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ABSTRACT The aim of this study is to assess the effects of once-daily oral orforglipron on weight and metabolic markers in adult patients. PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were systematically searched until February 2024 for randomized controlled trials (RCTs) comparing orforglipron versus placebo or other anti-obesity medications in adult patients. Weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) or risk differences for binary endpoints were computed, with 95% confidence intervals (CIs). Heterogeneity and risk of bias were assessed with I2 statistics and Rob-2, respectively. Statistical analyses were performed using R, version 4.2.2. A total of four studies were included, comprising 815 patients, of whom 620 (76.1%) were prescribed orforglipron. Compared with placebo, orforglipron reduced body weight (WMD -6.14 kg, 95% CI -9.62 to -2.66 kg), body mass index (WMD -2.87 kg/m2, 95% CI -4.65 to -1.10 kg/m2), and waist circumference (WMD -5.32 cm, 95% CI -9.13 to -1.51 cm). More patients treated with orforglipron than placebo achieved a weight loss of ≥ 5% (RR 3.31, 95% CI 2.23-4.93), ≥ 10% (RR 5.24, 95% CI 2.07-13.31), and ≥ 15% (RR 9.53, 95% CI 1.26-71.89). The most common adverse events were related to the gastrointestinal tract. In this meta-analysis, the use of once-daily oral orforglipron by adult patients was associated with a significant decrease in body weight, as compared with placebo, with an increase in non-severe gastrointestinal adverse events. Phase 3 RCTs are expected to shed further light on the efficacy and safety of once-daily oral orforglipron over the long term.

Abstract Background The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated. Methods We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results Three studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49–0.84; p

Abstract The objective of this work was to evaluate the physicochemical properties of coffee husk, elephant grass, and sugarcane alone or combined with each other or with commercial compounds, as well as their use as substrate for the production of clonal Coffea canephora seedlings. The experiment was carried out in two stages: one for the physicochemical characterization of the substrates, and the other for evaluations of the growth of coffee seedlings in these substrates. In the first stage, the treatments consisted of coffee husk (CH), elephant grass (EG), sugarcane (SC), commercial substrate (CS), vermiculite (VM), and their combinations. In the second stage, the standard substrate (soil) was also evaluated. CH presented a high electrical conductivity and density and a low aeration space and available water. SC stood out for its lower pH and density and its greater porosity. SC and EG were viable for coffee seedling production, not differing from the commercial and standard substrates. With the exception of CH+EG, CH+CS, and EG+SC, the combined substrates allowed of a greater seedling growth than the isolated ones. CH was only viable as a substrate when combined, especially with VM. Combining CH, SC, and EG to the standard substrate improves the quality of clonal C. canephora seedlings.

Resumo Fundamento Os antagonistas da vitamina K (AVKs) são o tratamento de primeira linha recomendado para trombo ventricular esquerdo (TVE); entretanto, os anticoagulantes orais diretos (AODs) têm sido considerados uma terapia alternativa. Objetivos Avaliar a eficácia e a segurança dos AODs em comparação com a terapia com AVKs em pacientes com TVE. Métodos PubMed, Embase e Cochrane foram sistematicamente pesquisados em busca de ensaios clínicos randomizados ou estudos de coorte que comparassem AODs versus AVKs para TVE. As razões de risco (RR) foram calculadas para desfechos binários, com intervalos de confiança (IC) de 95%. A significância estatística foi definida como valor de p < 0,05. Resultados Foram incluídos um total de 4 ensaios clínicos randomizados e 29 estudos de coorte, com 4.450 pacientes designados para AODs ou AVKs. Não houve diferença significativa entre os grupos para acidente vascular cerebral ou eventos embólicos sistêmicos (AVC/EES) (RR 0,84; IC 95% 0,65 a 1,07; p = 0,157), acidente vascular cerebral (RR 0,73; IC 95% 0,48 a 1,11; p = 0,140), eventos embólicos sistêmicos (EES) (RR 0,69; IC 95% 0,40 a 1,17; p = 0,166), resolução do trombo (RR 1,05; IC 95% 0,99 a 1,11; p = 0,077), qualquer sangramento (RR 0,78; IC 95% 0,60 a 1,00; p = 0,054), sangramento clinicamente relevante (RR 0,69; IC 95% 0,46 a 1,03; p = 0,066), sangramento menor (RR 0,73; IC 95% 0,43 a 1,23; p = 0,234), sangramento maior (RR 0,87; IC 95% 0,42 a 1,80; p = 0,705) e mortalidade por todas as causas (RR 1,05; IC 95% 0,79 a 1,39; p = 0,752). Em comparação com AVKs, a rivaroxabana reduziu significativamente AVC/EES (RR 0,35; IC 95% 0,16 a 0,91; p = 0,029) e EES (RR 0,39; IC 95% 0,16 a 0,95; p = 0,037). Conclusões Os AODs tiveram uma taxa semelhante de eventos tromboembólicos e hemorrágicos, bem como de resolução do trombo, em comparação com os AVKs no tratamento de TVE. A terapia com rivaroxabana teve uma redução significativa nos eventos tromboembólicos, em comparação com os AVKs.

ABSTRACT The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucose level was > 180 mg/dL (WMD -10.46%, 95% CI -13.99 to -6.93%) and the mean levels of glucose (WMD -16.67 mg/dL, 95% CI -22.25 to -11.09 mg/dL) and HbA1c (WMD -0.50%, 95% CI -0.68 to -0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or

Summary: Background: Patients with heart failure have high rehospitalisation rates and poor cardiovascular outcomes. Home-based monitoring (HBM) has emerged with promising results in different settings. However, its long-term effects on patients recently admitted for acute decompensated heart failure (ADHF) remain uncertain. Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomised controlled trials (RCTs) comparing HBM with usual care (UC) that were published between database inception and June 24, 2023. We included studies with patients admitted for ADHF in the previous 6 months and with a minimum follow-up of 6 months. We excluded studies with patients hospitalised for reasons other than ADHF and studies with disproportional education interventions between arms. Statistical analyses were performed using R software version 4.3.2. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for categorical and continuous outcomes, respectively. Cochrane Collaboration’s tool for assessing risk of bias in RCTs (RoB 2) was used to assess study quality. Publication bias was assessed via funnel plots and Egger’s test, and heterogeneity was assessed through I2 statistics and sensitivity analysis. The protocol for this systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023465359). Findings: We included 16 RCTs comprising 4629 patients, of whom 2393 (51.7%) were randomised to HBM and 3150 (68%) were men. Follow-up ranged from six to fifteen months. As compared with UC, HBM significantly reduced all-cause mortality (RR 0.75; 95% CI 0.61, 0.91; p = 0.005), all-cause hospitalisations (RR 0.82; 95% CI 0.70, 0.97; p = 0.018), cardiovascular (CV) mortality (RR 0.53; 95% CI 0.36, 0.79; p = 0.002), hospitalisations for heart failure (RR 0.75; 95% CI 0.62, 0.91; p = 0.004), and CV hospitalisations (RR 0.72; 95% CI 0.55, 0.95; p = 0.018). There were no significant differences in length of hospital stay (MD 0.97 days; 95% CI -0.90, 2.84; p = 0.308). Interpretation: In patients recently admitted with ADHF, HBM significantly reduces long-term all-cause mortality and hospitalisations, CV mortality and hospitalisations, and hospitalisations for heart failure, as compared with UC. This supports the implementation of HBM as a standard practice to optimise patient outcomes following admissions for ADHF. However, future studies are warranted to evaluate the efficacy and safety of implementing HBM in the real-world setting. Funding: None.

Modern technology progresses at an incredibly fast pace. With personal computers, mobile phones, tablets, and the Internet, technology is used in all spheres, affecting our daily lives greatly. Educational games are also taking advantage of the technological process, for example, many useful apps are available for children. Gaming and educational opportunities have expanded because of the development of tablets and smartphones. Teachers have the opportunity to combine physical and electronic objects when creating education materials, so they are not confined to the use of traditional physical objects. Storytelling remains one of the oldest teaching methods for children: the development of technology has given impetus to the creation of tangible digital storytelling, which combines programs with physical objects, creating a single field for learning. Creating stories in which a child can interact with his/her peers has also provided new opportunities for inclusion and cooperation in young children. Indeed, the increased use of speakers, videos, pictures, and other tools that can help to quickly create and easily adapt objects for children with various backgrounds has fostered inclusive teaching. This paper will consider the evolution of the storytelling practice, focusing specifically on tangible digital storytelling and its benefits in young children.

Modern technology progresses at an incredibly fast pace. With personal computers, mobile phones, tablets, and the Internet, technology is used in all spheres, affecting our daily lives greatly. Educational games are also taking advantage of the technological process, for example, many useful apps are available for children. Gaming and educational opportunities have expanded because of the development of tablets and smartphones. Teachers have the opportunity to combine physical and electronic objects when creating education materials, so they are not confined to the use of traditional physical objects. Storytelling remains one of the oldest teaching methods for children: the development of technology has given impetus to the creation of tangible digital storytelling, which combines programs with physical objects, creating a single field for learning. Creating stories in which a child can interact with his/her peers has also provided new opportunities for inclusion and cooperation in young children. Indeed, the increased use of speakers, videos, pictures, and other tools that can help to quickly create and easily adapt objects for children with various backgrounds has fostered inclusive teaching. This paper will consider the evolution of the storytelling practice, focusing specifically on tangible digital storytelling and its benefits in young children.

ABSTRACT Fusarium head blight, also known as fusariosis, is caused by a fungus called Fusarium graminearum that produces the mycotoxin deoxynivalenol (DON). This toxin causes problems to human and animal health. Ammonia gas has been shown to be effective in deactivating mycotoxins. The objectives of this study were to evaluate the effectiveness of ammonia gas in the deactivation of DON in wheat grains, the effect of this treatment on its protein composition and the toxicity in rats fed with ammoniated wheat grains. Wheat samples were exposed to ammonia gas at concentrations of 0% (Control), 0.5%, 1% and 1.5%. It was observed that ammonia gas was effective in deactivating DON at concentrations of 1% and 1.5%. There was no difference in crude protein observed in the bromatological analysis of treated wheat grains in relation to the control. Regarding the toxicity of wheat grains treated with ammonia in the feeding of Wistar rats (Rattus norvegicus), no histopathological alterations were observed in the liver, kidneys, intestine and in the hematological profile. The results of this study demonstrated that the treatment of wheat with ammonia gas can contribute to the deactivation of DON without compromising its protein composition and animal health.

Abstract Background Paclitaxel and carboplatin is the standard chemotherapy for the treatment of advanced or recurrent endometrial cancer. However, the benefit of adding programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors to chemotherapy is still unclear. Method We searched PubMed, Scopus, Cochrane, and Web of Science databases for randomized controlled trials that investigated PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer. We computed hazard ratios (HRs) or risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). We used DerSimonian and Laird random-effect models for all endpoints. Heterogeneity was assessed using I2 statistics. R, version 4.2.3, was used for statistical analyses. Results A total of three studies and 1,431 patients were included. Compared with carboplatin plus paclitaxel-based chemotherapy, progression-free survival (PFS) rate (HR 0.32; 95% CI 0.23–0.44; p

The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.

Governmental and private protected areas are a key focus of conservation concern, as they tend to be associated with greater biodiversity and abundance of threatened mammals than non-protected areas. Protected areas are also effective at limiting anthropogenic pressures that threaten endemic species. Behavioural shifts are often the most immediate response of animals to disturbance, indicating the importance of considering the direct links between the disturbance present in an ecosystem and the behavioural patterns of endemic species. Here, we assessed the effect of land cover protection along with anthropogenic disturbance factors (human and dog abundance, distance to the nearest house, percentage of native vegetation [relative to agricultural landscapes]) on the activity patterns and abundance of 6 mammal species in the Brazilian Atlantic Forest and Cerrado. Data were collected using camera traps employed during 2 dry seasons at 208 stations (6240 camera-days). Activity pattern analyses used the novel application of circular activity patterns and a direct circular outcome to assess the direct impact of protection status and anthropogenic disturbance on behavioural shifts in the mammal species. Relative abundance was calculated using the mean population size of individuals as well as the per-individual detection probability. Protection status significantly elicited behavioural shifts in 5 of the 6 mammals, with 4 of these mammals shifting more towards nocturnality in non-protected areas. Dog abundance was the most important covariate in activity pattern shifts in the giant anteater, with nocturnality increasing with dog abundance, whereas native vegetation was the most important covariate in activity pattern shifts in the agouti and puma, with nocturnality increasing with decreasing native vegetation. Relative abundance was significantly lower in non-protected areas in 2 mammals, one of which was the Vulnerable giant anteater. The findings here are the first time in which anthropogenic disturbance factors have been found to directly elicit shifts in the circular activity patterns of mammals, as well as highlight the importance of protected areas in mammal conservation. The methods used here can be applied to ecosystems globally to pinpoint the direct impact of disturbance factors on endemic species whilst also providing explicit information on how conservation initiatives can be strategically and effectively targeted.

A 37-year-old immunocompetent man was admitted to the emergency department due to recurrent pain and oedema of his right knee. Two months earlier, he had undergone surgery to repair his meniscus. Arthroscopic joint lavage was performed and Candida dubliniensis was recovered in culture. The authors describe the first case of septic arthritis caused by Candida dubliniensis.

Background Methods Results Conclusion The decision to perform segmental or extended colectomy in Lynch syndrome (LS) patients with colorectal cancer (CRC) is still controversial. Therefore, this systematic review and meta‐analysis aims to provide updated evidence for segmental versus extended colectomy in LS carriers with CRC.PubMed, Embase, and Cochrane Library were systematically searched for studies published until January 2024 comparing segmental and extended colectomies for CRC in patients with LS. Risk ratio (RR) was used to evaluate binary endpoints with 95% confidence intervals (CIs). Heterogeneity was assessed with the Cochran’s Q test and I2 statistics. Statistical analysis was performed using the R Software, version 4.2.3.A total of 14 studies comprising 2303 LS carriers with CRC, of whom 1724 (74.9%) patients underwent segmental colectomy and 579 (25.1%) patients underwent extended colectomy. Segmental colectomy significantly increased metachronous CRC (mCRC) (RR 2.87; 95% CI 2.03–4.07; and p < 0.01). There were no significant differences between groups for 5‐year overall survival (OS) (RR 0.92; 95% CI 0.82–1.03; and p = 0.14), 10‐year OS (RR 0.99; 95% CI 0.96–1.04; and p = 0.80), and mortality (RR 1.63; 95% CI 0.90–2.97; and p = 0.11). There were no significant linear associations between the outcome of mCRC and age at the time of primary CRC, sex, primary CRC location, and pathogenic LS variant.In this meta‐analysis, segmental colectomy significantly increased mCRC compared with extended colectomy after the first surgery for CRC in patients with LS. However, there were no significant differences between groups for 5‐ and 10‐year OS and mortality. [ABSTRACT FROM AUTHOR]