bluuebunny/crossref_metadata_2025 huggingface dataset:
The Protective Action of Coutarea hexandra (Rubiaceae) on the Neuromuscular Blockade Induced by Lachesis muta muta (Viperidae: Crotalinae) Venom
Authors: Pilon Grazielle D. , Farias-de-França Anna P. , Cantuária Nathalia M. , Silva Magali G. , Leão-Torres Aline G. , Floriano Rafael S. , dos Santos Marcio G. , da Silva Nelson Jorge , Gerlach Otto M. S. , Cechinel-Filho Valdir , Oshima-Franco Yoko
Published: November 2024

Envenomations by snakes represent a neglected health problem in tropical and subtropical countries. In South America, Lachesis muta occasionally causes severe human envenomation, with treatment being conditioned to an unspecific antivenom. In this work, we examined the neutralizing ability of Coutarea hexandra stem bark hydroalcoholic extract (Ch‐E), including the commercial phytochemicals coumarin and quinine, on the neuromuscular blockade induced by L. m. muta venom in mouse phrenic nerve‐diaphragm preparation. Biological assays were performed following conventional myographic technique ex vivo. Ch‐E was phytochemically characterized to detect the presence of coumarin and quinine using analytical methods. Ch‐E and commercial phytochemicals were tested separately or combined under pre‐ and post‐venom incubation protocols. Ch‐E attenuated the venom‐induced neuromuscular blockade only under the pre‐venom incubation protocol. Quinine was not detected in Ch‐E. Commercial coumarin and quinine exhibited a concentration‐dependent counteracting effect on the venom‐induced neuromuscular blockade. The pre‐venom incubation protocol showed to be efficient in attenuating the L. m. muta venom–induced neuromuscular blockade, most likely due to the presence of coumarin derivatives and unknown alkaloids in this extract.
Supplementary Table S1 from Hepatocellular Carcinoma Immune Microenvironment Analysis: A Comprehensive Assessment with Computational and Classical Pathology
Authors: Ercan Caner , Renne Salvatore Lorenzo , Di Tommaso Luca , Ng Charlotte K.Y. , Piscuoglio Salvatore , Terracciano Luigi M.
Published: November 2024

Supplementary Table S1. Overview of the hyperparameters used for the cell nucleus segmentation model.
Supplementary Table S5 from MEK Inhibitors Lead to PDGFR Pathway Upregulation and Sensitize Tumors to RAF Dimer Inhibitors in NF1-Deficient Malignant Peripheral Nerve Sheath Tumor
Authors: Miranda-Román Miguel A. , Lee Cindy J. , Fishinevich Eve , Ran Leili , Patel Amish J. , Yan Juan , Khudoynazarova Makhzuna N. , Warda Sarah , Pachai Mohini R. , Chen Yu , Chi Ping
Published: November 2024

Supplementary Table S5. sgRNAs used for CRISPR/Cas9 KOs.
Table 1 from GDF-15 Predicts Epithelioid Hemangioendothelioma Aggressiveness and Is Downregulated by Sirolimus through ATF4/ATF5 Suppression
Authors: Stacchiotti Silvia , Martini Silvia , Pasquali Sandro , Frezza Anna M. , Beretta Alessia , Percio Stefano , Lecchi Mara , Tortoreto Monica , Barisella Marta , Collini Paola , Dagrada Gian Paolo , Merlini Alessandra , Huang Paul H. , Jenks Andrew , Jones Robin L. , Tap William D. , Ingrosso Matilde , Morosi Carlo , Brich Silvia , Giani Claudia , Verderio Paolo , Casali Paolo G. , Leonard Hugh , Gronchi Alessandro , Zuco Valentina , Zaffaroni Nadia
Published: November 2024

Demographic and clinicopathologic characteristics of patients with EHE in the two study cohorts.
Supplementary Table 3 from GDF-15 Predicts Epithelioid Hemangioendothelioma Aggressiveness and Is Downregulated by Sirolimus through ATF4/ATF5 Suppression
Authors: Stacchiotti Silvia , Martini Silvia , Pasquali Sandro , Frezza Anna M. , Beretta Alessia , Percio Stefano , Lecchi Mara , Tortoreto Monica , Barisella Marta , Collini Paola , Dagrada Gian Paolo , Merlini Alessandra , Huang Paul H. , Jenks Andrew , Jones Robin L. , Tap William D. , Ingrosso Matilde , Morosi Carlo , Brich Silvia , Giani Claudia , Verderio Paolo , Casali Paolo G. , Leonard Hugh , Gronchi Alessandro , Zuco Valentina , Zaffaroni Nadia
Published: November 2024

Supplementary Table 3. Quantification of band intensities for blot reported in Figure 4C and E.
Supplementary Table S5 from A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6–Targeting Antibody–Drug Conjugate, in Patients with Small Cell Lung Cancer
Authors: Morgensztern Daniel , Ready Neal , Johnson Melissa L. , Dowlati Afshin , Choudhury Noura , Carbone David P. , Schaefer Eric , Arnold Susanne M. , Puri Sonam , Piotrowska Zofia , Hegde Aparna , Chiang Anne C. , Iams Wade , Tolcher Anthony , Nosaki Kaname , Kozuki Toshiyuki , Li Tianhong , Santana-Davila Rafael , Akamatsu Hiroaki , Murakami Haruyasu , Yokouchi Hiroshi , Wang Song , Zha Jiuhong , Li Rui , Robinson Randy R. , Hingorani Pooja , Jeng Edwin E. , Furqan Muhammad
Published: November 2024

Preliminary Pharmacokinetic Parameters of ABBV-011 ADC Following IV Infusion of ABBV-011 1 mg/kg in Cycle 1 (n=40)
Supplementary Table S3 from Long-Term Follow-up of Levonorgestrel Intrauterine Device for Atypical Hyperplasia and Early Endometrial Cancer Reveals Relapse Characterized by Immune Exhaustion
Authors: Bowen Mikayla B. , Melendez Brenda , Zhang Qian , Yang Richard K. , Fellman Bryan M. , Lawson Barrett C. , Adjei Naomi N. , Celestino Joseph , Wani Khalida M. , Singh Bhavana , Urbauer Diana L. , Lazar Alexander J. , Lu Karen H. , Wargo Jennifer A. , Westin Shannon N. , Yates Melinda S.
Published: November 2024

Supplementary Table S3. Digital spatial profiling log2-normalized gene expression data.
Figure 3 from GDF-15 Predicts Epithelioid Hemangioendothelioma Aggressiveness and Is Downregulated by Sirolimus through ATF4/ATF5 Suppression
Authors: Stacchiotti Silvia , Martini Silvia , Pasquali Sandro , Frezza Anna M. , Beretta Alessia , Percio Stefano , Lecchi Mara , Tortoreto Monica , Barisella Marta , Collini Paola , Dagrada Gian Paolo , Merlini Alessandra , Huang Paul H. , Jenks Andrew , Jones Robin L. , Tap William D. , Ingrosso Matilde , Morosi Carlo , Brich Silvia , Giani Claudia , Verderio Paolo , Casali Paolo G. , Leonard Hugh , Gronchi Alessandro , Zuco Valentina , Zaffaroni Nadia
Published: November 2024

Sirolimus inhibited the growth of patient-derived models of EHE. A, Cell growth inhibition curves obtained after exposure to different doses of doxorubicin or sirolimus. Data are reported as the percentage of drug-treated cells compared with control cells and represent mean ± SD of three independent experiments. B, Growth curves reporting the RTW (mean ± SEM) in control and doxorubicin- or sirolimus-treated mouse groups (nine mice/group), in which 1 indicates the tumor weight at the beginning of the treatment. The arrows indicate when drugs were administered. C, Histomorphologic evaluation of tumors obtained from untreated and drug-treated mice. D, Ki67 immunostaining of tumors obtained from untreated and drug-treated mice (top) and quantification of Ki67 index (bottom). Symbols reported in the represent counted fields. Histomorphologic analysis and Ki67 immunostaining were performed on tumors excised from mice at the end of drug treatment. Scale bar, 100 μm. Data are reported as means ± SD of three independent experiments. E, Western blot analysis of downstream mTOR pathway in untreated cells and cells treated with different sirolimus concentrations for 3 days (left) and in tumors removed from untreated and sirolimus-treated mice at the end of treatment with different drug doses (right). Cropped images of selected proteins are shown. RTW, relative tumor weight.
Supplementary Figure S2 from Metabolic Tumor Volume Response after Bridging Therapy Determines Chimeric Antigen Receptor T-Cell Outcomes in Large B-Cell Lymphoma
Authors: Hubbeling Harper , Leithner Doris , Silverman Emily A. , Flynn Jessica , Devlin Sean , Shah Gunjan , Fregonese Beatrice , Wills Beatriz , Bedmutha Akshay , Alarcon Tomas Ana , Parascondola Allison , Saldia Amethyst , Landego Ivan , Hajj Carla , Boardman Alexander P. , Dahi Parastoo B. , Ghosh Arnab , Giralt Sergio , Lin Richard J. , Park Jae , Scordo Michael , Salles Gilles , Yahalom Joachim , Palomba Maria L. , Schöder Heiko , Perales Miguel-Angel , Shouval Roni , Imber Brandon S.
Published: November 2024

Supplementary Figure S2. Patterns of first failure for RT bridged patients.
Supplementary Table S4 from Predictive and Dynamic Signature for Antiangiogenics in Combination with a PD1 Inhibitor in Soft-Tissue Sarcoma: Correlative Studies Linked to the IMMUNOSARC Trial
Authors: Moura David S. , Lopez-Marti Jesus M. , Benesova Iva , de Andrea Carlos , di Lernia Davide , Lacerenza Serena , Mondaza-Hernandez Jose L. , Martin-Ruiz Marta , Ramirez-Calvo Marta , Grignani Giovanni , Martinez-Trufero Javier , Redondo Andres , Valverde Claudia , Stacchiotti Silvia , Lopez-Pousa Antonio , Lopez-Guerrero José A. , Gutierrez Antonio , Encinas-Tobajas Victor , Hindi Nadia , Sangiolo Dario , Lopez-Martin Jose A. , Strizova Zuzana Ozaniak , Martin-Broto Javier
Published: November 2024

Supplementary Table S4. MAXSTAT cut-off calculated for the Δ of gene expression between week 13 and baseline samples.
Supplementary Table S1 from Epigenome Reprogramming Through H3K27 and H3K4 Trimethylation as a Resistance Mechanism to DNA Methylation Inhibition in BRAFV600E-Mutated Colorectal Cancer
Authors: Lee Hey Min , Saw Ajay Kumar , Morris Van K. , Napolitano Stefania , Bristow Christopher , Srinivasan Sanjana , Peoples Micheal , Sorokin Alexey , Kanikarla Marie Preeti , Schulz Jonathan , Singh Anand K. , Terranova Christopher , Coker Oluwadara , Jain Abhinav , Kopetz Scott , Rai Kunal
Published: November 2024

Mutation and characteristics of conventional and PDX-derived CRC cell lines
Supplementary Figure S6 from Epigenome Reprogramming Through H3K27 and H3K4 Trimethylation as a Resistance Mechanism to DNA Methylation Inhibition in BRAFV600E-Mutated Colorectal Cancer
Authors: Lee Hey Min , Saw Ajay Kumar , Morris Van K. , Napolitano Stefania , Bristow Christopher , Srinivasan Sanjana , Peoples Micheal , Sorokin Alexey , Kanikarla Marie Preeti , Schulz Jonathan , Singh Anand K. , Terranova Christopher , Coker Oluwadara , Jain Abhinav , Kopetz Scott , Rai Kunal
Published: November 2024

Proteomic analysis of histone post-translational modifications (PTMs), particularly lysine acetylation, upon 5-azacitidine treatment
Supplementary Figure S4 from Epigenome Reprogramming Through H3K27 and H3K4 Trimethylation as a Resistance Mechanism to DNA Methylation Inhibition in BRAFV600E-Mutated Colorectal Cancer
Authors: Lee Hey Min , Saw Ajay Kumar , Morris Van K. , Napolitano Stefania , Bristow Christopher , Srinivasan Sanjana , Peoples Micheal , Sorokin Alexey , Kanikarla Marie Preeti , Schulz Jonathan , Singh Anand K. , Terranova Christopher , Coker Oluwadara , Jain Abhinav , Kopetz Scott , Rai Kunal
Published: November 2024

Differential methylation and histone marks upon 5-azacitidine treatment around 5mC-regulated genes
Supplementary Figure S3 from Epigenome Reprogramming Through H3K27 and H3K4 Trimethylation as a Resistance Mechanism to DNA Methylation Inhibition in BRAFV600E-Mutated Colorectal Cancer
Authors: Lee Hey Min , Saw Ajay Kumar , Morris Van K. , Napolitano Stefania , Bristow Christopher , Srinivasan Sanjana , Peoples Micheal , Sorokin Alexey , Kanikarla Marie Preeti , Schulz Jonathan , Singh Anand K. , Terranova Christopher , Coker Oluwadara , Jain Abhinav , Kopetz Scott , Rai Kunal
Published: November 2024

Chromatin state profiles of control and 5-azacitidine-treated samples
Supplementary Table S5 from Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial
Authors: Wang Xin , Kang Xiaozheng , Zhang Ruixiang , Xue Liyan , Xu Jiaqi , Zhao Xiaotian , Ou Qiuxiang , Yu Nuo , Feng Guojie , Li Jiao , Zheng Ziyu , Chen Xiankai , Wang Zhen , Zheng Qingfeng , Li Yong , Qin Jianjun , Bi Nan , Li Yin
Published: November 2024

Supplementary Table 5. The association between PD-L1 expression and pathological outcomes in patients with R0 resection
Supplementary Table S3 from Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial
Authors: Wang Xin , Kang Xiaozheng , Zhang Ruixiang , Xue Liyan , Xu Jiaqi , Zhao Xiaotian , Ou Qiuxiang , Yu Nuo , Feng Guojie , Li Jiao , Zheng Ziyu , Chen Xiankai , Wang Zhen , Zheng Qingfeng , Li Yong , Qin Jianjun , Bi Nan , Li Yin
Published: November 2024

Supplementary Table 3. The LRFS and DMFS data for the R0 resection and non-surgery group
Supplementary Table S2 from Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial
Authors: Wang Xin , Kang Xiaozheng , Zhang Ruixiang , Xue Liyan , Xu Jiaqi , Zhao Xiaotian , Ou Qiuxiang , Yu Nuo , Feng Guojie , Li Jiao , Zheng Ziyu , Chen Xiankai , Wang Zhen , Zheng Qingfeng , Li Yong , Qin Jianjun , Bi Nan , Li Yin
Published: November 2024

Supplementary Table 2. The PFS and OS data for the pCR and non-pCR group
Supplementary Table S1 from Chemoradiotherapy and Subsequent Immunochemotherapy as Conversion Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Phase II NEXUS-1 Trial
Authors: Wang Xin , Kang Xiaozheng , Zhang Ruixiang , Xue Liyan , Xu Jiaqi , Zhao Xiaotian , Ou Qiuxiang , Yu Nuo , Feng Guojie , Li Jiao , Zheng Ziyu , Chen Xiankai , Wang Zhen , Zheng Qingfeng , Li Yong , Qin Jianjun , Bi Nan , Li Yin
Published: November 2024

Supplementary Table 1. Representativeness of Study Participants
Supplementary Figure S7 from ctDNA Dynamics and Mechanisms of Acquired Resistance in Patients Treated with Osimertinib with or without Bevacizumab from the Randomized Phase II ETOP-BOOSTER Trial
Authors: Soo Ross A. , Dafni Urania , Han Ji-Youn , Cho Byoung Chul , Nadal Ernest , Yeo Chong Ming , Carcereny Enric , de Castro Javier , Sala Maria Angeles , Coate Linda , Provencio Mariano , Britschgi Christian , Vagenknecht Patrick , Dimopoulou Georgia , Kammler Roswitha , Finn Stephen P. , Peters Solange , Stahel Rolf A.
Published: November 2024

Supplementary Figure S7. Progression-free survival by treatment arm and smoking status for patients (A) with EGFR T790M mutation (n=97) (B) without EGFR T790M mutation (n=39) at baseline.
Supplementary Figure S6 from ctDNA Dynamics and Mechanisms of Acquired Resistance in Patients Treated with Osimertinib with or without Bevacizumab from the Randomized Phase II ETOP-BOOSTER Trial
Authors: Soo Ross A. , Dafni Urania , Han Ji-Youn , Cho Byoung Chul , Nadal Ernest , Yeo Chong Ming , Carcereny Enric , de Castro Javier , Sala Maria Angeles , Coate Linda , Provencio Mariano , Britschgi Christian , Vagenknecht Patrick , Dimopoulou Georgia , Kammler Roswitha , Finn Stephen P. , Peters Solange , Stahel Rolf A.
Published: November 2024

Supplementary Figure S6. Association of EGFR T790M MAF with time, based on N=136 baseline, N=110 week 9 and N=65 progression samples.
Supplementary Figure S4 from ctDNA Dynamics and Mechanisms of Acquired Resistance in Patients Treated with Osimertinib with or without Bevacizumab from the Randomized Phase II ETOP-BOOSTER Trial
Authors: Soo Ross A. , Dafni Urania , Han Ji-Youn , Cho Byoung Chul , Nadal Ernest , Yeo Chong Ming , Carcereny Enric , de Castro Javier , Sala Maria Angeles , Coate Linda , Provencio Mariano , Britschgi Christian , Vagenknecht Patrick , Dimopoulou Georgia , Kammler Roswitha , Finn Stephen P. , Peters Solange , Stahel Rolf A.
Published: November 2024

Supplementary Figure S4. Evolution of EGFR T790M mutational status across time for the N=45 patients with available samples at all 3 timepoints.
Supplementary Table S6 from The Epstein–Barr Virus Nuclear Antigen 1 Variant Associated with Nasopharyngeal Carcinoma Defines the Sequence Criteria for Serologic Risk Prediction
Authors: Warner Benjamin E. , Patel Japan , Wang Renwei , Adams-Haduch Jennifer , Gao Yu-Tang , Koh Woon-Puay , Wong Ka Wo , Chiang Alan K.S. , Yuan Jian-Min , Shair Kathy H.Y.
Published: November 2024

Supplementary Table S6. Sensitivity and specificity of IgA to EBNA1 IDE2 amino acid substitution constructs by denaturing immunoblot assay in NPCs <7.5 years to diagnosis and healthy controls.
Supplementary Table S1 from The Epstein–Barr Virus Nuclear Antigen 1 Variant Associated with Nasopharyngeal Carcinoma Defines the Sequence Criteria for Serologic Risk Prediction
Authors: Warner Benjamin E. , Patel Japan , Wang Renwei , Adams-Haduch Jennifer , Gao Yu-Tang , Koh Woon-Puay , Wong Ka Wo , Chiang Alan K.S. , Yuan Jian-Min , Shair Kathy H.Y.
Published: November 2024

Supplementary Table S1. EBNA1 mammalian-expression library details.
Supplementary Figure S3 from The Epstein–Barr Virus Nuclear Antigen 1 Variant Associated with Nasopharyngeal Carcinoma Defines the Sequence Criteria for Serologic Risk Prediction
Authors: Warner Benjamin E. , Patel Japan , Wang Renwei , Adams-Haduch Jennifer , Gao Yu-Tang , Koh Woon-Puay , Wong Ka Wo , Chiang Alan K.S. , Yuan Jian-Min , Shair Kathy H.Y.
Published: November 2024

Supplementary Figure S3. EBNA1 IgA AUC-ROC curve analysis.
Data from A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6–Targeting Antibody–Drug Conjugate, in Patients with Small Cell Lung Cancer
Authors: Morgensztern Daniel , Ready Neal , Johnson Melissa L. , Dowlati Afshin , Choudhury Noura , Carbone David P. , Schaefer Eric , Arnold Susanne M. , Puri Sonam , Piotrowska Zofia , Hegde Aparna , Chiang Anne C. , Iams Wade , Tolcher Anthony , Nosaki Kaname , Kozuki Toshiyuki , Li Tianhong , Santana-Davila Rafael , Akamatsu Hiroaki , Murakami Haruyasu , Yokouchi Hiroshi , Wang Song , Zha Jiuhong , Li Rui , Robinson Randy R. , Hingorani Pooja , Jeng Edwin E. , Furqan Muhammad
Published: November 2024

AbstractPurpose:
Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy.
Patients and Methods:
ABBV-011 was administered intravenously once every 3 weeks during dose escalation (0.3–2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by IHC) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated.
Results:
As of August 2022, 99 patients received ABBV-011 monotherapy [dose escalation, n = 36; Japanese dose evaluation, n = 3; dose expansion, n = 60 (1 mg/kg, n = 40)]; the median age was 63 years (range, 41–79 years). Also, 32%, 41%, and 26% of patients received 1, 2, and ≥3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. The most common treatment-emergent adverse events were fatigue (50%), nausea (42%), and thrombocytopenia (41%). The most common hepatic treatment-emergent adverse events were increased aspartate aminotransferase (22%), increased γ-glutamyltransferase (21%), and hyperbilirubinemia (17%); two patients experienced veno-occlusive liver disease. The objective response rate was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n = 40), the objective response rate was 25%; the median response duration was 4.2 months (95% confidence interval, 2.6–6.7); and the median progression-free survival was 3.5 months (95% confidence interval, 1.5–4.2).
Conclusions:
ABBV-011 1.0 mg/kg every 3 weeks monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.
Data from Long-Term Follow-up of Levonorgestrel Intrauterine Device for Atypical Hyperplasia and Early Endometrial Cancer Reveals Relapse Characterized by Immune Exhaustion
Authors: Bowen Mikayla B. , Melendez Brenda , Zhang Qian , Yang Richard K. , Fellman Bryan M. , Lawson Barrett C. , Adjei Naomi N. , Celestino Joseph , Wani Khalida M. , Singh Bhavana , Urbauer Diana L. , Lazar Alexander J. , Lu Karen H. , Wargo Jennifer A. , Westin Shannon N. , Yates Melinda S.
Published: November 2024

AbstractPurpose:
Nonsurgical treatment options are increasingly needed for endometrial atypical hyperplasia (AH) and endometrioid endometrial cancer (EEC). Despite promising initial response rates, prospective long-term data and determinants for relapse are limited.
Materials and Methods:
Follow-up data from patients in our prospective phase II trial of levonorgestrel intrauterine device (LIUD) for AH/G1EEC were collected from medical records. Spatial transcriptomics (Nanostring GeoMX digital spatial profiling) with in silico cell type deconvolution and pathway analyses were employed on longitudinal biopsy samples from five patients across pre-treatment, on-treatment, and relapse.
Results:
Of 43 participants exhibiting initial response to LIUD, 41 had follow-up data. Sixteen (39%) experienced relapse. Clinical factors associated with shorter response duration included younger age, initial diagnosis of G1EEC, lack of response at 6 months, premenopausal status, and Hispanic ethnicity (P < 0.05), but only 6-month response status remained a significant predictor in a multivariate model (P = 0.023). LIUD increased abundance of NK cells (ΔMCP-counter score = 46.13, FDR = 0.004) and cytotoxic lymphocytes (ΔMCP-counter score = 277.67, FDR = 0.004), as well as lymphocyte cytotoxicity markers PRF1 (log2FC = 1.62, FDR = 0.025) and GZMA (log2FC = 2.47, FDR = 0.008). NK cells were reduced at relapse (ΔMCP-counter score = −55.96, FDR = 0.02). Immune-related pathways (IFNα response and TGFβ signaling) were enriched at relapse (FDR < 0.05). IDO1 expression, reflecting immune exhaustion, was upregulated at relapse (FDR < 0.05).
Conclusions:
Upfront resistance and relapse after initial response to LIUD for AH/G1EEC impacts nearly half of patients, remaining a major hurdle for nonsurgical treatment of AH/G1EEC. Molecular studies evaluating longitudinal biopsies from a small cohort implicate immune mechanisms at relapse, including reversal of progestin-related immunomodulation and increased immune exhaustion.

See related commentary by Johannet and Friedman, p. 5001
Increased Survival in Contemporary Parkinson’s Disease: A 47-Year Autopsy Study
Authors: Noyes Eric , Rajput Ali H. , Kim Minyoung , Rajput Alex
Published: November 2024

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The main clinical features are bradykinesia, rigidity, and resting tremor. Other neurodegenerative disorders such as progressive supranuclear palsy and multiple system atrophy share some of these clinical manifestations. All those disorders are collectively known as parkinsonism or Parkinson syndrome (PS). Definite diagnosis of PD requires brain autopsy. There is no known cure for PD. Since its discovery in the 1960s, levodopa (LD) has remained the best and most widely used medication in PD. The impact of that is important to understanding the neuroepidemiology of PD. The incidence of PD rises with advancing age. In the last six decades, life expectancy in the general population has increased resulting in a larger pool of at-risk persons. Onset age of PD is the most reliable indicator of PD survival as older onset cases have shorter survival. We report on survival in autopsy-confirmed PD cases with onset age <70 years treated with LD and compare that with similar onset-age cases of PD before the discovery of LD. Material and Methods: The Saskatchewan Movement Disorders Program (SMDP) has operated uninterrupted since 1968. Long follow-up and autopsy studies are a special interest of the SMDP. All PS cases followed by the SMPD during 47 years (1968–2015) that came to autopsy were considered. Those with autopsy-confirmed PD and onset <70 years were included and were compared with pre-LD cases of similar age of onset. Results: Overall, 392 PS cases were seen in our clinic between 1968 and 2015 and had brain pathology studies. A total of 314 (80%) of those had PD. Overall, 128 (41%) of the PD cases had onset <70 years and were included in this study. Their median survival was 18 years. Conclusion: Prior to widespread use of LD, nearly all PD cases had onset <70 years and mean survival was 9.4 years. Longer survival in our study is attributed primarily to modern treatment. Increased survival has resulted in a larger number of older, chronically treated, higher comorbidity, and complicated PD patients. These changes present new challenges. It requires a larger and increasingly diverse workforce for patient care and research.
I Feel I Remember: The Phenomenology of Autobiographical Recall in Individuals with Alcohol Use Disorder
Authors: De Groote Clara , Tison Philippe , Bertin Stéphanie , Cottencin Olivier , Nandrino Jean-Louis
Published: November 2024

Introduction: Beyond the memory deficits classically observed in individuals with alcohol use disorder (IwAUD), research has recently focused on the study of autobiographical memory (AM) processes in IwAUD by analysing the content of AM narratives, and the implications for self-conception have been discussed. However, little is known about how IwAUD subjectively experience autobiographical recall. Methods: Thirty-seven IwAUD and 37 control participants were invited to perform an AM task that involved recalling memories for 4 life periods (2 important memories per period). Then, they assessed their subjective experience during AM recall using 6 phenomenological scales evaluating emotional valence, emotional intensity, sensory details, distancing, sharing, and vividness. Anxiety and depression symptoms, interoceptive sensibility, and difficulties in emotion regulation were also measured. Results: The IwAUD experienced greater distancing during AM recall, except during childhood AM recall, indicating that IwAUD are more prone to feeling that the person they are today is different from the person in their retrieved AMs. Very few intergroup differences were observed for AMs from childhood, adolescence-young adulthood, and adulthood, and a greater number of differences were observed for AMs from the last year: the IwAUD experienced AMs with a more negative valence, greater emotional intensity, fewer sensory details, greater distancing, and less sharing. A positive correlation was observed between distancing and interoceptive sensibility in the IwAUD group. Conclusion: Although these results suggest good preservation of autonoetic consciousness in IwAUD, except for more recent AMs, it is insufficient for IwAUD to experience a sense of self-continuity. This difficulty in maintaining a continuous sense of self may constitute a risk for AUD relapse.
Efficacy and safety of transdermal medical cannabis (THC:CBD: CBN formula) to treat painful diabetic peripheral neuropathy
of the lower extremities
Authors: Seevathee Khachornsak , Kessomboon Pattapong , Manimmanakorn Nuttaset , Luangphimai Suyan , Thaneerat Tewan , Wanaratna Kulthanit , Plengphanich Sirichada , Thaenkham Thanamet , Sena Wijitra
Published: November 2024

Introduction: Diabetic peripheral neuropathy (DPN) represents a prevalent neurological complication affecting millions of patients globally. This clinical investigation evaluated the therapeutic efficacy and safety profile of a novel transdermal medical cannabis formulation (THC:CBD:CBN) in treating painful DPN of the lower extremities.
Methods: This phase III, double-blind, placebo-controlled, randomized clinical trial was conducted at Don Chan Hospital, Thailand, enrolling 100 participants over a 12-week intervention period. Using a computer-generated randomization sequence, participants were allocated to receive either the standardized cannabis formulation or a matched placebo. The primary outcome measure comprised pain intensity assessment using the validated Thai version of the Neuropathic Pain Symptom Inventory (NPSI-T). Secondary outcomes encompassed treatment-emergent adverse events and dermatological manifestations. Statistical analyses were performed using SPSS Version 28.0, incorporating Generalized Estimating Equation (GEE) modeling and Analysis of Covariance (ANCOVA). The study protocol received approval from the Institutional Review Board of Khon Kaen University and the Kalasin Provincial Public Health Office Ethics Committee, with trial registration in the Thai Clinical Trials Registry.
Results: The intervention group demonstrated statistically significant reductions in NPSI-T scores across all measured dimensions (p<0.001). Mean total NPSI-T scores decreased markedly from 25.60 to 5.57 in the treatment cohort, contrasting with minimal reduction from 25.24 to 22.85 in the placebo group. GEE analysis revealed significant pain amelioration at weeks 4, 8, and 12 (p<0.001). The cannabis formulation exhibited an excellent safety profile, with only 10% of participants reporting mild adverse events, comparable to placebo group outcomes.
Conclusion: This novel transdermal medical cannabis formulation (THC:CBD:CBN) demonstrated significant therapeutic efficacy in ameliorating painful DPN symptoms while maintaining a favorable safety profile. These findings provide robust clinical evidence supporting its potential as an innovative therapeutic option for managing painful diabetic peripheral neuropathy.
Clinical evaluation of periodontium tissues in the patients with low bone mineral density
Authors: Luchynskyi V. M. , Balaban T. I.
Published: November 2024

Summary. Diagnostics and treatment of periodontal diseases remain a topical problem of modern dentistry, the issue of their relationship with the changes in dento-alveolar complex and bone system is requiring thorough study.
The aim of the study – to study the condition of periodontium tissues in the patients with low bone mineral density.
Materials and Methods. 242 patients (116 men and 126 women), aged 18–60 years, have been examined. The females, in their turn, have been divided into 2 groups: Group 1 – 61 women of reproductive age, aged 18–49 years; Group 2 – 65 women, aged 50–60 years, with three and more postmenopausal years.
Results and Discussion. Uniform prevalence and nosological structure of periodontium tissue diseases have been found both in males and females, the frequency of periodontium disease detection being 85.34 percent for men and 88.88 percent – for women, р>0.05. However, the intensity of the course of dystrophic and inflammatory lesions of periodontium tissues was much more pronounced in females as compared with males that was confirmed by index assessment of periodontal indices.
Conclusions. Thus, high prevalence of periodontium tissue diseases (87.19±2.14) percent has been found in the patients with low bone mineral density, the intensity of disease course being much more pronounced in females in contrast to males.
Клініко-патогенетичні аспекти порушень стану органів порожнини рота в пацієнтів із постковідним синдромом
Authors: Гевкалюк Н. О. , Пальчевський Т. В.
Published: November 2024

Резюме. В основі патогенезу запальних захворювань пародонта лежить відповідна імунологічно зумовлена запальна реакція в тканинах пародонта під впливом специфічної мікрофлори. Суттєво впливає на стан органів порожнини рота, зокрема, на мікробіом, новий тяжкий гострий респіраторний синдром коронавірус-2 (SARS-CoV-2).
Мета дослідження – вивчити зв’язок між пародонтитом і постковідним синдромом через їхній цитокіновий зв’язок, щоби сформувати основу для рекомендацій пацієнтам із пародонтитом, які мають підвищений ризик прояву несприятливих наслідків під час COVID-19.
Матеріали і методи. Проведено стоматологічне обстеження 63 пацієнтів віком 25–45 років, у анамнезі яких COVID-19, із числа яких у 47 пацієнтів виявлено ураження тканин пародонта (основна група). Оцінку стану тканин пародонта проводили клінічно, за комбінованим пародонтальним індексом (РІ), рентгенологічним дослідженням. Визначення вмісту в ротовій рідині прозапальних (IL-1β, IL-6, TNF-α) та протизапальних цитокінів (IL-4, IL-10) проводили методом твердофазового імуноферментного аналізу.
Результати досліджень та їх обговорення. Визначення пародонтального статусу в хворих основної групи показало, що легкий ступінь гінгівіту було діагностовано у (19,15±2,12) % випадків, середній ступінь – у (25,53±3,15) %, тяжкий ступінь – в (31,91±6,26) %, пародонтит – у (23,41±4,26) % випадків. У пацієнтів віком 25–35 років частота виявлення початкових форм запально-деструктивних процесів становила (23,08±4,12) %, генералізований пародонтит  ІІ ст. – в (12,50±2,11) %. У пацієнтів віком 36–45 років ГП І ст. діагностовано в (11,53±1,21) %, ІІ ст. – у (41,17±11,23) %, ІІІ ст. – в (2,13±0,12) %. Пародонтальний індекс у хворих на ГП І ст. віком 25–35 років становив (0,45±0,05), в 36–45-річних – (0,78±0,07) бала. Rtg-індекс рецесії ясен в 25–35-річних складав 1,89±0,21 у віковій групі 36–45 років був у 1,5 раза вищим. Визначення вмісту IL-1β, IL-6, TNF-α у ротовій рідині хворих показало підвищення їх рівня в 2,46, 1,83, 1,45 раза відповідно, що корелювало з тяжкістю захворювання. Вміст протизапальних цитокінів IL-4 та IL-10 у ротовій рідині перевищував значення аналогічного показника в осіб групи контролю у 4,37 та 2,21 раза відповідно, що може свідчити про «цитокіновий шторм».
Висновки. Одним із патогенетичних механізмів, що виникає при захворюваннях тканин пародонта у постковідний період, є збільшення утворення про- та протизапальних цитокінів, яке забезпечує стабільно високий їх рівень. Спільний механізм патогенезу для стану пародонта та постковідного синдрому – «цитокіновий шторм» – має важливе значення для пошуку сучасних, своєчасних і коректних методів діагностики, раціонального підходу до лікування, узгоджених зі стандартами доказової медицини.
Фагоцитарна активність при експериментальному пародонтиті та за умови використання різних типів базисів знімних протезів
Authors: Полюхович Ю. І. , Демкович А. Є.
Published: November 2024

Резюме. Зміни у фагоцитарній активності лейкоцитів при бактеріально-імунному пародонтиті можуть бути важливим показником прогресування захворювання і впливу ортопедичних конструкцій на імунну реакцію організму при використанні протезних базисів.
Мета дослідження – з’ясувати патогенетичну роль неспецифічної ланки реактивності організму при експериментальному бактеріально-імунному пародонтиті та за умови використання різних типів знімних ортопедичних протезних конструкцій.
Матеріали і методи. Експерименти було проведено на білих щурах. Зубні протези виготовляли за стандартними методами: акрилові базиси шляхом термічної полімеризації з поліметакрилатного матеріалу, а нейлонові – з термопластичного матеріалу методом пресування під тиском. Експериментальний бактеріально-імунний пародонтит у дослідних тварин індуковано шляхом ін’єкційного введення суміші мікроорганізмів, суспендованих у яєчному білку  в тканини пародонта. Кров для дослідження отримували з механічно ушкоджених судин у ділянці запалення. Мазки готували і фарбували за методом Ціля – Нільсена. Результати виражали у вигляді фагоцитарного числа та фагоцитарного індексу.
Результати досліджень та їх обговорення. На 30-ту добу запального процесу в пародонтальному комплексі фагоцитарна активність зросла. Під час дослідження фагоцитарного індексу з використанням акрилових протезних базисів було виявлено його підвищення, порівняно з контрольними тваринами, цей індекс також був більшим, порівняно з групою щурів, які мали пародонтит без протезування. При пародонтиті з нейлоновими конструкціями фагоцитарний індекс гранулоцитів перевищував показник у контрольній групі. Зазначений індекс також був вищим, ніж показники без протезування та з акриловими протезними базисами. Фагоцитарне число за умов використання акрилових протезів збільшилось, порівняно з показниками контролю і групи без протезування, й отримані результати також були вищими. При застосуванні ней­лонової пластмаси даний показник значно перевищував рівень показника у тварин контрольної групи та виявився вищим від показників, що були у щурів без протезування. Порівняно з даними, отриманими в групі щурів з іншим типом базисної пластмаси – акрилом, фагоцитарне число було підвищене.
Висновки. Під час розвитку модельованого запального процесу в пародонтальному комплексі відзначалося підвищення фагоцитарної активності гранулоцитів у крові. Використання протезних базисів сприяло збільшенню значень фагоцитарного числа та фагоцитарного індексу. В тварин з акриловими базисами було виявлено підвищення рівня фагоцитарного числа та фагоцитарного індексу порівняно з групою тварин із запаленням і нейлоновими протезами.
Repercussões do isolamento social decorrente da pandemia da COVID-19 sobre sinais e sintomas de idosos com doença de Parkinson: revisão integrativa
Authors: Agranemam Juliana Paulino Dantas da Silva , Bernardo Figueirêdo Bárbara , Santos Jaqueline Severo dos , Asano Nadja Maria Jorge , Lins Carla Cabral dos Santos Accioly , Coriolano Maria das Graças Wanderley de Sales
Published: November 2024

Objective: To review the literature on the consequences of social isolation resulting from the COVID-19 pandemic on motor and non-motor signs and symptoms of elderly people with Parkinson's disease (PD). Method: This is an integrative review with a search in the following databases: PUBMED, LILACS and SCOPUS with filter for publications (November 2019), being proportional to the beginning of the COVID-19 outbreak (year 2020). Studies available in Portuguese, English or Spanish were included, with the elderly population (≥60 years) with PD, which assessed social isolation resulting from the pandemic as exposure and motor and/or non-motor symptoms of PD as an outcome. Studies that did not answer the guiding question and that did not comply with the proposed criteria were excluded. To analyze the methodological quality and the level of evidenced articles, the Critical Appraisal Skill Program and Agency for Health care and Research and Quality instruments were applied. To summarize the motor and non-motor signs and symptoms that worsened during social isolation, a coding criterion inspired by previous studies was used. Results: The final sample resulted in 8 articles. Elderly PD patients faced worsening motor symptoms, especially tremor and rigidity, and non-motor symptoms such as anxiety, depression, and fatigue. Conclusion: Social isolation resulting from the COVID-19 pandemic may have worsened the motor and non-motor symptoms of elderly people with Parkinson's disease. Therefore, it is important to implement multidisciplinary interventions, with a different perspective and care from the rehabilitation team in order to prevent biopsychosocial problems.
Avaliação biopsicossocial de pacientes com dor lombar de um hospital público no Brasil: estudo transversal observacional
Authors: Noal Barbara , Fukusawa Leandro , Cazarini Junior Claudio , Alves Vera Lucia dos Santos , Freitas Diego Galace de
Published: November 2024

Objective: This study aimed to characterize within the biopsychosocial understanding, patients with low back pain who sought for the physiotherapy service of a public hospital. Methods: Cross-sectional study carried out to assess biopsychosocial aspects related to pain in a public service in an underdeveloped country. To characterize patients with low back pain, considering the biopsychosocial aspect, data were collected regarding socioeconomic condition and lifestyle habits, pain intensity, functionality, considering psychological aspects, kinesiophobia, pain catastrophizing, central sensitization, depression and anxiety, were assessed with specific scales and questionnaires. Results: The study included 300 patients with low back pain, 70% of the sample was composed of women, with a mean age of 54 years and with socioeconomic vulnerability. The sample was marked by the high prevalence of previous treatments and imaging exams, showed an average level of disability and scores on psychological scales that suggest the presence of limiting beliefs and behaviors regarding pain and movement, in addition to 47% present a high risk for persistent disability and poor prognosis. Conclusion: The main descriptive findings of this study were a sample with chronic low back pain, mostly represented by an unemployed population, with low income, low education level, with a high average time of exposure to symptoms, and an average level of disability. With regard to psychosocial factors, a large part of the sample had a high risk of poor prognosis and persistent disability, in addition to scores that suggest the presence of catastrophic thoughts, anxiety, fear of movement, and central sensitization.
Prevalência de quedas em pessoas idosas e associação com fatores clínicos funcionais
Authors: Michalski Juliana , Grden Cloris Regina Blanski , Krum Everson Augusto , Bobato Geiza Rafaela , Bordin Danielle
Published: November 2024

Objective: To analyze the prevalence of two or more falls in the elderly in the last year and its association with functional clinical factors. Method: Cross-sectional and quantitative study, carried out with 670 hospitalized elderly people, in Paraná (2020-2021). Sociodemographic data were collected and the Clinical-Functional Vulnerability Index (IVCF-20) instrument was applied, assessing certain health factors. The dependent variable of the study was the occurrence of two or more falls in the last year. Data were analyzed using the chi-square test and logistic regression. Results: There was a predominance of males, aged between 60 and 74 years, married or in a stable relationship and with 1 to 4 years of study. The prevalence of two or more falls in the last year was 29.4%. Associated health factors were hearing impairment (OR= 1.77, 95%CI= 1.04-3.00, p= 0.033), negative self-perception of health (OR= 1.58, 95%CI= 1.09-2.30, p= 0.015), sphincter incontinence (OR= 1.62, 95%CI= 1.10-2.38, p= 0.014) and pre-frailty (OR= 2.72, 95%CI= 1.37-5.42) and frailty (OR= 5.36, 95%CI= 2.73-10.5, p<0.001). Conclusion: The prevalence of falls was high and was associated with hearing impairment, negative self-perception of health, sphincter incontinence and frailty.
Comportamento funcional de indivíduos após acidente vascular cerebral crônico: um estudo longitudinal
Authors: Dario Daniella Moura , Lelis Íris Marina Duarte Silva , Silva Silvia Lanziotti Azevedo da , Aguiar Larissa Tavares , Polese Janaine Cunha
Published: November 2024

Objetivo: Identificar o comportamento funcional de indivíduos após AVC crônico dezoito meses de evolução. Método: Estudo longitudinal prospectivo com coletas de dados realizadas entre fevereiro de 2019 e agosto de 2020. Foram coletados dados de indivíduos que tiveram AVC isquêmico ou hemorrágico há mais de 6 meses em indivíduos maiores de 18 anos. Foi realizada uma avaliação para coleta de dados sociodemográficos, coletadas informações sobre uso de órtese, prática de atividade física, realização de tratamento fisioterapêutico, histórico de tabagismo, frequência, ocorrências de quedas, entre outros. Além disso, foram realizados Teste de Caminhada de 10 metros (TC10m), questionário de Perfil de Atividade Humana (PAH), avaliação da cognição com Mini Exame do Estado Mental (Mini-Mental), escala internacional de auto eficácia de quedas (FESi) e avaliação da capacidade funcional pelo Duke Activity Status Index (DASI). Foi realizado um acompanhamento no período de 18 meses.  Resultados: O estudo obteve 44 indivíduos, entre os quais 35 tiveram AVC isquêmico, com uma média de idade de 65 anos e 60 meses após o AVC. Os indivíduos não apresentaram alterações no seu nível funcional, mantiveram a marcha independente com média de velocidade de marcha habitual de 0,75m/s, o uso de órtese, o alcance de objetos, a alimentação independente e o uso de banheiro independente. Conclusão: Após 18 meses de acompanhamento, os indivíduos mantiveram o seu comportamento funcional na maioria dos casos, podendo dizer-se que atingiram um patamar no seu estado de saúde.
Modelo preditivo do número de passos semanais, mediante a fragilidade física de centenários: Projeto SC100
Authors: Franco Pedro Silvelo , Fank Felipe , Capanema Bruna da Silva Vieira , Streit Inês Amanda , Bento Paulo , Mazo Giovana Zarpellon
Published: November 2024

Objective: To propose a predictive model of the number of weekly steps, according to the criteria of the frailty phenotype of centenarians, the sociodemographic factors, health conditions and life habits. Method: This is a cross-sectional research that is part of the "Projeto SC100: Estudo Multidimensional dos Centenários de Santa Catarina". The frailty phenotype criteria were: unintentional body mass loss, fatigue, muscle weakness, reduced walking speed, and low level of physical activity. The number of steps/day in a normal week was measured using a pedometer during 7 days of a normal week. Data were collected by previously trained researchers in the homes of the older adults. Binary logistic regression was employed to build the predictive models. Results: We evaluated 54 centenarians with a mean age of 101.8±2.8 years. Among the main results, centenarians who have fewer steps per week are 4.61 (95% CI: 1.34-15.94) times more likely to have the criterion low walking speed, this result was adjusted by socio-demographic variables. Also, centenarians who have fewer steps per week have 8.29 (95%CI: 2.05-33.37) times more chance of presenting the criterion low walking speed and 3.35 (95%CI: 1.02-11.38) times more chance of presenting the criterion fatigue, these results were adjusted by lifestyle variables. Conclusion: Centenarians with fewer steps per week present any of the frailty phenotype criteria (loss of unintentional body mass, fatigue, muscle weakness and reduced gait speed), regardless of socio-demographic variables (gender, education, marital status and income) and lifestyle habits (smoking history, alcoholism and sedentary behavior).
Avaliação do equilíbrio postural através do Teste de Integração Sensorial Modificado em uma população de não-caidores
Authors: Gois Thiago Michell Santos , Neves Eduardo Luis de Aquino
Published: November 2024

O equilíbrio postural estático depende da integração das aferências sensoriais de diversos sistemas. A perda desse controle postural aumenta o risco de quedas. Objetivo: Avaliar o equilíbrio postural através da medida da oscilação em graus durante o Teste Clínico de Integração Sensorial e Equilíbrio modificado (mCTSIB) em indivíduos não-caidores. Métodos: Estudo observacional transversal. Cento e sete indivíduos foram submetidos ao mCTSIB em três tipos de superfície com a mensuração da oscilação por meio de um smartphone fixo ao tronco. O desempenho no teste foi medido pela oscilação média e máxima do tronco, em graus. Análises de correlação, regressão, ANOVA e curvas ROC foram realizadas, dividindo o grupo em adultos jovens e adultos mais velhos. Resultados: A oscilação foi afetada pela superfície de apoio e pela privação da visão (p < 0,0001). O desempenho no teste é pior em adultos mais velhos e o risco de quedas cresce em 6% a cada aumento de 1 ano na idade (IC 95%: 1,02-1,10). As variáveis de média de oscilação total no teste e de média de oscilação com os olhos abertos apresentaram valores de corte com boa sensibilidade e especificidade para predizer o risco de quedas. Conclusão: A aplicação do mCTSIB com avaliação da oscilação medida em graus através de uso de dispositivo móvel forneceu uma avaliação objetiva e quantitativa do equilíbrio postural que pode ser utilizada em âmbito ambulatorial como ferramenta de baixo custo, fácil aplicação e alta acessibilidade a fim de discriminar o risco de quedas.