bluuebunny/crossref_metadata_2025 huggingface dataset:
Spurious Presentation of Pulmonary Kaposi Sarcoma as Unresolved Pneumonia Led to Fatal Outcome
Authors: Mann Baldeep Kaur , D’Assumpcao Carlos , Okumoto Lawrence , Aboaid Shatha , Abooed Ayham , Cobos Everardo , Heidari Arash
Published: November 2023

Acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma (KS) is an angioproliferative neoplasia caused by infection with human herpesvirus 8 (HHV-8). It typically presents with mucocutaneous involvement, but it can be disseminated. Initial presentation with primarily pulmonary KS is rare. We present a case of a 32-year-old male with untreated human immunodeficiency virus (HIV) diagnosed 1 year before presentation who developed progressively worsening cough and shortness of breath for 6 months. He was hospitalized twice and treated for unresolved pneumonia in an outside hospital. The patient concomitantly developed purplish nodules on his face, then the upper trunk, back, chest, and thighs bilaterally that gradually increased in size and number. Histopathology findings from skin lesions were consistent for KS. Bronchoscopy found multiple erythematous plaques throughout the tracheobronchial tree with telangiectasias and inflammation suggestive of pulmonary KS. His imaging findings and positive serum HHV-8 polymerase chain reaction (PCR) were consistent with disseminated KS. He started antiretroviral therapy (ART) to treat his HIV infection, followed by liposomal doxorubicin chemotherapy. But both ART and chemotherapy were interrupted due to adherence and insurance issues. The patient was readmitted with acute respiratory failure requiring mechanical ventilation with multiple vasopressors that led to the patient’s demise. The late recognition of KS diagnosis and delayed treatment can lead to worse outcomes.
Effective Separation of Raman Signals from Fluorescence Interference in Undyed and Dyed Textiles Using Shifted Excitation Raman Difference Spectroscopy (SERDS)
Authors: Sowoidnich Kay , Rudisch Katharina , Maiwald Martin , Sumpf Bernd , Pufahl Karsten
Published: November 2023

Textiles are an integral part of our everyday lives, e.g., in the form of clothing and furniture. Consequently, their analysis is of great interest in a wide range of application areas including quality control, textile recycling, forensics, and cultural heritage studies. Optical methods offer a large potential for rapid and nondestructive textile inspection. Raman spectroscopy is a particularly promising candidate for this task as it delivers a fingerprint of the sample on the molecular level, thus giving insights into the textile material composition. Currently, a major challenge preventing the widespread use of Raman spectroscopy for textile analysis is the strong fluorescence background originating from additives, e.g., dyes or the fiber material itself. To address this main limitation, this study applies shifted excitation Raman difference spectroscopy (SERDS) for the effective separation of Raman signals from interfering backgrounds. Using a customized Raman setup based on a dual-wavelength diode laser emitting at 785.2 and 784.6 nm, we present investigations for textile analysis and identification on a set of 22 dyed and undyed pure textiles and binary textile mixtures made of cotton, viscose, wool, polyester, and elastane. SERDS in combination with multivariate analysis is demonstrated as a powerful tool for a distinction between different fiber types and fibers of one material colored with various dyes. These results highlight the large potential of SERDS for textile material identification in selected application areas.
Regulation of lymphoid-myeloid lineage bias through regnase-1/3-mediated control of Nfkbiz
Authors: Uehata Takuya , Yamada Shinnosuke , Ori Daisuke , Vandenbon Alexis , Giladi Amir , Jelinski Adam , Murakawa Yasuhiro , Watanabe Hitomi , Takeuchi Kazuhiro , Toratani Kazunori , Mino Takashi , Kiryu Hisanori , Standley Daron M. , Tsujimura Tohru , Ikawa Tomokatsu , Kondoh Gen , Landthaler Markus , Kawamoto Hiroshi , Rodewald Hans-Reimer , Amit Ido , Yamamoto Ryo , Miyazaki Masaki , Takeuchi Osamu
Published: November 2023

Regulation of lineage biases in hematopoietic stem and progenitor cells (HSPCs) is pivotal for balanced hematopoietic output. However, little is known about the mechanism behind lineage choice in HSPCs. Here, we show that messenger RNA (mRNA) decay factors regnase-1 (Reg1; Zc3h12a) and regnase-3 (Reg3; Zc3h12c) are essential for determining lymphoid fate and restricting myeloid differentiation in HSPCs. Loss of Reg1 and Reg3 resulted in severe impairment of lymphopoiesis and a mild increase in myelopoiesis in the bone marrow. Single-cell RNA sequencing analysis revealed that Reg1 and Reg3 regulate lineage directions in HSPCs via the control of a set of myeloid-related genes. Reg1- and Reg3-mediated control of mRNA encoding Nfkbiz, a transcriptional and epigenetic regulator, was essential for balancing lymphoid/myeloid lineage output in HSPCs in vivo. Furthermore, single-cell assay for transposase-accessible chromatin sequencing analysis revealed that Reg1 and Reg3 control the epigenetic landscape on myeloid-related gene loci in early stage HSPCs via Nfkbiz. Consistently, an antisense oligonucleotide designed to inhibit Reg1- and Reg3-mediated Nfkbiz mRNA degradation primed hematopoietic stem cells toward myeloid lineages by enhancing Nfkbiz expression. Collectively, the collaboration between posttranscriptional control and chromatin remodeling by the Reg1/Reg3-Nfkbiz axis governs HSPC lineage biases, ultimately dictating the fate of lymphoid vs myeloid differentiation.
Diallel analysis of cowpea (Vigna unguiculata (L.) Walp.) genotypes under water deficit stress
Authors: Ezin Vincent , Tossou Thibaut A. W. , Chabi Ifagbémi Bienvenue , Ahanchede Adam
Published: November 2023

Combining ability is referred to as the hybridization value of the parental genotypes involved in the crossing to develop hybrids. The best parents are selected through combining ability methods and subsequently used to produce high yielding and resistant hybrids. Thus, the objectives of this study were to (i) understand the nature and action of genes controlling water deficit tolerance, and (ii) identify superior genotypes from the genetic breadth provided by hybridization in cowpea. Twenty-four genotypes were subjected to normal irrigation and water deficit condition to examine combining ability, genotypic and phenotypic correlations for traits directly related to water deficit (proline and chlorophylls), grain yield and yield components. The results showed the presence of the action of additive and non-additive genes under both water regime conditions. However, there was the predominance of the action of additive genes for most of the traits studied under both conditions. The parents KVX61-1, IT06K242-3, IT07K-211–1-8, Kpodjiguèguè, IT99K-573–1-1, Tawa and IT97K-206–1-1 were observed to be good general combiners for proline content, chlorophyll content and traits associated with yield, while KVX61-1 × KVX396-18, IT06K242-3 × KVX396-18, IT07K-211–1-1 × KVX396-18, Kpodjiguèguè x KVX396-18, KVX61 -1 × IT97K-206–1-1, IT06K242-3 × IT97K-206–1-1, IT07K-211–1-1 × IT97K-206–1-1 and Kpodjiguèguè x IT97K-206–1-1 were proven to be the best specific combiners for traits directly related to water deficit tolerance and yield. It should be noted that number of days to pod maturity, pod length, number of pods per plant and weight of hundred seeds were highly heritable traits in this study.
Prevalence of active cytomegalovirus infection at diagnosis of ovarian cancer and during chemotherapy and subsequent changes in cognitive functioning
Authors: Vogel Rachel I. , Stenzel Ashley E. , Lee Heewon , Hunter-Schlichting DeVon , Wesley Erin , Uppendahl Locke D. , Geller Melissa A. , Nelson Heather H.
Published: November 2023

Purpose

One of the most frequently reported effects of cancer and its treatments is cancer-related cognitive impairment (CRCI). Viral infections may affect inflammation and immune function and therefore may influence patient symptoms, including CRCI. The goal of this study was to describe the prevalence of cytomegalovirus (CMV) infections at diagnosis, during, and after chemotherapy in individuals with ovarian cancer and explore CMV infection at diagnosis with cancer-related cognitive impairment (CRCI) following chemotherapy.

Methods

We recruited adults newly diagnosed with ovarian, primary peritoneal or fallopian tube cancer at a single academic cancer center into two prospective studies. In Study 1 (N = 71), participants provided blood samples at diagnosis. In Study 2 (N = 18), participants provided blood samples and completed symptom surveys before, during and after front-line adjuvant chemotherapy. Serum CMV DNA levels were assessed using digital PCR; >100 copies/mL of serum was considered positive for active CMV infection (CMV+). CRCI was measured using the Functional Assessment of Cancer Therapy – Cognitive Function (FACT-Cog) questionnaire. Changes in FACT-Cog scores were compared by CMV status at diagnosis using t-tests at each time point.

Results

At diagnosis, 29.2% were CMV+ (28.2% in Study 1, 33.3% in Study 2). Following three cycles of chemotherapy (Study 2), CMV positivity rose to 60.0% and then back down to 31.3% after chemotherapy. We observed significant differences in CRCI following chemotherapy by CMV status at diagnosis.

Conclusion

Our data suggest that active CMV infection is common among patients undergoing treatment for ovarian cancer and may contribute to symptoms of CRCI.
Does right hemisphere compensate for the left in school-age children with large left middle fossa arachnoid cysts?
Authors: Zheng Wenjian , Guan Xueyi , Lu Zheng , Zhang Xianchang , Zhai Huina , Huang Guodong , Gong Jian
Published: November 2023

Background

To assess the cognitive function changes and brain network neuroplasticity in school-age children having large (diameter > 5 cm) left middle fossa arachnoid cyst (MFACs).

Methods

Eleven patients and 22 normal controls (NC) between 6 and 14 years of age were included. The CNS Vital Signs (CNS VS) were administered for cognitive assessment. The differences of cognitive data and functional connectivity (FC) in resting-state functional magnetic resonance imaging (rs-fMRI) were compared between the patient group and the NC group. The correlations between the altered FC and cognitive data in the patient group were assessed.

Results

Patient group had significantly poorer attention (including Complex Attention, Sustained Attention, Simple Attention, Cognitive Flexibility, and Executive Function) and memory function (Visual Memory and Working Memory) than the NC group (uncorrectedp-value,p-unc < 0.05). Whole-brain local correlation (LCOR) analysis showed an extensively lower LCOR in the patient group (voxel thresholdp-unc < 0.001, cluster-size threshold of false discovery rate adjustedp(p-FDR) < 0.001). Functional connectivity (FC) analysis showed that bilateral frontal and temporal lobes connectivity in the patient group was significantly lower than the NC group (p-FDR < 0.05). Seed-based FC analysis indicated that there was altered FC between the right temporal lobe and the left temporal-parietal/temporal-occipital area (p-FDR < 0.05). In the patient group, most of the altered FC had a negative correlation to the cognitive score, while the FC in the right temporal lobe-left temporal-occipital area positively correlated to Verbal/Visual Memory (r = 0.41–0.60,p-FDR < 0.05). In correlation analysis between clinical data and cognitive score, the only significant result was a low correlation between cyst size and Reaction Time (-0.30–-0.36,P-FDR < 0.05).

Conclusions

School-aged children with large left MFAC showed significantly lower cognitive performance primarily in attention and memory domains. Distinct from neuroplasticity in a unilateral brain lesion, compensation in the healthy hemisphere in MFAC patients was sparse.
Large-scale networks changes in Wilson’s disease associated with neuropsychiatric impairments: a resting-state functional magnetic resonance imaging study
Authors: Wang Anqin , Dong Ting , Wei Taohua , Wu Hongli , Yang Yulong , Ding Yufeng , Li Chuanfu , Yang Wenming
Published: November 2023

Background

In Wilson’s disease (WD) patients, network connections across the brain are disrupted, affecting multidomain function. However, the details of this neuropathophysiological mechanism remain unclear due to the rarity of WD. In this study, we aimed to investigate alterations in brain network connectivity at the whole-brain level (both intra- and inter-network) in WD patients through independent component analysis (ICA) and the relationship between alterations in these brain network functional connections (FCs) and clinical neuropsychiatric features to understand the underlying pathophysiological and central compensatory mechanisms.

Methods

Eighty-five patients with WD and age- and sex-matched 85 healthy control (HC) were recruited for resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We extracted the resting-state networks (RSNs) using the ICA method, analyzed the changes of FC in these networks and the correlation between alterations in FCs and clinical neuropsychiatric features.

Results

Compared with HC, WD showed widespread lower connectivity within RSNs, involving default mode network (DMN), frontoparietal network (FPN), somatomotor network (SMN), dorsal attention network (DAN), especially in patients with abnormal UWDRS scores. Furthermore, the decreased FCs in the left medial prefrontal cortex (L_ MPFC), left anterior cingulate gyrus (L_ACC), precuneus (PCUN)within DMN were negatively correlated with the Unified Wilson’s Disease Rating Scale-neurological characteristic examination (UWDRS-N), and the decreased FCs in the L_MPFC, PCUN within DMN were negatively correlated with the Unified Wilson’s Disease Rating Scale-psychiatric symptoms examination (UWDRS-P). We additionally discovered that the patients with WD exhibited significantly stronger FC between the FPN and DMN, between the DAN and DMN, and between the FPN and DAN compared to HC.

Conclusions

We have provided evidence that WD is a disease with widespread dysfunctional connectivity in resting networks in brain, leading to neurological features and psychiatric symptoms (e.g. higher-order cognitive control and motor control impairments). The alter intra- and inter-network in the brain may be the neural underpinnings for the neuropathological symptoms and the process of injury compensation in WD patients.
Diverse activity of miR-150 in Tumor development: shedding light on the potential mechanisms
Authors: Ameri Ali , Ahmed Hani Moslem , Pecho Renzon Daniel Cosme , Arabnozari Hesamoddin , Sarabadani Hoda , Esbati Romina , Mirabdali Seyedsaber , Yazdani Omid
Published: November 2023

There is a growing interest to understand the role and mechanism of action of microRNAs (miRNAs) in cancer. The miRNAs are defined as short non-coding RNAs (18-22nt) that regulate fundamental cellular processes through mRNA targeting in multicellular organisms. The miR-150 is one of the miRNAs that have a crucial role during tumor cell progression and metastasis. Based on accumulated evidence, miR-150 acts as a double-edged sword in malignant cells, leading to either tumor-suppressive or oncogenic function. An overview of miR-150 function and interactions with regulatory and signaling pathways helps to elucidate these inconsistent effects in metastatic cells. Aberrant levels of miR-150 are detectable in metastatic cells that are closely related to cancer cell migration, invasion, and angiogenesis. The ability of miR-150 in regulating of epithelial-mesenchymal transition (EMT) process, a critical stage in tumor cell migration and metastasis, has been highlighted. Depending on the cancer cells type and gene expression profile, levels of miR-150 and potential target genes in the fundamental cellular process can be different. Interaction between miR-150 and other non-coding RNAs, such as long non-coding RNAs and circular RNAs, can have a profound effect on the behavior of metastatic cells. MiR-150 plays a significant role in cancer metastasis and may be a potential therapeutic target for preventing or treating metastatic cancer.
Clinical and biological relevance of glial fibrillary acidic protein in Alzheimer’s disease
Authors: Yang Zhengshi , Sreenivasan Karthik , Toledano Strom Erin N. , Osse Amanda M. Leisgang , Pasia Lorenzo Gabriel , Cosme Celica Glenn , Mugosa Maya Rae N. , Chevalier Emma Léa , Ritter Aaron , Miller Justin B. , Cordes Dietmar , Cummings Jeffrey L. , Kinney Jefferson W.
Published: November 2023

Introduction

There is a tremendous need for identifying reliable blood-based biomarkers for Alzheimer’s disease (AD) that are tied to the biological ATN (amyloid, tau and neurodegeneration) framework as well as clinical assessment and progression.

Methods

One hundred forty-four elderly participants underwent 18F-AV45 positron emission tomography (PET) scan, structural magnetic resonance imaging (MRI) scan, and blood sample collection. The composite standardized uptake value ratio (SUVR) was derived from 18F-AV45 PET to assess brain amyloid burden, and the hippocampal volume was determined from structural MRI scans. Plasma glial fibrillary acidic protein (GFAP), phosphorylated tau-181 (ptau-181), and neurofilament light (NfL) measured by single molecular array (SIMOA) technology were assessed with respect to ATN framework, genetic risk factor, age, clinical assessment, and future functional decline among the participants.

Results

Among the three plasma markers, GFAP best discriminated participants stratified by clinical diagnosis and brain amyloid status. Age was strongly associated with NfL, followed by GFAP and ptau-181 at much weaker extent. Brain amyloid was strongly associated with plasma GFAP and ptau-181 and to a lesser extent with plasma NfL. Moderate association was observed between plasma markers. Hippocampal volume was weakly associated with all three markers. Elevated GFAP and ptau-181 were associated with worse cognition, and plasma GFAP was the most predictive of future functional decline. Combining GFAP and ptau-181 together was the best model to predict brain amyloid status across all participants (AUC = 0.86) or within cognitively impaired participants (AUC = 0.93); adding NfL as an additional predictor only had a marginal improvement.

Conclusion

Our findings indicate that GFAP is of potential clinical utility in screening amyloid pathology and predicting future cognitive decline. GFAP, NfL, and ptau-181 were moderately associated with each other, with discrepant relevance to age, sex, and AD genetic risk, suggesting their relevant but differential roles for AD assessment. The combination of GFAP with ptau-181 provides an accurate model to predict brain amyloid status, with the superior performance of GFAP over ptau-181 when the prediction is limited to cognitively impaired participants.
Mycosis fungoides with spongiosis: a case report
Authors: Kashabano Jesse Jonathan , Rugengamazi Eulade , Matiku Subira Bhoke , Mruma Rashid Mussa , Lugina Emmanuel L.
Published: November 2023

Background

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). CTCL are an uncommon, heterogeneous group of non-Hodgkin lymphomas (NHLs) of T- and B-cell origin where the skin is the primary organ of involvement. It is characterized by malignant CD4+ T-cells infiltrating the skin and other organs, leading to progressive skin and systemic involvement. Histopathologically, MF is characterized by atypical lymphocytes demonstrating epidermotropism without spongiosis. Spongiosis is the histological hallmark of intercellular epidermal edema, viewed as clear spaces within the epidermis, and is very common in benign inflammatory dermatoses. Very few studies have reported MF in sub-Saharan Africa (SSA). We are reporting a case of MF with a rare presentation of spongiosis treated successfully with a low dose total skin electron beam therapy (TSEBT) followed by maintenance therapy of low dose Methotrexate (MT) at the Ocean Road Cancer Institute (ORCI) in Tanzania. This is the first case of MF to be managed with low-dose TSEBT in Tanzania. The authors wish to create awareness of the disease among physicians and pathologists and expand on the data paucity in SSA.

Case description

We are reporting a case of a 31-year-old male of African origin who self-referred to our oncology center with a 4-year history of skin rashes throughout the body, which was unresponsive to topical steroid treatment. The biopsy was taken, and the patient was diagnosed with MF CD 3 positive with spongiosis. The patient was treated with radiotherapy, whereby he received low dose total skin electron beam therapy (TSEBT) 12 Gy in 3 fractions at a daily dose of 4 Gy, followed by maintenance therapy of low dose Methotrexate and attained an excellent therapeutic response.

Conclusion

Spongiosis is an infrequent presentation of MF. Low-dose TSEBT provides reliable and rapid reduction of disease burden in patients with MF, which could be administered safely multiple times during a patient's disease with an acceptable toxicity profile. Lack of tendency to perform skin biopsies and cost constraints in assessing multiple immunophenotypic markers lead to missing the diagnosis. Diagnosis and treatment of MF in resource-limited countries is challenging.
Evaluating the value of 18F-PSMA-1007 PET/CT in the detection and identification of prostate cancer using histopathology as the standard
Authors: Luo Liang , Zheng Anqi , Chang Ruxi , Li Yunxuan , Gao Jungang , Wang Zhuonan , Duan Xiaoyi
Published: November 2023

Background

Prostate-specific membrane antigen (PSMA) PET/CT is a highly regarded radionuclide imaging modality for prostate cancer (PCa). This study aimed to evaluate the diagnostic performance of 18F-PSMA-1007 PET/CT in detecting intraprostatic lesions of PCa using radical prostatectomy (RP) specimens as a reference standard and to establish an optimal maximum standardized uptake value (SUVmax) cutoff for distinguishing between PCa and non-PCa lesions.

Methods

We retrospectively collected 117 patients who underwent 18F-PSMA-1007 PET/CT before RP. The uptake of the index tumor and contralateral non-PCa lesion was assessed. Histopathology of RP specimens was used as the gold standard. Kappa test was used to evaluate the consistency of preoperative PSMA PET/CT staging and postoperative pathological staging. Finally, an SUVmax cutoff value was identified by receiver operating characteristic (ROC) curve analysis to distinguish PCa lesions from non-PCa lesions. A prospective cohort including 76 patients was used to validate the results.

Results

The detection rate of 18F-PSMA-1007 PET/CT for prostate cancer was 96.6% (113/117). 18F-PSMA-1007 had a sensitivity of 91.2% and a positive predictive value (PPV) of 89.8% for the identification of intraprostatic lesions. The consistency test (Kappa = 0.305) indicated poor agreement between the pathologic T-stage and PSMA PET/CT T-stage. Based on ROC curve analysis, the appropriate SUVmax to diagnose PCa lesions was 8.3 (sensitivity of 71.3% and specificity 96.8%) with an area under the curve (AUC) of 0.93 (P < 0.001). This SUVmax cutoff discriminated PCa lesions from non-PCa lesions with a sensitivity of 74.4%, a specificity of 95.8% in the prospective validation group.

Conclusions

18F-PSMA-1007 PET/CT demonstrated excellent performance in detecting PCa. An optimal SUVmax threshold (8.3) could be utilized to identify lesions of PCa by 18F-PSMA-1007 PET/CT.

Trial registration

ClinicalTrials.gov Identifier: NCT04521894, Registered: August 17, 2020.
Direct hydrogen peroxide MRI fistulography versus indirect (intravenous) MRI fistulography in patients with perianal fistula
Authors: Abdelhalim Ahmed Hossam , Ali Mohamed Abd el Aziz , Farouk Mohamed Amr , Gamal Eldeen Noha Mohamed
Published: November 2023

Background

Perianal fistula is a rather common disease; its symptoms range from mild to severe, impairing anal continence; accurate preoperative evaluation avoids recurrence following surgical procedures.

Aim of work

Our study examined the diagnostic accuracy of magnetic resonance imaging with direct percutaneous instillation of hydrogen peroxide mixed with gadolinium (direct fistulography) in comparison to intravenous gadolinium contrast-enhanced study (indirect fistulography).

Methods

This prospective study was conducted on patients referred to Airforce hospital radiology department and were diagnosed with perianal fistula, Direct and indirect MR fistulography were performed using a 1.5T MRI scanner. The type of fistulae, internal openings, secondary branches, and abscesses were compared to surgical findings.

Results

Our study included 35 male patients. Both direct and indirect methods detected primary tracts with 97.1% sensitivity and accuracy rates of 91.9% and 89.2%, respectively. The direct method was superior in detecting secondary branches and internal openings with accuracy rates of 97.37% and 93.3%, respectively, compared to 86.8% and 86.6% for the indirect method, while the indirect method was superior in detecting abscess collections with 100% accuracy rate compared to 89.2% accuracy rate for the direct method. None of the patients reported fever or bleeding after the procedure.

Conclusions

Both direct and indirect fistulography showed comparable abilities in detecting primary fistulous tracts. However, the direct fistulography was superior in detecting internal openings and secondary tracts particularly in chronic cases, whereas indirect Fistulography was superior in detecting abscess collections. Incorporating both methods into our routine could thus improve the efficacy of surgical procedures.
Prostate-Specific Membrane Antigen–Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of 225Ac-J591
Authors: Tagawa Scott T. , Thomas Charlene , Sartor A. Oliver , Sun Michael , Stangl-Kremser Judith , Bissassar Mahelia , Vallabhajosula Shankar , Castellanos Sandra Huicochea , Nauseef Jones T. , Sternberg Cora N. , Molina Ana , Ballman Karla , Nanus David M. , Osborne Joseph R. , Bander Neil H.
Published: November 2023

PURPOSE

Novel therapies are needed to extend survival in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific membrane antigen (PSMA), a cell surface antigen overexpressed in PC, provides a validated target. This dose-escalation study investigated the safety, efficacy, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) for 225Ac-J591, anti-PSMA monoclonal antibody J591 radiolabeled with the alpha emitter actinium-225.

METHODS

Following investigational new drug-enabling preclinical studies, we enrolled patients with progressive mCRPC that was refractory to or who refused standard treatment options (including androgen receptor pathway inhibitor and had received or been deemed ineligible for taxane chemotherapy). No selection for PSMA was performed. Patients received a single dose of 225Ac-J591 at one of seven dose-escalation levels followed by expansion at the highest dose. Primary end point of dose-escalation cohort was determination of dose-limiting toxicity (DLT) and RP2D.

RESULTS

Radiochemistry and animal studies were favorable. Thirty-two patients received 225Ac-J591 in an accelerated dose-escalation design (22 in dose escalation, 10 in expansion). One patient (1 of 22; 4.5%) experienced DLT in cohort 6 (80 KBq/kg) but none in cohort 7; MTD was not reached, and RP2D was the highest dose level (93.3 KBq/kg). The majority of high-grade adverse events (AEs) were hematologic with an apparent relationship with administered radioactivity. Nonhematologic AEs were generally of low grade. Prostate-specific antigen (PSA) declines and circulating tumor cell (CTC) control were observed: 46.9% had at least 50% PSA decline at any time (34.4% confirmed PSA response), and protocol-defined CTC count response occurred in 13 of 22 (59.1%).

CONCLUSION

To our knowledge, this is the first-in-human phase I dose-escalation trial of a single dose of 225Ac-J591 in 32 patients with pretreated progressive mCRPC demonstrated safety and preliminary efficacy signals. Further investigation is underway.
Digital Health to Patient-Facing Artificial Intelligence: Ethical Implications and Threats to Dignity for Patients With Cancer
Authors: Kelkar Amar H. , Hantel Andrew , Koranteng Erica , Cutler Corey S. , Hammer Marilyn J. , Abel Gregory A.
Published: November 2023

Ethical considerations for patient-facing AI for oncology: dignity, autonomy, safety, equity, inclusivity.
The chromatin source-sink hypothesis: a shared mode of chromatin-mediated regulations
Authors: Murphy Patrick J. , Berger Frédéric
Published: November 2023

We propose that several chromatin-mediated regulatory processes are dominated by source-sink relationships in which factors operate as ‘sources’ to produce or provide a resource and compete with each other to occupy separate ‘sinks’. In this model, large portions of genomic DNA operate as ‘sinks’, which are filled by ‘sources’, such as available histone variants, covalent modifications to histones, the readers of these modifications and non-coding RNAs. Competing occupation for the sinks by different sources leads to distinct states of genomic equilibrium in differentiated cells. During dynamic developmental events, such as sexual reproduction, we propose that dramatic and rapid reconfiguration of source-sink relationships modifies chromatin states. We envision that re-routing of sources could occur by altering the dimensions of the sink, by reconfiguration of existing sink occupation or by varying the size of the source, providing a central mechanism to explain a plethora of epigenetic phenomena, which contribute to phenotypic variegation, zygotic genome activation and nucleolar dominance.
Clinical Considerations in Returning Pediatric and Young Adults With Cancer to Physical Activity
Authors: Dykowski Sara , Simoneau Jillian , Smith Sean R. , Walling Emily , Lewno Adam
Published: November 2023

There is a gap in the literature on the best treatment of clinical sequelae within adolescent and young adult pediatric cancer populations. Children, adolescents, and young adults are at risk for a multitude of immediate and late effects of their disease and treatment that warrant a comprehensive, multidisciplinary team approach to optimize care. Sports medicine providers are well-equipped with their background to join the oncology rehabilitation team in diagnosing and managing cancer-related impairments to help these populations live a healthier and more active lifestyle. In this manuscript, four essential clinical components to consider when returning children, adolescents, and young adults with cancer history to physical activity are discussed: chemotherapy-induced peripheral neuropathy, cardiotoxicity, nutritional deficiencies, and deconditioning.
Transmission Impossible? Prospects for Decarbonizing the US Grid
Authors: Davis Lucas W. , Hausman Catherine , Rose Nancy L.
Published: November 2023

Encouraged by the declining cost of grid-scale renewables, recent analyses conclude that the United States could reach net zero carbon dioxide emissions by 2050 at relatively low cost using currently available technologies. While the cost of renewable generation has declined dramatically, integrating these renewables would require a large expansion in transmission to deliver that power. Already there is growing evidence that the United States has insufficient transmission capacity, and current levels of annual investment are well below what would be required for a renewables-dominated system. We describe a variety of challenges that make it difficult to build new transmission and potential policy responses to mitigate them, as well as possible substitutes for some new transmission capacity.
Why Did the Best Prepared Country in the World Fare So Poorly during COVID?
Authors: Nuzzo Jennifer B. , Ledesma Jorge R.
Published: November 2023

Though all countries struggled to respond to COVID-19, the United States’ poor performance during the pandemic was unexpected. Despite having more pandemic preparedness capacities than other countries, the United States experienced more than one million COVID-19 deaths, which has contributed to historic declines in national life expectancy. Though some have raised questions as to whether preparedness capacities matter, data that appropriately address cross-country differences in age structure and surveillance approaches show that higher levels of national preparedness was associated with reduced mortality during the pandemic. The United States, however, stands out as a clear outlier in COVID-19 mortality comparisons with other highly prepared countries. We subsequently discuss and summarize the specific gaps in US pandemic preparedness that may have hampered COVID-19 responses in the country. Additional data and research are urgently needed to more accurately understand why the US did not make better use of its prepandemic advantages.
Case Report: A very rare case of a Pleural Effusion revealing Multiple Myeloma
Authors: Daboussi Selsabil , Saidane Asma , Mhamdi Samira , Kacem Marwa , Essbaa Samia , Aichaouia Chiraz , Ghedira Hela , Gargouri Faten , Msakni Issam , Moatemri Zied
Published: November 2023

Multiple myeloma is a common malignant bone-based disease. Pleural effusions reported in these patients remain rare. It is commonly due to congestive heart disease, pulmonary embolism, nephrotic syndrome or a second neoplasia. The true myelomatous pleural effusion resulting from a direct tumoral invasion of the pleural are extremely rare. We report here the case of a massive pleural effusion revealing multiple myeloma in a 71-year-old patient. The chest ultrasound showed a massive pleural effusion in the left side with a multinodular thickening of the pleura. The medical thoracoscopy showed a grape-cluster appearance. The diagnosis was made by pleural guided biopsy revealing abnormal plasma cells with an intense positive CD 138 (plasma cell marker) and MUM1 (multiple myeloma oncogene1) staining with a light kappa chain in the protein electrophoresis associated with a myeloma. Unfortunately, our patient died one month after the initial diagnosis. We present also a review of the recent literature in order to highlight the clinical presentations of the myelomatous pleural effusion, the diagnostic tools, the therapeutic strategies as well as the outcomes.
How children learn
Authors: Dubiel Jan
Published: November 2023

In the first of a three-part series, Jan Dubiel sets out 12 key ‘Learning Behaviours’ that should underpin education in the early years
Less admin, more interaction
Authors: Hart Karen
Published: November 2023

How management software is supporting early years providers to work proactively and collaboratively with parents, benefiting settings and families alike. By Karen Hart
Gut microbiome: New perspectives for type 2 diabetes prevention and treatment
Authors: Li Shu-Xiao , Guo Yan
Published: November 2023

Type 2 diabetes mellitus (T2DM), which is distinguished by increased glucose levels in the bloodstream, is a metabolic disease with a rapidly increasing incidence worldwide. Nevertheless, the etiology and characteristics of the mechanism of T2DM remain unclear. Recently, abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM. The gut microbiome, the largest microecosystem, engages in material and energy metabolism in the human body. In this review, we concentrated on the correlation between the gut flora and T2DM. Meanwhile, we summarized the pathogenesis involving the intestinal flora in T2DM, as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM. Through the analysis presented here, we draw attention to further exploration of these research directions.
Does the advantage of transcutaneous oximetry measurements in diabetic foot ulcer apply equally to free flap reconstruction?
Authors: Lee Da Woon , Hwang Yong Seon , Byeon Je Yeon , Kim Jun Hyuk , Choi Hwan Jun
Published: November 2023

Type 2 diabetes mellitus (T2DM), which is distinguished by increased glucose levels in the bloodstream, is a metabolic disease with a rapidly increasing incidence worldwide. Nevertheless, the etiology and characteristics of the mechanism of T2DM remain unclear. Recently, abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM. The gut microbiome, the largest microecosystem, engages in material and energy metabolism in the human body. In this review, we concentrated on the correlation between the gut flora and T2DM. Meanwhile, we summarized the pathogenesis involving the intestinal flora in T2DM, as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM. Through the analysis presented here, we draw attention to further exploration of these research directions.
Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer
Authors: Yang Qing , Li Li-Yuan
Published: November 2023

Type 2 diabetes mellitus (T2DM), which is distinguished by increased glucose levels in the bloodstream, is a metabolic disease with a rapidly increasing incidence worldwide. Nevertheless, the etiology and characteristics of the mechanism of T2DM remain unclear. Recently, abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM. The gut microbiome, the largest microecosystem, engages in material and energy metabolism in the human body. In this review, we concentrated on the correlation between the gut flora and T2DM. Meanwhile, we summarized the pathogenesis involving the intestinal flora in T2DM, as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM. Through the analysis presented here, we draw attention to further exploration of these research directions.
Optical interference phase control method with single photodetector for interference lithography
Authors: Cao Lei , Lu Sen , Yang Kaiming , Zhang Ming , Zhu Yu
Published: November 2023

This study designs an optical phase control method for interference lithography system accompanied with severe disturbance. The system, which is designed based on the exponential reaching law of sliding mode control(SMCE), could adjust the interference phase with single photodetector. The model of system is derived and then the stability is proved through Lyapunov theorem. This paper also analyzes the behavior of the system under different reference voltages of photodetector. Both theoretical analysis and simulation experiment results suggest that this method can non-periodically achieve interference phase control with single photodetector by the switching module. Finally, the experimental device is set up, and the superiority of the SMCE method in transient response time and disturbance-resisting ability is demonstrated compared with the proportional–integral–derivative(PID) method.
Highly-enhanced active beam-wander-correction for free-space quantum communications
Authors: Lim Dohoon , Kim Dongkyu , Park Kyungdeuk , Im Dong-Gil , Sup Ihn Yong
Published: November 2023

In practical applications to free-space quantum communications, the utilization of active beam coupling and stabilization techniques offers notable advantages, particularly when dealing with limited detecting areas or coupling into single-mode fibers(SMFs) to mitigate background noise. In this work, we introduce highly-enhanced active beam-wander-correction technique, specifically tailored to efficiently couple and stabilize beams into SMFs, particularly in scenarios where initial optical alignment with the SMF is misaligned. To achieve this objective, we implement a SMF auto-coupling algorithm and a decoupled stabilization method, effectively and reliably correcting beam wander caused by atmospheric turbulence effects. The performance of the proposed technique is thoroughly validated through quantitative measurements of the temporal variation in coupling efficiency(coincidence counts) of a laser beam(entangled photons). The results show significant improvements in both mean values and standard deviations of the coupling efficiency, even in the presence of 2.6 km atmospheric turbulence effects. When utilizing a laser source, the coupling efficiency demonstrates a remarkable mean value increase of over 50 %, accompanied by a substantial 4.4-fold improvement in the standard deviation. For the entangled photon source, a fine mean value increase of 14 % and an approximate 2-fold improvement in the standard deviation are observed. Furthermore,the proposed technique successfully restores the fidelity of the polarization-entangled state, which has been compromised by atmospheric effects in the free-space channel, to a level close to the fidelity measured directly from the source. Our work will be helpful in designing spatial light-fiber coupling system not only for free-space quantum communications but also for high-speed laser communications.
Real-time low-complexity diversity combining algorithm for free space coherent optical communication systems over atmospheric turbulence channel
Authors: Xu Kejia , Song Jingwei , Li Yan , Chen Junjie , Qiu Jifang , Hong Xiaobin , Guo Hongxiang , Yang Zhisheng , Wu Jian
Published: November 2023

A novel diversity combining scheme, in conjunction with the complex-valued decision-directed least mean square (CV-DD-LMS) algorithm, is evaluated, and a real-time experimental validation is presented. This proposed scheme employs the CV-DD-LMS algorithm to concurrently perform beam combination and carrier phase recovery (CPR), thereby effectively reducing the overall complexity of digital signal processing. Furthermore, in the numerical simulation, under a low signal-to-noise ratio (SNR), a scheme utilizing the CV-DD-LMS algorithm effectively avoids cycle slips (CS) and outperforms schemes employing independent CPR modules. We experimentally validate this novel scheme by implementing it on an FPGA in a real-time 2.5Gb/s QPSK diversity-receiving system with three inputs. The back-to-back sensitivity is assessed using static received optical power, while the dynamic performance is evaluated by employing variable optical attenuators (VOAs) to simulate a power fluctuation at a frequency of 100kHz. The result proves that the implementation of the CV-DD-LMS algorithm yields stable performance while effectively reducing computational complexity.
Traveling itinerary problem in a scheduled multimodal transportation network for a fixed sequence of cities
Authors: Ali Rafaqat , Jiang Hai , Buzna Lubos
Published: November 2023

Developing an efficient and economical journey plan in multimodal transportation networks is of significant and fast-growing importance, but it is still an annoying experience for a traveler. This paper aims to find the journey plan at a combined cross-border and inter-regional level when visiting a sequence of cities while utilizing several transport modes to reduce travel costs and planning time. We study a traveling itinerary problem in a scheduled multimodal transportation network with constraints on both arcs and nodes as a new extension of the shortest path problem. We formulate a 0-1 integer linear programming model for the traveling itinerary problem and develop an exact algorithm that finds a combined cross-border and inter-regional low costs journey plan. We present case studies based on real-world transport data to illustrate the usefulness and computational efficiency of the proposed approaches. We compare the results with the previously proposed approach to demonstrate the benefits of multimodal journeys. Finally, we compare the results with the solution obtained by the general-purpose 0-1 integer linear programming solver to evaluate the computational time.
Exploring fraity and sarcopenia in older adults admitted to acute medical unit, looking at prevalence, trajectory, and outcomes: A protocol testing the feasibility and acceptability of the TYSON study
Authors: Kamwa Vicky , Jackson Thomas , Hassan-Smith Zaki , Sapey Elizabeth
Published: November 2023

Background

Frailty and sarcopenia are common in older people and are associated with adverse outcomes including increased mortality and morbidity. It is unclear whether screening for frailty and sarcopenia would identify specific populations most at risk of poor outcomes during unplanned hospital admissions, which screening tools should be used and what the trajectory of both conditions are over the course of an admission. The TYSON study is an observational cohort study aiming to determine the prevalence, trajectory and outcomes associated with frailty and sarcopenia in different patient cohorts. This protocol tests the feasibility and acceptability of TYSON processes.

Objectives

To determine in acutely admitted medical patients who are older adults: Primary: The feasibility and acceptability of frailty and sarcopenia assessments; Secondary: (1) Differences in community and hospital frailty assessments, as assessed by the medical team, the patient and elderly care physicians, (2) The dynamic changes in frailty and sarcopenia during a hospital admission, and patient outcomes; Exploratory: Inflammatory and metabolic mediators associated with frailty and sarcopenia.

Methods

A single centre, prospective observational study including patients aged ≥ 65 years admitted to an acute medical unit. Frailty assessments include the Rockwood clinical frailty and e-frailty index. Sarcopenia assessments include the Bilateral Anterior Thigh Thickness (BATT) measurement. Each participant will be asked to complete 5 visits, at day 0, day 3, day 7, month 3 and month 6. Blood samples will be collected to explore inflammatory and metabolic markers associated with frailty and sarcopenia. The study and protocol have been ethically approved by the Health Research Authority (REC 20/WA/0263).

Discussion

The study will determine the feasibility and acceptability of frailty and sarcopenia assessments in an acute hospital setting, and inform on the prevalence, trajectory and associated outcomes of frailty and sarcopenia in this group of patients. An inflammatory and metabolic profile will be explored in frailty and sarcopenia.