bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractEnhancing 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

Abstract
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

Abstract
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

Abstract
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

AbstractNanobodies 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 .