bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemoradiotherapy (CRT) followed by sequential tislelizumab (TIS) + CAPOX and TIS monotherapy for organ preservation in locally advanced low rectal cancer.
Authors: Tang Wentao , Wei Ye , Wang Guiying , Zhang Rui , Zhou Haiyang , Zhang Zizhen , Xu Jianmin
Published: January 2025

TPS315

Background:
CRT followed by total mesorectal excision (TME) is the standard care for patients with locally advanced low rectal cancer (≤ 5cm from the anal margin). However, TME may lead to permanent colostomy and severely impact quality of life. Organ preservation is, therefore, a critical unmet need for these patients. The proportion of patients achieving clinical complete response (cCR) after CRT is relatively low, with the literature reporting around 20%. Total neoadjuvant therapy (TNT) has been investigated to increase cCR rate. Several clinical trials demonstrated that PD-1 inhibitor combined with TNT could result in significate improvement in pathological complete response rate (pCR rate, 39.8% vs 15.3%, p < 0.001 in UNION study) or complete response rate (pCR+cCR rate, 44.8% vs 26.9%, p = 0.031 in a randomized phase 2 study) compared with TNT alone in rectal cancer patients. The RELIEVE-01 study (NCT06390982) was designed to evaluate the efficacy in organ preservation with CRT followed by sequential TIS + CAPOX and TIS monotherapy in patients with low rectal cancer.
Methods:
This multicenter, single-arm, phase 2 study will enroll 46 pts with histopathologically confirmed rectal adenocarcinoma (≤ 5cm from the anal margin), pMMR/MSI-L/MSS, cT1-3N1M0/T2-3N0M0, and ECOG PS ≤1. Pts will initially receive 6 weeks of CRT (50.4 Gy/28F, capecitabine 825 mg/m
2
, bid, d1-5 each week), followed by 4 cycles of TIS + CAPOX (TIS, 200 mg, IV, d1; capecitabine 1000 mg/m
2
, bid, d1-14; oxaliplatin 130 mg/m
2
, d1) in a 21-day cycle. Then, clinical response will be assessed to determine the subsequent treatment. Patients with cCR will receive TIS + CAPOX (4 cycles) and TIS (up to 9 cycles), and then be managed using the W&W strategy. Patients with non-cCR will undergo TME. Patients with near-cCR will be given local excision, and those achieving pCR will receive the same treatment as cCR patients, and for those with non-pCR after local excision, TME will be performed. The primary endpoint is rate of CR (cCR plus pCR post local resection). Secondary endpoints include organ-preserving rate, event-free survival rate and OS rate at 1, 2 and 3 years, respectively. Recruitment is ongoing.
Clinical trial information: NCT06390982
.
Randomized study to assess colonic microbiome changes in response to energy drink consumption (ROSANNA Trial).
Authors: Jang Tim , Kahramangil Doga , Lee Ji-Hyun , Kim George P. , Terracina Krista P. , Nordenstam Johan , Read Thomas , Thomas Ryan M. , Yang Ye , Tatum Sarah M , Jobin Christian , George Thomas J.
Published: January 2025

TPS325

Background:
Colorectal cancer (CRC), the second leading cause of cancer deaths in the US, is increasingly diagnosed in individuals under 50. This rise in early-onset CRC (eoCRC) led the U.S. Preventative Services Task Force to recommend a reduction in the age to begin colorectal cancer screening in average-risk persons, from 50 to 45. The etiology of eoCRC is multifaceted, with one postulated theory pointing to alterations in the young adult colonic microbiome. Hydrogen sulfide (H
2
S) producing bacteria, like
Bilophila wadsworthia
,
Fusobacterium nucleatum
and
Atopobium parvulum
, are typically minor gut microbiota components but are overrepresented in CRC cases, linked to inflammation, and may promote a pro-carcinogenic environment. These bacteria preferentially use taurine, an essential amino acid, as a primary energy source. Energy drinks represent one of the largest dietary sources (6-16x normal daily intake) of taurine in contemporary diets. Our hypothesis is that high taurine levels in energy drinks could exacerbate CRC risk by promoting preferential growth and metabolic activities of already present H
2
S-producing bacteria, contributing to the rise of eoCRC.
Methods:
This randomized open-label trial is actively enrolling up to 60 young adults (18-40 years) without personal or family history of CRC, other major GI disease/distress, and baseline infrequent energy drink consumption. Group 1 (Arm A; n=30), will consist of subjects consuming at least one of two protocol-specified energy drinks daily for 4 weeks. Group 2 (Arm B; n=30), will consist of usual dietary intake. Enrollments are randomized 1:1 and stratified, by gender, age (18-25 vs. 26-40), and baseline energy drink consumption (rare/none vs. 1-2 per week). Every subject will complete: 1) a daily dietary and fitness log, 2) a weekly wellness log, 3) collection of stool/saliva/skin/urine at 3 sequential time points (baseline, after 2 weeks, after 4 weeks), and 4) blood collection at the same time points. The primary endpoint is the change in H
2
S-metabolizing bacterial communities between baseline and 1 month of energy drink exposure within Arm A and also compared to those in Arm B using microbiome analysis (diversity, taxonomy, sulfur-enriched gene pathways). Several secondary and exploratory assessments include changes related to subject demographic and dietary differences, concordance of microbiome changes with dietary logs and in other biospecimens beyond stool, H
2
S-production measurements, and analyses of subject metabolic and immune function. Trial opened in February 2024 with active enrollment ongoing. Updated data on trial status and any amendment modifications will be presented at the meeting.
Clinical trial information: NCT06137248
.
A phase I trial of intraperitoneal (IP) mesothelin (MSLN)-targeted CAR T-cell therapy in patients with MSLN-positive esophagogastric cancer (EGC) with peritoneal carcinomatosis.
Authors: Choo Joan , Saini Jasmeen , Gonzalez - Aguirre Adrian , Dahi Parastoo , Hieronymi Sophie , Fernstedt Stacy , Tan Kay See , Adusumilli Prasad S. , Ku Geoffrey Yuyat
Published: January 2025

TPS513

Background:
Outcomes for patients with advanced EGC remain poor. The peritoneum is an immune-privileged niche and a common site of metastases occurring in up to 40% of patients with metastatic EGC; this is characterised by poor survival because of resistance to immunotherapy and a lack of measurable disease, which excludes trial participation. MSLN was selected as a target for CAR T cell therapy as it is overexpressed in up to 60% of EGC, is associated with aggressive disease biology and has low levels of expression in normal tissues. In pre-clinical
in vivo
models of peritoneal carcinomatosis, improved efficacy was observed with regional administration of IP CAR T cells, compared with systemic CAR T cells. No significant toxicity was observed at clinically relevant doses of IP administered CAR T-cells. M28z1XXPD1DNR CAR T-cells are a next-generation MSLN-targeted CAR, equipped with a modified CD3z (1XX), and a PD-1 dominant negative receptor (PD1DNR) that provides T-cell intrinsic checkpoint blockade.
Methods:
This is a single-arm phase I study assessing the safety, maximum tolerated dose (MTD) and preliminary efficacy of IP administered M28zXXPD1DNR CAR T cells in patients with MSLN-positive (IHC ≥ 25%) EGC with evidence of peritoneal carcinomatosis (imaging and/or cytology). Patients with concomitant extraperitoneal disease are eligible. Patients must have received at least one prior line of treatment for advanced or metastatic disease and have at least one measurable or evaluable lesion per RECIST 1.1. A minimum of 4 patients and maximum of 18 patients will be treated with 4 escalating doses (with 1 “fallback” dose) of CAR T cells to a maximum of 3 x 10
7
cells/kg administered via peritoneal catheter (Table). Lymphodepletion with fludarabine 30mg/m
2
/day and cyclophosphamide 300mg/m
2
/day is given for 3 days prior to the CAR T cell infusion. Adverse events, response rates (RECIST 1.1), survival outcomes and immuno-monitoring (immune cell phenotyping and serum/peritoneal fluid cytokine analysis) will be assessed. The trial is currently enrolling patients. Clinical trial information: Will be registered before ASCO GI.

Dose-escalation scheme based on the continuous reassessment method.

Dose Level
Dose (cells/kg)

1

1 x 10
6

2 (Starting dose)

3 x 10
6

3

6 x 10
6

4

1 x 10
7

5

3 x 10
7
A phase II study of agenT-797 (invariant natural killer T-cells), botensilimab (Fc-enhanced CTLA-4 inhibitor) and balstilimab (anti-PD-1) in patients with advanced, refractory gastroesophageal adenocarcinoma.
Authors: Cytryn Samuel Louis , Maron Steven Brad , Janjigian Yelena Y.
Published: January 2025

TPS515

Background:
Esophagogastric (EG) cancer, the fifth most common cancer worldwide and second leading cause of cancer-related mortality, results in 1.3 million deaths annually. Despite recent advances in frontline management, nearly all patients with metastatic disease experience progression, highlighting the urgent need for novel therapies. Botensilimab (BOT), an Fc-enhanced, multifunctional anti-CTLA-4 antibody, has shown promise in combination with balstilimab (BAL, anti-PD-1) across multiple treatment-refractory cancers. Additionally, agenT-797, an allogeneic off-the-shelf invariant Natural Killer T (iNKT) cell therapy, enhances immune responses, including in settings refractory to immune checkpoint inhibitors (ICI), without requiring HLA matching or lymphodepletion. In a cohort of 82 previously treated patients, agenT-797 demonstrated a favorable safety profile with no severe Cytokine Release Syndrome, Graft-versus-Host Disease, or immune effector cell-associated neurotoxicity syndrome. Notably, in patients with relapsed/refractory gastric cancer, agenT-797 plus anti-PD-1 showed important clinical activity that warrants further exploration. Given their complementary mechanisms of action in modulating anti-tumor immunity, we aimed to evaluate the safety and efficacy of combining BOT, BAL, and agenT-797 with standard ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) and paclitaxel chemotherapy in patients with advanced EG cancer who have progressed on frontline therapy.
Methods:
This is an investigator-initiated, single-arm phase II trial in adult patients (≥18 years) with esophageal, gastric, or gastro-esophageal junction (GEJ) adenocarcinoma who have received one prior line of therapy, performed at Memorial Sloan Kettering Cancer Center. Eligible patients receive a single infusion of agenT-797 on cycle 1 day 1, BOT 75 mg on day 1 of cycles 1 through 3, BAL 240 mg on days 1 and 15, ramucirumab 8 mg/kg on days 1 and 15, and paclitaxel chemotherapy 80 mg/m
2
on days 1, 8, and 15 of a 28-day cycle. Treatment is continued until disease progression (defined by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), unacceptable toxicity, or withdrawal of consent. The primary endpoint is overall response rate. The secondary endpoints are safety and tolerability, disease control rate, duration of response, progression-free survival, and overall survival. The regimen will be considered worthy of further investigation if at least 15 out of 37 patients achieve an objective response. To date, 12 patients have been enrolled and started on treatment. This trial is registered with ClinicalTrials.gov, NCT06251793.
Clinical trial information: NCT06251793
.
P-01 ADRENAL LESIONS IN A PATIENT WITH ACROMEGALY
Authors: Giannou Alexandra , Skoulikidi Stamatia , Emmanouilidis Panagiotis , Kanouta Fotini , Mitropoulou Marina , Vasileiou Vasiliki
Published: January 2025

A 41 year old woman diagnosed with acromegaly due to a pituitary somatotroph macroadenoma (3.2 x 2.2 x 2.2 cm) and bilateral adrenal lesions, presented after her first transsphenoidal debulking surgery (TSS). She initially seeked medical care due to uncontrolled hypertension and newly diagnosed diabetes mellitus. Αt the time of her first visit she was receiving octreotide.

The patient complained that her symptoms persisted, specifically that her blood pressure remained high, despite therapy with 4 different agents (not including mineralocorticoid receptor antagonist) and her glycemic control was unsatisfactory, despite medication regimen (liraglutide and metformin). She underwent repetitive brain MRI which depicted residual disease (1.6 x 1.5 x 2.2 cm). Her laboratory panel revealed markedly increased levels of both GH and IGF-1 confirming disease persistence (on octreotide).

Subsequently her regimen was changed to pasireotide. However, it also failed to ameliorate her symptoms leading to a second operation. After the second surgery, her glycemic control was normalized and her hypertension was improved, despite slightly elevated IGF-1 levels. At this point pasireotide was discontinued.

Her initial check up had also revealed bilateral adrenal lesions, which were characterized as primary bilateral macronodular adrenocortical hyperplasia (PBMAH), with concomitant high aldosterone and suppressed renin and potassium levels. Plasma metanephrines were measured preoperatively to exclude pheochromocytoma. They were within normal limits. Her ACTH levels remained relatively low at 12.1 pg/ml (<46) with basal cortisol at 12 μgr/dl. Multiple dexamethasone suppression tests (1 mg) were positive for mild autonomous cortisol suppression.

Due to the presence of concomitant high aldosterone and suppressed renin and potassium levels, she was submitted to a saline induced test (SIT) which was positive for primary hyperaldosteronism. Epleronone was started. Under this medication, her blood pressure remains well controlled and potassium levels have normalized.

This is a rare case of a patient with concomitant acromegaly and primary hyperaldosteronism on a base of PBMAH. Adrenal lesions in acromegalic patients have been mentioned mostly as non- functioning adenomas, though increased cortisol and aldosterone secretion has been recently described. The patient's symptoms remain under control to the moment, but as she hasn’t achieved biochemical remission of acromegaly we plan on reinitiating octreotide. We also plan to proceed to genetic screening to assess syndromic presentation and exclude aberrant receptor expression.Figure 1:CT of retroperitoneal regionright adrenal: 1.35 x 2.1 cm/-3HU left adrenal: outer limp 1.6 x 2 cm/-1HU inner limp 2 x 2.5cm/-5HU
O-15 CUTANEOUS SARCOIDOSIS PRESENTING AS ASYMPTOMATIC PTH-INDEPENDENT HYPERCALCEMIA
Authors: Bhakar Bhawna , Khan Arshiya , Saqlain Muhammad
Published: January 2025

Introduction

Sarcoidosis is a rare disease primarily affecting the pulmonary system in approximately 90% of cases. (1) Cutaneous involvement occurs in 20-35% of sarcoidosis patients and can present without systemic manifestations (2). The skin is the second most commonly affected organ after the lungs in sarcoidosis (3).

Clinical Case

We report a unique case of cutaneous sarcoidosis presenting with asymptomatic hypercalcemia. An 81-year-old White British woman with a medical history of type 2 diabetes mellitus, anemia, hypertension, and polymyalgia rheumatica (PMR) was managed for left leg cellulitis. Examination revealed a systolic murmur, clear chest, bilateral erythema, raised temperature, and pitting edema at the infection site. An admission chest x-ray showed a known large hiatus hernia. Routine blood tests revealed adjusted calcium levels of 3.52 mmol/L (2.20-2.60 mmol/L), and PTH levels were low at 0.9 pmol/L (1.6-6.9 pmol/L), indicating PTH-independent hypercalcemia.

Further blood tests showed normal vitamin D (129nmol/L, n>50nmol/L), ACE levels (<5 IU/L), and thyroid funct,on tests (TSH 7.17mU/L, n0.30-4.20mU/L, T4 15.6pmol/L, n11.9-21.6pmol/L, TPO antibody<10IU/mL, n0-34). Myeloma screen (no monoclonal bands, Serum Kappa Free Light Chain:31.03 mg/L,n 3.30 - 19.40; Serum Lambda Free Light Chain:22.57 mg/L,n:5.71 - 26.30) and autoimmune screens (IgG:7.8 g/L,n:6.0 - 16.0; IgA:1.26 g/L,n:0.80 - 4.00; IgM*0.41 g/L,n:0.50 - 2.00) were negative. Elevated 1,25-dihydroxy vitamin D (calcitriol) was noted at 246 pmol/L. Occult malignancy was ruled out via normal CT chest, abdomen, and pelvis, gastroscopy with biopsy, and CT head scans. Initial PET CT results were reported as normal.

Hypercalcemia management included intravenous fluids, zoledronic acid, denosumab, steroids, and cinacalcet. Subsequent detailed PET CT report revealed extensive moderate FDG uptake in the subcutaneous tissue of both arms. Physical examination identified subcutaneous nodules, and histology confirmed a florid dermal non-necrotizing granulomatous reaction, diagnosing extra-pulmonary cutaneous sarcoidosis.

Interestingly, the patient had been on long-term prednisolone (10 mg) for PMR, recently reduced to 4 mg prior to admission. Her calcium levels normalized (2.57 mmol/L) after weaning off prednisolone.

Conclusion

Hypercalcemia in cutaneous sarcoidosis without pulmonary involvement is rare. Long-term follow-up is essential, as patients with cutaneous sarcoidosis may develop systemic involvement. She was referred to pulmonary and dermatology specialists for further evaluation.
P-34 XX MALE SYNDROME DIAGNOSED AT AGE 52
Authors: Vinogradskaya Olga , Bublik Evgeniya , Gabidzashvili Nino , Farmanov Alexander , Zilov Alexey , Ryzhkova Ekaterina
Published: January 2025

Introduction

XX male syndrome (de la Chapelle syndrome) is a rare disorder of sex development linked to a 46,XX karyotype. Depending on the presence of the SRY gene, two variants of this disease are distinguished: SRY-positive and SRY-negative ones. The SRY (sex-determining region Y) gene is involved in the differentiation of Sertoli cells and development of the tests. Typically, de la Chapelle syndrome is diagnosed in childhood or adolescence. We present a case where XX male syndrome was diagnosed at age 52.

Clinical Case

A 52-year-old man came to our clinic complaining of excess weight, decreased libido, and fatigue with little physical activity.

Physical examination discovered full masculinization, microorchidism, gynecomastia, obesity.

At the time of his visit, he was undergoing chemotherapy for β-cell lymphoma. It is known that due to severe pain in the spine, he had been injecting himself with dexamethasone every day for six months, which led to secondary adrenal insufficiency. When he came, we stopped dexamethasone and initiated hydrocortisone. We reduced the dosage until it was completely discontinued over 4 months. The function of the adrenal glands was completely restored, which was shown by laboratory tests.

On the first visit patient said that over the past 9-10 years he had been periodically receiving testosterone therapy due to low testosterone level. The decrease in testosterone was explained by obesity. About 10 years ago, investigation was performed due to infertility. Investigation showed a low testosterone level, a high FSH and LH level, azoospermia, a small testicular volume in the ultrasound were detected. Hypergonadotropic hypogonadism was diagnosed. Karyotyping analysis revealed a chromosomal complement of 46,XX. Molecular genetic testing confirmed the SRY-positive variant of de la Chapelle syndrome. Thus, we understand the reason for patient's low testosterone, and replacement therapy with testosterone was prescribed. And we recommended assisted reproductive technologies using donor sperm.

Conclusion

It is important to remember that in men of any age with hypogonadism and infertility, chromosomal abnormalities must be excluded (and not only in children and adolescents).Figure 1:Karyogram of the patient, 46,XX
P-39 A LATE ONSET CASE OF CHYLOMICRON RETENTION DISEASE
Authors: Akcura Can , Alkan Samet , Güney Sedat Can , Sunbul Busra , Ozdemir Nilufer , Hekimsoy Zeliha
Published: January 2025

Introduction

Chylomicron retention disease (CRD) is an uncommon genetic disorder caused by a mutation in the SAR1B gene, which encodes the Sar1b protein. Sar1b plays a role in transporting chylomicrons from the endoplasmic reticulum to the Golgi apparatus. Often diagnosed in the early stages of life, CRD typically presents with failure to thrive, gastrointestinal symptoms and malabsorption of fat, which leads to secondary clinical conditions such as hepatomegaly, neuromuscular disorders, hypolipidemia and deficiencies of fat soluble vitamins (A, D, E, K).

Clinical Case

A 56-year-old male patient was referred to our endocrinology outpatient clinic with low blood lipid levels. He expressed pain on his hands and feet. He also described vomiting after fat-rich meals since his childhood. He had no history of smoking or alcohol consumption. His father had diabetes mellitus and hypertension, and his uncle had coronary artery disease. His physical examination was normal besides a peripheral sensorial neuropathy. His laboratory findings showed hypolipidemia and hypochromic microcytic anemia, alongside with vitamin B12, vitamin D and iron deficiency (Table 1). An abdominal ultrasonography was performed, the dimensions of both the liver and the spleen was normal, though a grade 1 hepatosteatosis was observed. An electromyelography was performed and the findings were compatible with axonal polyneuropathy. The patient was referred to the department of genetics for evaluation of familial lipid disorders. A genetic analysis was performed, and the analysis revealed a likely pathogenic heterozygous mutation in the NM_016103.4 c.243dupA p.A82fs*35 area of the SAR1B gene. The patient was diagnosed with chylomicron retention disease. He was referred to a dietetician for a low-fat diet. A bone mineral density scan was planned and oral vitamin D treatment was initiated, alongside with oral iron and vitamin B12 treatment. The patient was also referred to departments of neurology, ophtalmology and cardiology for possible systemic involvement. He was also referred to gastroenterology for endoscopic and colonoscopic scanning. Moreover, his close relatives were advised to be evaluated for CRD. Later on, one of his grandchildren was diagnosed with CRD and is currently under treatment in another institution.

Conclusion

Though rarely diagnosed during adulthood, CRD should still be included in the differential diagnosis of patients with hypolipidemia; especially in cases with vitamin deficiencies. Gastrointestinal symptoms often encountered during childhood may be absent or vague in adulthood, but careful systemic assessment and physical examination gives valuable clues in the diagnosis of CRD, alongside with appropriate laboratory and genetic analysis. Once diagnosed, other family members, especially children, of CRD patients should also be evaluated about this rare genetic disease.

Financial disclosures: None

Funding resources: NoneTable 1:Laboratory findings of the patient
P-70 THYMIC HYPERPLASIA AND GRAVES' DISEASE: IS THERE A HIDDEN AUTOIMMUNE DISORDER?
Authors: Slato Anida Divanović , Šakić Belma , Nalbani Spahić Elma , Burekovic Azra
Published: January 2025

Introduction

Thymic hyperplasia is reported in 10-38% of patients with Graves' disease.

Clinical Case

We present a case of a 45-year-old female with Graves' disease and thymic hyperplasia, exhibiting non-specific symptoms.

The patient was diagnosed with Graves' disease at age 42 and treated with thiamazole. While she was taking thiamazol she was felt muscle pain, spasms, and pulsations. Her pituitary and adrenal hormones were within normal limits. Three months after diagnosis, she was hospitalized for recurrent transient ischemic attacks. Myasthenia gravis was suspected, but acetylcholine receptor antibody tests, though initially elevated, were later normal.

The patient also experienced flushing, and neck and facial redness without a clear diagnosis. She developed erythematous changes on her thighs, arms, and cleavage. Mastocytosis was suspected, but skin biopsy and serum tryptase tests were negative. She also reported frequent nocturnal bowel movements. Tumor markers such as chromogranin A and glucagon were slightly elevated, but a Ga-68 Dotatoc PET CT scan showed no evidence of neuroendocrine tumors.

After six months of remission, the patient discontinued thiamazole, leading to symptom resolution and normalization of anti-TRAb levels. However, her TSH receptor antibodies increased seasonally, from February to August, over the next two years, resulting in hyperthyroidism. Thyroid ultrasound revealed changes consistent with autoimmune thyroid disease. The patient declined thymectomy and thyroidectomy. Due to adverse reactions to thiamazole and propranolol, possibly linked to Myasthenia gravis, she was switched to propylthiouracil with a good response.

The etiology of symptoms atypical for hyperthyroidism or thymic hyperplasia, such as facial muscle tingling, spasms, pulsations, and erythematous rash, may be related to other autoimmune or neurological conditions, including Stiff Person syndrome and Myastenia gravis. Additionally, the seasonal recurrence, from February to August, of Graves' disease over three consecutive years is notable. Given the high prevalence of thymic hyperplasia in Graves' disease, ruling out neurological autoimmune diseases is advisable, as specific symptoms can affect the quality of life and may be exacerbated by antithyroid therapy.
γ-secretase facilitates retromer-mediated retrograde transport
Authors: Takeo Yuka , Crite Mac , Mehmood Kashif , DiMaio Daniel
Published: January 2025

Retromer mediates retrograde transport of protein cargoes from endosomes to the trans-Golgi network (TGN). γ-secretase is a protease that cleaves the transmembrane domain of its target proteins. Although retromer can form a stable complex with γ-secretase, the functional consequences of this interaction are not known. Here, we report that retromer-mediated retrograde protein trafficking in cultured human epithelial cells is impaired by the γ-secretase inhibitor XXI or by knockout of PS1 (also known as PSEN1), the catalytic subunit of γ-secretase. These treatments inhibited endosome-to-TGN trafficking of retromer-dependent retrograde cellular cargoes, divalent metal transporter 1 isoform II, cation-independent mannose-6-phosphate receptor and shiga toxin, whereas trafficking of retromer-independent cargoes, cholera toxin and a mutant CIMPR unable to bind retromer was not affected. Moreover, we found that γ-secretase associates with retromer cargoes even in the absence of retromer. XXI treatment and PS1 knockout did not inhibit the ability of retromer or γ-secretase to associate with cargo and did not affect the expression of retromer subunits or Rab7-GTP, which regulates retromer–cargo interaction. These results imply that the γ-secretase–retromer interaction facilitates retromer-mediated retrograde trafficking of cellular transmembrane proteins.
Ο Σαίξπηρ ως όχημα για την πρωτοπορία
Authors: Ματσαμάκης Ιωάννης
Published: January 2025

Όπως είναι γνωστό τα έργα του Σαίξπηρ έχουν πολλαπλά μηνύματα. Για το λόγο αυτό και οι σκηνοθετικές προσεγγίσεις αποτελούν αντικείμενο μελέτης. Ιδιαίτερα από τον 20ο αιώνα και μετά, οι σκηνοθεσίες αρχίζουν να διαφοροποιούνται από τις κοινωνικές και πολιτικές συνθήκες της εποχής του συγγραφέα. Σε ένα πρώτο επίπεδο ανάλυσης, μπορούμε να παρατηρήσουμε ότι υπάρχουν βασικές διαφορές από το αρχικό κείμενο: διαφορετικό ιστορικό πλαίσιο και διαφοροποιημένη αισθητική προσέγγιση που σχετίζεται με υπαρξιακά, πολιτικά και κοινωνικά μοτίβα τα οποία προβάλλουν την διαμάχη μεταξύ του δραματικού κειμένου και της παράστασης. Αυτό επιτυγχάνεται με τις σκηνοθετικές ερμηνευτικές επιλογές και τις δραματικές επεμβάσεις όπως η αφαίρεση κάποιων σκηνών, μετατόπιση, προσθήκες και πολλά άλλα.
mimicINT: A workflow for microbe-host protein interaction inference
Authors: Choteau Sébastien A. , Maldonado Kevin , Bergon Aurélie , Cristianini Marceau , Boujeant Mégane , Drets Lilian , Brun Christine , Spinelli Lionel , Zanzoni Andreas
Published: January 2025

Background The increasing incidence of emerging infectious diseases is posing serious global threats. Therefore, there is a clear need for developing computational methods that can assist and speed up experimental research to better characterize the molecular mechanisms of microbial infections. Methods In this context, we developed mimicINT, an open-source computational workflow for large-scale protein-protein interaction inference between microbe and human by detecting putative molecular mimicry elements mediating the interaction with host proteins: short linear motifs (SLiMs) and host-like globular domains. mimicINT exploits these putative elements to infer the interaction with human proteins by using known templates of domain-domain and SLiM-domain interaction templates. mimicINT also provides (i) robust Monte-Carlo simulations to assess the statistical significance of SLiM detection which suffers from false positives, and (ii) an interaction specificity filter to account for differences between motif-binding domains of the same family. We have also made mimicINT available via a web server. Results In two use cases, mimicINT can identify potential interfaces in experimentally detected interaction between pathogenic Escherichia coli type-3 secreted effectors and human proteins and infer biologically relevant interactions between Marburg virus and human proteins. Conclusions The mimicINT workflow can be instrumental to better understand the molecular details of microbe-host interactions.
Elegie o straconych córkach – trauma indywidualna i kulturowa w powieściach The Painted Drum Louise Erdrich i Prudence Davida Treuera
Authors: Gondor-Wiercioch Agnieszka
Published: January 2025

W swoim artykule zamierzam porównać dwie współczesne powieści rdzennych Amerykanów ze społeczności Odżibuejów skonstruowane wokół tematu śmierci. The Painted Drum Louise Erdrich i Prudence Davida Treuera to elegijne opowieści o sposobach konfrontowania się z żałobą w kontekście indywidualnym i zbiorowym, w ujęciu kultury Zachodu (euro-amerykańskiej) i kultury Odżibuejów. W obydwu narracjach pojawiają się wątki historyczne mające przybliżyć losy rdzennych Amerykanów na tle dziejów Ameryki. Chciałabym wykazać, że chociaż wybrani prozaicy stawiają na zupełnie inne strategie włączania historii, ponieważ stosują odmienną konwencję (Erdrich realizm magiczny, a Treuer realizm społeczny), to więcej jest w ich prozie podobieństw niż różnic. Obie historie dotyczą żałoby po córkach (prawdziwych i przybranych) i ta tematyka łączy się z wątkami autodestrukcji, pamięci i wyparcia. Dodatkowo pomimo że u Erdrich dominuje perspektywa feministyczna, a u Treuera dominuje wątek męski, łącznikiem jest brak eksponowania radykalnej perspektywy gender. Kolejnym podobieństwem jest struktura polifoniczna, która dodatkowo uwypukla podziały w przedstawionym świecie nie tylko na poziomie podejścia do rdzennej tradycji, ale też asymilacji do kultury amerykańskiej, stereotypów o rodowodzie kolonialnym i popkulturowym (stoicyzm indiańskich mężczyzn, rozwiązłość kobiet) oraz stosunku do przyrody, która nie dla wszystkich jest animistyczną przestrzenią ożywioną. Moja interpretacja uwzględni też szerszy kontekst obecności historii Odżibuejów w Minneapolis (krótka analiza propozycji muzealnych i miejsc pamięci w przestrzeni publicznej). Postaram się odpowiedzieć na pytanie, jakie miejsce w tym spectrum zajmują propozycje Erdrich i Treuera. W mojej pracy będę używać określeń „Odżibue” wszędzie tam, gdzie pojawiają się odniesienia do tej konkretnie kultury, i „rdzenny” w kontekstach, które wykraczają poza doświadczenia Odżibuejów, np. historii szkół z internatem. Postaram się również wyjaśnić, dlaczego Treuer używa terminów „Indianin” i „indiański”.
„Wyznaczając ścieżkę z mapy na ląd”. Suwerenność cielesna w esejach Billy’ego-Raya Belcourta A History of My Brief Body
Authors: Ziarkowska Joanna
Published: January 2025

Autorka  artykułu analizuje sposoby, w jakich pisarz z narodu Driftpile Krii w Północnej Albercie, Billy-Ray Belcourt, wykorzystuje ciało i ucieleśnione doświadczenia, by stworzyć teoretyczne ramy dla dekolonizacji pojęć, takich jak seksualność, erotyzm i suwerenność. Według Belcourta indygeniczne ciało zostało nie tylko skolonizowane i ograniczone przez heteronormatywność osadników kolonialnych, ale również zignorowane przez rodzimych krytyków, artystów i pisarzy jako nieistotne w porównaniu z teorią indygeniczności. Dlatego w swoich tekstach Belcourt podkreśla centralną rolę ciała jako ramy teoretycznej, a także źródła (seksualnej) przyjemności w codziennym życiu. Opowiada się za „rdzenną radością”, która afirmuje tożsamości tubylczych mieszkańców we wszystkich ich wymiarach, w tym osób o dwóch duszach (ang. Two-Spirit) i queer, zapewniając im tym samym emocjonalne wsparcie w codziennej walce z przejawami kolonializmu osadniczego.
Troska i humor we współczesnej literaturze tubylczoamerykańskiej. Lektury osobiste
Authors: Kuligowski Waldemar
Published: January 2025

Literatura pisana przez pisarki i pisarzy wywodzących się z tubylczych społeczności Stanów Zjednoczonych i Kanady nie może dziś ograniczać się do zbiorów nostalgicznej poezji, antologii wzniosłych przemówień czy malowniczych wyborów mitów i legend. Literatura ta porusza niemal wszystkie tematy typowe dla współczesnej sztuki słowa, niewątpliwie należącej do „światowej republiki literatury”. Tezą artykułu jest to, że można wskazać dwa wyraźne – istotne także dla odbiorców zewnętrznych – tematy dla tego pisarstwa. Są to: głęboko przeżywana troska o środowisko oraz specyficzne poczucie humoru. Teza ta została zilustrowana przykładami prozy i poezji Natalie Diaz, Inés Hernández-Ávili, Thomasa Kinga, Tomsona Highwaya i Adama Fortunate’a Eagle’a. Ich prace wykraczają poza schematy obecne w większości realistycznej prozy i preferencje branży wydawniczej, prezentując inne, „organiczne” spojrzenie na świat.
Czy to jest wystarczająco indiańskie?
Authors: Maciołek Marek
Published: January 2025

Tłumaczenia tubylczej poezji i prozy amerykańskiej
 
nila northsun
jutro mam być indianką
Karenne Wood
Moja zwyczajowa odpowiedź
Jedna na trzy albo cztery
Lilie
Nazywanie
Marcie Rendon
Wytrzymałość
co ma zrobić indianka?
Hershman R. John
Ulewny Męski Deszcz
Beth Piatote
Lekcja koralików
David Heska Wanbli Weiden
Mikey
Bile cast nephropathy (cholemic nephropathy) associated with hepatitis A-induced acute liver failure and haemolysis in a patient with glucose-6-phosphate dehydrogenase deficiency
Authors: Hamdan Ali , Salem Johny , Karam Karam , Ziadeh Maria , Hani Pierre
Published: January 2025

Introduction: The hepatitis A virus (HAV) is a common cause of acute hepatitis, while glucose-6-phosphate dehydrogenase (G6PD) deficiency is a widespread enzyme disorder that predisposes individuals to haemolysis and hyperbilirubinemia. We report a case of a G6PD-deficient patient with hepatitis A-induced acute renal failure (ARF), highlighting the role of plasmapheresis and haemodialysis in management. Case description: A 40-year-old male with G6PD deficiency and hypertension was transferred for further care after presenting with fever, diarrhoea and jaundice. Laboratory results showed severe haemolysis and elevated bilirubin (70 µmol/l); hepatitis A serology was positive. The patient developed acute liver failure and ARF, with creatinine reaching 7.3 mg/dl. Plasmapheresis and haemodialysis were initiated, leading to stabilisation of renal function and a significant decrease in bilirubin by six weeks post-discharge. Discussion: G6PD deficiency increases the risk of haemolysis, especially during infections such as hepatitis A. This can lead to severe hyperbilirubinemia and complications including bile cast nephropathy. In this case, plasmapheresis effectively reduced bilirubin and inflammatory mediators, while haemodialysis addressed renal dysfunction. Together, these therapies were crucial in stabilising renal function. Conclusion: Bile cast nephropathy is an important cause of kidney injury in severe hyperbilirubinemia. This case highlights the effectiveness of plasmapheresis and haemodialysis in managing the condition and supporting renal recovery, especially in the absence of established treatment guidelines.
Method for evaluating the stray-light suppression performance of an internally occulted reflecting coronagraph in the Lyman alpha band
Authors: Zhang Guang , He Lingping , Wang Xiaodong , Wang Haifeng , Ren Shuai , Li Xinkai , Yu Sibo , Liu Shijie , Wang Shaojing , Tian Haoyang , Wu Xinye , Lu Qiyu , Chen Bo
Published: January 2025

The Lyman alpha (Lyman-α or Lyα) radiation emitted by hydrogen is the
strongest ultraviolet spectral line on the corona, which can provide
important coronal information that is difficult to obtain at other
wavelengths and of great significance to comprehensively study the
origin of the corona. In order to observe the Lyα corona and provide space weather
warning in time, the stray-light suppression performance with a
field-of-view (FOV) of 2.5R⊙ (R⊙ stands for the mean solar radius) for Lyα coronagraphs should be suppressed to 10−6B⊙ (B⊙ is the mean brightness of the solar
disk). Since there is no Lyα light source with high brightness or Lyα detector with high sensitivity, it is
difficult to measure the stray-light in Lyα wavebands directly. On the basis of
the correlation between stray-light and wavelength, an evaluation
method of stray-light in Lyα wavebands based on the measurement
and simulation results in visible-light and ultraviolet bands is
proposed. The parameters of the simulation model are modified by
comparing the measurement results, and the stray-light for the
internally occulted reflecting coronagraph in Lyα wavebands is analyzed with the
modified model. The results show that the stray-light in Lyα wavebands can be suppressed to 10−6B⊙ at 2.5R⊙, and this method can be used to
evaluate the stray-light level of all Lyα coronagraphs.
Single-shot digital image-correlation-assisted digital holography for simultaneous 3D shape and displacement measurement
Authors: Zhang Haiyu , Pan Bing , Qian Bo , Huang Peng , Wang Kaizhi , Yan Hao
Published: January 2025

To measure surface 3D shape and displacement of curved diffuse objects, existing holographic techniques usually rely on complex optical systems or multiple shots. This is because digital holography (DH) can only measure displacement along the direction of the sensitivity vector. To realize 3D displacement measurement, three DH setups are needed. Meanwhile, a single-wavelength DH setup cannot measure the 3D shape of curved diffuse objects. To accomplish the goal of simultaneous 3D shape and displacement measurement of curved diffuse objects, a single-shot DH with a simple setup is proposed. Based on the combination of dual-wavelength DH (DWDH), digital imaging correlation (DIC), and spectrum multiplexing, the proposed technique only adopts a simple DH setup to accomplish the above task in single-shot. Specifically, spectrum multiplexing enables single-shot recording. DWDH allows the 3D shape measurement of curved diffuse objects and extends depth displacement measurement range. DIC-assisted DWDH fully utilizes DWDH’s information for simultaneous 3D displacement measurement. Experiments performed on diffuse objects validated the proposed method, which would expand DH’s applications in 3D dynamic measurements and 3D large displacement measurements.
Optical coherence tomography guided automatic robotic craniotomy surgery platform
Authors: Li Haoyuan , Wang Yongchao , Chen Wei , Zhang Yanjun , Guo Xiangsen , Xu Luke , Bao Yuerong , Zhou Junxiong , Sun Heng , Bi Yuntian , Feng Huijuan , Wang Wenjin , Suo Sen , Tang Jianbo
Published: January 2025

A transparent craniotomy window is required for optical brain imaging; however, traditional surgical preparation requires well-trained surgeons, is time-consuming, and suffers from low success rates. To address this issue, we present an automatic craniotomy platform combining optical coherence tomography (OCT) with an automated drilling machine. The OCT provides 3D skull data to guide a homemade closed-loop high-precision drill for controlled craniotomies, achieving a 100% success rate in creating small, large, and thinned windows. A synthetic transparent window was installed after skull excision. This system enables high-quality OCT angiography, velocimetry, and ultrasound imaging, offering an efficient tool for brain research.
Topological structure synthesized by three-dimensional spin angular momentum of light
Authors: Cai Zizhe , Tang Yiyi , Zhang Fujun , Zhang Youmin , Meng Xindong , Wan Chenhao
Published: January 2025

Hopf links are important topological structures found in a range of disciplines. They represent the projection of higher-dimensional objects to three-dimensional (3D) physical space. Optical Hopf fibration texture has been demonstrated by synthesizing the transverse states of polarization and the phase. In this work, we demonstrate synthesizing Hopf links by 3D spin angular momentum (SAM) through tight focusing complex optical fields with a 4Pi confocal optical system. The focal volume under tight focusing provides a platform for manipulating the nonnegligible z-component of the electric field and thus the 3D states of polarization. Hopf links that consist of two and three disjoint and linked circles are shown as examples. Since Hopf links are topological objects that are projected from higher-dimensions, they may find applications in high-dimensional optical data storage and encryption or be exploited as information carriers.
Generalized method of moments for investigation of ultra-fast fiber amplifiers with gain-managed nonlinearity
Authors: Kozlov Maksim , Ivanov Mikhail , McKinstrie Colin J. , Sidorenko Pavel
Published: January 2025

Fiber-based ultrafast laser sources are rapidly expanding in both scientific and industrial domains, making them highly desirable for a variety of applications. The recently demonstrated gain-managed nonlinear (GMN) regime is particularly appealing because it enables the generation of high-energy, clean sub-50-fs pulses in a straightforward setup. However, the complex interaction between nonlinear pulse evolution and the longitudinally evolving gain shaping presents a scientific challenge in understanding how the parameters of GMN laser systems influence the characteristics of the output pulses. In this work, we introduce a computationally efficient approach using the generalized Method of Moments to analyze the dynamically evolving pulse characteristics. This method considers pulse asymmetry in GMN systems and assesses position- and frequency-dependent gain by solving population inversion rate equations. We apply our approach to demonstrate an effective multidimensional parameter optimization of a GMN amplifier.
Enhancing upconversion quantum yield by means of pulsed excitation modulation
Authors: Kho Kiang Wei , Riou Simon , Konugolu Sanathana , Komolibus Katarzyna , Matias Jean , Andersson-Engels Stefan
Published: January 2025

Upconversion luminescent nanomaterials have gained popularity recently due to their multitude of features that are attractive to a wide range of applications in the biomedical field. Unfortunately, their low quantum-yield (QY) has been a limiting factor. While attempts have been made to enhance their luminescence throughput over the past years, these solutions have been sub-optimal, particularly, for in vivo applications. Here, we investigate how a simple pulsed-excitation scheme can affect an enhancement in the upconversion luminescence QY up to several orders of magnitude using prudently selected pulse-widths. We perform numerical simulations using NaYF4:Yb,Tm as an example to illustrate the benefits of our proposed technique, and to derive experimental conditions for optimal QY enhancement.
Nonlinear optical response of BiVO4 and its application for ultrafast pulsed fiber lasers
Authors: Du Ruonan , Shi Aokun , Lian Yudong , Fang Huajing , Qi Yaoyao , Bai Zhenxu , Wang Yulei , Huang Feng , Ding Jie , Lu Zhiwei
Published: January 2025

Herein, we present aN Er-doped all-fiber laser with BiVO4 as the saturable absorber (SA). To illustrate the nonlinear optical response, a two-dimensional model of monoclinic and its electronic structure was calculated. The nonlinear absorption properties were evaluated utilizing the Z-scan technique, and a saturable absorber was fabricated for integration into a fiber laser, resulting in a stable Q-switched output. At a maximum pump power of 600 mW, the fiber laser achieved an average output power of 25.23 mW and a pulse energy of 330.76 nJ. This research confirms that BiVO4 material exhibits outstanding nonlinear optical characteristics, thereby broadening its scope of application in the realm of ultrafast pulsed fiber lasers.
Fast polarization independent tunable liquid crystal Solc filter using Sagnac configuration
Authors: Aisheh Majd Abu , Abdulhalim Ibrahim
Published: January 2025

Narrowband tunable filters play a key role in advancing the capabilities of multispectral and hyperspectral imaging (HSI and MSI) systems. Yet, some challenges limit their effectiveness including low optical throughput, slow response time, and limited tunability range. In this Letter, the common path Sagnac setup was employed to obtain a fast and polarization-independent narrowband tunable filter using liquid crystal (LC) wave plates at both the folded and fan Solc configurations. The filter provides full tunability over the visible range for multiple orders of transmission peaks. The setup allows the collection of both the S- and the P-polarization components with a total throughput twice that of the polarization-dependent Solc filter. The enhanced throughput enables using a larger number of LC retarders at relatively thin thicknesses, thus obtaining a shorter response time. The Sagnac common path configuration helps in miniaturization and minimizes the effects of LC thickness variations.
Diverse neuronal activity patterns contribute to the control of distraction in the prefrontal and parietal cortex
Authors: Sapountzis Panagiotis , Antoniadou Alexandra , Gregoriou Georgia G.
Published: January 2025

Goal-directed behavior requires the effective suppression of distractions to focus on the task at hand. Although experimental evidence suggests that brain areas in the prefrontal and parietal lobe contribute to the selection of task-relevant and the suppression of task-irrelevant stimuli, how conspicuous distractors are encoded and effectively ignored remains poorly understood. We recorded neuronal responses from 2 regions in the prefrontal and parietal cortex of macaques, the frontal eye field (FEF) and the lateral intraparietal (LIP) area, during a visual search task, in the presence and absence of a salient distractor. We found that in both areas, salient distractors are encoded by both response enhancement and suppression by distinct neuronal populations. In FEF, a larger proportion of units displayed suppression of responses to the salient distractor compared to LIP, with suppression effects in FEF being correlated with search time. Moreover, in FEF but not in LIP, the suppression for the salient distractor compared to non-salient distractors that shared the target color could not be accounted for by an enhancement of target features. These results reveal a distinct contribution of FEF in the suppression of salient distractors. Critically, we found that in both areas, the population level representations of the target and singleton locations were not orthogonal, suggesting a mechanism of interference from salient stimuli.