, social inconveniences, characteristics inherently linked to their sleep disorder and side effects, including mask discomfort, air leaks, nasal congestion, and the unnatural sensation of exhaling against positive pressure. All this often leads to reduced usage, limiting CPAP's potential to deliver long-term health benefits. This review revisits the dynamics of pharyngeal collapse during sleep on PAP, offering a new interpretation that challenges the long-standing view that higher inspiratory pressure is required to maintain pharyngeal patency. Emerging evidence, combined with the knowledge from older studies, suggests that airway collapse often occurs near end-expiration, which may be the only time that substantial positive airway pressure is required. Efforts to improve CPAP compliance have reduced expiratory pressure, leading to the introduction of bilevel PAP (BPAP) and expiratory pressure relief algorithms, which may cause airway destabilization, without yielding the improvements in adherence that were initially anticipated. Thus, despite over three decades of innovation, which have also seen heated humidifiers and tubes, customized 3D-printed masks and auto-titrating PAP come to market, there has been limited success in systematically increasing long-term CPAP adherence rates. In response, we discuss novel approaches such as V.-Com® and KairosPAP™ (KPAP™), which reduce inspiratory pressure and, in the case of KPAP™, also much of expiratory pressure, returning to full pressure only at the end of expiration. Recent studies suggest these technologies improve comfort and reduce unintentional leaks and may lead to better adherence without sacrificing treatment effectiveness. This aligns with the hypothesis that stabilizing the airway during end-expiration may be key to enhancing CPAP comfort and adherence. In conclusion, while technological advancements have improved the CPAP experience, further progress will likely come from solutions that better address patient comfort with the applied pressure. KPAP™ is one such innovation with the potential to enhance adherence, but additional research is needed to fully understand its long-term impact and effectiveness in PAP therapy for OSA.
“My Jijii would always tell me: We're getting you ready. We're getting you ready”: Indigenous presencing in adventure tourism
Authors: Koe Bobbi Rose , Loukes Keira A.
Published: December 2024

While there has been a general increase in Indigenous-owned and operated tourism companies across Turtle Island (currently known as North America), the same is not true for what is commonly referred to as “adventure tourism”, and specifically, in whitewater river canoe and raft guiding. There are still several barriers that continue to keep many prospective Indigenous guides out of the industry and off their traditional lands. This can work to perpetuate the myth that adventure tourism marketing relies on, that the rivers, lakes, and land they guide their clients on are an untouched and unpeopled “wilderness”. Peel River Watershed protector and activist Bobbi Rose Koe started an adventure tourism company, Dinjii Zhuh Adventures, to address these inequities. She aims to change the culture of guiding and tourism through introducing more Indigenous youth to their traditional watersheds, to train them as whitewater canoeing and rafting guides, and to support them in their employment and career development with the ultimate goal of land protection. This paper, co-written as a dialogue guided by the voice and perspective of Bobbi Rose, will weave together a story of the impact Indigenous presence has on the land, Indigenous youth, non-Indigenous guides and clients, other tourist operators, and the industry in general. Our conversation begins and ends with the role Indigenous presence plays in land and cultural governance and protection. We share these conversations, opportunities, challenges, and imagined futures to invite tourism researchers, operators, and guides to reflect, as well as to offer encouragement and camaraderie to other Indigenous guides and tourist operators.