bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurovascular dysregulation in systemic sclerosis: novel insights into pathophysiology, diagnosis, and treatment utilizing invasive cardiopulmonary exercise testing
Authors: Tarras Elizabeth , Joseph Phillip
Published: November 2024

Purpose of review

Pathologic abnormalities in skeletal muscle and the systemic vasculature are common in patients with systemic sclerosis (SSc). These abnormalities may lead to impaired systemic peripheral oxygen extraction (EO2), known as neurovascular dysregulation, which may be because of abnormal blood flow distribution in the vasculature, microvascular shunting, and/or skeletal muscle mitochondrial dysfunction. Findings from invasive cardiopulmonary exercising testing (iCPET) provide important insights and enable diagnosis and treatment of this SSc disease manifestation.

Recent findings

Recent findings from noninvasive cardiopulmonary exercise testing (niCPET) support the existence of neurovascular dysregulation in patients with SSc. Invasive cardiopulmonary exercise testing (iCPET) has pointed to reduced systemic vascular distensibility as a possible mechanism for neurovascular dysregulation in patients with connective tissue diseases, including SSc.

Neurovascular dysregulation is likely an underappreciated cause of exercise impairment and dyspnea in patients with SSc in the presence or absence of underlying cardiopulmonary disease. It is posited to be related to microcirculatory and muscle dysfunction. Further studies are needed to clarify the pathophysiology of neurovascular dysregulation in SSc and to identify novel treatment targets and additional therapies.
Evaluating N-acetylcysteine as a Protective Agent Against Chemotherapy-induced Neuropathy in Breast Cancer
Authors: Hassanzadeh Elyas , Sedighi Pashaki Abdolazim , Akbari Hamed Ehsan , Mehrpooya Maryam , Mohammadian Kamal , Bayani Reyhaneh , Sheikhi Kamran , Ranjbar Hossein , Abbasi Mohammad
Published: November 2024

Objectives:

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant clinical issue that affects patients’ quality of life and can limit the dosing of chemotherapeutic agents. N-acetylcysteine (NAC) has been proposed as a potential chemoprotective agent against CIPN due to its antioxidant properties. This study aimed to investigate the efficacy of oral NAC in preventing and controlling taxane-induced neuropathy in patients with breast cancer.

Methods:

This randomized, triple-blind, placebo-controlled trial included 80 breast cancer patients undergoing taxane-based chemotherapy. Participants were divided into 2 groups: an intervention group receiving 1200 mg of oral NAC in divided doses per day and a placebo group. Patients were evaluated for neuropathy grade and functional status at 1 and 12 weeks postintervention.

Results:

Our analysis revealed no significant difference in the incidence and severity of neuropathy between the intervention and placebo groups at 1 (P=0.328) and 12 weeks (P=0.569) postchemotherapy. Baseline characteristics such as age, number of treatment cycles, and disease stage were similar between groups, indicating a homogeneous population.

Conclusions:

Oral NAC at a dose of 1200 mg per day did not significantly reduce the incidence or severity of taxane-induced neuropathy. These findings suggest that the oral bioavailability of NAC may be insufficient to exert a protective effect and that future studies should consider alternative dosing strategies or routes of administration. The need for further research to optimize NAC’s chemoprotective role in CIPN remains evident.
Risk factors for screw loosening in patients with lumbar degenerative spondylolisthesis treated with Dynesys dynamic stabilization
Authors: Huang Yen-Chun , Lin Hsi-Hsien , Wang Shih-Tien , Chou Po-Hsin , Liu Chien-Lin , Yao Yu-Cheng
Published: November 2024

Background:

Posterior decompression with Dynesys dynamic stabilization (DDS) is an effective treatment option for degenerative spondylolisthesis. However, postoperative pedicle screw loosening (PSL) often results in poor outcomes. Determining possible risk factors may aid in making informed decisions. This study aimed to evaluate the incidence and risk factors for PSL in patients who underwent elective DDS.

Methods:

We conducted a retrospective analysis of 94 patients with L4-L5 grade I degenerative spondylolisthesis who underwent DSS at a single academic institution between May 2008 and February 2015. Screw loosening was defined as the presence of a halo or double-halo sign on plain radiography.

Results:

The rate of screw loosening was 4.8% among screws and 11.7% among patients. Multivariable analysis revealed that age >65 years, smoking, segmental range of motion (ROM) >13°, and L1 vertebral body Hounsfield unit <110 were risk factors for PSL after DDS. Five reoperations were performed; however, no instances of screw breakage were observed.

Conclusion:

Our study identified risk factors for PSL after DDS, including older age, smoking, larger preoperative segmental ROM, and lower L1 vertebral body HU, which could assist in preoperative decision-making and surgical planning.
Early impaired insulin tolerance among Vietnamese diabetes with or without dyslipidemia
Authors: Nguyen Mai Ly Thi , Bui Khac Cuong , Ngo Thu Hang , Nguyen Tai Suc , Nham Phuong Linh Thi , Pham Chi , Hoang Thi Minh , Huynh Quang Thuan , Tang Thanh Thuy , Dang Thanh Chung , Dang Thuy Linh , Nguyen Linh Toan , Can Van Mao
Published: November 2024

This study aims to evaluate impaired insulin tolerance among Vietnamese diabetes with or without dyslipidemia. Diabetes mellitus (DM) remains the serious global health and social burden that has increased over the past few decades. It progresses silently to vascular injury and disability of injured vascular-perfused tissues/organs. Insulin intolerance and dyslipidemia exacerbate and accelerate the implications of DM. Thus, early detection and more evidence of early insulin intolerance and dyslipidemia is needed for proactive management. This cross-sectional descriptive study recruited 100 healthy control (HC) and 297 DM patients in Military Hospital 103 from 2021 to 2023. Patients with DM were subgrouped into lipid metabolism disorder (LMD, n = 98) and non-LMD (NLMD, n = 99). The biochemists’ serum levels were measured automatically and the accuracy of the test result was strictly controlled. Insulin tolerance indices (HOMA2-IR, HOMA2-%S and HOMA2-%B) were compared between HC, DM with or without dyslipidemia as well as correlated with lipid ingredients (total Cholesterol, triglyceride, LDL-C and HDL-C). Among DM patients, HOMA2-IR was significantly high and HOMA2-%S and HOMA2-%B were significantly low. HOMA2-IR was higher and HOMA2-%S and HOMA2-%B were lower in DM with LMD than in DM without LMD. In addition, HOMA2-IR was positively correlated with serum cholesterol, triglyceride and LDL-C concentration, and negatively correlated to HDL-C concentration. In contrast, HOMA2-%S and HOMA2-%B was negatively correlated with serum cholesterol, triglyceride and LDL-C, and positively correlated with HDL-C. Impaired insulin intolerance occurred in early stage of DM, and more serious among DM with LMD, compared to DM with NLMD.
Exploring causal correlations between inflammatory cytokines and colorectal cancer: A 2-sample Mendelian randomization study
Authors: Zhou Heran , Yang Xuefei , Yang Qujia , Cai Zelin , Hu Keke , Huang Ting
Published: November 2024

Colorectal cancer (CRC) is a significant global public health concern. Several observational studies have examined the association between inflammatory cytokines and the risk of colorectal cancer, but the findings have been inconsistent. In this study, we employed a 2-sample Mendelian randomization (MR) analysis, primarily using the inverse variance weighted approach, to investigate the causal relationship between inflammatory cytokines and CRC. The forward MR analysis revealed a positive association between higher levels of interleukin (IL)-16 (OR: 1.37, P = .002), vascular endothelial growth factor (OR: 1.44, P = .001), and MIG (OR: 1.23, P = .040) with an increased risk of rectal cancer. Conversely, higher levels of macrophage colony-stimulating factor (OR: 0.80, P = .010) may potentially decrease the risk of colon cancer. In the reverse MR analysis, it was found that rectal cancer is linked to higher levels of IL-1b (OR: 0.93, P = .022), IL-1ra (OR: 0.90, P = .001), IL-5 (OR: 0.93, P = .022), IL-9 (OR: 0.93, P = .017), and TNF-a (OR: 0.91, P = .003). Additionally, colon cancer is associated with elevated levels of FGF-Basic (OR: 1.10, P = .028). Consistent results were also found in MR-Egger, weighted median, and weighted mode analysis. Our study presents novel evidence supporting the causal relationship between inflammatory cytokines and CRC.
The occurrence of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) after arthroplasty mimicking a periprosthetic joint infection: A case report and literature review
Authors: Araki Yoshihiro , Hirose Kei , Hirose Maki , Hayashi Katsuhiro , Demura Satoru
Published: November 2024

Rationale:

As the elderly population grows, the number of joint arthroplasty surgeries is also increasing. Periprosthetic joint infection (PJI) is a postoperative complication that occurs in 1%–2% of the arthroplasties. Once it occurs, PJI is refractory to treatment. Similar symptoms of PJI, including joint synovitis and elevated body temperature, sometimes arise because of crystal arthritis, rheumatoid arthritis, or other inflammatory diseases. Precise diagnosis is essential for determining the optimal treatment strategy.

Patient concerns:

An 81-year-old female patient with a history of bilateral knee arthroplasty presented with a high fever of 38 °C and was unable to walk due to swelling and pain in the bilateral lower extremities. Infectious conditions, such as cellulitis or PJI, were suspected. Imaging findings revealed bilateral knee joint synovitis with pitting edema around the lower extremities, and cultures of bilateral joint fluids were negative. No crystals were observed in the joint fluid. Laboratory data revealed highly elevated levels of inflammatory marker; however, antinuclear antibodies, including rheumatoid factor and cyclic citrullinated peptide, were not detected.

Diagnoses:

Based on bilateral synovitis with pitting edema in the lower extremities, in addition to negative culture findings and normal antinuclear antibodies, the diagnosis of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was made.

Interventions:

Steroid therapy was performed. The dose was gradually reduced, with the improvement of the symptoms.

Outcomes:

The inflammatory reaction promptly decreased and then normalized. With improved inflammation, the symptoms of pitting edema, pain in the bilateral lower extremities, and fluid effusion of the knee joints were reduced. She was able to walk without a cane, and her activities of daily living fully recovered.

Lessons:

High fever and synovitis after joint arthroplasty do not necessarily indicate an infectious condition. Clinicians should be familiar with the occurrence of RS3PE, regardless of whether arthroplasty is performed.
Development and validation of nomograms based on the SEER database for the risk factors and prognosis of distant metastasis in gastric signet ring cell carcinoma
Authors: Shi Haomin , Yang Huilian , Yan Su , Zhang Qi , Wang Xingbin
Published: November 2024

Poor prognosis in patients with distant metastasis of gastric signet ring cell carcinoma (GSRC), and there are few studies on the development and validation of the diagnosis and prognosis of distant metastasis of GSRC. The Surveillance, Epidemiology, and End Results database was used to identify patients with GSRC from 2004 to 2019. Univariate and multivariate logistic regression analysis were used to identify independent risk factors for distant metastasis of GSRC, while univariate and multivariate Cox proportional hazard regression analysis were used to determine independent prognostic factors for patients with distant metastasis of GSRC. Two nomograms were established, and model performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis. A total of 9703 cases with GSRC were enrolled, among which 2307 cases (23.78%) were diagnosed with distant metastasis at the time of diagnosis. Independent risk factors for distant metastasis included age, race, and T stage. Independent prognostic factors included T stage, chemotherapy, and surgery. The receiver operating characteristic curve, calibration curve, decision curve analysis curve, and Kaplan–Meier survival curve of the training set and validation set confirmed that the 2 nomograms could accurately predict the occurrence and prognosis of distant metastasis in GSRC. Two nomograms can serve as effective prediction tools for predicting distant metastasis in GSRC patients and the prognosis of patients with distant metastasis. They have a certain clinical reference value.
Effects of physical activity on blood pressure and mortality among aged hypertensive patients: A cross-sectional study
Authors: Zhang Zhi , Xu Cheng , Yu Wanqi , Du Changqing , Tang Lijiang , Liu Xiaowei
Published: November 2024

Previous research on physical activity (PA) has mostly concentrated on a single or small number of activities, with scant coverage of the effects of PA on hypertension (HTN) and all-cause mortality. Most studies examining HTN in the elderly have been too small or shown contradictory findings. We conducted a cross-sectional study using 10 cycles of the National Health and Nutrition Examination Survey data from 1999 to 2018. Our sample consisted of respondents aged 65 years or older with HTN, who underwent thorough in-person home interviews. We used a questionnaire to assess their PA levels and divided them into 2 groups: physically active and inactive. We then used logistic analysis to determine the association between PA and death in HTN patients. The gender distribution was nearly equal among the 11,258 participants, with a mean age of 74.36 ± 5.88 years. Nearly 80% of the survey respondents identified as non-Hispanic White. Patients in the physically active group were less likely to suffer from co-morbidities than those in the inactive group. A negative correlation was found between physically active and systolic blood pressure (P < .0001) and a positive correlation between physically active and diastolic blood pressure (P = .0007). There was a much higher risk of death from any cause and heart disease in the inactive group in the uncorrected COX model (HR 2.96, CI 2.65–3.32, P < .0001; HR 3.48, CI 2.64–4.58, P < .0001). The risk of death from any cause and HTN mortality was still significantly higher in the physically inactive group, even after controlling for age, sex, and race or taking all covariates into account. These results have the potential to significantly impact healthcare practices, particularly in the field of geriatric care, by emphasizing the importance of PA in reducing the risk of HTN and mortality in aged patients. The present study underscores the significant benefits of PA in patients aged 65 years and older with HTN. Notably, it was found to reduce systolic blood pressure and have a positive impact on the decrease of all-cause and hypertensive mortality. These findings highlight the crucial role of PA in the health and longevity of aged patients with HTN.
Staying home when peritoneal dialysis ends: the integrated home dialysis approach
Authors: Pecce Alex , Belhumeur Léa , Nadeau-Fredette Annie-Claire
Published: November 2024

Purpose of review

Home dialysis has been promoted for several years for patients starting dialysis. Although incident use of peritoneal dialysis (PD) and home hemodialysis (HHD) is increasing in several regions, patients on home dialysis remain at high risk of transfer to facility-hemodialysis (HD). The integrated home dialysis model, where patient start dialysis on PD and eventually transition to HHD when PD cannot be optimally continued has gain interest from dialysis stakeholders.

Recent findings

Transfers from PD to HHD are infrequently used among patients ending PD, representing between 2% and 6% of transfers to HD in registry studies. Nonetheless, this approach is associated with several clinical benefits as well as favorable cost-effectiveness.

In this review, we will present data pertaining to home dialysis and the integrated home dialysis model, with broad discussion of the implementation challenges, including identifying patients who could most benefit from this approach, timely planning of the transitions and challenges relating to unexpected PD endings.
Vascular changes in vascularized composite allotransplantation
Authors: Song Ethan Y. , Barrow Brooke E. , Cendales Linda C.
Published: November 2024

Purpose of review

Allograft vasculopathy in vascularized composite allografts (VCA) remains understudied. This review explores the vascular changes in VCA, focused on recent literature.

Recent findings

Allograft vasculopathy in VCA generally includes progressive concentric myointimal thickening and luminal narrowing of arterial vessels through endothelial deterioration and proliferation of smooth muscle cells. Microvascular changes are also noted, with thrombosis and lumen narrowing in microvessels of the skin even in the absence of large vessel vasculopathy. Histopathologic reports of skin containing VCA rejection document arteriosclerosis in deep vessels that are not always reflected in skin punch biopsies. The first revision of the Banff VCA scoring system 2022 was developed to include vascular changes in VCA. The scoring system for chronic changes and antibody mediated rejection continues to be under development.

The study of vascular changes in VCA continues to progress. Important data and advances in experimental and clinical VCA have been reported and continue to take place. Challenges ahead include capture of clinical data that will evolve beyond transient report forms and approaching on the problem of graft failure well grounded in sound scientific methodology.
Barriers to Family History Collection and Family Medical Screening Recommendation in the Sudden Death in the Young Case Registry
Authors: Machek Bailey , Buck Cassandra , MacLeod Heather , Keywan Christine
Published: November 2024

Sudden death in the young (SDY) poses a public health problem affecting thousands of individuals annually in the United States. The SDY Case Registry utilizes existing infrastructure of death investigation programs, including medical examiner/coroner (ME/C) systems, to enhance understanding of SDY causes and risk factors to inform prevention strategies. This includes identifying and promoting screening recommendations for at-risk family members. To explore barriers to family history collection and familial screening recommendation procedures across Registry sites, nine individuals from seven SDY sites were interviewed. Interviews focused on logistics, methods to address barriers, and recommendations for improvements. Despite variability in practices, data analysis revealed three common themes related to barriers of these processes: (1) timing and grief, (2) lack of family history in medical records, and (3) families lost to follow-up. This study offers insights into these processes within the Registry and sheds light on broader practices within the death investigation domain. Data analysis led to recommendations for the improvement of these practices including the prioritization of three key family history questions during the initial death investigation by a designated individual in each office/system.
The Effects of Perioperative Gender-affirming Hormone Therapy on Facial Feminization Surgery Adverse Events, Facial Features Addressed, and Esthetic Satisfaction: A Multimodal Analysis
Authors: Laspro Matteo , Hoffman Alexandra , Chinta Sachin , Abdalla Jasmina , Tran David , Oh Cheongeun , Robinson Isabel , Rodriguez Eduardo D.
Published: November 2024

Objective:

Facial feminization surgery (FFS) treats gender dysphoria in transfeminine patients by addressing the facial bony and soft tissue components. Individuals seeking FFS may be taking gender-affirming hormone replacement therapy [gender-affirming hormone therapy (GAHT)]. This study aims to better characterize the GAHT’s impact on venous thromboembolism (VTE) risk, surgical planning, and outcomes.

Methods:

A systematic review and meta-analysis of the literature were carried out to assess the effect of perioperative GAHT continuation on VTE. Cochrane Q and I
2 statistics measured study heterogeneity with the following meta-regression exploring these results. Simultaneously, a retrospective review of the senior author’s FFS cohort was conducted to investigate GAHT duration’s impact on FFS revision rate, complication incidence, and facial structures operated on.

Results:

Eleven articles were included: 602 patients stopped GAHT, of whom 3 VTEs were recorded (0.49%). This is compared with one episode among the 925 who continued GAHT perioperatively (0.11%). Study heterogeneity was low (0%), but limited VTE sample size precluded meta-analytic conclusions. Gender-affirming hormone therapy duration does not impact the incidence of all-cause complications (P = 0.478), wound infection (P = 0.283), hematoma (P = 0.283), or VTE (P = 1). The only procedures significantly less associated with higher GAHT were tracheal shaving (P = 0.002) and mandibuloplasty (P = 0.003). Finally, the FFS revision rate was not associated with GAHT duration (P = 0.06).

Conclusion:

There is a paucity of data to assess the safety or harm of continuing GAHT in the FFS perioperative period. Thus, a shared provider-patient decision-making process examining the risks and benefits of GAHT perioperative continuation is warranted. As patients seeking gender-affirming care are diverse, a “one-protocol-fits-all” is not appropriate.
Early integration of palliative care in haemato-oncology: latest developments
Authors: Papadopoulou Constantina , Johnston Bridget
Published: November 2024

Purpose of review

This review aimed to explore recent progress made in the past five years towards early access to, and integration of palliative care services within the haemato-oncology context to address the unique needs of patients with Haematological malignancies (HMs).

Recent findings

We included 14 articles in our review. We identified three themes, namely (i) disparities in the timing of referrals remain, (ii) specialist palliative care and impact on quality of life and (iii) perceptions on early integration. Patients with HM, receive less palliative care services, regardless of their higher symptom burden compared to patients with solid tumours. Structured approaches and models of early integration have shown substantial benefits, including improved pain and symptom management, shorter hospital stays and better end of life planning. Perceptions on existing barriers include the curative treatment focus, haematologists’ personal perceptions on timing of palliative care and lack of palliative care training.

For early integration to happen, it is crucial to address training gaps, improve communication skills, and foster interdisciplinary collaboration. Standardised organisational pathways can facilitate early and concurrent palliative care integration. System-level flexibility and supportive policies are essential to ensure that patients with HM receive comprehensive and high-quality care.
Decarbonizing the global steel industry in a resource-constrained future—a systems perspective
Authors: Watari Takuma , McLellan Benjamin
Published: November 2024

Decarbonizing the global steel industry hinges on three key limited resources: geological carbon storage, zero-emission electricity and end-of-life scrap. Existing system analysis calls for an accelerated expansion of the supply of these resources to meet the assumed ever-increasing steel demand. In this study, we propose a different view on how to decarbonize the global steel industry, based on the principle that resource supply can only expand in line with historical trends and actual construction plans. Our analysis shows that global steel production cannot grow any further within a Paris-compatible carbon budget, resulting in a shortfall of approximately 30% against 2050 demand. This trajectory involves the phasing out of blast furnaces, along with strong growth in scrap recycling and hydrogen-based production. These findings highlight critical yet often overlooked challenges: (i) reducing excess demand while providing essential services, (ii) producing high-grade steel through upcycling scrap, and (iii) ensuring an equitable distribution of limited production across the globe. These perspectives contrast with those of the current agenda, which largely emphasizes the need to invest in new production technologies. Grounded in a physical basis, this analysis offers a complementary perspective for a more balanced debate in policymaking and industrial strategy.

This article is part of the discussion meeting issue ‘Sustainable metals: science and systems’.
Supply security beyond mines and scrap recycling: valorization potential of metallurgical residues
Authors: Steinlechner Stefan , Witt Kerrin
Published: November 2024

In the context of the European Critical Raw Materials Act, this work attempts to demonstrate the potential of residual material flows from non-ferrous metallurgy and their possible contribution to the supply security of metals by locally available new secondary resources, assuming technically and economically viable processing. Based on the aluminium, zinc, copper and lead industries, the resulting waste streams are discussed and, in particular, the complex process consisting of physical, chemical and metallurgical steps is described. Their diversity, be it slags, dusts or even sludges, has a wide variety of morphologies and compositions due to the process of generation. In the past, many concepts for reprocessing were investigated, but the goal was usually only the recovery of one target element or to avoid landfilling by using it, for example, as a building material, whereby the metals contained are completely lost. If the target is the extraction of valuables, the required interdisciplinary process development must be based on an in-depth characterization to understand the behaviour of metals and trace elements in possible extraction steps and also to develop suitable strategies for influencing the behaviour of target elements with the aim of extraction. This starts with an in-depth comprehension of the formation process, which is the subject of this article and has a direct influence on the composition and morphology of the materials, thus forming the basis for understanding the behaviour in potential recycling processes. Furthermore, typical compositions of the residual material streams, sources and, if available, quantities are shown and, in summary, an attempt is made to evaluate the materials in a SWOT analysis and to address the challenges in developing extraction steps for processing. While mine tailings are mostly found outside of Europe, the potential of the residual materials from metallurgy is local due to the processing of the concentrates in Europe. This leads to several potential advantages in a possible reprocessing, such as no or shorter transport routes, which is linked to lower quantity of emissions, defined volume and known composition, no geopolitical risk, conservation of primary resources, and increasing Europe’s sustainability through a more comprehensive use of the raw materials.

This article is part of the discussion meeting issue ‘Sustainable metals: science and systems’.
What is the embodied CO
2
cost of getting building design wrong?
Authors: Dunant Cyrille F.
Published: November 2024

Today, carbon and cost-efficient construction are well matched. However, in the future, as steel production is increasingly done from recycled scrap in electric arc furnaces (EAFs) and concrete mix design is improved, the current balance of CO

⁣
2

impacts and costs can be altered. When this happens, structural designers need to update their design strategies, and incentives must be put in place to retain the alignment between environmental impact and cost. Here, I assess the potential of carbon taxation to improve the structural design. I also assess the discrepancy in embodied carbon outcomes if construction costs remain constant, but the embodied carbon of materials is varied. Finally, I look at the effect of an early-stage design tool, PANDA, on embodied carbon outcomes of real projects. I find that carbon taxes need to be extremely high to have an effect, and that this effect is limited to certain types of frames. Embodied carbon in construction can become disconnected from costs if the embodied carbon of materials varies heterogeneously. Finally, novel design tools can help designers substantially improve the embodied carbon of their design. This happens despite the absence of a significant monetary incentive to that effect.

This article is part of the discussion meeting issue ‘Sustainable metals: science and systems’.
System analysis with life cycle assessment for NiMH battery recycling
Authors: Korkmaz Kivanc , Junestedt Christian , Elginoz Nilay , Almemark Mats , Svärd Michael , Rasmuson Åke C. , Forsberg Kerstin M.
Published: November 2024

The nickel metal hydride (NiMH) battery technology has been designed for use in electric vehicles, solar-powered applications and power tools. These batteries contain the critical and strategic raw materials cobalt, nickel and several rare earth elements (REE). When designing a battery recycling process, there are several choices to be made regarding end-products and process chemicals. The aim of this study is to investigate and compare the environmental and economic sustainability of different recycling options for NiMH batteries by taking projected market developments into consideration and by applying life cycle assessment and life cycle costing methods. The comparative study is limited to recovery of the REEs. Two hydrometallurgical processes for recovery of the REEs from the anode material are compared with extraction of REEs from primary sources in China. The processes compared are a high-temperature sulfation roasting process and a process based on hydrochloric acid leaching followed by precipitation of REE oxalates. By comparing the different recycling approaches, the hydrochloric acid process performs best. However, the use of oxalic acid has a large impact on the overall sustainability footprint. For the sulfation roasting process, the energy, sodium hydroxide and sulphuric acid consumption contribute most to the total environmental footprint.

This article is part of the discussion meeting issue 'Sustainable metals: science and systems'.
Sustainable metals: integrating science and systems approaches
Authors: Allwood Julian M. , Raabe Dierk
Published: November 2024

This article introduces a special issue of the transactions arising from a Royal Society Discussion Meeting on ‘sustainable metals’. Recognizing that progress to date toward the goals of ‘sustainability’ has been limited, the meeting aimed to open up a new level of interdisciplinary dialogue, collaboration and discussion of disruptive approaches. In this paper, the major concerns of sustainability are enumerated, and climate change is identified as the most urgent. The constraints on deploying technical innovations at scale and speed are discussed, suggesting that much of the required change will require using existing technologies differently, and many opportunities of this type have been overlooked. These constraints also give useful direction for future research and suggest an expanded future role for scientists. Previously, scientists and technologists have aimed largely to ‘solve’ problems in sustainability through invention. This introductory paper argues that they have an equally important role as participants in the complex societal discussions required to identify pathways to change. Scientific expertise is as important for explaining what cannot be achieved in time or at scale, as it is for promoting the excitement of invention.

This article is part of the discussion meeting issue ‘Sustainable metals: science and systems’.
CLOZAPINE-RELATED BRAINNRN1EXPRESSION PATTERNS ARE ASSOCIATED WITH METHYLATION AND GENETIC VARIANTS IN SCHIZOPHRENIA
Authors: Almodóvar-Payá Carmen , Moreno Marcos , Guardiola-Ripoll Maria , Latorre-Guardia Mariona , Morentin Benito , Garcia-Ruíz Beatriz , Pomarol-Clotet Edith , Callado Luis F. , Gallego Carme , Fatjó-Vilas Mar
Published: November 2024

The Neuritin-1 gene (NRN1), involved in neurodevelopment and synaptic plasticity, is associated with schizophrenia (SZ) and related clinical, cognitive, and neuroimaging phenotypes. Additionally, it is one of the most differentially methylated genes in the prefrontal cortex (PFC) in SZ and is responsive to neurotherapeutic agents. We aimed to investigateNRN1’s molecular mechanisms in SZ by analyzing its expression, methylation, and genotypic profiles in PFC and hippocampus (HIPP) post-mortem samples from 30 control (CTL) subjects and 20 individuals with SZ (10 treated with clozapine, SZ-Clz, and 10 without antipsychotic drugs at death, SZ-ApFree). We comparedthe NRN1mRNA expression between groups, measured by qPCR, and methylation levels across three CpG islands, assessed through EpiTYPER. Sparse Partial Least Square Discriminant Analysis identified key CpG units contributing to group differences. We then explored the relationship betweenNRN1methylation and expression, considering the influence of 11 polymorphisms genotyped by qPCR. We found that SZ-Clz had lowerNRN1mRNA levels in the PFC than SZ-ApFree and CTL. SZ-Clz presented distinct methylation patterns across multiple CpG units in both brain regions compared to CTL. In the PFC, the methylation of the CpG units differentiating SZ-Clz from CTL correlated toNRN1expression, and theNRN1-rs12333117 andNRN1-rs2208870 polymorphisms influenced this effect. These findings reveal distinct correlations betweenNRN1epigenetic expression in SZ-Clz and CTL, shaped by genotypic variability. They emphasize region-specific alterations in SZ and underscore the importance of integrative approaches for a better understanding of the role of candidate genes in SZ etiology.
The Basel Long COVID Cohort Study (BALCoS): protocol of a prospective cohort study
Authors: Rohner Stefan , Schnepper Rebekka , Meinlschmidt Gunther , Schaefert Rainer , Mayr Michael , Bopp Katrin , Meienberg Andrea
Published: November 2024

Introduction

The recent severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic had a devasting global impact. Many people suffered from coronavirus disease 2019 (COVID-19) and some experienced persistent symptoms interrupting their lives even further. The World Health Organization (WHO) defined the condition of these persistent symptoms as post-COVID-19 condition (PCC). The most prevalent PCC symptoms are fatigue, dyspnea, sleep disturbances, coughing, anosmia and ageusia, chest pain, and headaches. This article describes the protocol of the Basel Long COVID Cohort Study (BALCoS), which aims at fostering understanding of PCC and investigating underlying mechanisms for the development and course of the condition by focusing on participants’ health status and symptoms with repeated measures over one year.

Methods and analysis

BALCoS is a prospective single site cohort study. Inclusion criteria are a confirmed PCC diagnosis according to WHO or a subjective attribution of persistent symptoms to PCC, proficiency in German to follow study procedures, and at least 18 years of age. It comprises blood sample collections, standardized neurocognitive and psychometric tests, physical performance measures, and ecological momentary assessments (EMAs). Standardized tests and EMAs are administered at baseline (BL), and at 3-, 6-, and 12-months follow-up. At BL and 12-month follow-up, physical performance and neurocognitive abilities are assessed. Participants provide blood samples at BL. The study is exploratory in nature and a sample size of at least 120 participants is targeted. The study is part of a larger Horizon Europe Long COVID project combining mechanistic, clinical, and intervention studies within an interdisciplinary European research consortium.

Ethics and dissemination

The Ethics Commission of Northwest and Central Switzerland approved the study (BASEC-ID: 2023-00359), which is registered atClinicalTrial.gov(ID:NCT05781893). All participants provide written informed consent. Key results from the study will be published in peer-reviewed journals.

Funding Details

BALCoS is primarily funded by the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 22.00094 in the context of the European Union’s Horizon Europe research and innovation program under grant agreement No. 101057553.
Transcriptome-wide association study of Alzheimer disease reveals many differentially expressed genes and multiple biological pathways in brain tissue from African American donors
Authors: Logue Mark W. , Labadorf Adam , O’Neill Nicholas K. , Dickson Dennis W. , Dugger Brittany N. , Flanagan Margaret E. , Frosch Matthew P. , Gearing Marla , Jin Lee-Way , Kofler Julia , Mayeux Richard , McKee Ann , Miller Carol A. , Murray Melissa E. , Nelson Peter T. , Perrin Richard J. , Schneider Julie A. , Stein Thor D. , Teich Andrew F. , Troncoso Juan C. , Wang Shih-Hsiu , Wolozin Benjamin , Mez Jesse , Farrer Lindsay A.
Published: November 2024

Background

The genetic basis of Alzheimer disease (AD) in African American (AA) individuals is much less well understood than in European-ancestry (EA) individuals. Furthermore, relatively few AA donors have been included in postmortem AD studies.

Methods

We generated transcriptome-wide bulk-level gene expression data derived from pre-frontal cortex (PFC) tissue obtained from 179 AA brain donors with a pathological diagnosis of AD or control. This sample was augmented by previously generated RNAseq data derived from PFC tissue from another group of 28 AA donors, yielding a total sample of 125 AD cases and 82 neuropathologically determined controls who were enrolled at 12 AD research centers across the United States. Expression of 33,611 genes was compared between AD cases and controls using LIMMA including covariates for age, sex, cell-type frequencies, and RNA integrity number. A false discovery rate corrected p-value (padj) was used to account for multiple testing. Gene-ontology (GO) term enrichment analysis was performed using GOseq.

Results

Transcriptome-wide significant differential expression was observed with 482 genes among which the most significant,ADAMTS2,showed 1.52 times higher expression in AD cases compared to controls (p=2.96×10−8, padj=0.0010). Many of the differentially expressed genes are involved in mitochondrial energy production. Examination of differentially expressed genes observed previously in brain tissue from EA AD cases and controls revealed that 385 (35%) were nominally significant, 65 (5.8%) were significant after multiple test correction, and most (89%) had the same effect direction in the AA sample. Several other significant associations were not observed in the EA cohort, and these genes may be especially relevant to AD risk in the AA population (e.g.,EFR3B,IRS4, andCA12). Examination of potential regulatory effects of AA GWAS-implicated AD risk variants identified several expression quantitative trait loci.

Conclusions

In this first large-scale transcriptome-wide gene expression study of AD in brain from AA donors, we identified many differentially expressed genes, includingADAMTS2which was recently reported to be differentially expressed in brain between pathologically confirmed EA AD cases with and without AD clinical symptoms. These results represent a substantial advance in knowledge about the genetic basis of AD in the AA population and suggest promising new targets for treatment.
Multimodal Hyperbolic Graph Learning for Alzheimer’s Disease Detection
Authors: Xie Chengyao , Zhou Wenhao , Peng Ciyuan , Hoshyar Azadeh Noori , Xu Chengpei , Naseem Usman , Xia Feng
Published: November 2024

Multimodal graph learning techniques have demonstrated significant potential in modeling brain networks for Alzheimer’s disease (AD) detection. However, most existing methods rely on Euclidean space representations and overlook the scale-free and small-world properties of brain networks, which are characterized by power-law distributions and dense local clustering of nodes. This oversight results in distortions when representing these complex structures. To address this issue, we propose a novel multimodal Poincaré Fréchet mean graph convolutional network (MochaGCN) for AD detection. MochaGCN leverages the exponential growth characteristics of hyperbolic space to capture the scale-free and small-world properties of multimodal brain networks. Specifically, we combine hyperbolic graph convolution and Poincaré Fréchet mean to extract features from multimodal brain networks, enhancing their rep-resentations in hyperbolic space. Our approach constructs multimodal brain networks by integrating information from diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) data. Experiments on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset demonstrate that the proposed method outperforms state-of-the-art techniques.
Chronic stress antagonizes formation of Stress Granules
Authors: Adachi Yuichiro , Williams Allison M. , Masuda Masashi , Taketani Yutaka , Anderson Paul J. , Ivanov Pavel
Published: November 2024

Chronic stress mediates cellular changes that can contribute to human disease. However, fluctuations in RNA metabolism caused by chronic stress have been largely neglected in the field. Stress granules (SGs) are cytoplasmic ribonucleoprotein condensates formed in response to stress-induced inhibition of mRNA translation and polysome disassembly. Despite the broad interest in SG assembly and disassembly in response to acute stress, SG assembly in response to chronic stress has not been extensively investigated. In this study, we show that cells pre-conditioned with low dose chronic (24-hour exposure) stresses such as oxidative stress, endoplasmic reticulum stress, mitochondrial stress, and starvation, fail to assemble SGs in response to acute stress. While translation is drastically decreased by acute stress in pre-conditioned cells, polysome profiling analysis reveals the partial preservation of polysomes resistant to puromycin-induced disassembly. We showed that chronic stress slows down the rate of mRNA translation at the elongation phase and triggers phosphorylation of translation elongation factor eEF2. Polysome profiling followed by RNase treatment confirmed that chronic stress induces ribosome stalling. Chronic stress-induced ribosome stalling is distinct from ribosome collisions that are known to trigger a specific stress response pathway. In summary, chronic stress triggers ribosome stalling, which blocks polysome disassembly and SG formation by subsequent acute stress.

Significant statements

Stress granules (SGs) are dynamic cytoplasmic biocondensates assembled in response to stress-induced inhibition of mRNA translation and polysome disassembly. SGs have been proposed to contribute to the survival of cells exposed to toxic conditions. Although the mechanisms of SG assembly and disassembly in the acute stress response are well understood, the role of SGs in modulating the response to chronic stress is unclear. Here, we show that human cells pre-conditioned with chronic stress fail to assemble SGs in response to acute stress despite inhibition of mRNA translation. Mechanistically, chronic stress induces ribosome stalling, which prevents polysome disassembly and subsequent SG formation. This finding suggests that chronically stressed or diseased human cells may have a dysfunctional SG response that could inhibit cell survival and promote disease.
TACSTD2expression marks the early transition to colon adenomas
Authors: Siskova Anna , Huebner Kerstin , Ferrero Giulio , Gehring Annemarie , Hampel Chuanpit , Naccarati Alessio , Pardini Barbara , Tarallo Sonia , Geppert Carol I. , Prochazka Jan , Tureckova Jolana , Jungwirth Jiri , Hucl Tomas , Kral Jan , Vodickova Ludmila , Erlenbach-Wuensch Katharina , Hartmann Arndt , Honkova Katerina , Matej Radoslav , Vodicka Pavel , Vymetalkova Veronika , Schneider-Stock Regine
Published: November 2024

This study aimed to address new molecular events occurring in precancerous stages of colorectal cancer (CRC) by integrated analysis of gene expression data and DNA methylation profiles.

Whole-transcriptome sequencing analysis was performed on 16 fresh frozen colorectal adenoma and matched mucosa specimens along with validation of candidates in an independent cohort of 20 fresh frozen paired adenoma and adjacent mucosa tissues as well as eight independent public datasets (335 cases). Genome-wide methylation profiles were determined for 5 adenoma pairs and confirmed by pyrosequencing on 20 tissue pairs used for validation. Functional analysis was performedin vitroandin vivousing the inflammation-associated azoxymethane/dextran sodium sulfate (AOM/DSS) and the sporadic colorectal carcinogenesis (six AOM injections) mouse models as well asApcMin/+mice. Candidates were investigated by immunohistochemical staining of human adenomas and early-stage (pT1) CRC tumors.

A total of 1,917 differentially expressed genes and 148,191 differentially methylated CpG sites were detected in adenomas compared with adjacent mucosa samples. Based on the transcriptome data and relevance to CRC,TACSTD2, MMP7, MMP1, CLDN2, CLDN1, and ETV4, were selected for further validation.TACSTD2promoter hypomethylation in adenoma tissues was validated in 20 additional tissue pairs and corresponded with increasedTACSTD2expression.TACSTD2was also overexpressed in anin vitrotransformation model of human colonic epithelial cells. TheTACSTD2protein TROP2 was elevated in human adenomas, pT1 tumors, and in murine adenomas, while it was absent in the unaffected adjacent mucosa. TROP2 overexpression might trigger the development of precancerous lesions and could help identify early transformation foci in colon biopsies.

Graphical abstract
Kaizen: Decomposing cellular images with VQ-VAE
Authors: Majoral Daniel , Domnich Marharyta
Published: November 2024

A fundamental problem in cell and tissue biology is finding cells in microscopy images. Traditionally, this detection has been performed by segmenting the pixel intensities. However, these methods struggle to delineate cells in more densely packed micrographs, where local decisions about boundaries are not trivial. Here, we develop a new methodology to decompose microscopy images into individual cells by making object-level decisions. We formulate the segmentation problem as training a flexible factorized representation of the image. To this end, we introduce Kaizen, an approach inspired by predictive coding in the brain that maintains an internal representation of an image while generating object hypotheses over the external image, and keeping the ones that improve the consistency of internal and external representations. We achieve this by training a Vector Quantised-Variational AutoEncoder (VQ-VAE). During inference, the VQ-VAE is iteratively applied on locations where the internal representation differs from the external image, making new guesses, and keeping only the ones that improve the overall image prediction until the internal representation matches the input. We demonstrate Kaizen’s merits on two fluorescence microscopy datasets, improving the separation of nuclei and neuronal cells in cell culture images.