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Foramen ovale is a small communication between the left and the right atrium and its restriction is a rare congenital heart anomaly. There is no consensus on diagnosis and management of fetal restrictive foramen ovale (RFO). In our paper we included 11 studies about fetuses affected by isolated RFO, RFO with D-Transposition of the Great Arteries (dTGA) and RFO with hypoplastic left heart syndrome (HLHS). While fetuses affected from HLHS and dTGA with RFO have a poor prognosis, premature RFO in an otherwise structurally normal heart, if found in later gestation, have an overall good outcome.

Purpose: The most appropriate therapy for HR + /HER2-positive (HER2 +) advanced breast cancer (ABC) is a matter of debate. Co-targeting of both receptors represents an attractive strategy to overcome the cross-talk between them. Methods: The HERMIONE 9 is an observational retrospective multicentric study which aimed to describe the clinical outcome of patients with HR + /HER2 + ABC who received the combination of Fulvestrant (F) and Trastuzumab (T) as part of their routine treatment at 10 Italian Institutions. Results: Eighty-seven patients were included. Median age was 63 (range, 35–87) years. The median number of previous treatments was 3 (range, 0–10) and F and T were administered as ≥ 3rd line in 67 patients. Among the 86 evaluable patients, 6 (6.9%) achieved CR, 18 (20.7%) PR, and 44 (50.6%) had SD ≥ 24 weeks with an overall CBR of 78.2%. At a median follow-up of 33.6 months, mPFS of the entire cohort was 12.9 months (range, 2.47–128.67). No difference was observed in mPFS between patients treated after progression or as maintenance therapy (mPFS 12.9 and 13.9 months in 64 and 23 patients, respectively), neither considering the number of previous treatment lines (≤ 3 or < 3). Conclusion: The combination of F and T was active in this cohort at poor prognosis and deserves further investigations possibly in combination with pertuzumab in patients with high ER expression.

Two series of 4,6-disubstituted 1,3,5-triazin-2-amines were prepared by cesium carbonate-promoted cotrimerization of aromatic nitriles with guanidine and the reaction of (hetero)aryl nitriles with N-acetylguanidine. The first series of 4,6-bis(hetero)aryl-1,3,5-triazin-2-amines was synthesized in yields of 56–85% by adapting a traditional approach that starts from readily available substrates but requires strong and hard-to-handle bases as well as presents serious scope limitations. In this line, the method developed here used a mild base and overcame the scope limitation for p-substituted benzonitrile with electron-releasing group. The second series of 4-(hetero)aryl-6-methyl-1,3,5-triazin-2-amines comprises unsymmetrically substituted symmetrical triazines, which were synthesized in yields of 58–75%. In summary, this work highlighted a synthetic method, which tolerates broad range of substrates, including o- and p-substituted benzonitriles as well as heteroaromatic nitriles.

The objective of the meta-analysis was to evaluate the effects of beef cows weight variation during the 2nd and / or 3rd trimester pregnancy on some parameters of the progeny carcass. The cow weight gain during this gestational period was calculated to standardize the treatments: moderate loss (ML= cows that lost 0 to 5 % of weight) and moderate gain (MG= cows that gained 0 to 5 % of weight). The effect size for all parameters was calculated as medium difference (MD) with a 95% confidence interval and heterogeneity determined using the Q test and the I2 statistic. A random effects meta-analysis was performed for each indicator separately as the medium control and experimental groups. The cow’s weight variation during the studied time variation did not influence the progeny carcass characteristics (P>0.05). Although, a trend towards greater hot carcass weight (P=0.15) and thickness of subcutaneous fat (P=0.10) was observed in calves from MG cows in relation to calves from ML cows. However, the meta-analysis demonstrated that small variations in cow weight during the final half of pregnancy do not affect progeny carcass characteristics.

A cidade, entendida como produto das relações sociais, é constituída de formas, funções, estruturas e processos. Vista como uma totalidade social, é possível analisála como um complexo fragmentado e dinâmico que espelha as relações de poder da sociedade em questão. Especificamente, o município de Santa Maria tem importante destaque na história da formação do Estado Brasileiro, apresentando características ímpares, válidas de atenção e análise, contribuindo, assim, para os estudos do espaço urbano brasileiro. Diante disso, o presente trabalho tem como objetivo analisar a expansão urbana, seus processos e consequências, na RSC 287, “Faixa Nova de Camobi”, no município de Santa Maria, RS, no período de 1990 à 2023. De forma específica, objetivou-se: (1) Diagnosticar as formas e estruturas urbanas no tempo e os impactos sócio-espaciais na RSC-287; (2) Definir unidades de diferenciação sócioespaciais e suas especificidades; (3) Debater a aplicação das legislações urbanas e ambientais. Para tanto, utiliza-se metodologia baseada principalmente na Geografia Crítica, com abordagem quali-quantitativa, na qual foram realizadas pesquisas bibliográficas acerca do tema, além de pesquisa em fontes secundárias para levantamento de dados quantitativos e quanto aos dados primários, têm-se as observações e análises realizadas a partir de trabalho de campo. Deste modo, partindo de um arcabouço metodológico foram definidas quatro Unidades de Diferenciação Sócio-espacial a partir do contexto atual e do histórico da região, identificando os conflitos sócio-ambientais em cada unidade, assim como de conflitos que podem ocorrer posteriormente seguindo a lógica exposta. Por fim, a pesquisa aplicada apresenta um potencial metodológico para uma análise integradora, contribuindo com a Ciência Geográfica nos estudos do Espaço Urbano. &nbsp

In everyday activities, humans move alike to manipulate objects. Prior works suggest that hand movements are built by a limited set of basic building blocks consisting of a set of common postures. However, how the low dimensionality of hand movements supports the adaptability and flexibility of natural behavior is unknown. Through a sensorized glove, we collected kinematics data from thirty‐six participants preparing and having breakfast in naturalistic conditions. By means of an unbiased analysis, we identified a repertoire of hand states. Then, we tracked their transitions over time. We found that manual behavior can be described in space through a complex organization of basic configurations. These, even in an unconstrained experiment, recurred across subjects. A specific temporal structure, highly consistent within the sample, seems to integrate such identified hand shapes to realize skilled movements. These findings suggest that the simplification of the motor commands unravels in the temporal dimension more than in the spatial one.

Cancer stem cells (CSCs) are a subpopulation of cancer cells endowed with high tumorigenic, chemoresistant and metastatic potential. Nongenetic mechanisms of acquired resistance are increasingly being discovered, but molecular insights into the evolutionary process of CSCs are limited. Here, we show that type I interferons (IFNs-I) function as molecular hubs of resistance during immunogenic chemotherapy, triggering the epigenetic regulator demethylase 1B (KDM1B) to promote an adaptive, yet reversible, transcriptional rewiring of cancer cells towards stemness and immune escape. Accordingly, KDM1B inhibition prevents the appearance of IFN-I-induced CSCs, both in vitro and in vivo. Notably, IFN-I-induced CSCs are heterogeneous in terms of multidrug resistance, plasticity, invasiveness and immunogenicity. Moreover, in breast cancer (BC) patients receiving anthracycline-based chemotherapy, KDM1B positively correlated with CSC signatures. Our study identifies an IFN-I → KDM1B axis as a potent engine of cancer cell reprogramming, supporting KDM1B targeting as an attractive adjunctive to immunogenic drugs to prevent CSC expansion and increase the long-term benefit of therapy.

The broad application of 1H-indazoles has prompted the development of several approaches for the synthesis of such compounds, including metal-free, palladium-, or copper-promoted intramolecular N-arylation of in situ-generated or isolated o-haloarylhydrazones. Such methods mainly start from o-bromo derivatives due to the better yield observed when compared to those obtained from o-chloroarylhydrazones. However, the o-chloroarylaldehydes and o-chloroarylketones used to prepare the arylhydrazones are more commercially available and less expensive than brominated analogs. Seeking to cover a lack in the literature, this work reports a convenient protocol for the synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of o-chlorinated arylhydrazones. Therefore, a series of seven N-phenyl derivatives and a series of six novel N-thiazolyl derivatives was obtained in 10–70% and 12–35% yield, respectively, after stirring the o-chlorinated arylhydrazones, CuI, KOH, and 1,10-phenantroline for 12–48 hours in DMF at 120 °C. The products were isolated by column chromatography on silica gel. All products were fully characterized by HRMS as well as 1H and 13C NMR spectroscopy. Thus, this approach is valuable for promoting the synthesis of N-phenyl-1H-indazoles in a higher yield than that reported in the literature using copper catalysis and the same substrates. This study also prompted the first reported synthesis of pharmacologically interesting N-thiazolyl derivatives.

We address an assortment-and-cutting problem arising in the glass industry. The objective is to provide minimum waste solutions that are robust against such raw material imperfections as those possibly occurring with float glass production technology. The stochastic realization of defects is modeled as a spatial Poisson point process. A mixed integer program in the classical vein of robust optimization is presented and tested on data taken from a real plant application. Defective final products must in any case be discarded as waste but, if a recourse strategy is adopted, faults in glass sheets can sometimes be recovered. Closed forms for the computation of faulty item probabilities are provided in simple cases, and obtained via Monte Carlo simulation in more complex ones. The computational results demonstrate the benefits of the robust approach in terms of the reduction of back-orders and overproduction, thereby showing that recourse strategies can enable nonnegligible improvements. Encouraged by this result, the management is presently evaluating the possibility of adopting the proposed model in plant operation.

Pensar a formação docente mediante às vivências e a realidade escolar é fundamental para constituição do(a) professor(a). Nesse sentido, o objetivo do presente artigo foi apresentar as narrativas que embasaram a disciplina de Vivências Pedagógicas I (GCC 1085), do Curso de Geografia (Licenciatura Plena) da UFSM. A disciplina buscou identificar a existência de formas de organização de ensino e apresentar os diferentes contextos escolares, considerando a necessidade de ajustamento/adaptação das abordagens geográficas em diferentes níveis, sistemas de ensino, modalidades e contextos socioespaciais. Dessa forma, no que diz respeito à metodologia, apresentamos uma síntese de debates de aula, bem como entrevistas e questionários aplicados para docentes, com a intenção de refletir sobre suas práticas pedagógicas escolares e formação de professores. Através disso, concluímos que, mesmo em REDE, a disciplina colaborou com a formação dos(as) professores(as), para percebermos a importância do reconhecimento do outro na nossa formação, bem como da valorização das nossas trajetórias na produção de saberes profissionais docentes.

Cortical columns of direction-selective neurons in the motion sensitive area (MT) have been successfully established as a microscopic feature of the neocortex in animals. The same property has been investigated at mesoscale (

Introdução: A Fitoterapia é uma prática estratégica para as ações em saúde, que amplia as possibilidades terapêuticas e contribui para a atenção integral aos usuários do Sistema Único de Saúde (SUS). Objetivo: O presente artigo apresenta um estudo descritivo do mapeamento dos fitoterápicos e das plantas medicinais oferta dos nas farmácias municipais no Rio Grande do Sul. Método: Foi utilizado um formulário semiestruturado o qual foi aplicado aos municípios do estado. Resultados: Foi verificado que trinta e sete porcento (37%) dos municípios que preencheram o formulário dispensam medicamentos fitoterápicos à população com predomínio dos medicamentos industrializados, visto que apenas três municípios manipulam fitoterápicos. Além disso, seis municípios ofertam chá medicinal e dezessete dispõem de horto de plantas medicinais, principalmente para uso educativo sobre a planta fresca e distribuição de espécies vegetais e/ou mudas para os usuários. Conclusão: A quase totalidade, noventa e três porcento (93%) dos entrevistados, considerou a fitoterapia importante, o que mostra a necessidade de maior estruturação desta abordagem terapêutica no âmbito do SUS.

In the last years 3D printing has progressively gained widespread interest for its several applications in many medical fields. Among the most common diagnostic imaging techniques, computed tomography (CT) and magnetic resonance imaging (MRI) allow only two-dimensional images to obtain information on different pathologies. This requires excellent visualization skills from not specialized medical doctors. The 3D printing has been developed to overcome the current disadvantages of conventional imaging techniques. The 3D models are created from the diagnostic studies of the patient (MRI, CT, PET or a combination of those) with a process that fuse advanced medical imaging algorithms and medical image processing, which are supervised by specialized radiologists. Hereby we describe the cases of two patients with giant incisional hernias. The patients underwent 3D study before botulinum toxin treatment and another 3D model a months after the botulin toxin. With the 3D model we calculated the abdominal cavity volume before and after the treatment with botulinum toxin. Six weeks after the toxin we planned the surgery. The operation time was 180 min and 150 min respectively. The patient's diet was resumed on the first day postsurgery, and the postoperative hospital stay was five days. Our experience gives an overview of the current use of 3D-techniques, more specifically in the field of abdominal wall defect.

Giant inguinoscrotal (GIS) hernias are rarely encountered in clinical settings and are oftenassociated with mental neglect for many years. This type of hernia is defined as “giant” if it descends belowthe mid-point of the inner thigh of a patient in an upright position. The laparoscopic repair approach of aGIS hernia is technically challenging. It has been claimed that laparoscopic surgery has several advantagesover the open surgical approach, with less pain and an earlier recovery. The aim of this video is to evaluatethe efficacy of TAPP (laparoscopic transabdominal preperitoneal) in order to treat a GIS hernia. A 65-year-old male without a relevant past medical history was admitted to theemergency service with abdominal pain, belching and nausea. He denied any other symptoms, and noprevious surgical operations were recorded. Physical examination showed a large mass in the left scrotumbelow the mid-point of the inner thigh of the patient in an upright position. A CT scan confirmed thediagnosis of a GIS. A laparoscopic TAPP procedure was decided upon as the best course of treatment. Results The patient underwent a successful repair procedure. The operation time was 150 min. Nointraoperative blood transfusion was necessary. The patient's diet was resumed on the first day postsurgery, and the postoperative hospital stay was three days. Laparoscopic TAPP repair is a safe and feasible method for surgically managing GIS hernias.

First release upon acceptance of the paper.

Digital health tools such as apps are being increasingly used by women to access pregnancy-related information. Conducted during the COVID-19 pandemic, this study investigated: (i) pregnant women’s current usage of digital health tools to self-monitor and (ii) their interest in theoretical pregnancy app features (a direct patient-to-healthcare-professional communication tool and a body measurement tool). Using a mixed methods approach, 108 pregnant women were surveyed and 15 currently or recently pregnant women were interviewed online. We found that pregnant women used digital health tools to mainly access pregnancy related information and less so to self-monitor. Most participants were interested and enthusiastic about a patient-to-healthcare-professional communication tool. About half of the survey participants (49%) felt comfortable using a body measurement tool to monitor their body parts and 80% of interview participants were interested in using the body measurement to track leg/ankle swelling. Participants also shared additional pregnancy app features that they thought would be beneficial such as a “Digital Wallet” and a desire for a holistic pregnancy app that allowed for more continuous and personalised care. This study highlights the gaps and needs of pregnant women and should inform all stakeholders designing pregnancy digital healthcare. This study offers a unique insight into the needs of pregnant women during a very particular and unique period in human history.

TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate.

Background: Thanks to the introduction of radiomics, 3d reconstruction can be able to analyse tissues and recognise true hypertrophy from non-functioning tissue in patients treated with major hepatectomies with hepatic modulation.The aim of this study is to evaluate the performance of 3D Imaging Modelling in predict liver failure. Methods: Patients submitted to major hepatectomies after hepatic modulation at Sanchinarro University Hospital from May 2015 to October 2019 were analysed. Three dimensional reconstruction was realised before and after surgical treatment. The volumetry of Future Liver Remnant was calculated, distinguishing in Functional Future Liver Remnant (FRFx) i.e. true hypertrophy tissue and Anatomic Future Liver Remnant (FRL) i.e. hypertrophy plus no functional tissue (edema/congestion) These volumeswere analysed in patients with and without post hepatic liver failure. Results: Twenty-four procedures were realised (11 ALPPS and 13 PVE followed by major hepatectomy). Post hepatic liver failure grade B and C occurred in 6 patients. The ROC curve showed a better AUC for FRFxV (74%) with respect to FRLV (54%) in prediction PHLF>B. The increase of anatomical FRL (iFRL) was superior in the ALPPS group (120%) with respect to the PVE group (73%) (p=0,041), while the increase of functional FRFX (iFRFx) was 35% in the ALLPS group and 46% in the PVE group (p>0,05), showing no difference in the two groups. Conclusion: The 3D reconstruction model can allow optimal surgical planning, and through the use of specific algorithms, can contribute to differential functioning liver parenchyma of the FLR.

Metronomic chemotherapy (mCHT) refers to the minimum biologically effective dose of a chemotherapy agent given as a continuous dosing regimen, with no prolonged drug-free breaks, that leads to antitumor activity. Aim of the present study is to describe the use of mCHT in a retrospective cohort of metastatic breast cancer (MBC) patients in order to collect data regarding the different types and regimens of drugs employed, their efficacy and safety. Between January 2011 and December 2016, data of 584 metastatic breast cancer patients treated with mCHT were collected. The use of VRL-based regimens increased during the time of observation (2011: 16.8% - 2016: 29.8%), as well as CTX-based ones (2011: 17.1% - 2016: 25.6%), whereas CAPE-based and MTX-based regimens remained stable. In the 1st-line setting, the highest ORR and DCR were observed for VRL-based regimens (single agent: 44% and 88%; combination: 36.7% and 82.4%, respectively). Assuming VRL-single agent as the referee treatment (median PFS: 7.2 months, 95% CI: 5.3–10.3), the longest median PFS were observed in VRL-combination regimens (9.5, 95%CI 88.8–11.3, HR = 0.72) and in CAPE-single agent (10.7, 95%CI 8.3–15.8, HR = 0.70). The VICTOR-6 study provides new data coming from the real-life setting, by adding new information regarding the use of mCHT as an option of treatment for MBC patients.

Background: The aim of this study is to evaluate the future liver remnant after major hepatectomy with 3D modelling treated, respectively, with associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) and portal vein embolization (PVE). Methods: Patients submitted to ALPPS at our centre were compared with a group of patents submitted to the PVE followed by major hepatectomy. 3D reconstruction was realised before and after surgical treatment, and anatomic future liver remnant (FRL) and functional future liver remnant (FRFx) were calculated and compared with clinical outcomes. Results: From May 2011 to October 2019, 11 ALPPS procedures were realised at Sanchinarro University Hospital, Madrid. They were compared to a control group composed of 13 patients who underwent PVE followed by hepatectomy. The increase of anatomical FRL (iFRL) was superior in the ALPPS group (120%) with respect to the PVE group (73%) (p=0,041), while the increase of functional FRFX (iFRFx) was 35% in the ALLPS group and 46% in the PVE group (p>0,05), showing no difference in the two groups. PHLF grade B and C occurred in 6 patients. The ROC curve showed a better AUC for FRFxVpost (74%) with respect to FRLVpost (54%) in prediction PHLF>B. Conclusion: The 3D reconstruction model can allow optimal surgical planning, and through the use of specific algorithms, can contribute to differential functioning liver parenchyma of the FLR.

OHBM 2023 - Poster Number: 145

OHBM 2023 - Poster Number: 743

Pensar novas estratégias e ferramentas para as práticas geoescolares é essencial. Dessa forma, os Multiletramentos e uma proposição de debates interdisciplinares com a Literatura, podem fomentar muitas inserções na Geografia. Dessa maneira, o presente trabalho busca apresentar diferentes plataformas como uma possibilidade para o estímulo e inserção dos alunos na leitura como fonte de lazer e instrumento de aprendizagem de diferentes assuntos. Juntamente da exposição de que forma algumas obras literárias são capazes de desenvolver o interesse dos alunos para o olhar geográfico, aproximando-os da disciplina e contribuindo para um raciocínio mais aguçado do funcionamento dos sistemas que cercam o funcionamento do mundo e as consequências provocadas pelos humanos no mesmo. Conclui-se que, os Multiletramentos, como ferramenta de integração entre Geografia e Literatura, potencializam compartilhamento e a criação de produções que levam a motivação dos estudantes na sistematização de novas interpretações do mundo e do espaço geográfico. Essa diversificada abordagem, pautada no incentivo à leitura de livros para fomentar a leitura de mundo, potencializa a interrelação entre essas áreas dos conhecimentos e pode promover novos olhares sobre as práticas geoescolares.

Introduction Apical Hypertrophic Cardiomyopathy (ApHCM) characterized by persistent diastolic apical contraction results in dynamic apical small-vessel obstruction with microvascular ischemia. Of note, endomyocardial fibrosis (EMF) and calcification are described only in few patients. Case presentation We report 5 cases of ApHCM with apical intramyocardial calcification. They presented characteristic ECG pattern and fibrosis at echocardiogram. All patients presented a preserved ejection fraction (EF), except for one patient with mild reduced EF. Global longitudinal strain was reduced in 3 patients. Diastolic dysfunction was evidenced in 3 patients. Right ventricle involvement was detected in one patient only.On cardiac magnetic resonance, a superficial hypo-intense component, compatible with calcium and a deep layer featured by late gadolinium enhancement (LGE) related to fibrotic tissue, were revealed. LGE was present in all of patients in the apex. One patient presented an apical aneurysm, with high ESC-SCD risk score and ICD implantation. Conclusion EMF pathologic hallmarks were the endocardium and myocardium scarring, evolving to dystrophic calcification. In clinical practice, only a minority of ApHCM patients develops EMF and calcifications. Our clinical series is the largest one in literature. Analyzing patients’ history, a microvascular inflammatory trigger was evident in all of them, particularly severe chronic kidney disease, diabetes, high degree obesity, malaria infection, peripheral microangiopathy and form of thalassemia. This series could demonstrate the pathophysiological relation between apical fibrosis, calcification and microvascular ischemia due to hypertrophy and inflammatory conditions coexistence. A broader case series could evaluate any correlation with their long-term outcome and management strategies.

Background Cabotegravir/rilpivirine (CAB/RPV) long-acting (LA) injectable was recently approved as a switch therapy for people living with HIV (PLWHIV) who are virologically suppressed on oral combination antiretroviral therapy (cART). Data demonstrates RPV resistance associated mutations (RAMs) correlated with CAB/RPV treatment failure. This is the first real-world retrospective, observational study evaluating epidemiology of RPV and CAB RAMs in a heavily treatment experienced population of PLWHIV. Methods A cohort of PLWHIV were screened for transition eligibility to CAB/RPV therapy in a large clinic in the Southeastern U.S. between April 1, 2021 and January 31, 2022. The following baseline characteristics were collected: gender, age, race, Charlson Comorbidity Index, current cART, and prior cART exposure. The Stanford University HIV Drug Resistance Database was utilized to evaluate the inferred resistance level for reverse transcriptase (RT), integrase strand transfer inhibitor (INSTI), and protease inhibitor (PI) sequences. Results Among 115 patients included, 64.3% were males who were predominately African American (83.4%), with a median age of 37 years old and Charlson Comorbidity Index of 1.65. Ten (8.69%) individuals had at least one RPV or CAB RAM. Among these, 7 (6%) and 3 (2.6%) displayed RPV and CAB resistance, respectively. The most prevalent types of RAMs for RPV specifically were Y181I/C (n = 4) and E138A (n = 2). Five of 7 individuals with RPV RAMs had history of cART use without documented exposure to RPV-containing regimens. Moreover, 2 of 3 individuals with CAB RAMs had history of cART with exposure to an integrase-containing regimen. Conclusion This is the first study that characterizes susceptibility patterns that may affect CAB/RPV in clinical practice. Within this rural Southeastern population, prevalence of RPV RAMs is higher than CAB RAMs, and RPV RAMs were commonly observed as transmitted resistance whereas CAB RAMs were typically associated with prior history of exposure to INSTI-containing regimen. It is pertinent to assess the genotypic resistance profile of RTs and history of cART exposure prior to transitioning to CAB/RPV to decrease the risk of virologic failure due to RAMs. Disclosures P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant.

Background Serology and PCR testing methods have increased ability to diagnose Bartonella spp. invasive infections. Current treatment recommendations are based primarily on case series and aging data published before newly available diagnostic techniques. These recommendations are limited in safety and effectiveness outcomes. This multicenter, retrospective cohort study describes the epidemiology and treatment outcomes of invasive bartonellosis among patients in the U.S. Methods Collaborating sites were selected from SERGE-45 (Southeastern Research Group Endeavor) research network. Data were collected through REDCap. Subjects were screened from adult patients with invasive bartonellosis diagnosis codes, positive Bartonella spp. serologies, PCR, 16/18S tests, cultures, and Karius® tests from blood or tissue between January 1, 2014, and September 1, 2021. Eligible patients had at least one positive test result, evidence of invasive bartonellosis, and received treatment for bartonellosis. Treatment failure was defined as admission or readmission while on treatment, mortality during treatment or within 30 days after end of treatment, required escalation or extended duration of therapy, premature discontinuation of therapy, or necessitated change in regimen. Those not meeting treatment failure criteria were considered treatment success. Results Of the 169 patients screened, 32 were included, with 19 having treatment success. Bartonella henselae was the most common causative pathogen (n = 31, 97%). Endocarditis was the most common invasive manifestation (n = 18, 56%). Treatment regimens are displayed in Table 1. Primary reasons for treatment failure included necessitated escalation of therapy during treatment course (n = 4, 30.8%) and discontinuation of therapy due to adverse effect (n = 4, 30.8%). Conclusion Doxycycline with rifampin was the most common treatment regimen for invasive bartonellosis, with extended durations used compared to often referenced 6-week courses for invasive infections. It is important to consider adverse drug effects, toxicities, and tolerability in patients being treated for invasive bartonellosis. Disclosures P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant.

Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.

Background: The phase 3 GIMEMA-MMY-3006 trial, which compared bortezomib, thalidomide, and dexamethasone (VTD) combination therapy with thalidomide and dexamethasone (TD) as induction therapy before and consolidation therapy after double autologous haematopoietic stem-cell transplantation (HSCT) for newly diagnosed multiple myeloma, showed the superiority of the triplet regimen over the doublet in terms of increased complete response rate and improved progression-free survival. We report the results from the final analysis of the study. Methods: In this randomised, open-label, phase 3 study, patients aged 18–65 years with previously untreated symptomatic multiple myeloma and a Karnofsky Performance Status of 60% or higher were enrolled at 73 centres in Italy. Patients were randomised (1:1) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily orally for the first 14 days and 200 mg daily thereafter) plus dexamethasone (total 320 mg per cycle; 40 mg on days 1–2, 4–5, 8–9, and 11–12 in the VTD regimen, and 40 mg on days 1–4 and 9–12 in the TD regimen), either alone (TD group) or with bortezomib (1·3 mg/m2 intravenously on days 1, 4, 8, and 11; VTD group). After double autologous HSCT, patients received two 35-day cycles of either the VTD or TD regimen, according to random assignment, as consolidation therapy. The primary outcome was the rate of complete response and near complete response after induction (already reported). In this updated analysis we assessed long-term progression-free survival and overall survival (secondary endpoints of the study) with an extended 10-year median follow-up, and analysed the variables influencing survival. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, NCT01134484. Findings: Between May 10, 2006, and April 30, 2008, 480 patients were enrolled and randomly assigned to receive VTD (241 patients) or TD (239 patients). Six patients withdrew consent before start of treatment. 236 (99 [42%] women) in the VTD group and 238 (102 [43%] women) in the TD group were included in the intention-to-treat analysis. The data cutoff date for this analysis was May 31, 2018. Median follow-up for surviving patients was 124·1 months (IQR 117·2–131·7). The 10-year progression-free survival estimate for patients in the VTD group was 34% (95% CI 28–41) compared with 17% (13–23) for the TD group (hazard ratio [HR] 0·62 [95% CI 0·50–0·77]; p

Certain animal species use the earth's magnetic field (i.e., magnetoreception) in conjunction with other sensory modalities to navigate long distances. It is hypothesized that several animals use combinations of magnetic inclination and intensity as unique signatures for localization, potentially enabling migration without a pre-surveyed map. However, it is unknown how animals use magnetic signatures to generate guidance commands. While animal experiments have been invaluable in advancing this area, it is a difficult phenomenon to study in vivo or in situ. Modeling and simulation present a powerful complementary tool that can be used to investigate whether and how animals use magnetic signatures to navigate. This perspective article summarizes work we have conducted that systematically and mechanistically uses modeling and simulation to study the use of magnetic signatures. We have studied this phenomenon from simulated agents that navigate in simple and abstract environments, to physical devices that navigate in realistic environments. The results have consistently demonstrated that this is a plausible way in which animals might navigate, and provided early insights into the environmental and animal-specific factors that are most important to this navigation strategy.

Totally implanted venous access ports (TIVAPs) have been established as effective and safe devices for oncologic patients. In breast cancer setting, the implant of the reservoir at mid-arm allows the absence of additional scars on the chest and the easier access to the port with significant cosmetic and psychological advantages. In the last decades, breast surgery has made great progresses to ameliorate the cosmetic results even in mastectomy techniques. In fact, many studies have demonstrated that negative body image perception affects physical and psychological wellbeing of survivors. Despite this evidence, limited importance is still reserved to TIVAPs placement site, which is traditionally the chest. It is not unusual to see patients after a nipple-sparing mastectomy with excellent cosmetic result who show a disfiguring scar on their upper chest due to TIVAP placement. We report the case of a young woman with BRCA2-related breast cancer who underwent bilateral nipple sparing mastectomy with immediate reconstruction and adjuvant chemotherapy. Her TIVAP was located at the mid-arm, which is still an uncommon site compared to the upper chest. An optimal cosmetic result was obtained both in breast reconstruction and in the arm site of port, with high-rate patient satisfaction. This case presentation aims to raise awareness towards women’s body image preservation, particularly in the choice of TIVAP placement: in most cases neckline and upper chest should be avoided for a better patient related outcome.

Fetal Nuchal fluid collections can manifest with two distinct presentations attributable to the same phenotypic spectrum: increased nuchal translucency (iNT) and cystic hygroma. The prenatal detection of these findings should prompt an accurate assessment through genetic counseling and testing, including karyotype, chromosomal microarray analysis (CMA) and multigene RASopathy panel. We performed a systematic review of the literature and meta-analysis, to calculate diagnostic yields of genetic testing in fetuses with iNT and cystic hygroma. We compared the results with a cohort of 96 fetuses with these isolated findings. Fetuses with isolated NT ≥ 2.5 mm showed karyotype anomalies in 22.76% of cases and CMA presented an incremental detection rate of 2.35%. Fetuses with isolated NT ≥ 3 mm presented aneuploidies in 14.36% of cases and CMA had an incremental detection rate of 3.89%. When the isolated NT measured at least 3.5 mm the diagnostic yield of karyotyping was 34.35%, the incremental CMA detection rate was 4.1%, the incremental diagnostic rate of the RASopathy panel was 1.44% and it was 2.44% for exome sequencing. Interestingly, CMA presents a considerable diagnostic yield in the group of fetuses with NT ≥ 3.5 mm. Similarly, exome sequencing appears to show promising results and could be considered after a negative CMA result.

Digital health tools such as apps are being increasingly used by women to access pregnancy-related information. Conducted during the COVID-19 pandemic, this study investigated pregnant women’s usage of digital health tools and self-monitoring behaviours. In addition, views and interest in theoretical pregnancy app features: (1) a direct patient-to-healthcare-professional communication tool and (2) a novel body measurement tool was assessed. Using a mixed methods approach, 108 pregnant women were surveyed and 15 currently or recently pregnant women were interviewed online. We found that the COVID-19 pandemic had impacts on multiple dimensions of the experiences of pregnant women including their experiences with healthcare, their relationships with themselves and their social circle. Most participants said that they would use the theoretical app features we described and also identified a gap in the availability of evidence-based educational information. Other features that they would include in a pregnancy app were a “Digital Wallet” and a desire for a holistic pregnancy app that allowed for more continuous and personalised care. The main factor that influenced how likely participants were to use pregnancy apps were concerns about data privacy and security. This study highlights the gaps and needs of pregnant women and should inform all stakeholders designing pregnancy digital healthcare. This study offers a unique insight into the experiences of pregnant women during a very particular and unique period in human history.

In everyday activities, humans use a finite number of postural hand configurations, but how do they flow into each other to create sophisticated manual behavior? We hypothesized that hand movement emerges through the temporal dynamics of a set of recurrent hand shapes characterized by specific transitions. Through a sensorized glove, we collected kinematics data from thirty-six participants preparing and having breakfast in naturalistic conditions. By means of a combined PCA/clustering- based approach, we identified a repertoire of hand states and their transitions over time. We found that manual behavior can be described in space through a complex organization of basic configurations. These, even in an unconstrained experiment, recurred across subjects. A specific temporal structure, highly consistent within the sample, seems to integrate such identified hand shapes to realize skilled movements. Our findings suggest that the simplification of the motor commands unravels in the temporal dimension more than in the spatial one.

Cellular senescence plays a very important role in organismal aging increasing with age and in age-related diseases (ARDs). This process involves physiological, structural, biochemical, and molecular changes of cells, leading to a characteristic trait referred to “senescence-associated secretory phenotype (SASP).” In particular, with aging, stem cells (SCs) in situ exhibit a diminished capacity of self-renewal and show a decline in their functionality. The identification of interventions able to prevent the accumulation of senescent SCs in the organism or to pretreat cultured multipotent mesenchymal stromal cells (MSCs) prior to employing them for cell therapy is a main purpose of medical research. Many approaches have been investigated and resulted effective to prevent or counteract SC senescence in humans, as well as other animal models. In this work, we have reviewed the chance of using a number of herb-derived products as novel tools in the treatment of cell senescence, highlighting the efficacy of these agents, often still far from being clearly understood.

MG-MAMPOSST is a FORTRAN90 code to perform tests of General Relativity (GR) through the analysis of kinematic observations of galaxy clusters. The code solves the Jeans equation, building on the MAMPOSST method of Mamon et al. (2013). It extends this method through new parametrisations of the gravitational potential for general families of gravity theories beyond GR aimed to explain the late-time accelerated expansion of the universe Perlmutter et al. (1999). Through appropriate input of the projected positions and line-of-sight velocities of a cluster’s member galaxies, MG-MAMPOSST reconstructs the cluster mass profile and the velocity anisotropy profile in modified gravity, jointly constraining the kinematics (mass and anisotropy profile) and modified gravity parameters. The code is further supplemented with a new capability to produce weak lensing forecasts for joint kinematic and lensing analysis, offering a valuable tool for studying the nature of gravity at cluster scales.

In the present study, the antimicrobial and antibiofilm activities of two 4,5-dihydro-1H-pyrazole-1-carboximidamide hydrochloride, (trifluoromethyl) phenyl-substituted (compound 1) and bromophenyl-substituted (compound 2), were evaluated against four Salmonella spp. serotypes through broth microdilution and biofilm-forming activity. Further, the cytotoxicity of the compounds was evaluated by cell viability assays using cultures of HeLa and Vero cell lines, and the mutagenic potential was assessed by the Ames test. In the broth microdilution test, compound 1 inhibited 90% of the strains tested at the minimum inhibitory concentration of 62.5 μg mL−1. Furthermore, both compounds prevented biofilm formation, with a reduction of up to 5.2 log10. HeLa and Vero cells exhibited 100% viability in the presence of compound 1. In contrast, low cell viability was observed in the presence of 15 µg mL−1 of compound 2. Furthermore, no mutagenic potential was detected at any of the tested concentrations of compound 1.