Tolerability and Preliminary Outcomes of Adjuvant T-DM1 in HER2-Positive Breast Cancer After Neoadjuvant Therapy: The ATD Study.

Background/objectives: HER2-positive breast cancer (HER2BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting.

Axon guidance genes are regulated by TDP-43 and RGNEF through long-intron removal.

Rho guanine nucleotide exchange factor (RGNEF) is a guanine nucleotide exchange factor (GEF) mainly involved in regulating the activity of Rho-family GTPases. It is a bi-functional protein, acting both as a guanine exchange factor and as an RNA-binding protein. RGNEF is known to act as a destabilizing factor of neurofilament light chain RNA (NEFL) and it could potentially contribute to their sequestration in nuclear cytoplasmic inclusions.

Location and function of TDP-43 in platelets, alterations in neurodegenerative diseases and arising considerations for current plasma biobank protocols.

The TAR DNA Binding Protein 43 (TDP-43) has been implicated in the pathogenesis of human neurodegenerative diseases and exhibits hallmark neuropathology in amyotrophic lateral sclerosis (ALS). Here, we explore its tractability as a plasma biomarker of disease and describe its localization and possible functions in the cytosol of platelets. Novel TDP-43 immunoassays were developed on three different technical platforms and qualified for specificity, signal-to-noise ratio, detection range, variation, spike recovery and dilution linearity in human plasma samples.

Plant diversity drives positive microbial associations in the rhizosphere enhancing carbon use efficiency in agricultural soils.

Expanding and intensifying agriculture has led to a loss of soil carbon. As agroecosystems cover over 40% of Earth's land surface, they must be part of the solution put in action to mitigate climate change. Development of efficient management practices to maximize soil carbon retention is currently limited, in part, by a poor understanding of how plants, which input carbon to soil, and microbes, which determine its fate there, interact.

DNA Damage Response in Early Breast Cancer: A Phase III Cohort in the Phobos Study.

We assessed the impact of DNA damage response and repair (DDR) biomarker expressions in 222 node-positive early breast cancer (BC) patients from a previous Phase III GOIM 9902 trial of adjuvant taxanes. At a median follow-up of 64 months, the original study showed no disease-free survival (DFS) or overall survival (OS) differences with the addition of docetaxel (D) to epirubicine-cyclophosphamide (EC). Immunohistochemistry was employed to assess the expression of DDR phosphoproteins (pATM, pATR, pCHK1, γH2AX, pRPA32, and pWEE1) in tumor tissue, and their association with clinical outcomes was evaluated through the Cox elastic net model.

Efficacy and safety of ramucirumab plus carboplatin and paclitaxel in untreated metastatic thymic carcinoma: RELEVENT phase II trial (NCT03921671).

Background: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients.

Takotsubo Syndrome After Pacemaker Implantation: A Case Report and Literature Review.

A 78-year-old male patient with complete atrioventricular block underwent an uncomplicated pacemaker implantation. After 24 h, he presented acute chest pain, dyspnea, ST-segment-elevation in the anterior leads, left ventricular apical ballooning, and an ejection fraction of 35%. His coronary angiogram was normal.

Case Report: Efficacy, safety, and favorable long-term outcome of early treatment with IL-1 inhibitors in a patient with chronic infantile neurological cutaneous articular (CINCA) syndrome caused by NLRP3 mosaicism.

Chronic infantile neurological cutaneous articular (CINCA) syndrome is an autoinflammatory disease encompassed in the group of cryopyrin-associated periodic syndromes (CAPS). Patients suffering from CINCA have an elevated risk of developing chronic sequelae, including deforming arthropathy, chronic meningitis, neurodevelopmental delay, and neurosensorial hearing loss. The diagnosis of CINCA presents several difficulties, as the clinical phenotype could be difficult to recognize, and almost half of the patients have negative genetic testing.

HER2 mutation as an emerging target in advanced breast cancer.

HER2 activating mutations have emerged as oncogenic drivers and therapeutic targets in a variety of human tumors. In breast cancer, these deregulations occur at low frequency, and are mostly detected in HER2-nonamplified, metastatic disease. Preclinical evidence has clarified the role of hotspot mutations in HER2 constitutive activation, defining them as an alternative mechanism to HER2 gene amplification.

Nitrogen availability and plant functional composition modify biodiversity-multifunctionality relationships.

Biodiversity typically increases multiple ecosystem functions simultaneously (multifunctionality) but variation in the strength and direction of biodiversity effects between studies suggests context dependency. To determine how different factors modulate the diversity effect on multifunctionality, we established a large grassland experiment manipulating plant species richness, resource addition, functional composition (exploitative vs. conservative species), functional diversity and enemy abundance.

Roux-en-Y Gastric Bypass after Laparoscopic Sleeve Gastrectomy Failure: Could the Number of Previous Operations Influence the Outcome?

After a failed laparoscopic adjustable gastric band (LAGB), laparoscopic sleeve gastrectomy (LSG) has been proposed as revisional surgery. Those patients that receive a second restrictive procedure fall into a small subgroup of patients with more than one restrictive procedure (MRP). If also the second restrictive procedure fails, the correct surgical strategy is a challenge for the surgeon.

Dynamic changes in T-wave and QTc interval during tilt table testing: Innocent until proven otherwise.

A16-year-old female underwent tilt table testing, which resulted positive for reflex vasodepressive syncope. 12‑lead ECG during syncope showed T-wave inversion in infero-lateral leads, along with QTc interval increase >100 msec compared to baseline. These abnormalities rapidly disappeared in supine position with resumption of consciousness.

Ataxia Telangiectasia Arising as Immunodeficiency: The Intriguing Differential Diagnosis.

Ataxia telangiectasia (AT) is a rare disease characterized by the early onset and slow progression of neurodegenerative defects, mainly affecting the cerebellum, associated with immunodeficiency and teleangiectasias. Ataxia is the hallmark of the disease and usually its first manifestation. Overt cerebellar ataxia usually becomes evident between 16 and 18 months of age, after the onset of walking, and is characterized by frequent falls and an ataxic gait with an enlarged base.

TDP-43 Epigenetic Facets and Their Neurodegenerative Implications.

Since its initial involvement in numerous neurodegenerative pathologies in 2006, either as a principal actor or as a cofactor, new pathologies implicating transactive response (TAR) DNA-binding protein 43 (TDP-43) are regularly emerging also beyond the neuronal system. This reflects the fact that TDP-43 functions are particularly complex and broad in a great variety of human cells. In neurodegenerative diseases, this protein is often pathologically delocalized to the cytoplasm, where it irreversibly aggregates and is subjected to various post-translational modifications such as phosphorylation, polyubiquitination, and cleavage.

A high-performance xylene-free tissue-clearing agent for routine histology: Preliminary histomorphological results.

After the discovery of the hazardous effects of xylene, less toxic substitutes were proposed for routine histology in the last years. However, the introduction of new xylene-free substitutes in histological processes requires a careful evaluation of their performance in terms of morphological and microscopic details to permit a solid diagnosis as well as good quality immunohistochemical and biomolecular analyses. In this study, we analyzed the performance of a new commercially available xylene-free Tissue-Tek® Tissue-Clear® agent in comparison with another routine xylene-free solvent yet available and employed in routine histological process.

Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from , a multicentric, observational study.

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available.

Pleural Effusion in COVID-19 Pneumonia: Clinical and Prognostic Implications-An Observational, Retrospective Study.

Background: COVID-19 presents with a wide spectrum of clinical and radiological manifestations, including pleural effusion. The prevalence and prognostic impact of pleural effusion are still not entirely clear.

Patients And Methods: This is a retrospective, single-center study including a population of consecutive patients admitted to the University Hospital of Cisanello (Pisa) from March 2020 to January 2021 with a positive SARS-CoV-2 nasopharyngeal swab and SARS-CoV-2-related pneumonia.

Reverse strategy to locally advanced breast implant-associated anaplastic large cell lymphoma: A case report.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare T-cell lymphoma associated with textured breast implants. The most common presentation is a periprosthetic seroma that occurs at least 1 year after an aesthetic or reconstructive implantation, and in these cases, the surgical treatment seems to be successful. More rarely, BIA-ALCL presents with locally advanced mass-formed disease and a related regional lymph node involvement.

Reviewing the Potential Links between Viral Infections and TDP-43 Proteinopathies.

Transactive response DNA binding protein 43 kDa (TDP-43) was discovered in 2001 as a cellular factor capable to inhibit HIV-1 gene expression. Successively, it was brought to new life as the most prevalent RNA-binding protein involved in several neurological disorders, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the fact that these two research areas could be considered very distant from each other, in recent years an increasing number of publications pointed out the existence of a potentially important connection.

Structure and Surface Relaxation of CeO Nanoparticles Unveiled by Combining Real and Reciprocal Space Total Scattering Analysis.

We present a combined real and reciprocal space structural and microstructural characterization of CeO nanoparticles (NPs) exhibiting different crystallite sizes; ~3 nm CeO NPs were produced by an inverse micellae wet synthetic path and then annealed at different temperatures. X-ray total scattering data were analyzed by combining real-space-based Pair Distribution Function analysis and the reciprocal-space-based Debye Scattering Equation method with atomistic models. Subtle atomic-scale relaxations occur at the nanocrystal surface.