bluuebunny/crossref_metadata_2025 huggingface dataset:
Giving Form to Refugee Memory: Ann Le’s Embody Wallpaper Portraits
Authors: Ching Kylie
Published: January 2024

In Vietnamese American artist Ann Le’s 2012 Embody Wallpaper Portraits series, wallpaper designs of repeating collaged and silhouetted documentary Vietnam War photographs cover the skin and faces of the artist’s own family portraits. The bodies of these haunting and preserved figures serve as sites of forged encounter between public and private photographic archives and commemoration. This article considers two works from this series, titled Mother Refuge and Re Education Graduation, which examine motherhood and the nation-state of the United States as sites that (un)make refuge(es) and question the relationship between re-education camps in Vietnam and the US education system as sites of indoctrination respectively. Theorizing collage as an art practice that prompts a relational analysis of the different war events, I argue that by suturing together seemingly disparate histories, memories, places, and photographs, Le makes visible and invisible the gendered and racial violence that sustains US imperial projects.
The last missing species born of a confusing puzzle: Leopoldia nigdeensis (Asparagaceae, Scilloideae), a new species from Türkiye
Authors: EKER İSMAİL , EROĞLU HÜSEYİN
Published: January 2024

The concept of Muscari massayanum (=Leopoldia massayana), previously treated by Davis & Stuart in the Flora of Turkey, was found to be a mixed species assemblage and included the species Muscari erdalii (=Leopoldia erdalii) and Muscari erzincanicum (=Leopoldia erzincanica), which arose from this confusion. However, in the latest evaluations by the authors of this article, the last missing piece of the confusing puzzle has been put forward in this study. Thus, a new species Leopoldia nigdeensis from Anatolia is described in this study. The new species is morphologically partly similar to Leopoldia massayana, L. erzincanica, L. oztasii, L. tenuiflora and L. erdalii, but differs from all of them with clear features in flower, fruit and seed characteristics.
Revision of the genus Nephelobotys Munroe & Mutuura, 1970 (Lepidoptera, Crambidae, Pyraustinae)
Authors: ZHANG DANDAN , CHEN KAI , XIANG LANBIN , KOU ZONGQING
Published: January 2024

The genus Nephelobotys Munroe & Mutuura, 1970 is revised to include eight species. Three species, N. apiculata sp. nov., N. semicircularis sp. nov. and N. brevis sp. nov. are described as new to science. Two new combinations, N. habisalis (Walker, 1859) comb. nov. and N. flavicilialis (Snellen, 1890) comb. nov., are proposed. N. forcipatus Ko & Bae, 2022 syn. nov. is found to be identical with N. habisalis (Walker, 1859). Diagnoses for all species are provided, with illustrations of external features and genitalia.
A remarkable new synthemistid from New Caledonia (Odonata: Anisoptera: Synthemistidae s. str.). Taxonomic and phylogenetic note on New Caledonian Synthemistidae and erection of a new genus
Authors: FLECK GÜNTHER
Published: January 2024

The new species, Calesynthemis jeanlegrandi sp. nov., dedicated to the late Jean Legrand, is described and illustrated based on a single pair of specimens from Mont Panié, New Caledonia. The male of this large species has unusual strongly sinuous and distally down curved white cerci 7 mm long and exhibits on abdominal segment 10 a remarkable clump of strong setae mimicking a dorsal horn. The female wingspan slightly exceeds 100 mm. In addition, on the basis of adult and larval characters, Neocaledosynthemis gen. nov. is erected to accommodate two other New Caledonian synthemistids, Synthemis fenella Campion (type species) and Synthemis ariadne Lieftinck. New Caledonian synthemistids are probably more closely related to Parasynthemis Carle than to Synthemis Selys Longchamps, both from Australia.
Three new species of Promicrogaster Brues & Richardson (Hymenoptera: Braconidae) from India
Authors: RANJITH A.P. , FERNANDEZ-TRIANA JOSE , SUSHAMA V. , RAJMOHANA K. , PRIYADARSANAN DHARMA RAJAN
Published: January 2024

The Indian fauna of the microgastrine genus Promicrogaster is reviewed and three new species are described: P. constricta, P. flava, and P. incompleta, all authored by Ranjith & Fernandez-Triana. Until now only one species had been reported from India. An illustrated key for the Oriental region, including all previously described species, is also provided.
A consideration of CYP2D6 genetic variations in the Ghanaian population as a potential ‘culprit’ for the tramadol ‘abuse crisis’
Authors: Thomford Nicholas Ekow , Abraham Susanna Aba , Nyarko Samuel Badu , Biney Robert Peter
Published: January 2024

Background

Cytochrome P450 2D6 is involved in the metabolism of several important medicines including opioids. Variations in CYP2D6 have been implicated in drug response and according to the Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, dosing for CYP2D6 substrates should be based on variants carried by individuals. Although CYP2D6 variations in Ghana had been previously recorded, not all variants have been reported in the Ghanaian population. In this exploratory study we set to investigate certain unreported variations in the Ghanaian population in addition to the previously reported ones and use that to understand the tramadol ‘abuse’ crisis that is currently being experienced in Ghana.

Methods

This study employed a convenience sampling approach to include 106 unrelated participants who were recruited as part of the PHARMABIOME project. We successfully genotyped 106 samples using Iplex GOLD SNP genotyping protocol after extracting DNA from these individuals. Allele and diplotype frequencies were undertaken by counting from observed genotypes. Comparison of alleles reported from various studies were done.

Results

Unreported alleles such as *3, *9 and *41 which are classified as no function and decreased function were observed in our study cohort. In addition, variants such as (*1, *2, *4, *5, *10, *17 and *29 were observed with different frequencies. Our study showed 26% representation of intermediate metabolizers (IM) and 2% poor metabolizers (PM) in the study population.

Conclusion

The implications for informal sector workers who use tramadol for recreational purposes, is that IMs and PMs will overdose as they may have reduced analgesic effects which will translate into increased risks of unforeseen adverse events. We therefore propose that CYP2D6 should be considered in opioid dosage while making use of these observed variations to implement new approaches to tackle the tramadol ‘abuse crisis’ in Ghana.
Association between the triglyceride-glucose index and impaired cardiovascular fitness in non-diabetic young population
Authors: Guo Dachuan , Wu Zhenguo , Xue Fei , Chen Sha , Ran Xiangzhen , Zhang Cheng , Yang Jianmin
Published: January 2024

Background

The triglyceride-glucose (TyG) index has been linked to the onset, progression, and prognosis of cardiovascular disease (CVD) in middle-aged and elderly individuals. Nevertheless, the relationship between the TyG index and impaired cardiovascular fitness (CVF) remains unexplored in non-diabetic young population.

Methods

We used data from the National Health and Nutrition Examination Survey (NHANES) study (1999–2004) to conduct a cross-sectional study of 3364 participants who completed an examination of CVF. Impaired CVF was defined as low and moderate CVF levels determined by estimated maximal oxygen consumption (Vo2max), based on sex- and age-specific criteria. The TyG index was calculated by $$Ln[TG(mg/dL)\times FPG(mg/dl)/2]$$

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Results

The age (median with interquartile range) of the study population was 28 (19–37) years, and the TyG index (median ± standard deviation) was 8.36 ± 0.52. A significant association between the TyG index and impaired CVF was found in multivariable logistical regression analysis (per 1-unit increase in the TyG index: OR, 1.46; 95% Cl 1.13–1.90). A dose‒response relationship between the TyG index and impaired CVF was presented by restricted cubic splines (RCS). A significant interaction (p = 0.027) between sex and the TyG index for impaired CVF was found in the population aged < 20 years.

Conclusions

In non-diabetic young population, individuals with higher TyG index values are at an increased likelihood of encountering impaired CVF. Furthermore, sex may exert an impact on CVF, as males tend to be more susceptible to impaired CVF under comparable TyG index conditions.
Multiplexed MRM-based proteomics for identification of circulating proteins as biomarkers of cardiovascular damage progression associated with diabetes mellitus
Authors: Piarulli Francesco , Banfi Cristina , Ragazzi Eugenio , Gianazza Erica , Munno Marco , Carollo Massimo , Traldi Pietro , Lapolla Annunziata , Sartore Giovanni
Published: January 2024

Background

Type 2 diabetes mellitus (T2DM) increases the risk of coronary heart disease (CHD) by 2–4 fold, and is associated with endothelial dysfunction, dyslipidaemia, insulin resistance, and chronic hyperglycaemia. The aim of this investigation was to assess, by a multimarker mass spectrometry approach, the predictive role of circulating proteins as biomarkers of cardiovascular damage progression associated with diabetes mellitus.

Methods

The study considered 34 patients with both T2DM and CHD, 31 patients with T2DM and without CHD, and 30 patients without diabetes with a diagnosis of CHD. Plasma samples of subjects were analysed through a multiplexed targeted liquid chromatography mass spectrometry (LC-MS)-based assay, namely Multiple Reaction Monitoring (MRM), allowing the simultaneous detection of peptides derived from a protein of interest. Gene Ontology (GO) Analysis was employed to identify enriched GO terms in the biological process, molecular function, or cellular component categories. Non-parametric multivariate methods were used to classify samples from patients and evaluate the relevance of the analysed proteins’ panel.

Results

A total of 81 proteins were successfully quantified in the human plasma samples. Gene Ontology analysis assessed terms related to blood microparticles, extracellular exosomes and collagen-containing extracellular matrix. Preliminary evaluation using analysis of variance (ANOVA) of the differences in the proteomic profile among patient groups identified 13 out of the 81 proteins as significantly different. Multivariate analysis, including cluster analysis and principal component analysis, identified relevant grouping of the 13 proteins. The first main cluster comprises apolipoprotein C-III, apolipoprotein C-II, apolipoprotein A-IV, retinol-binding protein 4, lysozyme C and cystatin-C; the second one includes, albeit with sub-grouping, alpha 2 macroglobulin, afamin, kininogen 1, vitronectin, vitamin K-dependent protein S, complement factor B and mannan-binding lectin serine protease 2. Receiver operating characteristic (ROC) curves obtained with the 13 selected proteins using a nominal logistic regression indicated a significant overall distinction (p < 0.001) among the three groups of subjects, with area under the ROC curve (AUC) ranging 0.91–0.97, and sensitivity and specificity ranging from 85 to 100%.

Conclusions

Targeted mass spectrometry approach indicated 13 multiple circulating proteins as possible biomarkers of cardiovascular damage progression associated with T2DM, with excellent classification results in terms of sensitivity and specificity.
Diabetes mellitus is associated to high-risk late gadolinium enhancement and worse outcomes in patients with nonischemic dilated cardiomyopathy
Authors: Zulet Pablo , Islas Fabián , Ferrández-Escarabajal Marcos , Bustos Ana , Cabeza Beatriz , Gil-Abizanda Sandra , Vidal María , Martín-Lores Irene , Hernández-Mateo Paula , de Agustín J. Alberto , Olmos Carmen
Published: January 2024

Background

Diabetes mellitus (DM) is associated with a worse prognosis in patients with heart failure. Our aim was to analyze the clinical and imaging features of patients with DM and their association with outcomes in comparison to nondiabetic patients in a cohort of patients with nonischemic dilated cardiomyopathy (DCM).

Methods

This is a prospective cohort study of patients with DCM evaluated in a tertiary care center from 2018 to 2021. Transthoracic echocardiography and cardiac magnetic resonance findings were assessed. A high-risk late gadolinium enhancement (LGE) pattern was defined as epicardial, transmural, or septal plus free-wall. The primary outcome was a composite of heart failure hospitalizations and all-cause mortality. Multivariable analyses were performed to evaluate the impact of DM on outcomes.

Results

We studied 192 patients, of which 51 (26.6%) had DM. The median left ventricular ejection fraction was 30%, and 106 (55.2%) had LGE. No significant differences were found in systolic function parameters between patients with and without DM. E/e values were higher (15 vs. 11.9, p = 0.025), and both LGE (68.6% vs. 50.4%; p = 0.025) and a high-risk LGE pattern (31.4% vs. 18.5%; p = 0.047) were more frequently found in patients with DM. The primary outcome occurred more frequently in diabetic patients (41.2% vs. 23.6%, p = 0.017). DM was an independent predictor of outcomes (OR 2.01; p = 0.049) and of LGE presence (OR 2.15; p = 0.048) in the multivariable analysis. Patients with both DM and LGE had the highest risk of events (HR 3.1; p = 0.003).

Conclusion

DM is related to a higher presence of LGE in DCM patients and is an independent predictor of outcomes. Patients with DM and LGE had a threefold risk of events. A multimodality imaging approach allows better risk stratification of these patients and may influence therapeutic options.
Pulmonary co-infections by Pneumocystis jirovecii and Herpesviridae: a seven-year retrospective study
Authors: Rucar Alan , Totet Anne , Le Govic Yohann , Demey Baptiste , Damiani Céline
Published: January 2024

Background

Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungus responsible for Pneumocystis pneumonia (PCP) in deeply immunocompromised patients and for pulmonary colonization in individuals with mild immunosuppression or impaired respiratory function. PCP and Cytomegalovirus (CMV) co-infections have been widely described whereas those involving other Herpesviruses (HVs) such as Epstein-Barr virus (EBV), Herpes simplex virus type 1 and type 2 (HSV-1 and  -2), and Varicella zoster virus (VZV) remain scarce. To date, no data are available concerning HVs co-infections in P. jirovecii colonization.

Methods

Our main objective was to evaluate the frequency of HVs in bronchoalveolar lavage fluid (BALF) samples from patients with PCP or with pulmonary colonization. The secondary objective was to assess the relationship between HVs and the mortality rate in PCP patients. A retrospective single-center study over a seven-year period was conducted. All patients with P. jirovecii detected using PCR in a BALF sample and for whom a PCR assay for HVs detection was performed were included in the study.

Results

One hundred and twenty-five patients were included, corresponding to 77 patients with PCP and 48 colonized patients. At least one HV was detected in 54/77 (70.1%) PCP patients and in 28/48 (58.3%) colonized patients. EBV was the most frequent in both groups. Furthermore, the 30-day survival rate in PCP patients was significantly lower with [EBV + CMV] co-infection than that with EBV co-infection, [EBV + HSV-1] co-infection and without HV co-infection.

Conclusion

Our results show that the frequency of HV, alone or in combination is similar in PCP and colonization. They also suggest that [EBV + CMV] detection in BALF samples from PCP patients is associated with an increased mortality rate, underlying the significance to detect HVs in the course of PCP.
Reported xylazine exposure highly associated with overdose outcomes in a rapid community assessment among people who inject drugs in Baltimore
Authors: German Danielle , Genberg Becky , Sugarman Olivia , Saloner Brendon , Sawyer Anne , Glick Jennifer L. , Gribbin Molly , Flynn Colin
Published: January 2024

Background

Addressing xylazine harms are now a critical harm reduction priority, but relatively little epidemiological information exists to determine prevalence, magnitude, and correlates of xylazine use or related outcomes.

Methods

We conducted a rapid behavioral survey among people who inject drugs (n = 96) in Baltimore November–December 2022. Using a novel indicator of self-reported presumed xylazine effects, we examined prevalence and sociodemographic correlates of past year presumed xylazine effects and association with overdose and wound-related outcomes. Chi-square and descriptive statistics were used to examine bivariate associations overall and separately for those who reported xylazine by name and by reported fentanyl use frequency.

Results

Almost two-thirds (61.5%) reported experiencing xylazine effects. There were no differences by socio-demographics, but xylazine effects were more commonly reported among those who reported injecting alone (66% vs 38%%, p < 0.007) and daily fentanyl use (47% vs 24% p < 0.003). Those reporting xylazine exposure was three times as likely to report overdose (32% vs 11%, p < 0.03) and twice as likely to have used naloxone (78% vs 46%, p < 0.003). They also more commonly reported knowing someone who died of an overdose (92% vs 76%, p < 0.09) and to report an abscess requiring medical attention (36% vs 19%, p < 0.80). These associations were higher among respondents who specifically named xylazine and those who used fentanyl more frequently, but fentanyl frequency did not fully explain the heightened associations with xylazine effects.

Conclusions

This study provides insight into the scope of xylazine exposure and associated health concerns among community-based PWID and suggests measures that may be instrumental for urgently needed research.
Mortality and morbidity after colorectal cancer resection surgery in elderly patients: a retrospective population-based study in Sweden
Authors: Normann Maria , Ekerstad Niklas , Angenete Eva , Prytz Mattias
Published: January 2024

Background

Colorectal cancer is primarily a condition of older adults, and surgery is the cornerstone of treatment. As life expectancy is increasing and surgical techniques and perioperative care are developing, curative surgery is often conducted even in ageing populations. However, the risk of morbidity, functional decline, and mortality following colorectal cancer resection surgery are known to increase with increasing age. This study aims to describe real-world data about postoperative mortality and morbidity after resection surgery for colorectal cancer in the elderly (≥ 70 years) compared to younger patients (< 70 years), in a Swedish setting.

Methods

A cohort study including all patients diagnosed with colorectal cancer in a Swedish region of 1.7 million inhabitants between January 2016 and May 2020. Patients were identified through the Swedish Colorectal Cancer Registry, and all baseline and outcome variables were extracted from the registry. The following outcome measures were compared between the two age groups: 90-day mortality rates, postoperative complications, postoperative intensive care, reoperations, readmissions, and 1-year mortality. To adjust the analyses for baseline confounders in the comparison of the outcome variables, the following methods were used: marginal matching, calliper (ID matching), and logistic regression adjusted for baseline confounders.

Results

The cohort consisted of 5246 patients, of which 3849 (73%) underwent resection surgery. Patients that underwent resection surgery were significantly younger than those who did not (mean ± SD, 70.9 ± 11.4 years vs 73.7 ± 12.8 years, p < 0.001). Multivariable analyses revealed that both 90-day and 1-year mortality rates were higher in older patients that underwent resection surgery (90-day mortality OR 2.12 [95% CI 1.26–3.59], p < 0.005). However, there were no significant differences in postoperative intensive care, postoperative complications, reoperations, or readmissions.

Conclusion

Elderly patients suffer increased postoperative mortality after resection surgery for colorectal cancer compared to younger individuals. Given the growing elderly population that will continue to require surgery for colorectal cancer, more efficient ways of determining and handling individual risk for older adults need to be implemented in clinical practice.
Matrix stiffness affects tumor-associated macrophage functional polarization and its potential in tumor therapy
Authors: Xiong Jiaqiang , Xiao Rourou , Zhao Jiahui , Zhao Qiuyan , Luo Manwen , Li Feng , Zhang Wei , Wu Meng
Published: January 2024

The extracellular matrix (ECM) plays critical roles in cytoskeletal support, biomechanical transduction and biochemical signal transformation. Tumor-associated macrophage (TAM) function is regulated by matrix stiffness in solid tumors and is often associated with poor prognosis. ECM stiffness-induced mechanical cues can activate cell membrane mechanoreceptors and corresponding mechanotransducers in the cytoplasm, modulating the phenotype of TAMs. Currently, tuning TAM polarization through matrix stiffness-induced mechanical stimulation has received increasing attention, whereas its effect on TAM fate has rarely been summarized. A better understanding of the relationship between matrix stiffness and macrophage function will contribute to the development of new strategies for cancer therapy. In this review, we first introduced the overall relationship between macrophage polarization and matrix stiffness, analyzed the changes in mechanoreceptors and mechanotransducers mediated by matrix stiffness on macrophage function and tumor progression, and finally summarized the effects of targeting ECM stiffness on tumor prognosis to provide insight into this new field.
Long-term monitoring of fatty acid oxidation defects: results from a MetabERN survey
Authors: Schwantje Marit , Grünert Sarah C. , Fuchs Sabine A.
Published: January 2024

Background

Implementation of long-chain fatty acid oxidation defects (LCFAOD) in newborn screening (NBS) programs allows for pre-symptomatic diagnosis and treatment. The long-term natural history of NBS LCFAOD patients is largely unknown and may differ from clinically diagnosed pre-NBS patients. This complicates long-term monitoring of LCFAOD and may cause high monitoring variability. To gain insight in current clinical practice, we performed a web-based questionnaire among all metabolic members of the European Reference Network for Hereditary Metabolic Disorders (MetabERN).

Results

Thirty-seven colleagues representing at least 35 European metabolic centres shared their experience and results were discussed at the European Metabolic Group (EMG) meeting 2022. The centres concurred in many aspects of long-term monitoring of LCFAOD including the frequency of clinical visits, determination of laboratory parameters, cardiac monitoring and retinopathy screening. Main discrepancies comprised hepatic imaging, glucose monitoring and electrophysiological investigations.

Conclusions

Discrepancies may reflect differences in local availability of monitoring tools, the inclusion of LCFAOD in NBS programs as well as differences in local genotypes and phenotypes. Because monitoring strategies are largely based on the natural disease course of clinically identified patients, there might be over-monitoring of some NBS patients. Nevertheless, we advocate long-term monitoring because resulting information is essential to further characterize the natural disease course, develop evidence-based guidelines and provide a basis for evaluation of future therapies.
Evaluating the development and well-being assessment (DAWBA) in pediatric anxiety and depression
Authors: Amelio Paia , Antonacci Chase , Khosravi Parmis , Haller Simone , Kircanski Katharina , Berman Erin , Cullins Lisa , Lewis Krystal , Davis Mollie , Engel Chana , Towbin Kenneth , Stringaris Argyris , Pine Daniel S.
Published: January 2024

Enhancing screening practices and developing scalable diagnostic tools are imperative in response to the increasing prevalence of youth mental health challenges. Structured lay psychiatric interviews have emerged as one such promising tool. However, there remains limited research evaluating structured psychiatric interviews, specifically their characterization of internalizing disorders in treatment-seeking youth. This study evaluates the relationship between the Development and Well-Being Assessment (DAWBA), a structured psychiatric interview, and established measures of pediatric anxiety and depression, including the Screen for Child Anxiety Related Disorders (SCARED), the Pediatric Anxiety Rating Scale (PARS), and the Mood and Feelings Questionnaire (MFQ). The study comprised two independent clinical samples of treatment-seeking youth: sample one included 55 youth with anxiety and 29 healthy volunteers (HV), while sample two included 127 youth with Major Depressive Disorder and 73 HVs. We examined the association between the DAWBA band scores, indicating predicted risk for diagnosis, the SCARED and PARS (sample one), and the MFQ (sample two). An exploratory analysis was conducted in a subset of participants to test whether DAWBA band scores predicted the change in anxiety symptoms (SCARED, PARS) across a 12-week course of cognitive behavioral therapy. The results revealed that the DAWBA significantly predicted the SCARED, PARS and MFQ measures at baseline; however, it did not predict changes in anxiety symptoms across treatment. These findings suggest that the DAWBA may be a helpful screening tool for indexing anxiety and depression in treatment-seeking youth but is not especially predictive of longitudinal trajectories in symptomatology across psychotherapy.
Societal costs of sepsis in the Netherlands
Authors: Luijks Erik C. N. , van der Slikke Elisabeth C. , van Zanten Arthur R. H. , ter Maaten Jan C. , Postma Maarten J. , Hilderink Henk B. M. , Henning Robert H. , Bouma Hjalmar R.
Published: January 2024

Background

Sepsis is a life-threatening syndrome characterized by acute loss of organ function due to infection. Sepsis survivors are at risk for long-term comorbidities, have a reduced Quality of Life (QoL), and are prone to increased long-term mortality. The societal impact of sepsis includes its disease burden and indirect economic costs. However, these societal costs of sepsis are not fully understood. This study assessed sepsis’s disease-related and indirect economic costs in the Netherlands.

Methods

Sepsis prevalence, incidence, sepsis-related mortality, hospitalizations, life expectancy, QoL population norms, QoL reduction after sepsis, and healthcare use post-sepsis were obtained from previous literature and Statistics Netherlands. We used these data to estimate annual Quality-adjusted Life Years (QALYs), productivity loss, and increase in healthcare use post-sepsis. A sensitivity analysis was performed to analyze the burden and indirect economic costs of sepsis under alternative assumptions, resulting in a baseline, low, and high estimated burden. The results are presented as a baseline (low–high burden) estimate.

Results

The annual disease burden of sepsis is approximately 57,304 (24,398–96,244; low–high burden) QALYs. Of this, mortality accounts for 26,898 (23,166–31,577) QALYs, QoL decrease post-sepsis accounts for 30,406 (1232–64,667) QALYs. The indirect economic burden, attributed to lost productivity and increased healthcare expenditure, is estimated at €416.1 (147.1–610.7) million utilizing the friction cost approach and €3.1 (0.4–5.7) billion using the human capital method. Cumulatively, the combined disease and indirect economic burdens range from €3.8 billion (friction method) to €6.5 billion (human capital method) annually within the Netherlands.

Conclusions

Sepsis and its complications pose a substantial disease and indirect economic burden to the Netherlands, with an indirect economic burden due to production loss that is potentially larger than the burden due to coronary heart disease or stroke. Our results emphasize the need for future studies to prevent sepsis, saving downstream costs and decreasing the economic burden.
Sequential catalytic lignin valorization and bioethanol production: an integrated biorefinery strategy
Authors: Wu Yilu , Su Changsheng , Liao Zicheng , Zhang Gege , Jiang Yongjie , Wang Yankun , Zhang Changwei , Cai Di , Qin Peiyong , Tan Tianwei
Published: January 2024

Background

The effective valorization of lignin and carbohydrates in lignocellulose matrix under the concept of biorefinery is a primary strategy to produce sustainable chemicals and fuels. Based on the reductive catalytic fractionation (RCF), lignin in lignocelluloses can be depolymerized into viscous oils, while the highly delignified pulps with high polysaccharides retention can be transformed into various chemicals.

Results

A biorefinery paradigm for sequentially valorization of the main components in poplar sawdust was constructed. In this process, the well-defined low-molecular-weight phenols and bioethanol were co-generated by tandem chemo-catalysis in the RCF stage and bio-catalysis in fermentation stage. In the RCF stage, hydrogen transfer reactions were conducted in one-pot process using Raney Ni as catalyst, while the isopropanol (2-PrOH) in the initial liquor was served as a hydrogen donor and the solvent for lignin dissolution. Results indicated the proportion of the 2-PrOH in the initial liquor of RCF influenced the chemical constitution and yield of the lignin oil, which also affected the characteristics of the pulps and the following bioethanol production. A 67.48 ± 0.44% delignification with 20.65 ± 0.31% of monolignols yield were realized when the 2-PrOH:H2O ratio in initial liquor was 7:3 (6.67 wt% of the catalyst loading, 200 °C for 3 h). The RCF pulp had higher carbohydrates retention (57.96 ± 2.78 wt%), which was converted to 21.61 ± 0.62 g/L of bioethanol with a yield of 0.429 ± 0.010 g/g in fermentation using an engineered S. cerevisiae strain. Based on the mass balance analysis, 104.4 g of ethanol and 206.5 g of lignin oil can be produced from 1000 g of the raw poplar sawdust.

Conclusions

The main chemical components in poplar sawdust can be effectively transformed into lignin oil and bioethanol. The attractive results from the biorefinery process exhibit great promise for the production of valuable biofuels and chemicals from abundant lignocellulosic materials.
Novel ABCD1 variant causes phenotype of adrenomyeloneuropathy with cerebral involvement in Ukrainian siblings: first adult hematopoietic stem cell transplantation for ALD in Ukraine: a case report
Authors: Shchubelka Khrystyna , Herasymenko Olga , Budzyn Andrii , Lysytsia Oleksandr , Rusyn Anastasiia , Oleksyk Olga , Tynta Svitlana , Oleksyk Taras
Published: January 2024

Background

This article presents a case study of two white male siblings of 24 and 31 years of age of self-reported Ukrainian ethnicity diagnosed with adrenomyeloneuropathy (AMN) associated with a novel splice site mutation in the ABCD1 gene. AMN represents a form of X-linked adrenoleukodystrophy (X-ALD) characterized by demyelination of the spinal cord and peripheral nerves. The case also presents the first adult haematopoietic stem cell transplant (HSCT) for adrenomyeloneuropathy in Ukraine. The rarity of this mutation and its cerebral involvement and the treatment make this case noteworthy and underscore the significance of reporting it to contribute to the existing medical knowledge.

Case presentation

The patients of 24 and 31 years initially exhibited progressive gait disturbance, lower extremity pain, and urinary incontinence, with the older sibling experiencing more advanced symptoms of speech, hearing, and vision disturbances. A comprehensive genetic analysis identified an unreported splice site mutation in exon 3 of the ABCD1 gene, leading to the manifestation of AMN. The inheritance pattern was consistent with X-linked recessive transmission. The article also outlines the clinical features, magnetic resonance imaging (MRI), and nerve conduction study (NCS) findings. Moreover, it discusses the genetic profile of the affected individuals and female carriers within the family. The younger sibling underwent HSCT, which was complicated by mediastinal lymph node and lung tuberculosis, adding to the complexity of managing adult ALD patients.

Conclusions

This report emphasizes the importance of genetic testing in diagnosing and comprehending the underlying mechanisms of rare genetic disorders, such as AMN with cerebral involvement. The identification of a novel splice site mutation expands our understanding of the genetic landscape of this condition. Additionally, the challenges and complications encountered during the hematopoietic stem cell transplant procedure underscore the need for cautious consideration and personalized approaches in adult ALD patients.
Nanobodies as potential tools for microbiological testing of live biotherapeutic products
Authors: Dorosky Robert J. , Schreier Jeremy E. , Lola Stephanie L. , Sava Rosa L. , Coryell Michael P. , Akue Adovi , KuKuruga Mark , Carlson Paul E. , Dreher-Lesnick Sheila M. , Stibitz Scott
Published: January 2024

Nanobodies are highly specific binding domains derived from naturally occurring single chain camelid antibodies. Live biotherapeutic products (LBPs) are biological products containing preparations of live organisms, such as Lactobacillus, that are intended for use as drugs, i.e. to address a specific disease or condition. Demonstrating potency of multi-strain LBPs can be challenging. The approach investigated here is to use strain-specific nanobody reagents in LBP potency assays. Llamas were immunized with radiation-killed Lactobacillus jensenii or L. crispatus whole cell preparations. A nanobody phage-display library was constructed and panned against bacterial preparations to identify nanobodies specific for each species. Nanobody-encoding DNA sequences were subcloned and the nanobodies were expressed, purified, and characterized. Colony immunoblots and flow cytometry showed that binding by Lj75 and Lj94 nanobodies were limited to a subset of L. jensenii strains while binding by Lc38 and Lc58 nanobodies were limited to L. crispatus strains. Mass spectrometry was used to demonstrate that Lj75 specifically bound a peptidase of L. jensenii, and that Lc58 bound an S-layer protein of L. crispatus. The utility of fluorescent nanobodies in evaluating multi-strain LBP potency assays was assessed by evaluating a L. crispatus and L. jensenii mixture by fluorescence microscopy, flow cytometry, and colony immunoblots. Our results showed that the fluorescent nanobody labelling enabled differentiation and quantitation of the strains in mixture by these methods. Development of these nanobody reagents represents a potential advance in LBP testing, informing the advancement of future LBP potency assays and, thereby, facilitation of clinical investigation of LBPs.
Lenvatinib plus hepatic arterial infusion chemotherapy with cisplatin for advanced hepatocellular carcinoma.
Authors: Yamamoto Makoto , Terashima Takeshi , Yamashita Tatsuya , Yanagi Masahiro , Nakagawa Hidetoshi , Seki Akihiro , Nio Kouki , Arai Kuniaki , Toyama Tadashi , Yamashita Taro
Published: January 2024

496

Background: A recent phase II study demonstrated that combination therapy with lenvatinib and hepatic arterial infusion chemotherapy using cisplatin (Lenva+CDDP) had high anti-tumor effects for patients with advanced hepatocellular carcinoma (HCC) with no prior history of systemic chemotherapy; however, whether the efficacy of Lenva+CDDP is superior to lenvatinib monotherapy remains unclear. Methods: We retrospectively reviewed the medical records of patients with advanced HCC and a Child–Pugh score of 5, 6, or 7 who were treated with Lenva+CDDP or lenvatinib, and compared the efficacy between the treatments. Patients in both groups received a once daily dose of lenvatinib (8 mg or 12 mg according to their weight), and the Lenva+CDDP group also received 65 mg/m2 of CDDP via the hepatic artery every 4 weeks. Treatment was repeated until tumor progression or unacceptable toxicity were observed. Results: A total of 140 patients (40 in the Lenva+CDDP group and 100 in the lenvatinib group) were included in this analysis. Patient backgrounds were comparable between the two groups, and 12 and 19 patients were previously treated with immunotherapy in the Lenva+CDDP group and lenvatinib group, respectively. The objective response rate and tumor control rate, assessed by RECIST ver1.1, in the Lenva+CDDP group were 67.5% and 100%, respectively, which was higher than in the lenvatinib group (17.0% and 87.0%, respectively). Median progression-free survival (PFS) and overall survival (OS) were 8.8 months and 19.6 months, respectively, in the Lenva+CDDP group, and 5.6 months and 20.3 months, respectively, in the lenvatinib group. Among patients who previously received immunotherapy, the median PFS, median OS, and 1-year survival rate were 9.7 months, not reached, and 87.5%, respectively, in the Lenva+CDDP group, and 4.7 months, 15.8 months, and 64.7%, respectively, in the lenvatinib group. Hematological toxicities were the main grade 3–4 adverse events (AEs) more frequently observed in the Lenva+CDDP group compared with the lenvatinib group. However, all grade 3–4 AEs were reversible, and there were no treatment-related deaths in either group. Conclusions: Lenva+CDDP demonstrated a better response and patient outcome than lenvatinib, and was well-tolerated in patients with advanced HCC. We are currently conducting a randomized controlled trial comparing the efficacy of these treatments.
Metastatic site and clinical outcome of patients with deficient mismatch repair metastatic colorectal cancer treated with an immune checkpoint inhibitor in the first-line setting.
Authors: Saberzadeh Ardestani Bahar , Jones Jeremy Clifton , McWilliams Robert R. , Tougeron David , Halfdanarson Thorvardur Ragnar , Guimbaud Rosine , Hubbard Joleen M. , Flecchia Clémence , Shi Qian , Alouani Emily Linda , Sonbol Bassam Bassam , Ticku Jonathan , Jin Zhaohui , Taieb Julien , Sinicrope Frank A.
Published: January 2024

55

Background: Nearly one-half of deficient mismatch repair (d-MMR) metastatic colorectal cancers (mCRC) demonstrate durable responses to immune checkpoint inhibitors (ICIs). Given preclinical data indicating that liver metastases sequester activated CD8+ T cells from systemic circulation, we examined clinical outcome by metastatic site. Methods: In a retrospective cohort of patients with d-MMR mCRCs treated at multiple centers in France (n=66), we sought to validate data from a U.S. cohort, and then performed pooled analysis (n=104). All patients received first-line ICI monotherapy. Metastatic site was analyzed in relationship to tumor response (RECIST version 1.1), and progression-free survival (PFS) by multivariable stratified Cox regression after adjustment for covariates. Results: Objective responses were achieved in 38/66 (58%) patients in the validation cohort. Best tumor response included 13 (20%) complete responses (CR), 25 (38%) partial responses (PR), 16 (25%) stable disease, and 11 (17%) progressive disease (PD). One-year and 5-year PFS rates were 73% and 67%, respectively; 18 (27%) patients progressed during immunotherapy. Best tumor response was attenuated in patients with liver metastasis ( P=0.03). Presence of liver metastasis, but not other sites, was associated with significantly poorer PFS after adjustment for covariates (HRadj 2.82; 95%CI, 1.08-7.39; Padj=0.03). In a pooled analysis, liver metastasis remained significantly and independently associated with poorer PFS (HRadj 3.18; 95%CI, 1.52-6.67; Padj=0.002) and with attenuated tumor best response (P=0.01). Conclusions: Metastasis to the liver, but not other sites, was validated as an independent factor associated with poorer response and survival after ICI treatment in d-MMR mCRCs. These data underscore the need for novel therapeutic strategies in these patients. [Table: see text]
A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors.
Authors: Schlechter Benjamin L. , Dumbrava Ecaterina Elena , George Mridula Annette , Saibil Samuel , Butler Marcus O. , Giordano Antonio , Surana Rishi , Liao Chih-Yi , Weiss Jordan , Pieke Brooke , Gavriliuc Miriam , Lichtenstein Emily , Apostolopoulou Maria , Burke Courtney , Qureshi Bushra , Adib Deyaa R , Olson Daniel
Published: January 2024

747

Background: Despite therapeutic developments for patients with advanced HER2+ solid tumors, significant unmet medical needs still exist. The T cell antigen coupler (TAC) technology is an approach to modifying T cells ex vivo, which allows recognition and cytotoxicity of tumor cells by co-opting the natural T cell receptor. TAC T cells demonstrate a safer profile than chimeric antigen receptor T cells. TAC01-HER2 is an autologous T-cell product comprising T cells expressing HER2 TAC. Methods: The ongoing clinical trial (NCT04727151) is evaluating the safety and preliminary anti-tumor activity of TAC01-HER2 treatment of HER2+ solid tumors. Subjects undergo leukapheresis followed by low-intensity lymphodepletion chemotherapy prior to TAC01-HER2 infusion. In phase I dose escalation, TAC01-HER2 is administered at increasing doses (Cohorts 1-4) in adult subjects after ≥2 lines of therapy. Dose limiting toxicities (DLT) are assessed up to 28 days from TAC01-HER2 infusion. In Phase II, dose expansion groups will further evaluate the efficacy, safety, and pharmacokinetics of the optimal TAC01-HER2 dose in gastric/GEJ tumors. Results: As of 31 August 2023, 20 patients with solid tumors have been treated in Cohorts 1-4. Subjects had a median of 4 prior therapies (2-12) and all had maintained HER2 expression on central review at enrollment. Three subjects were HER2 1+ or 2+/FISH-. One DLT event of grade 3 (G3) pneumonitis has been reported in 1 subject in Cohort 4. No neurotoxicity has been reported. Most subjects treated at Cohorts 3-4 experienced cytokine release syndrome (CRS) which resolved with supportive therapy. Fifteen subjects have reported a total of 31 serious adverse events, with 1 G3 pneumonitis and 5 CRS (one G1, three G2 and one G3) related to TAC01-HER2. A 68.8% disease control rate (DCR) was observed in Cohorts 2-4 at first restaging after TAC01-HER2 infusion. For gastric/GEJ subjects of the same Cohorts, DCR was 85.7%. 3 months after TAC01-HER2 infusion, DCR was 30.8% for all subjects of Cohorts 2-4 and 28.6% for gastric/GEJ subjects. Two patients had a partial response (PR). At Cohort 4, a PR was observed in a subject with GEJ (HER2 2+, FISH+) with 100% reduction of target lesion. This patient had progressed on 4 prior lines of therapy including trastuzumab and trastuzumab deruxtecan. Conclusions: Treatment with TAC01-HER2 showed manageable safety and promising clinical activity in a heavily pre-treated cancer population. The recommended phase 2 dose was identified as dose level 4 (6-8 x 106 cells/kg). Clinical trial information: NCT04727151 .
A two-arm randomized open-label prospective design superiority phase III clinical trial to compare the efficacy of docetaxel-oxaliplatin-capecitabine/5 fluorouracil (DOC/F) followed by docetaxel versus CAPOX/mFOLFOX-7 in advanced gastric cancers (DOC-GC study).
Authors: Ramaswamy Anant , Bhargava Prabhat Ghanshyam , Dubashi Biswajit , Kapoor Akhil , Srinivas Sujay , Shetty Omshree , Kaushal Rajiv Kumar , Shah Aekta , Noronha Vanita , Joshi Amit , Menon Nandini Sharrel , Nashikkar Chaitali , Gupta Anuj , Mishra Bal Krishna , Kayal Smita , Ananthakrishnan Ramesh , Kumar Suman , Ganesan Prasanth , Prabhash Kumar , Ostwal Vikas S.
Published: January 2024

LBA248

Background: The choice of optimal chemotherapy in advanced (unresectable/metastatic) gastroesophageal junction and gastric (GEJ/G) adenocarcinomas remains undecided with regard to the addition of docetaxel to a FOLFOX/CAPOX backbone in improving outcomes with equipoise with regard to the optimal duration of chemotherapy as well. Methods: The DOC GC study is a multicentric open-label, randomized controlled phase III trial, in adults ≥18 years with advanced GEJ/G adenocarcinoma and adequate end-organ function. Patients were randomized 1:1 to one of two arms: Arm A - modified CAPOX (3 weekly) or modified FOLFOX-7 (2 weekly) for a maximum of 6 months and then observation OR Arm B: modified FLOT (5-FU/leucovorin /Oxaliplatin/Docetaxel) or DOX (docetaxel/oxaliplatin/capecitabine) every 2 weeks for a maximum of four months followed by Docetaxel (60mg/m2) every 3 weeks till disease progression, unacceptable toxicity, or patient's decision to withdraw. The primary endpoint of the study is Overall survival (OS), as calculated by Kaplan-Meier method, while key secondary endpoints include Progression-free survival, and adverse event rates. Results: Of the 324 patients randomized between July 2020 and November 2022, 305 patients were evaluable for analysis (Arm A: 156; Arm B: 149). With a median follow-up time of 19.2 months (95% CI: 16.5 – 21.9) for the entire cohort, the median OS was 10.1 months (95%: 9.2-10.9) in Arm A and 8.9 months (95% CI: 7.3-10.5) in arm B and this difference was not statistically significant [p=0.70]. There were no statistical differences in median PFS between the two arms [Arm A: 7.1 months (95% CI: 6.1-8.1); Arm B: 6.2 months (95% CI: 5.7 – 6.8); p=0.39]. An increased proportion of grade 3/4 neutropenia (21% vs. 5.1%; p<0.001) was seen in patients in Arm B, with other treatment related side effects being comparable between the two arms. A greater proportion of patients in Arm A tended to receive second line therapy compared to Arm B (38% vs. 26%; p=0.07). Conclusions: The addition of docetaxel to a doublet regimen comprising 5-fluorouracil/capecitabine and oxaliplatin did not improve overall survival in patients with advanced GEJ/G cancers. Continuing chemotherapy beyond six months also does not appear to improve survival in this group of cancers. Clinical trial information: CTRI/2020/03/023944 .